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Respiratory and other health effects reported in children exposed to the World Trade Center disaster of 11 September 2001. | Effects of the World Trade Center (WTC) disaster on children's respiratory health have not been definitively established. This report describes respiratory health findings among children who were < 18 years of age on 11 September 2001 (9/11) and examine associations between disaster-related exposures and respiratory health. Children recruited for the WTC Health Registry (WTCHR) included child residents and students (kindergarten through 12th grade) in Manhattan south of Canal Street, children who were south of Chambers Street on 9/11, and adolescent disaster-related workers or volunteers. We collected data via computer-assisted telephone interviews in 2003-2004, with interview by adult proxy for children still < 18 years of age at that time. We compared age-specific asthma prevalence with National Health Interview Survey estimates. Among 3,184 children enrolled, 28% were < 5 years of age on 9/11; 34%, 5-11 years; and 39%, 12-17 years. Forty-five percent had a report of dust cloud exposure on 9/11. Half (53%) reported at least one new or worsened respiratory symptom, and 5.7% reported new asthma diagnoses. Before 9/11, age-specific asthma prevalence in enrolled children was similar to national estimates, but prevalence at interview was elevated among enrollees < 5 years of age. Dust cloud exposure was associated with new asthma diagnosis (adjusted odds ratio = 2.3; 95% confidence interval, 1.5-3.5). Asthma prevalence after 9/11 among WTCHR enrollees < 5 years of age was higher than national estimates, and new asthma diagnosis was associated with dust cloud exposure in all age groups. We will determine severity of asthma and persistence of other respiratory symptoms on follow-up surveys. | 18,941,582 |
Case-control study of blood lead levels and attention deficit hyperactivity disorder in Chinese children. | Attention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children. Our goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables. We conducted a pair-matching case-control study with 630 ADHD cases and 630 non-ADHD controls 4-12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD. There was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs >or= 10 microg/dL vs. <or= 5 microg/dL; OR = 6.0; 95% confidence interval (CI) = 4.10-8.77, p < 0.01; 5-10 microg/dL vs.<or= 5 microg/dL, OR = 4.9; 95% CI = 3.47-6.98, p < 0.01]. These results were not modified by age and sex variables. This was the largest sample size case-control study to date to study the association between BLLs and ADHD in Chinese children. ADHD may be an additional deleterious outcome of lead exposure during childhood, even when BLLs are < 10 microg/dL. | 18,941,585 |
Urinary porphyrin excretion in children is associated with exposure to organochlorine compounds. | Hexachlorobenzene (HCB) and other organochlorines induce porphyria cutanea tarda (PCT) in animal studies. Evidence in humans, however, is contradictory. In neonates and adults from a population historically highly exposed to HCB (Flix, Catalonia, Spain), no relation with PCT or with porphyrin excretion was found. We aimed to analyze the association between urinary porphyrin excretion and exposure to HCB and other organochlorinated compounds in children 4 years of age. Our birth cohort included all newborns from Flix and the five surrounding towns (where no airborne pollution occurred). Among the 68 children with porphyrins we measured in cord blood, 52 children 4 years of age provided blood to measure organochlorine compounds, hair for methylmercury, and urine for porphyrin excretion pattern. Quantitative porphyrin excretion was within the normal values. However, total porphyrins, coproporphyrin I (CPI), and coproporphyrin III (CPIII) adjusted to creatinine excretion increased with increasing levels of HCB, 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT), and polychlorinated biphenyl congener 153 (PCB-153). We found no association with methylmercury. When we fitted multiple pollutant models, p,p'-DDE had the strongest association. We found these associations in children from both Flix and other towns, and they were independent of breast-feeding and of organochlorine and porphyrin levels at birth. HCB at current levels did not induce porphyria or increase uroporphyrins. However, the increase of urinary coproporphyrins suggests an incipient toxic effect of the organochlorines, especially for p,p'-DDE, on the hepatic heme-synthesis pathway that differs from the major effects seen in PCT. | 18,941,586 |
The role of an aromatic group in remote chiral induction during conjugate addition of alpha-sulfonylallylic carbanions to ethyl crotonate. | The impact of a remote aromatic nucleus on the stereochemical outcome of the conjugate addition of alpha-sulfonylallylic carbanions to an alpha,beta-unsaturated ester was investigated. alpha-Regioselectivity coupled with anti-diastereoselectivity is accompanied by a prominent preference for relative configuration 3 over 4. The 9-anthryl moiety has shown itself greatly superior over all other groups in this bias. A lithium ion-aromatic pi interaction has been postulated as decisive for the remote transmission of chirality. | 18,941,617 |
Incompetence of neutrophils to invasive group A streptococcus is attributed to induction of plural virulence factors by dysfunction of a regulator. | Group A streptococcus (GAS) causes variety of diseases ranging from common pharyngitis to life-threatening severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock-like syndrome. The characteristic of invasive GAS infections has been thought to attribute to genetic changes in bacteria, however, no clear evidence has shown due to lack of an intriguingly study using serotype-matched isolates from clinical severe invasive GAS infections. In addition, rare outbreaks of invasive infections and their distinctive pathology in which infectious foci without neutrophil infiltration hypothesized us invasive GAS could evade host defense, especially neutrophil functions. Herein we report that a panel of serotype-matched GAS, which were clinically isolated from severe invasive but not from non-invaive infections, could abrogate functions of human polymorphnuclear neutrophils (PMN) in at least two independent ways; due to inducing necrosis to PMN by enhanced production of a pore-forming toxin streptolysin O (SLO) and due to impairment of PMN migration via digesting interleukin-8, a PMN attracting chemokine, by increased production of a serine protease ScpC. Expression of genes was upregulated by a loss of repressive function with the mutation of csrS gene in the all emm49 severe invasive GAS isolates. The csrS mutants from clinical severe invasive GAS isolates exhibited high mortality and disseminated infection with paucity of neutrophils, a characteristic pathology seen in human invasive GAS infection, in a mouse model. However, GAS which lack either SLO or ScpC exhibit much less mortality than the csrS-mutated parent invasive GAS isolate to the infected mice. These results suggest that the abilities of GAS to abrogate PMN functions can determine the onset and severity of invasive GAS infection. | 18,941,623 |
Origination of the split structure of spliceosomal genes from random genetic sequences. | The mechanism by which protein-coding portions of eukaryotic genes came to be separated by long non-coding stretches of DNA, and the purpose for this perplexing arrangement, have remained unresolved fundamental biological problems for three decades. We report here a plausible solution to this problem based on analysis of open reading frame (ORF) length constraints in the genomes of nine diverse species. If primordial nucleic acid sequences were random in sequence, functional proteins that are innately long would not be encoded due to the frequent occurrence of stop codons. The best possible way that a long protein-coding sequence could have been derived was by evolving a split-structure from the random DNA (or RNA) sequence. Results of the systematic analyses of nine complete genome sequences presented here suggests that perhaps the major underlying structural features of split-genes have evolved due to the indigenous occurrence of split protein-coding genes in primordial random nucleotide sequence. The results also suggest that intron-rich genes containing short exons may have been the original form of genes intrinsically occurring in random DNA, and that intron-poor genes containing long exons were perhaps derived from the original intron-rich genes. | 18,941,625 |
Cardiac autotransplantation for malignant or complex primary left-heart tumors. | Malignant or complex benign tumors of the left heart can present a formidable challenge for complete resection, due to anatomic inaccessibility. Cardiac autotransplantation (cardiac explantation, ex-vivo tumor resection, reconstruction, and reimplantation) was introduced for complex benign primary left-heart cardiac tumors by Cooley and for malignant left-heart tumors by Reardon. Herein, we update our previously reported experience.From April 1998 through July 2008, 20 patients underwent 21 cardiac autotransplantations for complex left-sided cardiac tumors that were nonresectable by traditional means. Demographics, tumor histology, operative data, and mortality rates were analyzed. Follow-up was complete in all patients.Of the 20 patients, 17 had malignant lesions, and 3 had benign disease. Two patients had left ventricular lesions and the rest had left atrial lesions. Histology showed 7 malignant fibrous histiocytomas, 5 undifferentiated sarcomas, 3 leiomyosarcomas, 1 malignant osteosarcoma, 1 myxoid sarcoma, 2 paragangliomas, and 1 myxoma. Fourteen patients had previous resection of their cardiac tumors, and 1 patient had repeat autotransplantation for recurrent disease. There were no operative deaths in patients undergoing autotransplantation alone (0/15), and 3 operative deaths in patients undergoing combined cardiac autotransplantation and pneumonectomy (3/6, 50%). All 3 patients with benign disease survived surgery and are alive without recurrent disease. Local recurrence occurred in 3/18 patients with malignant disease: 1 underwent successful repeat autotransplantation and 2 are receiving chemotherapy. The mean survival for all patients with sarcoma is 22 months.Cardiac autotransplantation enables complete resection and accurate reconstruction in many primary malignant and complex benign left-heart tumors. | 18,941,651 |
Bonding properties and bond activation of ylides: recent findings and outlook. | The interaction of phosphorus and nitrogen ylides with metallic precursors has been examined from different points of view. The first one is related to the bonding properties of the ylides. Ylides with a unique stabilizing group bond through different atoms (the Calpha or the heteroatoms); while ylides with two stabilizing groups never coordinate through the Calpha atom. In the second section we examine the cause of the stereoselective coordination of bisylides of phosphorus, nitrogen and arsenic, and of mixed bisylides. We describe here the very interesting conformational preferences found in these systems, which have been determined and characterized. The DFT study of these bisylides has allowed for the characterization of strong intramolecular PO and AsO interactions, as well as moderate CHO[double bond, length as m-dash]C hydrogen bonds as the source of these conformational preferences. The third topic is related to the amazing reactivity of phosphorus ylides in bond activation processes. Depending on the nature of the metallic precursors, ylides can behave as sources of carbenes, of phosphine derivatives, of other ylides or of orthometallated complexes through P[double bond, length as m-dash]C, P-C or C-H bond activation reactions. | 18,941,652 |
Continuous particle separation in spiral microchannels using Dean flows and differential migration. | Microparticle separation and concentration based on size has become indispensable in many biomedical and environmental applications. In this paper we describe a passive microfluidic device with spiral microchannel geometry for complete separation of particles. The design takes advantage of the inertial lift and viscous drag forces acting on particles of various sizes to achieve differential migration, and hence separation, of microparticles. The dominant inertial forces and the Dean rotation force due to the spiral microchannel geometry cause the larger particles to occupy a single equilibrium position near the inner microchannel wall. The smaller particles migrate to the outer half of the channel under the influence of Dean forces resulting in the formation of two distinct particle streams which are collected in two separate outputs. This is the first demonstration that takes advantage of the dual role of Dean forces for focusing larger particles in a single equilibrium position and transposing the smaller particles from the inner half to the outer half of the microchannel cross-section. The 5-loop spiral microchannel 100 microm wide and 50 microm high was used to successfully demonstrate a complete separation of 7.32 microm and 1.9 microm particles at Dean number De = 0.47. Analytical analysis supporting the experiments and models is also presented. The simple planar structure of the separator offers simple fabrication and makes it ideal for integration with on-chip microfluidic systems, such as micro total analysis systems (muTAS) or lab-on-a-chip (LOC) for continuous filtration and separation applications. | 18,941,692 |
Physiological stress of high NH (4) (+) concentration in water column on the submersed macrophyte Vallisneria Natans L. | The submersed macrophyte, Vallisneria natans L., was cultured in laboratory with NH (4) (+) -enriched tap water (1 mg L(-1) NH(4)-N) for 2 months and the stressful effects of high ammonium (NH (4) (+) ) concentrations in the water column on this species was evaluated. The plant growth was severely inhibited by the NH (4) (+) supplement in the water column. The plant carbon and nitrogen metabolisms were disturbed by the NH (4) (+) supplement as indicated by the accumulation of free amino acids and the depletion of soluble carbohydrates in the plant tissues. The results suggested that high NH (4) (+) concentrations in the water column may hamper the restoration of submersed vegetation in eutrophic lakes. | 18,941,702 |
Alzheimer's disease and other dementing conditions. | Dementia is a common and growing problem, with 20% of those over 80 years of age suffering from this disorder. The prospect of more effective treatments has caused an increasing demand for a more accurate and earlier diagnosis of different dementia syndromes. Neuroimaging techniques may have an important role in the clinical evaluation of dementia for early diagnosis, differential diagnosis and may help in the prediction of conversion to dementia in individuals at a higher risk of developing the disorder. Moreover, new MRI techniques might not only further broaden our understanding of the pathophysiology but also accelerate treatment discovery. This review will focus on the use of conventional and non-conventional MRI techniques to investigate dementias. | 18,941,718 |
