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Two novel myocilin mutations in a Chinese family with primary open-angle glaucoma.
To investigate the genetic linkage of primary open-angle glaucoma (POAG) in a Chinese family. We have screened for myocilin (MYOC) gene mutations in a glaucoma family of five generations. There are fifty-six members of whom 11 were confirmed to have POAG , two with ocular hypertension were considered as POAG suspect, and the remaining 43 were asymptomatic. We also recruited 200 unrelated healthy Chinese subjects as normal control. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing were used to identify mutations in the three exons of MYOC. Presymptomatic diagnoses were made for the family members seeking consultation based on the results of both clinical examination and genetic analysis. Among three allelic variants identified in this pedigree (Pro13Leu [38 C-->T], Arg76Lys [227G-->A], and Gln337Stop [1009C del]), Pro13Leu and Gln337Stop were reported to be novel mutations while Arg76Lys has been previously documented. Our results show that all 11 POAG patients carry the Gln337Stop mutation and that four POAG patients and one POAG suspect (V:2) were found to have the Pro13Leu mutation. In addition, Arg76Lys polymorphism was identified in two patients and a POAG suspect (V:5). Pro13Leu and Gln337Stop mutations of MYOC are likely responsible for the etiology of POAG in this pedigree, but the causative mechanism needs further research.
18,776,955
Percutaneous septal ablation after unsuccessful surgical myectomy for patients with hypertrophic obstructive cardiomyopathy.
To evaluate the long-term outcome of percutaneous septal ablation (PTSMA) after a previous myectomy. Myectomy usually results in symptomatic improvement and reduction of dynamic obstruction in hypertrophic obstructive cardiomyopathy patients (HOCM-pts.). However, a few pts. remain with severe symptoms and obstruction, and need additional interventions. We reviewed our database of 450 pts. who underwent PTSMA in our institution, and identified 11 (7 women, 4 men, mean age: 50 +/- 14 years) with residual or recurrent NYHA class symptoms > or =III and significant left ventricular outflow obstruction (LVOTO) despite a previous myectomy 4 +/- 5 years ago. In-hospital and follow-up data covering 6 +/- 4 years, focusing on mortality and morbidity, symptoms, exercise capacity, and echocardiographic measures were collected. PTSMA was performed by injection of 3.6 +/- 2.9 ml of alcohol. There was no peri-procedural or late death in this cohort. CK peaked at 614 +/- 434 U/l. In addition to two pts. who already had a pacemaker implanted, two more (18%) who both had pre-existing left bundle branch block were pacemaker-dependent after PTSMA. During follow-up, 9 pts. (81%) reported significant and stable improvement. Two pts. (18%) developed progressive class III symptoms until their last follow-up, one of these together with persistent AF and a non-fatal stroke, the other received an ICD for primary prophylaxis and entered our pre-transplant program. Echo-Doppler showed sustained LVOTO elimination without global LV dilatation in all cases. PTSMA is an effective non-surgical option for treating symptoms and residual or recurrent LVOTO after a previous surgical myectomy. The high rate of conduction disturbances in this post-surgical cohort translated into a higher rate of pacemaker dependency after PTSMA.
18,777,001
Wheat germ lipase catalyzed kinetic resolution of secondary alcohols in non-aqueous media.
The lipase from wheat germ was used for the kinetic resolution of secondary alcohols. It has the opposite enantioselectivity against the Kazlauskas rule and acts as an anti-Kazlauskas catalyst. The effect of initial water activity, organic solvent, acyl donor and temperature were investigated. Wheat germ lipase had a high activity and enantioselectivity only in n-hexane with a high initial water activity (alpha(w) = 0.97), especially with 1-phenylethanol (C 32%, E > 200). Its performance changed little with the chain length of acyl donor and temperature.
18,777,014
[Lupus erythematodes--evidence-based recommendations for monitoring and therapy].
Standard care of patients with systemic lupus erythematosus (SLE) covers continuous extended diagnostics including the search for new disease manifestations, evaluation of disease activity and of comorbidities requiring treatment and, in particular, accompanying infections. Immunosuppressive medication is determined by active organ manifestations and global disease activity, which is measured by standardized scores. In this context, it is important to differentiate between activity and damage, since damage is mostly treated symptomatically and, by definition, cannot be changed by immunosuppression. Activity and damage are the keystones estimating prognosis, especially since validated surrogate markers are lacking. The standard forms of immunosuppressive therapy for SLE have not changed in recent years, but the strategies are new. Antimalarials are indicated in every lupus patient as long as there are no contraindications. In proliferative nephritis, cyclophosphamide should be limited to the induction phase.
18,777,026
[Effectiveness of arthroscopic synovectomy in rheumatoid arthritis].
Arthroscopic synovectomy in rheumatoid arthritis has proven beneficial in terms of pain relief and joint function, both for upper limb joints (shoulder, elbow, wrist) and the knee. The clinical long-term improvement, such as pain reduction and improved joint mobility, seems more distinct in joints with no or mild joint destruction (early synovectomy) compared to advanced joint damage (late synovectomy). Late-stage elbow arthritis, synovitis of the metacarpophalangeal and proximal interphalangeal joints and the rheumatoid ankle can better be addressed by an open approach. Although a real joint-preserving effect has not been demonstrated, pain reduction and improvement in joint function recommend arthroscopic synovectomy as a substantial treatment option in patients with rheumatoid arthritis.
18,777,027
Incidence of diabetes mellitus among children of Italian migrants substantiates the role of genetic factors in the pathogenesis of type 1 diabetes.
To investigate the role of genetic and environmental factors in the pathogenesis of type 1 diabetes mellitus (T1D), we carried out a study in Germany aimed at comparing the prevalence and incidence of T1D among children of migrant Italians from high-risk (Sardinia) and low-risk (continental Italy) regions versus German children. Children from Italy were identified by the "Baden-Wuerttemberg (BW) Diabetes Incidence Registry", which registered 4017 newly diagnosed T1D patients, aged 0-14 years, between 1987 and 2003. Data relating to T1D children from Sardinia were elicited from more than 2000 questionnaires. Our findings were: (1) T1D is more frequent among German children than among children of Italian migrants [incidence rate (IR) 14.8/100,000/year, 95% confidence interval (CI) 14.4-15.4 vs. IR 10.8/100,000/year, 95% CI 8.2-13.6); (2) the incidence of T1D among Italian children residing in Germany is similar to that of Italian children in the home country (IR 10.8/100,000/year, 95% CI 8.2-13.6 vs. 8.4/100,000/year, 95% CI 7.9-8.9); (3) the prevalence of T1D among Sardinian children is higher than that among German children (0.11%, 95% CI 0.11-0.12) independent of the place where the Sardinian children are living (Sardinian children in Germany 2.3%, 95% CI 0.5-6.5 vs. Sardinian children in Sardinia 0.30%, 95% CI 0.27-0.32). Children from high- and low-risk areas of Italy have incidence rates of T1D that are closer to those of their native regions than to those of German children, indicating that genetic factors play a predominant role in the pathogenesis of T1D.
18,777,043
Flow curves of colloidal dispersions close to the glass transition. Asymptotic scaling laws in a schematic model of mode coupling theory.
The flow curves, viz. the curves of stationary stress under steady shearing, are obtained close to the glass transition in dense colloidal dispersions using asymptotic expansions in the schematic F₁₂(γ)-model of mode coupling theory. The shear thinning of the viscosity in fluid states and the yielding of glassy states is discussed. At the transition between fluid and shear-molten glass, simple and generalized Herschel-Bulkley laws are derived with power law exponents that can be computed for different particle interactions from the equilibrium structure factor.
18,777,045
Endothelial dysfunction and inflammatory reactions of elderly and middle-aged men with obstructive sleep apnea syndrome.
Obstructive sleep apnea syndrome (OSAS) is considered to be associated with cardiovascular complications, and atherosclerosis could mediate this relationship. Cardiovascular risk factors of OSAS still need to be elucidated in elderly patients, since studies about the association between OSAS and cardiovascular diseases have been done mainly in middle-aged adults. To investigate whether endothelial dysfunction, as an early marker of atherosclerosis, and inflammatory responses in OSAS were affected by age, we studied flow-mediated dilatation (FMD) and C-reactive protein (CRP) in elderly and middle-aged patients with OSAS. This study enrolled 161 male subjects of 117 middle-aged (35-59 years old) and 44 elderly (>or=60 years old) patients with OSAS. After they finished nocturnal polysomnography (NPSG), FMD was measured on the brachial artery and blood samples were obtained to determine serum CRP levels. FMD was significantly lower in the elderly patients (p = 0.04), but no difference was observed between two age groups in body mass index (BMI), neck circumference, waist-to-hip ratio, apnea hypopnea index (AHI), serum CRP level, or NPSG findings related with nocturnal hypoxemia such as average O(2) saturation, percentage of time below 90% O(2) saturation, and oxygen desaturation index (ODI). From the results of stepwise multiple linear regression analysis, the lowest oxygen saturation was a significant determinant of FMD (beta = 0.25, p < 0.01, adjusted R (2) = 6%), and BMI (beta = 0.22, p < 0.05) and waist-to-hip ratio (beta = 0.21, p < 0.05) were significant variables to explain CRP (adjusted R (2) = 11%, p < 0.01) in the middle aged patients. In the elderly patients, no variable was significant for predicting FMD, but AHI was significant determinant of CRP (beta = 0.46, p < 0.01, adjusted R (2) = 19%, p < 0.01). In predicting cardiovascular risks of OSAS, both hypoxia and obesity should be considered in the middle-aged group, whereas nocturnal respiratory disturbances are important in the elderly group.
18,777,130
Feed intake, digestibility, body weight and carcass parameters of Afar rams fed tef (Eragrostis tef) straw supplemented with graded levels of concentrate mix.
The experiment was conducted at Alamata Agricultural Research Center, Ethiopia using 20 Afar rams with an initial body weight (BW) of 18.2 +/- 1.76 (mean +/- SD) kg. The objectives were to study the effect of supplementation with concentrate mix consisting of wheat bran (WB), noug seed cake (NSC) and sesame seed cake (SSC) at the ratio of 2:1:1 on dry matter (DM) basis, respectively on feed intake, digestibility, BW gain and carcass parameters of Afar rams fed tef (Eragrostis tef) straw basal diet. The experiment was arranged with four treatments and five replications in a randomized complete block design. The treatments included feeding sole tef straw (T1, control), and daily supplementation with the concentrate mix offered at 150 (T2, low), 250 (T3, medium) and 350 (T4, high) g DM per head. Total DM intake, crude protein (CP) digestibility, daily BW gain (P < 0.001), DM and organic matter (OM) digestibility, and carcass parameters (P < 0.05) were higher in the supplemented than in the control treatment. Intake of tef straw reduced as the level of supplementation increased, whereas the contrary was true for CP intake. Performance in carcass parameters was better for the medium compared to the low level of concentrate mix supplementation. Moreover, the medium level of supplementation did not substitute tef straw intake. Therefore, it is concluded that the medium level of concentrate mix supplement maintained the utilization of the roughage feed and resulted in better carcass parameters.
18,777,140
Acute toxicity of atrazine, endosulfan sulphate and chlorpyrifos to Vibrio fischeri, Thamnocephalus platyurus and Daphnia magna, relative to their concentrations in surface waters from the Alentejo region of Portugal.
Ecotoxicological effects of the herbicide atrazine and the insecticides endosulfan sulphate and chlorpyrifos were evaluated using a test battery comprising aquatic organisms from different trophic levels. According to the categories established in the EU legislation, atrazine can be considered non-harmful for the species tested, while the insecticides can be considered very toxic for the crustaceans. The results of acute toxicity tests showed that the sensitivity of organisms were as follows: Thamnocephalus platyurus > Daphnia magna > Vibrio fischeri. Chlorpyrifos may act as a toxic compound in the aquatic environment of Guadiana River, as it may be detected in water at levels that promote toxic effects.
18,777,155
Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control.
Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0+/-4.1 years (mean+/-SE), body weight 82.5+/-5.0 kg, BMI (body mass index) 27.7+/-1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.
18,777,156
Ethanol production from H(2)SO (3)-steam-pretreated fresh sweet sorghum stem by simultaneous saccharification and fermentation.
