Venous sinus pulsatility and the potential role of dural incompetence in idiopathic intracranial hypertension.
Idiopathic intracranial hypertension (IIH) remains a poorly understood and therapeutically challenging disease. Enthusiasm has emerged for endovascular therapy with stent reconstruction of dural sinus narrowing; however, a complete understanding of the hydrodynamic dysequilibrium is lacking. To review and characterize catheter manometry findings including pulsatility changes within the venous sinuses in IIH. Cases of venous sinus stent implantation for IIH were retrospectively reviewed. Three cases of venous sinus stent implantation for treatment of IIH are reported. All cases demonstrated severe narrowing (>70%) within the transverse sinus and a high pressure gradient across the lesion (>30 mm Hg). Stent implantation resulted in pulsatility attenuation, correction of pressure gradient, and improvement of flow. We report the finding of high venous sinus pulsatility attenuation after stent implantation for dural sinus narrowing and propose the hypothesis that this finding is a marker of advanced dural sinus incompetence. This characteristic may be useful in identifying patients who would benefit from endovascular stent remodeling.


Bacillus coagulans R11 maintained intestinal villus health and decreased intestinal injury in lead-exposed mice by regulating the intestinal microbiota and influenced the function of faecal microRNAs.
Lead contamination is an environmental problem, especially in developing countries; due to the nondegradable characteristics of lead, it is easily deposited in human and animal bodies by the food chain. Probiotics are regarded as a good tool to remove lead ions in the intestine and maintain gut health conditions, but previous studies failed to elucidate the relationship among probiotics, the host and the gut microbiota. In the present study, B. coagulans R11 was employed as the "lead removal tool" in lead-exposed mouse, and the effects of B. coagulans R11 on intestinal cells, the microbiota and faecal microRNAs were tested. The results indicated that B. coagulans R11 had no negative effects on mouse intestine model cells and helped keep cells in a normal proliferation ratio and reduce the reactive oxygen species and apoptosis ratios under lead exposure conditions. An in vivo mouse experiment also showed that B. coagulans R11 feeding could reduce the intestinal villi damage caused by lead through adjusting the microbiota structure and function, such as increasing the genus abundance of Akkermansia and Alistipes, decreasing the genus abundance of Alloprevotella, Lachnospiraceae, Parabacteroides and Ruminiclostridium, and keeping the protein dltD existing. Host faecal microRNAs may be influenced by lead and B. coagulans R11, which may change the microbiota structure. Thus, B. coagulans R11 has the potential to be developed and considered as the probiotic that protects the host gut against villi damage and gut microbiota structure and function disorders during lead exposure.


[Preparation of controlled release microsphere incorporating bFGF and its effect on Schwann cells].
To study the preparation method of bFGF microspheres and to investigate the bioactivities of bFGF, which were released from the bFGF microspheres, on the cultured schwann cells. bFGF was microcapsulated with the multiple emulsion encapsulative method using PLGA as coating material. Its morphology, particle size distribution, drug loading-embedding rate and in vitro release property were studied. The cultured schwann cells were grouped according to the different ingredients being added to the culture medium: bFGF group, bFGF-PLGA group. Then the number, the viability and the cell cycle of schwann cells were measured. The morphology and the particle size distribution of the bFGF-PLGA microspheres were even and good; the drug-loading and drug-embedding rate of microspheres were (27.18 x 10(-3)) % +/- (0.51 x 10(-3)) %, 66. 43% +/- 1.24%; the release property of microspheres in vitro was good and the overall release rate was 72. 47% in 11 days. The in vitro cellular study showed: 1, 2 days after plate culture, the cell number and cell viability of bFGF group was much better than that of bFGF-PLGA group; 3, 4 days after plate culture, the cell number and cell viability of bFGF group and bFGF-PLGA group were not different statistically; 6, 8 days after plate culture, the cell number and cell viability of bFGF-PLGA group was much better than that of bFGF group. Through the flow cytometry examination: 2 days after plate culture, the GJ/M+S percentage of bFGF group was higher than that of bFGF-PLGA group; 4, 8 days after plate culture, the G2/M+S percentage of bFGF-PLGA group was higher than that of bFGF group. So, it is practical to prepare the bFGF-PLGA microspheres with the multiple emulsion encapsulative method. bFGF-PLGA microspheres can preserve the bioactivities of bFGF effectively and promotes the proliferation of schwann cells in a long period because of the controlled release of bFGF from microspheres.


The surgical management of tuberculosis.
Due to unpredicted factors, the incidence of tuberculosis is increasing in the United States. Despite excellent anti-tuberculous medication, some patients will require surgical management. The majority of these patients present with multi-drug-resistant tuberculosis (MDRTB). Surgery is indicated, but only after the best possible anti-tuberculous regime has been instituted. In those patients who become sputum-negative and have a destructive pulmonary process, or in those patients with persistent positive sputum and destroyed pulmonary parenchyma, operative management may be beneficial. Surgery can be done with a low mortality and morbidity incidence. Muscle flaps are useful in minimizing postoperative complications. Continued postoperative medical therapy combined with surgery offers a cure in more than 90% of patients. In patients with MDRTB and localized parenchyma disease, surgery combined with continued medical therapy is the treatment of choice in the majority of patients.


