title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Investigations with infrared spectroscopy on films of the ionic liquid [EMIM]Tf2N. | The reflection-absorption infrared (RAIRS) spectra of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM]Tf 2N) are presented as a function of temperature between 114 and 292 K. A comparison is made with the corresponding infrared spectra (obtained with transmission spectroscopy) from bulk [EMIM]Tf 2N. The liquid and amorphous films show rather similar spectra, indicating that the film structure is similar in both cases. On the other hand, these spectra differ considerably from those of crystalline films. Characteristic differences seen between the film and bulk spectra are attributed to the different structures of the respective networks. There are, however, indications that under all studied conditions the cation-anion interaction is between the C-H groups of the [EMIM] ring and the SO 2 groups of the anion. | 18,798,600 |
X-ray crystal structure of human heme oxygenase-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone: a common binding mode for imidazole-based heme oxygenase-1 inhibitors. | Development of inhibitors specific for heme oxygenases (HOs) should aid our understanding of the HO system and facilitate future therapeutic applications. The crystal structure of human HO-1 complexed with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone (3) was determined. This inhibitor binds to the HO-1 distal pocket such that the imidazolyl moiety coordinates with heme iron while the adamantyl group is stabilized by a hydrophobic binding pocket. Distal helix flexibility, coupled with shifts in proximal residues and heme, acts to expand the distal pocket, thus accommodating the bulky inhibitor without displacing heme. Inhibitor binding effectively displaces the catalytically critical distal water ligand. Comparison with the binding of 2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane (2) revealed a common binding mode, despite differing chemical structures beyond the imidazolyl moiety. The inhibitor binding pocket is flexible, yet contains well-defined subpockets to accommodate appropriate functional groups. On the basis of these structural insights, we rationalize binding features to optimize inhibitor design. | 18,798,608 |
Thermal C1-C5 diradical cyclization of enediynes. | Computational studies at the BLYP/6-31G(d) level (supplemented by BCCD(T)/cc-pVDZ calculations) suggest that in aryl-substituted 1,2-diethynylbenzenes, steric effects disfavor the thermal C1-C6 diradical cyclization reaction (Bergman) and electronic effects favor the regiovariant C1-C5 cyclization to the extent that the C1-C5 process should become an important reaction pathway in the thermolyses of such compounds. Experimentally, thermolyses of 1,2-bis(2,4,6-trichlorophenylethynyl)benzene, a particularly favorable case, yields only products derived from C1-C5 cyclization [specifically, 1-(2,4,6-trichlorobenzylidene)-2-(2,4,6-trichlorophenyl)-1H-indene and its hydrogenation product 3-(2,4,6-trichlorobenzyl)-2-(2,4,6-trichlorophenyl)-1H-indene], and even for the parent hydrocarbon 1,2-bis(phenylethynyl)benzene, the formation of C1-C5 cyclization products is competitive with the major Bergman reaction. Although some C1-C5 cyclization products are probably formed by transfer hydrogenation from 1,4-cyclohexadiene (commonly included in such reactions), thermolyses in the absence of 1,4-CHD as well as deuterium labeling studies confirm the existence of direct C1-C5 diradical cyclizations for diaryl-substituted enediynes. | 18,798,628 |
A formal total synthesis of platencin. | The readily available and enantiomerically pure trienes 12 undergo a thermally induced intramolecular Diels-Alder reaction to give the corresponding mixture of compounds 13 and 14. This mixture has been elaborated to an advanced intermediate associated with Nicolaou's recently reported total synthesis of the natural enantiomeric form of the antibiotic platencin (2). | 18,798,641 |
Structure, dynamics, and selectivity of the sodium channel blocker mu-conotoxin SIIIA. | mu-SIIIA, a novel mu-conotoxin from Conus striatus, appeared to be a selective blocker of tetrodotoxin-resistant sodium channels in frog preparations. It also exhibited potent analgesic activity in mice, although its selectivity profile against mammalian sodium channels remains unknown. We have determined the structure of mu-SIIIA in aqueous solution and characterized its backbone dynamics by NMR and its functional properties electrophysiologically. Consistent with the absence of hydroxyprolines, mu-SIIIA adopts a single conformation with all peptide bonds in the trans conformation. The C-terminal region contains a well-defined helix encompassing residues 11-16, while residues 3-5 in the N-terminal region form a helix-like turn resembling 3 10-helix. The Trp12 and His16 side chains are close together, as in the related conotoxin mu-SmIIIA, but Asn2 is more distant. Dynamics measurements show that the N-terminus and Ser9 have larger-magnitude motions on the subnanosecond time scale, while the C-terminus is more rigid. Cys4, Trp12, and Cys13 undergo significant conformational exchange on microsecond to millisecond time scales. mu-SIIIA is a potent, nearly irreversible blocker of Na V1.2 but also blocks Na V1.4 and Na V1.6 with submicromolar potency. The selectivity profile of mu-SIIIA, including poor activity against the cardiac sodium channel, Na V1.5, is similar to that of the closely related mu-KIIIA, suggesting that the C-terminal regions of both are critical for blocking neuronal Na V1.2. The structural and functional characterization described in this paper of an analgesic mu-conotoxin that targets neuronal subtypes of mammalian sodium channels provides a basis for the design of novel analogues with an improved selectivity profile. | 18,798,648 |
Synthesis and characterization of diazonium functionalized nanoparticles for deposition on metal surfaces. | Silica nanoparticles were surface-functionalized with diazonium groups. The reaction steps leading to the formation of the diazonium functionality were followed with IR and XPS, and the structure of the diazonium-functionalized nanoparticle was confirmed with solid state NMR. Nanoparticle size distribution was determined with DLS, SEM, and TEM. The nanoparticles were then covalently bonded to gold and iron surfaces. Their spatial distribution over the metal surface was analyzed by SEM. Diazonium modification of nanoparticles represents a new method for the covalent attachment of nanoparticles to metal surfaces. | 18,798,659 |
Novel biodegradable shape memory material based on partial inclusion complex formation between alpha-cyclodextrin and poly(epsilon-caprolactone). | A novel shape memory material was prepared based on the formation of inclusion complexes between alpha-cyclodextrin (alpha-CD) and poly(epsilon-caprolactone) (PCL); the PCL-alpha-CD inclusion crystallites serve as a fixing phase, while free PCL crystallites serve as a reversible phase. The characteristics of the material were investigated and a mechanism for the shape memory behavior was proposed. This material showed good shape memory properties, with the recovery ratio exceeding 90% and the recovery time being less than 6 s at 90 degrees C. This PCL-alpha-CD partial inclusion complex lost about 50% (47.4 +/- 4.4%) weight within 45 days in presence of lipase, indicating its degradability. The shape memory and biodegradation properties of the well-designed polymer-alpha-CD complexes indicate great promise for this novel shape memory material. | 18,798,668 |
General, regiodefined access to alpha-substituted butenolides through metal-halogen exchange of 3-bromo-2-silyloxyfurans. Efficient synthesis of an anti-inflammatory gorgonian lipid. | A variety of alpha-substituted butenolides were efficiently prepared from 3-bromo-2-triisopropylsilyloxyfuran via lithium-bromine exchange and in situ quench with carbon or heteroatom electrophiles. The inherent flexibility of this methodology is illustrated by a short and efficient synthesis of an anti-inflammatory marine natural product. | 18,798,671 |
Scanning tunneling microscopy images of alkane derivatives on graphite: role of electronic effects. | Scanning tunneling microscopy (STM) images of self-assembled monolayers of close-packed alkane chains on highly oriented pyrolitic graphite often display an alternating bright and dark spot pattern. Classical simulations suggest that a tilt of the alkane backbone is unstable and, therefore, unlikely to account for the contrast variation. First principles calculations based on density functional theory show that an electronic effect can explain the observed alternation. Furthermore, the asymmetric spot pattern associated with the minimum energy alignment is modulated depending on the registry of the alkane adsorbate relative to the graphite surface, explaining the characteristic moiré pattern that is often observed in STM images with close packed alkyl assemblies. | 18,798,685 |
Plasmon resonance in silver nanoparticles arrays grown by atomic terrace low-angle shadowing. | The plasmonic properties of aligned silver nanoparticles grown by atomic terrace low-angle shadowing (ATLAS) were studied by optical transmission spectroscopy. ATLAS is a novel nanofabrication technique that combines the advantages of self-assembly with control of the nanostructure features. The silver nanoarrays were optically characterized and distinct optical responses with strong polarization dependence were obtained indicating the existence of a strong near-field coupling between the particles. We found that different morphologies gave rise to a similar optical response due to the local contributions to the overall response. Numerical model based on discrete dipole approximation was used to give a qualitative insight into the studied phenomena. | 18,798,686 |
Dose calculation of anticancer drugs. | Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also have their limitations. Just as important as the initial dose selection is the subsequent dose revision to ensure the dose is correct. To provide an insight into the different dose individualization and dose adjustment methods, their feasibility and applicability in daily oncology practice and to suggest a practical framework for dose calculation and a basis for future research. Review of relevant literature related to dose calculation of anticancer drugs. Strategies using clinical parameters, genotype and phenotype markers, and therapeutic drug monitoring all have potential and each has a role for specific drugs. However, no one method is a practical dose calculation strategy for many or all drugs. Given that BSA-dosing leads to significant underdosing it is not reasonable to use this as the sole method of dose calculation. Because of wide disparity in individual patient characteristics and elimination mechanisms, we are unlikely to find the 'Holy Grail' of a single individualized dosing strategy for every patient and anticancer drug in the near future. We propose a pragmatic, although invalidated system for initial dose calculation using dose clusters and structured subsequent dose revision based on treatment-related toxicities and therapeutic drug monitoring. These models need to be tested in clinical trials. | 18,798,700 |
A review of telbivudine for the management of chronic hepatitis B virus infection. | Chronic hepatitis B is a worldwide health problem. Research interests have focused on the development of potent and safe antiviral agents with low resistance rates. Telbivudine is a nucleoside analogue that has been approved for treatment of chronic hepatitis B. This review article concentrates on the pharmacokinetics and therapeutic efficacy of telbivudine. The resistance and safety profiles are also addressed. Relevant publications were identified from searches of MEDLINE (1996-June 2007), the Cochrane Library and BIOSIS (1993-June 2007). Search items included, but were not limited to, telbivudine, pharmacokinetics, hepatitis B, resistance and adverse events. Clinical trials demonstrated telbivudine to be a safe and potent antiviral agent for treatment of chronic hepatitis B. Telbivudine has superior efficacy compared to lamivudine and adefovir. | 18,798,704 |
Role of vector control in the global program to eliminate lymphatic filariasis. | Lymphatic filariasis (LF) is a major cause of acute and chronic morbidity in the tropical and subtropical parts of the world. The availability of safe, single-dose, drug treatment regimens capable of suppressing microfilaremia to very low levels, along with improvements in techniques for diagnosing infection, has resulted in the targeting of this major mosquito-borne disease for global elimination. The Global Program to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the principal objective of breaking the cycles of transmission of Wuchereria bancrofti and Brugia spp. through the application of annual mass drug administrations (MDAs) to entire at-risk populations. Although significant progress in initiating MDA programs in endemic countries has been made, emerging challenges to this approach have raised questions regarding the effectiveness of using MDA alone to eliminate LF without the inclusion of supplementary vector control. Here, we review advances in knowledge of vector ecology, vector-parasite relationships, and both empirical and theoretical evidence regarding vector management to assess the feasibility and strategic value of including vector control in the GPELF initiative to achieve the global elimination of LF. | 18,798,707 |
Effects of bradykinin on venous capacitance in health and treated chronic heart failure. | In the present study, we investigated the effects of basal and intra-arterial infusion of bradykinin on unstressed forearm vascular volume (a measure of venous tone) and blood flow in healthy volunteers (n=20) and in chronic heart failure patients treated with ACEIs [ACE (angiotensin-converting enzyme) inhibitors] (n=16) and ARBs (angiotensin receptor blockers) (n=14). We used radionuclide plethysmography to examine the effects of bradykinin and of the bradykinin antagonists B9340 [B1 (type 1)/B2 (type 2) receptor antagonist] and HOE140 (B2 antagonist). Bradykinin infusion increased unstressed forearm vascular volume in a similar dose-dependent manner in healthy volunteers and ARB-treated CHF patients (healthy volunteers maximum 12.3+/-2.1%, P<0.001 compared with baseline; ARB-treated CHF patients maximum 9.3+/-3.3%, P<0.05 compared with baseline; P=not significant for difference between groups), but the increase in unstressed volume in ACEI-treated CHF patients was higher (maximum 28.8+/-7.8%, P<0.001 compared with baseline; P<0.05 for the difference between groups). In contrast, while the increase in blood flow in healthy volunteers (maximum 362+/-9%, P<0.001) and in ACEI-treated CHF patients (maximum 376+/-12%, P<0.001) was similar (P=not significant for the difference between groups), the increase in ARB-treated CHF patients was less (maximum 335+/-7%, P<0.001; P<0.05 for the difference between groups). Infusion of each receptor antagonist alone similarly reduced basal unstressed volume and blood flow in ACEI-treated CHF patients, but not in healthy volunteers or ARB-treated CHF patients. In conclusion, bradykinin does not contribute to basal venous tone in health, but in ACEI-treated chronic heart failure it does. In ARB-treated heart failure, venous responses to bradykinin are preserved but arterial responses are reduced compared with healthy controls. Bradykinin-mediated vascular responses in both health and heart failure are mediated by the B2, rather than the B1, receptor. | 18,798,730 |
Protection afforded by sunscreens containing inorganic sunscreening agents against blue light sensitivity induced by aminolevulinic acid. | Application of aminolevulinic acid (ALA) for photodynamic therapy induces significant sensitivity to visible light. To determine whether sunscreens containing inorganic agents are effective against sensitivity to blue light induced by ALA application. Twenty subjects received application of ALA on the arm. Thirty minutes before blue light exposure, two sun protection factor 50 inorganic-based sunscreens containing iron oxide 3.2% and 0.2% were applied on separate areas where ALA was applied; a third area received no sunscreen. Small areas of skin were exposed to increasing fluences of blue light 3 or 18 hours later, and the minimal phototoxic dose (MPD) was noted. Three hours after ALA application MPD was 29.2 and 22.6 J/cm(2) for skin protected with sunscreen containing iron oxide 3.2% and 0.2%, respectively, and 10.6 J/cm(2) for unprotected skin (p=.003 and .0497 respectively). At 18 hours after ALA application, MPD for sunscreen containing iron oxide 3.2% was 5.78, compared with 0.33 for unprotected skin (p<.001) with a blue light protection factor of 21. The sunscreen containing iron oxide 3.2% afforded significant protection against blue light sensitivity induced by ALA application. | 18,798,755 |