The present work presents an alternative approach to ethanol production from sweet sorghum: without detoxification, acid-impregnated fresh sweet sorghum stem which contains soluble (glucose and sucrose) and insoluble carbohydrates (cellulose and hemicellulose) was steam pretreated under mild temperature of 100 degrees C. Simultaneous saccharification and fermentation experiments were performed on the pretreated slurries using Saccharomyces cerevisiae. Experimentally, ground fresh sweet sorghum stem was combined with H(2)SO(3) at dosages of 0.25, 0.50, and 0.75 g/g dry matter (DM) and steam pretreated by varying the residence time (60, 120, or 240 min). According to enzymatic hydrolysis results and ethanol yields, H(2)SO(3) was a powerful and mild acid for improving enzymatic digestibility of sorghum stem. At a solid loading of 10% (w/v) and acid dosage of 0.25 g/g DM H(2)SO(3) at 100 degrees C for 120 min, 44.5 g/L ethanol was obtained after 48 +/- 4 h of simultaneous saccharification and fermentation. This corresponded to an overall ethanol yield of 110% of the theoretical one, based on the soluble carbohydrates in the fresh sweet sorghum stem. The concentrations of hydroxymethylfurfural and furfural of the sulfurous acid pretreated samples were below 0.4 g/L. Ethanol would not inhibit the cellulase activity, at least under the concentration of 34 g/L.
18,777,165
Transformation of different barley (Hordeum vulgare L.) cultivars by Agrobacterium tumefaciens infection of in vitro cultured ovules.
Most cultivars of higher plants display poor regeneration capacity of explants due to yet unknown genotypic determined mechanisms. This implies that technologies such as transformation often are restricted to model cultivars with good tissue characteristics. In the present paper, we add further evidence to our previous hypothesis that regeneration from young barley embryos derived from in vitro-cultured ovules is genotype independent. We investigated the ovule culture ability of four cultivars Femina, Salome, Corniche and Alexis, known to have poor response in other types of tissue culture, and compared that to the data for the model cultivar, Golden Promise. Subsequently, we analyzed the transformation efficiencies of the four cultivars using the protocol for Agrobacterium infection of ovules, previously developed for Golden Promise. Agrobacterium tumefaciens strain AGL0, carrying the binary vector pVec8-GFP harboring a hygromycin resistance gene and the green fluorescence protein (GFP) gene, was used for transformation. The results strongly indicate that the tissue culture response level in ovule culture is genotype independent. However, we did observe differences between cultivars with respect to frequencies of GFP-expressing embryos and frequencies of regeneration from the GFP-expressing embryos under hygromycin selection. The final frequencies of transformed plants per ovule were lower for the four cultivars than that for Golden Promise but the differences were not statistically significant. We conclude that ovule culture transformation can be used successfully to transform cultivars other than Golden Promise. Similar to that observed for Golden Promise, the ovule culture technique allows for the rapid and direct generation of high quality transgenic plants.
18,777,178
Differences in perceptions of communication, tourism benefits, and management issues in a protected area of rural Kenya.
With record-breaking tourist visits in Kenya in 2005-2006, communities near the country's renowned protected areas must undertake or revisit planning efforts to conserve and enhance the region's natural, social, and economic resources. This article examines the differences between two stakeholder groups in the Samburu region of central Kenya: (1) protected area leadership and staff; and (2) members of the communities adjacent to the protected areas. Based on the results and analysis of 30 in-depth interviews, the authors identify differences between protected area staff and their community members regarding perceptions about communication between the two groups, and the economic benefits of tourism. The different stakeholders agreed, however, about challenges related to equitable distribution of tourism-based employment and revenue. The results indicate a need to reach consensus about what constitutes sufficient communication between national reserves and their community, and to what extent tourism-related revenue and employment should be distributed within the region. A discussion of the potential role of indicators and standards to make such decisions is presented.
18,777,191
Collecting 48,000 CT exams for the lung screening study of the National Lung Screening Trial.
From 2002-2004, the Lung Screening Study (LSS) of the National Lung Screening Trial (NLST) enrolled 34,614 participants, aged 55-74 years, at increased risk for lung cancer due to heavy cigarette smoking. Participants, randomized to standard chest X-ray (CXR) or computed tomography (CT) arms at ten screening centers, received up to three imaging screens for lung cancer at annual intervals. Participant medical histories and radiologist-interpreted screening results were transmitted to the LSS coordinating center, while all images were retained at local screening centers. From 2005-2007, all CT exams were uniformly de-identified and delivered to a central repository, the CT Image Library (CTIL), on external hard drives (94%) or CD/DVD (5.9%), or over a secure Internet connection (0.1%). Of 48,723 CT screens performed, only 176 (0.3%) were unavailable (lost, corrupted, compressed) while 48,547 (99.7%) were delivered to the CTIL. Described here is the experience organizing, implementing, and adapting the clinical-trial workflow surrounding the image retrieval, de-identification, delivery, and archiving of available LSS-NLST CT exams for the CTIL, together with the quality assurance procedures associated with those collection tasks. This collection of CT exams, obtained in a specific, well-defined participant population under a common protocol at evenly spaced intervals, and its attending demographic and clinical information, are now available to lung-disease investigators and developers of computer-aided-diagnosis algorithms. The approach to large scale, multi-center trial CT image collection detailed here may serve as a useful model, while the experience reported should be valuable in the planning and execution of future equivalent endeavors.
18,777,192
Efficacy of the electrothermal bipolar vessel sealer in laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein.
Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with conservation of the splenic artery and vein has recently been performed as a minimally invasive surgery to retain splenic function in the treatment of pancreatic diseases. As the branches of the splenic vessels are very delicate, division of these branches increases the risk of bleeding. To overcome this problem, we have used the electrothermal bipolar vessel sealer (EBVS) to divide branches of the splenic vessels in LSPDP while conserving the splenic vessels themselves. The EBVS reliably provided excellent and safe hemostasis, minimizing the risk of serious blood loss. Use of the EBVS is safe and efficient in LSPDP with conservation of the splenic vessels.
18,777,196
Improving recruitment and retention for an online randomized controlled trial: experience from the Youthnet study.
The objective of the study was to present recruitment and retention findings for an Internet based HIV prevention trial evaluated using a randomized controlled design among 15-25-year-olds accessing a website on the Internet. We used a combination of automated electronic and personalized approaches to increase and diversify recruitment, verify participant eligibility and increase retention. We posted 3.5 million banner advertisements, 9354 individuals clicked on the advertisement, 8950 completed an eligibility screener and 3298 a baseline survey; we flagged 675 of these as suspicious and enrolled 2623 individuals. Of these, 2082 (79%) completed a follow-up at one-month and 1398 (53%) completed a two-month follow-up. This retention rate is the highest we have seen for an Internet-based HIV-prevention trial. Our procedures can be replicated in other trials. We stress the importance of using a combination of automated and personalized techniques to increase enrollment, verify eligibility and promote retention.
18,777,217
Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough?
Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV/AIDS in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, we estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. We found that patients face significant financial barriers to even qualify for the free ARV program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient's clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident's annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing ARV drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher ARV drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs.
18,777,223
Impact of substance-induced and general medical condition exclusion criteria on the prevalence of common mental disorders as defined by the CIDI.
It has been previously argued that the methodology used by the Composite International Diagnostic Interview version 2.1 to assess the substance-induced and general medical condition exclusion criteria are inadequate. As a result prevalence estimates generated from epidemiological studies using this interview may be underestimated. The purpose of the current study was to examine the substance-induced and general medical condition exclusion criteria in the Australian National Survey for Mental Health and Well-being and determine the impact that they have on prevalence estimates of the common mental disorders. Data from the 1997 Australian National Survey of Mental Health and Well-being were analysed. Frequencies were generated as an indication of how many respondents believed that their psychiatric symptoms were always due to a substance or general medical condition. New DSM-IV prevalence estimates were calculated ignoring the application of the substance-induced and general medical condition exclusion criteria and compared to standard DSM-IV prevalence estimates. The effect of the substance-induced and general medical condition exclusion criteria on final prevalence rates were minimal, with approximately a 0.1% increase when the exclusions were ignored. This equates to a relative difference ranging from no difference for generalized anxiety disorder to an increase of 12% of the base prevalence estimate for agoraphobia. In surveys that use the Composite International Diagnostic Interview version 2.1 the substance-induced and general medical condition exclusion criteria have a minor impact on determining final case definition in the majority of mental disorders.
18,777,235
Application of ion exchange resin in floating drug delivery system.
The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.
18,777,244
Characterization of alpha,alpha-trehalase released in the intestinal lumen by the probiotic Saccharomyces boulardii.
Trehalose intolerance due to alpha,alpha-trehalase deficiency has scarcely been studied. The purpose of this study was to measure alpha,alpha-trehalase activity in intestinal biopsy samples from 200 consecutive patients over a period of 6 months, and to characterize alpha,alpha-trehalase released by the probiotic Saccharomyces boulardii (S. boulardii). Enzyme activities were measured in human and rat intestinal mucosal samples using the micromethod of Messer & Dalqvist. alpha,alpha-trehalase from S. boulardii was immunoprecipitated and Western blotted using an IgG purified antibody raised against a 23 amino acid peptide of alpha,alpha-trehalase of S. cerevisiae. Among 200 patients, most of whom complained of abdominal symptoms and diarrhoea, 18 (9%) had total alpha,alpha-trehalase deficiency (0-12 U/g mucosa) and 39 had partial deficiency (3-12 U/g mucosa). Only 4 patients (2%) presented selective alpha,alpha-trehalase deficiency with otherwise normal disaccharidases. Expressed per gram of powder, alpha,alpha-trehalase from S. boulardii delivered in vitro an activity 175 times higher than that of human trehalase per gram of intestinal mucosa. V(max) (22+/-0.43 micromol) and K(m) (5 mM) were close to that of the human enzyme, whereas Western blot revealed a signal of two subunits of 82 kDa. Finally, treatment of rats with S. boulardii resulted in increases in alpha,alpha-trehalase activities of 25 to 45% (p<0.01) in endoluminal fluid and intestinal mucosa compared with in controls. Our data suggest that alpha,alpha-trehalase deficiency is more common than is believed and that oral administration of S. boulardii could be beneficial in patients with digestive symptoms caused by trehalose intolerance.
18,777,247
Chlortetracycline impregnated food-pellets for the prophylaxis and therapy of psittacosis/ornithosis in psittacines and pigeons.
Medicated food containing 5000 p.p.m. chlortetracycline (CTC) was used for the prophylaxis and therapy of psittacosis/ornithosis in approximately 3800 seed-eating psittacines representing 40 species of 22 genera, as well as 600 pigeons. On the basis of high blood levels of CTC (mostly over 1 mug/ml) in psittacines and failure to isolate Chlamydiae from pigeons after treatment, the medicated pellets seem to be effective for elimination of the causal agent. Owing to the consistently high blood levels the development of CTC-resistant strains is largely prevented.
18,777,265
The specific characters of the Eimeria, with special reference to the coccidia of the fowl.
The differentiation of species of Eimeria is discussed with special reference to those occurring in the domestic fowl. Details of the morphology of the oocysts and other developmental stages of the parasites, their location in the host and the characteristics of the lesions produced, the timing of the patent and prepatent periods, host- and site-specificity and immunological specificity may be used as aids for specific identification. A single criterion is usually insufficient for differentiation and depending upon the species, different characters vary in significance. Quantitative cross-immunity tests appear to be the most satisfactory means available for the differentiation of species of Eimeria affecting chickens.
18,777,269
Observations on the serological and dermal responses of turkeys to a single subcutaneous inoculation of inactivated Newcastle disease vaccine in mineral oil adjuvant.
Each of 10 growing turkeys given a primary subcutaneous inoculation of inactivated Newcastle disease vaccine in mineral oil adjuvant responded with the production of virus-neutralizing (VN) and haemagglutination-inhibiting (HI) antibodies. Biphasic modulation of the serological response was more evident with HI than with VN antibodies. At the inoculation site there developed a discrete swelling that regressed within the 10 week period of observation. Histologically the swelling consisted of an inflammatory granulomatous reaction, with an accumulation of macrophages containing phagocytosed droplets of vaccine. Plasma cells were also present. No inflammatory swelling developed in chickens and pheasants similarly vaccinated but comparable cellular changes were noted around the dispersed vaccine.
