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Stochastic separation theorems. The problem of non-iterative one-shot and non-destructive correction of unavoidable mistakes arises in all Artificial Intelligence applications in the real world. Its solution requires robust separation of samples with errors from samples where the system works properly. We demonstrate that in (moderately) high dimension this separation could be achieved with probability close to one by linear discriminants. Based on fundamental properties of measure concentration, we show that for M<aexp(bn) random M-element sets in Rn are linearly separable with probability p, p>1-ϑ, where 1>ϑ>0 is a given small constant. Exact values of a,b>0 depend on the probability distribution that determines how the random M-element sets are drawn, and on the constant ϑ. These stochastic separation theorems provide a new instrument for the development, analysis, and assessment of machine learning methods and algorithms in high dimension. Theoretical statements are illustrated with numerical examples.
Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them. We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic among injection drug users (IDUs) seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to São Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.
Synthesis of a natural gamma-butyrolactone from nerylacetone by Acremonium roseum and Fusarium oxysporum cultures. Natural gamma-butyrolactone - (4R, 5R)-5-(4'-methyl-3'pentenyl)-4-hydroxy-5-methyl-dihydrofuran-2-one (2) was isolated as the product of microbial transformation of nerylacetone (1) by fungal strains. This product was obtained as the enantiomer (+) in high yields 24% and 61% with ee=94% and 82% by the biotransformation in the cultures of Acremonium roseum AM336 and Fusarium oxysporum AM13 respectively.
Outcomes from the trial implementation of a multidisciplinary online learning program in rural mental health emergency care. Emergency Departments (EDs) are often the first point of contact for people with acute mental health problems. The impact of the Mental Health Emergency Care (MHEC) online learning program on the knowledge and skills development of clinicians and support staff was evaluated, and options for sustainable implementation of the program were proposed. Participants were recruited from the four rural health services and the rural areas of one metropolitan health service in New South Wales, Australia. The MHEC course was conducted online over 24 weeks and comprised four sequential modules, each based on a clinical scenario that demonstrated a typical, acute mental health presentation to a general hospital ED. The course was designed to model collaborative practice in mental health emergency care. Participants were surveyed before and after completing the MHEC course. Statistically significant improvements were detected in participant confidence in managing key mental health problems, perceived self-efficacy in dealing with challenging, aggressive behaviours and confidence in key online learning skills. Participants also reported very positive experiences in relation to the course content and structure, instructor support, multidisciplinary discussion and feedback, and improvements in their knowledge and skills about emergency mental healthcare. This study provides evidence for the effectiveness and acceptability of an online educational program in developing the capacity of front-line staff to respond effectively to people who present to EDs with acute mental health problems. The positive outcomes and evaluations of the MHEC course provide support for the deployment of online learning programs that address mental health emergency care.
[Study of the effect of parotitis vaccine on DNA repair in human lymphocytes]. The effect of parotitis vaccine virus (strain L-3) on the DNA repair synthesis induced by 4-nitroquinoline-1-oxide has been studied. The efficiency of the repair synthesis depends on individual properties of the human body, viral multiplicity and concentration of the mutagen. A two-fold increase in DNA repair synthesis was obtained after infection of cells with low viral multiplicity (0.001 HADU50 per cell) and using 2.5 x 10(-7) M concentration of the mutagen A ten-fold increase in mutagen concentration affecting the infected cells was accompanied by the inhibition of DNA repair synthesis. Lymphocytes from children studied 7 days after vaccination by the attenuated virus did not reveal any changes in DNA repair synthesis as compared with the cells from nonvaccinated children.
Effectively addressing the mid- and long-term needs of young people affected by the tsunami in Aceh: an on-site assessment. Within two months of the Asian tsunami, a team of four individuals conducted an assessment on the post-disaster needs of young people in Aceh Province. In addition to assessing current needs, the team examined the extent to which young people (aged 14-24) were involved in the planning and implementation of ongoing rebuilding and relief efforts. Finally, the team assessed the degree to which young people could be involved in such efforts as the recovery process moves forward. The team: reviewed all existing documents developed and/or compiled by the UN Office for Coordination of Humanitarian Assistance (UNOCHA) from the inception of the disaster relief response to the present; met with approximately 20 organizations including UN agencies as well as international and local programs presently working in Banda Aceh and Maulaboh; and conducted direct discussions with young people in a variety of settings.
Lung donation after circulatory death. The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience. Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges. Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT.
Nucleotide sequence of class D tetracycline resistance genes from Salmonella ordonez. Plasmid pIP173, isolated from Salmonella ordonez strain BM2000, confers resistance to tetracycline and a number of other antibiotics. We determined the nucleotide sequence of the pIP173 tetR repressor and tetA resistance genes. The pIP173 tetR gene is essentially identical to the class D tetR gene from plasmid RA1. The pIP173 tet genes are flanked by directly repeated copies of the insertion sequence IS26. Interestingly, the 3' end of the tetR gene, encoding the C-terminal 16 amino acids of the TetR protein, extends into the flanking IS26 sequence. The relationships between the class A, B, C, and D TetA sequences parallel the relationships between the corresponding TetR sequences; class D is more closely related to class B than to either class A or C. Overall, the four TetA sequences show 38% identity and 57% similarity.
An item analysis of the Conditional Reasoning Test of Aggression. This manuscript uses item response theory (IRT) to estimate item characteristics of the Conditional Reasoning Test of Aggression (CRT-A). Using a sample size of 5,511 respondents, the present analysis provides an accurate assessment of the capability of the CRT-A to measure latent aggression. The one-parameter logistic (1PL) model, two-parameter logistic (2PL) model, and three-parameter logistic (3PL) model are compared before the item analysis. Results suggest that the 2PL model is the most appropriate dichotomous IRT model for describing the item characteristics of the CRT-A. Potential multdimensionality in the CRT-A is also examined. Results suggest that CRT-A items work as theoretically intended, with the probability of selecting an aggressive response increasing with latent trait levels. Information curves indicate that the CRT-A is best suited for use with individuals who are high on latent aggression. Exploratory analyses include an examination of polytomous IRT models and DIF comparing student and employee respondents. The results have implications for future research using the CRT-A as well as the identification of populations appropriate for measurement using this assessment tool.
Cytotoxic and antioxidative potentials of ethanolic extract of Eugenia uniflora L. (Myrtaceae) leaves on human blood cells. Eugenia uniflora is used in the Brazilian folk medicine to treat intestinal disorders and hypertension. However, scanty information exist on its potential toxicity to human, and little is known on its antioxidant activity in biological system. Hence, we investigated for the first time the potential toxic effects of ethanolic extract (EtOH) of E. uniflora (EEEU) in human leukocytes and erythrocytes, as well as its influence on membrane erythrocytes osmotic fragility. In addition, EEEU was chemically characterized and its antioxidant capacity was evaluated. We found that EEEU (1-480μg/mL) caused neither cytotoxicity nor DNA damage evaluated by Trypan blue and Comet assay, respectively. EEEU (1-480μg/mL) did not have any effect on membrane erythrocytes fragility. In addition, EEEU inhibited Fe2+-induced lipid peroxidation in rat brain and liver homogenates, and scavenged the DPPH radical. EEEU presented some polyphenolic compounds with high content such as quercetin, quercitrin, isoquercitrin, luteolin and ellagic acid, which may be at least in part responsible for its beneficial effects. Our results suggest that consumption of EEEU at relatively higher concentrations may not result in toxicity. However, further in vitro and in vivo studies should be conducted to ascertain its safety.
[Comparative clinical assessment of the factors determining the volume of operations for sarcomas of the extremity soft tissues]. In an analysis of data of 526 patients with carcomas of the extremity soft tissues the factors influencing the decision on the volume of surgery were determine. The 5 year survival of patients subjected to amputations was considerably lower than after sparing operations. Amputations were mostly made for local recurrences of the disease, neoplasm larger than 15 cm in diameter, low-differentiated sarcomas, with infiltration of the tumor into the bone and/or periosteum and localization of the tumor in distal parts of extremities. The rates of 5 year survival among the patients with malignant tumors of the extremity soft tissues subjected to sparing operations were found to be higher after combined program of treatment (operation + radiation therapy).
Divergent flow isoelectric focusing. Continuous-flow isoelectric focusing (IEF) has the potential to be an important method in proteome analysis. The current devices do not fully use the advantages of IEF, because they do not utilize all its important features including changes in background conductivity during the focusing. A novel continuous-flow IEF method has been developed based on planar divergent flow and control of local electric field by conductivity of electrode electrolytes. A hydrophilized polypropylene nonwoven fabric was used for creation of flow and electric manifold, making the assembled device cheap, flexible and easy to set up and operate. By using the colored low-molecular-weight pI markers we demonstrated much higher speed of focusing in the new designed channel in comparison with a channel based on currently used rectangular geometry. The developed divergent-flow IEF combines the speed of micro flow channels with the separation efficiency and sample load capacity of preparative devices.
Robot-assisted laparoscopic renal artery aneurysm repair with selective arterial clamping. Renal artery aneurysms represent a rare clinical entity, and most are managed with endovascular techniques when treatment is indicated. Laparoscopic and robot-assisted repair of renal artery aneurysms has been described; however, few reports exist in the literature. We describe our experience with the surgical management of a 1.6-cm right-sided renal artery aneurysms in a 35-year-old man who presented with flank pain. Using the DaVinci Si surgical platform (Intuitive, Sunnyvale, CA, USA), the aneurysm was resected and the renal artery was reconstructed. Segmental branches of the renal artery were dissected and selectively clamped during resection, allowing for regional rather than global renal ischemia. Operative time was 240 min, with an estimated blood loss of 200 cc. Warm ischemia time was only regional, for a duration of 44 min. Follow-up functional analysis showed preserved renal function in the right kidney. We describe our technique and show the technical feasibility of robot-assisted renal artery aneurysm repair. Furthermore, use of the DaVinci Si system facilitates segmental artery dissection, and allows for selective clamping during reconstruction. This avoids global renal ischemia and optimizes functional preservation.
The GI clinical nurse specialist: a generic role delineation. SGNA Masters Prepared Special Interest Group. We may have a role but find it difficult to specifically define it. As various specialties have emerged, roles have developed based on patient or physician need or practitioner innovation. This article is an attempt to present an organized structure of the contribution that can be made by the masters prepared gastroenterology nurse.
A Bibliometric Survey of Paraffin/Olefin Separation Using Membranes. Bibliometric studies allow to collect, organize and process information that can be used to guide the development of research and innovation and to provide basis for decision-making. Paraffin/olefin separations constitute an important industrial issue because cryogenic separation methods are frequently needed in industrial sites and are very expensive. As a consequence, the use of membrane separation processes has been extensively encouraged and has become an attractive alternative for commercial separation processes, as this may lead to reduction of production costs, equipment size, energy consumption and waste generation. For these reasons, a bibliometric survey of paraffin/olefin membrane separation processes is carried out in the present study in order to evaluate the maturity of the technology for this specific application. Although different studies have proposed the use of distinct alternatives for olefin/paraffin separations, the present work makes clear that consensus has yet to be reached among researchers and technicians regarding the specific membranes and operation conditions that will make these processes scalable for large-scale commercial applications.
Clinical application of modified Anyang type 2 esophageal intubation instrument--a new esophageal intubation method. The preliminary experience in the clinical use of Anyang Type 2 esophageal intubation instrument, designed by ourselves, in 11 patients with severe esophageal obstruction due to advanced carcinoma of the esophageal was reported. The diagnosis of all 11 cases was confirmed by barium-meal roentgenography. After intubation, all the patients could take liquid or soft diet by mouth. There was no operative mortality and the patients survived 2 to 14 months (mean 5.7 months). All of them could take food by mouth before death. The clinical application proved that the intubation has been a safe and suitable management.
Uptake of N-methyl-4-phenylpyridinium ion (MPP(+)) into PC12h pheochromocytoma cells. The uptake and accumulation of N-methyl-4-phenylpyridinium ion (MPP(+)), a neurotoxin produced by oxidation of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), into PC12h pheochromocytoma cells were examined. Concentration gradients of MPP(+) were established at its low concentrations of 10 to 100 nM. Uptake of MPP(+) into PC12h cells was mediated by saturable, carrier mediated transport systems with two different kinetic properties; a high-affinity and low-capacity system and a low-affinity and high-capacity system. The apparent K(m) values of these two systems were obtained to be 254.4 +/- 96.5 nM and 23.1 +/- 6.9 ?M, respectively, and the maximal uptake velocity was obtained to be 8.47 +/- 1.72 and 28.6 +/- 5.2 pmol/min/mg protein, respectively. The uptake by a high-affinity system was mediated by a carrier system common to dopamine and noradrenalin and MPTP itself proved to be taken up by this system, which was further confirmed by the inhibition of the MPP(+) uptake by nomifensine and mazindol. The uptake was inhibited by metabolic inhibitors, such as carbonyl cyanide m-chlorophenyl hydrazone, sodium cyanide and 2,4-dinitrophenol, and the uptake was inhibited by ouabain and nigercin. By subcellular fractionation, MPP(+) taken up was found to be localized mainly in cytosol fraction, but a definite amount of MPP(+) was found also in mitochondrial fraction.