Efficacy and adverse effects of Q-switched ruby laser on solar lentigines: a prospective study of 91 patients with Fitzpatrick skin type II, III, and IV. | Laser-induced postinflammatory hyperpigmentation could be a limiting factor for selecting patients appropriate for the use of ruby laser in the treatment of lentigenes, especially in dark-skinned individuals. To evaluate the efficacy and adverse effects of Q-switched ruby laser light (694 nm) on solar lentigines in patients with Fitzpatrick skin type II, III, and IV. Controlled comparison study in a university-based laser clinic center. Ninety-one solar lentigines in patients with skin type II, III, and IV were enrolled. All patients were followed for 6 months for frequency of side effects. Before-and-after photographs and images from all follow-up sessions were taken and then assessed by a blinded dermatologist for the evaluation of side effects. Complete clearance was achieved in all patients. Postinflammatory dyspigmentation occurred in 7.8% patients with Fitzpatrick skin type II, 9.8% patients with type III, and 16.6 patients with type IV (p=.67); all improved over a 6-month follow-up period. Q-switched ruby laser treatment is a safe procedure for the treatment of solar lentigines even in dark-skinned individuals. Considering routine factors in addition to melanin content alone is required for minimizing side effects, especially postinflammatory hyperpigmentation in darker skin. | 18,798,756 |
Do different stakeholder groups share mental health research priorities? A four-arm Delphi study. | Despite considerable investment in research priority setting within diverse fields of healthcare, little is known about the extent to which different stakeholder groups share research priorities. Conflicting priorities may jeopardize stakeholder engagement in research. To identify the research priorities of different stakeholder groups within mental health care and examine the extent and nature of agreement between them. Using a Delphi technique, we conducted parallel consultation processes within four different stakeholder groups. Each group process consisted of three rounds. The study was carried out within a mental health and learning disabilities trust in southern England. Participants were recruited from the following groups: mental health service users (34), informal carers (26), mental health practitioners (35) and service managers (23). There were striking differences between the four groups in respect of their ability and willingness to make priority decisions. These differences notwithstanding, there was considerable overlap in respect of their research interests. All groups identified and attached high importance to issues relating to the promotion of independence, self-esteem and recovery. The quality of in-patient care, the place of psychological therapies and the relationship between physical and mental health also emerged across the board. The confluence of four different stakeholder groups around a number of clear themes is highly encouraging, providing a framework within which to construct a research agenda and suggesting that mental health research can be built on solid partnerships. | 18,798,760 |
Common variable immunodeficiency: 20-yr experience at a single centre. | Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It can present at any age in patients with a history of recurrent bacterial infections, with or without a family history of other primary immunodeficiencies (PID), and shows a wide range of clinical manifestations and immunological data. Diagnosis is based on low IgG, IgM and/or IgA levels. Delayed diagnosis and therapy can lead to bronchiectasis and malabsorption. The aim of this study was to describe a paediatric population diagnosed of CVID and its evolution in the population. Memory B-cell (MB) classification carried out in these patients was correlated with clinical manifestations and outcome. Clinical and immunological data of 22 CVID children under 18 yr treated at our centre between 1985 and 2005 are presented. Immunological studies included those for diagnosis and MB quantification. Differences in form of presentation, familial incidence and MB classification were reviewed. A statistical descriptive analysis was made. Infections were the commonest manifestation, affecting mainly respiratory (19/22) and gastrointestinal (10/22) tracts. Bronchiectasis was present in seven cases, and detected prior to CVID diagnosis in five. Replacement therapy led to a significant reduction in the number of infections. Severe complications appeared mostly in patients without MB. Patients of the same family share the same MB group. Family members had also been diagnosed of CVID in seven cases. Early diagnosis and therapy are essential to improve outcome in these patients. MB studies are useful in children to orient prognosis and further genetic studies. | 18,798,799 |
CTG repeats at the myotonic protein kinase gene in a healthy Chilean population sample. | To study the variability at the myotonic dystrophy protein kinase (DMPK) gene in a Chilean sample of healthy people. DM1 is an autosomal dominant disorder caused by an expansion of a (CTG) repeat at the 3'-UTR of the gene DMPK. Healthy individuals have alleles under 35 repeats and diseased individuals have over 50. Genotyping the number of (CTG) repeats at this gene in a sample of healthy Chilean people. Allele frequencies were significantly different from those of other populations. The most frequent allele was with five repeats. The frequency of larger alleles (>18 CTG repeats) was 11%, close to the European frequency (12%) and higher than the Japanese (8%) and Aboriginal Pehuenche samples (8%). Allelic frequencies in the Chilean sample studied were intermediate between those of the two ancestral populations (European and Pehuenche). | 18,798,829 |
A distinct cellular profile is seen in the human endocervix during Chlamydia trachomatis infection. | The endocervix is a major target of Chlamydia trachomatis infection, but little is known about the immune repertoire in this tissue, or its response to these common bacteria. Using a cytobrush, we isolated cells from the endocervix of 20 women during C. trachomatis infection, and post-antibiotic treatment. Endocervical swabs and blood were taken in parallel. Endocervical cells were enumerated, and endocervical and blood T cells immunophenotyped. Chlamydia trachomatis was genotyped by sequence analysis of the OmpA gene, and quantified by culture. Chlamydia trachomatis genotypes were D, E, F and Ia, and infectious burden varied considerably. Endocervical T cell and neutrophil numbers were highly elevated during infection, with both CD4 and CD8 T-cell subsets accumulating. Regardless of the presence or absence of infection, the endocervical cell infiltrate was dominated by effector memory T cells, and the numbers of CCR5 and CD103 expressing T cells was significantly higher than in the blood. Human leukocyte antigen (HLA-DR) expression by endocervical T cells was significantly increased during infection. The human endocervix exhibits a distinct cellular response to C. trachomatis infection that can be longitudinally evaluated by cytobrush sampling. Infecting organisms can be sampled and analyzed in parallel. | 18,798,835 |
New powerful approaches for family-based association tests with longitudinal measurements. | We discuss several new powerful family-based approaches for testing genetic association when the traits are obtained from longitudinal or repeated measurement studies. The popular approach FBAT-PC is based on a linear combination of the individual traits. We propose a one-sided modification, FBAT-PCM, which has a closed-form expression and is always more powerful. We also present two approaches FBAT-LC and FBAT-LCC based on linear combination of the univariate test statistics. Furthermore, all three approaches are shown to be unified to a general form. Through simulation studies, we compare the power of these tests under different models of genetic effect sizes. Compared to original FBAT-PC, our modification achieves a power gain of up to 50%. In addition, all three new approaches gain substantial power compared to the ordinary approach of Bonferroni correction, with the relative performance depending upon the underlying model. Application of these approaches for testing an association between Body Mass Index and a previously reported candidate SNP confirms our results. | 18,798,838 |
Skin cancer surveillance in renal transplant recipients: re-evaluation of U.K. practice and comparison with Australian experience. | Nonmelanoma skin cancer (NMSC) is the most common tumour following solid organ transplantation. In 2000 a survey of U.K. centres managing renal transplant recipients (RTRs) showed that only 21% offered skin cancer surveillance. The survey was repeated in 2006 in the U.K. and Australia. The aims were to determine if U.K. practice had changed since 2000, to define skin cancer surveillance practice in Australian RTRs and to compare this with that in the U.K. Questionnaires were sent to 84 U.K. and 45 Australian centres providing long-term RTR follow-up. Fifty-six (67%) U.K. centres caring for 82% (n = 16 349) of the RTR population replied. Sixty-six per cent provided annual skin cancer surveillance and 39% offered full skin examination (FSE) compared with 21% and 20% in 2000. Eighty-one per cent of surveillance was performed by nondermatologists (n = 30), nine (30%) of whom had received formal training for the role. Thirty-one (69%) Australian centres covering 86% (n = 5392) of the RTR population responded. Ninety-seven per cent provided skin cancer surveillance, and 61% offered FSE. Forty per cent (n = 12) of skin cancer surveillance was conducted by nondermatologists. Two nondermatologists had received formal training. Despite a substantial improvement in the provision of skin cancer surveillance for RTRs in the U.K. between 2000 and 2006, only 39% of units offer FSE. In contrast, virtually all Australian centres offer annual skin cancer surveillance, with more dermatology involvement. Lack of training for nondermatologists involved in skin cancer surveillance is evident in both countries. The availability of dermatologists and the variation in NMSC risk between the populations may explain the different practices observed. | 18,798,841 |
A clinical and genetic study of the Say/Barber/Biesecker/Young-Simpson type of Ohdo syndrome. | We report a series of eight patients with the Say/Barber/Biesecker/Young-Simpson (SBBYS) type of Ohdo syndrome, which is the largest cohort described to date. We expand on the type, frequency and severity of the clinical characteristics in this condition; comment on the natural history of Ohdo syndrome and further refine previously published diagnostic criteria. Cytogenetic investigations and microarray CGH analysis undertaken in this cohort of patients failed to identify a chromosomal aetiology. It remains possible that this rare condition is heterogeneous and therefore caution must be undertaken during counselling until the underlying genetic mechanism(s) is (are) identified. | 18,798,845 |
Cerebral aspergillosis caused by Aspergillus ustus following orthotopic heart transplantation: case report and review of the literature. | This report describes the first case of cerebral aspergillosis in a heart transplantation patient caused by Aspergillus ustus and reviews 15 previously reported cases of invasive aspergillosis in immunocompromised hosts caused by this mold. The utility of molecular analysis for the identification of unusual fungal pathogens is also described. The refractory nature of A. ustus to treatment is similar to other Aspergillus species and treatment options are reviewed. | 18,798,849 |
Cognitive distortions in child sex offenders: an overview of theory, research & practice. | A great deal of clinical and research attention has been paid to understanding and explaining child sex offenders' social cognition. Cognitive distortions have been implicated as a core feature of child sex offenders' offense supportive cognition. The primary aim of this paper is to critically evaluate the phenomenon of cognitive distortions as currently understood with respect to child sex offenders: it reviews the theoretical and research literature and highlights the implications for clinical practice. | 18,798,877 |
Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study. | Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed. | 18,798,975 |
Coining and defining novel nursing terminology. Part 1: critical incident nursing diagnosis. | In the first of a three-part series, a novel nursing terminology is introduced and proposed for inclusion in the North American Nursing Diagnosis Association (NANDA) International Classification--Critical incident nursing diagnosis (CIND)--defined as the recognition of an acute life-threatening event that occurs as a result of disease, surgery, treatment, or medication. The literature, research studies, and meta-analyses from a variety of disciplines, and personal clinical experience serve as the data sources for this article. The current nursing diagnoses in the NANDA International Classification are inaccurate or inadequate for describing nursing care during life-threatening situations. The lack of standardized nursing terminology creates a barrier that may impede critical communication and patient care during life-threatening situations. Coining and defining a novel nursing terminology, CIND, for patient care during life-threatening situations are important and fill the gap in the current standardized nursing terminology. IMPLICATIONS FOR NURSING PRACTICE. Refining the NANDA International Classification will permit nursing researchers, among others, to conduct studies on nursing diagnoses in conjunction with the proposed novel nursing terminology: CIND. Parts 2 and 3 of this series will propose additional nursing terminology: critical incident nursing intervention and critical incident control, respectively. | 18,798,939 |
On the neural networks of empathy: A principal component analysis of an fMRI study. | Human emotional expressions serve an important communicatory role allowing the rapid transmission of valence information among individuals. We aimed at exploring the neural networks mediating the recognition of and empathy with human facial expressions of emotion. A principal component analysis was applied to event-related functional magnetic imaging (fMRI) data of 14 right-handed healthy volunteers (29 +/- 6 years). During scanning, subjects viewed happy, sad and neutral face expressions in the following conditions: emotion recognition, empathizing with emotion, and a control condition of simple object detection. Functionally relevant principal components (PCs) were identified by planned comparisons at an alpha level of p < 0.001. Four PCs revealed significant differences in variance patterns of the conditions, thereby revealing distinct neural networks: mediating facial identification (PC 1), identification of an expressed emotion (PC 2), attention to an expressed emotion (PC 12), and sense of an emotional state (PC 27). Our findings further the notion that the appraisal of human facial expressions involves multiple neural circuits that process highly differentiated cognitive aspects of emotion. | 18,798,977 |
Passive tobacco exposure may impair symptomatic improvement in patients with chronic angina undergoing enhanced external counterpulsation. | The adverse effects of tobacco abuse on cardiovascular outcomes are well-known. However, the impact of passive smoke exposure on angina status and therapeutic response is less well-established. We examined the impact of second-hand smoke (SHS) exposure on symptomatic improvement in patients with chronic ischemic coronary disease undergoing enhanced external counterpulsation (EECP). This observational study included 1,026 non-smokers (108 exposed and 918 not-exposed to SHS) from the Second International EECP Patient Registry. We also assessed angina response in 363 current smokers. Patient demographics, symptomatic improvement and quality of life assessment were determined by self-report prior and after EECP treatment. Non-smoking SHS subjects had a lower prevalence of prior revascularization (85% vs 90%), and had an increased prevalence of stroke (13% vs 7%) and prior smoking (72% vs 61%; all p < 0.05) compared to non-smokers without SHS exposure. Despite comparable degrees of coronary disease, baseline angina class, medical regimens and side effects during EECP, fewer SHS non-smokers completed a full 35-hour treatment course (77% vs 85%, p = 0.020) compared to non-smokers without SHS. Compared to non-smokers without SHS, non-smoking SHS subjects had less angina relief after EECP (angina class decreased > or = 1 class: 68% vs 79%; p = 0.0082), both higher than that achieved in current smokers (66%). By multivariable logistic regression, SHS exposure was an independent predictor of failure to symptomatic improvement after EECP among non-smokers (OR 1.81, 95% confidence intervals 1.16-2.83). Non-smokers with SHS exposure had an attenuated improvement in anginal symptoms compared to those without SHS following EECP. | 18,798,998 |