18,777,275
Fowl peritoneal exudate cells: collection and use for the macrophage migration inhibition test.
A method for the collection of fowl peritoneal exudate cells and their use in macrophage migration inhibition tests is described.
18,777,285
A technique for separating oocysts from faeces.
A technique to separate oocysts from large amounts of faeces by a "Continuous-Flow-Different-Density-Flotation" method is presented. Measures to save labour and to decrease the risk of contaminating the laboratory as well as the oocyst isolate during the centrifugation and harvesting of the oocysts from the centrifuge are described.
18,777,295
Spray vaccination of turkeys against Newcastle disease.
Turkeys poults were vaccinated against Newcastle disease by spray vaccination using Hitchner B1 and La Sota vaccines. Turkeys with maternally derived immunity vaccinated at 7, 35 and 63 days of age developed an active immunity. Each revaccination resulted in higher levels of haemagglutination-inhibiting and neutralising antibodies. Challenge with virulent virus showed that turkeys, serologically free from antibodies against Newcastle disease were less sensitive than specific pathogen free chicks to Newcastle disease.
18,777,335
Clinical and pathological observations on field and experimental zoalene poisoning in broiler chicks and the effect of the drug on laying hens.
Depression and ataxia was seen in 24-day-old chicks accidentally fed excess zoalene from 14 days of age. The presence of a small amount of furazolidone in the ration probably exacerbated the effect. There were no deaths. No other causes could be found for the condition and replacing the rations with food containing less than the recommended level of zoalene and no furazolidone resulted in recovery within 4 to 5 days. In an experimental study the syndrome was reproduced in baby chicks with as little as 2(1/2) times the recommended level of zoalene in the food. Increasing the amount of zoalene hastened the onset and increased the severity of symptoms and markedly depressed weight gains; the addition of a small amount of furazolidone had a synergistic effect. Inappetance may be largely responsible for the depression in weight gain, and damage to Purkinje cells seems to account for the ataxia and nervous signs. In laying birds 10 times the recommended level of zoalene in the food over 30 days caused inappetance, cessation of egg production, and progressive weakness, but no nervous signs.
18,777,343
[Influence of Eimeria acervulina duodenal coccidiosis on intestinal absorption of lysine and on the movement of water and electrolytes].
The absorption rate of 14C L-lysine and net flux of water and mineral ions (Na+, K+) were studied in 4-week-old male chickens infected with Eimeria acervulina (10(6) sporulated oocysts/chicken). Intestinal coccidiosis significantly decreased absorption rate of 14C-lysine. This effect was particularly pronounced in the jejunum. Net flux of water was also modified: its absorption was decreased in the middle and distal small intestine. In the duodenum a net absorption of water was converted to a net excretion. These effects were accompanied by an increase in tissue water content and in secretion rate of Na+ and K+.
18,777,344
Determination of haematology and blood chemistry values in healthy six-week old broiler hybrids.
Fourteen "comparison values" were determined for 6-week-old broilers. A total of 980 birds were sampled from 21 flocks to provide "comparison values" for body weight and blood characteristics. Production and management details are described and sources of variation in the "comparison values" within and between flocks are discussed. The presence of correlations between "comparison values" and between performance and "comparison values", both within and between flocks, is investigated.
18,777,356
Resistance of field isolates of Eimeria species to anticoccidial drugs.
A study was made of the incidence of coccidial oocysts in the litter of a broiler house used for commercial trials. The following anticoccidial drugs were under investigation: zoalene, Pancoxin, Lerbek and monensin. Monensin was the only drug able to suppress the numbers of oocysts appearing in the litter. Two species of Eimeria were isolated from this site and their response to anticoccidial agents studied in the laboratory. The isolate of E. tenella was not controlled by zoalene, clopidol or monensin but was controlled by amprolium, sulphaquinoxaline, methyl benzoquate and robenidine. The isolate of E. acervulina was not controlled by zoalene, amprolium, sulphaquinoxaline, methyl benzoquate, clopidol or robenidine. The only treatment successful in controlling the isolate of E. acervulina was monensin. Results obtained indicate that the lack of activity of certain drugs was due to drug resistance of the Eimeria species concerned.
18,777,357
Mycoplasma synoviae in the guinea-fowl.
A mycoplasma strain, isolated from natural synovitis of guinea-fowl, was identified as Mycoplasma synoviae. In experimental infection this agent showed clear pathogenicity for guinea-fowl, and to a lesser degree for chickens. In guinea-fowl the strain was more likely to result in synovitis and amyloidosis when inoculated by the intravenous route and to produce sinusitis after intrasinusal inoculation.
18,777,358
Titers of precipitins in strains of chickens exposed to Marek's disease.
Titers of precipitating antibody against Marek's disease (MD) herpesvirus were determined on serum collected from five strains of chickens at intervals throughout the 411 day test period. The average titers for the genetically resistant Cornell K strain were consistently higher (P <.01) than for the genetically susceptible Cornell S strain. This relationship between disease resistance and antibody titers may have been fortuitous because the titers of three other strains varied in relationship to each other and did not appear to be related to resistance against MD. However, when strain effect was removed there was some relationship between antibody titer and resistance to the disease since chickens that died from MD had lower titers up to 139 days (P <.05) than did others.
18,777,379
An age-related resistance of chickens to Marek's disease: some preliminary observations.
Chickens of 2 strains, 20 to 22 weeks of age and free of prior infection, were substantially more resistant than l-day-old chicks to mortality and tumor induction caused by exposure to Marek's disease virus. These older chickens were refractory to inoculation with up to 10(4) chick tumor-inducing doses of Marek's disease virus and, following contact infection, lesion frequencies were 8 to 30% of corresponding responses in chick controls. Resistance in contact exposed chickens was observed as early as the 8th week and, although variable, did not increase appreciably through the 20th week. Median latent periods to death were similar regardless of age at exposure. Older birds were fully susceptible to infection with Marek's disease virus and were only slightly resistant to development of microscopic lesions, thus suggesting that this resistance might be 'mediated through enhancement of lesion regression. Age-related resistance was confirmed to be unrelated to previously described tumor resistance caused by prior infection or genetic constitution:
18,777,381
Delayed hypersensitivity and leucocyte migration inhibition in chickens with BCG or Marek's disease infection.
Production of Migration Inhibition Factor in vitro by lymphocytes from chickens with delayed hypersensitivity was examined. Chickens were sensitized with Bacille Calmette-Guerin (BCG) and others with Marek's Disease (MD) virus. Peripheral blood was used as a source of cells for in vitro radial migration inhibition. Using purified Band 24 antigen from Mycobacterium bovis and >>A<< antigen from MD virus, migration inhibition was demonstrated in BCG and MD sensitized chickens respectively, and not in controls. Results correlated well with intra-dermal skin reactions. Old Tuberculin and crude MD antigens inhibited radial migration of leucocytes from control chickens. The use of peripheral blood as a source of lymphocytes facilitates repeated sampling, both prior to and following sensitization. As a result, the role of the bursa and thymus in the induction and maintenance of delayed hypersensitivity can be studied in vitro. Furthermore, the role of cellular immunity and humoral antibodies as contributors to oncogenicity and/or protection in MD can be examined.
18,777,382
Observations on host range and control of goose virus hepatitis.
A number of experiments were done with a strain of goose hepatitis virus (isolated from sick goslings in the Netherlands in 1969. This virus was easily grown in embryonating eggs of the Muscovy duck (Cairina moschata) as well as in embryonating goose eggs. It also proved possible to adapt it to White Pekin duck eggs. The susceptibility of embryonating eggs obtained by crossing Muscovy drakes with Pekin ducks was intermediate between that of eggs from the two parental breeds. It was not possible to adapt goose hepatitis virus to growth in chicken embryos. The sensitivity of goslings to the goose hepatitis virus was found to vary considerably according to the farms from which they came. These differences were caused by variations 'in the quantity of parentally derived antibodies. One day-old Muscovy ducklings appeared to be at least as sensitive to the virus as goslings. However, disease symptoms could not be produced with goose hepatitis virus in Pekin ducklings nor in ducklings obtained by crossing Muscovy drakes and Pekin ducks. Treatment with homologous immune serum protected susceptible goslings and Muscovy ducklings against the disease. Under farm conditions, mortality was reduced from 30 to 3%. A breeding flock of adult Muscovy ducks, which had by serum therapy survived a goose hepatitis infection at an early age, produced ducklings resistant to the goose hepatitis virus. Over 100 flocks of geese, totalling more than 6,000 birds, were actively immunized with goose hepatitis Virus. The progeny produced in the following breeding season resisted, almost without exception, a challenge at one day of age with virulent goose hepatitis virus.
18,777,395
Lead poisoning in domestic and wild ducks.
The results of clinical, radiological, hematological, histomorphological and toxicological research carried out on experimental lead poisoning of domestic and Wild ducks are reported and discussed. Radiological, histological and toxicological investigations were aimed at determining the most characteristic features for diagnosis. These experiments support previous research on spontaneous lead poisoning of ducks kept in private reserves (Del Bono, 1970) and toxicological researches carried out recently (Sivieri, Buggiani and Rindi, 1972) on many breeds of migratory birds and confirm the serious consequences of this disease on many breeds of wild birds in Italy.
18,777,397
Continuing medical education: AMEE Education Guide No 35.
This guide is designed to provide a foundation for developing effective continuing medical education (CME) for practicing physicians. For the purposes of this work, continuing medical education is defined as any activity which serves to maintain, develop, or increase the knowledge, skills and professional performance and relationships that a physician uses to provide services for patients, the public, or the profession (American Medical Association 2007; Accreditation Council for CME 2007). The term continuing professional development (CPD) is broader and has become more popular in many areas of the world. As defined by Stanton and Grant, CPD includes educational methods beyond the didactic, embodies concepts of self-directed learning and personal development and considers organizational and systemic factors (Stanton & Grant 1997). In fact, this guide describes many modalities that may be defined as CME or CPD. In the interest of simplicity, we will use the term continuing medical education (CME) throughout, with the understanding that the same strategies may be applied to non-clinical continuing professional education. For those who do not work exclusively in CME, many terms and processes may be unfamiliar. This guide is intended to provide a broad overview of the discipline of CME as well as a pragmatic approach to the practice of CME. The format provides an overview of CME including history and rationale for the discipline, followed by a practical approach to developing CME activities, the management of the overall CME programme and finally, future trends. At the end of the guide you will find resources including readings, websites and professional associations to assist in the development and management of CME programmes.
18,777,424
Learning and metaphors.
All thought and talk about learning involves the use of metaphors. Whilst metaphors aid our understanding of things by suggesting novel insights, they can also mislead if too much is read into the supposed likenesses. Acquisition and transfer are easily the most popular metaphors used to understand learning. This article argues that these metaphors commonly mislead when we take them to mean that learning is located inside of learners, and, hence, that the individual is the appropriate unit for understanding learning. This article discusses the strengths and limitations of the alternative metaphors invoked in some more recent theories of learning, metaphors including participation, construction/re-construction, and becoming. A consideration of these alternative metaphors reveals the multi-facetted nature of learning. It also highlights important kinds of learning, by groups, teams or communities, learning that are not plausibly located inside of individuals. Any rich account of professional practice needs to encompass the roles of both individual and group learning.
18,777,427
Bus use and older people: a literature review applying the Person-Environment-Occupation model in macro practice.
The same reasons that prompt older people to give up driving can also result in difficulties with accessing public transport. Difficulties using public transport can limit older people's participation in society, thereby impacting negatively on their health. Focusing on public buses, this review explicates the link between bus usability and the health of older people and frames existing evidence on bus usability issues. The Person-Environment-Occupation (PEO) model offers a framework by which bus usability can be assessed. A combination of person-centred, environmental, and occupation-related factors, including bus design, service provision and performance, information, and the attitudes of staff and the community, impact on older people's ability to catch buses. More systematic research needs to take place in order to develop a comprehensive understanding of bus usability. Occupational therapy has a key role to play in conceptualizing, implementing, and evaluating improvements in bus usability for older people.
18,777,441
The vascular trigger of type II diabetes mellitus.