[Complications in mediastinoscopy - a possibility of direct therapy]. Complications in diagnostic mediastinoscopy are between 0, 7 percent and 1,8 per cent. Lesions of the great vessels end letal in most cases. A possibility is reported how to treat lesions of the tracheobronchial system in emergency cases with lyophilised dura and a histoacryl-adhesive for tissue.
[Innovation in the incorporation of macronutrients to enteral nutrition formulas]. Enteral nutrition consists of the administration of chemically defined nutrients which are partially or fully metabolised in the intestinal tract, by the oral route or through a tube, to get an adequate and efficient nutritional supply. Enteral nutrition is the first option when one needs artificial nutrition, keeping parenteral nutrition only for those cases for which enteral nutrition would be insufficient or impossible. Enteral nutrition formulas are classified according to their composition with complete or uncompleted supply of nutrients, administration route, and protein content, energy density and type and content of fibre, and in second term according to general or special purposes utilization. Indeed, enteral nutrition formulas can be grouped as polymeric, oligomeric, organ-specific, therapeutic formulas, and nutrition supplements and modules. All these formulas are susceptible of improvement and innovation based mainly on the knowledge of diseases physiopathology, composition and functionality of food ingredients, which in turn contain a number of specific nutrients and bioactive compounds able to exert particular effects on the patient, and on technological treatment technology that will result in the amelioration of nutrient bioavailability. The present work reviews some of the most relevant functional ingredients used today in the innovation of enteral formulas, as well as their main physiological and biochemical effects in selected pathologies.
[Erythema nodosum in sarcoidosis. 37 cases]. Erythema nodosum was seen in 37 out of 564 cases of sarcoidosis, i.e. 6.4. per cent. The female preponderance of the association was 56.8 per cent. It was accompanied by fever in 84 per cent of cases and with an increased sedimentation rate, greater than 50 mm in the first hour, in 44 per cent of cases. Articular manifestations (arthralgia or arthritis) were seen in 73 per cent of cases, with a predilection for the ankles. Progression by acute excerbations of the erythema nodosum and/or articular manifestations was rare. Mediastino-pulmonary involvement accompanying the erythema nodosum included mediastinal lymphadenopathy in all cases. Infiltration of the pulmonary parenchyma was seen in 27 per cent. Spontaneous resolution of the mediastino-pulmonary lesions occurred in 82 per cent of cases, regardless of the initial radiological appearance.
Sunlight exposure and development of rickets in Indian toddlers. To study the role of sunlight exposure in determining the vitamin D status of underprivileged toddlers. Height and weight were measured, clinical examination was performed, Food Frequency Questionnaire was administered and history of sunlight exposure was obtained in all (61) toddlers attending daytime crèche (Group B). Ionised calcium (iCa), inorganic Phosphorous (iP), alkaline phosphatase activity (ALP), serum parathyroid hormone (PTH) and 25 Hydroxy vitamin D (25OHD) were measured. Data were compared with results of a survey measuring similar parameters in 51 (of 251 eligible) toddlers from the same slum (Group A). 111 children (mean age 2.6 yr (0.7), boys 56) were studied. Prevalence of hypovitaminosis D was 77% in group B toddlers (46 of 60) and 16.4% (10 of 61) had rickets, while none of the group A toddlers had 25OHD levels below 30 nmol/L. Four children (7.8%) from Group A as against 24 (42.9%) from Group B, had sunshine exposure of < 30 minutes per day. Underprivileged toddlers who were deprived of sunlight had a much greater incidence of hypovitaminosis D and frank rickets. The study has important public health implications and underscores the necessity for sunlight exposure in young children.
Fate of pharmaceuticals in rivers: Deriving a benchmark dataset at favorable attenuation conditions. Pharmaceutical residues are commonly detected organic micropollutants in the aquatic environment. Their actual fate in rivers is still incompletely understood as their elimination is highly substance specific and studies often report contradictory results. To elucidate the ceiling of attenuation rates of pharmaceuticals in rivers we carried out a study at a river with favorable conditions for the elimination of organic micropollutants. Experiments were carried out at a small stream in Germany. Composite samples were taken at both ends of a 12.5 km long river stretch located downstream of a sewage treatment plant and analyzed for 10 pharmaceuticals. Moreover, pore water samples were taken and in situ photolysis experiments at several sites within the river stretch were performed to assess the importance of these individual elimination mechanisms. Pharmaceutical concentration in the surface water at the first sampling site ranged from 3.5 ng L(-1) for propranolol to 1400 ng L(-1) for diclofenac. In comparison to carbamazepine which was used as persistent tracer, all other pharmaceuticals were attenuated along the river stretch. Their elimination was higher in a sunny, dry weather period (period I) compared to a period with elevated discharge after a heavy rainfall (period II). Overall, the measured elimination rates ranged from 25% for sulfamethoxazole (period II) to 70% for propranolol (period I). Photolysis was only a relevant elimination process for diclofenac and potentially also for sotalol; for these compounds phototransformation half-life times of some hours were determined in the unshaded parts of the river. Biotransformation in the sediments was also an important attenuation process since the concentrations of the other pharmaceuticals in the sediments decreased relative to carbamazepine with depth. For the chiral betablocker metoprolol this biotransformation was also confirmed by a decrease in the enantiomer fractionation from 0.49 at site A to 0.43 at site B and to <0.40 in the deeper sediments.
Single-molecule detection with a two-photon fluorescence microscope with fast-scanning capabilities and polarization sensitivity. We describe a laser-scanning two-photon fluorescence microscope that is capable of observing single molecules with excellent temporal resolution and three-dimensional spatial resolution. To demonstrate the capabilities of the instrument we present single-molecule fluorescence data obtained in several different scanning modes. In addition, a polarization-sensitive detection scheme can provide detailed three-dimensional information about the orientations of molecules in any of these scanning modes.
AGGRESCAN: method, application, and perspectives for drug design. Protein aggregation underlies the development of an increasing number of conformational human diseases of growing incidence, such as Alzheimer's and Parkinson's diseases. Furthermore, the accumulation of recombinant proteins as intracellular aggregates represents a critical obstacle for the biotechnological production of polypeptides. Also, ordered protein aggregates constitute novel and versatile nanobiomaterials. Consequently, there is an increasing interest in the development of methods able to forecast the aggregation properties of polypeptides in order to modulate their intrinsic solubility. In this context, we have developed AGGRESCAN, a simple and fast algorithm that predicts aggregation-prone segments in protein sequences, compares the aggregation properties of different proteins or protein sets and analyses the effect of mutations on protein aggregation propensities.
Pulmonary vascular disease in ventricular septal defect: structural and functional correlations in lung biopsies from 85 patients, with outcome of intracardiac repair. Pulmonary vascular structure was analysed using morphometric techniques, and arterial wall abnormalities in lung biopsy specimens taken from 85 cases of ventricular septal defect, aged 3 weeks to 30 years were described. The defect was closed in 53 patients, 12 died at operation and 11 survivors were recatheterized. Structural examination revealed a characteristic pathological picture which appeared to precede classical grade IV pulmonary vascular disease. This predilatation phase was identified by finding pre-acinar obstructive intimal proliferation or fibrosis, associated with only a slight increase in intra-acinar arterial muscularity, in the absence of stigmata of grade IV disease in patients with a pulmonary resistance greater than 6 units m2. Predilatation features occurred in 62 per cent of patients who either died at repair or who had post-operative pulmonary hypertension. These findings help identify a high risk group in whom resistance is higher than expected in the absence of classical grade IV changes. In addition, a marked increase in muscularity without intimal obstruction can also be associated with a pre-operative resistance of more than 6 units m2. The presence of medial hypertrophy only does not ensure either survival or a normal post-operative pulmonary arterial pressure. Early intra-cardiac repair is recommended before obstructive intimal fibrosis develops during the second year.
Systemic chemotherapy for gastric cancer with early recurrence after adjuvant S-1 monotherapy: a multicenter retrospective study. S-1 monotherapy is one of the standard adjuvant treatments for patients with stage II and III gastric cancers. Early recurrence after S-1 adjuvant therapy has a poor prognosis. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens. This was a multicenter retrospective study. Among gastric cancer patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy, patients who experienced a recurrence while receiving adjuvant therapy or within 6 months after completion and started systemic chemotherapy at four institutions between 2005 and 2015 were eligible. A total of 112 patients were included. The main treatment regimens were weekly paclitaxel (n = 38, 34%), irinotecan plus cisplatin (n = 31, 28%), capecitabine plus cisplatin (n = 7, 6%), and irinotecan monotherapy (n = 6, 5%). For all patients, median progression-free survival and overall survival were 3.7 and 11.4 months, respectively. Among 77 patients with measurable lesions, the overall response and disease control rates were 24.7% and 62.3%, respectively. Multivariate analyses for overall survival showed that Eastern Cooperative Oncology Group performance status 2 [hazard ratio (HR) 3.71; 95% confidence interval (CI) 1.78-7.73] and undifferentiated histological type (HR 2.04; 95% CI 1.35-3.44) were independent prognostic factors, and treatment regimens were not prognostic. Exploratory comparisons did not show statistically significant differences between treatment regimens. This study of the largest number of patients with early recurrence after S-1 adjuvant monotherapy demonstrated that the prognosis for patients treated by all regimens was similar and poor.
[Vitamin K deficiency in patients with CF despite supplementation]. Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. Vitamin K supplementation dose has not been clearly defined, and the effects of the supplementation are very ambiguous. Therefore, the aim of the present study was to assess body resources of vitamin K and determine the suitability of the coagulation parameters in the assessment of vitamin K deficiency in patients undergoing supplementation. The study comprised 30 CF patients aged from 1.5 to 32 years. In all patients, the concentration of the undercarboxylated prothrombin (prothrombin induced by vitamin K deficiency--PIVKA-II), as a marker of vitamin K deficiency, was estimated. For comparison of the diagnostic value of existing methods of assessment of vitamin K status, the coagulation parameters were evaluated (prothrombin ratio and INR). In spite of applied supplementation vitamin K status was not normal in all CF patients. Increased PIVKA-II concentrations (3.3-97 ng/ml) were found in 8 out of 30 (26.7%) patients, when the cut-off value of 2 ng/ml was used. Abnormal PIVKA-II levels corresponded to pathological values of the coagulation parameters only in one patient. In the remaining 7 CF subjects with increased concentration of the undercarboxylated prothrombin, coagulation parameters were normal. Vitamin K deficiency occurs in CF patients despite applied supplementation. The accurate supplementation dose should be estimated individually and the assessment of its effectiveness requires studies allowing to determine the real body resources of vitamin K. The coagulation parameters are not a good indicator of vitamin K deficiency.
Tumor detection with radiopharmaceuticals. The most common primary ocular tumor in adults is malignant melanoma of the choroid. Metastatic tumors to the choroid occur with the same frequency. The radioactive phosphorous uptake test is used most often as a nuclear diagnostic test. The test does not differentiate melanomas from metastases, and it is necessary to perform surgery for proper placement of a detection device within a distance of 1-2 mm of the tumor. These deficiencies leave ophthalmologists with a pressing need for a gamma-emitting radiopharmaceutical that would facilitate noninvasive identification of choroidal melanoma. This need is made more urgent by the fact that recently, radiation therapy has been used to treat these tumors rather than enucleation. Eyes then harbor irradiated melanoma whose status is unknown. The tumor rarely decreases in size more than 25% to 50%. There is thus a need for a specific diagnostic test to assess the nature of the tumor and the effectiveness of therapy.
Short range order at the amorphous TiO(2)-water interface probed by silicic acid adsorption and interfacial oligomerization: an ATR-IR and 29Si MAS-NMR study. Adsorption and oligomerization of H(4)SiO(4) at the amorphous TiO(2)-aqueous interface were studied using in situ Attenuated Total Reflectance Infrared (ATR-IR) and ex situ solid state (29)Si nuclear magnetic resonance (NMR). The ATR-IR spectra indicate that a monomeric silicate species is present at low silicate surface concentration (Γ(Si)). Above a threshold Γ(Si) linear silicate oligomers are formed and these oligomers dominate the surface at high Γ(Si). Interestingly the ATR-IR spectra of H(4)SiO(4) on the TiO(2) surface are very similar to those previously observed on the poorly ordered iron oxide phase ferrihydrite. The (29)Si NMR spectrum of silicate on the TiO(2) surface shows the presence of Si in three states with chemical shifts corresponding to isolated monomers (Q(0)), the ends of linear oligomers (Q(1)) and the middle of linear oligomers (Q(2)). The ratio of the area of the Q(1) and Q(2) peaks was ≈2:1 which is consistent with the proposed formation of linear silicate trimers by insertion of a solution H(4)SiO(4) between adjacent suitably orientated adsorbed silicate monomers. A structural interpretation indicates that the observed interfacial silicate oligomerization behavior is a general phenomenon whereby bidentate silicate monomers on oxide surfaces are disposed towards forming linear oligomers by condensation reactions involving their two terminal Si-OH groups. The high surface curvature of nanometer sized spheres inhibits the formation of interfacial silicates with a higher degree of polymerization.