Hope, despair and transformation: Climate change and the promotion of mental health and wellbeing. | This article aims to provide an introduction to emerging evidence and debate about the relationship between climate change and mental health. The authors argue that:i) the direct impacts of climate change such as extreme weather events will have significant mental health implications;ii) climate change is already impacting on the social, economic and environmental determinants of mental health with the most severe consequences being felt by disadvantaged communities and populations; iii) understanding the full extent of the long term social and environmental challenges posed by climate change has the potential to create emotional distress and anxiety; and iv) understanding the psycho-social implications of climate change is also an important starting point for informed action to prevent dangerous climate change at individual, community and societal levels. | 18,799,005 |
PCR diagnostics of Mycobacterium tuberculosis in historic human long bone remains from 18th century burials in Kaiserebersdorf, Austria. | In the present pilot study we applied recently published protocols for detecting Mycobacterium tuberculosis in human remains. We screened long bones from an 18th century cemetery and skulls from the anatomical "Weisbach collection" (19th century). In addition, besides the study of abundance of tuberculosis in inmates of the poorhouse itself, we were interested to test whether in this particular instance tuberculosis can be identified from cortical bones, which are rarely affected by tuberculosis, but mostly better preserved than the vertebral bodies or epiphyses. The DNA extractions from the bone samples were obtained following established ancient DNA protocols. Subsequently extracts were subjected to a series of PCR amplifications using primer pairs published previously 12. PCR products of the expected size were subsequently sequenced. Only primers targeting the repetitive IS6110 insertion sequence yielded PCR products of appropriate size. In one sample only (skull sample WB354 of the "Weisbach collection") sequence analysis revealed an authentic M. tuberculosis sequence that matched to a reference sequence from GenBank. With a variety of established PCR approaches we failed to detect M. tuberculosis DNA in historic human femurs from an 18th century cemetery relating to a poor house in Kaiserebersdorf, Austria. Our data may indicate that in this particular case, thoracic or lumbar vertebrae, i.e. bones that are severely affected by the disease, would be more suitable for molecular diagnostics than long bones. However, the unpredictable state of DNA preservation in bones from museum collections does not allow any general recommendation of any type of bone. | 18,799,009 |
Onset of meiosis in the chicken embryo; evidence of a role for retinoic acid. | Meiosis in higher vertebrates shows a dramatic sexual dimorphism: germ cells enter meiosis and arrest at prophase I during embryogenesis in females, whereas in males they enter mitotic arrest during embryogenesis and enter meiosis only after birth. Here we report the molecular analysis of meiosis onset in the chicken model and provide evidence for conserved regulation by retinoic acid. Meiosis in the chicken embryo is initiated late in embryogenesis (day 15.5), relative to gonadal sex differentiation (from day 6). Meiotic germ cells are first detectable only in female gonads from day 15.5, correlating with the expression of the meiosis marker, SCP3. Gonads isolated from day 10.5 female embryos and grown in serum-free medium could still initiate meiosis at day 16.5, suggesting that this process is controlled by an endogenous clock in the germ cells themselves, and/or that germ cells are already committed to meiosis at the time of explantation. Early commitment is supported by the analysis of chicken STRA8, a pre-meiotic marker shown to be essential for meiosis in mouse. Chicken STRA8 is expressed female-specifically from embryonic day 12.5, preceding morphological evidence of meiosis at day 15.5. Previous studies have shown that, in the mouse embryo, female-specific induction of STRA8 and meiosis are triggered by retinoic acid. A comprehensive analysis of genes regulating retinoic acid metabolism in chicken embryos reveals dynamic expression in the gonads. In particular, the retinoic acid-synthesising enzyme, RALDH2, is expressed in the left ovarian cortex at the time of STRA8 up-regulation, prior to meiosis. This study presents the first molecular analysis of meiosis onset in an avian embryo. Although aspects of avian meiosis differ from that of mammals, a role for retinoic acid may be conserved. | 18,799,012 |
Stress and psychological factors before a migraine attack: a time-based analysis. | The objective of this study is to examine the stress and mood changes of Japanese subjects over the 1-3 days before a migraine headache. The study participants were 16 patients with migraines who consented to participate in this study. Each subject kept a headache diary four times a day for two weeks. They evaluated the number of stressful events, daily hassles, domestic and non-domestic stress, anxiety, depressive tendency and irritability by visual analog scales. The days were classified into migraine days, pre-migraine days, buffer days and control days based on the intensity of the headaches and accompanying symptoms, and a comparative study was conducted for each factor on the migraine days, pre-migraine days and control days. The stressful event value of pre-migraine days showed no significant difference compared to other days. The daily hassle value of pre-migraine days was the highest and was significantly higher than that of buffer days. In non-domestic stress, values on migraine days were significantly higher than on other days, and there was no significant difference between pre-migraine days and buffer days or between pre-migraine days and control days. There was no significant difference in the values of domestic stress between the categories. In non-domestic stress, values on migraine days were significantly higher than other days, and there was no significant difference between pre-migraine days and buffer days or between pre-migraine days and control days.There was little difference in sleep quality on migraine and pre-migraine days, but other psychological factors were higher on migraine days than on pre-migraine days. Psychosocial stress preceding the onset of migraines by several days was suggested to play an important role in the occurrence of migraines. However, stress 2-3 days before a migraine attack was not so high as it has been reported to be in the United States and Europe. There was no significant difference in the values of psychological factors between pre-migraine days and other days. | 18,799,013 |
Hydration status and physiological workload of UAE construction workers: A prospective longitudinal observational study. | The objective of the study was to investigate the physiological responses of construction workers labouring in thermally stressful environments in the UAE using Thermal Work Limit (TWL) as a method of environmental risk assessment. The study was undertaken in May 2006. Aural temperature, fluid intake, and urine specific gravity were recorded and continuous heart rate monitoring was used to assess fatigue. Subjects were monitored over 3 consecutive shifts. TWL and WBGT were used to assess the thermal stress. Most subjects commenced work euhydrated and maintained this status over a 12-hour shift. The average fluid intake was 5.44 L. There were no changes in core temperature or average heart rate between day 1 and day 3, nor between shift start and finish, despite substantial changes in thermal stress. The results obtained indicated that the workers were not physiologically challenged despite fluctuating harsh environmental conditions. Core body temperatures were not elevated suggesting satisfactory thermoregulation. The data demonstrate that people can work, without adverse physiological effects, in hot conditions if they are provided with the appropriate fluids and are allowed to self-pace. The findings suggested that workers will self-pace according to the conditions. The data also demonstrated that the use of WBGT (a widely used risk assessment tool) as a thermal index is inappropriate for use in Gulf conditions, however TWL was found to be a valuable tool in assessing thermal stress. | 18,799,015 |
[Role of high mobility group box 1 in adriamycin-induced apoptosis in leukemia K562 cells]. | High mobility group box l (HMGB1), a nuclear DNA-binding protein, stabilizes the structure and function of chromatin, regulates gene transcription. Recent studies found that HMGB1 is associated with the proliferation and metastasis of many tumors, including breast cancer, colon carcinoma, and melanoma, and is rich in various solid cancer tissues and immature cells. This study was to explore the role of HMGB1 in adriamycin (ADM)-induced apoptosis in leukemia K562 cells. K562 cells were transiently transfected with recombinant plasmid pcDNA3.1-HMGB1. The expression of HMGB1 in K562 cells were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The 50% inhibition concentration (IC(50)) of ADM for K562 cells was determined by WST-8 assay. Cell apoptosis was assessed by flow cytometry. The protein level of Bcl-2 was detected by Western blot. The activities of Caspase-3 and Caspase-9 were assayed with Caspase Colorimetric Assay Kit. The mRNA and protein levels of HMGB1 in K562 cells transfected with pcDNA3.1-HMGB1 were increased by about 85% and 56% respectively as compared with those in K562 cells transfected with pcDNA3.1. Overexpression of HMGB1 in K562 cells by transient transfection significantly increased the resistance to ADM; the IC(50) of ADM was increased from (0.06+/-0.00) microg/mL to (3.46+/-0.06) microg/mL. When treated with 1 microg/mL ADM, the apoptosis rate was significantly lower in HMGB1-transfected K562 cells than in pcDNA3.1-transfected K562 cells [(12.00+/-1.26)% vs. (44.50+/-1.87)%, P<0.05]. Overexpression of HMGB1 in K562 cells significantly inhibited ADM-induced down-regulation of Bcl-2 protein. After treatment of ADM, the activities of Caspase-3 and Caspase-9 in HMGB1-transfected K562 cells were inhibited as compared with those in pcDNA3.1-transfected K562 cells (Caspase-3: 1.55+/-0.06 vs. 2.55+/-0.06 at 12 h, 1.86+/-0.10 vs. 2.85+/-0.06 at 24 h, P<0.05; Caspase-9: 1.40+/-0.08 vs. 2.03+/-0.05 at 12 h, 1.55+/-0.06 vs. 2.22+/-0.05 at 24 h, P<0.05). HMGB1 overexpression could inhibit ADM-induced apoptosis in leukemia K562 cells through regulating the protein level of Bcl-2 and the activities of Caspase-3 and Caspase-9. | 18,799,030 |
[Impact of alpha1,2-fucosyl transferase gene transfection on cancer-related gene expression profile of human ovarian cancer cell line RMG-1]. | The malignant biological behaviors are enhanced in human ovarian cancer cell line RMG-1 after transfection of alpha1,2-fucosyl transferase (alpha1,2-FT) gene. This study was to investigate the influence of alpha1,2-FT gene transfection on cancer-related gene expression profile of RMG-1 cells. Gene expressing vector pcDNA3.1-HFT-H and empty vector pcDNA3.1 were transfected into RMG-1 cells to produce RMG-1-H and RMG-1-C cells separately. Gene expression profiles of these two cell lines were detected by gene chip assay. The acquired data were inquired on the GoMiner online database. After transfection, comparing with those in RMG-1-C cells, 88 differentially expressed genes were identified in RMG-1-H cells: 60 were up-regulated and 28 were down-regulated. These genes are involved in protein binding, nucleotide binding, cell proliferation, DNA-dependent regulation of transcription, signal transduction, protein amino acid phosphorylation, transcription, cell adhesion, and so on. The transfection of alpha1,2-FT gene causes the changes of gene expression profile in ovarian cancer RMG-1 cells. | 18,799,031 |
[Prognosis analysis of 83 cases of cervical adenosquamous carcinoma]. | Cervical adenosquamous carcinoma is a special histological type of cervical carcinoma. Its clinic-pathologic characteristics and prognostic factors have seldom been reported. This study was to explore the clinic-pathologic characteristics and prognostic factors of cervical adenosquamous carcinoma. Clinical data of 83 pathologically confirmed adenosquamous cervical carcinoma patients in Sun Yat-sen University Cancer Center from Nov. 1982 to May 2006 were analyzed. The median overall survival (OS) of 83 patients was 47 months and the median disease-free survival was 43 months. The 5-year survival rate was 74.0%, and the recurrence rate (DFS) was 30.1% (25/83). The median OS and DFS were 58 months and 54 months versus 37 months and 21 months in patients with or without lymph node metastasis (P=0.005, P<0.001). The median DFS was 47 months and 16 months for patients with the tumor diameter >4 or < or =4 cm (P=0.015), respectively. Lymph node metastasis was correlated to FIGO stage, tumor diameter and invasion depth. The recurrence rate of patients with ovarian preservation was 33.3% (3/9). Lymph node metastasis is an independent risk factor for prognosis in cervical adenosquamous carcinoma. Adjunctive postoperative irradiation would improve the OS and DFS. Tumor diameter greater than 4cm is an independent prognostic risk of DFS. The impact of ovarian preservation on prognosis is unclear. | 18,799,035 |
[Clinical analysis of 14 cases of urachal carcinoma]. | Urachal carcinoma is a rare malignancy. This study was to summarize our clinical experience in the diagnosis and treatment of urachal carcinoma. Fourteen cases of urachal carcinoma treated from May 1994 to April 2007 at Cancer Center and The First Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed and analyzed. The most common complaints of the 14 patients were hematuria and irrigative bladder symptoms. Cystoscopy mainly revealed broad-based tumors located at the dome of the bladder. Soft-tissue masses between the bladder dome and the abdominal wall were detected by imaging examinations; the wall of the bladder was often invaded. Thirteen patients were found adenocarcinoma, the other one was malignant stromal cell tumor. Seven patients underwent extensive partial excision of the bladder, among which one case developed local recurrence 24 months after operation, while the other six cases were followed up for 14-120 months, with a median follow-up of 42 months without recurrence. Three patients underwent radical bladder resection and urinary diversion, two of which were followed up for 16 months and 84 months respectively without recurrence, while the other one died from surgical complications 3 months after operation. One case underwent partial cystectomy at another hospital developed recurrence 10 months after operation. Three advanced cancer patients received chemotherapy, two of which achieved progression free survival for seven and eight months respectively, while the other one died three months after chemotherapy. The one- and five-year survival rates were 85.7% and 61.2%, respectively. Extensive partial excision of the bladder is recommended for urachal carcinoma. Radical removal of the tumor during the first treatment and comprehensive therapies for advanced cancer patients and patients with recurrence or metastasis after operation are critical to improve the treatment efficacy of urachal carcinoma. | 18,799,037 |
Prevalence and impact of fibromyalgia on function and quality of life in individuals from the general population: results from a nationwide study in Spain. | To estimate the prevalence of fibromyalgia (FM) and to compare some descriptive epidemiological and quality of life data between persons with and without FM criteria in a representative sample of the general Spanish population. Cross sectional study of 2,192 Spaniards aged 20 or above, selected by cluster sampling. Subjects were invited to a structured interview carried out by trained rheumatologists to ascertain various musculoskeletal disorders. The visit included screening and examination, validated instruments for measuring function (HAQ) and quality of life (SF-12) and questions about socio-demographic characteristics and musculoskeletal, mental, and other general symptoms. FM was suspected in subjects with widespread pain for more than three months. FM was defined by theAmerican College of Rheumatology classification criteria. All estimates are adjusted to sampling scheme. The prevalence of FM in Spain is 2.4% (95% CI: 1.5-3.2). FM is significantly more frequent in women (4.2%) than in men (0.2%), with an OR for women of 22.5 (95%CI: 7.2- 69.9), mainly in the 40-49 years age interval. It is more frequent in rural (4.1%) than in urban settings (1.7%), with an OR for rural settings of 2.5 (95%CI: 1.03-5.9). FM is associated with a low educational level, to a low social class, and to self-reported depression. The scores in the HAQ and in the SF-12 were significantly lower in FM subjects, despite adjustment by covariates. FM has a high prevalence in the general population. FM is associated to female gender, comorbidities, age between 40 and 59 years, and a rural setting. Persons fulfilling FM criteria show impaired functioning and quality of life. | 18,799,079 |