Type II diabetes mellitus is associated with obesity and insulin resistance. However, many humans with these symptoms never develop diabetes. This raises the key question of the difference that determines why one obese individual develops diabetes, whereas another one does not. Here we review the experimental support for our hypothesis that mutual signaling between insulin producing beta cells and pancreatic endothelial cells determines whether a person develops type II diabetes. According to our hypothesis, a disturbance of this mutual signaling leads to diabetes in an insulin-resistant individual. We discuss that most type II diabetes-associated genes have a function in the vascular system, and that endoplasmic reticulum (ER) stress in beta cells can result from vascular defects in pancreatic islets. Whereas vascular complications have been widely accepted as a result of type II diabetes, we suggest that changes within the vascular system may act at an earlier stage and trigger the onset of type II diabetes.
18,777,448
[Thenar hammer syndrome].
Chronic traumatic aneurysm of the distal radial artery is rare. The literature offers only 20 cases of chronic traumatic vascular lesions of the thenar region. We present the case of a 58-year-old cheese maker who had done manual work for years and who experienced swelling at the thenar eminence, pain, cold and warm paresthesia and circulatory disturbance in his index finger. Duplex ultrasound and CT angiography revealed an aneurysm of the superficial branch of the radial artery indicating a thenar hammer syndrome. He was subjected to a microsurgical end-to-end repair after resection of the aneurysm. This is the first closely documented case of a true aneurysm of the superficial branch of the radial artery. We also present a comprehensive survey of published studies of chronic vascular lesions of the thenar region related to thenar hammer syndrome and patient occupation, symptoms, diagnostis and therapy.
18,777,469
Considerations in the choice of an antiepileptic drug in the treatment of epilepsy.
The advent of multiple new antiepileptic drugs (AEDs) in the past 15 years has provided new options for clinicians treating patients with epilepsy, but has also created a need for guidelines in AED use. For selection of the most appropriate AED, the neurologist must know the pharmacological properties of the AEDs and has to balance their benefits and potential risks for the individual patient. A key consideration in AED selection is spectrum of efficacy for seizure types and epileptic syndrome. Other factors in AED selection include safety and tolerability, ease of use and titration rate, potential interactions, and efficacy in coexisting nonepileptic conditions. Comorbid conditions may favor or exclude the use of certain AEDs in a particular patient. Special considerations apply in specific epilepsy populations, such as women of childbearing age, children, and the elderly. This article analyzes the various factors involved in choosing an AED.
18,777,477
T1rho-prepared balanced gradient echo for rapid 3D T1rho MRI.
To develop a T1rho-prepared, balanced gradient echo (b-GRE) pulse sequence for rapid three-dimensional (3D) T1rho relaxation mapping within the time constraints of a clinical exam (<10 minutes), examine the effect of acquisition on the measured T1rho relaxation time and optimize 3D T1rho pulse sequences for the knee joint and spine. A pulse sequence consisting of inversion recovery-prepared, fat saturation, T1rho-preparation, and b-GRE image acquisition was used to obtain 3D volume coverage of the patellofemoral and tibiofemoral cartilage and lower lumbar spine. Multiple T1rho-weighted images at various contrast times (spin-lock pulse duration [TSL]) were used to construct a T1rho relaxation map in both phantoms and in the knee joint and spine in vivo. The transient signal decay during b-GRE image acquisition was corrected using a k-space filter. The T1rho-prepared b-GRE sequence was compared to a standard T1rho-prepared spin echo (SE) sequence and pulse sequence parameters were optimized numerically using the Bloch equations. The b-GRE transient signal decay was found to depend on the initial T1rho-preparation and the corresponding T1rho map was altered by variations in the point spread function with TSL. In a two compartment phantom, the steady state response was found to elevate T1rho from 91.4+/-6.5 to 293.8+/-31 and 66.9+/-3.5 to 661+/-207 with no change in the goodness-of-fit parameter R2. Phase encoding along the longest cartilage dimension and a transient signal decay k-space filter retained T1rho contrast. Measurement of T1rho using the T1rho-prepared b-GRE sequence matches standard T1rho-prepared SE in the medial patellar and lateral patellar cartilage compartments. T1rho-preparedb-GRE T1rho was found to have low interscan variability between four separate scans. Mean patellar cartilage T1rho was elevated compared to femoral and tibial cartilage T1rho. The T1rho-prepared b-GRE acquisition rapidly and reliably accelerates T1rho quantification of tissues offset partially by a TSL-dependent point spread function.
18,777,535
MRI diagnosis of brown tumor based on magnetic susceptibility.
A 56-year-old male with chronic renal failure was incidentally found to have lytic bone lesions in the pubic symphysis, left femoral head, left acetabulum, left iliac bone, and L1 vertebra on computed tomography (CT). Subsequent magnetic resonance imaging (MRI) of the abdomen was performed (for evaluation of a renal lesion) which demonstrated marked loss of signal intensity in the L1 bone lesion on increasing TE gradient echo images, consistent with magnetic susceptibility effect due to hemosiderin. Brown tumor was confirmed at biopsy. The susceptibility imaging probes one particular histological characteristic of tissues and allows a restricted differential of lytic tumors that contain significant hemosiderin, including brown tumor.
18,777,537
Evaluation of locally recurrent pelvic malignancy: performance of T2- and diffusion-weighted MRI with image fusion.
To evaluate the performance of T2- and diffusion-weighted magnetic resonance imaging (MRI) with image fusion for detection of locally recurrent pelvic malignancy. The study group consisted of 28 patients (27 female, 1 male) who underwent pelvic MRI at 1.5 T after treatment of pelvic malignancy. MR images were reviewed independently by three blinded readers. The performance of the four sequences for detecting local recurrence was evaluated using receiver operating characteristic analysis: T2-weighted fast spin-echo (FSE), diffusion-weighted echo-planar imaging (DWI), dynamic contrast-enhanced (DCE) fat-suppressed T1-weighted spoiled gradient echo (SPGR), and T2-DWI with image fusion, the latter created using OsiriX Medical Imaging Software. Local recurrence was confirmed at biopsy in 16 patients. Twelve patients showed no evidence of recurrence on two consecutive MRI studies. The Az value for T2-DWI with image fusion (0.949) was statistically greater than that for T2-weighted FSE (0.849) (P<0.05). The sensitivity and specificity was 87.5% and 47.2%, respectively, for T2-weighted FSE, 100.0% and 50.0% for DWI, 95.8% and 58.3% for DCE fat-suppressed T1-weighted SPGR, and 93.8% and 72.2% for T2-DWI with image fusion. For depicting locally recurrent pelvic malignancy, T2-DWI with image fusion outperforms standard T2-weighted FSE and DWI and is comparable to DCE fat-suppressed T1-weighted SPGR.
18,777,555
Assessment of fluctuating velocities in disturbed cardiovascular blood flow: in vivo feasibility of generalized phase-contrast MRI.
To evaluate the feasibility of generalized phase-contrast magnetic resonance imaging (PC-MRI) for the noninvasive assessment of fluctuating velocities in cardiovascular blood flow. Multidimensional PC-MRI was used in a generalized manner to map mean flow velocities and intravoxel velocity standard deviation (IVSD) values in one healthy aorta and in three patients with different cardiovascular diseases. The acquired data were used to assess the kinetic energy of both the mean (MKE) and the fluctuating (TKE) velocity field. In all of the subjects, both mean and fluctuating flow data were successfully acquired. The highest TKE values in the patients were found at sites characterized by abnormal flow conditions. No regional increase in TKE was found in the normal aorta. PC-MRI IVSD mapping is able to detect flow abnormalities in a variety of human cardiovascular conditions and shows promise for the quantitative assessment of turbulence. This approach may assist in clarifying the role of disturbed hemodynamics in cardiovascular diseases.
18,777,557
Stromal myofibroblasts are drivers of invasive cancer growth.
Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.
18,777,559
Discriminating accuracy of medial temporal lobe volumetry and fMRI in mild cognitive impairment.
We investigated structural and functional changes in the medial temporal lobe (MTL) using magnetic resonance imaging (MRI) and compared the discriminative power of these measures with neuropsychological testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Functional MRI (fMRI) was performed in 21 elderly controls, 14 MCI subjects, and 15 mild AD patients during encoding and cued retrieval of word-picture pairs. A region-of-interest-based approach in SPM2 was used to extract the extent of hippocampal activation. The volumes of the hippocampus and entorhinal cortex (EC) were manually outlined from anatomical MR images. Discriminant analyses were conducted to assess the ability of hippocampal fMRI, MTL volumetry, and neuropsychological measures to classify subjects into clinical groups. Entorhinal but not hippocampal volumes differed significantly between the control and MCI subjects. Both entorhinal and hippocampal volumes differed between MCI and AD patients. There were no significant differences in the extent of hippocampal fMRI activation during encoding or retrieval between the groups. Entorhinal volume was the best discriminator with a discriminating accuracy of 85.7% between controls and MCI, 86.2% between MCI and AD, and 97.2% between controls and AD. Delayed recall of a wordlist classified the subjects, second best, with a discriminating accuracy of 81.8% between controls and MCI, 75% between MCI and AD and 93.5% between controls and AD. The accuracy of hippocampal volumetry ranged from 42.9 to 69.4%, and hippocampal fMRI activation during encoding and retrieval had a classification accuracy of only 41.4-57.7% between the groups. Our results suggest that evaluation of entorhinal atrophy, in addition to the prevailing diagnostic criteria, seems promising in the identification of prodromal AD. Future technical improvements may improve the utilization of hippocampal fMRI for early diagnostic purposes.
18,777,563
Accumulation of yolk in a caecilian (Gegeneophis ramaswamii) oocyte: a light and transmission electron microscopic study.
There is a paucity of information on the female reproductive biology of the caecilian amphibians when compared with the other vertebrate groups. Hence, the accumulation of nutrient reserves in the form of yolk and formation of yolk platelets were studied in Gegeneophis ramaswamii, adopting light microscopic histological and transmission electron microscopy analysis. Previtellogenic as well as vitellogenic follicles were observed in appropriate preparations. On the basis of the source and the routes of entry, we identified four types of yolk precursor materials, precursors 1 to 4. The earliest material appearing in the oocyte consists of abundant lipid vesicles during the previtellogenic phase, i.e., much before the follicular epithelium is fully established. This is a contribution from the oocyte mitochondria, which we identified as yolk precursor material 1, and it is autosynthetic. Once the follicle cell-oocyte interface is fully established, there is an accumulation of the principal component of the heterosynthetic yolk by sequestration from the blood through the intercellular spaces between follicle cells in a pinocytic process. This we identified as yolk precursor material 2. There was also an indication of a lipidic yolk material synthesis in the follicle cells sequestered from maternal blood through the follicle cells in an endocytic process in which the macrovilli of follicle cells and the microvilli of the oocyte play a role. This we identified as yolk precursor material 3. Contribution to the yolk of peptidic, glycosidic, and/or lipidic material synthesized in the vitellogenic oocyte was also indicated. This we identified as yolk precursor material 4. The sequential development of intercellular associations and indications of synthesis/sequestration of the yolk have been traced. Thus, we report the mechanistic details of synthesis/sequestration of the yolk materials in a caecilian.
18,777,571
Protein adsorption resistance and oxygen permeability of chemically crosslinked phospholipid polymer hydrogel for ophthalmologic biomaterials.
The biomimetic structure of a polymer hydrogel bearing phosphorylcholine groups was obtained from 2-methacryloyloxyethylphosphorylcholline (MPC) and a novel crosslinker, 2-(methacryloyloxy)ethyl-N-(2-methacryloyloxy)ethyl]phosphorylcholine (MMPC), to prepare biocompatible ocular materials. MMPC is a dimethacrylate with phosphorylcholine-analogous linkage. Previous reports clarified that the affinity of MMPC to MPC enables the water contents and mechanical properties of the poly(MPC) hydrogels to be varied without disturbing the bulk phases. In this study, we examined the protein adsorption resistance, water wettability, oxygen permeability, and electrolyte permeability of the mechanically enhanced poly(MPC) hydrogel crosslinked with MMPC. The amount of protein adsorbed on this hydrogel was 0.9 microg/cm(2), which accounted for 30% of Omafilcon A and 3% of Etafilcon A. Water contact angle experiments revealed the high wettability of the poly(MPC) hydrogels. The oxygen permeability and NaCl diffusion constant of the poly(MPC) hydrogels were 64 barrer and 48 x 10(-6) cm(2)/s, respectively. This high permeability resulted from the high water content, similar to the case of the human cornea. These results suggested that poly(MPC) hydrogels have good potential for use in ophthalmologic biomaterials.