Deduction of intracellular sub-systems from a topological description of the network.
Non-linear behaviour of biochemical networks, such as intracellular gene, protein or metabolic networks, is commonly represented using graphs of the underlying topology. Nodes represent abundance of molecules and edges interactions between pairs of molecules. These graphs are linear and thus based on an implicit linearization of the kinetic reactions in one or several dynamic modes of the total system. It is common to use data from different sources -- experiments conducted under different conditions or even on different species -- meaning that the graph will be a superposition of linearizations made in many different modes. The mixing of different modes makes it hard to identify functional modules, that is sub-systems that carry out a specific biological function, since the graph will contain many interactions that do not naturally occur at the same time. The ability to establish a boundary between the sub-system and its environment is critical in the definition of a module, contrary to a motif in which only internal interactions count. Identification of functional modules should therefore be done on graphs depicting the mode in which their function is carried out, i.e. graphs that only contain edges representing interactions active in the specific mode. In general, when an interaction between two molecules is established, one should always state the mode of the system in which it is active.


The Jacobi diffusion process as a neuronal model.
The Jacobi process is a stochastic diffusion characterized by a linear drift and a special form of multiplicative noise which keeps the process confined between two boundaries. One example of such a process can be obtained as the diffusion limit of the Stein's model of membrane depolarization which includes both excitatory and inhibitory reversal potentials. The reversal potentials create the two boundaries between which the process is confined. Solving the first-passage-time problem for the Jacobi process, we found closed-form expressions for mean, variance, and third moment that are easy to implement numerically. The first two moments are used here to determine the role played by the parameters of the neuronal model; namely, the effect of multiplicative noise on the output of the Jacobi neuronal model with input-dependent parameters is examined in detail and compared with the properties of the generic Jacobi diffusion. It appears that the dependence of the model parameters on the rate of inhibition turns out to be of primary importance to observe a change in the slope of the response curves. This dependence also affects the variability of the output as reflected by the coefficient of variation. It often takes values larger than one, and it is not always a monotonic function in dependency on the rate of excitation.


Cardiorespiratory fitness and vigorous leisure-time physical activity modify the association of small size at birth with the metabolic syndrome.
Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome. Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and VO(2max) were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study. Men with a ponderal index (kg/m(3)) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in <25 min/wk of vigorous LTPA and in men with a VO(2max) <28.6 ml x kg(-1) x min(-1) or <2.44 l/min. In active and fit men, however, the association was absent. Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.


Preliminary results from follow-up of a large-scale population survey of antibodies to gliadin, reticulin and endomysium.
Coeliac disease is often under-diagnosed, particularly in cases which are atypical or asymptomatic. The aim of this study was to comprehensively assess the prevalence and clinical profile of adult coeliac disease in our community. One-hundred-and-thirteen subjects from the most recent MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease)1991/2 survey with positive serology were followed up 3 years after initial screening and assessed by means of (i) a clinical questionnaire, (ii) screening blood tests, and (iii) jejunal biopsy. Forty-six subjects (21 male, mean age 51 years) have been followed up to date. Prior to follow-up, two of these subjects were diagnosed as having coeliac disease. Ten (3 male, mean age 51 years) of 44 subjects had enteropathy. Three of these 10 subjects were relatively asymptomatic, 3 had folate deficiency and 3 had iron deficiency. Thus 12 of the 1823 initially screened had enteropathy consistent with coeliac disease. Coeliac disease is more prevalent than previous estimations and was found to be at least 1 in 152.


Atomistic Simulation of Gas Uptake and Interface-Induced Disordering in Solid Phases of an Organic Ionic Plastic Crystal.
Organic ionic plastic crystals (OIPCs) are a unique class of materials that exhibit a short-range disorder on the molecular level but are ordered at higher length scales. Recent experiments in our group have shown that the OIPC methyl(diethyl)isobutylphosphonium hexafluorophosphate ([P122i4][PF6]) exhibits a high ideal selectivity of 30 with respect to CO2 and N2 at 35 °C. Here, we employ classical molecular dynamics simulations for studying gas uptake in the OIPC [P122i4][PF6] at different temperatures. Both adsorption and absorption of the gases CO2, N2, O2, and CH4 were estimated using a gas/solid interface model. The observed trend in gas uptake was CO2 > CH4 > O2 > N2. The CO2 uptake was found to be dependent on both the OIPC structure and temperature. Owing to phase transitions and intermolecular motions, the solid gets disordered with increasing temperatures. The study finds that such disordering effects can also be caused by interface effects, which can enhance gas absorption. The results qualitatively confirmed that the OIPC can be effective in separating CO2 not only from N2, as per the previous experimental study, but also from O2 and CH4. However, strategies to improve the free volume in the material become important.