Tumours. | Detection of a brain lesion is the first diagnostic step in patients with symptoms and signs suggesting the presence of a brain tumour. Imaging is primarily done to prove or rule out the presence of such a lesion. The first diagnostic evaluation is based on neuroradiological imaging, and when the diagnosis of brain tumour is highly suspicious, the type of tumour should be characterized along with its grade of malignancy, as morphological imaging alone in not specific enough to give full comprehension of brain lesions. In recent years, after continuous developments in MRI, neuroimaging has evolved into a comprehensive diagnostic tool that allows the characterization of morphological and biological alterations to diagnose and grade brain tumours and to monitor and assess treatment response and patient prognosis. | 18,941,724 |
[Adrenal tumors]. | Adrenal tumors can be primary or secondary entities. Primary tumors are able to secrete hormones which may cause significant effects clinically. Typical tumor-related adrenal diseases are Conn's syndrome (hyperaldosteronism), Cushing's syndrome (hypercortisolism), and pheochromocytoma (catacholamine excess). Primary adrenal tumors are rarely malignant, but adrenocortical neoplasias show a relation between tumor size and rate of malignancy. Diagnostic methods for adrenal tumors include hormone tests and imaging. The first choice of treatment is surgical removal, today preferably by minimally invasive approaches. | 18,941,729 |
Focal adhesion kinase as an immunotherapeutic target. | Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses. To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients. Two synthetic peptides, FAK(143-157) and FAK(1,000-1,014), induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients. Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors. | 18,941,742 |
Expression of ADAMTS-4 by chondrocytes in the surface zone of human osteoarthritic cartilage is regulated by epigenetic DNA de-methylation. | The two major aggrecanases involved in osteoarthritis (OA) are ADAMTS-4 and ADAMTS-5. Knock-out studies suggested that ADAMTS-5, but not ADAMTS-4, is the major aggrecanase in murine OA. However, studies of human articular cartilage suggest that ADAMTS-4 also contributes to aggrecan degradation in human OA. This study investigated ADAMTS-4 in human OA. While ADAMTS-4 was virtually absent in control cartilage, numerous ADAMTS-4 immuno-positive chondrocytes were present in OA cartilage and their numbers increased with disease severity. RT-PCR confirmed expression, especially in the surface zone. DNA methylation was lost at specific CpG sites in the ADAMTS-4 promoter in OA chondrocytes, suggesting that the increased gene expression was more than a simple up-regulation, but involved loss of DNA methylation at specific CpG sites, resulting in a heritable and permanent expression of ADAMTS-4 in OA chondrocytes. These results suggest that ADAMTS-4 is epigenetically regulated and plays a role in aggrecan degradation in human OA. | 18,941,754 |
D3 lymphadenectomy using a medial to lateral approach for curable right-sided colon cancer. | The extended D3 lymphadenectomy using a medial to lateral (MtL) approach for the treatment of curable right-sided colon cancer is performed with a view to improving oncologic surgery outcomes. However, the feasibility and safety of this procedure has not been fully examined. The present study investigated the feasibility and safety of D3 lymphadenectomy using the MtL approach for curable right-sided colon cancers. Between January 2005 and May 2007, 42 patients underwent a curative-intent right (25) or extended right (17) hemicolectomy including D3 lymphadenectomy using the MtL approach performed by the same single surgeon. The extent of the D3 lymphadenectomy followed the recommendations of the Japanese Society for Cancer of the Colon and Rectum. There were 27 male and 15 female patients, with a mean age of 59.2 years (range, 30-83). The mean operation time was 172.5 min (range, 55-274) and the mean blood loss was 128.3 ml (range, 50-500). All procedures were successful and no conversions to open surgery were required in laparoscopic cases (32 patients, 76.2%). The mean number of harvested lymph nodes was 45 (range, 18-92). There was no surgical mortality or morbidity, except one case of postoperative ileus which was conservatively managed. The mean postoperative hospital stay was 8.6 days (range, 6-15). The findings indicate that a D3 lymphadenectomy using the MtL approach is a feasible and safe procedure for the treatment of curable right-sided colon cancer. | 18,941,759 |
Exacerbation of liver cirrhosis in pregnancy: a complex emerging clinical situation. | Pregnancy in women with liver cirrhosis is an infrequent situation. In general the incidence of cirrhosis in pregnancy is very low and it is estimated approximately about 1 in 5,950 pregnancies. We report a descriptive management of pregnancy in a woman suffering from chronic viral hepatitis B with D and C coinfection exacerbated finally to severe cirrhosis of the liver. Caesarean section was performed giving birth to a viable male infant. Two months after the operation the patient underwent a liver transplantation with good outcome. Management of such severe cases requires a multidisciplinary medical approach. Data regarding cirrhosis caused by chronic viral agents in pregnancy are limited. | 18,941,761 |
[Anxiety and depression in headache patients. The example of managed care of chronic headache patients in Bavaria]. | The prevalence of anxiety and depression and the influence of headache severity on these illnesses were examined in patients who were part of the managed care of headache in Bavaria. A total of 181 patients with headache were screened for anxiety and depression with the German version of the Hospital Anxiety and Depression Scale (HADS-D). Headache severity was evaluated using the Migraine Disability Assessment Questionnaire (MIDAS). Apart from purely descriptive evaluations, Spearman's coefficients of correlation were calculated. Of the patients 22.7% and 44.7% obtained results at or above the limit of the normal range of depression and anxiety, respectively and 19.3% had results at or above the limit of the normal range for both illnesses. There were significant coefficients of correlation between the severity of headache and both anxiety and depression. The results confirm the necessity for an interdisciplinary procedure in treating headache patients in order to achieve a successful therapy. Such a treatment can be realised with the concept of managed care. | 18,941,799 |
[Measurement of success of treatment for chronic back pain. Can general effects in an entire sample of patients with chronic back pain be transferred to specific effects in individuals?]. | The multimodal therapy has proved to be useful for the treatment of patients with chronic back pain. The aim of this methodical study was to test whether specific effects for the individual can be inferred from general effects of the entire sample, in order to define criteria for the success of treatment. These could be helpful when deciding to which patients the multimodal therapy can best be applied. A total of 408 patients with chronic back pain took part in a 3-week multimodal therapy program in a day hospital. The patients were questioned regarding parameters such as pain intensity, depression, functional back capacity and quality of life before therapy as well as 6 months after therapy. On average, a significant improvement of all parameters could be shown after 6 months. However, scatterplots and correlations showed that general results of the entire sample should not be transferred to the individual patient Taking into account principles of classical test theory this study showed that sufficient systematic coherence of the data must be proven before changes can be calculated. As long as neither an adequate systematic nor useful criteria can be found, there seems to be no reason to exclude any patient from multimodal therapy using pre-selection criteria. | 18,941,800 |
Identification of novel acetylenic alcohols and a new dihydrothiopyranone from the tropical sponge Reniochalina sp. | Two new acetylenic alcohols (1-2) and a new dihydrothiopyranone (3) were isolated from the tropical sponge Reniochalina sp. Their structures were determined by spectroscopic and chemical methods to be (3R)-hydroxyoctatriacont-(4E)-en-1-yne (1), 5-hydroxyheptatriacont-(3Z)-en-1-yne (2) and 2-hexadecyl-2,3-dihydrothiopyran-4-one (3). The acetylenic alcohol (1) exhibited significant growth inhibitory effect against human tumor cell lines. | 18,941,819 |
[Mechanical ventilation of morbidly obese patients in anaesthesia and intensive care]. | Sculptures from the Stone Age hint at the possibility that morbidly obese humans have always existed. Today, obesity represents a global epidemic with far-reaching consequences affecting health systems worldwide. Increasingly often, anaesthetists and intensivists are challenged with the treatment of extremely obese patients perioperatively. In addition to insufficient logistics and inappropriate technical equipment, the large number of obesity-related diseases, combined with the distinct pathophysiological changes of the respiratory system, put the morbidly obese patient at a significantly increased risk of perioperative complications. If, however, elaborate logistics and adequate airway management--followed by lung protective mechanical ventilation--are combined with appropriately conducted anaesthesia and intensive care, the morbidly obese patients' intensive care survival rates and hospital survival rates can be similar to those of patients of normal weight. | 18,941,825 |
Muscular and hepatic pollution biomarkers in the fishes Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus in the Blanes Submarine Canyon (NW Mediterranean). | Submarine canyons are regarded as a sink for pollutants. In order to determine if this theory applied to deep-sea species from an important fishing ground (the Blanes submarine canyon) located in the NW Mediterranean, we sampled the commercial fish Phycis blennoides and Micromesistius poutassou and the crustacean Aristeus antennatus. Specimens were sampled inside and outside (in the open continental slope) the submarine canyon; both are regarded as potentially affected by exposure to different anthropogenic chemicals. Several pollution biomarkers in muscle (activity of cholinesterases) and liver/hepatopancreas (catalase, glutathione S-transferases, carboxylesterases, ethoxyresorufin O-deethylase in fish or mixed function oxygenase (MFO)-related reductases in crustacean, and lipid peroxidation levels) were measured. Chemical analysis of the persistent organic pollutants, namely polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) was also performed on the fish and crustacean muscle. Biomarker activities and levels were discussed in relation to pollutant exposure, habitat, and parameters including sex, size, and species. Biochemical responses and chemical analysis of PCBs evidenced interspecies differences as well as sex and size-related ones, mainly in A. antennatus. An indication of higher exposure to pollutants inside the canyon was observed, which was more clearly reflected in the fish than in the crustacean. However, further research is required to confirm this observation. | 18,941,829 |
Primary vaginal reconstruction at the time of pelvic exenteration for gynecologic cancer: morbidity revisited. | The aim of this study is to analyze our experience about the benefits and morbidity of primary vaginal reconstruction in pelvic exenteration. Over a 10-year period, 64 patients underwent a pelvic exenteration for gynecologic cancer, except for ovarian and fallopian cancer. Twenty-nine patients underwent pelvic exenteration with vaginal reconstruction [21 cases with transverse rectus-abdominis myocutaneous (TRAM) flap and eight cases with Singapore fascio-cutaneous flap]. Thirty-five patients did not undergo vaginal reconstruction. Postoperative morbidity was recorded and a comparative analysis of morbidity between groups was made. Pelvic abscess and small bowel fistula occurred more frequently in the no neovagina group (20% versus 6.9% and 20% versus 3.4%, respectively). There were no differences between groups regarding fever, colorectal anastomosis (CRA) dehiscence-leakage, prolonged ileus, deep venous thrombosis, pulmonary embolism or wound complications. Surgery time was significantly longer for the neovagina group. There was only one perioperative death, which occurred in the neovagina group. Vaginal stenosis, necrosis, and shortness occurred less frequently for TRAM flap compared with Singapore flap (19.0% versus 28.6%, 14.5% versus 50% and 0% versus 100%, respectively). CRA dehiscence-leakage appeared more frequently (83.3% versus 28.6%) in the Singapore group. Nevertheless, this complication was statistically associated (p = 0.0009) with low CRA (<5 cm). TRAM flap seems to be the preferable option for reconstructing the vagina after pelvic exenteration. The Singapore fascio-cutaneous flap carries a higher rate of complications, does not work as functional neovagina after pelvic exenteration, and does not seem to be a good choice in cases of low colorectal anastomosis. | 18,941,843 |
Synergistic effect of Kalpaamruthaa on antiarthritic and antiinflammatory properties--its mechanism of action. | The present study was designed to evaluate the antiinflammatory properties of Kalpaamruthaa (KA) a modified indigenous Siddha formulation constituting Semecarpus anacardium nut milk extract (SA), Emblica officinalis (EO) and honey in acute and chronic antiinflammatory studies. A dose of 150 mg/kg b.wt. of SA and KA were used for the present studies. The effect of KA was compared with standard drug diclofenac sodium. It was observed that the drug KA exhibited enhanced effect on antiinflammatory and antiarthritic properties than sole SA treatment and the collective effect of KA might be due to the combined interactions of the phytochemicals such as flavonoids, tannins and other compounds such as vitamin c present in KA. | 18,941,878 |
Dimensional structure of the autism phenotype: relations between early development and current presentation. | The dimensional structure of higher functioning autism phenotype was investigated by factor analysis. The goal of this study was to identify the degree to which early symptoms of autism (measured using the ADI-R) could be predictive of the current symptoms of autism as identified using the ADOS, the adaptive behavior scales, IQ scores and theory of mind scores. Participants included 140 subjects with Full Scale IQ > 70 (104 with autism spectrum diagnosis, 36 with non autism diagnosis, age range 6-24). For the early development as well as for the current presentation a multi-factor solution was found. In line with other studies we found that the social interaction and communication domains are closely related to one factor namely: Social communication. An additional factor implies anxious and compulsive behavior which is associated with current social communication functioning. | 18,941,880 |