18,777,582
Enhanced therapeutic effects for human pancreatic cancer by application K-ras and IGF-IR antisense oligodeoxynucleotides.
To investigate the combined effects of K-ras antisense oligodeoxynucleotide (K-ras ASODN) specific to GTT point mutation at codon 12 and type I insulin-like growth factor receptor (IGF-IR) antisense oligodeoxynucleotide (IGF-IR ASODN) on proliferation and apoptosis of human pancreatic cancer Patu8988 cells in vitro and in vivo. K-ras gene point mutation and its style at codon 12 of human pancreatic cancer cell line Patu8988 were detected by using polymerase chain reaction with special sequence primers (PCR-SSP) and sequence analysis. According to the mutation style, K-ras mutation ASODN specific to K-ras point mutation at codon 12 was designed and composed. After K-ras ASODN and IGF-IR ASODN treated on Patu8988 cells respectively or cooperatively, the proliferation and morphological change of Patu8988 cells were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony forming assay and transmission electron microscopy; the expression of K-ras and IGF-IR mRNA and protein in the treated cells was measured by reverse-transcript polymerase chain reaction (RT-PCR) and flow cytometry respectively; apoptosis was determined by flow cytometry. The combined antitumor activity of K-ras ASODN and IGF-IR ASODN was evaluated in BALB/c nude mice bearing human pancreatic cancer inoculated with Patu8988 cells. The results of PCR-SSP and sequence analysis showed that the human pancreatic cancer cell line Patu8988 had point mutation at codon 12, and the mutation style was GGT-->GTT. 2-32 microg/mL K-ras ASODN and 2-32 microg/mL IGF-IR ASODN could inhibit Patu8988 cells' growth, induce apoptosis and decrease the expression of K-ras and IGF-IR mRNA and protein alone. However, there was much more effective inhibition of growth and induction of apoptosis by their combination than by each one alone. In tumor bearing mice, the combination of K-ras ASODN and IGF-IR ASODN showed a significant inhibitory effect on the growth of transplanted pancreatic cancer, resulting in a statistically significant difference compared with each alone. It has been found that K-ras ASODN combined with IGF-IR ASODN could cooperatively inhibit the growth of Patu8988 cells, and induce their apoptosis via reinforcing specific down regulation of K-ras and IGF-IR mRNA and protein expression.
18,777,594
Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver.
To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sativa (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrificed. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxidative status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. The levels of liver enzymes in group 3 were significantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were significantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury.
18,777,598
Innate immunity to Paracoccidioides brasiliensis infection.
Innate immunity is based in pre-existing elements of the immune system that directly interact with all types of microbes leading to their destruction or growth inhibition. Several elements of this early defense mechanism act in concert to control initial pathogen growth and have profound effect on the adaptative immune response that further develops. Although most studies in paracoccidioidomycosis have been dedicated to understand cellular and humoral immune responses, innate immunity remains poorly defined. Hence, the main purpose of this review is to present and discuss some mechanisms of innate immunity developed by resistant and susceptible mice to Paracoccidioides brasiliensis infection, trying to understand how this initial host-pathogen interface interferes with the protective or deleterious adaptative immune response that will dictate disease outcome. An analysis of some mechanisms and mediators of innate immunity such as the activation of complement proteins, the microbicidal activity of natural killer cells and phagocytes, the production of inflammatory eicosanoids, cytokines, and chemokines among others, is presented trying to show the important role played by innate immunity in the host response to P. brasiliensis infection.
18,777,631
Coma falsely attributed to Lyme disease.
Neuroborreliosis has very low prevalence in Kentucky and coma due to Lyme disease is uncommon in North America. A patient diagnosed with Lyme disease in Kentucky, based on coma, typical inflammatory changes on brain imaging, and a positive ELISA resulted in an erroneous clinical impression. Diagnosis should have been confirmed by a positive result on Western Blot, polymerase chain reaction (PCR), or real-time polymerase chain reaction (RT-PCR) testing. Physicians must apply careful consideration before diagnosing a rare disease in areas where that condition is uncommon without first eliminating other differential options. Neuroborreliosis clinicalfindings are nonspecific and often require confirmatory testing, especially in nonclassical case presentations.
18,777,697
[Frequency of diseases and injuries in the Swiss horse population].
Through a written questionnaire, which was sent to a representatively distributed and randomly selected sample of Swiss horse owners, data of 2912 horses and ponies were acquired to extrapolate prevalence data of health disorders. General questions about the horse and associated factors of housing and use, as well as questions about the current health status and the occurrence of diseases and injuries had been asked. 718 horses (24.7% of the sample) had been examined by a veterinarian within the 12 months prior to the survey. Orthopaedic and traumatic disorders (41.5%) had the largest proportion, followed by gastrointestinal--(27.1%) and respiratory (14.0%) diseases. Half of the lameness cases occurred as a direct consequence of a injury. The injuries were associated with pasture/paddock (38.1%), kicking and biting (21.6%), boxstall (7.8%), terrain and hacking (13.4%), training (3.5%), competition (3.5%), transportation (3.0%) or other circumstances (9.1%). A change in feeding management up to 4 weeks before development of a colic episode occurred in 26.5% of all colic cases. In 13.8% of all respiratory cases the same disease was diagnosed in other horses in the same barn. 8.1% of all cases had to be treated surgically, 6.7% required hospitalization for several days. Information about diagnostic or therapeutic procedures was related to specific disease categories. In 25.6% of all cases diagnosed by a veterinarian alternative therapeutic methods were used either in addition to traditional medicine or exclusively.
18,777,726
[Acromioclavicular lesions: diagnosis and treatment].
Acromioclavicular trauma is a frequent pathology of the upper limb. Stages 1 and 2 don't required surgery. On the other hand more severe lesions (stages 3-6) often need a surgical care, even if there is not any consensus about the most appropriate treatment. We reviewed here the main steps in the diagnosis and treatment of the acromioclavicular lesions.
18,777,734
[Treatment by enlargement of septal perforations].
Assessment of surgical posterior enlargement for septal perforation. Ten patients included had a symptomatic perforation in area 2 and/or 3 of Cottle. The size of the perforations was superior at 10 mm. This is a retrospective study. The surgical procedure has consisted of an initial corection of anterior septal deviation, nasal deviation and supra-lobular depression. Afterwards, perforations were extended towards the back by respecting the choanal arch. Nasal obstruction, headache, epistaxis, crusting and nasal profil were assessed in preoperative and post surgical period at 2 months and at the time of a sent questionnaire. A visual analogue scale for nasal obstruction and headache was used. The patient's mean age was 53.9 years. The mean follow-up period was 16 months. The average hospital stay was 24 hours. In first step, two supra-lobular depresion and one nasal deviation were corected. The mean score of nasal obstruction was 7.6. All patient's were free of this symptom after surgery (10/10) (p < 0.00016). The mean score of headache was 7.8 and only five of the six patients were free of symptom (p < 0.01). Crusting and epistaxis were diseappared in seven of the height patients. The rate of success for the different symptom were 100% for nasal obstruction, 83.3% for headache and 87.5% for crusting and epistaxis. The surgical posterior enlargement for septal perforation is an effective procedure, reliable, simple, with very low morbidity.
18,777,768
[Reconstruction of a transfixing partial loss of substance from the wing of nose with the upper pedicled nasolabial flap].
The reconstruction of the wing of the nose is a surgical challenge. The aim of the reconstruction is both aesthetic and functional. The nasolabial flap with upper pedicule returned, described by Préaux in 1994, appears to be successful for this challenge. The advantages of this flap include simplicity, reliability, one-step procedure and good results. Nevertheless it presents functional and aesthetic disadvantages. We present a variant which allows to correct these disadvantages.
18,777,769
Post-traumatic otosclerosis: coincidence or trigger factor?
The etiology of otosclerosis is poorly understood and environmental as well as genetic factors have been implicated. In this paper we will present 3 cases of otosclerosis with a clinical history of trauma and we will discuss with a literature review the place of trauma in otosclerosis etiology. 3 patients with clinically diagnosed otosclerosis, operated, and with a clinical history of previous head trauma. It is probable that environmental factors could be involved in the development of the disease and we think that trauma could be one of them. The mechanisms by which it could results in otosclerosis remain unknown. However these cases appear to be rare and under studied.
18,777,771
Pain relief to a point.
Acupuncture can help to relieve some of the discomfort and pain associated with pregnancy. Midwife Sarah Budd has been practising the technique for 20 years.
18,777,832
Correlation of Fourier domain optical coherence tomography retinal nerve fiber layer maps with visual fields in nonarteritic ischemic optic neuropathy.
To correlate peripapillary retinal nerve fiber layer (NFL) loss and visual field defects in nonarteritic ischemic optic neuropathy (NAION). Patients with NAION and control subjects were enrolled in a case-control study. Participants were scanned with a Fourier domain optical coherence tomography (OCT) system. Peripapillary NFL thickness was averaged in hemispheric, quadrant, and octant divisions. Standard achromatic static perimetry was used to assess visual fields. The reproducibility of peripapillary NFL parameters was excellent in both the healthy and NAION groups. Eyes in the NAION group showed a significant decrease of peripapillary NFL thickness in terms of the overall average, all quadrant averages, and all octants. There were statistically significant correlations between the peripapillary NFL and visual fields in terms of both overall averages and superior-inferior differences. In NAION, the visual field and peripapillary NFL losses are correlated in both severity and location. Fourier domain OCT provides reproducible measurement of the peripapillary NFL and may be useful in the assessment of NAION.
18,777,877
These are wonderful people.
The position of academic dean in a dental school affords an opportunity to observe young men and women growing into professionals. I have seen numerous quite acts of thoughtful kindness and unselfish service. I have also witnessed the personal struggles of students working through their academic dishonesty and the challenges of balancing patients' needs with their own. Professional education is transformative, and faculty members play a key role as models and guides helping students become ethical practitioners.
18,777,884
Dental students persuade the Michigan Dental Association to strengthen its codes of ethics: do actions speak louder than words?
This is a case study of how four different groups viewed proposed language in professional ethics codes regarding personal relationships with patients. The ADA Council on Ethics, Bylaws, and Judicial Affairs; the House of Delegates of the Michigan State Dental Association; and first-year students at the University of Michigan School of Dentistry favored a strongly worded statement in their codes, while the House of Delegates of the ADA passed a statement that was more "advisory" in nature. Support material concerning the statement on personal relationships is presented as an ethics case, and suggestions are presented regarding the ethical principles underlying positions on the issue.
18,777,889
Novel approach for the Monte Carlo calculation of free-air chamber correction factors.
A self-consistent approach for the Monte Carlo calculation of free-air chamber (FAC) correction factors needed to convert the chamber reading into the quantity air-kerma at the point of measurement is introduced, and its implementation in the new EGSnrc user code egs_fac is discussed. To validate the method, comparisons between computed and measured FAC correction factors for attenuation Ax, scatter (Ascat), and electron loss (Aeloss) are performed in the medium energy range where the experimental determination is believed to be accurate. The Monte Carlo calculations utilize a full simulation of the x-ray tube with BEAMnrc and a detailed model of the parallel-plate FAC. Excellent agreement between the computed Ascat and Aeloss and the measured values for these correction factors currently used in the National Research Council (NRC) of Canada primary FAC standard is observed. Our simulations also agree with previous Monte Carlo results for Ascat and Aeloss for the 135 and 250 kVp Consultative Committee for Ionizing Radiation reference beam qualities. The computed attenuation correction agrees with the measured Aatt within the stated uncertainties, although the authors' simulations demonstrate that the evacuated-tube technique employed at NRC to measure the attenuation correction slightly overestimates Aatt in the medium energy range. The newly introduced corrections for backscatter, beam geometry, and lack of charged particle equilibrium along the beam axis are found to be negligible. On the other hand, the correction for photons leaking through the FAC aperture, currently ignored in the NRC standard, is shown to be significant.