Facilitating chlamydia testing among young people: a randomised controlled trial in cyberspace. Chlamydia notifications have been rising in Australia for over a decade and are highest in young people. This study aimed to evaluate the impact of an internet-based intervention on chlamydia testing among young people 16-25 years. In this randomised controlled trial, recruitment, data collection, study interventions and follow-up occurred entirely in cyberspace, facilitated by a website. Eligible participants were aged 16-25 years and resided in Australia. The intervention group received personalised emails inviting interaction about chlamydia testing, while the control group received regular impersonal emails. Primary outcome was self-reported chlamydia testing at 6-month follow-up; secondary outcomes were condom use and changes in knowledge and attitudes. 704 young people completed baseline information, 40 were excluded and five withdrew prior to follow-up. The follow-up rate was 47.3% overall. In the intervention group, 40.6% (95% CI 30.7% to 51.1%) reported having had a chlamydia test at follow-up compared with 31.0% (95% CI 24.8% to 37.2%) in the control group (p=0.07). A per-protocol analysis found that those who engaged in email interaction were more likely to report chlamydia test uptake compared with those in the control group (52.5%, 95% CI 39.3 to 65.4% cf 31.0%, 95% CI 24.8% to 37.2%, p=0.002). There were no differences in secondary outcomes between groups. This is the first randomised controlled trial undertaken in cyberspace to promote chlamydia testing. E-technology may be useful in promoting chlamydia testing and healthcare seeking behaviour in young people.
Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase. Angiogenesis plays an important role in tumor growth and metastasis. Thymidine phosphorylase (TP), as well as vascular endothelial growth factor (VEGF), is known to be an angiogenic factor. The aim of this study was to clarify whether TP regulates angiogenesis and to determine the clinicopathological role of TP expression in gallbladder cancer. Thirty-seven patients with gallbladder cancer who underwent curative surgical resection were included in this study, and we evaluated results in 21 of these patients in whom TP gene expression could be measured. Intratumoral TP gene expression was evaluated using the Danenberg tumor profile method. TP gene expression was classified into two groups according to median values: high and low. Tissue TP expression was classified into two groups (positive and negative) by a pathologist. Clinicopathological variables were compared between groups with high and low TP gene expression (TP high and TP low groups). No correlation was observed between TP gene expression (high and low groups) and any clinicopathological variables except survival rate. However, the survival rate was significantly lower in the TP high group (P<0.05). TP gene expression was associated with tissue TP expression evaluated by immunohistochemical staining (P<0.05). In addition, tumor microvessel density was significantly higher in the TP high group (P<0.05). Expression of the TP gene in gallbladder carcinoma is associated with angiogenesis and may be a new independent prognostic parameter.
Tear condition following unilateral ptosis surgery. To evaluate changes in tear film condition following unilateral ptosis surgery. This interventional case series includes patients with unilateral blepharoptosis scheduled for ptosis surgery with no prior history of eye disease and surgery over a 2-year period. Tear film evaluation before surgery were performed, which included Schirmer test with and without anesthesia, and tear break up time (TBUT). Ptosis surgery included levator resection and frontalis sling. The previously mentioned tests were repeated 1, 3, and 6 months after surgery. Subjective symptoms related to dry eye also evaluated before and after surgery. A total of 83 patients including 46 (55.4%) male subjects with mean age of 26.2 ± 16.2 years were enrolled in the study. The most common cause of ptosis was congenital in 77 (92.8%) patients. Surgical intervention included levator resection in 56 (67.5%) cases and frontalis sling procedure in 27 (32.5%) cases. The result of surgery was good in 47 (56.6%) patients while under- and overcorrection were observed in 32 (39.8%) and 3 (3.6%) patients, respectively. Schirmer's test with and without anesthesia and TBUT after surgery revealed a decrease in tear quantity and quality after surgery with time. Patients who had subjective complaints from dryness after surgery only had shorter TBUT among the objective signs. Ptosis surgery can decrease the quantity and quality of tears in operated eyes. Since some of these patients may need other types of operations in future, such as refractive or cataract surgery, evaluation of the tear condition before further surgery is prudent.
The value of the MMPI conversion 'V' in the assessment of psychogenic pain. The conversion 'V' is a familiar MMPI pattern which is traditionally used as a clinical marker of psychogenic pain. The 'V' form is assumed to arise because conversion suppresses depression thereby lowering scores on scale D, and exacerbates physical sensations thereby increasing scores on Hs and Hy. An inverse relationship between scales Hs and Hy, and D is therefore expected. These assumptions were tested in 102 patients with low back pain and organic findings, and 93 patients with non-organic findings. The pattern of correlation among the three scales did not distinguish organic patients from non-organic patients in which conversion is assumed to account for pain. Scale D was not inversely related to scales Hs and Hy in the non-organic group as expected from theory. The findings do not support the use of the conversion 'V' as a clinical marker.
Phase I/II study of bi-weekly XELIRI plus bevacizumab treatment in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2-8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934). The recommended dose of capecitabine was determined to be 2000 mg/m2. Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1-10.9 months], and median overall survival was 18.9 months (95% CI 11.6-28.4 months). Response rate was 17.4% (95% CI 6.4-28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (<10%). Bi-weekly XELIRI plus bevacizumab was found to be a safe and effective second-line treatment in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy.
Oculocutaneous albinism and analysis of tyrosinase gene in Japanese patients. Oculocutaneous albinism (OCA) is a heterogeneous groups of autosomal-recessive genetic disorders. The molecular pathogenesis of several types of OCA have been clarified in the ten years since our first report in 1989 on a pathologic mutation of the tyrosinase gene. In this article, a new classification of OCA based on genetic evidence is briefly reviewed, and our study on Japanese patients with tyrosinase-negative OCA is summarized.
The combined effect of silanols and the reversed-phase ligand on the retention of positively charged analytes. The nature of the interaction of positively charged analytes with the surface of reversed-phase bonded phases has been investigated as a function of both pH and volume fraction of organic modifier. Studies of the combined effect of both the parameters have been previously reported by us, and the data presented here further demonstrate a multiplicative interaction between pH and the concentration of organic modifier in the mobile phase. Fitting of the data as functions of pH and eluent composition clearly shows that the hydrophobically assisted ion-exchange process dominates over a purely reversed-phase or a pure ion-exchange retention mechanism. The underlying theory is developed in detail, and the mechanism is elucidated using several reversed-phase packings of substantially different character.
The influence of communication and information sources upon decision-making around complementary and alternative medicine use for back pain among Australian women aged 60-65 years. This study examined factors influencing decision-making on complementary and alternative medicine (CAM) use for back pain and back pain sufferers' communication about CAM use. A cross-sectional postal survey was conducted in 2011/2012 as a sub-study of the Australian Longitudinal Study on Women's Health (ALSWH). The sample contained 1620 women from the 1945-1951 cohort of the ALSWH, aged 60-65 years who were eligible for the sub-study, as they had experienced back pain during 12 months prior to the survey. Of these, 1310 (80.9%) returned completed questionnaires. A significant proportion of women consulted a CAM practitioner (76%, n = 1001) and/or had self-prescribed CAM treatment (75%, n = 985). Of the women who used CAM for their back pain, 20% consulted their general practitioner (GP) prior to using CAM and 34% always informed their GP following CAM use. Forty-three per cent of the women were influenced by their doctors, 39% by friends/colleagues, 36% by family/relatives, 33% by their partner, 30% by a CAM practitioner, 20% by a pharmacist, 16% by a book/magazine, 11% by mass media, 10% by an allied health worker and 6% by the Internet. Our results show that information sources used by women for their decision-making on CAM use differed according to the symptoms. While non-professional information sources (e.g. family/relatives) positively influenced women in their decision to use CAM for a range of back pain-related symptoms (e.g. headaches/migraines), doctors and allied health workers (e.g. nurses) negatively influenced women in their decision to consult a CAM practitioner for a range of back pain-related symptoms (e.g. headaches/migraines, neck pain). Women seek information from a wide range of professional and non-professional sources with regard to their decision-making around CAM use for back pain. Back pain care providers need to ensure effective communication with their back pain patients regarding safe, effective and co-ordinated back pain care options.
Enantioselective effects of optically active alpha-methylbenzyl-s-triazine on the root growth of rice and Echinochloa plants and their herbicidal activity. The chiral requirement on the alpha-methylbenzyl moiety of 2,4-diamino-6-chloro-s-triazine for sufficient inhibition of root growth was similar towards both rice and barnyard millet. With the monoalkylamino series, the most suitable configuration was markedly changed by the substituent on the other amino moiety. However, for the dialkylamino series, the (S)-enantiomer was an active inhibitor. Clear species selectivity between rice and barnyard millet was observed in the series for the (R)-enantiomers, providing high herbicidal activity toward Echinochloa plants and safety toward rice. The enantioselectivity against barnyard millet increased with increasing inhibitory activity of the active enantiomers, following Pfeiffer's rule. R-EtNH (3) controlled the growth of barnyardgrass with leaf-burning (LB) under paddy conditions, and S-EtNH (4) and S-Et2N (20) controlled the growth without LB. The RS-EtNH derivative is an interesting inhibitor controlling the growth of barnyardgrass from the just-germinated stage (by the (R)-enantiomer) to early-middle growth stage (by the (S)-enantiomer).
Role of NO and endothelin in hemoglobin-induced pulmonary vasoconstriction. The underlying mechanisms of hemoglobin (Hb)-induced vasoconstriction are not yet well understood. The aim of this study was to elucidate the influence of nitric oxide (NO) and endothelin (ET) on Hb-induced pulmonary vasoconstriction. Therefore, an autologous Hb preparation was administered into isolated rabbit lungs, in which pulmonary artery pressure (PAP) and weight gain was monitored. Either glyceroltrinitrate (GTN; 10(-5) M; n=6), L-arginine (10(-2) M; n=6), L-NAME (10(-4)M; n=6), ET(A)- or ET(B)-receptor antagonists (BQ,23, 10 6M, n=6) or (BQ788, 10(-6) M, n=6) were added to the perfusion fluid and NOx and thromboxane A2 levels were measured. In the control group the Hb-stimulation resulted in a pressure response up to 25.1+/-2.1 mmHg (p < .05), which was 136+/-6% of the reference value. The PAP increase was significantly (p < .05) blunted after GTN (71+/-5%), L-arginine (93+/-6%) and BQ788 (88+/-7%). Pretreatment with L-NAME (139+/-13%) or BQ123 (115+/-9%) did not show significant changes in PAP. The reduction of the Hb-induced pulmonary hypertension by NO-donors points toward the inactivation of NO by free hemoglobin. Likewise, ET(B)-receptor mediated vasoconstrictive effects without changes in NOx concentrations seem to play a pathogenetic role in the Hb-induced pulmonary vasoconstriction.
GHz-bandwidth optical filters based on high-order silicon ring resonators. Previously demonstrated high-order silicon ring filters typically have bandwidths larger than 100 GHz. Here we demonstrate 1-2 GHz-bandwidth filters with very high extinction ratios (~50 dB). The silicon waveguides employed to construct these filters have propagation losses of ~0.5 dB/cm. Each ring of a filter is thermally controlled by metal heaters situated on the top of the ring. With a power dissipation of ~72 mW, the ring resonance can be tuned by one free spectral range, resulting in wavelength-tunable optical filters. Both second-order and fifth-order ring resonators are presented, which can find ready application in microwave/radio frequency signal processing.
Historical note: "the epileptic constitution": the psychoanalytic concept of epilepsy. The rise of the psychoanalytic approach to behavioral medicine in the early part of the 20th century created a unique concept of the nature and the aetiology of epilepsy based upon dynamic psychopathology. As a direct result of this a radical change in both medical and community perception of this condition was generated, and this was to persist up to and beyond the mid-century mark. This historical note details the adoption, and the rise and fall of this concept of "the epileptic constitution", and a consideration of the negative effects that flowed from this, permeating all areas of psychiatry, neurology and even the criminal justice system.
Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Roquin function in T cells is essential for the prevention of autoimmune disease. Roquin interacts with the 3' untranslated regions (UTRs) of co-stimulatory receptors and controls T-cell activation and differentiation. Here we show that the N-terminal ROQ domain from mouse roquin adopts an extended winged-helix (WH) fold, which is sufficient for binding to the constitutive decay element (CDE) in the Tnf 3' UTR. The crystal structure of the ROQ domain in complex with a prototypical CDE RNA stem-loop reveals tight recognition of the RNA stem and its triloop. Surprisingly, roquin uses mainly non-sequence-specific contacts to the RNA, thus suggesting a relaxed CDE consensus and implicating a broader spectrum of target mRNAs than previously anticipated. Consistently with this, NMR and binding experiments with CDE-like stem-loops together with cell-based assays confirm roquin-dependent regulation of relaxed CDE consensus motifs in natural 3' UTRs.
The geriatric certificate program: collaborative partnerships for building capacity for a competent workforce. Many practicing health care providers find themselves ill-prepared to meet the complex care needs of older adults. The Geriatric Certificate Program (GCP) represents a collaborative partnership leveraging existing educational courses, with new courses developed to fill existing education gaps, aimed at improving quality of care for older adults. This paper describes the GCP and examines its impact on knowledge, skills, clinical practice, as well as confidence, comfort, and competence in providing geriatric care. Upon program completion, all graduates (N = 146; 100%) completed an online evaluation survey. The majority of graduates reported (5-point scale: 1 = much less now; 5 = much more now) being more confident (88%), comfortable (83%), and competent (89%) to provide optimal geriatric care than prior to the program. The GCP provides a significant opportunity for health care providers to build their capacity for the care of older adults. Key lessons learned in implementing the GCP and suggestions for further development are discussed.
Occult hepatitis B virus infection in Japanese chronic hemodialysis patients. We investigated the prevalence of occult hepatitis B virus (HBV) infection in Japanese chronic hemodialysis patients. Hemodialysis patients (n = 1041) were screened for occult HBV. The presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (anti-HBc) was determined by various chemiluminescent immunoassays. HBV-DNA was quantified in patients positive for anti-HBc using quantitative real-time polymerase chain reaction. Among the 1041 patients, six (0.6%) were HBsAg-positive and 218 (20.9%) were anti-HBc-positive. All HBsAg-positive patients also tested positive for the presence of HBV DNA. Of 212 HBsAg-negative and anti-HBc-positive patients, three were positive for HBV DNA. Our study showed that the prevalence of occult HBV infection in chronic hemodialysis patients from eastern Japan was 0.3%.
Hepatic Progenitor Cells: An Update. Liver regeneration is a fascinating and complex process with many medical implications. An important component of this regenerative process is the hepatic progenitor cell (HPC). These appealing cells are able to participate in the renewal of hepatocytes and cholangiocytes when the normal homeostatic regeneration is exhausted. Moreover, the HPC niche is of vital importance toward the activation, differentiation, and proliferation of the HPC. This niche provides a rich microenvironment for the regulation of the HPC, thanks to the intercellular secretion of molecules. New findings indicate that the regenerative possibilities in the liver could provide a diverse basis for therapeutic targets.
Correlation between the charge of polymer particles in solution and in the gas phase investigated by zeta-potential measurements and electrospray ionization mass spectrometry. The relationship between the effective charge of polymer nanoparticles (PNP) in solution and the charge states of ionized particles produced in the gas phase by electrospray ionization was investigated. Charge detection mass spectrometry was used to measure both the mass and charge of individual electrosprayed ions. The effective charges extracted from the measured zeta-potential of PNPs in solution are partially correlated with the average values of charge of PNPs in the gas phase. The correlation between the magnitude of charging of PNPs ions produced in the gas phase with the PNPs surface charge in solution demonstrates that the mass spectrometry-based analysis described in this work is an alternative and promising way for a fast and systematic characterization of charges on colloidal particles.
Tromsø eye study: prevalence and risk factors of diabetic retinopathy. To determine the prevalence of visual impairment, retinopathy and macular oedema, and assess risk factors for retinopathy in persons with diabetes. The present study included 514 participants with diabetes aged 46-87 years from the Tromsø Eye Study, a sub-study of the population-based Tromsø Study in Norway. Visual acuity was measured using an auto-refractor. Retinal images from both eyes were graded for retinopathy and macular oedema. We collected data on risk factor exposure from self-report questionnaires, clinical examinations, laboratory measurements and case note reviews. Regression models assessed the cross-sectional relationship between potential risk factors and diabetic retinopathy. The prevalence of visual impairment (corrected Snellen visual acuity <20/60 in the better-seeing eye) was 1.6%. The prevalence of diabetic retinopathy was 26.8% and macular oedema 3.9%. In a multivariable logistic regression model, retinopathy was associated with longer diabetes duration (odds ratio, OR 1.07, 95% CI 1.03-1.11), insulin use (OR 2.14, 95% CI 1.19-3.85), nonfasting glucose (OR 1.07, 95% CI 1.00-1.15) and microalbuminuria (OR 1.89, 95% CI 1.28-2.81). Sub-group analyses showed association between retinopathy and even low levels of microalbuminuria (1.16 mg/mmol). The findings suggest that low levels of microalbuminuria may be a useful risk predictor for identifying individuals with diabetes at high risk of retinopathy. The study confirms previous findings that insulin use, longer diabetes duration and higher levels of blood glucose are associated with retinopathy in persons with diabetes. The prevalence of diabetic retinopathy was similar as reported in other studies.
Effects of extradural anaesthesia on human fetal blood flow in utero. Comparison of three local anaesthetic solutions. Twenty-seven women, scheduled for elective Caesarean section under extradural anaesthesia were allocated randomly to one of three groups: group Ea received 1.5% etidocaine with adrenaline, group Bp 0.5% bupivacaine plain, and group Ba 0.5% bupivacaine with adrenaline. There was no difference in the quality and distribution of sensory blockade between the three groups. Motor blockade was most profound in group Ea. Maternal heart rate and arterial pressure were only slightly affected in the three groups. Before induction of extradural anaesthesia, and 15 and 30 min after, fetal umbilical and aortic blood flows were examined using a combination of real-time ultrasonography and the pulsed Doppler technique. Blood flow in the umbilical vein was not affected in any of the groups, and blood flow in the fetal aorta remained unchanged in groups Ea and Bp, but was increased by 12% after 30 min in group Ba. We conclude that, with the three local anaesthetic solutions studied during extradural anaesthesia for elective Caesarean section, fetal circulatory variables remained stable and within normal limits, when in association with normal values of maternal arterial pressure.
Abnormal chemotaxis in patients with cutaneous anergy. Chemotaxis of polymorphonuclear leukocytes and mononuclear leukocytes was studied in six patients who had persistent cutaneous anergy. Four had previous infections (three fungal and one caused by Mycobacterium kansasii), one had sarcoidosis, and one had late-onset immunoglobulin deficiency. Our data indicate that some patients with persistent cutaneous anergy have a combined defect of leukocyte function. Lymphocytes incubated in vitro with mitogen failed to elaborate active lymphocyte-derived chemotactic factor when compared with controls. Polymorphonuclear leukocytes and mononuclear leukocytes responded poorly to normal chematactic factors compared with controls. The abnormal mononuclear leukocyte chemotaxis may play a role in the persistent cutaneous anergy of these patients.
Prevalence and significance of the MEFV gene mutations in childhood Henoch-Schönlein purpura without FMF symptoms. Familial Mediterranean fever (FMF) has been reported more frequently in patients presenting with Henoch-Schönlein purpura (HSP) than in the general population. But, there is no clear knowledge about MEFV mutations in patients with HSP. We investigated the prevalence of MEFV mutations in children with HSP and without FMF whether these mutations have any effect on the disease course or complications. A total of 76 children with HSP who had no typical symptoms of FMF were screened for the mutations in exon 2 and exon 10 of the MEFV gene. Eleven of 76 patients (14.4 %) were heterozygous (E148Q in 5, M694V in 4, M680I in 1, E148V in 1), 5 (6.6 %) were homozygous (M694V/M694V in 4, V726A/V726A in 1), and 2 (2.6 %) were compound heterozygous (E148Q/M694V mutations in 1 and L110P/E148Q mutations in 1). Altogether, 7 patients carried 2 mutated MEFV alleles (9.2 %), which was higher than that observed in the general Turkish population (1 %). No significant differences in joint, gastrointestinal, renal involvement, or subcutaneous edema, and also acute phase reactants including leukocyte count, erythrocyte sedimentation rate, and serum C-reactive protein concentration were found between the groups. The prevalence of the two allele-MEFV mutations in patients with HSP was found higher than that of the general population. However, it seems that MEFV gene mutations may not have any effect on the clinical presentation of HSP.
Urinary phenylethylamine excretion: gas chromatographic assay with electron-capture detection of the pentafluorobenzoyl derivative. Phenylethylamine was extracted into n-hexane from alkaline urine saturated with sodium chloride, and back-extracted into dilute acid. The extract was freeze-dried and the residue converted to a pentafluorobenzoyl derivative for analysis by gas chromatography on a column of OV-225 with electron-capture detection. Quantification was achieved by adding an internal standard of tolylethylamine to each sample prior to extraction. Output values in normal subjects and in some patients with phenylketonuria and hyperphenylalaninaemia were in agreement with those in some other recent reports.
Ion pores made of mitochondrial ATP synthase subunit c in the neuronal plasma membrane and Batten disease. A hypothesis is outlined that the neurodegeneration of the Batten disease syndromes that involve an overaccumulation of subunit c is caused by a newly characterized function of the protein, its ability to assemble in the plasma membrane into ion pores (J. E. M. McGeoch and G. Guidotti, Brain Res 766: 188-194, 1997), rendering the cell liable to constant electrical excitability to a degree that causes cell death.
Immunological and ultrastructural study of the surface of isolated rat testis germinal cells. In the present study, cross absorption tests and indirect immunofluorescence detected antigenic differences between isolated testicular cell populations from 21 and 38 day old rats, respectively. Qualitatively, spermatids were the only cell type difference between these populations. Spermatozoa from adult rats were also studied. Our findings suggest that spermatocytes, spermatids and spermatozoa shared on or more antigens; spermatids and spermatozoa seemed to share one or more antigens not observed in spermatocytes by indirect immunofluorescence. Various patterns of immunofluorescence were encountered, suggesting differences in amount and distribution of antigens among the cells studied. The supramolecular appearance of the surface of spermatocyte enriched populations and of spermatid enriched populations were compared by scanning electron microscopy (SEM) and no striking difference was observed between both cell populations.
Effect of povidone iodine and hydrogen peroxide on fracture healing: a histomorphometric study on rats. To evaluate the effect of povidone iodine and hydrogen peroxide on fracture healing in a rat model. The middle section of the right femur of 36 male Sprague Dawley rats was osteotomised with a saw. In the control group (n=9), the wound was irrigated with 100 ml 0.9% saline. In the 10% povidone iodine (n=9), 1% povidone iodine (n=9), and 3% hydrogen peroxide (n=9) groups, the wound was completely soaked with the respective solution for 2 minutes, and then irrigated with 100 ml saline. The osteotomy was fixed with an intramedullary Kirschner wire. Rats were euthanised at week 1, 2, and 5. In each femur, the percentage area of osseous, cartilaginous, and fibrous tissue in the callus was evaluated in 3 slides (one median and 2 paramedian). The control group differed significantly to the other 3 groups (p=0.023 to p<0.001) in weeks 1, 2, and 5, except for the 1% povidone iodine group in terms of percentage of osseous (p=0.349) and fibrous (p=0.999) tissue. The healing process was similar in the 1% povidone iodine group and the control group, whereas healing was impaired in the 10% povidone iodine group and 3% hydrogen peroxide group, as indicated by the lower percentage of osseous tissue, higher percentage of fibrous tissue, and increased percentage of cartilaginous tissue between weeks 2 and 5 (delayed bone healing). The 1% povidone iodine solution is recommended as the irrigation adjuvant in fracture surgery.
Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue. The passive biocompatibility of silicon-based electrode arrays was studied in feline cortical tissue. Three types of arrays were used: uncoated, coated with polyimide, and coated with polyimide over an adhesion promoter. Fifteen arrays were implanted for 24 h to determine early tissue reaction to the implantation procedure, and twelve arrays were implanted for 6 months to determine structural and material biocompatibility. Edema and hemorrhage were present around the short-term implants, but involved less than 6% of the total area of the tissue covered by the array. With chronic implants, leukocytes were rarely present and macrophages were found around roughly one-third of the tracks. Remnants of foreign material from the electrodes could be identified in less than 10% of the tracks. Gliosis was found around all tracks, forming an annulus between 20 and 40 microns thick. A capsule was not always present, and never exceeded a thickness of 9 microns. These results suggest that the implantation procedure produces limited amounts of tissue damage, and that the arrays are biocompatible. However, the arrays insulated with polyimide over a primer had significantly greater involvement of macrophages, gliosis, and capsule formation than uncoated arrays and arrays insulated with polyimide without printer, perhaps indicating a reaction to aluminum oxide in the primer.