Lanthanum chloride suppresses hydrogen peroxide-enhanced calcification in rat calcifying vascular cells. | Lanthanum chloride (LaCl(3)) has been shown to retard the progression of established atherosclerotic lesions in animal models, and used as a calcium channel blocker in various cellular experiments. In this study, we assessed the role of lanthanum chloride (LaCl(3)) in H(2)O(2)-enhanced calcification in rat calcifying vascular cells (CVCs) and examined the involvement of MAPK signaling pathways. H(2)O(2) induced growth inhibition of CVCs, as well as increases in intracellular levels of calcium and reactive oxygen species, ALP activity, apoptosis and calcium deposition. These effects of H(2)O(2) were suppressed by pretreatment of the cells with 1 muM of LaCl(3) for 2 h. In addition, H(2)O(2) activated the phosphorylation of ERK1/2, JNK and p38 MAPK, but only the last two were associated with the ALP activity. Our findings demonstrate that H(2)O(2)-enhanced osteoblastic differentiation and apoptosis are responsible for the increased calcification in rat CVCs, and LaCl(3) can counteract these effects by suppressing the activation of JNK (JNK2, but not JNK1) and p38 MAPK signaling pathway. | 18,941,904 |
Potential for seed-mediated gene flow in agroecosystems from transgenic safflower (Carthamus tinctorius L.) intended for plant molecular farming. | Safflower has been transformed for field scale molecular farming of high-value proteins including several pharmaceuticals. Viable safflower seed remaining in the soil seed bank after harvest could facilitate seed and pollen-mediated gene flow. Seeds may germinate in subsequent years and volunteer plants may flower and potentially outcross with commodity safflower and/or produce seed. Seeds from volunteers could become admixed with conventional crops at harvest, and/or replenish the seed bank. Seed in following crops could be transported locally and internationally and facilitate gene flow in locations where regulatory thresholds and public acceptance differ from Canada. Seed-mediated gene flow was examined in three studies. Safflower seed loss and viability following harvest of commercial fields of a non-transgenic cultivar were determined. We assessed seed longevity of transgenic and non-transgenic safflower, on the soil surface and buried at two depths. Finally, we surveyed commercial safflower fields at different sites and measured density and growth stage of safflower volunteers, in other crops the following year and documented volunteer survival and viable seed production. Total seed loss at harvest in commercial fields, ranged from 231 to 1,069 seeds m(-2) and the number of viable seeds ranged from 81 to 518 seeds m(-2). Safflower has a relatively short longevity in the seed bank and no viable seeds were found after 2 years. Based on the seed burial studies it is predicted that winter conditions would reduce safflower seed viability on the soil surface by >50%, leaving between 40 and 260 viable seeds m(-2). The density of safflower volunteers emerging in the early spring of the following year ranged from 3 to 11 seedlings m(-2). Safflower volunteers did not survive in fields under chemical fallow, but in some cereal fields small numbers of volunteers did survive and generate viable seed. Results will be used to make recommendations for best management practices to reduce seed-mediated gene flow from commercial production of plant molecular farming with safflower. | 18,941,919 |
Redefining ecological ethics: science, policy, and philosophy at Cape Horn. | In the twentieth century, philosophy (especially within the United States) embraced the notion of disciplinary expertise: philosophical research consists of working with and writing for other philosophers. Projects that involve non-philosophers earn the deprecating title of "applied" philosophy. The University of North Texas (UNT) doctoral program in philosophy exemplifies the possibility of a new model for philosophy, where graduate students are trained in academic philosophy and in how to work with scientists, engineers, and policy makers. This "field" (rather than "applied") approach emphasizes the inter- and transdisciplinary nature of the philosophical enterprise where theory and practice dialectically inform one another. UNT's field station in philosophy at Cape Horn, Patagonia, Chile is one site for developing this ongoing experiment in the theory and practice of interdisciplinary philosophic research and education. | 18,941,926 |
Rehabilitation of sensorimotor integration deficits in balance impairment of patients with stroke hemiparesis: a before/after pilot study. | Balance impairment in patients with stroke hemiparesis is frequently related to deficits of central integration of afferent inputs (somatosensory, visual, vestibular). Our aim was to evaluate whether balance exercises performed under various sensory input manipulations can improve postural stability and/or walking ability in patients with stroke. Seven chronic hemiparetic subjects were recruited. Patient performance was assessed before, immediately after and one week after treatment (consisting of 20 one-hour daily sessions of several balance exercises) by means of the Sensory Organization Balance Test and the Ten Metre Walking Test. Before treatment, all patients showed balance impairment with difficulty integrating somatosensory information from the lower extremities and excessive reliance upon visual input in standing balance control. After treatment, balance and walking speed significantly increased and this improvement was maintained for one week. These findings indicate that rehabilitation of sensorimotor integration deficits can improve balance in patients with stroke hemiparesis. | 18,941,933 |
Cerebral sinus venous thrombosis in a subject with thyrotoxicosis and MTHFR gene polymorphism. | We report a case of cerebral venous thrombosis (CVT) due to tyrotoxicosis in a patient with methylenetetrahydro-folate-reductase (MTHFR) gene polymorphism C677T, (genotype 677TT), in which discontinuation of intravenous heparin was followed by clinical and radiological worsening despite warfarin treatment. We discuss the relationship between CVT, MTHFR hyperthiroidism and anticoagulant therapy. | 18,941,937 |
Unawareness of "illnesses": a case of right-sided hemiballism. | The Authors describe a non-demented patient who, after a left subthalamic haemorrhage causing hemiballism, was completely unaware of both neurological (i.e., dyskinesias) and non-neurological (i.e., cough) symptoms occurring after the stroke. In contrast, he was perfectly able to acknowledge pathological conditions affecting him before the brain damage. Neuropsychological assessment showed no cognitive defects, but revealed the presence of frontal behaviours (e.g., perseverations and utilization behaviours). This unusual clinical picture was ascribed to damage of frontal-subcortical circuits involved in conscious representation of current bodily states. | 18,941,938 |
A novel heterozygous mutation in the NOTCH3 gene causing CADASIL. | Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an identifiable cause of inherited stroke among young adults, characterised by diffuse leukoencephalopathy with prominent involvement of the temporal poles and external capsule. The disease is caused by mutations in the NOTCH3 gene encoding a NOTCH3 receptor protein. The clinical course is relentlessly progressive with early transient ischaemic attacks (TIA) or strokes, dementia and finally death in the mid-60s. We describe a 40-year-old patient with clinical features of CADASIL and a positive family history who was a carrier of a new mutation at the exon 4 of the NOTCH3 gene: C162R. Regardless of the distinctive clinical and neuroimaging features one of his siblings had been mistakenly diagnosed as suffering from multiple sclerosis (MS), suggesting that the disease can occasionally be misdiagnosed as MS. | 18,941,948 |
Interaction of articaine hydrochloride with prokaryotic membrane lipids. | Local anesthetics are the most commonly used drugs in dentistry, with a wide range of effects, including antimicrobial activity. High antimicrobial effects have recently been reported on oral microbes from articaine hydrochloride, revealed by the minimum inhibitory concentration and minimal bactericidal concentration. Additionally, articaine has recently been used as an alkaline component in endodontic materials with a proposed antibacterial activity. However, the detailed mechanisms of action have not been discussed. We determined the Langmuir surface pressure/molecular area isotherms of prokaryotic lipid monolayers, as well as the phospholipid phase transitions, by employing differential scanning calorimetry on unilamellar prokaryotic liposomes (bilayers). Articaine hydrochloride was found to interact with the prokaryotic membrane lipids in both monolayers and bilayers. An increase of the phospholipid molecular area of acidic glycerophospholipids as well as a decrease in phase transition temperature and enthalpy were found with increasing articaine hydrochloride concentration. The thermodynamic changes by adding articaine hydrochloride to prokaryotic membrane lipids are potentially related to the effects observed from antimicrobial peptides resulting from membrane insertion, aggregate composition, pore formation, and lysis. Interaction of articaine hydrochloride with prokaryotic membrane lipids is indicated. Hence, further research is necessary to gain insight into where these compounds exert their effects at the molecular level. | 18,941,950 |
The classification of vigilance tasks in the real world. | The ability to generalise vigilance research to operational environments has been questioned, largely due to differences between laboratory research and real-world settings. The taxonomy of vigilance tasks proposed by Parasuraman and Davies (1977) represents an attempt to classify vigilance tasks so that tasks with similar information-processing demands can be compared and the ability to generalise results enhanced. Although the taxonomy originally included complexity, the term specifically referred to multiple sources of information. Complexity has been overlooked in much of the traditional vigilance literature, although it is included in more recent studies of jobs such as air traffic control. In this paper, the taxonomy is evaluated in relation to two vigilance intensive jobs - closed circuit television surveillance operators and air traffic controllers. In its present form, the existing taxonomy of experimental settings has limited applicability to these operational settings. Therefore, recommendations for expanding the taxonomy to include more aspects of complexity are made. It is argued that the revised taxonomy be used in conjunction with situation awareness, which makes provision for the cognitive processes involved in these jobs. | 18,941,972 |
Validation of a three-dimensional hand scanning and dimension extraction method with dimension data. | A three-level experiment was developed to validate a 3-D hand scanning and dimension extraction method with dimension data. At the first level, a resin hand model of a participant was fabricated to test the repeatability of the dimension data obtained by the 3-D method. At the second level, the actual hand of that participant was measured repeatedly using both the 3-D method and the traditional manual measurement method. The repeatability for both methods was investigated and compared. The influence of posture keeping, surface deformation and other human issues were also examined on the second level. At the third level, a group of participants were recruited and their hands were measured using both methods to examine any differences between the two methods on statistical descriptives. Significant differences, which varied among dimension types (length, depth/breadth, and circumference), were found between the 3-D method and the traditional method. 3-D anthropometric measurement and dimension extraction has become a prospective technology. The proposed three-level experiment provides a systematic method for validation of the repeatability of a 3-D method and compatibility between dimension data from a 3-D method and a traditional method. | 18,941,974 |
Sex-related differences in foot shape. | The purpose of the study was to investigate sex-related differences in foot morphology. In total, 847 subjects were scanned using a 3-D-footscanner. Three different analysis methods were used: (1) comparisons were made for absolute foot measures within 250-270 mm foot length (FL); (2) and for averaged measures (% FL) across all sizes; (3) the feet were then classified using a cluster analysis. Within 250-270 mm FL, male feet were wider and higher (mean differences (MD) 1.3-5.9 mm). No relevant sex-related differences could be found in the comparison of averaged measures (MD 0.3-0.6% FL). Foot types were categorised into voluminous, flat-pointed and slender. Shorter feet were more often voluminous, longer feet were more likely to be narrow and flat. However, the definition of 'short' and 'long' was sex-related; thus, allometry of foot measures was different. For shoe design, measures should be derived for each size and sex separately. Different foot types should be considered to account for the variety in foot shape. Improper footwear can cause foot pain and deformity. Therefore, knowledge of sex-related differences in foot measures is important to assist proper shoe fit in both men and women. The present study supplements the field of knowledge within this context with recommendations for the manufacturing of shoes. | 18,941,975 |
Effects of a feedback signal in a computer mouse on movement behaviour, muscle load, productivity, comfort and user friendliness. | To study the effects of a tactile feedback signal in a computer mouse on reduction of hovering behaviour and consequently on changes in muscle load, productivity, comfort and user friendliness, a comparative, experimental study with repeated measures was conducted. Fifteen subjects performed five trials with different mouse actions and a standardised task, once with a mouse with the feedback signal and once with a mouse without the feedback signal. Holding the hand just above the mouse caused higher muscle loading than clicking and scrolling. Holding the hand on the mouse caused higher muscle loading than resting the hand on the desk. The feedback signal effectively decreased hovering behaviour. It also led to a more dynamic activation pattern of the extensor muscles of the forearm. The overall opinion of the feedback signal for future use was rated as somewhat variable. No effects on discomfort or productivity were found. The use of a mouse with a tactile vibrating feedback signal seems promising for preventing arm complaints, although more research is needed to establish the clinical relevance. | 18,941,979 |