Diagnostic values of history and clinical examination to predict ultrasound signs of chronic and acute enthesitis. | To examine the diagnostic values of history of chronic enthesitic pain and clinical signs of acutely inflamed entheses to predict ultrasound (US) signs of enthesitis. Cohort study of 21 consecutive rheumatic out-patients (female/male 18/3) with suspected multiple enthesitis and 12 controls (female/male 10/2). 429 enthesal sites according to the Maastricht Ankylosing Spondylitis Entheses Score (MASES) were evaluated by history, clinical examination, B-mode and power Doppler US. Sensitivity and specificity of history suggesting chronic enthesitic pain and clinical examination suggesting acute enthesitis were calculated using corresponding US findings as reference standard. Diagnostic accuracy widely varied between different MASES sites. Sensitivity and specificity of selected MASES points were 66.7 - 86.4% and 85.0 - 91.7% for history and 71.4 - 87.0% and 47.4 - 75.0% for clinical examination, respectively (p<0.05 for each). At specific enthesal sites, history of chronic enthesitic pain and clinical signs of acute inflammation are sensitive and specific for the diagnosis of chronic and/or acute inflammation. | 18,799,083 |
Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response. | Pannus in osteoarthritis (OA) has only recently been characterized. Little is known, however, regarding the behavior of OA pannus in vitro compared to rheumatoid arthritis (RA) pannus. The purpose of our study was to compare OA with RA pannus. Pannus and synovial tissue co-cultures from 5 patients with OA and 5 patients with RA obtained during arthroplasty were studied. Pannus was defined as the microscopic invasive granulation tissue covering the articular surface. Tissues were cultured for 7 days and stained with Alcian Blue technique. Interleukin-1beta (IL-1beta), IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma) were also determined in supernatants by ELISA. Cartilage oligomeric matrix protein (COMP), type II collagen, TNF-alpha, IL-10 and Ki-67 expression were also detected by immunohistochemistry. All patients had vascular or fibrous pannus. Synovial proliferation, inflammatory infiltrates and a decrease of extracellular matrix proteins were observed in all tissue samples. Chondrocyte proliferation was lower in OA than RA cartilage. OA synovial tissue expressed lower levels of proteoglycans than RA synoyium. Type II collagen levels were lower in OA than in RA cartilage. Significantly higher levels of IL-1beta were found in the supernatants of RA pannus compared to OA pannus (p<0.05). High but similar levels of TNF-alpha, IL-8 and TIMP-1 were detected in OA and RA pannus supernatants. IL-10, IL-12 and IFN-gamma were undetectable. RA and OA pannus had similar pro-inflammatory and anti-inflammatory cytokine profile expression. OA cartilage, synovial tissue and pannus had lower production of proteoglycans, type II collagen and IL-1beta. It remains to be elucidated why OA pannus invades the cartilage surface but does not cause the marginal erosions typically seen in RA. | 18,799,084 |
Synovial pathology in an ovine model of osteoarthritis: effect of intraarticular hyaluronan (Hyalgan). | Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan). OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy. | 18,799,085 |
Serum levels of heat shock protein 70, a biomarker of cellular stress, are elevated in patients with systemic sclerosis: association with fibrosis and vascular damage. | To determine the clinical significance of heat shock protein (Hsp) 70, a sensitive biomarker for monitoring cellular stress, in systemic sclerosis (SSc), we investigated the prevalence and clinical correlation of serum Hsp70 levels in SSc patients. Serum Hsp70 levels were examined in 48 patients with SSc by enzyme-linked immunosorbent assay. Serum Hsp70 levels were significantly elevated in SSc patients compared to normal controls (n=30), and were similar between patients with diffuse cutaneous SSc (n=26) and those with limited cutaneous SSc (n=22). Serum Hsp70 levels were elevated in 27% of total SSc patients with 30% of diffuse cutaneous SSc patients and 23% of limited cutaneous SSc patients. Hsp70 levels were significantly increased in SSc patients with pulmonary fibrosis or contracture of phalanges compared with those without pulmonary fibrosis or contracture of phalanges. Serum Hsp70 levels correlated positively with modified Rodnan total skin thickness score, renal vascular resistance, serum levels of monocyte chemotactic protein-1, C-reacting protein, and serum levels of 8-isoprostane. Serum Hsp70 levels were increased in SSc patients and were associated with pulmonary fibrosis, skin sclerosis, renal vascular damage, oxidative stress, and inflammation. These results suggest that Hsp70 is a useful serological marker for evaluating cellular stresses and the disease severity in SSc. | 18,799,101 |
Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis. | To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial. | 18,799,107 |
The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration. | A central focus of aging research is to determine how calorie restriction (CR) extends lifespan and delays diseases of aging. SIRT1, the mammalian ortholog of Sir2 in yeast, is a longevity factor which mediates dietary restriction in diverse species. In addition, SIRT1 plays a protective role in several models of neurodegenerative disease. We tested the role of SIRT1 in mediating the effects of CR in a mouse model of prion disease. Prion diseases are protein misfolding disorders of the central nervous system with many similarities to other neurodegenerative diseases, including deposition of aggregated protein, gliosis, and loss of synapses and neurons. We report that the onset of prion disease is delayed by CR and in the SIRT1 KO mice fed ad libitum. CR exerts no further effect on the SIRT1 KO strain, suggesting the effects of CR and SIRT1 deletion are mechanistically coupled. In conjunction, SIRT1 is downregulated in certain brain regions of CR mice. The expression of PrP mRNA and protein is reduced in the brains of CR mice and in SIRT1 knockout mice, suggesting a possible mechanism for the delayed onset of disease, as PrP levels are a critical determinant of how quickly mice succumb to prion disease. Surprisingly, CR greatly shortens the duration of clinical symptoms of prion disease and ultimately shortens lifespan of prion-inoculated mice in a manner that is independent of SIRT1. Taken together, our results suggest a more complex interplay between CR, SIRT1, and neurodegenerative diseases than previously appreciated. | 18,799,131 |
TNF-alpha mediates pseudorabies virus-induced apoptosis via the activation of p38 MAPK and JNK/SAPK signaling. | PRV infection causes apoptosis in vitro and in vivo. However, the significance of PRV-induced apoptosis and its signaling pathways is still unknown. This work investigates the role of MAPK pathways in mediating PRV-induced apoptosis. Flow cytometry, apoptosis ELISA and western blotting using antibodies against cleaved caspase-3, -6 and PARP demonstrated that PRV induces apoptosis in a time- and dose-dependent manner. p38 and JNK/SAPK inhibitors significantly protected cells from PRV-induced apoptosis. Inhibitor treatment did not affect Us3a gene transcription and progeny virus production. Western blotting revealed that PRV activates p38 and JNK/SAPK signaling. Inhibition of NF-kappaB had no effect on PRV-mediated apoptosis. Non-replicative PRV failed to activate p38 and JNK/SAPK or induce apoptosis. PRV infection increases TNF-alpha transcription, translation and secretion, as well as TNF-alpha receptor expression. Inhibition of p38 and JNK/SAPK reduced PRV-induced TNF-alpha up-regulation. Neutralization assay confirmed that TNF-alpha is a key mediator involved in PRV-induced apoptosis. | 18,799,179 |
Hepatobiliary effects of 90yttrium microsphere therapy for unresectable hepatocellular carcinoma. | (90)Yttrium (Therasphere) microspheres administered via hepatic artery are a valuable option for treatment of hepatocellular carcinoma. This therapy targets tumor nodules while largely sparing hepatic parenchyma. This retrospective study examines liver explants from 13 adult patients with hepatocellular carcinoma who received intrahepatic Theraspheres and subsequently underwent liver transplantation. Histopathologic and laboratory reviews are performed. Theraspheres preferentially migrated to the lobe(s) supplied by the injected artery branches and frequently localized to tumors. Tumors showed a chronology of changes beginning with confluent necrosis typically accompanied by hemorrhage and later by fibrinoid change. This was followed by fibrosis with regenerative activity at tumor peripheries. Adjacent hepatic parenchyma went through a similar sequence of injury and repair that could lead to markedly fibrotic cirrhotic nodules in the vicinity of treated tumors. No consistent pattern of thrombomodulin loss was seen in endothelial cells of the tumors or adjacent parenchyma, suggesting that direct endothelial cell injury was likely not a major contributor to the necrotic process. However, the pattern of injury and repair is suggestive of a localized and subclinical form of radiation-induced liver disease. The pathologist should be aware of these changes to distinguish them from the diffuse "radiation hepatitis" associated with older forms of radiotherapy. | 18,799,190 |
The metastatic capacity of multifocal breast carcinomas: extensive tumors versus tumors of limited extent. | The extent and distribution of lesions in breast carcinomas are important morphologic prognostic parameters that influence the type and results of surgical intervention, as well as the propensity for metastasis. We investigated how the extent of disease influences the risk of metastasis in a consecutive series of 519 invasive breast carcinomas that were documented in large-format histology sections. Breast carcinomas of limited extent (demonstrable invasive, in situ, and intravascular tumor structures occupied a tissue space <40 mm in the largest dimension) were delineated from extensive tumors; and the proportions of cases with lymph vessel invasion, lymph node macrometastasis, and mastectomy were registered. The risks of lymph vessel invasion and lymph node metastasis were elevated substantially for extensive multifocal invasive cancers and for multifocal tumors of limited extent compared with the risks for unifocal cancers (47%, 44%, and 21%, respectively, for lymph vessel invasion; 53%, 40%, and 20%, respectively, for lymph node metastasis). The odds ratio for having lymph node metastasis was 12.4 when extensive carcinomas with diffuse invasive component were compared with unifocal invasive tumors of limited extent. Although the risks of lymph vessel invasion and lymph node metastasis increased gradually with tumor size, they remained elevated in multifocal carcinomas in every size category. The risk of lymph node metastasis was not elevated in unifocal invasive breast carcinomas with multifocal in situ component. These results confirm that the extent and distribution of lesions in breast carcinomas are important biological prognostic factors and indicate a need for special histopathologic techniques for adequate assessment of these parameters. | 18,799,193 |
Clinical, pathological and thin-section CT features of persistent multiple ground-glass opacity nodules: comparison with solitary ground-glass opacity nodule. | To retrospectively compare the clinical, pathological, and thin-section CT features of persistent multiple ground-glass opacity (GGO) nodules with those of solitary GGO nodules. Histopathologic specimens were obtained from 193 GGO nodules in 136 patients (87 women, 49 men; mean age, 57; age range 33-81). The clinical data, pathologic findings, and thin-section CT features of multiple and solitary GGO nodules were compared by using t-test or Fisher's exact test. Multiple GGO nodules (n=105) included atypical adenomatous hyperplasia (AAH) (n=31), bronchioloalveolar carcinoma (BAC) (n=33), adenocarcinoma (n=34) and focal interstitial fibrosis (n=7). Solitary GGO nodules included AAH (n=8), BAC (n=15), adenocarcinoma (n=55) and focal interstitial fibrosis (n=10). AAH (P=.001) and BAC (P=.029) were more frequent in multiple GGO nodules, whereas adenocarcinoma (P<.001) was more frequent in solitary GGO nodules. Female sex (P<.001), nonsmoker (P=.012) and multiple primary lung cancers (P<.001) were more frequent for multiple GGO nodules, which were smaller (12 mm+/-7.9) than solitary GGO nodules (17 mm+/-8.1) (P<.001). Air-bronchogram (P=.019), bubble-lucency (P=.004), and pleural retraction (P<.001) were more frequent in solitary GGO nodules. There was no postoperative recurrence except for one patient with multiple GGO nodules and one with solitary GGO nodule. Clinical, pathological, and thin-section CT features of persistent multiple GGO nodules were found to differ from those of solitary GGO nodules. Nevertheless, the two nodule types can probably be followed up and managed in a similar manner because their prognoses were found to be similar. | 18,799,230 |
Hospital outbreak of Burkholderia stabilis bacteraemia related to contaminated chlorhexidine in haematological malignancy patients with indwelling catheters. | Burkholderia cepacia complex (BCC) is an opportunistic pathogen that occasionally causes hospital outbreaks. This paper describes an outbreak of BCC bacteraemia in haematological malignancy patients related to a contaminated chlorhexidine gluconate solution. Eight BCC isolates were obtained from patients hospitalised in the same ward of a cancer centre in a Korean hospital. A further three BCC isolates were obtained from 0.5% chlorhexidine gluconate used in the same ward. The isolates were identified as B. stabilis and exhibited identical pulsed-field gel electrophoresis profiles. All patients with B. stabilis bacteraemia had indwelling intravenous catheters, which were treated with chlorhexidine to disinfect the catheters. Following identification of the source of contamination, strict controls regarding surveillance cultures for disinfectants have been enforced. No further B. stabilis infections have been found in the hospital. | 18,799,235 |
Experience with the use of palivizumab together with infection control measures to prevent respiratory syncytial virus outbreaks in neonatal intensive care units. | Respiratory syncytial virus (RSV) frequently causes nosocomial outbreaks in general paediatric wards and occasionally in neonatal intensive care units (NICUs). Conventional infection control measures often fail to prevent the spread of RSV, and it can cause significant morbidity especially in preterm and young infants. We report our experience in preventing an outbreak on a NICU after RSV had been detected in a premature infant. The index case was a 34-day-old premature infant who presented with clinical infection and RSV was detected in a clinical specimen. There were 11 patients in the ward at the time including the index case. The RSV-positive patient was isolated, the ward closed to admissions and infection control measures were implemented. Two patients were transferred to another hospital. Palivizumab 15 mg/kg i.m. was given to all patients and no further cases occurred. All subsequent RSV tests on nasal secretions were negative. Palivizumab combined with conventional infection control measures appeared to prevent the spread of RSV in this NICU. Strategies for the prevention of RSV outbreaks on NICUs all recommend the reinforcement of routine infection control measures. Recommendations concerning the use of palivizumab range from monthly prophylaxis to all infants at risk, to prophylaxis of selected cases only. Currently there are no guidelines for the use of palivizumab in NICUs or for the control of RSV outbreaks. | 18,799,241 |
Raman spectroscopy as a process analytical technology (PAT) tool for the in-line monitoring and understanding of a powder blending process. | The aim of this study is to propose a strategy to implement a PAT system in the blending step of pharmaceutical production processes. It was examined whether Raman spectroscopy can be used as PAT tool for the in-line and real-time endpoint monitoring and understanding of a powder blending process. A screening design was used to identify and understand the significant effects of two process variables (blending speed and loading of the blender) and of a formulation variable (concentration of active pharmaceutical ingredient (API): diltiazem hydrochloride) upon the required blending time (response variable). Interactions between the variables were investigated as well. A Soft Independent Modelling of Class Analogy (SIMCA) model was developed to determine the homogeneity of the blends in-line and real-time using Raman spectroscopy in combination with a fiber optical immersion probe. One blending experiment was monitored using Raman and NIR spectroscopy simultaneously. This was done to verify whether two independent monitoring tools can confirm each other's endpoint conclusions. The analysis of the experimental design results showed that the measured endpoints were excessively rounded due to the large measurement intervals relative to the first blending times. This resulted in effects and critical effects which cannot be interpreted properly. To be able to study the effects properly, the ratio between the blending times and the measurement intervals should be sufficiently high. In this study, it anyway was demonstrated that Raman spectroscopy is a suitable PAT tool for the endpoint control of a powder blending process. Raman spectroscopy not only allowed in-line and real-time monitoring of the blend homogeneity, but also helped to understand the process better in combination with experimental design. Furthermore, the correctness of the Raman endpoint conclusions was demonstrated for one process by using a second independent endpoint monitoring tool (NIR spectroscopy). Hence, the use of two independent techniques for the control of one response variable not only means a mutual confirmation of both methods, but also provides a higher certainty in the determined endpoint. | 18,799,281 |
HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV induced thyroid autoimmunity. | HCV infection is well-known to be associated with autoimmune thyroiditis. However, the mechanisms by which HCV triggers thyroiditis are unknown. We hypothesized that HCV envelope proteins could induce thyroidal inflammation directly, thereby triggering thyroiditis by a bystander activation mechanism. To test this hypothesis we examined whether the HCV receptor CD81 was expressed and functional on thyroid cells. We found significant levels of CD81 mRNA by QPCR analysis, as well as CD81 protein by flow cytometric (FACS) analysis. Incubation of thyroid cells with HCV envelope glycoprotein E2 resulted in E2 binding to thyroid cells and activation of IL-8, an important pro-inflammatory cytokine. Intriguingly, thyroid cells incubated with E2 continued to proliferate normally and did not undergo apoptosis, as was reported in hepatocytes. We conclude that: (1) HCV envelope glycoprotein E2 can bind to CD81 receptors which are expressed on thyroid cells and induce a cascade of signaling pathway leading to IL-8 release; and (2) HCV may trigger thyroiditis in genetically susceptible individuals by bystander activation mechanisms. | 18,799,285 |
Characterisation and stability of lipid-DNA complexes. | A combination of complementary analytical techniques has provided valuable information on the physicochemical properties of lipid-DNA complexes such as their size, shape, structure and surface charge. The experimental conditions for producing small and stable lipid-DNA complexes were determined. These complexes consist of spherical primary particles of approximately 60 nm in diameter connected to each other by DNA strands to form small clusters of approximately 70-200 nm in diameter. At high salt concentrations these complexes were not stable and aggregated. Several methods were used to stabilise the lipid-DNA complexes at physiological salt concentrations. | 18,799,295 |
Structure and reactivity of a(n) and a(n) peptide fragments investigated using isotope labeling, tandem mass spectrometry, and density functional theory calculations. | Extensive (15)N labeling and multiple-stage tandem mass spectrometry were used to investigate the fragmentation pathways of the model peptide FGGFL during low-energy collision-induced-dissociation (CID) in an ion-trap mass spectrometer. Of particular interest was formation of a(4) from b(4) and a(4) (a(4)-NH(3)) from a(4) ions correspondingly, and apparent rearrangement and scrambling of peptide sequence during CID. It is suggested that the original FGGF(oxa)b(4) structure undergoes b-type scrambling to form GGFF(oxa). These two isomers fragment further by elimination of CO and (14)NH(3) or (15)NH(3) to form the corresponding a(4)and a(4) isomers, respectively. For ((15)N-F)GGFL and FGG((15)N-F)L the a(4) ion population appears as two distinct peaks separated by 1 mass unit. These two peaks could be separated and fragmented individually in subsequent CID stages to provide a useful tool for exploration of potential mechanisms along the a(4) --> a(4) pathway reported previously in the literature (Vachet et al. J. Am. Chem. Soc.1997, 119, 5481, and Cooper et al. J. Am. Soc. Mass Spectrom.2006, 17, 1654). These mechanisms result in formally the same a(4) structures but differ in the position of the expelled nitrogen atom. Detailed analysis of the observed fragmentation patterns for the separated light and heavy a(4) ion fractions of ((15)N-F)GGFL indicates that the mechanism proposed by Cooper et al. is consistent with the experimental findings, while the mechanism proposed by Vachet et al. cannot account for the labeling data. In addition, a new rearrangement pathway is presented for a(4)-CO ions that effectively transfers the former C-terminal amino acid residue to the N-terminus. | 18,799,319 |
Bifurcating fragmentation behavior of gas-phase tryptic peptide dications in collisional activation. | Collision-activated dissociation (CAD) of tryptic peptides is a cornerstone of mass spectrometry-based proteomics research. Principal component analysis of a database containing 15,000 high-resolution CAD mass spectra of gas-phase tryptic peptide dications revealed that they fall into two classes with a good separation between the classes. The main factor determining the class identity is the relative abundance of the peptide bond cleavage after the first two N-terminal residues. A possible scenario explaining this bifurcation involves trans- to cis-isomerization of the N-terminal peptide bond, which facilitates solvation of the N-terminal charge on the second backbone amide and formation of stable b(2) ions in the form of protonated diketopiperazines. Evidence supporting this scenario is derived from statistical analysis of the high-resolution CAD MS/MS database. It includes the observation of the strong deficit of a(3) ions and anomalous amino acid preferences for b(2) ion formation. | 18,799,320 |
Ion trap collision-induced dissociation of multiply deprotonated RNA: c/y-ions versus (a-B)/w-ions. | The dissociation of model RNA anions has been studied as a function of anion charge state and excitation amplitude using ion trap collisional activation. Similar to DNA anions, the precursor ion charge state of an RNA anion plays an important role in directing the preferred dissociation channels. Generally, the complementary c/y-ions from 5' P-O bond cleavage dominate at low to intermediate charge states, while other backbone cleavages appear to a limited extent but increase in number and relative abundance at higher excitation energies. The competition between base loss, either as a neutral or as an anion, as well as the preference for the identity of the lost base are also observed to be charge-state dependent. To gain further insight into the partitioning of the dissociation products among the various possible channels, model dinucleotide anions have been subjected to a systematic study. In comparison to DNA, the 2'-OH group on RNA significantly facilitates the dissociation of the 5' P-O bond. However, the degree of excitation required for a 5' base loss and the subsequent 3' C-O bond cleavage are similar for the analogous RNA and DNA dinucleotides. Data collected for protonated dinucleotides, however, suggest that the 2'-OH group in RNA can stabilize the glycosidic bond of a protonated base. Therefore, base loss from low charge state oligonucleotide anions, in which protonation of one or more bases via intramolecular proton transfer can occur, may also be stabilized in RNA anions relative to corresponding DNA anions. | 18,799,321 |
The effect of the long head of the biceps on glenohumeral kinematics. | The long head of the biceps has been described as a stabilizing force in the setting of glenohumeral instability. However, data are lacking on the effect of loading the long head of the biceps on glenohumeral kinematics. Six cadaveric shoulders were tested for glenohumeral rotational range of motion and translation using a custom shoulder testing system and the Microscribe 3DLX (Immersion, San Jose, CA). The path of glenohumeral articulation (PGA) was measured by calculating the humeral head center with respect to the glenoid articular surface at maximal internal rotation, 30 degrees, 60 degrees, 90 degrees, and maximal external rotation. Significant decreases in glenohumeral rotational range of motion and translation were found with 22-N biceps loading vs the unloaded group. With respect to the PGA, the humeral rotation center was shifted posterior with biceps loading at maximal internal rotation, 30 degrees, and 60 degrees of external rotation. Loading the long head of the biceps significantly affects glenohumeral rotational range of motion, translations, and kinematics. | 18,799,325 |
Charcot-Marie-Tooth type 1a in a child with Long QT syndrome. | Charcot-Marie-Tooth disease (CMTD) is a hereditary demyelinating peripheral neuropathy clinically presenting with sensory and motor defects, but rarely affecting cardiac function. Long QT syndrome (LQTS) is a congenital or acquired cardiovascular disorder characterized by ventricular depolarization defect. No studies reported CMTD in association with LQTS. We describe a child and his family who had both CMT1A and LQTS. | 18,799,333 |
A microRNA expression ratio defining the invasive phenotype in bladder tumors. | The goal of this study was to identify a microRNA (miRNA) signature in bladder cancer capable of differentiating superficial from invasive disease. Expression profiling of 343 miRNAs was performed in a microarray format using noninvasive and invasive bladder carcinoma cell lines with differential expression confirmed using a single molecule detection platform assay. miR-21 and miR-205 expression levels were determined in 53 bladder tumors (28 superficial and 25 invasive). Sensitivity, specificity, and a ROC curve were calculated to determine the discriminatory power of the miRNA ratio to predict invasion. Knockdown and forced expression of miRNAs was performed to evaluate their role in invasion. Expression profiling of 343 miRNAs, using noninvasive and invasive bladder cell lines, revealed significant differential expression of 9 miRNAs. Cell lines characterized as invasive showed a miR-21:miR-205 ratio at least 10-fold higher than the quantitative ratio obtained from non-invasive cell lines. The same expression ratio was determined in 53 bladder tumors. From these results, we recorded a sensitivity and specificity of 100% and 78%, respectively, using a cutoff of 1.79 to predict an invasive lesion. The area under the receiver operator characteristic curve was 0.89. Using in vitro invasion assays, we have demonstrated a role for miR-21 in establishing the invasive phenotype of bladder carcinoma cells. In this study, we identified a miR-21:miR-205 expression ratio that has the ability to distinguish between invasive and noninvasive bladder tumors with high sensitivity and specificity, with the potential to identify superficial lesions at high risk to progress. | 18,799,331 |
High-flip-angle slice-selective parallel RF transmission with 8 channels at 7 T. | At high magnetic field, B(1)(+) non-uniformity causes undesired inhomogeneity in SNR and image contrast. Parallel RF transmission using tailored 3D k-space trajectory design has been shown to correct for this problem and produce highly uniform in-plane magnetization with good slice selection profile within a relatively short excitation duration. However, at large flip angles the excitation k-space based design method fails. Consequently, several large-flip-angle parallel transmission designs have recently been suggested. In this work, we propose and demonstrate a large-flip-angle parallel excitation design for 90 degrees and 180 degrees spin-echo slice-selective excitations that mitigate severe B(1)(+) inhomogeneity. The method was validated on an 8-channel transmit array at 7T using a water phantom with B(1)(+) inhomogeneity similar to that seen in human brain in vivo. Slice-selective excitations with parallel RF systems offer means to implement conventional high-flip excitation sequences without a severe pulse-duration penalty, even at very high B(0) field strengths where large B(1)(+) inhomogeneity is present. | 18,799,336 |
FT-IR spectroscopic investigation of ionic interactions in PPG 4000: AgCF3SO3 polymer electrolyte. | The effect of salt concentration on the ubiquitous ionic interactions observed in the case of the silver ion conducting polymer electrolyte system poly(propylene glycol) (PPG)-silver triflate has been investigated using Fourier transform infrared (FT-IR) spectroscopy as a probe for the characterization of the local environment of the triflate ion in PPG-based polymer electrolytes. The maximum free anion concentrations of symmetric and asymmetric SO(3) stretching modes in the case of poly(propylene glycol) complexed with silver triflate (AgCF(3)SO(3)) corresponding to the ether oxygen metal cation ratios from 2:1 to 6:1 have been investigated in detail. The present Fourier transform infrared spectral studies of the C-O-C stretching mode have shown reduction in the intensity, due to the decrease of salt concentration. The splitting of vibrational modes has been analyzed in terms of free ions, ion pairs and aggregates. The bands of SO(3) symmetric stretching mode appearing at 1032 and 1038 cm(-1) in the chosen polymer electrolyte material have been assigned to free ions and ion pairs respectively. | 18,799,349 |
Body mass index and quality of life: examining blacks and whites with chronic pain. | Obesity contributes to several chronic pain conditions, negatively affecting quality of life (QOL). However, obesity's relationship with chronic pain is poorly understood. This prospective survey study examines obesity's role in chronic pain and subsequent impact on QOL. Black and white patients with chronic pain (N = 183, 18-50 years of age, 64% women, 50% black) were studied to determine predictors for the presence of body mass index (BMI) information in medical records, group BMI differences, and how BMI and pain contribute to mental/physical outcomes. BMI was calculated by using medical records nearest the enrollment date. Sociodemographic data, sleep, pain, functioning, disability, and depression were measured. BMI data were available for 143 subjects (78%), with blacks having a higher BMI (P = .002). Black (P = .08), people with higher pain (P < .01), affective distress (P < .01), and post-traumatic stress disorder scores (P = .07) were less likely to have their BMI recorded. Path analysis tested relationships between sociodemographics, BMI and pain with functioning, depression, and disability. BMI was positively associated with black race and age and predicted poorer physical functioning and greater disability. Pain was not predicted by race or age but was associated with all outcomes. These findings support assessing BMI when managing chronic pain and its negative impact on QOL, especially for minority patients. This study examines the relationships among sociodemographic factors, BMI, and QOL in chronic pain. Our results demonstrate significant racial disparity among chronic pain patients in assessing BMI and quality of pain care. These findings support obesity's negative impact on overall health and the importance of measuring BMI in patients with chronic pain, especially racial and ethnic minorities. | 18,799,358 |
Prospective, randomized, pathologist-blinded study of disposable alligator-jaw biopsy forceps for gastric mucosal biopsy. | Endoscopic biopsy forceps differ in the size and shape of the biopsy cup and the presence or absence of a needle. We compared four different "large cup" forceps (three with needles) designed for 2.8mm biopsy channels. A gastric antral and corpus biopsy were obtained with each. Parameters examined included: weight (mg), length (mm), orientation (poor, good), intactness (1, 2, or 3 pieces), depth (superficial, above muscularis mucosae, included muscularis mucosae), crush artefact (yes, no), and overall adequacy (inadequate, suboptimal, adequate). Twenty-four patients were enrolled (191 biopsies). The median length was approximately 5mm (range 1.1-8.2mm). Histologically inadequate specimens were present in 4% with the forceps without needle compared to 16% of those with needles (P=0.061) and there were significantly fewer specimens in three or more pieces than did the forceps with needles 2.1% vs. 12.6% (P<0.05). Current alligator style forceps provide a high proportion of acceptable specimens with only minor differences between brands. Forceps from one source were least preferred by endoscopy assistants and had the highest rates of inadequate biopsies and biopsies with crush artefact. Forceps without needles provide histologically acceptable samples slightly more frequently than those with needles. | 18,799,373 |