18,777,925
Accuracy of cranial coplanar beam therapy using an oblique, stereoscopic x-ray image guidance system.
A system for measuring two-dimensional (2D) dose distributions in orthogonal anatomical planes in the cranium was developed and used to evaluate the accuracy of coplanar conformal therapy using ExacTrac image guidance. Dose distributions were measured in the axial, sagittal, and coronal planes using a CIRS (Computerized Imaging Reference Systems, Inc.) anthropomorphic head phantom with a custom internal film cassette. Sections of radiographic Kodak EDR2 film were cut, processed, and digitized using custom templates. Spatial and dosimetric accuracy and precision of the film system were assessed. BrainScan planned a coplanar-beam treatment to conformally irradiate a 2-cm-diameter x 2-cm-long cylindrical planning target volume. Prior to delivery, phantom misalignments were imposed in combinations of +/- 8 mm offsets in each of the principal directions. ExacTrac x-ray correction was applied until the phantom was within an acceptance criteria of 1 mm/1 degrees (first two measurement sets) or 0.4 mm/0.4 degrees (last two measurement sets). Measured dose distributions from film were registered to the treatment plan dose calculations and compared. Alignment errors, displacement between midpoints of planned and measured 70% isodose contours (Deltac), and positional errors of the 80% isodose line were evaluated using 49 2D film measurements (98 profiles). Comparison of common, but independent measurements of Deltac showed that systematic errors in the measurement technique were 0.2 mm or less along all three anatomical axes and that random error averaged [formula: see text] 0.29+/-0.06 mm for the acceptance criteria of 1 mm/1 degrees and 0.15 +/- 0.02 mm for the acceptance criteria of 0.4 mm/0.4 degrees. The latter was consistent with independent estimates that showed the precision of the measurement system was 0.3 mm (2sigma). Values of Deltac were as great as 0.9, 0.3, and 1.0 mm along the P-A, R-L, and I-S axes, respectively. Variations in Deltac along the P-A axis were correlated to misalignments between laser isocenter and radiation isocenter as documented by daily clinical Lutz tests. Based on results of comparisons of measured with calculated positions of the 80% dose lines along the major anatomical axes, a 1.25, 1.0, and 1.0 mm (0.75, 0.5, and 0.25 mm) gross tumor volume (GTV)-planning target volume (PTV) margin to account for delivery error would be appropriate for the P-A, R-L, and I-S axes, respectively, for an acceptance criteria of 1 mm/1 degrees (0.4 mm/0.4 degrees). It typically took 2 (3) ExacTrac x-ray image sets to achieve and verify acceptance criteria of 1 mm/1 degrees (0.4 mm/0.4 degrees). Our results demonstrated a measurement technique using a CIRS anthropomorphic head phantom with a modified film cassette, radiographic film (Kodak EDR2) with a custom film cutting template, and film dosimetry software has been developed and successfully applied to our clinic. It is recommended that a third party offer this service. Our goal of achieving accuracy of delivery of 1 mm or better in each of the three major anatomical axes was almost, but not quite achieved, not because of the accuracy of the image guidance system, but likely due to inaccuracy of laser isocenter and other systematic errors.
18,777,940
Helping parents decide on ADHD treatment for their children.
In the United States, medication is often the first intervention used to treat attention-deficit/hyperactivity disorder (ADHD). Yet psychosocial interventions with both parents and teachers working together to shape the child's behavior can also be an effective approach, enabling smaller amounts of medication to be used with fewer side effects. An overview of behavioral interventions is provided with a focus on parent training in child behavior management and teacher training in classroom management. Key nursing interventions on behalf of children with ADHD include assessing parental knowledge about treatment, listening supportively to parents, and promoting partnerships among parents, teachers, and providers.
18,777,965
Health services utilization and cost utility analysis of a walking program for residential community elderly.
Promoting the health and improving the ability and confidence of the elderly to live independently can reduce health care expenditures and increase the health of society as a whole. However, the evidence to promote physical activity in order to promote health among the aged population is weak, especially in regards to the economic evaluation of a walking program. These researchers confirmed that the cost utility of a 12-week walking training program is acceptable. Therefore, an outpatient clinic-based walking program for older adults is worth promoting. Cost utility analysis is the critical evaluation method in exercise programs. Health professionals are encouraged to apply the integrated indicators such as the Health Utility Index and the Incremental Cost Utility Ratio to clarify the effects of health-promotion interventions.
18,777,976
[Anticardiolipin and anti-beta2 glycoprotein-1 antibodies patients with breast carcinoma: a pilot study].
Thrombosis - the main manifestation of antiphospholipid syndrome (APS) - is at the same time observed in some patients with malignancies. Evaluation of prevalence of some antiphospholipid antibodies (aPL) in serum of patients with breast carcinoma and the possible correlation between aPL seropositivity and clinical symptoms. 40 patients with breast carcinoma and 38 patients with non-malignant diseases of breast were studied. Anticardiolipin antibodies (aCL) and antibodies to beta2 glycoprotein-I (anti-beta2GPI) were detected by ELISA. The aCL as well as anti-beta2GPI were positive in 1 patient with breast carcinoma, who at the same time presented with symptoms of APS. In the control group 2 patients were positive for anti-beta2GPI. We have not observed a difference of aPL prevalence between the group of patients with breast carcinoma and controls. The association of breast cancer and aPL seropositivity deserves further investigations.
18,778,015
[The management of pregnant women with antiphospholipid syndrome].
Antiphospholipid syndrome (APS) is associated with several pregnancy complications as: intrauterine growth restriction, preeclampsia, premature abrubtion of the placenta as well as an increased risk of deep vein thrombosis (DVT). Treatment in this disease is still equivocal. The aim is to reduce the level of circulating antibodies and to prevent from placental thrombosis. Currently used therapeutic schemes involve aspirin and heparins - preferable low molecular weight heparins. Aspirin increases the level of prostacyclins and reduces the level of tromboksan - the platelets prothrombotic factor. Heparins, apart from their anticlotting properties, have anti-inflammatory function. Doses and duration of therapy depend on the history of thrombosis, pregnancy complications and the level of antibodies. Steroids and immunoglobulins are not routinely used, due to their side effects and high costs. In patients unresponsive to listed medications with a high risk of pregnancy loss, it is allowed to perform plasma exchange. Treatment in APS prevents from pregnancy complications and episodes of DVT in susceptible patients. Administrating in early pregnancy increases chances for life delivery to 80%.
18,778,021
[Beta2 glycoprotein-I--the main antigen in antiphospholipid syndrome].
The term "antiphospholipid antibodies" describing a laboratory hallmark of antiphospholipid syndrome (APS) is a misnomer. It suggests that antibodies are directed against phospholipids. Meanwhile the specific antigens are in fact proteins demonstrating an affinity to phospholipids. In APS antibodies directed against a serum protein, beta2 glycoprotein-I, play most probably a pathogenic role and are strongly associated with clinical symptoms of the syndrome. Putative mechanisms of action of anti-beta2 glycoprotein-I antibodies are discussed.
18,778,023
[Therapy resistance antiphosholipid syndrome in the course of systemic lupus erythematosus: case report].
Antiphospholipid syndrome (APS) is one of the most common reasons of thromboembolic complications in the course of connective tissue diseases. There is a strong relationship between presence of antiphospholipid antibodies and the risk of thrombosis. APS related thromboembolic complications range from superficial vein thrombosis up to rapidly developing, life threatening, multi-organ embolism. We present a case of a 21-year old female who presented with myocardial infarction as the first symptom of systemic lupus erythematosus and APS. Afterwards she was consequently treated with antithrombotic and anti-aggregation agents but it did not prevent her from reoccurrence of middle retinal vein. During the 10-year follow up she presented with reoccurring neurological symptoms i.e.: headache, memory deficits, concentration loss and impairment of the cognitive functions. She was found many times to be positive for IgG and IgM anticardiolipin antibodies, anti-beta2glicoprotein-I antibodies and lupus anticoagulant.
18,778,025
Directed assembly of chiral oxidovanadium(V) methoxides into C4-symmetric metal(I) vanadate-centered quadruplexes: synergistic K+- and Ag+-specific transport.
A directed assembly process to form C4-symmetric, vanadate-centered quadruplexes, for the first time, from a given chiral oxidovanadium(V) complex allows for highly efficient K+- and Ag+-specific transport from aqueous phase containing three other alkali metal cations into organic solvents, reminiscent of the K+ specific transport exerted by four homochiral glycine residues of the opening site in KcsA membrane protein.
18,778,056
Intra/intermolecular direct allylic alkylation via Pd(II)-catalyzed allylic C-H activation.
The first catalytic direct alkylation of allylic C-H bonds via Pd(II)-catalysis is described in the absence of base. Polysubstituted cyclic compounds can also be constructed by the intramolecular direct allylic alkylation.
18,778,061
Energy transfer in new D-pi-A conjugated dendrimers: their synthesis and photophysical properties.
A series of new D-pi-A conjugated dendrimers based on benzothiadiazole and triphenylamine were developed via facile synthetic approaches. By changing the types of bridges between the different functional moieties of these dendrimers, their photophysical properties, especially the intramolecular energy transfer process, were effectively modulated.
18,778,080
Identification of cytochrome P450 enzymes involved in the metabolism of the designer drugs N-(1-phenylcyclohexyl)-3-ethoxypropanamine and N-(1-phenylcyclohexyl)-3-methoxypropanamine.
The involvement of human hepatic cytochrome P450 isoenzymes (P450s) in the metabolism of the designer drugs N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA) and N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA) to the common metabolite N-(1-phenylcyclohexyl)-3-hydroxypropanamine (PCHPA) was studied using insect cell microsomes with cDNA-expressed human P450s and human liver microsomes (HLMs). Incubation samples were analyzed by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry. Among the tested isoenzymes, P450 2B6, P450 2C19, P450 2D6, and P450 3A4 catalyzed PCEPA O-deethylation, and P450 2B6, P450 2C19, and P450 2D6 catalyzed PCMPA O-demethylation. According to the relative activity factor approach, these enzymes accounted for 22, 3, 30, and 45% of the net clearance for PCEPA and 51, 8, and 40% of the net clearance for PCMPA, respectively. At 1 microM PCEPA, the chemical inhibitors 4-(4-chlorobenzyl)pyridine for P450 2B6 and quinidine for P450 2D6 reduced metabolite formation in pooled HLMs by 37 and 73%, respectively, and at 10 microM PCEPA, they reduced metabolite formation by 57 and 26%, respectively. At 1 microM PCMPA, 4-(4-chlorobenzyl)pyridine and quinidine reduced metabolite formation in pooled HLMs by 25 and 39%, respectively, and at 10 microM PCMPA, they reduced metabolite formation by 62 and 27%, respectively. The experiments with the MAB inhibitory to P450 3A4 and the chemical inhibitor ketoconazole for P450 3A4 showed no inhibitory effect concerning PCEPA O-dealkylation. Experiments with HLMs from P450 2D6 poor metabolizers showed a reduction of metabolite formation as compared to pooled HLM of 73 and 25% (1 microM and 10 microM PCEPA) and 40 and 38% (1 microM and 10 microM PCMPA), respectively. In conclusion, the main metabolic step was catalyzed by different P450s.
18,778,087
Potent inhibition of human phosphodiesterase-5 by icariin derivatives.
Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 microg/mL) and its active principle icariin (1) (IC50 5.9 microM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.
18,778,098
Intramolecular 1,8-hydrogen atom transfer. Stereoselectivity of the hexopyranos-5'-yl radical reactions in Hex p-(1-->4)-Hex p disaccharide systems.
The stereoselective reduction of hexopyranos-5'-yl radicals in alpha-D-Hex p-(1-->4)-D-Hex p disaccharide models is described. These radicals are generated from a 6-O-yl radical located in the other monosaccharic unit through a 1,8-hydrogen atom transfer. The reaction, which is strongly influenced by steric and stereoelectronic effects, permits in some cases the transformation of alpha-D-Hex p-(1-->4)-D-Hex p into beta-L-Hex p-(1-->4)-D-Hex p disaccharides in a single step with high diastereoselectivity.
18,778,104
Spotlight on enoxaparin in ST-segment elevation myocardial infarction.