Toxic effects of chlorpromazine on Carassius auratus and its oxidative stress. | Under laboratory conditions, ecotoxicological effects of chlorpromazine (CPZ) on freshwater goldfish (Carassius auratus) were examined using the toxic culture experiment. The results showed that the median lethal concentration (LC(50)) of CPZ toxic to Carassius auratus in 24, 48 and 96 h was 1.11, 0.43 and 0.32 mg/L, respectively. Thus, CPZ is an extreme toxicant to goldfish. Furthermore, there were significantly positive correlations between the ecotoxicological effects of CPZ and its concentrations, and the toxicity became higher as the exposure time increased. The activity of superoxide dismutase (SOD) and catalase (CAT) in goldfish livers was significantly influenced by CPZ. At the same exposure time, the activity of SOD reduced first, and increased then, whereas the activity of CAT enhanced first and decreased then. At the same exposure levels of CPZ, the activity of SOD and CAT changed similarly, decreased first, then increased and decreased at last. Within the range of exposure concentrations, the changes in the activity of CAT can more easily reflect the oxidation stress in Carassius auratus by CPZ than those of SOD. | 18,941,986 |
Level of contamination and impact of pesticides in cupped oyster, Crassostrea gigas, reared in a shellfish production area in Normandy (France). | Over the last decade, oysters in the Bay of Veys (Northwest France) have sporadically experienced significant summer mortality events which appear to be due to a combination of extrinsic and intrinsic factors. In the present work, the involvement of pesticides (as additional stressors) was investigated using both artificial exposure and field studies (at two sites). Six herbicides were detected in seawater following tests for a total of 15 herbicides. The most estuarine site was the most contaminated, showing relatively high values compared with those recorded in a neighboring river. No pesticides were detected in the flesh of oysters in the field but exposure experiments led to an accumulation of two substituted ureas (diuron and isoproturon, from 0.5 micro g/L and 1 micro gL(- 1) respectively). Some physiological effects were observed in terms of reproduction (partial spawning) and histopathology (atrophy of the digestive tubule epithelium) but results related to other tissue alterations and to neutral red retention (NRR) assays were not conclusive and require further investigation. | 18,941,988 |
Development of IC-ELISA for detection of organophosphorus pesticides in water. | Diethyl (carboxymethyl) phosphonate (DECP) was used as the hapten to develop an indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) for detecting organophosphorus pesticides (OPs). Conjugator of DECP with bovin serum albumin (BSA) was used as the immunogen for producing the polyclonal antibodies (PcAbs). Three antisera were obtained after the immune procedure. Characterization studies of the PcAbs indicated that the titer of antiserum-1 was highest in 3 antisera, and antiserum-1 had high affinity and specificity to the parathion, dichlorvos and pirimiphos. The IC-ELISA showed an IC50 of 0.428 micro g/mL with a detection limit of 0.0125 micro g/mL to parathion. The assay also indicated that the IC50 values of pirimiphos and dichlorvos were 0.331 micro g/mL and 1.25 micro g/mL respectively, and the detection limits of pirimiphos and dichlorvos were 0.0116 micro g/mL and 0.048 micro g/mL respectively. Recoveries of parathion, pirimiphos and dichlorvos spiked into water samples ranged from 90% to 160%. The results indicated that the ELISA could be a convenient and supplemental analytical tool for monitoring OPs residues in environmental water samples. | 18,941,995 |
Sensitivity of intestinal fibroblasts to TNF-related apoptosis-inducing ligand-mediated apoptosis in Crohn's disease. | Strictures and fistulas are common complications of Crohn's disease (CD). Collagen deposit and fibroblast proliferation can contribute to their development. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) binds two pro-apoptotic (TRAIL-R1, TRAIL-R2) and three anti-apoptotic (TRAIL-R3, TRAIL-R4, osteoprotegerin (OPG)) receptors. The aim of this work was to study TRAIL expression and the effects on intestinal fibroblasts (IFs) in CD. Intestinal samples from 25 CD (with or without fibrostenosing areas) and 38 control patients (with or without inflammation) were used. TRAIL, TRAIL R2 and TRAIL R3 expression in the intestine and in human IFs was studied by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining in IF and intestinal samples. TRAIL-induced IF cell death was studied in the presence or absence of OPG and cytokines. Western blots for poly ADP-ribose polymerase (PARP) and caspase-8 were performed to confirm apoptosis in IFs. Transcripts for TRAIL and its receptors were confirmed in the intestine. Immunostaining showed intestinal expression of TRAIL, TRAIL-R2 and TRAIL-R3 in fibroblasts, immune cells and epithelial cells, mainly in fibrostenosing areas. TRAIL-R3 mRNA expression was lower in IFs from fibrostenosing CD. The sensitivity of IFs to TRAIL-mediated apoptosis was higher in the fibrostenosing areas of CD. The effect of TRAIL was decreased by IL-6 and its soluble receptor and almost completely reversed by OPG in the CD patients involved. TRAIL is expressed in the intestine and influences fibroblast survival. Variations in TRAIL expression and in TRAIL-mediated apoptosis could be involved in the tissue remodelling associated with CD. | 18,942,021 |
Acute scrotal oedema complicating peritoneal dialysis. | A case of extraperitoneal leakage of dialysate producing massive acute scrotal oedema complicating peritoneal dialysis is presented. Important diagnostic features including select clinical images, the role of imaging modalities and appropriate management are discussed. | 18,942,023 |
Children's Color Trails Test 1 & 2: test-retest reliability and factorial validity. | This investigation examined the test-retest reliability and the factorial validity of the Children's Color Trails Test 1 & 2 (CCTT) using two distinct and independent studies and their respective research samples. The reliability of the CCTT was evaluated in a study with 6-12-year-old children (n = 54) strictly selected and diagnosed with attention-deficit/hyperactivity disorder from an interventional protocol using test-retest coefficients at 8- and 16-week time intervals. Factorial validity was investigated using groups of children with traumatic brain injury (TBI) (n = 137), children with other types of trauma than brain or head injury (Other Injury) (n = 132), and healthy controls (n = 114) from a protocol assessing the neuropsychological sequelae of traumatic brain injury. The results revealed completion time test-retest reliability in the moderate range, which may be considered modest (r(tt) =.46-.68) in this sample of children with ADHD. Interference reliability coefficients were greater and in the moderate-high range (r(tt) =.75-.78). Factorial analytic results revealed a three-factor structure solution for all three groups (TBI, Other Injury, and controls). As a result of CCTT's factorial loadings, Factor 1 was labeled speed of perceptual tracking and susceptibility to interference, Factor 2 was labeled inattention and impulsivity, and Factor 3 was labeled simple inattention. Relative limitations and strengths associated with this investigation including practice effects associated with repeated CCTT administrations also were addressed within the context of the extant findings and existing trail-making test literature. | 18,942,031 |
Births resulting from oocyte cryopreservation using a slow freezing protocol with propanediol and sucrose. | The human mature oocyte is particularly sensitive to cooling and low temperatures in addition to freeze-thaw damage. The efficiency of oocyte cryopreservation including the pregnancy outcome is still low. The aim of our study is to briefly introduce our preliminary clinical results achieved with oocyte cryopreservation (CP). Our work focused on the use of a slow cooling procedure using the cryoprotectants propanediol (1.5 M) and sucrose (0.3 M). Following a short incubation of 4-6 hours thawed oocytes were injected with a single sperm (ICSI) and fertilization was assessed 12-16 hours later. Laser assisted hatching (LAH) was performed on all transferred embryos and embryo transfer (ET) was carried out 48-72 hours after ICSI. One-hundred and ten eggs were thawed and a survival rate of 76% (84/110) was obtained. Of the 84 oocytes which survived, 64 subsequently fertilized (64/84; 76%) following ICSI and on the following day 55 of those had cleaved (55/64; 86%). Fifty-two embryos were transferred in 29 patients (1.8 embryo/patient), and 7 (7/29; 24%) resulted in clinical pregnancy (1 twin pregnancy). One of the pregnancies encountered first trimester abortion (1/7; 14%). Implantation rate of 15.4% per embryo transferred (8/52) and 7.3% per egg thawed (8/110) were obtained. In all cases, chorion biopsy was performed and chromosomal anomalities were not detected. Our results provide further evidence that the procedure can be applied safely and with good success in clinical assisted reproduction. However, more work is needed since the survival and implantation rate should be improved. | 18,942,028 |
Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. | Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder. | 18,942,064 |
Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. | Therapy for gastrointestinal stromal tumors (GIST) has changed significantly with the use of imatinib mesylate (IM). Despite the success of this drug in metastatic GIST, disease progression remains a perplexing clinical issue suggesting the need for multimodality management. There have been no prospective studies either evaluating the neoadjuvant use of IM in primary GIST or as a preoperative cytoreduction agent for metastatic GIST. RTOG 0132/ACRIN 6665 was a prospective phase II study evaluating safety and efficacy of neoadjuvant IM (600 mg/day) for patients with primary GIST or the preop use of IM in patients with operable metastatic GIST. The trial continued postop IM for 2 years. Sixty-three patients were entered (52 analyzable), 30 patients with primary GIST (Group A) and 22 with recurrent metastatic GIST (Group B). Response (RECIST) in Group A was (7% partial, 83% stable, 10% unknown), in Group B (4.5% partial, 91% stable, 4.5% progression). Two-year progression free survival (Group A 83%, Group B 77%). Estimated overall survival (Group A 93%, Group B 91%). Complications of surgery and IM toxicity were minimal. This trial represents the first prospective report of preop IM in GIST. This approach is feasible, requires multidisciplinary consultations, and is not associated with notable postop complications. | 18,942,073 |
Surgical exposures for distal humerus fractures: a review. | The majority of distal humerus fractures have complex fracture patterns, with displaced articular segments, requiring operative intervention. The goals of surgery are anatomic reduction and rigid internal fixation via an operative approach that balances maximum required exposure with minimum soft tissue or bony disruption that may necessitate postoperative protection. The selection of a surgical approach depends on multiple factors, including, fracture pattern, extent of articular involvement, associated soft tissue injury, rehabilitation protocols, and surgeon preference. This review focuses on the various surgical approaches to the distal humerus. | 18,942,078 |
Dihydrotestosterone sensitises LNCaP cells to death induced by epigallocatechin-3-Gallate (EGCG) or an IGF-I receptor inhibitor. | Compelling evidence has accumulated for chemopreventive effects for the active component of green tea Epigallocatechin-3-Gallate (EGCG) particularly for prostate cancer (CaP). We have assessed interactions between the effects of EGCG and two main regulators of prostate cell function, dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-I). Using LNCaP (androgen-sensitive), PC3 and DU145 (androgen-resistant) CaP cell lines, we assessed the effect of EGCG alone on growth (0-200 microM) and on cell death (0-50 microM). EGCG decreased the proliferation of all the CaP cancer cells in a dose-dependent manner with an increase in apoptosis from 30 to 50 microM. With DU145 cells, a sub-apoptotic dose of EGCG (10-20 microM) reduced IGF-induced growth. With LNCaP cells, a sub-apoptotic dose of EGCG (8 microM) switched DHT from a growth promoter to a growth inhibitor. A similar reversal of DHT effect was seen in the presence of an IGF-I receptor inhibitor, AG1024 (1 microM). These responses appeared to be due to DHT sensitizing the cells to apoptosis by EGCG and AG1024 (P < 0.01 and P < 0.001 respectively). Our data suggests that both green tea and AG1024 are effective in inhibiting cell growth and inducing death in CaP cells but the effects of both are more effective in the presence of androgen. | 18,942,120 |
Comparison of sirolimus-eluting stent and paclitaxel-eluting stent for long-term cardiac adverse events in diabetic patients: the Korean Multicenter Angioplasty Team (KOMATE) Registry. | There is some controversy on long-term cardiac outcomes between sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM). We compared cardiac adverse events after SES and PES implantation in patients with DM over a period of 3 year. A total of 634 patients with DM treated with SES (n = 428) or PES (n = 206) were consecutively enrolled in the KOMATE registry from 2003 to 2004. We assessed major adverse cardiac events (MACEs, cardiovascular death, nonfatal myocardial infarction, ischemia driven target vessel revascularization) and stent thrombosis (ST) according to the definitions set by the Academic Research Consortium. Propensity score (PS) analysis was performed to adjust different baseline characteristics. The mean follow-up duration was 38 +/- 8 month (at least 36 month and up to 53 month). The 3-year MACE rate did not show a significant difference between the two groups [52 (12.1%) in SES vs. 29 (14.1%) in PES, P = 0.496]. The definite and probable ST at 3 year were similar in both SES and PES [12 (2.8%) in SES vs. 7 (3.4%) in PES, P = 0.681]. There were no differences in hazard ratio for MACE and ST between two stents [MACE, crude: 0.844 (0.536-1.330) and adjusted for PS: 0.858 (0.530-1.389); ST, crude: 0.820 (0.323-2.083) and adjusted for PS: 0.960 (0.357-2.587)]. The present study demonstrated that long-tem cardiac outcomes including ST were not significantly different between SES and PES in patients with DM. | 18,942,123 |