[Cerebrovascular complications of non-bacterial thrombotic endocarditis: value of transesophageal echocardiography].
Non bacterial thrombotic endocarditis is a frequent cause of cerebrovascular complications in patients with cancer. Clinical features are often misleading and symptoms are hardly linked to valvular thrombosis in the absence of systemic embolism. We describe here a case mainly illustrating two aspects: clinical and neuroradiological manifestations of multiple distal brain infarcts and the value of transoesophageal echocardiography for the diagnosis.


Current approaches in ovarian cancer vaccines.
Much of the current approaches in the treatment of advanced ovarian cancer are directed towards prolongation of duration between primary treatment and remission. Immunotherapy is regarded as one attractive option for consolidation of initial therapeutic responses. In fact, immune reactivity against ovarian carcinoma can be induced by various immunotherapeutical approaches including antibodies, peptides or dendritic cell vaccines. This review provides an overview of recent clinical trials using various concepts of immunotherapy for the treatment of ovarian cancer. Possible reasons for limited clinical success as well as further progress to improve efficacy of current immune intervention strategies, e.g. by vaccines targeting a broader range of tumor-derived antigenic structures or activating diverse host immune functions, will be discussed.


Use of social network sites and instant messaging does not lead to increased offline social network size, or to emotionally closer relationships with offline network members.
The effect of Internet use on social relationships is still a matter of intense debate. This study examined the relationships between use of social media (instant messaging and social network sites), network size, and emotional closeness in a sample of 117 individuals aged 18 to 63 years old. Time spent using social media was associated with a larger number of online social network "friends." However, time spent using social media was not associated with larger offline networks, or feeling emotionally closer to offline network members. Further, those that used social media, as compared to non-users of social media, did not have larger offline networks, and were not emotionally closer to offline network members. These results highlight the importance of considering potential time and cognitive constraints on offline social networks when examining the impact of social media use on social relationships.


Systems biology strategies to study lipidomes in health and disease.
Lipids are a diverse group of metabolites that have many key biological functions, acting as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Due to their importance lipids are under tight homeostatic control and exhibit spatial and dynamic complexity at multiple levels. It is thus not surprising that altered lipid metabolism plays important roles in the pathogenesis of most of the common diseases. Lipidomics emerged as a discipline which is dedicated to global study of lipidomes, including pathways and networks of lipids in biological systems. When studying the lipidomes at a systems level, one of the key challenges is how to address the lipid functionality at many physiological levels, from metabolic and signaling pathways to spatial systems such as cellular membranes and lipoprotein particles. Besides the better analytical techniques to study lipids, computational techniques have started to emerge which enable modeling of lipidomes in their spatial and dynamic context. Together, the recent methodological advances in lipidomics have a potential to open novel avenues for predictive and preventive medicine. This review focuses on progress in systems approaches to study lipids in health and disease, with specific emphasis on clinical applications.


Respecting the Roles: TMA Battles Another Round of Scope of Practice Bills.
When nonmedical professionals ask the Texas Legislature for the authority to practice medicine, TMA mounts a full-court press, letting lawmakers know why there are some roles only physicians can fill.


Needs of relatives of critical care patients: perceptions of relatives, physicians and nurses.
This study investigated differences between the perceptions of relatives, physicians and nurses concerning the needs of relatives of critical care patients. Perceived needs were assessed in 200 relatives, 38 physicians, and 143 nurses using a 45-item questionnaire. Data were gathered at the intensive care unit of the University Hospital Gasthuisberg. The overall rankings of the needs by the three groups are very similar. Information emerges as most important factor, with considerably less importance attached to comfort and support. There were significant differences between the groups on all categories and on 24 individual needs. Regarding the need categories, both nurses and physicians underestimate the relatives' need for information and proximity to the patient. Physicians also underestimate the relatives' need for assurance. On the individual need items, relatives' needs are generally underestimated by the staff, but in some cases overestimations are found.


Oncologic emergencies: implications for nurses.
Oncologic emergencies can be grouped into the following categories: neurologic, cardiopulmonary, metabolic, hematologic, infectious, gastrointestinal, genitourinary, and infusion-related. Each crisis produces characteristic symptoms, physical findings, and laboratory abnormalities. Skills required of nurses include patient assessment by organ system, management of intravenous lines, monitoring of laboratory results, and recognition of allergic reactions and extravasation. Anticipating these clinical syndromes allows for prevention or early detection with better outcomes.