Stability and transient effects in nanosecond ultraviolet light filaments in air. We investigate the transient behavior and stability of nanosecond duration ultraviolet pulses propagating in air. Both the transient behavior arising from the finite pulse duration and the modulational instability, are found to cause pulses to fragment over lengths on the scale of meters. We discuss the theoretical and experimental implications of the instability and transient effects for long duration pulse propagating in air and generating filaments. In particular, our results imply that continuous-wave models are very limited when used to predict dynamical properties of pulse propagation.
Clinical epidemiology of inflammatory bowel disease in Lebanon. The objectives of this study were to determine the prevalence and incidence of inflammatory bowel disease (IBD) in a representative Lebanese cohort and to describe practice prevalence trends, disease characteristics, and impact on quality of life (QoL) of IBD patients in Lebanon. All of a university-based health program's 2000-2004 computerized records that listed a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were reviewed. In addition, data on patients seen in the gastroenterology clinics and data from the IBD registry at the American University of Beirut Medical Center (AUBMC) from the same period were analyzed. Of 15,073 insured individuals, 8 had a diagnosis of CD and 16 of UC, giving an age-adjusted prevalence of 53.1 per 100,000 people for CD and 106.2 per 100,000 people for UC. The mean age at diagnosis for patients with CD and UC was 28.8 +/- 11.1 and 32.0 +/- 13.4 years, respectively, and there was a slight female predominance. The mean annual incidence was 4.1 per 100,000 people for UC and 1.4 per 100,000 people for CD (range, 0-6.9/100,000 for both). Of the 10,383 patients seen in the gastroenterology clinic from 2000 to 2004, 251 (2.4%) had IBD (142 UC, 100 CD, and 9 indeterminate), a ratio that trended upward over time (range, 1.8%-2.7%). The median IBD Quality-of-Life (IBDQ) questionnaire score was 124.9 +/- 30.5, indicating that the disease had a moderately severe impact on QoL. The prevalence of IBD in this representative Lebanese cohort falls in the intermediate range of that reported for white populations in Europe and North America. Future studies are needed to examine local risk factors, disease genotypes and phenotypes, and epidemiologic time trends. The psychosocial burden of IBD in Lebanon appears significant.
A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels. IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.
[Comparison between solis fixation fusion and titanium plate fixation by cervical anterior approach]. To investigate the effect difference between the Solis fixation fusion and the titanium plate fixation by the cervical anterior approach after decompression and bone graft implantation. Of the 104 patients with cervical disease from September 2001 to March 2004, 36 were treated with the Solis implantation after decompression by the cervical anterior approach, and 68 were treated with the titanium plate fixation after decompression and bone graft implantation. The recovery of the neurological function in all the patients were assessed with the JOA Scoring at 6 weeks, 3, 6, 12, 24 and 36 months. The fragment fusion and its stability as well as the changes in the intervertebral height were assessed with X-ray examination. According to the JOA Scoring, the excellent and good outcomes accounted for 94.4% in the Solis group and 94.1% in the titanium plate group. In all the patients, the fragment fusion was achieved in 3 months. The change in the Cobb angle of the fused fragment was less than 5 degrees at the flexion-extension posture, 3.6 +/- 0.8 degrees in the Solis group, 2.4 +/- 0.7 degrees in the titanium plate group. There was significant differences between the two groups (P < 0.05). The intervertebral height of the operation fragment in the Solis group increased 1.6 +/- 0.7 mm, which was higher than that in the titanium plate group (P < 0.05). Clinical effects of the two internal fixation operations are good; however, the Solis fixation has more advantages because of its simpler performance, less trauma, and fewer complications.
Systematic evaluation of tumoral 99mTc-MAA uptake using SPECT and SPECT/CT in 502 patients before 90Y radioembolization. The aim of this study was to evaluate the (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) uptake of primary and secondary liver tumors in a large patient cohort before (90)Y radioembolization. We included 502 patients during the years 2005-2013 (55% male; mean age, 62 ± 11 y), who were examined with (99m)Tc-MAA SPECT or SPECT/CT before planned radioembolization. The patients had colorectal cancer (CRC; n = 195, 38.8%), neuroendocrine tumors (NET; n = 77, 15.3%), mammary cancer (MAM; n = 68, 13.5%), hepatocellular carcinoma (HCC; n = 59, 11.8%), cholangiocellular carcinoma (CCC; n = 40, 8.0%), or urologic tumors (URO; n = 14, 2.8%). SPECT with coregistered contrast-enhanced CT or MR imaging and SPECT/CT images of these patients were analyzed using dedicated software with regard to the (99m)Tc-MAA uptake of the liver tumors. Regions of interest were drawn around the lesions manually and quantified the uptake of up to 3 lesions per patient and also adjacent healthy liver tissue without evidence of tumor. We quantified maximum and mean counts per pixel and calculated tumor-to-background ratio (TBR). Data are reported as mean ± SD. Lesion uptake was classified as being homogeneously high (grade 1), heterogeneously high (grade 2), equal to that of the liver (grade 3), or low (grade 4). Grade 1 uptake was seen in 230 of 1,008 lesions (with the highest rates in sarcoma [47%], MAM [37%], and NET [32%]), grade 2 in 706 lesions (with the highest rates in CRC [77%], HCC [75%], and CCC [74%]), grade 4 in 57 lesions (with the highest rates in pancreatic cancer [17%], sarcoma [SAR] [13%], and MAM [8%]), and grade 3 in only 15 lesions. In quantitative analysis, the mean TBRmax of all lesions was 4.8 ± 4.1 (range, 0.2-50.1), with the highest values in HCC (6.0 ± 4.7; range, 1.4-21.6), NET (5.4 ± 4.9; range, 0.8-43.0), pancreatic cancer (4.0 ± 2.8; range, 0.9-12.2), and CCC (4.7 ± 2.9; range, 0.9-11.6), and the lowest values in SAR (3.5 ± 1.8; range, 0.8-2.7) and MAM (3.6 ± 2.2; range, 0.9-11.6). The mean TBRmean was 1.9 ± 1.0 (range, 0.1-7.2), with the highest values in NET (2.2 ± 1.2; range, 0.2-7.2), HCC (2.1 ± 1.2; range, 0.3-6.3), and CCC (2.0 ± 1.0; range, 0.2-6.3) and the lowest values in MAM (1.7 ± 0.8; range, 0.2-4.1), CRC (1.8 ± 0.9; range, 0.4-6.6), and SAR (1.7 ± 1.1; range, 0.3-3.9). The (99m)Tc-MAA uptake of different tumor entities shows a wide variation, with generally highest values for NET, HCC, and CCC and lowest values for MAM, CRC, and SAR. However, the variation of uptake within the different tumor entities is high.
[Interleukin-6, tumor necrosis factor alpha and their soluble receptors in Bence-Jones nephropathy. Possible role in pathogenesis andthe importance in the determination of prognosis in renal insufficiency]. Bence-Jones nephropathy, the most serious form of which is renal failure, is one of the frequent complications in multiple myeloma (MM). Precise pathogenetic mechanism of renal injury remains unclear. Experimental study points to the possible role of some cytokines in the development of this type of nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with plasmocytoma. The group comprised 49 patients with plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in patients with irreversible renal insufficiency and/or failure (group A-median 13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group B-median 3.1-range 1.8-38.4) (p < 0.01) and those with normal renal functions (group C-median 2.3-range 0.97-7.41) (p < 0.01). Significant difference was also found between the groups B and C (p < 0.05). Analysis of variance with the use of various factors showed that the correlation between IL-6 and prognosis of renal disease was stronger (p < 0.001) than the correlation between cytokine levels and the clinical phase of MM (p < 0.05). The difference of IL-6 levels between various clinical stages of MM was not significant. The levels of sIL-6R were significantly increased in patients with both reversible and irreversible renal insufficiency comparing the group with unaffected renal functions (p < 0.05 and p < 0.01 respectively). TNF-alpha levels did not differ between all 3 groups of patients, however, significantly increased values of sTNF-R II were observed in group A vs B and group B vs C (p < 0.05). We conclude, that some cytokines, especially IL-6/sIL-6R, could play an important role in development of renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6 levels could be predictive factor for renal insufficiency recovery.
Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke. Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Δ and -0.40 for ε). This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.
The role of natriuretic peptides in cardiovascular disorders and human cardiac allografts (Review). The human myocardium is composed of a variety of cardiac cell types that synthesise cardioactive factors with autocrine, paracrine and endocrine functions. These cardioactive factors include a family of structurally and functionally related peptides, natriuretic peptides (NPs), that act as cardiovascular cell growth modulatory factors and have significant influence on the regulation of cardiovascular function. The three members of the NP family are atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide. NPs are ubiquitously expressed in cardiovascular tissues and have specific receptors in cardiac cells, brain cells, vascular endothelial cells and extracardiac tissues through which they elicit a variety of biological responses including natriuresis, diuresis and vasodilation. Cardiac transplantation is the most effective and definitive treatment for end-stage cardiac failure in humans. Orthotopic cardiac transplantation and cardiovascular disorders including hypertension, cardiac hypertrophy, cardiac failure, result in increased myocardial expression of NPs, suggesting a pathophysiological role for these peptides in the heart. The mechanism by which the expression of NPs is regulated in the transplanted human heart is not well understood. Understanding the mechanism of local expression of NPs and their interactions with other putative growth regulatory factors in the human heart may have important implications for potential management of cardiovascular disorders and cardiac transplantation. This article will discuss the current knowledge of NPs in cardiovascular disorders. Most of the emphasis will focus on their possible role in human cardiac allografts as there have been no reviews on this important topic.
Roles of Ca2+ and protein kinase C in regulation of prostaglandin E2 release by cultured rabbit gastric epithelial cells. Prostaglandin (PG) has been reported to be one of the important protective factors in the gastric mucosa. However the mechanism of the regulation of endogenous PG production has not been well studied. We investigated the possible roles of Ca2+, cAMP, and protein kinase C (PKC) in the regulation of PGE2 release from cultured rabbit gastric mucosal cells. PGE2 was measured by radioimmunoassay. A23187 (Ca2+ ionophore) at 2 x 10(-6) M significantly increased PGE2 release. Deprivation of Ca2+ from the medium blocked the A23187-induced increase of PGE2. TMB-8 (a putative inhibitor of Ca2+ release from intracellular stores) did not have any significant effects on the increase of PGE2-induced by A23187. Thus, A23187 increased PGE2 through the influx of extracellular Ca2+. W7 or compound 48/80 (calmodulin inhibitors) did not alter the response of PGE2 caused by A23187. Exogenous administration of cAMP, forskolin (an activator of adenylate cyclase), or 2-chloroadenosine (a possible activator of adenylate cyclase through adenosine A2 receptor) had neither significant effects on PGE2 release nor an effect on A23187-induced increase of PGE2 release. 12-O-tetradecanoylphorbol 13-acetate (TPA, an activator of PKC) significantly stimulated PGE2 release in a dose-dependent fashion, whereas another phorbol ester with no biological activity did not. A23187 at 0.8 x 10(-6) M, but not cAMP, potentiated the TPA-induced increase of PGE2. Mepacrine (a phospholipase A2 inhibitor) reduced the A23187- and TPA-induced increase of PGE2. These results suggest that Ca2+ and protein kinase C may play important roles in the regulation of PGE2 release by cultured rabbit gastric cells.
Meso-substituted cationic porphyrins of biological interest. Photophysical and physicochemical properties in solution and bound to liposomes. A series of cationic porphyrins with 1-4 positive charges are studied: mono(N-methyl-4-pyridyl)triphenylporphine chloride [Mono], cis(N-methyl-4-pyridyl)diphenylporphine chloride [Cis], tri(N-methyl-4-pyridyl)monophenylporphine chloride [Tri] and tetra(N-methyl-4-pyridyl)porphine chloride [Tetra]. Their photophysical properties are measured in small unilamellar vesicles and compared with those in homogeneous solution. Liposomes of L-alpha-dimyristoyl-phosphatidylcholine (100 nm diameter) and L-alpha-dipalmitoyl-phosphatidylcholine (50 nm diameter) in phosphate-buffered saline (pH = 7.4) or D2O 0.15 M NaCl were used. The effect of the medium microheterogeinity is discussed. The triplet quantum yields in liposomes for all the porphyrins are about 0.7, similar to the value obtained for Tetra in aqueous media. The singlet molecular oxygen quantum yields for the hydrophilic compounds Tri and Tetra are greater than those of the hydrophobic ones, Mono and Cis. Also, association constants (KL) of the dyes to liposomes and their localization within the membranes are determined from fluorescence and fluorescence polarization measurements, respectively. KL values are in the range of 10(4)-10(5) M-1 for all the compounds, indicating that hydrophobic and coulombic interactions between porphyrins and liposomes are responsible for the dye association. Fluorescence polarization experiments indicate that Mono and Cis can penetrate into the lipidic phase, and that Tri and Tetra are located near the polar heads of the lipidic molecules.