Comparison of two transcatheter device strategies for occlusion of the patent ductus arteriosus. | The present study evaluates two transcatheter closure strategies utilized at a single center and makes recommendations for device selection when occluding the patent ductus arteriosus. A variety of devices are available for transcatheter closure of the patent ductus arteriosus (PDA) but no guidelines exist to guide operator device choice. A total of 132 patients underwent attempted transcatheter PDA closure utilizing one of two consecutive closure strategies between January 2000 and June 2005. Strategy A (n = 64; January 2000-May 2003) utilized Gianturco coils only. Strategy B (n = 68; June 2003-June 2005) utilized a single Gianturco coil for the PDA with a minimal diameter <or=1 mm (n = 28) or an Amplatzer Duct Occluder (ADO) if the PDA diameter exceeded 1 mm (n = 40). Success was defined as complete occlusion on a follow up echocardiogram. 58 of 64 (90.6%) patients treated utilizing strategy A had successful coil implantation. 68 of 68 (100%) patients treated utilizing strategy B had successful coil/device implantation. At follow up echocardiography, 32 of 44 (72.7%) strategy A patients had complete ductal closure, as compared with 57 of 58 (98.3%) strategy B patients (P < 0.0001). Stepwise logistic regression analysis identified closure strategy as the most powerful predictor of procedural success (OR = 85.9; CI 5.6-9.99). A transcatheter PDA closure strategy consisting of a single Gianturco coil for PDA <or= 1 mm or an ADO for larger sized PDA (strategy B) achieves superior outcomes compared to the use of coils alone. | 18,942,128 |
Generation and expression of a Hoxa11eGFP targeted allele in mice. | Hox genes are crucial for body axis specification during embryonic development. Hoxa11 plays a role in anteroposterior patterning of the axial skeleton, development of the urogenital tract of both sexes, and proximodistal patterning of the limbs. Hoxa11 expression is also observed in the neural tube. Herein, we report the generation of a Hoxa11eGFP targeted knock-in allele in mice in which eGFP replaces the first coding exon of Hoxa11 as an in-frame fusion. This allele closely recapitulates the reported mRNA expression patterns for Hoxa11. Hoxa11eGFP can be visualized in the tail, neural tube, limbs, kidneys, and reproductive tract of both sexes. Additionally, homozygous mutants recapitulate reported phenotypes for Hoxa11 loss of function mice, exhibiting loss of fertility in both males and females. This targeted mouse line will prove useful as a vital marker for Hoxa11 protein localization during control (heterozygous) or mutant organogenesis. | 18,942,146 |
Wnt11r is required for cranial neural crest migration. | wnt11r is a recently identified member of the Wnt family of genes, which has been proposed to be the true Xenopus homologue to the mammalian wnt11 gene. In this study we have examined the role of wnt11r on neural crest development. Expression analysis of wnt11r and comparison with the neural crest marker snail2 and the noncanonical Wnt, wnt11, shows wnt11r is expressed at the medial or neural plate side of the neural crest while wnt11 is expressed at the lateral or epidermal side. Injection of wnt11r morpholino leads to strong inhibition of neural crest migration with no effect on neural crest induction or maintenance. This effect can be rescued by co-injection of Wnt11r but not by Wnt11 mRNA, demonstrating the specificity of the loss of function treatment. Finally, neural crest graft experiments show that wnt11r is required in a non-cell-autonomous manner to control neural crest migration. | 18,942,153 |
Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function. | Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane alpha-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family--the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY)--have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational "switching" mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible "switch" mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.(23) We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a "tilt" of 9 degrees -10 degrees rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the "tilted" structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while the "rocker switch" may apply to certain MFS transporters, intermediate "tilted" states may exist under certain circumstances or as transitional structures. Although wet lab experimental confirmation is required, our results suggest that transport mechanisms in this transporter family should probably not be assumed to be conserved simply based on standard structural homology considerations. Furthermore, steered molecular dynamics elucidating energetic interactions of ligands with amino acid residues in an appropriately modeled transporter may have predictive value in understanding the impact of mutations and/or polymorphisms on transporter function. | 18,942,157 |
Kinetic modeling of ace operon genetic regulation in Escherichia coli. | A family of kinetic models has been developed that takes into account available experimental information on the regulation of ace operon expression in Escherichia coli. This has allowed us to study and analyze possible versions of regulation of the ace operon and to test their possibilities. Based on literature analysis, we found that there is an ambiguity of properties of IclR (main repressor of ace operon). The main aspect of this ambiguity are two different forms of IclR purified from E. coli K strain and different coeffector sets for IclR purified from E. coli K and B strains. It has been shown that the full-length form of IclR is physiologically relevant and that IclR truncation is a result of purification of the protein from E. coli K strains. We also found that the IclR protein purified from E. coli B strain carries two coeffector binding sites. Using model-developed levels of steady state aceBAK expression against physiological ranges of coeffectors, concentration has been predicted. | 18,942,160 |
Prediction of loop regions in protein sequence. | We suggest an algorithm that inputs a protein sequence and outputs a decomposition of the protein chain into a regular part including secondary structures and a nonregular part corresponding to loop regions. We have analyzed loop regions in a protein dataset of 3,769 globular domains and defined the optimal parameters for this prediction: the threshold between regular and nonregular regions and the optimal window size for averaging procedures using the scale of the expected number of contacts in a globular state and entropy scale as the number of degrees of freedom for the angles phi, psi, and chi for each amino acid. Comparison with known methods demonstrates that our method gives the same results as the well-known ALB method based on physical properties of amino acids (the percentage of true predictions is 64% against 66%), and worse prediction for regular and nonregular regions than PSIPRED (Protein Structure Prediction Server) without alignment of homologous proteins (the percentage of true predictions is 73%). The potential advantage of the suggested approach is that the predicted set of loops can be used to find patterns of rigid and flexible loops as possible candidates to play a structure/function role as well as a role of antigenic determinants. | 18,942,165 |
Chronic obstructive lung disease: perioperative management. | Inflammatory mediators play a major role in pulmonary and extra pulmonary manifestations of COPD. In the preoperative risk evaluation, composite scoring systems like ASA physical status are more efficacious than any single risk factor. Intraoperative ventilator graphics help in managing respiratory mechanics and reducing dynamic hyperinflation. Preoperative optimization of respiratory status and use of postoperative lung expansion maneuvers are effective measures for prevention of PPCs. Lastly, anesthesiologists need to evolve strategies based on the pathophysiology of the disease to ensure that their patients receive optimal perioperative care. | 18,942,241 |
Quadriplegia due to lead-contaminated opium--case report. | Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. The delayed treatment of lead poisoning may lead to irreversible motor neuron defect. | 18,942,257 |
Global health priorities for developing countries: some equity and ethical considerations. | Although the need to make health priorities equitable in addressing health disparities among populations of the world is widely acknowledged, there are presently no clearcut mechanisms for achieving this goal at the global level. This paper highlights some of the limitations associated with priority setting based exclusively on the interplay of burden of disease and cost-effectiveness analysis, and identifies occasions when equity considerations may favor conditions lacking immediate evidence on cost-effectiveness but associated with substantial burden in individuals and the society and for which optimal interventions are time bound. It also highlights the implications of overlooking conditions and issues that are deserving of high-priority status by global health actors and are in the longer-term interest of donor recipients. It concludes by exploring how representative mechanisms for societal preferences such as the periodic resolutions of the World Health Assembly backed by commitments of national governments provide a framework for making global health priorities more equitable. | 18,942,284 |
Outpatient pre-operative assessment in joint replacement surgery. | An anaesthetist-led outpatient pre-operative assessment (OPA) clinic was introduced in our unit in an effort to improve patient care and cost-effectiveness. To assess the efficiency of the clinic, 112 patients who attended the OPA clinic (attendance rate 98%) during the first year were assessed prospectively and compared with 118 patients who did not undergo OPA the year before. There were fewer cancellations among those who attended the OPA clinic (13.6% compared to 3.6%), and the hospital stay was shortened from an average of 10.7 days to 7.0 days. This has resulted in more efficient utilization of operating theatre, reduced hospital costs and improved patient satisfaction. More extensive use of the pre-admission clinic is recommended and should be explored in other clinical settings. | 18,942,292 |
Endoscopic dacryocystorhinostomy. | A review of 45 patients who underwent endoscopic dacryocystorhinostomy (EDCR) from 1998 to 2005 was done. Only patients who had complete notes and had Jones tube removed at least three months before the study were included. Our experience with EDCR concludes it to be an easy, efficient treatment for nasolacrimal duct obstruction with minimal complications. | 18,942,302 |
Insulinoma in Saudi Arabia: a twenty-year hospital study. | The study was designed to assess retrospectively clinical pattern of insulinoma at a national referral center in the Kingdom of Saudi Arabia. All cases of insulinoma recorded at King Khalid University Hospital Riyadh between January 1987 and December 2006 were reviewed. During the 20-year period five patients were seen comprising three females (ages 38, 40, and 70 years) and two males (17 and 34 years). The duration of symptoms prior to diagnosis ranged between one and eight years. The commonest mode of presentation before diagnosis was inability to observe Ramadan fasting. Other notable symptoms included dizziness and loss of consciousness. All the five patients proceeded to operation. At surgery all were found to be benign tumors. Post-operatively, three of the patients developed pseudocyst, which resolved upon undergoing second surgery. Though clinical presentation of insulinoma in Saudi subjects is similar to those reported in the literature, our study revealed prominent symptoms occurring during yearly ramadan religious fast could be a useful information in history taking. Further studies on a larger population are needed to further characterize our findings. | 18,942,316 |
[Distinct clinical characteristics of inflammatory bowel disease in children younger than 5 years]. | In the last decades an increase in morbidity of inflammatory bowel disease, particularly of Crohn disease, in children has been observed. Assessment of clinical course and activity of inflammatory bowel disease in children younger than 5 years was the goal of the study. The study comprised 21 children aged 2 to 5 years (13 boys and 8 girls) who were diagnosed with: Leśniowski-Crohn disease (7 children), ulcerative colitis (7 children) and indeterminate colitis (remaining 7 children). Among studied children boys prevailed (61.9%). In 6 children the disease started in the first and second year of life; the average age of disease onset was 26.9 months and the time between the onset of the disease and the diagnosis was 16.6 months. 46% of patients came from the cities with population above 100000 when only 23% lived in the country. Autoimmune diseases were diagnosed in the families of 6 children, food or pollen allergy in the families of 11 children. Abdominal pain, diarrhea, presence of blood and mucous in the stool, fever and lack of thrive were most apparent in the clinical picture. The pathological changes were present mainly in the large intestine and only in one case in the upper part of the alimentary tract and jejunum. The observed course of the disease was severe or moderate. In two children aged 3 years colectomy was performed. In children younger than 5 years severe and moderate course of the Leśniowski-Crohn disease and ulcerative colitis is apparent. Fever, abdominal pain, diarrhea, presence of blood and mucous in the stool and lack of appetite were the most often seen symptoms. Pathological changes in children younger than 5 years were present mainly in the large intestine and only in single cases in the upper part of the alimentary tract and jejunum. In children with inflammatory bowel disease a frequent occurrence of allergy, bronchitis, pneumonia and urinary tract infection, which required antibiotics, was observed. | 18,942,331 |
[Characteristic of bioamine-containing dental pulp structures under normal conditions and in pathology (a luminescence histochemical study)]. | Neurotransmitter biogenic amines (BA) are known to be important tissue differentiation inducers and promoters of mutual influence of the epithelial and mesenchymal structures during the process of tooth development in the antenatal period. The aim of this investigation was the study of BA-containing dental pulp structures in the adult humans under normal conditions, and in patients with dental caries and its complications in combination with periodontitis. Using luminescent-histochemical methods, the contents of neurotransmitters (cateholamines, serotonin, histamine) was determined in the dental pulp under normal conditions and in pathology. Qualitative and quantitative changes of BA-containing dental pulp structures are described in patients with dental caries and its complications in combination with periodontitis. It was demonstrated that mast and granular luminescent cells, together with the nerve fibers, were involved in the neurotransmitter control of homeostasis in the dental pulp, both under normal conditions and in pathology, by providing the dental pulp structures with BA. The changes in the content of the neurotransmitter BA were noted already at the stage of initial dental hard tissue lesions and were found to precede the development of an acute pulpitis in combination with intermediate degree periodontitis. | 18,942,356 |