Enoxaparin (enoxaparin sodium; Lovenox) is a low-molecular-weight heparin (LMWH) that has recently been approved by the US FDA for use in patients with medically managed ST-segment myocardial infarction (STEMI), or STEMI with subsequent percutaneous coronary intervention. It binds to and potentiates the action of antithrombin, and inhibits coagulation factors XIa, IXa, Xa, and IIa (thrombin), thereby preventing formation of blood clots. Unfractionated heparin (UFH) has long been regarded as the antithrombotic agent of choice in the adjunctive treatment of patients with STEMI. However, compared with UFH, enoxaparin has many advantages in terms of its pharmacodynamic profile and, potentially, also its efficacy. Enoxaparin was significantly more effective than UFH in patients presenting with STEMI who underwent fibrinolytic therapy in terms of the 30-day combined incidence of all-cause mortality plus recurrent nonfatal myocardial infarction (MI) [primary endpoint], and all-cause mortality plus recurrent nonfatal MI plus urgent revascularization (secondary endpoint) in the ExTRACT-TIMI 25 trial. The significant difference in the incidence of the composite primary endpoint between these two groups was maintained at the 1-year follow-up. Although bleeding was reported more frequently with enoxaparin than with UFH in the ExTRACT-TIMI 25 trial, enoxaparin was associated with a net clinical benefit relative to UFH. Patients in this trial received enoxaparin as an initial 30 mg intravenous bolus, followed by 1 mg/kg subcutaneously within 15 minutes and then every 12 hours for up to 8 days; the first two subcutaneous dosages were not to exceed 100 mg. Patients > or =75 years of age did not receive the initial bolus of enoxaparin and the 12-hourly dosages were reduced to 0.75 mg/kg; the dose was also reduced to 1 mg/kg every 24 hours in patients of any age who had an estimated creatinine clearance of <30 mL/min. Data from several earlier randomized, multicentre, phase III trials support these results.
18,778,116
The magnitude of binocular disparity modulates search time for targets defined by a conjunction of depth and colour.
Nakayama and Silverman (1986) proposed that, when searching for a target defined by a conjunction of color and stereoscopic depth, observers partition 3D space into separate depth planes and then rapidly search each such plane in turn, thereby turning a conjunctive search into a "feature" search. In their study, they found, consistent with their hypothesis, shallow search slopes when searching depth planes separated by large binocular disparities. Here, the authors investigated whether the search slope depends upon the extent of the stereoscopically induced separation between the planes to be searched (i.e., upon the magnitude of the binocular disparity. The obtained slope shows that (1) a rapid search only occurs with disparities greater than 6 min of arc, a value that vastly exceeds the stereo threshold, and that (2) the steepness of this slope increases in a major way at lower disparities. The ability to implement the search mode envisaged by Nakayama and Silverman is thus clearly limited to large disparities; less efficient search strategies are mandated by lower disparity values, as under such conditions items from one depth plane may be more likely to "intrude" upon the other.
18,778,143
Assessment of generalized anxiety disorder diagnostic criteria in the National Comorbidity Survey and Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.
The authors investigated measurement properties of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, generalized anxiety disorder (GAD) criteria in the National Comorbidity Survey and the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD). The two studies used different widely used instruments. There were significant (p < .001) differences in measurement of GAD due to age, study, and age-study interaction on item thresholds and factor loadings of GAD, especially when different stem-probe structures of interviews were taken into account. Item thresholds were estimated to differ by as much as -.74 as a function of age and .40 as a function of study. Despite these differences, factor scores derived from symptom criteria strongly predicted categorical diagnostic outcomes based on symptom count. It is concluded that interview structure, especially the stem-probe format of structured interviews, and wording had significant effects on study findings; that future studies in psychiatric epidemiology should use common structured interviews as much as possible; and that factor scores can be used in conjunction with sum scores as cut points to retain the advantages of both dimensional and categorical classification.
18,778,157
Analyzing the convergent and discriminant validity of states and traits: development and applications of multimethod latent state-trait models.
The analysis of convergent and discriminant validity is an integral part of the construct validation process. Models for analyzing the convergent and discriminant validity have typically been developed for cross-sectional data. There exist, however, only a few approaches for longitudinal data that can be applied for analyzing the construct validity of fluctuating states. In this article, the authors show how models of latent state-trait theory can be combined with models of multitrait-multimethod analysis to develop a model that allows for analyzing convergent and discriminant validity in time: the multimethod latent state-trait model. The model allows for identifying different sources of variance (trait consistency, trait-method specificity, occasion-specific consistency, occasion-specific method specificity, and unreliability). It is applied to the repeated measurement of depression and anxiety in children, which was assessed by self and teacher reports (N = 375). The application shows that the proposed models fit the data well and allow a deeper understanding of method effects in clinical assessment.
18,778,163
On the dimensionality of the Dispositional Hope Scale.
The Dispositional Hope Scale (DHS; C. R. Snyder et al., 1991) consists of two subsets of items measuring Agency and Pathways. The authors used bifactor analysis to evaluate the dimensionality structure of the scale. Data from 676 persons (295 psychiatric patients, 112 delinquents, and 269 students) were analyzed. The authors conclude that although the Pathway items seem to explain some additional variance when the Hope scale variance is partionalized out, the DHS allows unidimensional measurement.
18,778,168
Advances in the medical management of Cushing's syndrome.
Management of Cushing's syndrome, that is, excess cortisol secretion, has undergone considerable advances since the pioneering studies by Harvey Cushing. Surgery is clearly first choice for all etiologies of Cushing's syndrome, and medical therapy is largely administered in the interim between other therapeutic options. The limited use of medical therapy is a consequence of the lack of a truly efficacious compound to restrain adrenocorticotrophic hormone or cortisol secretion, but this will hopefully change in the near future as molecules developed over the past few years are tested. This paper illustrates present and perspective medical treatments for Cushing's syndrome.
18,778,181
Effects of shielding adenoviral vectors with polyethylene glycol on vector-specific and vaccine-mediated immune responses.
Many individuals have been previously exposed to human adenovirus serotype 5 (Ad5). This prior immunity has long been known to hinder its use for gene therapy and as a gene-based vaccine. Given these immunogenicity problems, we have tested whether polyethylene glycol (PEG) can blunt immune effects against Ad5 during systemic and mucosal vaccination. Ad5 vectors were covalently modified with 5-, 20-, and 35-kDa linear PEG polymers and evaluated for their ability to produce immune responses against transgene antigen products and the vector itself. We show that shielding Ad5 with different-sized PEGs generally reduces transduction and primary antibody responses by the intramuscular or intranasal route. In contrast, PEGylated vectors generally appear better at boosting antibody responses in Ad-immune animals. Displaying either glucose or galactose on PEG mediated increased transduction and antibody responses by the intranasal, but not the intramuscular, route. In naive animals, PEGylated vectors generated T cell responses that were equal to or better than those by unmodified Ad. Priming by PEGylated vectors generally enabled better subsequent T cell responses after boost. Priming and boosting by PEGylated vectors produced T cell responses after boost that were equal to or higher than those produced by unmodified vectors. These data indicate that PEGylation can enable more effective application of Ad5 and perhaps other Ad serotype vaccines during prime-boost vaccination.
18,778,197
Effect of IL-6 deficiency on susceptibility to HSV-1 respiratory infection and intrinsic macrophage antiviral resistance.
Cytokines play important roles in the mechanisms of disease development. Interleukin-6 (IL-6) is associated with clearance of herpes simplex virus (HSV) infections and in virus-induced immunopathology. However, the importance of IL-6 in host defense against HSV-1 respiratory infection is unknown. This study tested the effect of knockout mice deficient for IL-6 on susceptibility to HSV-1 respiratory infection and on intrinsic macrophage antiviral resistance to HSV-1. Control C57BL/6 IL-6+/+ mice and IL-6 knockout mice (IL-6-/-) were intranasally inoculated with 50 microL of a standardized dose (3.2 x 10(5)) of HSV-1. Morbidity, mortality, and symptom severity were monitored for 21 days. A subset of mice was sacrificed at 48-h postinfection and lungs were analyzed for viral titers. Peritoneal macrophages were obtained from a third set of mice and assayed for antiviral resistance to HSV-1. IL-6-/- increased morbidity by 84%, mortality by 84%, and symptom severity score on days 7.5 through 11 (p < 0.05). IL-6-/- increased virus titers in the lung 4-fold (p < 0.01) and resulted in a decrease in macrophage antiviral resistance (p < 0.001). Results indicate that IL-6 plays an important role in susceptibility to respiratory infection in mice, which may be mediated at least in part by its effect on macrophage antiviral resistance.
18,778,200
Assessing the validity of measures of an instrument designed to measure employees' perceptions of workplace breastfeeding support.
Breastfeeding rates among working mothers are lower than among mothers who are not employed. An ecological framework suggests that health behaviors, such as breastfeeding, are influenced by intrapersonal and environmental factors. There is no existing instrument to measure women's perception of the workplace environment in providing breastfeeding support. The objective of this study was to pilot an instrument measuring perceptions of the work climate for breastfeeding support among working women. Data were collected from self-administered mailed questionnaires filled out by 104 pregnant women or women who had recently given birth and were employed and breastfeeding. Dimensionally analyses supported the two-dimensional model suggested by the literature. Internal consistency reliability coefficients were high (near 0.90), and the correlation between the subscales was moderately strong (0.68). Only a single item exhibited misfit to the scaling model, and that item was revised after review.
18,778,210
Health care-associated infection (HAI): a critical appraisal of the emerging threat-proceedings of the HAI Summit.
During the Health Care-Associated Pneumonia Summit conducted in June 2007, it was found that there is a need for educational efforts in several areas of health care-associated infections (HAI) that extend beyond pneumonia. This supplement to Clinical Infectious Diseases represents the proceedings of the HAI Summit, a diverse panel of clinical investigators whose goal was to assess the quality of evidence regarding issues surrounding HAI and to discuss potential implications for its diagnosis and treatment in the future.
18,778,223
A low-cost flow cytometric assay for the detection and quantification of apoptosis using an anionic halogenated fluorescein dye.
We describe here a technical improvement of an established colorimetric method used to detect and measure the occurrence of apoptosis in mammalian cells during in vitro cell culture. This assay uses an anionic halogenated fluorescein dye that is taken up by apoptotic cells at the stage of phosphatidylserine externalization. We demonstrate that apoptotic cells stained with this dye can be detected by flow cytometric analysis. Furthermore, we show that the modified method compares well with the standard annexin-V-based apoptosis assay and that it is significantly more cost-effective than the annexin-V assay.
18,778,255
Modeling the effects of anthropogenic habitat change on savanna snake invasions into African rainforest.
We used a species-distribution modeling approach, ground-based climate data sets, and newly available remote-sensing data on vegetation from the MODIS and Quick Scatterometer sensors to investigate the combined effects of human-caused habitat alterations and climate on potential invasions of rainforest by 3 savanna snake species in Cameroon, Central Africa: the night adder (Causus maculatus), olympic lined snake (Dromophis lineatus), and African house snake (Lamprophis fuliginosus). Models with contemporary climate variables and localities from native savanna habitats showed that the current climate in undisturbed rainforest was unsuitable for any of the snake species due to high precipitation. Limited availability of thermally suitable nest sites and mismatches between important life-history events and prey availability are a likely explanation for the predicted exclusion from undisturbed rainforest. Models with only MODIS-derived vegetation variables and savanna localities predicted invasion in disturbed areas within the rainforest zone, which suggests that human removal of forest cover creates suitable microhabitats that facilitate invasions into rainforest. Models with a combination of contemporary climate, MODIS- and Quick Scatterometer-derived vegetation variables, and forest and savanna localities predicted extensive invasion into rainforest caused by rainforest loss. In contrast, a projection of the present-day species-climate envelope on future climate suggested a reduction in invasion potential within the rainforest zone as a consequence of predicted increases in precipitation. These results emphasize that the combined responses of deforestation and climate change will likely be complex in tropical rainforest systems.
18,778,269
Comparative genome analysis of a Saccharomyces cerevisiae wine strain.