Keratin polypeptide profile in psoriatic epidermis normalized by treatment with etretinate (aromatic retinoid Ro 10-9359).
The variations in the expression of epidermal keratins occurring during retinoid therapy were studied in patients with psoriasis before and during oral administration of etretinate (aromatic retinoid Ro 10-9359) and compared with normal epidermis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis densitometric readings were performed on keratins extracted from epidermal cells obtained through trypsinization of skin specimens. Epidermal cells were also tested by immunofluorescence (IF) for the presence of BMZ antigens as markers of basal cells and for the presence of TK and KP (67 K, 63 K, and 55 K) with sera with antibodies against BMZ antigens and specific antisera for TK and KP. In psoriasis-involved epidermis, SDS-PAGE anaLysis showed lower amounts of 67 K and increased amounts of 63 K and 55 K, as compared with normal epidermis. Low proportions of cells expressing by IF the 67 K and the 63 K were also noted, with a defective expression of these two KP by suprabasal keratinocytes in psoriasis-involved epidermis. During etretinate administration, a return toward the normal electrophoretic pattern and a correction of the defective cellular expression of these two KP were obtained parallel with clinical improvement. These findings indicate the presence in involved psoriatic epidermis of a population of suprabasal keratinocytes that do not express the high-molecular-weight KP and show a normalization of the relative proportions of the KP with etretinate.


Evaluation of an in vitro percutaneous permeation model with two oxidative hair dyes.
Synopsis The percutaneous permeation of two oxidative hair dyes was measured by means of pig skin in a flow-through diffusion cell system entirely constructed from Teflon. Pig skin membranes were prepared by reducing full thickness skin with a dermatome to a more in vivo-like barrier layer and their integrity was checked by measuring the steady-state permeation of tritiated water. Initially, the inter- and intraindividual variability of percutaneous permeation was determined with an aqueous solution of 1-(2'-hydroxyethyl)-amino-3,4-methylenedioxybenzene-hydrochloride, an oxidative hair dye component. In the same way the proper flow rate of elution fluid through the receptor cell was found to be most favourable at 10 ml h(-1), the thickness of permeation membranes was fixed at 1 mm, and it was shown that storage of the skin at -20 degrees C for up to 35 days did not change the permeability. The percutaneous permeation of the same hair dye component and of 4-amino-2-hydroxymethylphenol-hydrochloride was determined after application to pig skin membranes under practical conditions of hair dyeing. The in vitro skin permeation was in the same order of magnitude as results from comparable in vivo skin absorption studies in rats. Perméation percutanée in vitro de colorants d'oxydation pour cheveux.


Inferring causality assessments from predictive responses: cue interaction without cue competition.
The authors criticize the use of participants' predictive responses during a learning phase as a measure of causal assessments. Simulations demonstrate that a general aim to minimize error as required in the prediction task will produce results in accordance with those observed, in particular apparent cue interaction effects. It is argued that measures estimated from prediction responses do not reflect causal ratings, but are side-effects of learning explained by adaptation in strategy to changes in presented cell frequencies. The results are reinterpreted to be in line with a causal model view, not requiring dual processes or cue competition of lower level associative processes.


Modulation of Electron-Phonon Coupling in One-Dimensionally Nanorippled Graphene on a Macrofacet of 6H-SiC.
Local electron-phonon coupling of a one-dimensionally nanorippled graphene is studied on a SiC(0001) vicinal substrate. We have characterized local atomic and electronic structures of a periodically nanorippled graphene (3.4 nm period) prepared on a macrofacet of the 6H-SiC crystal using scanning tunneling microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES). The rippled graphene on the macrofacets distributes homogeneously over the 6H-SiC substrate in a millimeter scale, and thus replica bands are detected by the macroscopic ARPES. The STM/STS results indicate the strength of electron-phonon coupling to the out-of-plane phonon at the K̅ points of graphene is periodically modified in accordance with the ripple structure. We propose an interface carbon nanostructure with graphene nanoribbons between the surface rippled graphene and the substrate SiC that periodically modifies the electron-phonon coupling in the surface graphene.


Tolerance to and accumulation of cadmium by the mycelium of the fungi Scleroderma citrinum and Pisolithus tinctorius.
The behavior of ectomycorrhizal (ECM) fungi on exposure to cadmium dependent upon isolation remains a poorly understood phenomenon. The in vitro growth, tolerance, and accumulation of Cd were studied in three strains of ECM fungi exposed to six Cd concentrations (0-10 mg L(-1)). The fungi studied were a strain of Scleroderma citrinum Persoon (Sc) isolated from a tailings heap containing 5 mg kg(-1) available Cd, and two strains of Pisolithus tinctorius (Pers.) Coker and Couch from unpolluted sites (Pt1 and Pt2), both common ECM fungi used for remediation. The growth kinetic (36 days) of Sc was not affected by Cd concentration. By contrast, the ED(50) in Pt1 and Pt2 occurred at 4.8 and 6.9 mg L(-1) of Cd, respectively. The biomass of the three fungi exposed to the highest Cd concentration (10 mg L(-1)) was significantly different. Sc presented the highest biomass, while this was strongly reduced for Pt1 and Pt2. The tolerance index for Sc ranged from 78% to 95% at all Cd concentrations tested, while for Pt1 it was 49% and 31%, and for Pt2 it was 62% and 35% at 5 and 10 mg of Cd L(-1), respectively. The mycelium of both Pt strains accumulated more Cd than the Sc mycelium. At the highest Cd concentration, Pt1 and Pt2 accumulated 1.9 and 1.7 times more Cd than Sc. This study suggests that regardless of the differences in tolerance to Cd by the three ECM fungi, they could have biotechnological applications for soil remediation. However, Sc has greater possibilities of being used successfully when high concentrations of Cd prevail in the environment.