Inferior gluteal artery perforator flap: a viable alternative for ischial pressure sores. | The ischial area is by far the most common site for pressure sores in wheelchair-bound paraplegic patients, because most of the pressure of the body is exerted on this area in the seated position. Even after a series of successful pressure sore treatments, the site is very prone to relapse from the simplest everyday tasks. Therefore, it is crucial to preserve the main pedicle during primary surgery. Several surgical procedures, such as myocutaneous flap and perforator flap, have been introduced for the treatment of pressure sores. During a 4-year time period at our institute, we found favourable clinical results using the inferior gluteal artery perforator (IGAP) procedure for ischial sore treatment. A total of 23 patients (20 males and three females) received IGAP flap surgery in our hospital from January 2003 to January 2007. Surgery was performed on the same site again in 10 (43%) patients who had originally relapsed after undergoing the conventional method of pressure sore surgery. The average age of patients was 47.4 years (range 26-71 years). Most of the patients were paraplegic (16 cases, 70%) and others were either quadriplegic (four cases, 17%) or ambulatory (three cases, 13%). Based on hospital records and clinical photographs, we attempted to assess the feasibility and practicability of the IGAP flap procedure through comparative analysis of several parameters including the size of the defective area, treatment modalities, relapses, complications, and postoperative treatments. The average follow-up duration for 23 subjects was 25.4 months (range 5-42 months). All flaps survived without major complications. Partial flap necrosis developed in one case but secondary healing was achieved and the final outcome was not impaired. Most of the cases healed well during the follow-up period. Postoperative complications such as wound dehiscence and fistula developed in some subjects, but all healed well with a secondary treatment. A total of five cases relapsed after surgery due to tissue deficit and these were treated with bursectomy and muscle transposition flap to fill the dead space. We propose that the IGAP flap should be considered a viable alternative to other methods of ischial pressure sore surgery owing to its many advantages, which include the ability to preserve peripheral muscle tissue, the variability of flap designs, relatively good durability, and the low donor site morbidity rate. | 18,799,379 |
[Metabolic imaging--PET, PET/CT--in oncologic surgery]. | The availability of PET/CT examinations in Hungary has significantly improved in the past few years. In the three Hungarian centres approximately 10,000 examinations can be performed yearly, which are financed by the national healthcare system. The PET/CT technique using FDG has become an efficient tumour diagnostic method due to its outstanding sensitivity and specificity. Similarly to other medical imaging techniques, PET/CT is a useful and cost-beneficial diagnostic modality in the hand of those clinicians, who clearly know its advantages and limitations. In the present paper the most frequent indications of PET/CT examinations are reviewed, with special attention to cases relevant to the everyday surgical practice. The applicability of this technique is also considered. | 18,799,405 |
[Enterobius vermicularis causing symptoms of acute appendicitis]. | The authors present a case of enterobiasis of the appendix. Enterobius infection is an uncommon cause of acute appendicitis. Preoperative diagnosis of pinworm infestation is almost impossible unless there is a strong clinical suspicion. Parasites may produce symptoms which resemble acute appendicitis. Careful observation of the appendix stump may lead to intraoperative diagnosis of enterobiasis. A quick diagnosis and appropriate treatment may prevent future complications. | 18,799,410 |
Investigating children as cultural magnets: do young children transmit redundant information along diffusion chains? | The primary goal of this study was to investigate cultural transmission in young children, with specific reference to the phenomenon of overimitation. Diffusion chains were used to compare the imitation of 2- and 3-year-olds on a task in which the initial child in each chain performed a series of relevant and irrelevant actions on a puzzle box in order to retrieve a reward. Children in the chains witnessed the actions performed on one of two boxes, one which was transparent and so the lack of causality of the irrelevant actions was obvious, while the other was opaque and so the lack of causal relevance was not obvious. Unlike previous dyadic research in which children overimitate a model, the irrelevant actions were parsed out early in the diffusion chains. Even though children parsed out irrelevant actions, they showed fidelity to the method used to perform a relevant action both within dyads and across groups. This was true of 3-year-olds, and also 2-year-olds, therefore extending findings from previous research. | 18,799,417 |
Blunted opiate modulation of hypothalamic-pituitary-adrenocortical activity in men and women who smoke. | To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers. Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test. Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers. We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers. | 18,799,426 |
Individual and neighborhood socioeconomic status characteristics and prevalence of metabolic syndrome: the Atherosclerosis Risk in Communities (ARIC) Study. | The objective of this study was to examine the association of individual socioeconomic status (iSES) and neighborhood SES (nSES) on the prevalence of metabolic syndrome (MetS) in the Atherosclerosis Risk in Communities Study (1987-1999). Participants included 2932 black and 9777 white men and women aged 45 to 64 years without diabetes at baseline. Total combined family income for the past 12 months and six census tract socioeconomic measures combined into a composite index were used to quantify iSES and nSES, respectively. Poisson regression was used to assess associations of the joint contribution of iSES and nSES on the MetS, stratified by gender and race and adjusting for multiple covariates. For analyses that included nSES, hierarchical modeling techniques were used. Using 2005 Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults criteria, MetS was identified in 40% of black women, 30% of white women, 28% of black men, and 35% of white men. Among black and white men, there was no association between MetS and iSES or nSES. In contrast, after adjustment for risk factors, black and white women with low (L)-iSES and medium (M)-iSES were more likely to have MetS than those with high (H)-iSES. Similar but weaker patterns were noted for L-nSES and M-nSES. In summary, both iSES and nSES were independently associated with an increased prevalence of MetS among women but not men. Efforts aimed at understanding the causes of these gender differences may offer insight into avenues for reducing the prevalence of the MetS and its chronic disease sequelae. | 18,799,428 |
Outcomes in adults with bicuspid aortic valves. | Bicuspid aortic valve is the most common congenital cardiac anomaly in the adult population. Cardiac outcomes in a contemporary population of adults with bicuspid aortic valve have not been systematically determined. To determine the frequency and predictors of cardiac outcomes in a large consecutive series of adults with bicuspid aortic valve. Cohort study examining cardiac outcomes in 642 consecutive ambulatory adults (mean [SD] age, 35 [16] years; 68% male) with bicuspid aortic valve presenting to a Canadian congenital cardiac center from 1994 through 2001 and followed up for a mean (SD) period of 9 (5) years. Frequency and predictors of major cardiac events were determined by multivariate analysis. Mortality rate in the study group was compared with age- and sex-matched population estimates. Mortality and cause of death were determined. Primary cardiac events were defined as the occurrence of any of the following complications: cardiac death, intervention on the aortic valve or ascending aorta, aortic dissection or aneurysm, or congestive heart failure requiring hospital admission during the follow-up period. During the follow-up period, there were 28 deaths (mean [SD], 4% [1%]). One or more primary cardiac events occurred in 161 patients (mean [SD], 25% [2%]), which included cardiac death in 17 patients (mean [SD], 3% [1%]), intervention on aortic valve or ascending aorta in 142 patients (mean [SD], 22% [2%]), aortic dissection or aneurysm in 11 patients (mean [SD], 2% [1%]), or congestive heart failure requiring hospital admission in 16 patients (mean [SD], 2% [1%]). Independent predictors of primary cardiac events were age older than 30 years (hazard ratio [HR], 3.01; 95% confidence interval [CI], 2.15-4.19; P<.001), moderate or severe aortic stenosis (HR, 5.67; 95% CI, 4.16-7.80; P<.001), and moderate or severe aortic regurgitation (HR, 2.68; 95% CI, 1.93-3.76; P<.001). The 10-year survival rate of the study group (mean [SD], 96% [1%]) was not significantly different from population estimates (mean [SD], 97% [1%]; P = .71). At last follow-up, 280 patients (mean [SD], 45% [2%]) had dilated aortic sinus and/or ascending aorta. In this study population of young adults with bicuspid aortic valve, age, severity of aortic stenosis, and severity of aortic regurgitation were independently associated with primary cardiac events. Over the mean follow-up duration of 9 years, survival rates were not lower than for the general population. | 18,799,444 |
Antibody-mediated targeting of the urokinase-type plasminogen activator proteolytic function neutralizes fibrinolysis in vivo. | Urokinase-type plasminogen activator (uPA) plays a central role in tissue remodeling processes. Most of our understanding of the role of uPA in vivo is derived from studies using gene-targeted uPA-deficient mice. To enable in vivo studies on the specific interference with uPA functionality in mouse models, we have now developed murine monoclonal antibodies (mAbs) directed against murine uPA by immunization of uPA-deficient mice with the recombinant protein. Guided by enzyme-linked immunosorbent assay, Western blotting, surface plasmon resonance, and enzyme kinetic analyses, we have selected two highly potent and inhibitory anti-uPA mAbs (mU1 and mU3). Both mAbs recognize epitopes located on the B-chain of uPA that encompasses the catalytic site. In enzyme activity assays in vitro, mU1 blocked uPA-catalyzed plasminogen activation as well as plasmin-mediated pro-uPA activation, whereas mU3 only was directed against the first of these reactions. We additionally provide evidence that mU1, but not mU3, successfully targets uPA-dependent processes in vivo. Hence, systemic administration of mU1 (i) rescued mice treated with a uPA-activable anthrax protoxin and (ii) impaired uPA-mediated hepatic fibrinolysis in tissue-type plasminogen activator (tPA)-deficient mice, resulting in a phenotype mimicking that of uPA;tPA double deficient mice. Importantly, this is the first report demonstrating specific antagonist-directed targeting of mouse uPA at the enzyme activity level in a normal physiological process in vivo. | 18,799,467 |
Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin. | Myotendinous strain injury is the most common injury of human skeletal muscles because the majority of muscle forces are transmitted through this region. Although the immediate response to strain injury is well characterized, the chronic response to myotendinous strain injury is less clear. Here we examined the molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a microdystrophin transgene (microdystrophin(DeltaR4-R23)). We found that muscles with myotendinous strain injury had an increased expression of utrophin and alpha7-integrin together with the dramatic restructuring of peripheral myofibrils into concentric rings. The sarcolemma of the microdystrophin(DeltaR4-R23)/mdx gastrocnemius muscles was highly protected from experimental lengthening contractions, better than wild-type muscles. We also found a positive correlation between myotendinous strain injury and ringed fibers in the HSA(LR) (human skeletal actin, long repeat) mouse model of myotonic dystrophy. We suggest that changes in protein expression and the formation of rings are adaptations to myotendinous strain injury that help to prevent muscle necrosis and retain the function of necessary muscles during injury, ageing and disease. | 18,799,475 |
Identification of Arx transcriptional targets in the developing basal forebrain. | Mutations in the aristaless-related homeobox (ARX) gene are associated with multiple neurologic disorders in humans. Studies in mice indicate Arx plays a role in neuronal progenitor proliferation and development of the cerebral cortex, thalamus, hippocampus, striatum, and olfactory bulbs. Specific defects associated with Arx loss of function include abnormal interneuron migration and subtype differentiation. How disruptions in ARX result in human disease and how loss of Arx in mice results in these phenotypes remains poorly understood. To gain insight into the biological functions of Arx, we performed a genome-wide expression screen to identify transcriptional changes within the subpallium in the absence of Arx. We have identified 84 genes whose expression was dysregulated in the absence of Arx. This population was enriched in genes involved in cell migration, axonal guidance, neurogenesis, and regulation of transcription and includes genes implicated in autism, epilepsy, and mental retardation; all features recognized in patients with ARX mutations. Additionally, we found Arx directly repressed three of the identified transcription factors: Lmo1, Ebf3 and Shox2. To further understand how the identified genes are involved in neural development, we used gene set enrichment algorithms to compare the Arx gene regulatory network (GRN) to the Dlx1/2 GRN and interneuron transcriptome. These analyses identified a subset of genes in the Arx GRN that are shared with that of the Dlx1/2 GRN and that are enriched in the interneuron transcriptome. These data indicate Arx plays multiple roles in forebrain development, both dependent and independent of Dlx1/2, and thus provides further insights into the understanding of the mechanisms underlying the pathology of mental retardation and epilepsy phenotypes resulting from ARX mutations. | 18,799,476 |
Fewer partners or more condoms? Modelling the effectiveness of STI prevention interventions. | Some advocates of HIV prevention have counterposed programmes aimed at reducing numbers of sex partners to programmes aimed at increasing condom use. In this polarised debate, arguments about their relative effectiveness have been based on limited evidence. To explore the theoretical impact of changing partner acquisition rates and condom use on the population level incidence of sexually transmitted infections different in different populations. A standard deterministic compartmental model of the transmission dynamics of a sexually transmitted disease is solved numerically. The change in behaviour required to prevent a single case of infection is calculated for a range of scenarios. When the transmission probability per sex act is low across partnerships, the incidence of infection responds similarly to changes in partner numbers and numbers of unprotected sex acts. High transmission probabilities alter the relationships, with the effectiveness of increasing condom use improving as the background number of unprotected sex acts decreases. The divergence in patterns of impact is marked when there is heterogeneity in the transmission probability per act across partnerships. Both reducing numbers of sex partners and increasing condom use can lower the incidence of sexually transmitted infections. Unfortunately, there is no simple and general rule that will allow the efficiency of interventions to be calculated. Heterogeneity in transmission probability across infections, which may occur for both bacterial and viral infections, can reduce the effectiveness of condom use as an intervention if that use is inconsistent. | 18,799,491 |
Interpreting declines in HIV prevalence: impact of spatial aggregation and migration on expected declines in prevalence. | Declines in the prevalence of HIV might occur due to natural epidemic dynamics rather than changes in risk behaviour. Determining the cause of an observed decline is important in understanding the epidemiology of HIV. To explore how patterns of recruitment and interactions between subpopulations in different areas influence the predicted decline in the prevalence of HIV in the absence of reductions in risk behaviour. A deterministic mathematical model of the heterosexual transmission of HIV in high prevalence endemic settings incorporating various patterns of recruitment to high-risk behaviour groups, population growth and migration was solved numerically. The possibility that apparent trends are generated or obscured through aggregating data from across areas experiencing different epidemics is also considered. Declines in the prevalence of HIV can occur even if individuals do not change behaviour, raising the possibility that epidemic downturns could be wrongly attributed to interventions. This effect is greatest when individuals do not enter higher risk groups to compensate for reductions in size caused by deaths from AIDS and when migration is non-random with respect to risk or infectious status and migration patterns change as the epidemic matures. In contrast, aggregating prevalence data from subregions with different epidemic profiles tends to mask declines in prevalence. Interpreting surveillance data is important in understanding widespread responses to HIV epidemics. The results show that understanding patterns of adoption of risk behaviours and patterns of migration is important in interpreting declines in the prevalence of HIV. | 18,799,492 |