Primary gastric lymphoma. To evaluate the clinico-pathological status of Primary Gastric Lymphoma (PGL) at presentation in King Fahad Hospital, Madina Munawra, Kingdom of Saudi Arabia (KSA). A case series. PLACE AND DURATION OF SUDY: Oncology Department of King Fahad Hospital, Madina Munawra, KSA, from 1990 to 1998. Case records of 22 patients with a histologically-confirmed diagnosis of PGL were analyzed. Tumors were staged according to the Ann Arbor Classification and divided according to the Rappaport working formulation. According to the treatment modality, different groups were established. Any other histopathological type was excluded from the study. Data were analyzed by frequency calculations. Survival was calculated from the date of surgery. All cases were Non-Hodgkin Lymphoma (NHL). The peak age was in the sixth decades with a slight male preponderance. Most common presenting symptoms were epigastric or upper abdominal pain with or without mass. There were 10 (45%) patients with stage II, and 6 (27%) patients each with stage III and IV diseases. Diffuse large cell lymphoma was found in 12 (55%), poorly differentiated lymphoma in 3 (14%) and diffuse mixed in 7 (32%). Helicobacter pylori infection was found in 2 (9%). Sixteen (73%) patients underwent chemotherapy with some surgical resection, in 5 (23%) surgical procedure was palliative bypass and 11 (50%) had partial gastrectomy. Three (14%) had only chemotherapy after endoscopic biopsy. Two (9%) patients needed urgent surgical intervention. One (5%) patient had total gastrectomy followed by radiotherapy. Eleven (50%) had more than 3 years survival. PGL is usually of NHL type, presenting in the sixth decade, and can be successfully treated with both surgery and chemotherapy when patients presented at stage II. Chemotherapy after sub-total gastrectomy or biopsy was the best treatment option.
Increases of CRF in the amygdala are responsible for reinstatement of methamphetamine-seeking behavior induced by footshock. Recent evidence suggests the involvement of corticotropin-releasing factor (CRF) in drug abuse. Here, we evaluated whether CRF modulates the reinstatement of methamphetamine (METH)-seeking behavior induced by stress using a drug-self administration paradigm in rats. Rats were trained to lever-press for intravenous METH (0.02 mg/infusion) accompanied by light and tone (drug-associated cues) and then underwent extinction training (saline substituted for METH without cues). Under the extinction condition, the inhibitory effects of a CRF receptor antagonist on the stress-induced reinstatement of METH-seeking behavior were assessed. Anxiety-like behaviors during METH withdrawal in METH self-administered rats were also evaluated. The non-selective CRF receptor antagonist α-helical CRF(9-41) attenuated METH-seeking behavior induced by footshock stress. CRF levels both in the amygdala and in plasma were significantly increased on day 10 of withdrawal after METH self-administration. However, plasma corticosterone concentrations were unchanged during the withdrawal. In addition, METH-seeking behavior was not affected by an inhibitor of corticosterone synthesis, metyrapone. In the elevated plus maze test, METH self-administered rats showed a decrease in the duration of time spent in the open arms on day 10 of withdrawal. The increased CRF levels in the amygdala may, at least in part, contribute to the footshock-induced reinstatement of METH-seeking behavior and the increase in anxiety-like behavior. The present findings indicate that CRF receptor antagonists would be useful as a therapeutic agent for METH-dependence.
Future Trends in Vascular Access Creation. Delivery of a prescribed dialysis dose, which is critical for longevity on hemodialysis, is directly dependent on vascular access (VA). However, VA is fraught with high failure rates and has room for innovation. Arteriovenous fistula (AVF), considered the 'best choice', has a high 'failure to mature' rate. Arteriovenous grafts (AVGs) are considered when patients are poor candidates for or have failed AVF, but have a high incidence of infections and thrombosis. Due to associated morbidity and mortality from complications, central venous catheters are considered only as 'bridging short-term access' when there is an urgent need for dialysis. The observation from current data that there is a significant center effect in the rate of AVF maturation supports investigation to identify factors that contribute to success in high-performing centers that create AVF and establish 'best practice' approaches to improve outcomes. Biocompatible AVG constructs that promote rapid tissue incorporation withstand needle punctures due to better integrity and can improve current AVG outcomes. Stenosis in the 'access circuit' is a major cause for short- and long-term permanent access failure. While the pathology of stenosis development is well understood, factors responsible for this problem are poorly studied. Increased flow in the access circuit likely plays a major role in the development of such stenosis. Investigation into understanding the hemodynamics of this flow may help identify etiology and stenosis sites perhaps even prior to the event, thus providing potential targets to mitigate the stenotic response. In summary, this chapter reflects on the shortcomings of current access modalities and discusses potential avenues to improve VA outcomes in the future.
Sudden cardiac death: biobehavioral perspective. Increasing evidence indicates that sudden death resulting from ventricular fibrillation may be triggered in some patients by behavioral and neural factors. In animal preparations, diverse psychologic stressors and augmented sympathetic neural traffic to the heart lower the vulnerable period threshold for ventricular fibrillation. Epidemiologic studies have demonstrated increased cardiac fatality after bereavement and unemployment, as it relates to social class and cultural dislocation, and as a function of level of education, psychologic stress, and social isolation. Ventricular premature beats (VPBs), which may be risk indicators of susceptibility to sudden death, are not affected by perturbations of the peripheral autonomic nervous system. However, differing psychologic stressors increase, whereas their abatement diminishes, VPB frequency and grade. The most potent stressors relate to the recall of emotionally charged experiences. Such stressors are uniquely individual and cannot be readily replicated. Among the most significant factors to reduce VPBs are non-rapid eye movement sleep and increases in vagal neural activity. Psychological precipitants are demonstrable in about 20% of patients experiencing malignant ventricular arrhythmias. A promising new avenue for investigation relates to the role of various central neurotransmitters and their dietary precursors in cardiac neural traffic. Augmenting central serotonin by administering its tryptophan precursor reduces sympathetic neural activity and protects the heart against ventricular fibrillation.
Assessment of neural dynamic coupling and causal interactions between independent EEG components from cognitive tasks using linear and nonlinear methods. Over the past few years there has been an increased interest in studying the underlying neural mechanism of cognitive brain activity. In this direction, we study the brain activity based on its independent components instead of the EEG signal itself. Both linear and nonlinear synchronization measures are applied to EEG components, which are free of volume conduction effects and background noise. More specifically, a robust nonlinear state-space generalized synchronization assessment method and the recently introduced partial directed coherence are investigated in a working memory paradigm, during mental rehearsal of pictures. The latter is a linear method able to assess not only the independence of the brain regions, but also the direction of the statistically significant relationships. The results are in accordance with previous psychophysiology studies suggesting increased synchrony between prefrontal and parietal components during the rehearsal process, most prominently in gamma (ca. 40 Hz) band. This study indicates that functional connectivity during cognitive processes may be successfully assessed using independent components, which reflect distinct spatial patterns of activity.
Treatment of multiple sclerosis with interferon beta 1b. Interferon beta 1b is now an established therapeutic option for relapsing remitting multiple sclerosis. More recently, it has also been shown to slow down disease progression in secondary progressive multiple sclerosis. Interferon beta 1b's clinical effect is reflected in MRI studies demonstrating a dramatic effect in reducing disease activity. The drug is generally well tolerated, but its efficacy can be compromised in some patients by the emergence of neutralizing antibodies. This chapter will focus on interferon beta 1b (Betaseron) treatment for multiple sclerosis, its clinical and MRI effects, and its putative mechanism of action.
(+/-)-Pindolol has beta 2-adrenoceptor antagonist but not agonist action on the costo-uterine muscle of the rat. 1. The effects of isoprenaline and (+/-)-pindolol on rat isolated costo-uterine muscle have been compared. 2. Isoprenaline produced reproducible concentration-dependent inhibition of contractions, and maximal doses (less than 0.1 mumol/l) produced mean inhibition of 87, 94 and 97% of field, carbachol and potassium-stimulated preparations, respectively. 3. (+/-)-Pindolol, when effective, produced inhibition only in concentrations greater than its pA2 value (9.87) as an antagonist of isoprenaline; mean maximal effects were less than 60% of those produced by isoprenaline. 4. It is concluded that (+/-)-pindolol is a potent antagonist, but has only variable agonist action, at the beta 2-adrenoceptors of the rat costo-uterine muscle.
[Evaluation of left ventricular function in patients with chronic obstructive pulmonary disease]. Patients with right ventricle (RV) pressure overload often have impaired left ventricular (LV) diastolic function. Objectives. The aim of study was to evaluate LV function in patients with chronic obstructive pulmonary disease (COPD). Patients and methods. Thirty-five patients (mean age: 62.1 +/- 7.7 y) with COPD without additional cardiac diseases and 25 age--and sex-matched healthy subjects were enrolled into the study. All patients underwent resting ECG tracing, blood pressure, spirometry, standard and tissue Doppler echocardiography. The mean value of forced expiratory volume in one second (FEV1) in the COPD group was 40 +/- 8.9% of the predicted value. We found no significant differences in LV end-diastolic and systolic diameter and interventricular septum as well between COPD patients and controls. RV end-diastolic diameter and RV wall thickness were significantly larger and right ventricle systolic pressure--RVSP (38 +/- 11.2 vs. 20 +/- 2.5 mm Hg) significantly higher in the COPD group. Both peak early to peak atrial filling velocities ratio--E/A and peak annular velocity during early diastole to peak annular velocity during atrial contraction--Em/Am were significantly lower in COPD compared to controls. Moreover, there was a strong inverse correlation between Em/Am and RVSP (r = -0.75; p < 0.001) and between E/A (r = -0.6; p < 0.001) as well. We found no significant differences in parameters assessing the LV systolic function between both groups. In COPD patients LV diastolic function is significantly impaired and its magnitude is related with increase in pulmonary artery pressure, while systolic LV function is well preserved.
Spreading of Bubbles after Contacting the Lower Side of an Aerophilic Slide Immersed in Water. While the dynamics of complete wetting has been widely studied for liquids, the way a gas spreads on a solid is by far less known. We report here the events following the rise of a millimeter-size air bubble towards a textured material immersed in water and covered by a thin plastron of air. Bubbles contact the material either directly at the end of the rise, or after a few rebounds, which affects the initial shape of the bubble and the resulting dynamics of contact. Then, air spreads on the material, owing to surface tension and later buoyance, which tends to flatten further the bubble. The corresponding dynamics are shown to result from the inertial resistance of water, which explains how spreading bubbles reach centimeter sizes in typically 10 ms.
Levels of serum cathepsin L and several glycosidases in patients operated for colorectal cancer. The activities of several glycosidases and cathepsin L were determined in the blood serum of a control group of ten healthy humans in comparison with a group (group I: 32 subjects) of preoperative colorectal cancer patients (1 week before surgical exeresis) and with another two groups: group II, comprising 18 operated subjects (1 week after surgery), and group III, of 15 operated subjects (4 months after surgery). All subjects were 48-88 years old. Both 'enzyme activity' and 'specific activity' determinations of serum beta-galactosidase, alpha-L-fucosidase and cathepsin L revealed peculiar profiles that differed from one another. Control values differed from those of some stages of the pathological groups, but not of others. These values were compared also with the levels of total, lipid- and glycoprotein-associated serum sialic acid. The usefulness of some assays (especially cathepsin L activity measurement) in the follow-up of the health status of humans operated for colorectal cancer is discussed.
Four Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting Cervical Cancer. Circulation long non-coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and might be applied for cancer diagnosis, prognosis, or potential therapeutic targets. In this study, we aimed to explore whether the circulation lncRNA could predict the tumorigenesis of surgical squamous cervical cancer (CC). In this study, we applied the lncRNA microarray to screen the potential biomarker for CC. Real-time quantitate polymerase chain reaction was conducted for further validation in a larger sample size. The multi-stage validation and risk score formula analysis were used to examine the sensitivity and specificity. We discovered 4 lncRNAs including HOTAIR, PVT1, XLOC_000303, and AL592284.1, which were upregulated in CC comparing with the cancer-free controls. Further, the receiver operating characteristic curve (ROC) analysis by risk score formula revealed the combined 4 factors with a high diagnostic ability with the area under ROC curve value of 0.875 and 0.958 in training set and validation set respectively. We finally confirmed the stable detection of the 4 lncRNAs by 5 cycles of freezing and thawing. HOTAIR, PVT1, XLOC_000303, and AL592284.1 might be the potential biomarkers for predicting the tumorigenesis of CC in the future.