The role of dietary cholesterol in the regulation of postprandial apolipoprotein B48 levels in diabetes.
The atherogenicity of intestinally derived postprandial lipoproteins has been confirmed in a number of recent studies. We have shown abnormalities in postprandial lipoprotein metabolism in diabetic patients, a group with an increased susceptibility to atherosclerosis. This study examined the relationship between dietary cholesterol and the postprandial, intestinally derived, apolipoprotein B48 and apolipoprotein B100 from the liver. We compared 10 non-insulin-dependent (Type 2, NIDDM) diabetic patients and 10 age-matched non-diabetic control subjects. Fasting blood was taken and subjects were fed a cholesterol-free, high fat meal. Blood samples were repeated at 2 h, 4 h, 6 h, and 8 h postprandial. The following week fasting blood was collected and subjects were given the same meal with 1 g of added cholesterol. Blood was collected at the same time points. Chylomicrons and very low density lipoprotein were isolated by sequential ultracentrifugation and their lipoprotein composition determined. Apolipoproteins B48 and B100 were separated by gradient gel electrophoresis and quantified by densitometric scanning using a low density lipoprotein apolipoprotein B100 standard. Post prandial chylomicron cholesterol and triglyceride increased after the high cholesterol meal in both groups (p < 0.001). The postprandial chylomicron apolipoprotein B48 response of both diabetic and control subjects to the cholesterol meal was less than to the cholesterol-free meal (p < 0.001). Fasting very low density lipoprotein apolipoprotein B48 was higher in diabetic patients compared to control subjects and their postprandial increase following the cholesterol-free meal was significantly greater (p < 0.001). There was a 10-fold increase in the incremental postprandial VLDL apolipoprotein B48 area under the curve after the cholesterol-rich meal in the diabetic patients compared to a 3-fold increase in control subjects. The postprandial very low density lipoprotein apolipoprotein B100 was similar in the two groups with both meals. The study demonstrates a very significant increase in the amount of intestinally derived small apolipoprotein B48-associated particles in the very low density lipoprotein fraction following a cholesterol-rich meal in diabetic patients. Synthesis rather than clearance may be the major cause of the increase in these atherogenic postprandial particles.


Quantitative design of the skeleton in bird hatchlings: Does tissue compartmentalization limit posthatching growth rates?
Based on a detailed description of hatchling skeletons of the precocial buttonquail (Turnix suscitator) and the altricial budgerigar (Melopsittacus undulatus), this report presents the hypothesis that the rate of avian posthatching growth is limited by the quantitative design (i.e., relative volumes of cartilage, bone, and marrow) of the hatchling skeletons. A Jarge portion of bone in the skeletal elements and fast growth are hypothesized to be mutually exclusive. This hypothesis is tested by morphometric techniques and by statistical comparison of morphometric and growth data. All predictions are met by the data, and the design of hatchling skeletons is described as determined by a tradeoff between tissue composition of skeletal elements and maximum rates of posthatching growth. The precocial design shows large bony areas that supposedly resist mechanical stress of locomotion; however, the relatively small cartilaginous areas exclude high growth rates. The altricial design shows the reverse relationship with small bony areas and a lack of locomotion on the one side but large cartilaginous areas and fast posthatching growth on the other side. © 1994 Wiley-Liss, Inc.


[What worries the oncology patient's caretaker?].
The authors describe and evaluate the main worries which are manifested by those who care for terminal phase oncology patients during the time a patient receives care in a palliative unit. By means of a semi-structured interview, the authors have analyzed the main worries expressed by 50 caretakers who attend to their respective terminal phase cancer patients. The results of this study show that those worries which have a psychosocial character receive a higher degree of worry by caretakers while those which are based on physical symptoms due to the illness are more important for the patients. On the other hand, these worries decrease significantly as the moment of death approaches. Knowing these concrete caretaker worries has made it possible to intervene at opportune moments, which has led to an increase in patients' wellbeing. This research project was carried out, in part, due to the help granted by the General Administration for Scientific and Technical Investigation of the Education and Culture Ministry (PB97-0212).