Numb mediates the interaction between Wnt and Notch to modulate primitive erythropoietic specification from the hemangioblast. | During embryonic development, the establishment of the primitive erythroid lineage in the yolk sac is a temporally and spatially restricted program that defines the onset of hematopoiesis. In this report, we have used the embryonic stem cell differentiation system to investigate the regulation of primitive erythroid development at the level of the hemangioblast. We show that the combination of Wnt signaling with inhibition of the Notch pathway is required for the development of this lineage. Inhibition of Notch signaling at this stage appears to be mediated by the transient expression of Numb in the hemangioblast-derived blast cell colonies. Activation of the Notch pathway was found to inhibit primitive erythropoiesis efficiently through the upregulation of inhibitors of the Wnt pathway. Together, these findings demonstrate that specification of the primitive erythroid lineage is controlled, in part, by the coordinated interaction of the Wnt and Notch pathways, and position Numb as a key mediator of this process. | 18,799,543 |
Crystal structure of the avian reovirus inner capsid protein sigmaA. | Avian reovirus, an important avian pathogen, expresses eight structural and four nonstructural proteins. The structural sigmaA protein is a major component of the inner capsid, clamping together lambdaA building blocks. sigmaA has also been implicated in the resistance of avian reovirus to the antiviral action of interferon by strongly binding double-stranded RNA in the host cell cytoplasm and thus inhibiting activation of the double-stranded RNA-dependent protein kinase. We have solved the structure of bacterially expressed sigmaA by molecular replacement and refined it using data to 2.3-A resolution. Twelve sigmaA molecules are present in the P1 unit cell, arranged as two short double helical hexamers. A positively charged patch is apparent on the surface of sigmaA on the inside of this helix and mutation of either of two key arginine residues (Arg155 and Arg273) within this patch abolishes double-stranded RNA binding. The structural data, together with gel shift assay, electron microscopy, and sedimentation velocity centrifugation results, provide evidence for cooperative binding of sigmaA to double-stranded RNA. The minimal length of double-stranded RNA required for sigmaA binding was observed to be 14 to 18 bp. | 18,799,570 |
Identification and characterization of PWWP domain residues critical for LEDGF/p75 chromatin binding and human immunodeficiency virus type 1 infectivity. | Lens epithelium-derived growth factor (LEDGF)/p75 functions as a bimodal tether during lentiviral DNA integration: its C-terminal integrase-binding domain interacts with the viral preintegration complex, whereas the N-terminal PWWP domain can bind to cellular chromatin. The molecular basis for the integrase-LEDGF/p75 interaction is understood, while the mechanism of chromatin binding is unknown. The PWWP domain is homologous to other protein interaction modules that together comprise the Tudor clan. Based on primary amino acid sequence and three-dimensional structural similarities, 24 residues of the LEDGF/p75 PWWP domain were mutagenized to garner essential details of its function during human immunodeficiency virus type 1 (HIV-1) infection. Mutating either Trp-21 or Ala-51, which line the inner wall of a hydrophobic cavity that is common to Tudor clan members, disrupts chromatin binding and virus infectivity. Consistent with a role for chromatin-associated LEDGF/p75 in stimulating integrase activity during infection, recombinant W21A protein is preferentially defective for enhancing integration into chromatinized target DNA in vitro. The A51P mutation corresponds to the S270P change in DNA methyltransferase 3B that causes human immunodeficiency, centromeric instability, and facial anomaly syndrome, revealing a critical role for this amino acid position in the chromatin binding functions of varied PWWP domains. Our results furthermore highlight the requirement for a conserved Glu in the hydrophobic core that mediates interactions between other Tudor clan members and their substrates. This initial systematic mutagenesis of a PWWP domain identifies amino acid residues critical for chromatin binding function and the consequences of their changes on HIV-1 integration and infection. | 18,799,576 |
Baseline resistance of primary human immunodeficiency virus type 1 strains to the CXCR4 inhibitor AMD3100. | We screened a panel of R5X4 and X4 human immunodeficiency virus type 1 (HIV-1) strains for their sensitivities to AMD3100, a small-molecule CXCR4 antagonist that blocks HIV-1 infection via this coreceptor. While no longer under clinical development, AMD3100 is a useful tool with which to probe interactions between the viral envelope (Env) protein and CXCR4 and to identify pathways by which HIV-1 may become resistant to this class of antiviral agents. While infection by most virus strains was completely blocked by AMD3100, we identified several R5X4 and X4 isolates that exhibited plateau effects: as the AMD3100 concentration was increased, virus infection and membrane fusion diminished to variable degrees. Once saturating concentrations of AMD3100 were achieved, further inhibition was not observed, indicating a noncompetitive mode of viral resistance to the drug. The magnitude of the plateau varied depending on the virus isolate, as well as the cell type used, with considerable variation observed when primary human T cells from different human donors were used. Structure-function studies indicated that the V1/V2 region of the R5X4 HIV-1 isolate DH12 was necessary for AMD3100 resistance and could confer this property on two heterologous Env proteins. We conclude that some R5X4 and X4 HIV-1 isolates can utilize the AMD3100-bound conformation of CXCR4, with the efficiency being influenced by both viral and host factors. Baseline resistance to this CXCR4 antagonist could influence the clinical use of such compounds. | 18,799,588 |
Dynamic translation of surface coarseness into whisker vibrations. | Rodents in their natural environment use their whiskers to distinguish between surfaces having subtly different textures and shapes. They do so by actively sweeping their whiskers across surfaces in a rhythmic motion. To determine how textures are transformed into vibration signals in whiskers and how these vibrations are expressed in neuronal discharges, we induced active whisking in anesthetized rats, monitored the movement of whiskers across surfaces, and concurrently recorded from trigeminal ganglion (TG) neurons. We show that tactile information is transmitted through high-frequency micromotions superimposed on whisking macro motions. Consistent with this, we find that in most TG neurons, spike activity, and high-frequency micromotions are closely correlated. To determine whether these vibration signals can support texture discrimination, we examined their dependence on surface roughness and found that both vibration signals carry information about surface coarseness. Despite a large variability in this translation process, different textures are translated into distinct vibrations profiles. These profiles depend on whiskers properties, on radial distance to the surface, and on whisking frequency. Using the characteristics of these signals, we employ linear discriminant analysis and found that all whiskers were able to discriminate between different textures. While deteriorating with radial distance, this classification did not depend on whisking frequency. Finally, increasing the number of whisks and integrating tactile information from multiple whiskers improved texture discrimination. These results indicate that surface roughness is translated into distinct whisker vibration signals that result in neuronal discharges. However, due to the dynamic nature of this translation process, we propose that texture discrimination may require the integration of signals from multiple spatial and temporal sensory channels to disambiguate surface roughness. | 18,799,602 |
Cardiolipin mediates cross-talk between mitochondria and the vacuole. | Cardiolipin (CL) is an anionic phospholipid with a dimeric structure predominantly localized in the mitochondrial inner membrane, where it is closely associated with mitochondrial function, biogenesis, and genome stability (Daum, 1985; Janitor and Subik, 1993; Jiang et al., 2000; Schlame et al., 2000; Zhong et al., 2004). Previous studies have shown that yeast mutant cells lacking CL due to a disruption in CRD1, the structural gene encoding CL synthase, exhibit defective colony formation at elevated temperature even on glucose medium (Jiang et al., 1999; Zhong et al., 2004), suggesting a role for CL in cellular processes apart from mitochondrial bioenergetics. In the current study, we present evidence that the crd1Delta mutant exhibits severe vacuolar defects, including swollen vacuole morphology and loss of vacuolar acidification, at 37 degrees C. Moreover, vacuoles from crd1Delta show decreased vacuolar H(+)-ATPase activity and proton pumping, which may contribute to loss of vacuolar acidification. Deletion mutants in RTG2 and NHX1, which mediate vacuolar pH and ion homeostasis, rescue the defective colony formation phenotype of crd1Delta, strongly suggesting that the temperature sensitivity of crd1Delta is a consequence of the vacuolar defects. Our results demonstrate the existence of a novel mitochondria-vacuole signaling pathway mediated by CL synthesis. | 18,799,619 |
Health seeking for ambiguous symptoms in two cultural groups: a comparative study. | This study examined cultural differences in health seeking for medically ambiguous symptoms in women from two culturally diverse communities. Thirty-five South Asian immigrants and 36 European Americans participated in a health history interview. Though the types and relative frequencies of practices were similar across the two groups, the goals and underlying logic supporting practices differed sharply. Among European Americans, practices were focused on the need to increase energy, creativity, and output; among South Asians, practices emphasized storing up strength through increased consumption or reduced expenditure. We conclude that the relationship between conceptual models of cause and cure depends on the ;match' of both to broader, unarticulated cultural models of health and illness. | 18,799,641 |
Evaluation of a commercial Echinococcus Western Blot assay for serological follow-up of patients with alveolar echinococcosis. | A total of 20 patients with alveolar echinococcosis in different clinical stages according to the WHO-PNM staging system (P, parasitic mass in the liver; N, involvement of neighboring organs; M, metastasis) were followed up serologically with the commercial Echinococcus Western Blot IgG assay and a crude antigen extract enzyme-linked immunosorbent assay (ELISA). The cohort included patients after curative resection and patients who had unresectable lesions with stable disease or progressive infection. There were visible correlations of the crude antigen ELISA index and the presence and intensity of diagnostic bands in the Western blot. In most patients after curative resection, bands at 7, 16, and 18 kDa markedly decreased or vanished after 1 to 4 years. In a patient with a nonviable lesion (it died out), bands at 16 and 18 kDa vanished after 4 years. Among individuals with unresectable lesions but stable disease under antiparasitic chemotherapy, a decrease of all diagnostic bands was visible after 2 to 3 years in half of the patients, whereas the other half had unchanged blot results after 4 to 6 years. Patients with progressive disease showed increasing intensities of bands at 16, 18, and 7 kDa. The change of banding patterns was not influenced by the PNM stage in patients after curative surgery or with unresectable lesions. Our data indicate a correlation of the 7-, 16-, and 18-kDa-Western blot bands with disease activity independent of the PNM stage. This study demonstrated the usefulness of the Echinococcus Western Blot IgG assay as an additional serological test for the follow-up of patients with alveolar echinococcosis. | 18,799,646 |
Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork. | Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, is poorly understood. The role of RhoA GTPase-mediated actomyosin organization, cell adhesive interactions, and gene expression in regulation of aqueous humor outflow was investigated using adenoviral vector-driven expression of constitutively active mutant of RhoA (RhoAV14). Organ-cultured anterior segments from porcine eyes expressing RhoAV14 exhibited significant reduction of aqueous humor outflow. Cultured TM cells expressing RhoAV14 exhibited a pronounced contractile morphology, increased actin stress fibers, and focal adhesions and increased levels of phosphorylated myosin light chain (MLC), collagen IV, fibronectin, and laminin. cDNA microarray analysis of RNA extracted from RhoAV14-expressing human TM cells revealed a significant increase in the expression of genes encoding extracellular matrix (ECM) proteins, cytokines, integrins, cytoskeletal proteins, and signaling proteins. Conversely, various ECM proteins stimulated robust increases in phosphorylation of MLC, paxillin, and focal adhesion kinase and activated Rho GTPase and actin stress fiber formation in TM cells, indicating a potential regulatory feedback interaction between ECM-induced mechanical strain and Rho GTPase-induced isometric tension in TM cells. Collectively, these data demonstrate that sustained activation of Rho GTPase signaling in the aqueous humor outflow pathway increases resistance to aqueous humor outflow through the trabecular pathway by influencing the actomyosin assembly, cell adhesive interactions, and the expression of ECM proteins and cytokines in TM cells. | 18,799,648 |
Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling. | The actin cytoskeleton regulates exocytosis in all secretory cells. In neutrophils, Rac2 GTPase has been shown to control primary (azurophilic) granule exocytosis. In this report, we propose that Rac2 is required for actin cytoskeletal remodeling to promote primary granule exocytosis. Treatment of neutrophils with low doses (< or = 10 microM) of the actin-depolymerizing drugs latrunculin B (Lat B) or cytochalasin B (CB) enhanced both formyl peptide receptor- and Ca(2+) ionophore-stimulated exocytosis. Higher concentrations of CB or Lat B, or stabilization of F-actin with jasplakinolide (JP), inhibited primary granule exocytosis measured as myeloperoxidase release but did not affect secondary granule exocytosis determined by lactoferrin release. These results suggest an obligatory role for F-actin disassembly before primary granule exocytosis. However, lysates from secretagogue-stimulated neutrophils showed enhanced actin polymerization activity in vitro. Microscopic analysis showed that resting neutrophils contain significant cortical F-actin, which was redistributed to sites of primary granule translocation when stimulated. Exocytosis and actin remodeling was highly polarized when cells were primed with CB; however, polarization was reduced by Lat B preincubation, and both polarization and exocytosis were blocked when F-actin was stabilized with JP. Treatment of cells with the small molecule Rac inhibitor NSC23766 also inhibited actin remodeling and primary granule exocytosis induced by Lat B/fMLF or CB/fMLF, but not by Ca(2+) ionophore. Therefore, we propose a role for F-actin depolymerization at the cell cortex coupled with Rac-dependent F-actin polymerization in the cell cytoplasm to promote primary granule exocytosis. | 18,799,653 |
A stress-inducible resveratrol O-methyltransferase involved in the biosynthesis of pterostilbene in grapevine. | Stilbenes are considered the most important phytoalexin group in grapevine (Vitis vinifera) and they are known to contribute to the protection against various pathogens. The main stilbenes in grapevine are resveratrol and its derivatives and, among these, pterostilbene has recently attracted much attention due both to its antifungal and pharmacological properties. Indeed, pterostilbene is 5 to 10 times more fungitoxic than resveratrol in vitro and recent studies have shown that pterostilbene exhibits anticancer, hypolipidemic, and antidiabetic properties. A candidate gene approach was used to identify a grapevine resveratrol O-methyltransferase (ROMT) cDNA and the activity of the corresponding protein was characterized after expression in Escherichia coli. Transient coexpression of ROMT and grapevine stilbene synthase in tobacco (Nicotiana benthamiana) using the agroinfiltration technique resulted in the accumulation of pterostilbene in tobacco tissues. Taken together, these results showed that ROMT was able to catalyze the biosynthesis of pterostilbene from resveratrol both in vitro and in planta. ROMT gene expression in grapevine leaves was induced by different stresses, including downy mildew (Plasmopara viticola) infection, ultraviolet light, and AlCl(3) treatment. | 18,799,660 |