[S. P. Botkin--the founder of the domestic clinical gerontology]. | The first in the world large-scale gerontology investigation where 2620 elderly patients were examined was carried out by guidance professor S. P. Botkin in St.-Petersburg. The results were published in 1890 in the special book and consisted of 93 papers, including 102 tables. | 18,942,358 |
[Comparative study on the efficacy of cefuroxime, amoxycillin/clavulanic acid and fosfomycin in prophylaxis of nosocomial infections in oncologic patients after surgical operations]. | Rational antibiotic prophylaxis and antibacterial therapy of nosocomial infections is an actual problem in surgery. Improvement of antimicrobial chemotherapy and prophylaxis of nosocomial infections is of special importance in urgent cases in oncologic units. Data on the design of rational schemes for antibacterial prophylaxis of nosocomial infections developing during the postoperative period in patients with cancer of the urinary bladder as one of the unfavourable complications of the main disease treatment are presented. The use of fosfomycin in the schemes of the antibiotic prophylaxis was shown to be more efficient vs. the use of the traditional beta-lactam antibiotics. | 18,942,388 |
[Immunohistochemical markers as prognosticators in gynecologic oncology]. | Cyclooxygenase and particularly COX-2 expression impaired survival in patients operated on for endometrial adenocarcinoma of the uterus: 5-year overall and relapse-free survival in absence of expression was 92% and 88%, respectively, while in cases of distinct expression, it fell down to 52% and 48%, respectively (p = 0.0004; 0.0005). Similar correlations were observed for COX-1, although with lower significance (p = 0.02). Particularly unfavorable prognosis is associated with high expression of combination of COX-2 and COX-1. The end-results of radiotherapy were associated with proliferative levels of squamous cell cervical carcinoma: for Ki-67--below median of < or = 50%, 5-year survival rate was 77%, mean survival--80 months; for Ki-67 above median of > or = 50%, the indices were 47% and 47 months, respectively, (p = 0.002). There were similar correlations for mutated suppressor-gene 53: 67%--for absence of expression and 53%--for its presence (p = 0/03). Immunohistochemical markers COX-2, Ki-67 and p53 can be used as sole prognosticators and their predictive significance is higher than that of either stage (II or III) or cell differentiation grading. | 18,942,401 |
[A comparison of the pulsatile and nonpulsatile regimens of artificial blood circulation in operations of aortocoronary shunting]. | The work is based on a clinical-laboratory analysis of the pulsatile and non-pulsatile regimens of artificial blood circulation. During operation under investigation were indices of gases of the arterial and venous blood. They were compared with those of gases obtained using the monitor of transcutaneous gases of blood. In the postoperative period a comparison was made between clinical and biochemical indices of blood and coagulogram. The data obtained have shown less negative influence of pulsatile regimen of blood circulation which manifests itself during artificial blood circulation as an increased delivery and extraction of oxygen by tissues, after operation--as improved blood indices. | 18,942,431 |
[Peculiar features of the clinical picture of associated cranio-cerebral trauma]. | An investigation of the clinical picture of 4671 patients with associated cranio-cerebral traumas treated at the hospitals of Saint Petersburg in 2004 has shown that the clinical picture of associated traumas unlike that of isolated cranio-cerebral traumas have an atypical character with the development of pseudo-syndromes of injury of the brain. Extracranial injuries also have atypical manifestations with little symptoms. The diagnosis of associated cranio-cerebral trauma must include radial and little-invasive methods of examination. | 18,942,435 |
[Fetal osteomyelitis]. | The clinical course of fetal osteomyelitis was analyzed in 5 newborns. All of them had poorly manifested course of osteomyelitis, the absence of abscess formation and low information on traditional laboratory tests. The prenatal aspects of the intrauterine infection of the fetus responsible for the development of osteomyelitis, methods of diagnosing and treatment of fetal osteomyelitis were described. Long-tern results of treatment of children with this pathology are studied. The "beam" symptom characteristic of newborn osteomyelitis is also described. | 18,942,439 |
[Closed retrograde intubation of the small intestine]. | The article describes a method of closed retrograde intubation of the small intestine, indications for using and structure of the corresponding probe-intubator (industrial patent No 2290212). The application of the closed retrograde intubation of the small intestine was made in the clinic. | 18,942,447 |
[Patterns of biochemical disorders under exposure to neurotoxic chemicals varying in nature]. | The article covers results of examination of workers engaged into chemical production and contacting neurotoxic factors varying in nature. Findings are disorders of cholesterol metabolism in individuals engaged into vinylchloride and metallic mercury production, modified protein metabolism, activated lipid peroxidation and depressed antioxidant | 18,942,463 |
[Experimental modelling of toxic encephalopathy]. | The article covers problem of experimental biologic modelling of toxic encephalopathies. The authors represent major methodic approaches to modelling, criteria and methods to evaluate pathologic condition of CNS, present results of own research in creating models of toxic encephalopathies caused by metallic mercury and vinylchloride inhalation. | 18,942,466 |
Ethical, legal and social issues related to cell therapy. | The author analyses the implications of cell therapy from a legal study that regulates the use of embryonic material: the regulation of the obtaining of cells, of research with embryos and their research and therapeutic use. There is a detailed look at the provisions in the Convention on Human Rights and Biomedicine of the Council of Europe and concludes that "therapeutic cloning" is not prohibited in our legal regulation. | 18,942,509 |
Clinical perspectives on portable do-not-resuscitate orders. | A do-not-resuscitate (DNR) order is a written medical order that documents a patient's wishes regarding resuscitation and, more specifically, the patient's desire to avoid cardiopulmonary resuscitation (CPR). A DNR order is one of the most important patient care directives that can be issued because it has dramatic and irreversible consequences. A portable DNR order is a do-not-resuscitate directive that travels with the patient. One way to improve continuity among providers and organizations is to develop statewide portable DNR and end-of-life orders that ensure patients' wishes are followed regardless of setting. | 18,942,535 |
Place of death for people with noncancer and cancer illness in South Australia: a population-based survey. | A large representative population survey of 9,500 households reports the association between place of death, diagnosis (cancer vs. noncancer), and use of palliative care services of terminally ill South Australians. Thirty-one percent (1,920) indicated that someone close to them had died of a terminal illness in the preceding five years; 18% had died of noncancer illness and 82% of cancer. Sixty-two percent of deceased individuals accessed palliative care services. More patients with cancer than noncancer had had palliative care (65% vs. 48%; p < 0.0001). Compared with cancer patients, those with noncancer illness had died in hospices less frequently (9% vs. 15%; p = 0.0015) and in nursing homes more frequently (15% vs. 5%; p < 0.0001). Similar proportions had died in hospital (60%) and at home (16%-20%). Palliative care service involvement did not reduce institutional deaths, but shifted them from hospital to hospice. | 18,942,564 |
Effects of feeding low protein diets to piglets on plasma urea nitrogen, faecal ammonia nitrogen, the incidence of diarrhoea and performance after weaning. | This study evaluated the effects of feeding pigs low protein (LP) diets for different lengths of time after weaning on indices of protein fermentation, the incidence of postweaning diarrhoea (PWD), growth performance, and total-tract apparent digestibility. Sixty weaner pigs weighing 6.1 +/- 0.13 kg (mean +/- SEM) were used in a completely randomised design having five treatments: (i) a high protein diet (HP, 243 g/kg CP) fed for 14 d after weaning (HP14); (ii) a low protein diet (LP, 173 g CP/kg) fed for 5 d after weaning (LP5); (iii) LP diet fed for 7 d after weaning (LP7); (iv) LP diet fed for 10 d after weaning (LP10), and (v) LP diet fed for 14 d after weaning (LP14). All diets were supplemented with lysine, methionine, tryptophan and threonine, with all LP diets additionally fortified with crystalline isoleucine and valine to conform to a proposed ideal amino acid (AA) pattern. A second-stage diet (215 g CP/kg) was fed to pigs at the conclusion of each treatment. None of the diets contained antimicrobial compounds. Feeding a LP diet, regardless of duration of feeding, decreased plasma urea nitrogen (p < 0.001) and faecal ammonia-nitrogen (p < 0.001) contents. Feeding a LP diet, irrespective of feeding duration, decreased the incidence of PWD at day 8 after weaning (p = 0.044), and pigs fed diets LP7, LP010 and LP14 had firmer faeces (p = 0.030, p = 0.047 and p = 0.007, respectively) between days 10 and 12 after weaning. Treatments LP5, LP7, LP10 and LP14 did not reduce (p > 0.05) growth performance up to 106 days after weaning compared to pigs fed the HP diet. Total-tract apparent digestibility of dry matter, energy and crude protein were similar (p > 0.05) between treatments. Our data suggest that feeding a LP diet, supplemented with AA to conform to an ideal AA pattern, for 7-10 days after weaning can reduce PWD in pigs fed antibiotic-free diets without compromising production. | 18,942,582 |
Performance and tissue fatty acid profiles in veal calves fed diets supplemented with conjugated linoleic acids. | Three groups of six calves each were fed a milk replacer at 0.8 kg and a starter concentrate ad libitum. Calves of the control group received the basal diet supplemented with rapeseed oil at 10 g per kg of feed solids. Calves of treatment groups were fed diets supplemented with a synthetically produced oil containing 62.3% methyl esters of CLA. The CLA-oil was added to milk at expense of rapeseed oil and fed at 5 and 10 g x kg(-1) feed solids for 63 days. Calves were slaughtered at 115 days of age. There was no significant effect of CLA on growth, intake of starter, feed conversion, chemical composition of meat and its oxidative stability. Dietary supplementation with CLA at 10 g x kg(-1) significantly increased CLA content in m. longissimus dorsi (MLD) from 5.6 to 19.3 mg x 100 g(-1), in liver from 13.1 to 68.8 mg x 100 g(-1), and in perirenal fat from 0.37 to 3.17 g x 100 g(-1). Dietary CLA decreased the ratio of cis-9, trans-11 and trans-10, cis-12 isomers of CLA in tissues, concentration of monounsaturated fatty acids in the MLD and fat, as well as the concentration of fatty acids with 20 and 22 carbon atoms. It can be concluded that in veal calves unprotected CLA apparently escaped ruminal hydrogenation, but was preferentially incorporated into depot fat. | 18,942,584 |
Potential for dissemination of the nonnative salmonid parasite Myxobolus cerebralis in Alaska. | Myxobolus cerebralis, the myxozoan parasite responsible for whirling disease in salmonids, was first introduced into the United States in 1958 and has since spread across the country, causing severe declines in wild trout populations in the intermountain western United States. The recent detection of the parasite in Alaska is further evidence of the species' capability to invade and colonize new habitat. This study qualitatively assesses the risk of further spread and establishment of M. cerebralis in Alaska. We examine four potential routes of dissemination: human movement of fish, natural dispersal by salmonid predators and straying salmon, recreational activities, and commercial seafood processing. Potential for establishment was evaluated by examining water temperatures, spatial and temporal overlap of hosts, and the distribution and genetic composition of the oligochaete host, Tubifex tubifex. The most likely pathway of M. cerebralis transport in Alaska is human movement of fish by stocking. The extent of M. cerebralis infection in Alaskan salmonid populations is unknown, but if the parasite becomes dispersed, conditions are appropriate for establishment and propagation of the parasite life cycle in areas of south-central Alaska. The probability of further establishment is greatest in Ship Creek, where the abundance of susceptible T. tubifex, the presence of susceptible rainbow trout Oncorhynchus mykiss, and the proximity of this system to the known area of infection make conditions particularly suitable for spread of the parasite. | 18,942,590 |
Permanent tooth development in children with cleft lip and palate. | The purposes of this study were to: (1) quantify and compare permanent tooth development of cleft lip and palate (CLP) patients to age- and gender-matched controls; (2) relate these findings to cleft type and severity; and (3) examine delays in individual permanent maxillary teeth related to their proximity to the cleft. Standardized methods using panoramic radiographs were employed to stage dental development and dental age for 49 children with clefts and 49 matched controls. Data were analyzed with a mixed linear model. Analyses indicated a correlation between delayed permanent tooth development and CLP with an overall delay of 0.52 years (P = .02) and with boys accounting for all the delay. No differences were found between subjects with unilateral or bilateral clefts. A nonsignificant trend was noted for greater delay in subjects with clefts of the primary and secondary palates vs primary palate alone. Teeth most often affected by the delay were maxillary first and second premolars and maxillary second molars. While permanent tooth development is delayed in cleft lip and palate patients, this delay is: found in boys only; is independent of the cleft type and severity; and is not correlated with proximity to the cleft. | 18,942,600 |
Dutch primary schoolchildren's attitudes toward their dental appearance. | This study's purpose was to examine children's attitudes toward dental appearance and compare these with attitudes toward general health, body shape, grades in school, friends, money, and sports. The study also explored whether subjects reporting that they have attractive teeth believed themselves to have higher grades in school, more friends, a slim body shape, and better health than subjects reporting that they have unattractive teeth. A sample of 216 9- to 13-year-old Dutch children participated. The methods of paired comparisons and direct ranking were used to investigate children's judgments about the importance of dental appearance. The subjects were also asked to indicate how strongly they believed that they had high grades in school, a lot of friends, money, success in sports, attractive teeth, a slim body shape, and good health. High grades in school, a slim body shape, good health, a lot of friends, and more money were preferred to attractive teeth. Children reporting that they have attractive teeth believed themselves to have higher grades in school, a slimmer body shape, more friends, more money, and better health than children reporting that they have unattractive teeth. Although attractive teeth are highly valued in general, children give priority to other issues in their lives. | 18,942,606 |