Fitting valence charge densities at a crystal surface.
A procedure is reported for obtaining a much better initial parameterization of the charge density than that possible from a neutral atom model. This procedure involves the parameterization of a bulk charge density model in terms of simple variables such as bond lengths, which can then be transferred to the problem of interest, for instance a surface. Parameterization is accomplished through the fitting of density functional theory calculations for a variety of crystal distortions. The details of the parameterization are discussed for the specific case of silicon. This parameterized model can then be applied to surfaces or to other problems where an initial higher-order model is needed without the addition of any extra fitted parameters. The non-convexity of the charge density problem is also discussed.


A practical method for analyzing factorial designs with heteroscedastic data.
The Type I error rates and powers of three recent tests for analyzing nonorthogonal factorial designs under departures from the assumptions of homogeneity and normality were evaluated using Monte Carlo simulation. Specifically, this work compared the performance of the modified Brown-Forsythe procedure, the generalization of Box's method proposed by Brunner, Dette, and Munk, and the mixed-model procedure adjusted by the Kenward-Roger solution available in the SAS statistical package. With regard to robustness, the three approaches adequately controlled Type I error when the data were generated from symmetric distributions; however, this study's results indicate that, when the data were extracted from asymmetric distributions, the modified Brown-Forsythe approach controlled the Type I error slightly better than the other procedures. With regard to sensitivity, the higher power rates were obtained when the analyses were done with the MIXED procedure of the SAS program. Furthermore, results also identified that, when the data were generated from symmetric distributions, little power was sacrificed by using the generalization of Box's method in place of the modified Brown-Forsythe procedure.


Cortical pedicle screw placement in lumbar spinal surgery with a patient-matched targeting guide: A cadaveric study.
Cortical pedicle screw placement is an attractive technique in terms of both fixation strength and less invasiveness. However, to insert the screw with penetrating cortical bone on the ideal trajectory is technically demanding. The use of three-dimensional (3D) patient-matched guides may facilitate the use of this technique. To examine the accuracy of cortical screw placement using a patient-matched targeting guide with a cadaveric study assessing the accuracy. The 3D planning of the pedicle screw placement, including the location at which the screw would pass through the center of the pedicle, sagittal/transverse trajectory (angle), length, and diameter, was developed using 3D CAD design software. Three-dimensional guides based on the preoperative planning were created for three cadaveric specimens (L1 to S1, 36 pedicles). Screws (n = 18) and pins (n = 18) were placed using K-wire or drill-based guides, without X-ray exposure. Actual positioning was compared to the preoperative plan by superimposing the inserted screws/pins based on postoperative CT. The placement accuracy was graded based on the degree of perforation of the pedicle by the pedicle screw or pin using an acceptance criterion (no perforation; Grade A, 0-2 mm; Grade B, 2-4 mm; and Grade C, >4 mm). The mean deviation between the planned and inserted screw positions on the coronal plane at the midpoint of the pedicle was compared to the accuracy of screw guide for traditional pedicle screw trajectory (0.70 mm). Of 35 evaluated screws and pins, 32 (91.4%) were inserted completely inside the pedicle. All pedicle perforation was within 2 mm. The mean deviation from the plan at the midpoint of pedicle was 0.66 mm; thus, the accuracy was within the predefined criteria. Cortical pedicle screw placement using 3D-patient matched guides is accurate. Further clinical studies are required to confirm the radiographic and clinical effects.


[Autism and Early Neurodevelopmental Milestones].
Autism spectrum disorder, also referred to in this study as autism, is a neurodevelopmental chronic disease that manifests early in childhood by impairment in social interaction, communication and repetitive behavior. Since there are no specific biomarkers available, the diagnosis is based exclusively on clinical criteria. The purpose of the present study is to determine which are the early psychomotor development or neurodevelopmental milestones that present a significant correlation with the severity of the main symptoms of autism, development quotients, and adaptive function. We performed a retrospective study on a sample of 1572 individuals with a diagnosis of autism that were monitored at Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra, in the Neurodevelopment and Autism Unit. We analyzed six early psychomotor developmental milestones: age of acquisition of 'walking', 'first words', 'first phrases', 'daytime control of bladder sphincter', 'night-time control of bladder sphincter', and age of first complaints. Afterwards, we divided the sample in three subgroups regarding clinical severity, according to the Childhood Autism Rating Scale, and we analyzed significant differences among each other concerning the six milestones established beforehand. The milestone 'age of first phrases' was, from the six milestones, the one with a stronger correlation with the variables of clinical manifestations of autism, development/intelligence quotients, and adaptive function. In division of the sample into subgroups of clinical severity, it was the most severe that showed later ages of acquisition of the neurodevelopmental milestones and earlier ages of first complaints. This study proves the clinical utility to know the age of achievement of early psychomotor developmental skills, since they act as predictors of clinical severity of autism, cognition, and adaptive function of a wide population with autism. Therefore, this data contribute for prognostic and prediction of autism progression. Taking into account the results of this study, it is strongly recommended to all clinicians who have contact with autistic children, to record the 'age of acquisition of first phrases'.