Fidelity of complex spike-mediated synaptic transmission between inhibitory interneurons. | Complex spikes are high-frequency bursts of Na+ spikes, often riding on a slower Ca2+-dependent waveform. Although complex spikes may propagate into axons, given their unusual shape it is not clear how reliably these bursts reach nerve terminals, whether their spikes are efficiently transmitted as a cluster of postsynaptic responses, or what function is served by such a concentrated postsynaptic signal. We examined these questions by recording from synaptically coupled pairs of cartwheel cells, neurons which fire complex spikes and form an inhibitory network in the dorsal cochlear nucleus. Complex spikes in the presynaptic soma were reliably propagated to nerve terminals and elicited powerful, temporally precise postsynaptic responses. Single presynaptic neurons could prevent their postsynaptic partner from firing complex but not simple spikes, dramatically reducing dendritic Ca2+ signals in the postsynaptic neuron. We suggest that rapid transmission of complex spikes may control the susceptibility of neighboring neurons to Ca2+-dependent plasticity. | 18,799,676 |
Growth of white matter in the adolescent brain: role of testosterone and androgen receptor. | The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath. | 18,799,683 |
Sympathetic activation in chronic renal failure. | The potential involvement of sympathetic overactivity has been neglected in this population despite accumulating experimental and clinical evidence suggesting a crucial role of sympathetic activation for both progression of renal failure and the high rate of cardiovascular events in patients with chronic kidney disease. The contribution of sympathetic neural mechanisms to the occurrence of cardiac arrhythmias, the development of hypertension, and the progression of heart failure are well established; however, the exact mechanisms contributing to heightened sympathetic tone in patients with chronic kidney disease are unclear. This review analyses potential mechanisms underlying sympathetic activation in chronic kidney disease, the range of adverse consequences associated with this activation, and potential therapeutic implications resulting from this relationship. | 18,799,718 |
FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging. | Stress or aging of tissue-specific stem cells is considered central to the decline of tissue homeostasis in the elderly, although little is known of molecular mechanisms underlying hematopoietic stem cell (HSC) aging and stress resistance. Here, we report that mice lacking the transcription factor forkhead box O3a (FoxO3a) develop neutrophilia associated with inhibition of the up-regulation of negative regulator of cell proliferation, Sprouty-related Ena/VASP homology 1 domain-containing proteins 2 (Spred2) and AKT and ERK activation, in HSCs during hematopoietic recovery following myelosuppressive stress conditions. Compared with aged wild-type mice, more severe neutrophilia was also observed in aged Foxo3a-deficient mice. AKT and ERK activation and inhibition of Spred2 were detected in HSCs from aged FoxO3a-deficient mice. Spred2-deficient mice also developed neutrophilia during hematopoietic recovery following myelosuppressive stress, indicating that FoxO3a plays a pivotal role in maintenance, integrity, and stress resistance of HSCs through negative feedback pathways for proliferation. This will provide new insight into the hematopoietic homeostasis in conditions of aging and stress. | 18,799,725 |
Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function. | Down-regulation of the forkhead transcription factor Foxp1 by integrin engagement controls monocyte differentiation in vitro. To determine whether Foxp1 plays a critical role in monocyte differentiation and macrophage functions in vivo, we generated transgenic mice (macFoxp1tg) overexpressing human FOXP1 in monocyte/macrophage lineage cells using the CD68 promoter. Circulating blood monocytes from macFoxp1tg mice have reduced expression of the receptor for macrophage colony-stimulating factor (c-Fms/M-CSFR), impaired migratory capacity, and diminished accumulation as splenic macrophages. Macrophage functions, including cytokine production, phagocytosis, and respiratory burst were globally impaired in macFoxp1tg compared with wild-type cells. Osteoclastogenesis and bone resorption activity were also attenuated in macFoxp1tg mice. In models of chemical and bacterial peritonitis, macFoxp1tg mice exhibited reduced macrophage accumulation, bacterial clearance, and survival. Enforced overexpression of c-Fms/M-CSFR reversed the cytokine production and phagocytosis defects in macFoxp1tg macrophages, indicating that repression of c-fms/M-CSFR is likely the dominant mechanism responsible for Foxp1 action in monocyte differentiation and macrophage function. Taken together, these observations identify down-regulation of Foxp1 as critical for monocyte differentiation and macrophage functions in vivo. | 18,799,727 |
Bill Kane passionate practitioner. | William "Bill" M. Kane, PhD, CHES. William "Bill" M. Kane, PhD, CHES, was a man with public health credentials that could impress just about anyone. He served as executive director of both the American College of Preventive Medicine and the Association for the Advancement of Health Education. He was a professor of health education at the University of New Mexico, and taught at several other colleges and universities over the course of his career. He spent time as director of school health programs at ETR Associates, and served on the boards of several nonprofit organizations devoted to public health and health education. He received many honors, and wrote or coauthored over 50 books and curricula focused on health. Bill Kane was undoubtedly a man who got a lot done. But, even more important for those of us who work in public health, he remains a consummate model of how to do this work with passion. | 18,799,766 |
Neighborhoods and obesity in later life. | We examined the influence of neighborhood environment on the weight status of adults 55 years and older. We conducted a 2-level logistic regression analysis of data from the 2002 wave of the Health and Retirement Study. We included 8 neighborhood scales: economic advantage, economic disadvantage, air pollution, crime and segregation, street connectivity, density, immigrant concentration, and residential stability. When we controlled for individual- and family-level confounders, living in a neighborhood with a high level of economic advantage was associated with a lower likelihood of being obese for both men (odds ratio [OR] = 0.86; 95% confidence interval [CI] = 0.80, 0.94) and women (OR = 0.83; 95% CI = 0.77, 0.89). Men living in areas with a high concentration of immigrants and women living in areas of high residential stability were more likely to be obese. Women living in areas of high street connectivity were less likely to be overweight or obese. The mechanisms by which neighborhood environment and weight status are linked in later life differ by gender, with economic and social environment aspects being important for men and built environment aspects being salient for women. | 18,799,770 |
Quantitative tissue and gene-specific differences and developmental changes in Nat1, Nat2, and Nat3 mRNA expression in the rat. | Human N-acetyltransferase 1 (NAT1) and 2 (NAT2) are important phase II enzymes involved in the biotransformation of xenobiotics. In toxicity and carcinogenicity studies, functional polymorphism of rat N-acetyltransferase is considered a model for similar human variability. To accurately quantitate expression of the three rat N-acetyltransferases, we developed sensitive, specific assays for Nat1, Nat2, and Nat3 mRNAs. In male F344 rats, tissue-specific expression varied over a limited range for both Nat1 (approximately 19-fold) and Nat2 (approximately 30-fold), with the highest expression of both genes in colon. Expression of Nat3 mRNA was at least 2 to 3 orders of magnitude less than that of Nat1 or Nat2. Comparison of Nat1 and Nat2 mRNA expression in bladder, colon, liver, and lung of male and female F344 rats detected no significant gender-specific difference. In Sprague-Dawley and F344 rats ranging in age from neonate to mature adult, colon showed a >10-fold increase in Nat2 during the first postnatal month that did not correlate with changes in Nat1. In contrast, Nat2 showed no developmental change in Sprague-Dawley or F344 liver as Nat1 increased modestly. These measures of rat Nat expression confirm that Nat3 expression is negligible and that Nat1 and Nat2 are the primary determinants of arylamine acetylation activity in all tissues tested. The findings demonstrate differential tissue-specific and developmental regulation of the rat Nat1 and Nat2 genes and contribute to more complete understanding of tissue-, gender-, and development-specific expression patterns of the cognate N-acetyltransferase genes of humans and other species. | 18,799,802 |
Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs. | Secondary metabolites of Solanaceae plants, sharing tropane skeleton as a common structural feature, are sharply divided into two classes: tropine and ecgonine derivatives. The first group, represented by well known alkaloids: atropine and scopolamine, which are considered to be model anticholinergic drugs, continues to provide inspiration in the search for more selective muscarinic receptor antagonists. The second class accommodates one of the principal drugs of abuse, cocaine. Synthesis of much needed cocaine antagonists, despite extensive research, has not been particularly successful. Therefore, new concepts of cocaine abuse treatment resort to immunotherapy and biotechnology. Contemporary pharmaceutical industry manufactures over 20 active pharmaceutical substances containing tropane moiety in their structure, which are applied as mydriatics, antiemetics, antispasmodics, anesthetics and bronchodilators. There are two sources of raw materials for this industrial activity: natural products isolated from cultivated transgenic plants (mainly scopolamine and atropine from Australian Duboisia) and chemical synthesis based on common intermediate: tropinone, which can be further transformed by synthetic means to the following classes of compounds: tropine and its esters (tropeines), scopine and nortropine derivatives, and tropane quaternary ammonium salts. This survey focuses on new developments in chemistry and pharmacology of tropane derivatives, particularly in view of their prospective industrial applications as therapeutics. | 18,799,813 |
CPU0213, a novel endothelin receptor antagonist, suppresses the upregulation of matrix metalloproteinases and connexin 43 in hyperthyroid myocardium. | It has been verified that endothelin-1 (ET-1) activates matrix metalloproteinase (MMP) in the process of myocardial remodeling. Sustained high thyroid hormone level gives rise to left ventricular hypertrophy, in which the ET-1 system is probably involved.We attempted to study the effects of CPU0213, a novel endothelin receptor antagonist, on myocardial remodeling induced by high dose L-thyroxin. Adult male Sprague-Dawley rats were treated with L-thyroxin (0.4 mg/kg/d, sc) for 10 days to induce left ventricular hypertrophy. Asubset of rats was given CPU0213 from day 6 to 10. Alterations in MMP, tissue inhibitor of metalloproteinase (TIMP), and connexin 43 were measured by reverse transcription polymerase chain reaction (RT-PCR), zymography, and Western blot assays. L-thyroxin treatment resulted in increased mRNA expression and MMP-2 and MMP-9 activities, along with decreased TIMP-1 and TIMP-2 mRNA expression. CPU0213 suppressed the increased activity of MMP, and prevented the downregulation of TIMP expression. The expression of connexin 43 was upregulated at both mRNAand protein levels after L-thyroxin treatment, which was attenuated by CPU0213. In addition, L-thyroxin caused upregulation of mRNA expression of preproET-1 (ppET-1) and endothelin converting enzyme (ECE). These results suggest that the ET receptors mediate high dose L-thyroxin induced myocardial remodeling by changing MMP, TIMP activities and connexin 43. | 18,799,821 |
Serum and intraerythrocyte antioxidant enzymes and lipid peroxides in children with migraine. | The oxidant-antioxidant balance disorders underlie a number of acute and chronic diseases of the central nervous system (CNS). It is believed that oxidative stress plays a role in the pathogenesis of migraine. The study objective was to assess the processes of lipid peroxidation with malondialdehyde (MDA) as its major indicator and to determine the activities of antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R) in the serum and erythrocytes of patients at developmental age with migraine with and without aura. The study group consisted of 34 patients at the age of 10-18 years (mean +/- standard deviation: 14.04 +/- 2.29 years), suffering from migraine. The control group included 38 patients, aged 4-17 years (mean age 12.11 +/- 3.46). MDA concentration and activities of SOD, GSH-Px and GSSG-R were determined in serum and erythrocytes of all the patients. In the migraine group, the MDA levels in serum and erythrocytes were statistically significantly lower than in control subjects (p < 0.001). In the migraine group, serum GSH-Px activity was significantly higher (p < 0.05). The GSSG-R activity in the erythrocytes of migraine children was significantly higher compared to controls (p < 0.001). SOD activity was decreased and GSH-Px was increased (non-significantly) in erythrocytes of migraineurs. Our results confirm the disturbances of lipid peroxidation processes in migraine and suggest the activation of antioxidant mechanisms. Its important indicator seems to be the increase in the GSSG-R activity in the erythrocytes and the GSH-Px activity in serum between migraine attacks. Further studies are necessary. | 18,799,823 |
Energy-resolved computed tomography: first experimental results. | First experimental results with energy-resolved computed tomography (CT) are reported. The contrast-to-noise ratio (CNR) in CT has been improved with x-ray energy weighting for the first time. Further, x-ray energy weighting improved the CNR in material decomposition CT when applied to CT projections prior to dual-energy subtraction. The existing CT systems use an energy (charge) integrating x-ray detector that provides a signal proportional to the energy of the x-ray photon. Thus, the x-ray photons with lower energies are scored less than those with higher energies. This underestimates contribution of lower energy photons that would provide higher contrast. The highest CNR can be achieved if the x-ray photons are scored by a factor that would increase as the x-ray energy decreases. This could be performed by detecting each x-ray photon separately and measuring its energy. The energy selective CT data could then be saved, and any weighting factor could be applied digitally to a detected x-ray photon. The CT system includes a photon counting detector with linear arrays of pixels made from cadmium zinc telluride (CZT) semiconductor. A cylindrical phantom with 10.2 cm diameter made from tissue-equivalent material was used for CT imaging. The phantom included contrast elements representing calcifications, iodine, adipose and glandular tissue. The x-ray tube voltage was 120 kVp. The energy selective CT data were acquired, and used to generate energy-weighted and material-selective CT images. The energy-weighted and material decomposition CT images were generated using a single CT scan at a fixed x-ray tube voltage. For material decomposition the x-ray spectrum was digitally spilt into low- and high-energy parts and dual-energy subtraction was applied. The x-ray energy weighting resulted in CNR improvement of calcifications and iodine by a factor of 1.40 and 1.63, respectively, as compared to conventional charge integrating CT. The x-ray energy weighting was also applied to low- and high-energy CT projections used for material decomposition. This improved the CNR in images of decomposed calcification and iodine by a factor of 1.57 and 1.46, respectively, as compared to conventional charge integrating CT. Some limitations were observed due to hole trapping in CZT and charge sharing between the detector pixels. First experimental results demonstrate that energy-resolved CT is coming close to its practical applications. Although hole trapping and charge sharing in CZT deteriorates x-ray spectrum and limits CNR improvement with energy weighting and detector count rate, this problem has a feasible solution, which is discussed in this paper and is a matter of ongoing research. | 18,799,830 |
Optically stimulated luminescence (OSL) dosimetry in medicine. | This paper reviews fundamental and practical aspects of optically stimulated luminescence (OSL) dosimetry pertaining to applications in medicine, having particularly in mind new researchers and medical physicists interested in gaining familiarity with the field. A basic phenomenological model for OSL is presented and the key processes affecting the outcome of an OSL measurement are discussed. Practical aspects discussed include stimulation modalities (continuous-wave OSL, pulsed OSL and linear modulation OSL), basic experimental setup, available OSL readers, optical fiber systems and basic properties of available OSL dosimeters. Finally, results from the recent literature on applications of OSL in radiotherapy, radiodiagnostics and heavy charged particle dosimetry are discussed in light of the theoretical and practical framework presented in this review. Open questions and future challenges in OSL dosimetry are highlighted as a guide to the research needed to further advance the field. | 18,799,833 |
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