Skin-sparing mastectomy: a survey based approach to defining standard of care. | Skin-sparing mastectomy (SSM) followed by immediate reconstruction has been advocated as an effective treatment option for patients with early-stage breast carcinoma. It markedly improves the quality of breast reconstruction through preservation of the natural skin envelope and a smaller incision. The purpose of this study was to investigate general surgeons' attitudes towards SSM. A postal questionnaire survey of California general surgeons was conducted regarding SSM. Of 370 respondents who stated they performed breast cancer surgery, 331 perform mastectomy for cancer with planned immediate reconstruction. Ninety per cent of respondents did not feel that SSM resulted in higher rates of local recurrence. In addition, 70 per cent felt that the cosmetic results of immediate breast reconstruction after SSM were better than those after a standard mastectomy. Despite this, only 61 per cent perform SSM in most cases when immediate breast reconstruction is planned. The majority of general surgeons perform SSM and therefore it should be considered standard of care. Despite a growing body of literature demonstrating high rates of patient satisfaction and long-term oncologic safety with SSM, there remains significant variation in practice patterns among general surgeons. Additional effort in general surgery education regarding the feasibility and safety of SSM is needed. | 18,942,610 |
Changing concepts in the pathogenesis, evaluation, and management of solitary rectal ulcer syndrome. | The purpose of this study was to assess the impact of new technology on both the understanding of the underlying pathophysiology and treatment of solitary rectal ulcer syndrome (SRUS). This study is a retrospective review of patients with a histologic diagnosis of SRUS (1993 to 2007) complimented with a prospective database of those patients studied with defecography and dynamic pelvic MRI. Thirty patients were available for evaluation. A polyp or mass was present in 74 per cent. Ulcers were found in only 23 per cent. All 12 patients undergoing defecography demonstrated rectorectal intussusception. Dynamic MRI of the pelvis revealed pronounced anorectal redundancy and lack of mesorectosacral fixation with mild to severe pelvic floor descent in all four patients studied. Fiber with or without stool softeners was the initial treatment in all patients with resolution of symptoms in 65 per cent. One patient with refractory symptoms underwent a stapled transanal rectal resection with complete resolution of symptoms. Occult rectorectal intussusception appears to be the operant anatomic pathology in SRUS. Anorectal redundancy with lack of mesorectosacral fixation may contribute to the process. All patients should be studied with defecography and dynamic MRI. Stapled transanal rectal resection may offer a promising surgical option. | 18,942,624 |
Management of high-grade splenic injury in children. | Using the National Trauma Databank, we identified 413 children (age < or = 14 years) who sustained high-grade blunt splenic injury (Abbreviated Injury Scale scores > or = 4) from 2001 to 2005. Overall mortality was 13.5 per cent. Early operation within 6 hours of injury (EOM) was performed in 128 patients (31%). Patients not undergoing EOM (n = 285) were assumed to have been treated with initial nonoperative management (NOM). NOM was successful in 84 per cent of patients. Operative intervention was necessary in 42 per cent of cases with 74 per cent of these undergoing early operation (EOM). Total splenectomy was the most common procedure (83%). EOM and failure of NOM were both associated with lower systolic blood pressure and lower Glasgow Coma Scale score at admission, higher Injury Severity Score, longer hospital stay, and higher mortality. Need for surgery was independent of patient age and gender. Failure of NOM was associated with increased mortality compared with successful NOM, but had similar mortality and length of hospital or intensive care unit stay compared with EOM. We conclude that operative treatment is necessary in nearly half of pediatric patients with high-grade splenic injury. With careful selection, nonoperative management is usually successful but must include close monitoring, because 16 per cent required delayed operation. | 18,942,629 |
100 robotic-assisted laparoscopic gastric bypasses at a community hospital. | Laparoscopic Roux-en-Y gastric bypass (LGB) is one of the most popular surgeries for morbid obesity. Robotic use is also on the rise. Data concerning outcomes is limited, hence the need for more information. The first 100 robotic-assisted bypasses by one surgeon in one institution were studied. Data obtained from clinic notes and hospital records included all who underwent the procedure. There were 79 females and 21 males. Mean age and body mass index were 42 years and 48 kg/m2, respectively. Comorbidities included diabetes, 22 per cent; hypertension, 47 per cent, gastroesophageal reflux disease, 40 per cent; obstructive sleep apnea, 53 per cent; dyslipidemia, 17 per cent; and heart disease, 8 per cent. Prior surgeries included cesarean -section, 26 per cent; cholecystectomy, 17 per cent; hysterectomy, 3 per cent; hernia, 1 per cent, and other abdominal surgery, 27 per cent. Intraoperatively procedures included adhesiolysis, 22 per cent; cholecystectomy, 16 per cent; and herniorrhaphy, 3 per cent. Average time was 177.7 minutes. Mean stay was 1.51 days. Thirty-day mortality was 0. Emergency department re-evaluations included 13. Most were minor problems. There was one gastrojejunal leak. Early complications included leak, thrombosis, and bleeding requiring transfusion in four patients. There were four strictures. Overall follow up was greater than 90 per cent. Average weight loss was 21.2 per cent of excess body weight by Month 1, 33.8 per cent by Month 3, and 50.7 per cent by Month 6. Learning curves for time and major complications were 30 and 50 cases, respectively (P = 0.03, 0.04). Robotic use in bariatrics is possible in community hospitals. Although technologies are still in their infancy, complication rates and weight loss are comparable to nonrobotic procedures. | 18,942,636 |
The value of endoscopic ultrasonography in predicting resectability and margins of resection for periampullary tumors. | Cure of pancreatic head and other periampullary neoplasms continues to be infrequent and is unattainable unless clear surgical margins are achieved during Whipple pancreaticoduodenectomy. Endoscopic ultrasonography (EUS) is a relatively recent gastrointestinal tumor imaging modality and may be superior to other techniques used in locoregional staging. We hypothesized that EUS can accurately predict not only tumor resectability, but also negative resection margins with Whipple resection. A retrospective review was undertaken of 81 consecutive patients with periampullary tumors who underwent preoperative CT and EUS followed by surgical exploration for intended Whipple resection. Correlations among preoperative EUS results, successful resection, and surgical margins on final histopathology were investigated. Of the 81 patients, 61 (75%) underwent successful Whipple resection, and 20 (25%) were found to be unresectable at laparotomy. Resection was achieved in 57 (86%) of 66 patients predicted to be resectable by EUS. Of the 61 resected patients, 52 (85%) had negative margins and nine (15%) had positive margins on final pathology. Margins were determined to be negative in 50 (88%) of 57 resected patients predicted to have negative margins by EUS. We conclude that EUS is a powerful and desirable imaging modality in the preoperative assessment of periampullary neoplasms. | 18,942,637 |
Blunt thoracic aortic injury. | Blunt thoracic aortic injury (BAI) is a rare but often fatal injury that occurs with severe polytrauma. Immediate diagnosis and treatment of BAI are essential for a successful outcome. We reviewed our experience with 20 patients with BAI treated at a Level I trauma center between 1995 and 2006. The mean Injury Severity Score was 38 +/- 14 and 14 patients had an abnormal Glasgow Coma Score; associated injuries included abdomen in 13 patients, extremity in 12, and head in six. Chest x-ray (CXR) findings were suggestive of aortic injury in 15 patients, equivocal in three, and showed no evidence of aortic injury in two. Diagnosis was made by CT angiography (CTA) in 17 patients, transesophageal echocardiography (TEE) in two, and formal angiography in one. Sixteen patients underwent operative repair of BAI. Of these, eight also underwent laparotomy, six had operative repair of extremity fractures, and three had pelvic embolization. Five patients died, three of whom were treated nonoperatively, and length of hospitalization in survivors was 32 +/- 20 days. BAI is rare and often associated with multiple life-threatening injuries complicating diagnosis and treatment. Our data support the aggressive use of CTA even when classic CXR findings are not present. When CT must be delayed for abdominal exploration, intraoperative TEE is useful. | 18,942,639 |
Anterolateral thigh flap pedicle for interposition artery and vein grafts in head and neck reconstruction: a case report. | The selection of receiving vessels is one of the most critical steps in ensuring a successful outcome in microvascular surgery. The use of interposition grafts in microsurgery offers the surgeon valuable options when the free flaps vascular pedicles are too short to be anastomosed directly to the recipient vessels. Here, we present a case in which artery and vein grafts were used in microsurgical reconstruction of an anterior maxillary defect with an iliac free flap. As donor vessels, we used the descending branch of the lateral circumflex femoral artery and one of the two venae commitantes. The flap survived without major or minor complications. The anterolateral thigh flap pedicle allowed us to harvest safe, reliable grafts easily, with a suitable vessel length and diameter. | 18,942,655 |
Burnout in nurses and physicians working at an oncology department. | Burnout is associated with decreased job performance and commitment, predicts stress-related health problems, and low career satisfaction. The specific objectives in our study were to assess the levels of burnout and to investigate the interrelationships between demographic characteristics and burnout health-care professionals working with cancer patients in Turkey. A questionnaire-based study was conducted in 77 physicians and 56 nurses working in an oncology clinic at the university hospital. We used quantitative survey to assess burnout levels in participants as well as sociodemographic variables. Data were collected using a Turkish version of the Maslach Burnout Inventory (MBI). Nurses had significantly higher scores of emotional exhaustion (EE) when compared with the physicians, but no significant difference was found between two groups regarding other burnout components. Significant correlations were found in three different components of the MBI, as well as between each component, age and work experience in nurses and physicians. There were statistical significant differences for each of MBI subscales according to age groups in physicians. EE and depersonalization (D) were significantly higher in the < or =29 years of age group than in the older age groups, while personal accomplishment (PA) score was significantly lower in this age group. EE, D, PA were significantly higher in single physicians compared with married physicians. Low level of PA was relatively high among Turkish physicians and nurses working in oncology department compared with previous studies. Younger and single physicians had higher burnout levels compared with older and married ones. | 18,942,658 |
The impact of follicular (FL) and other indolent non-Hodgkin's lymphomas (NHL) on work productivity-a preliminary analysis. | Although much is known about the efficacy, toxicity, and direct costs of treatment for follicular lymphoma (FL), there is no data assessing the impact of this diagnosis on the work productivity of affected individuals. We conducted a cross-sectional survey study of consecutive patients attending a malignant haematology clinic at a large multi-disciplinary cancer centre. Patients with a diagnosis of FL or other indolent non-Hodgkin's lymphoma completed questionnaires assessing health status, work productivity, and activity impairment. Eighty-four patients completed the survey study (95% response). Patients who continued to work reported a minimal impact on their work productivity (10%+/-standard deviation SD 20; 0%=no effect and 100%=complete impairment of activity) and on their daily activities (13%+/-SD 25) attributable to their cancer. Prior to lymphoma diagnosis, over 71% of patients were working while 14% were retired. At the time of survey administration, only 41% of patients were still able to work with a significant proportion of patients having transitioned to retirement (36%), sick leave (10%), or unemployment (4%). On multivariate analysis, significant activity impairment (daily activity impairment>50%) was predicted by poor self-rated health status (OR 32.1; 95% CI: 5.9-174.2; p<0.0001) and active chemotherapy treatment (OR 14.5; 95% CI: 0.91-230.9; p=0.059). Although few patients with indolent lymphoma identified significant impairment in productivity, many were unable to continue employment following diagnosis, needed to miss days from work, or imposed a significant burden on caregivers. The greatest impact on activity is apparent in patients who rate their health status as poor and in those who are currently receiving systemic therapy. | 18,942,670 |