Rabbit mucosal receptors for an enteropathogenic Escherichia coli strain: appearance of bacterial receptor activity at weaning. Adherence studies using the rabbit enteropathogenic Escherichia coli strain RDEC-1 indicate that this strain attaches in a species-specific manner to receptors located on its host intestinal epithelial cells. Because intestinal epithelial cells undergo marked developmental changes within the first few weeks of life, we designed a study to determine whether the presence of bacterial receptors on rabbit brush borders changed during this time. The adherence of RDEC-1 to rabbit brush borders isolated from rabbits aged 2-35 days and from adult rabbits was examined. No adherence of RDEC-1 was detected to rabbit brush borders isolated from rabbits 15 days or younger. Receptors for RDEC-1 were first detected on rabbit brush borders from 21-day-old rabbits and by 35 days, RDEC-1 receptor activity on rabbit brush borders had reached adult levels. Piliated, enteroadherent, human Escherichia coli pathogens did not adhere to rabbit brush borders of any age group indicating that nonspecific adherence did not occur.
Epitaxial Growth of Thin Ferroelectric Polymer Films on Graphene Layer for Fully Transparent and Flexible Nonvolatile Memory. Enhancing the device performance of organic memory devices while providing high optical transparency and mechanical flexibility requires an optimized combination of functional materials and smart device architecture design. However, it remains a great challenge to realize fully functional transparent and mechanically durable nonvolatile memory because of the limitations of conventional rigid, opaque metal electrodes. Here, we demonstrate ferroelectric nonvolatile memory devices that use graphene electrodes as the epitaxial growth substrate for crystalline poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) polymer. The strong crystallographic interaction between PVDF-TrFE and graphene results in the orientation of the crystals with distinct symmetry, which is favorable for polarization switching upon the electric field. The epitaxial growth of PVDF-TrFE on a graphene layer thus provides excellent ferroelectric performance with high remnant polarization in metal/ferroelectric polymer/metal devices. Furthermore, a fully transparent and flexible array of ferroelectric field effect transistors was successfully realized by adopting transparent poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] semiconducting polymer.
Intrathoracic bifurcation of the left common carotid artery associated with rib fusion and Klippel-Feil syndrome. Common carotid artery usually bifurcates at the superior border of thyroid cartilage, corresponding to the C3-4 junction, however bifurcation level may vary. Common carotid bifurcation may have rare variations like separate origins of left internal and external carotid arteries from aortic arch, or bifurcation of common carotid artery within thoracic cavity. Intrathoracic carotid bifurcation is a rare variation with limited number of cases reported. The occurrence of a low carotid bifurcation seems to be embryologically related to the persistence of the ductus caroticus. Additionally, intrathoracic carotid bifurcation can be accompanied by findings of Klippel-Feil syndrome. Herein, we present imaging findings of an incidentally detected intrathoracic left common carotid artery bifurcation in a pediatric patient accompanied by fusion of the cervical vertebrae and ribs.
Occlusion pressure and breathing pattern in healthy children. The breathing pattern was investigated in 62 children aged 4 to 16 years together with the mouth pressure generated 0.1 s after an occlusion at the endexpiratory level (P0.1). A group of 20 adults (18 to 32 years old) were tested in a similar way. The values of P0.1 obtained during room air breathing at rest in the children decreased with age as a power function P0.1 = 8.51 A-0.62 (where A is age in years), r = -0.74. Adult values of P0.1 were achieved at about 13 years. After O2 inhalation P0.1 decreased in children, but the changes in P0.1 were independent of age. Respiratory frequency decreased with age while inspiratory time (TI) increased, both reaching adult values at about 13 years. The ratio of TI over the total respiratory cycle duration did not change significantly with age in the entire population. The absolute value of tidal volume (VT) increased with age, but not when normalized for body weight (BW). The mean inspiratory flow (VT/TI) normalized for BW decreased with age in children as did P0.1. There was a significant relationship between P0.1 and VT/TI normalized for body weight (r = 0.63).
Evaluating the agreement of two quantitative assays with repeated measurements. A common task in assay validation is to show the agreement between an assay under investigation and a reference assay. Hence, in the hypothesis setup, we should choose nonagreement as the null hypothesis so that when the null hypothesis is rejected at 5% level of significance, we have a 95% statistical assurance to claim the agreement between two assays. In this paper, we propose a statistical test with nonagreement as the null hypothesis. The calculation of sample size is also given. Some simulation results are provided for illustration.
Analytic image concept combined to SENSE reconstruction. Two approaches of reconstructing undersampled partial k-space data, acquired with multiple coils are compared: homodyne detection combined with SENSE (HM_SENSE) and analytic image reconstruction combined with SENSE (AI_SENSE). The latter overcomes limitations of HM_ SENSE by considering aliased images as analytic thus avoiding the need for phase correction required for HM_SENSE. In vivo imaging experiments were carried out in male Lewis rats using both gradient echo and spin echo sequences. Accelerated images obtained by using the various reconstruction algorithms were compared to fully sampled reference images both qualitatively and quantitatively. For the various sampling patterns evaluated, both HM_SENSE and AI_SENSE were found to yield robust image reconstruction with small deviations from the reference image. Even for high acceleration factors AI_SENSE still provided useful results and was found superior compared to HM_SENSE. Combination of partial k-space sampling and parallel image acquisition allows for further acceleration of data acquisition as compared to each method alone. Image reconstruction from undersampled data sets using the AI_SENSE algorithm was found to considerably reduce reconstruction errors and artifacts observed for HM_SENSE reconstruction caused by errors in phase estimation.
Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion. Hydroxypropylcellulose (HPC) films containing drugs or hydrophilic or hydrophobic plasticizers were prepared by a hot melt extrusion process. Polyethylene glycol 8000 (PEG 8000) 2%, triethyl citrate (TEC) 2%, acetyltributyl citrate (ATBC) 2%, and polyethylene glycol 400 (PEG 400) 1% were the plasticizing agents studied. In addition, either hydrocortisone (HC) 1% or chlorpheniramine maleate (CPM) 1% was incorporated into the films as a model drug. The physical-mechanical properties of the films that were investigated included tensile strength (TS), percentage elongation (%E), and Young's modulus (YM). Differential scanning calorimetry (DSC) was utilized to determine glass transition temperatures (Tg's). These parameters were studied as a function of time and temperature. The glass transition temperatures initially decreased with the inclusion of the drugs and plasticizers. However, after 6 months aging, films containing PEG 400 and HC showed a marked increase in Tg. The films containing PEG 400 showed physical-mechanical instability in all parameters studied. All extruded films exhibited a marked decrease in TS in contrast to a large increase in %E when testing was performed perpendicular to flow versus in the direction of flow. In addition, a consistent film of HPC in the absence of drugs or plasticizers could not be extruded due to the excessive stress on the equipment. Although the theoretical percentage of CPM on aging remained fairly constant over the processing temperature ranges in this study, the HC levels remaining in the extruded films during storage were a function of time and temperature.
[Headache following laparotomy; chronic subdural haematoma following epidural anaesthesia]. A 63-year-old man underwent an exploratory laparotomy because of rectal carcinoma. The operation was performed under general anaesthesia in combination with epidural anaesthesia. Since the operation the patient complained of a headache. Eight weeks after the operation he was hospitalized because of worsening of the headache and also drowsiness. A physical examination showed a slight tendency to incline to the left. A CT scan showed a subdural haematoma, which was relieved with surgery. We suspected that accidental puncture of the dura caused the haematoma. The incidence, causes, symptoms, diagnosis and treatment of this rare complication are discussed.
Oxidation by oxygen and sulfur of Tin(IV) derivatives containing a redox-active o-amidophenolate ligand. Oxidation of tin(IV) o-amidophenolate complexes [Sn(ap)Ph(2)] (1) and [Sn(ap)Et(2)(thf)] (2) (ap=dianion of 4,6-di-tert-butyl-N-(2,6-diisopropylphenyl)-o-iminobenzoquinone (ImQ)) with molecular oxygen and sulfur in toluene solutions was investigated. The reaction of oxygen with 1 at room temperature forms a paramagnetic derivative [Sn(isq)(2)Ph(2)] (3) (isq=radical anion of ImQ) and diphenyltin(IV) oxide [{Ph(2)SnO}(n)]. Interaction of 1 with sulfur gives another monophenyl-substituted paramagnetic tin(IV) complex, [Sn(ap)(isq)Ph] (4), and the sulfide, [Ph(3)Sn](2)S. The oxidation of 2 with oxygen and with sulfur proceeds through the derivative [Sn(isq)(2)Et(2)] (7), which undergoes alkyl elimination to give two new tin(IV) compounds, [Sn(ap)(isq)Et] (5) and [Sn(ap)(EtImQ)Et] (6) (EtImQ=2,4-di-tert-butyl-6-(2,6-diisopropylphenylimino)-3-ethylcyclohexa-1,4-dienolate ligand), respectively, along with the corresponding alkyltin(IV) oxide and sulfide. Complexes 3-5 and 7 were studied by EPR spectroscopy. The structures of 3, 4 and 6 were investigated by X-ray analysis.
Syntactic autonomy. Why there is no autonomy without symbols and how self-organizing systems might evolve them. Two different types of agency are discussed that are based on dynamically coherent and incoherent couplings with an environment, respectively. I propose that until a private syntax (syntactic autonomy) is discovered by dynamically coherent agents, there are no significant or interesting types of closure or autonomy. When syntactic autonomy is established, then, because of a process of description-based selected self-organization, open-ended evolution is enabled. At this stage, in addition to dynamics, agents depend on localized, symbolic memory, thus adding a level of dynamic incoherence to their interaction with the environment. Furthermore, it is the appearance of syntactic autonomy that enables much more interesting types of closures among agents sharing the same syntax. To investigate how we can study the emergence of syntax from dynamic systems, experiments with cellular automata leading to emergent computation that solves nontrivial tasks are discussed. RNA editing is also mentioned as a process that may have been used to obtain a primordial biological code necessary for open-ended evolution.
Catalyst-Free Synthesis of Aryl Diamines via a Three-Step Reaction Process. The formation of C-N bonds with aryl amines is one of the most widely studied reactions in organic chemistry. Despite this, it is still highly challenging, often requiring expensive, precious metal-based catalysts. Here we report an easy catalyst-free methodology for constructing C-N bonds. The method, which proceeds via the in situ formation of closed ring amidinium ions, allows the preparation of a series of symmetrical and/or unsymmetrical aryl diamines in notably high yields (82-98%) and purity and with a variety of different substituents. The methodology is shown successful for the preparation of aryl diamines having para- and/or meta-substituted carboxyl, nitro, bromo, methoxy, or methyl groups. This green synthetic pathway, which is catalyst free, requires only three steps, and proceeds without the need for purification. Further, it is a new sustainable, economically viable method to achieve an otherwise challenging bond formation.
Polyamines increase Ca2+ sensitivity in permeabilized smooth muscle of guinea pig ileum. The effects of polyamines were investigated in strips of smooth muscle from guinea pig ileum permeabilized with beta-escin (0.005%). Spermine (1 mM) inhibited transient contractions induced in Ca(2+)-free medium by carbachol (0.1 mM) and GTP gamma S (0.1 mM) but potentiated responses to caffeine (20 mM) and D-myo-inositol 1,4,5-trisphosphate (40 microM). At high ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid concentration (10 mM) and in the presence of A-23187 (10 microM), force at optimal and suboptimal Ca2+ concentrations was increased both by spermine and by carbachol. Spermine did not potentiate contraction in Ca(2+)-free medium or after full thiophosphorylation of the regulatory 20-kDa myosin light chains but slightly potentiated contractions produced by partial thiophosphorylation. Also, spermidine and putrescine, as well as the aminoglycoside antibiotic neomycin, increased sensitivity to Ca2+, with potency correlating with number of positive charges. After permeabilization by a high concentration (0.1%) of beta-escin, the sensitivity to Ca2+ was increased by spermine but not by GTP gamma S. In preparations permeabilized by Triton X-100, spermine slightly increased Ca2+ sensitivity but not maximal force. Tissue contents of putrescine, spermidine, and spermine in intact ileum muscle were 8, 98, and 184 nmol/g, respectively. Permeabilization by 0.005 and 0.1% beta-escin reduced spermine contents by 40 and 53%, respectively. Effects of added polyamines in permeabilized preparations may thus reflect physiological effects of endogenous polyamines modulating contraction in the intact tissue.