Many industrial strains of Saccharomyces cerevisiae have been selected primarily for their ability to convert sugars into ethanol efficiently despite exposure to a variety of stresses. To begin investigation of the genetic basis of phenotypic variation in industrial strains of S. cerevisiae, we have sequenced the genome of a wine yeast, AWRI1631, and have compared this sequence with both the laboratory strain S288c and the human pathogenic isolate YJM789. AWRI1631 was found to be substantially different from S288c and YJM789, especially at the level of single-nucleotide polymorphisms, which were present, on average, every 150 bp between all three strains. In addition, there were major differences in the arrangement and number of Ty elements between the strains, as well as several regions of DNA that were specific to AWRI1631 and that were predicted to encode proteins that are unique to this industrial strain.
18,778,279
Genomic expression analysis by single-cell mRNA differential display of quiescent CD8 T cells from tumour-infiltrating lymphocytes obtained from in vivo liver tumours.
We performed a genomic study combining single-cell mRNA differential display and RNA subtractive hybridization to elucidate CD8 T-cell quiescence/ignorance. By comparing actively maintained quiescent CD8 T cells from liver tumour tumour-infiltrating lymphocytes (TILs) with quiescent T cells at the single-cell level, we identified differentially expressed candidate genes by high-throughput screening and comparative analysis of expressed sequence tags (ESTs). While genes for the T-cell receptor, tumour necrosis factor (TNF) receptor, TNF-related apoptosis inducing ligand (TRAIL) and perforin were down-regulated, key genes such as Tob, transforming growth factor (TGF)-beta, lung Krüpple-like factor (LKLF), Sno-A, Ski, Myc, Ets-2 repressor factor (ERF) and RE1-silencing transcription factor (REST/NRSF) complex were highly expressed in the quiescent TIL CD8 cells. Real-time polymerase chain reaction (PCR) further confirmed these results. A regulation model is proposed for actively maintained quiescence in CD8 T cells, including three components: up-regulation of the TGF-beta pathway, a shift in the MYC web and inhibition of the cell cycle.
18,778,280
Increased secretion of hyperimmune antibodies following lipopolysaccharide stimulation of CD40-activated human B cells in vitro.
Human B cells can be cultured ex vivo for a few weeks, following stimulation of the CD40 cell surface molecule in the presence of recombinant cytokines such as interleukin-4 (IL-4). However, attempts to produce polyclonal antigen-specific human antibodies by in vitro culture of human B cells obtained from immunized donors have not been successful. It has been shown in mice that lipopolysaccharide (LPS) is a potent mitogen for B cells and plays an important role in the generation of antigen-specific antibody responses. Although it has long been believed that LPS has no direct effect on human B cells, recent data indicating that IL-4-activated human B cells are induced to express Toll-like receptor-4, the main LPS receptor, prompted us to study the effects of LPS on the proliferation and antibody secretion of human B cells. Our results showed that LPS caused a reduction in the expansion of CD40-activated human B cells, accompanied by an increase in antigen-specific antibody secretion. This result suggested that some, but not all, B cells were able to differentiate into antibody-secreting cells in response to LPS. This increased differentiation could be explained by the observation that LPS-stimulated human B cells were induced to secrete higher amounts of IL-6, a pleiotropic cytokine well-known for its B-cell differentiation activity. In vivo, the effect of LPS on cytokine secretion by B cells may not only enhance B-cell differentiation but also help to sustain a local ongoing immune response to invading Gram-negative bacteria, until all pathogens have been cleared from the organism.
18,778,289
Characterization of the recognition and functional heterogeneity exhibited by cytokine-induced killer cell subsets against acute myeloid leukaemia target cell.
The polyclonal cytokine-induced killer (CIK) cells exhibit potent cytotoxicity against a variety of tumour cells including autologous and allogeneic acute myeloid leukaemic (AML) targets. At maturity, three lymphocyte subsets: CD3(-) CD56(+), CD3(+) CD56(-) and CD3(+) CD56(+), constitute the bulk of the CIK cell culture. The CD3(-) CD56(+) subset behaves like classical natural killer (NK) cells where cytotoxicity is potentiated by blocking the human leucocyte antigen Class I molecules in the AML targets. Both the CD3(+) CD56(+) and CD3(+) CD56(-) subsets, though known to kill autologous and allogeneic targets to a comparable degree and therefore non-major histocompatibility complex (MHC)-restricted, nevertheless require the presence of the MHC molecule on the target, which interacts with their CD3-T-cell receptor complex. Although CIK cells are often termed 'NK-like' T cells, we have demonstrated that the well-characterized NK receptors KIR, NKG2C/E, NKG2D and DNAM-1 are not involved in the process of AML recognition for the CD3(+) CD56(-) and CD3(+) CD56(+) subsets. The CD3(+) CD56(+) and CD3(+) CD56(-) subsets express a polyclonal and comparable TCRVbeta repertoire in a Gaussian distribution. The CD3(+) CD56(+) subset kills AML targets more efficiently than its CD3(+) CD56(-) counterpart because of the presence of a higher proportion of CD8(+) cells. The CD3(+) CD56(+) subset comprise more terminally differentiated late effector T cells that bear the CD27(+) CD28(-) or CD27(-) CD28(-) phenotype, with a higher granzyme A content. In comparison, the phenotype of the CD3(+) CD56(-) subset is consistent with early effector T cells that are CD27(+) CD28(+) and CD62L(+), known to be less cytotoxic but possess greater proliferative potential.
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Mechanisms for recycling and biosynthesis of endogenous cannabinoids anandamide and 2-arachidonylglycerol.
The mechanisms of endogenous cannabinoid biosynthesis are not completely understood. We hypothesized that anandamide could be recycled by the cell to form new endocannabinoid molecules and released into the extracellular space. We determined that new endocannabinoids derived from exogenous anandamide or arachidonic acid were synthesized and released from RBL-2H3 cells in response to ionomycin. Treatment of RBL-2H3 cells with nystatin and progesterone, agents that disrupt organization of lipid raft/caveolae, resulted in the attenuation of anandamide and 2-arachidonyl glycerol synthesis and/or release in response to stimulation with ionomycin suggesting a role for these membrane microdomains in endocannabinoid biosynthesis. Furthermore, anandamide synthesis may be independent of N-acyl phosphatidylethanolamine phospholipase D as expression of the enzyme was not detected in RBL-2H3 cells. We also established that extracellular calcium is necessary for endocannabinoid biosynthesis because release of intracellular calcium stores alone does not promote endocannabinoid biosynthesis. Next, we examined the role of calcium as a 'switch' to activate the synthesis of anandamide and simultaneously reduce uptake. Indeed, [(3)H] anandamide uptake was reduced in the presence of calcium. Our findings suggest a mechanism indicative of calcium-modulated activation of anandamide synthesis and simultaneous termination of uptake.
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Obesity status and sick leave: a systematic review.
This review identified 36 studies on the relation between obesity status and sick leave. Pooling of effect estimates was not possible due to great heterogeneity between studies regarding definition of sick leave (short-term/long-term), measure of obesity (body mass index/waist circumference/percentage body fat), definition of obesity status (World Health Organization standards/other), study population (sex/age/occupation/country) and exposure and outcome ascertainment (self-reported/objectively assessed). Nevertheless, a clear trend towards greater sick leave among obese compared with normal weight workers could be discerned, especially for spells of longer duration. In studies from the USA, which consistently reported about five times lower number of sick leave days per person-year than European, obese workers had about 1-3 extra days of absence per person-year compared with their normal weight counterparts. In European studies, the corresponding difference was about 10 d. For overweight workers the data were conflicting, indicating either increased or neutral level of sick leave compared with normal weight. Regarding underweight, the studies were very few and concerns regarding direction of causality were greater. Finally, in all four interventional studies identified substantial weight loss in obese subjects resulted in reduced sick leave, at least temporarily. In conclusion, increasing obesity in children and adults is likely to negatively affect future productivity as obesity increases the risk of sick leave, disability pension and death.
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Expression of rat beta(1,4)-N-acetylglucosaminyltransferase III in Nicotiana tabacum remodels the plant-specific N-glycosylation.
Plant N-linked glycans differ substantially from their mammalian counterparts, mainly with respect to modifications of the core glycan, which typically contains a beta(1,2)-xylose and an alpha(1,3)-fucose. The addition of a bisecting N-acetylglucosamine residue by beta(1,4)-N-acetylglucosaminyltransferase III (GnTIII) is known to control the processing of N-linked glycans in mammals, for example by preventing alpha(1,6)-fucosylation of the core glycan. In order to outcompete plant-specific beta(1,2)-xylose and alpha(1,3)-fucose modifications, rat GnTIII was expressed either with its native localization domain (GnTIII) or with the cytoplasmic tail, transmembrane domain and stem region (CTS) of Arabidopsis thaliana mannosidase II (ManII) (GnTIII(A.th.)). Both CTSs targeted enhanced yellow fluorescent protein (eYFP) to a brefeldin A-sensitive compartment, indicative of Golgi localization. GnTIII expression increased the fraction of N-glycans devoid of xylose and fucose from 13% +/- 7% in wild-type plants to 60% +/- 8% in plants expressing GnTIII(A.th.). N-Glycans of plants expressing rat GnTIII contained three major glycan structures of complex bisected, complex, or hybrid bisected type, accounting for 70%-85% of the total N-glycans. On expression of GnTIII(A.th.), N-glycans displayed a higher heterogeneity and were of hybrid type. Co-expression of A. thaliana ManII significantly increased the amount of complex bisected structures relative to the plants expressing GnTIII or GnTIII(A.th.), whereas co-expression of human ManII did not redirect the pool of hybrid structures towards complex-type structures. The method described offers the advantage that it can be implemented in any desired plant system for effective removal of beta(1,2)-xylose and alpha(1,3)-fucose from the N-glycan.
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Syntactic anomaly elicits a lexico-semantic (N400) ERP effect in the second language but not the first.
Recent brain potential research into first versus second language (L1 vs. L2) processing revealed striking responses to morphosyntactic features absent in the mother tongue. The aim of the present study was to establish whether the presence of comparable morphosyntactic features in L1 leads to more similar electrophysiological L1 and L2 profiles. ERPs were acquired while German-English bilinguals and native speakers of English read sentences. Some sentences were meaningful and well formed, whereas others contained morphosyntactic or semantic violations in the final word. In addition to the expected P600 component, morphosyntactic violations in L2 but not L1 led to an enhanced N400. This effect may suggest either that resolution of morphosyntactic anomalies in L2 relies on the lexico-semantic system or that the weaker/slower morphological mechanisms in L2 lead to greater sentence wrap-up difficulties known to result in N400 enhancement.
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Polymorphism of HLA-DRB1, -DQB1 and -DPB1 genes in Bai ethnic group in southwestern China.
In this work, polymorphism of human leukocyte antigen (HLA)-DRB1, -DQB1 and -DPB1 genes was detected using polymerase chain reaction-sequence-based typing method in 128 healthy unrelated volunteers from the Bai ethnic group of Yunnan province of southwest China. Among all the 28 alleles detected for the DRB1 gene, the most common allele was DRB1*120201 with a frequency of 16.41%, followed by DRB1*090102, DRB1*080302, DRB1*1404, DRB1*150101, DRB1*140101 and DRB1*160201, with frequencies of 10.16%, 9.77%, 9.38%, 8.98%, 8.59% and 8.21%, respectively. Among 19 DQB1 alleles detected, the most frequent allele was DQB1*030101/0309 (35.94%), followed by DQB1*050201 (11.33%), DQB1*060101/060103 (10.54%) and DQB1*0401 (10.16%). For the DPB1 locus, the most common alleles were DPB1*0501 (42.19%), DPB1*1301 (13.28%), DPB1*020102 (10.93%) and DPB1*040101 (9.77%). The comparison of HLA class II allele frequencies of Bais with those of other Chinese populations suggested that the Bai ethnic group belonged to the southern group of Chinese.
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Harry Moss Traquair (1875-1954), Scottish ophthalmologist and perimetrist.
Harry Moss Traquair (1875-1954) was an Edinburgh Ophthalmologist, who was especially involved in the studies of perimetry and neuro-ophthalmology. In his monumental work, An Introduction to Clinical Perimetry, which for years was the standard textbook of perimetry, he included the description of the visual field as "an island of vision or hill of vision surrounded by a sea of blindness". His name continues to be recalled in the use of the term "Traquair Junctional Scotoma". In this history of Ophthalmology research, Traquair's life and work, including his major achievements, are discussed.
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