Living radical polymerization of acrylates mediated by 1,3-bis(2-pyridylimino)isoindolatocobalt(II) complexes: monitoring the chain growth at the metal. | A new type of mediator for cobalt(II)-mediated radical polymerization is reported which is based on 1,3-bis(2-pyridylimino)isoindolate (bpi) as ancillary ligand. The modular synthesis of the bis(pyridylimino)isoindoles (bpiH) employed in this work is based on the condensation of 2-aminopyridines with phthalodinitriles. Reaction of the bpiH protio-ligands with a twofold excess of cobalt(II) acetate or cobalt(II) acetylacetonate in methanol gave [Co(bpi)(OAc)], which crystallize as coordination polymers, and a series of [Co(acac)(bpi)(MeOH)], which are mononuclear octahedral complexes. Upon heating the [Co(acac)(bpi)(MeOH)] compounds to 100 degrees C under high vacuum, the coordinated methanol was removed to give the five-coordinate complexes [Co(acac)(bpi)]. The polymerization of methyl acrylate at 60 degrees C was investigated by using one molar equivalent of the relatively short-lived radical source 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as initiator (monomer/catalyst/V-70: 600:1:1). The low solubility of the acetato complexes inhibits their significant activity as mediators in this reaction, whereas the acetylacetonate complexes control the radical polymerization of methyl acrylate more effectively. The radical polymerizations of the hexacoordinate complexes did not show a linear increase in number-average molecular weight (M(n)) with conversion; however, the polydispersities were relatively low (PDI=1.12-1.40). By using the pentacoordinate complexes [Co(acac)(bpi)] as mediators, a linear increase in M(n) values with conversion, which were very close to the theoretical values for living systems, and very low polydispersities (PDI<1.13) were obtained. This was also achieved in the block copolymerization of methyl acrylate and n-butyl acrylate. The intermediates with the growing acrylate polymer radical ((.)PA) were identified by liquid injection field desorption/ionization mass spectrometry as following the general formula [Co(acac)(4-methoxy-bpi)-(MA)(n)-R] (MA: methyl acrylate; R: C(CH(3))(CH(2)C(CH(3))(2)OCH(3))CN), a notion also confirmed by NMR end-group analysis. | 18,942,701 |
WebMTA: a web-interface for ab initio geometry optimization of large molecules using molecular tailoring approach. | A web-interface for geometry optimization of large molecules using a linear scaling method, i.e., cardinality guided molecular tailoring approach (CG-MTA), is presented. CG-MTA is a cut-and-stitch, fragmentation-based method developed in our laboratory, for linear scaling of conventional ab initio techniques. This interface provides limited access to CG-MTA-enabled GAMESS. It can be used to obtain fragmentation schemes for a given spatially extended molecule depending on the maximum allowed fragment size and minimum cut radius values provided by the user. Currently, we support submission of single point or geometry optimization jobs at Hartree-Fock and density functional theory levels of theory for systems containing between 80 to 200 first row atoms and comprising up to 1000 basis functions. The graphical user interface is built using HTML and Python at the back end. The back end farms out the jobs on an in-house Linux-based cluster running on Pentium-4 Class or higher machines using an @Home-based parallelization scheme (http://chem.unipune.ernet.in/ approximately tcg/mtaweb/). | 18,942,724 |
Theoretical study of electronic properties of organic photovoltaic materials. | It has been proved that fullerene derivatives, in which an oligophenylenevinylene (OPV) group is attached to C(60), present an interesting photophysical phenomenon and can be incorporated into photovoltaic cells. In these systems, the OPV acts as electron donor upon excitation, and then fullerene absorbs photoexcited electrons. These new organic semiconductor materials offer the prospect of lower manufacturing costs and they present several advantages: easy fabrication, large area, flexible and light weight devices when compared with inorganic counter parts. In the present theoretical study, oligomeric chains of p-phenylenevinylene (n-PPV, n = 3-8 units) and C(60)-OPV hybrids have been studied by density functional theory (DFT). Electronic properties such as electronic absorption and emission spectra were calculated in order to determinate how the increment of spectroscopic units affects their electronic behavior. These properties were carried out with time dependent-density functional theory (TD-DFT) and ZINDO semiempirical method. The theoretical calculations of the structural properties of n-PPV and fullerene-OPV hybrids were obtained using PBE1PBE/6-31G and ONIOM two-layered version, respectively. All calculations were done with Gaussian 03W program package. | 18,942,732 |
CASSCF and multireference CI with singles and doubles study of low-lying valence and Rydberg states of 2H-tetrazole. | Complete active space self-consistent field (CASSCF) and multireference CI with singles and doubles (MR-CISD) calculations [including extensivity corrections, at MR-CISD+Q and multireference averaged quadratic coupled cluster (MR-AQCC) levels] have been performed to characterize the low-lying valence and the Rydberg states of 2H-tetrazole. The highest level results (MR-AQCC/d'-aug'-cc-pVDZ) indicate the following ordering of the valence singlet excited states: S(1) (n-pi*), 6.06 eV; S(2) (n-pi*), 6.55 eV; S(3) (pi-pi*), 6.55 eV. The MR-CISD+Q/d'-aug'-cc-pVDZ results indicate the same ordering, but at slight higher energies: 6.16, 6.68, and 6.69 eV, respectively. According to our MR-CISD+Q/d'-aug'-cc-pVDZ results, the next two states are Rydberg states, at 7.69 eV (pi-3s) and 7.89 eV (n-3s). The calculated energies of these two states, as well as their proximity, are consistent with the conclusion reached by Palmer and Beveridge (Chem Phys 1987, 111, 249) that the first band of the photoelectron spectrum of 2H-tetrazole is likely to be associated to the first two ionizations processes (of pi and N lone pair electrons), at energies close to 11.3 eV. | 18,942,735 |
Pouchitis, similar to active ulcerative colitis, is associated with impaired butyrate oxidation by intestinal mucosa. | Healthy colonic mucosa uses butyrate as the major energy source. In ulcerative colitis (UC) butyrate oxidation has been shown to be disturbed, but it remains unclear whether this is a primary defect. The aim of this study was to measure mucosal butyrate oxidation in UC (involved and noninvolved colon) and in pouchitis and to study the relationship with endoscopic as well as histological disease activity. Butyrate oxidation was measured in 73 UC patients, 22 pouchitis patients, and 112 controls (95 colon, 17 ileum) by incubating biopsies with 1 mM 14C-labeled Na-butyrate and measuring the released 14CO2. Compared with that in normal colon, butyrate oxidation was significantly impaired in endoscopically active but not in quiescent disease or uninvolved colon segments. The severity of the metabolic defect was related to histological disease activity and decreased epithelial cell height. In active pouchitis, butyrate oxidation was significantly decreased compared with that in normal ileum and excluded pouches without inflammation. The histological pouchitis score correlated significantly with butyrate oxidation. Active UC and pouchitis show the same inflammation-related metabolic defect. Our data suggest that the defect is a consequence of inflammation and that pouchitis is metabolically similar to active UC. | 18,942,762 |
Artificial chemokines: combining chemistry and molecular biology for the elucidation of interleukin-8 functionality. | How can we understand the contribution of individual parts or segments to complex structures? A typical strategy to answer this question is simulation of a segmental replacement followed by realization and investigation of the resulting effect in structure-activity studies. For proteins, this problem is commonly addressed by site-directed mutagenesis. A more general approach represents the exchange of whole secondary structure elements by rationally designed segments. For a demonstration of this possibility we identified the alpha-helix at the C-terminus of human interleukin-8 (hIL-8). Since this chemokine possesses four conserved cysteine residues, it can easily be altered by ligation strategies. A set of different segments, which are able to form amphiphilic helices, was synthesized to mimic the C-terminal alpha-helix. Beside sequences of alpha-amino acids, oligomers of non-natural beta(3)-amino acids with the side chains of canonical amino acids were introduced. Such beta-peptides form helices, which differ from the alpha-helix in handedness and dipole orientation. Variants of the semisynthetic hIL-8 proteins demonstrated clearly that the exact side chain orientation is of more importance than helix handedness and dipole orientation. The activity of a chimeric protein with a beta-peptide helix that mimics the side chain orientation of the native alpha-helix most perfectly is comparable to that of the native hIL-8. Concepts like this could be a first step toward the synthesis of proteins consisting of large artificial secondary structure elements. | 18,942,784 |
Covalent bond fragmentation suitable to describe solids in the fragment molecular orbital method. | To improve the accuracy of the fragment molecular orbital method (FMO), we introduce a new fragmentation scheme based on using frozen orbitals to describe fractioned bonds. By applying this scheme to a set of polyalanine systems of up to 40 residues for the alpha-helix and beta-strand isomers, we established its accuracy, which is considerably improved compared to the original hybrid orbital projection method used for detaching bonds in FMO. For instance, at the two-body FMO expansion with the 6-311G* basis set, the error was typically reduced 2-4 times, and for 6-31G* the accuracy increase was even larger (10 times in terms of the maximum error). For the Trp-cage protein (PDB file 1L2Y) with many charged residues, a fairly large error was observed, which was shown to become small with a larger fragment size or at the three-body level. Consequently, we applied the new scheme to the adsorption of toluene and phenol on a faujasite zeolite, and we demonstrated that good accuracy can be achieved in reproducing ab initio results. | 18,942,816 |
Clustering and classifying diverse HIV entry inhibitors using a novel consensus shape-based virtual screening approach: further evidence for multiple binding sites within the CCR5 extracellular pocket. | HIV entry inhibitors have emerged as a new generation of antiretroviral drugs that block viral fusion with the CXCR4 and CCR5 membrane coreceptors. Several small molecule antagonists for these coreceptors have been developed, some of which are currently in clinical trials. However, because no crystal structures for the coreceptor proteins are available, the binding modes of the known inhibitors within the coreceptor extracellular pockets need to be analyzed by means of site-directed mutagenesis and computational experiments. Previous studies have indicated that there is more than one binding site within the CCR5 extracellular pocket. This article investigates and develops this hypothesis using a novel spherical harmonic-based consensus shape clustering approach. The consensus shape approach is evaluated using retrospective virtual screening of CXCR4 and CCR5 inhibitors. Multiple combinations of CCR5 ligands in multiple trial superpositions are constructed to find consensus queries that give high virtual screening enrichments. Receiver-operator-characteristic performance analyses for both CXCR4 and CCR5 inhibitors show that the new consensus shape matching approach gives better virtual screening enrichments than existing shape matching and docking virtual screening techniques. The results obtained also provide strong evidence to support the notion that there are three main binding sites within the CCR5 extracellular cavity. | 18,942,828 |
Preparation and biological properties of a melibiose binding lectin from Bauhinia variegata seeds. | A dimeric 64-kDa melibiose-binding lectin was isolated from the seeds of Bauhinia variegata. The isolation procedure comprised affinity chromatography on Affi-gel blue gel, ion exchange chromatography on Mono Q, and gel filtration on Superdex 75. The lectin was adsorbed on the first two chromatographic media. Its hemagglutinating activity was stable after 30-min exposure to temperatures up to 70 degrees C. Since lectins may demonstrate biological activities such as antiproliferative, immunomodulatory, antifungal, antiviral, and HIV-1 reverse transcriptase inhibitory activities, the isolated lectin was tested for these activities. It was found that the lectin inhibited proliferation in hepatoma HepG2 cells and breast cancer MCF7 cells with an IC(50) of 1.4 microM and 0.18 microM, respectively. HIV-1 reverse transcriptase activity was inhibited with an IC(50) of 1.02 microM. The lectin and concanavalin A (Con A) evoked maximal mitogenic response from mouse splenocytes at similar concentrations, but the maximal response to B. variegata lectin was only 1/5 of that induced by Con A in magnitude. B. variegata lectin was devoid of antifungal activity. | 18,942,841 |
Analyzing the catalytic mechanism of the Fe-type nitrile hydratase from Comamonas testosteroni Ni1. | In order to gain insight into the catalytic mechanism of Fe-type nitrile hydratases (NHase), the pH and temperature dependence of the kinetic parameters k cat, K m, and k cat/ K m along with the solvent isotope effect were examined for the Fe-type NHase from Comamonas testosteroni Ni1 ( CtNHase). CtNHase was found to exhibit a bell-shaped curve for plots of relative activity vs pH over pH values 4-10 for the hydration of acrylonitrile and was found to display maximal activity at pH approximately 7.2. Fits of these data provided a p K ES1 value of 6.1 +/- 0.1, a p K ES2 value of 9.1 +/- 0.2 ( k' cat = 10.1 +/- 0.3 s (-1)), a p K E1 value of 6.2 +/- 0.1, and a p K E2 value of 9.2 +/- 0.1 ( k' cat/ K' m of 2.0 +/- 0.2 s (-1) mM (-1)). Proton inventory studies indicate that two protons are transferred in the rate-limiting step of the reaction at pH 7.2. Since CtNHase is stable to 25 degrees C, an Arrhenius plot was constructed by plotting ln( k cat) vs 1/ T, providing an E a of 33.3 +/- 1.5 kJ/mol. Delta H degrees of ionization values were also determined, thus helping to identify the ionizing groups exhibiting the p K ES1 and p K ES2 values. Based on Delta H degrees ion data, p K ES1 is assigned to betaTyr68 while p K ES2 is assigned to betaArg52, betaArg157, or alphaSer116 (NHases are alpha 2beta 2 heterotetramers). Given the strong similarities in the kinetic data obtained for both Co- and Fe-type NHase enzymes, both types of NHase enzymes likely hydrate nitriles in a similar fashion. | 18,942,853 |
Formation and characterization of fluid lipid bilayers on alumina. | Fluid lipid bilayers were deposited on alumina substrates with the use of bubble collapse deposition (BCD). Previous studies using vesicle rupture have required the use of charged lipids or surface functionalization to induce bilayer formation on alumina, but these modifications are not necessary with BCD. Photobleaching experiments reveal that the diffusion coefficient of POPC on alumina is 0.6 microm (2)/s, which is much lower than the 1.4-2.0 microm (2)/s reported on silica. Systematically accounting for roughness, immobile regions and membrane viscosity shows that pinning sites account for about half of this drop in diffusivity. The remainder of the difference is attributed to a more tightly bound water state on the alumina surface, which induces a larger drag on the bilayer. | 18,942,863 |
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