Elevated serum pro-MMP2 levels in patients with stage IV thymoma. There is increasing evidence that matrix metalloproteinases (MMPs) play important roles in tumor invasion and metastasis. Using a one-step sandwich enzyme immunoassay, we investigated whether serum pro-MMP2 levels could be predictors of the development and extension of thymoma. The subjects of this study were 33 patients with thymoma and 26 patients with nonmalignant thoracic disease. Serum pro-MMP2 levels were elevated in patients with stage IV thymoma (938.6+/-80.2ng/ml) compared with those in the controls (P = 0.03). Patients with stage IVb thymoma had significantly higher serum pro-MMP2 levels than patients with other stages, being 1088.7+/-440ng/ml in stage IVb, 686.0+/-74.0ng/ml in stage I (P = 0.01), 685.8+/-48.6ng/ml in stage II (P = 0.01), and 691.7+/-74.0 ng/ml in stage III (P = 0.02). Serum pro-MMP2 levels were elevated in patients with polygonal cell type thymoma compared with those with mixed cell type thymoma, being 823.1+/-55.5ng/ml vs 613.6+/-59.9ng/ml, respectively (P = 0.04). Using the reference limit of 850ng/ml (mean +/- 2SD) set from analyses in the control group, all patients who had pro-MMP2 levels below the cutoff level survived. On the other hand, four of nine patients who had an elevated pro-MMP2 level died from recurrence. Serum pro-MMP2 levels may serve as a marker that could be used as an indicator of distant metastases in thymoma. Elevated pro-MMP2 levels may be correlated with poor survival.
Large angular dispersion by a virtually imaged phased array and its application to a wavelength demultiplexer. A new scheme that shows large angular dispersion is proposed and demonstrated. The key idea to this method is a virtually imaged phased array (VIPA). The angular dispersion of a VIPA is 10-20 times larger than those of common diffraction gratings, which have blaze angles of ~30 deg. With the VIPA, wavelength demultiplexing for 10 channels with 0.8-nm spacing is achieved. Low polarization-state dependence (~0.1 dB) is also confirmed.
Advantages of PARAFAC calibration in the determination of malachite green and its metabolite in fish by liquid chromatography-tandem mass spectrometry. This paper reports the properties and advantages of the three-way calibration models based on parallel factor analysis (PARAFAC) in the simultaneous determination of malachite green (MG) and its metabolite (leucomalachite green, LMG) in trout. A recently method proposed by community reference laboratory AFSSA-LERMVD (Fougères, France) has been used. The method is based on liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) in multiple reaction monitoring (MRM) mode. The validation of the method has been carried out taking into account the Decision 2002/657/EC. The figures of merit for PARAFAC and univariate calibration models of six non-consecutive days analyzed during a month were evaluated. With the samples of the first 3 days, calibration models were built and the fish fortification samples of the other days were predicted. Decision limits (CCalpha, alpha=0.01), detection capabilities (CCbeta, beta=0.05) and mean relative errors in absolute value (in calibration and with test samples) obtained with PARAFAC calibrations were more homogeneous than the ones obtained with the univariate calibrations, especially in LMG. These figures of merit were in the range of 0.2-0.83 microg kg(-1) (CCbeta) and 0.2-0.49 microg kg(-1) (CCalpha), whereas mean relative errors in absolute value were in the range of 1.1-7.4% in calibration and 3-12% in test samples for MG and LMG with PARAFAC calibrations. The PARAFAC calibrations allow detecting the test samples which are not similar to the calibration samples and in this way their wrong quantification is avoided.
Translational repression of human matrix metalloproteinases-13 by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (TIAR). Human matrix metalloproteinases-13 (HMMP13) shows a wide substrate specificity, and its expression is limited to pathological situations such as chronic inflammation and cancer. The coding sequence for HMMP13 is 86% identical to rat matrix metalloproteinases-13 (RMMP13); however, the regulation of HMMP13 and RMMP13 protein synthesis in renal mesangial cells is strikingly different. In human cells there is a discordance between HMMP13 mRNA levels and protein expression. Following IL-1 beta or TGF-beta(1) stimulation, HMMP13 mRNA levels increase significantly, whereas the protein expression is absent. This discordance is because of a species-dependent translational repression. In addition to the 3'-untranslated region of the matrix metalloproteinases-13 (MMP13) gene, the differential expression of an alternatively spliced transcript of the RNA-binding protein TIAR in human cell cultures is also critical for this post-transcriptional regulation. Transient expression of the 17-amino acid insert of the alternatively spliced form of TIAR reverses the HMMP13 mRNA silencing observed in human and primate species. In addition, co-transfection of the alternatively spliced form of TIAR and HMMP13 into Rat2 cells suppresses HMMP13 protein expression. Thus, we report for the first time that a species-dependent TIAR isoform plays a major role in the post-transcriptional silencing for HMMP13.
Moisture diffusivity in the lean tissue of dry-cured ham at different process times. The aim of this study was to determine the effective moisture diffusivity coefficient (D(e)) during dry-cured ham processing in two muscles, an internal one (Biceps femoris, BF) and an external one (Semimembranosus, SM), at different temperatures. Two adjacent samples, which included both SM and BF muscles, were selected after salting (PS), after resting (PR), after 4 months of drying (D1) and at the end of the process (D2). One was used to determine the initial profiles of moisture and NaCl/moisture and the other to determine D(e) at different temperatures (1 and 5°C in PS; 5 and 12°C in PR; 12, 19 and 26°C in D1; 19 and 33°C in D2). D(e) was higher in the muscle with the higher moisture content (BF) except in PS and PR, where a gradient of NaCl/moisture ratio was observed in SM muscle. There was a positive effect of temperature on D(e), but it decreased during processing of the dry-cured ham. A simple diffusive model, with a unique and constant moisture diffusivity coefficient or with a coefficient depending only on temperature, does not explain the whole drying process correctly. The effects of moisture content and the gradient of NaCl/moisture ratio on D(e) have to be considered.
Morphological changes of striatal dopaminergic presynaptic boutons following intrastriatal kainate injection. Bouton-sparing properties of kainic acid were re-investigated at the fine structural level. Two to 42 days after kainic acid (2.2-5.0 nmol) injection into the rat striatum, nigrostriatal dopaminergic boutons were examined at the injection site using tyrosine hydroxylase immunohistochemistry. Injection of the toxin produced marked dilatations of intensely tyrosine hydroxylase-positive boutons with tremendous amounts of vacuoles. Active astroglial processes reacted with those enlarged, immunoreactive boutons. Thus these boutons, if not all, are interpreted as being in the process of degeneration. Such enlarged boutons were observed more frequently at longer survival times than at shorter ones, suggesting an indirect effect of kainic acid resulting from severe loss of postsynaptic neuronal elements. Morphological changes described here may explain biochemical features that tyrosine hydroxylase level of the kainic acid affected striatum, following initial elevation, gradually decreases at a later stage.
Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. The nucleus accumbens (NAc) is a key component of the brain's reward pathway, yet little is known of how NAc cells respond to primary rewarding or aversive stimuli. Here, naive rats received brief intraoral infusions of sucrose and quinine paired with cues in a classical conditioning paradigm while the electrophysiological activity of individual NAc neurons was recorded. NAc neurons (102) were typically inhibited by sucrose (39 of 52, 75%) or excited by quinine (30 of 40, 75%) infusions. Changes in firing rate were correlated with the oromotor response to intraoral infusions. Most taste-responsive neurons responded to only one of the stimuli. NAc neurons developed responses to the cues paired with sucrose and quinine. Thus, NAc neurons are innately tuned to rewarding and aversive stimuli and rapidly develop responses to predictive cues. The results indicate that the output of the NAc is very different when rats taste rewarding versus aversive stimuli.
Influence of cholesterol derivatives on cytoskeletal organization of human carcinoma cells. Recent developments of immunotherapeutic approaches have shown that artificial ordering of tumor cell membranes with cholesterol hemisuccinate (CHS) or 25-hydroxycholesterol (25-OH) may significantly enhance the immunogenicity of human renal adenocarcinoma cells. To gain further insight into the molecular mechanism of these sterols, we investigated cytoskeletal modification, which is related to the cell membrane. After treatment of human renal carcinoma cells with these cholesterol (at 10(-6) and 10(-7) M) for 5 days, we observed a disorganization of the submembrane end of the cytoplasmic actin stress fibers by cytofluorescence. The microtubule network was not affected. Thus, in the present study, we found that changes in membrane physicochemical properties impaired the anchorage of actin microfilaments in the plasma membrane of human renal cancer cells. Under the same experimental conditions, such modifications were not observed in normal cells (human fibroblasts) or in human hepatoma cells. We suggest that incubation of cancer cells with these sterols induced a redistribution of the cholesterol-rich membrane microdomains which are linked to the cytoskeleton through submembrane proteins.
Dose-response of ritonavir on hepatic CYP3A activity and elvitegravir oral exposure. Ritonavir, a potent inhibitor of cytochrome P450 isoform 3A (CYP3A) activity, is frequently used to boost the effects of protease inhibitors at doses of 100-400 mg per day; however, human data regarding the optimal dose required for boosting are limited. This study systematically evaluated the ritonavir dose-response relationship on presystemic and systemic CYP3A metabolism using the human immunodeficiency virus integrase inhibitor elvitegravir and midazolam as probe substrates. Ritonavir administered once daily with elvitegravir exhibited nonlinear pharmacokinetics, with a 119-fold increase in the area under the plasma concentration-time curve over the dosing interval over a 20- to 200-mg dose range. The 20-mg dose of ritonavir substantially reduced CYP3A-mediated clearance (CL), as evidenced by a 66% reduction in midazolam CL that plateaued to 17% of baseline activity at a 100-mg dose. Maximum inhibition of elvitegravir apparent oral CL was achieved with ritonavir doses of 50-100 mg. Elvitegravir and ritonavir were generally well tolerated in this study. These data provide a critical understanding of ritonavir's dose-response relationship for inhibition of CYP3A activity in humans.
Tumor induction in Sencar mice in response to ultraviolet radiation. The purpose of this study was to ascertain whether Sencar mice, which are extremely susceptible to two-stage skin carcinogenesis by chemical carcinogens, also exhibit increased susceptibility to carcinogenesis by ultraviolet radiation (UVR). Sencar and CD-1 mice were given a single treatment of UVR from FS40 sunlamps and received no subsequent treatments with chemical or physical promoters. The doses administered were 0, 2.88, 5.76, or 11.52 x 10(4) J/m2. No tumors were observed in either treated or untreated CD-1 mice at 30 weeks after irradiation. Papillomas began to appear at 6 weeks after irradiation in Sencar mice; the cumulative incidence of tumors at 30 weeks after irradiation was 40 and 45% for the two highest UVR dose groups. Approximately 50% of the tumors regressed spontaneously. In several cases, however, the remaining tumors progressed to squamous cell carcinomas. These results indicate that the hypersensitivity of Sencar mice to tumor induction in skin exists not only with respect to chemical carcinogens but also with respect to at least one physical carcinogen (UVR).
Humoral immunity in the spontaneously diabetic BB rat. Litters of BB rats with an expected high and low incidence of insulin-dependent diabetes were followed from weaning until the age of about 140 days. Islet cell surface antibodies (ICSA) and lymphocyte antibodies (LA) were determined in a radioligand assay with fixed rat insulinoma (RIN 5F) cells, an insulin-secreting cell line, or spleen lymphocytes. In the low-incidence litter, 2 out of 14 rats had ICSA and LA; one showed insulitis at the end of the study. In the high-incidence litter, 3 out of 7 developed diabetes; all 3 showed ICSA at weaning. The remaining 4 showed insulitis. All 7 diabetes-susceptible rats had ICSA and LA at some time during the study. It is concluded that there is a high incidence of circulating ICSA and LA in the spontaneously diabetic BB rat. The antibodies can often be detected before the onset of diabetes, and may be implicated in the beta-cell destructive process and in the lymphocytopenia characteristic of the syndrome.
Rejection of parental meth-a tumor on concomitant inoculation of meth-a cells infected retrovirally with the interferon-gamma gene into (balb/cxc57bl/6)f-1 mice. The IFN-gamma gene was introduced retrovirally into Meth A cells. IFN-gamma gene infected Meth A (K gamma) cells were highly antigenic and regressed in CB6F(1) mice. Concomitant immunization of CB6F(1), mice with IFN-gamma gene infected Meth A (K gamma) cells after inoculation of parental Meth A protected the mice from parental tumor growth. 1x10(6) infectant Meth A (K gamma) cells protected the mice from growth of 1x10(6) parental Meth A cells, but 2x10(6) infectant cells did not, suggesting that there was an optimal dose of infectant cells for rejection of the parental tumor. Specificity analysis revealed that growth of CMS13 tumor was slightly inhibited by Meth A (K gamma) cells but that of CMS5 was not inhibited. The findings are consistent to those obtained with parental Meth A cells and indicated that the relevant rejection antigen on Meth A (K gamma) cells was identical to the parental Meth A rejection antigen.

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