Parameters related to lipid metabolism as markers of myelination in mouse brain.
Myelination, during both normal development and with respect to disorders of myelination, is commonly studied by morphological and/or biochemical techniques that assay as their end-points the extent of myelination. The rate of myelination is potentially a more useful parameter, but it is difficult and time-consuming to establish, requiring a complete developmental study with labor-intensive methodology. We report herein development of methodology to assay the absolute rate of myelination at any desired time during development. This involves intraperitoneal injection of (3)H(2)O to label body water pools, followed by determination of label in the myelin-specific lipid, cerebroside. The absolute amount of cerebroside synthesized can then be calculated from the specific radioactivity of body water and knowledge of the number of hydrogens from water incorporated into cerebroside. During development, the rate of cerebroside synthesis correlated well with the rate of accumulation of the myelin-specific components, myelin basic protein and cerebroside. For purposes of control, we also tested other putative, albeit less quantitative, indices of the rate of myelination. Levels of mRNA for ceramide galactosyltransferase (rate-limiting enzyme in cerebroside synthesis) and for myelin basic protein did not closely correlate with myelination at all times. Cholesterol synthesis closely matched the rate of cholesterol accumulation but did not track well with myelination. Synthesis of fatty acids did not correlate well with accumulation of either fatty acids (phospholipids) or myelin markers. We conclude that measurement of cerebroside synthesis rates provides a good measure of the rate of myelination. This approach may be useful as an additional parameter for examining the effects of environmental or genetic alterations on the rate of myelination.


[Effect of free-air CO2 enrichment on soil microbe in paddy field].
Utilizing FACE research site in Anzhen of Wuxi, the effect of CO2 concentration increasing on soil microbe was studied in a paddy field under the condition of local cultivation, irrigation and fertilization. The results showed that soil respiration intensity was 31.88 ml.kg-1 and bacteria number was 1.51 x 10(6) ind.g-1 dry soil in FACE area, which were greater than those in control area (soil respiration intensity 27.83 ml.kg-1, bacteria number was 1.25 x 10(6) ind.g-1 dry soil, but the differences were not significant.


Delivery of antisense oligonucleotide to the cornea by iontophoresis.
We wished to evaluate the potential of iontophoresis to promote the delivery of antisense oligonucleotides (ODN) directed at the vascular endothelial growth factor (VEGF)-R2 receptor (KDR/Flk) to the cornea of the rat eye. Fluorescence (CY5)-labeled ODNs in phosphate-buffered saline (PBS) (20 microM) were locally administered to rat eyes, and their fate within the anterior segment was studied. Thirty-four male, 5-week-old Wistar rats were used for all experiments. The rats were divided in four groups. In group I (12 rats, 12 eyes), the ODNs (20 microM) were delivered by iontophoresis (300 microA for 5 minutes) using a specially designed corneal applicator. In group II (12 rats, 12 eyes), the ODNs (20 microM) were delivered using the same applicator, but no electrical current was applied. In group III (6 rats, 6 eyes), a corneal neovascular reaction was induced prior to the application of ODNs (20 microM), and iontophoresis electrical current was delivered as for group I rats. Group IV (4 rats, 4 eyes) received ODN (60 microM) iontophoresis application (300 microA for 5 minutes) and were used for ODN integrity studies. The animals were killed 5 minutes, 90 minutes, and 24 hours after a single ODN application and studied. Topically applied ODNs using the same iontophoresis applicator but without current do not penetrate the cornea and remain confined to the superficial epithelial layer. ODNs delivered with transcorneoscleral iontophoresis penetrate into all corneal layers and are also detected in the iris. In corneas with neovascularization, ODNs were particularly localized within the vascular endothelial cells of the stroma. ODNs extracted from eye tissues 24 hours after iontophoresis remained unaltered. The iontophoresis current did not cause any detectable ocular damage under these conditions. Iontophoresis promotes the delivery of ODNs to the anterior segment of the eye, including all corneal layers. Iontophoresis of ODNs directed at VEGF-R2 may be used for the design of specific antiangiogenic strategy in diseases of the cornea.


Robotically performed excimer laser coronary atherectomy: Proof of feasibility.
The feasibility, safety, and high technical success of robotically assisted percutaneous coronary intervention (PCI) for the treatment of both simple and complex coronary disease has been demonstrated. As the current generation robotic platform is limited to a rapid exchange system, orbital or rotational atherectomy cannot be performed robotically. However, excimer laser coronary atherectomy is performed with a rapid exchange catheter but its feasibility during robotically assisted PCI is unknown. We report the successful use of laser atherectomy during two complex robotically assisted PCI procedures using the CorPath GRX robotic system.


Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene A (CagA) may predict future gastric cancer better than simple seropositivity against H. pylori CagA or against H. pylori.
To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer. A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose. H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers. A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.


Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution.
Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI-LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains. This event expels tumour necrosis factor receptor 1 into the disordered lipid phase for its spontaneous trimerization without its ligand and drives caspase 3-caspase 8-mediated apoptosis. In vivo, P. aeruginosa releases N-(3-oxo-dodecanoyl) homoserine lactone to suppress host immunity for its own better survival; conversely, blockage of caspases strongly reduces the severity of the infection. This work reveals an unknown communication method between microorganisms and the mammalian host and suggests interventions of bacterial infections by intercepting quorum-sensing signalling.


Mercury distribution and deposition in glacier snow over western China.
Western China is home to the largest aggregate of glaciers outside the polar regions, yet little is known about how the glaciers in this area affect the transport and cycling of mercury (Hg) regionally and globally. From 2005 to 2010, extensive glacier snow sampling campaigns were carried out in 14 snowpits from 9 glaciers over western China, and the vertical distribution profiles of Hg were obtained. The Total Hg (THg) concentrations in the glacier snow ranged from <1 to 43.6 ng L(-1), and exhibited clear seasonal variations with lower values in summer than in winter. Spatially, higher THg concentrations were typically observed in glacier snows from the northern region where atmospheric particulate loading is comparably high. Glacier snowpit Hg was largely dependent on particulate matters and was associated with particulate Hg, which is less prone to postdepositional changes, thus providing a valuable record of atmospheric Hg deposition. Estimated atmospheric Hg depositional fluxes ranged from 0.74 to 7.89 μg m(-2) yr(-1), agreeing very well with the global natural values, but are one to two orders of magnitude lower than that of the neighboring East Asia. Elevated Hg concentrations were observed in refrozen ice layers in several snowpits subjected to intense melt, indicating that Hg can be potentially released to meltwater.


Effect of chitosan-based edible coating on preservation of white shrimp during partially frozen storage.
Chitosan and chitooligosaccharides are preservatives with proven antibacterial activity, while glutathione has antioxidant activity. This study investigated the effects of chitosan coating combined with chitooligosaccharides and glutathione (0.8% glutathione+1% chitooligosaccharides+1% chitosan) on preservation of white shrimp (Penaeus vannamei) during partially frozen storage. Chitosan-based coating treatments effectively inhibited bacterial growth, reduced total volatile basic nitrogen and malondialdehyde, and basically maintained the sensory properties of white shrimp (P. vannamei) during partially frozen storage. Therefore, chitosan-based edible coating combined with chitooligosaccharides and glutathione could be a promising antimicrobial and oxidant method to prevent metamorphism of white shrimp with extended shelf life.


Quantitation of microtubule-associated protein MAP-1B in brain and other tissues.
1. The presence of microtubule-associated protein MAP-1B in all mammalian tissues tested, as well as in brain, has been demonstrated by immunoblotting using a monospecific polyclonal antibody. 2. The expression of brain MAP-1B is developmentally controlled, as it is less abundant in adult than in newborn rat brain, where it is a major microtubule assembly promoting factor. 3. The level of MAP-1B in tissues other than brain is lower than it is in brain; but the relative ratios of MAP-1B to tubulin are very similar in all tissues, thus differing from the observed for MAP-2 or tau. 4. The amount of MAP-1B in non-nervous tissues seems not to be under developmental control. 5. These results are consistent with a role for MAP-1B in the assembly of microtubules in most cells.


Differential single-stranded DNA binding properties of the paralogous SsbA and SsbB proteins from Streptococcus pneumoniae.
The naturally transformable Gram-positive bacterium Streptococcus pneumoniae has two single-stranded DNA-binding (SSB) proteins, designated SsbA and SsbB. The SsbA protein is similar in size to the well characterized SSB protein from Escherichia coli (SsbEc). The SsbB protein, in contrast, is a smaller protein that is specifically induced during natural transformation and has no counterpart in E. coli. In this report, the single-stranded DNA (ssDNA) binding properties of the SsbA and SsbB proteins were examined and compared with those of the SsbEc protein. The ssDNA binding characteristics of the SsbA protein were similar to those of the SsbEc protein in every ssDNA binding assay used in this study. The SsbB protein differed from the SsbA and SsbEc proteins, however, both in its binding to short homopolymeric dT(n) oligomers (as judged by polyacrylamide gel-shift assays) and in its binding to the longer naturally occurring X and M13 ssDNAs (as judged by agarose gel-shift assays and electron microscopic analysis). The results indicate that an individual SsbB protein binds to ssDNA with an affinity that is similar or higher than that of the SsbA and SsbEc proteins. However, the manner in which multiple SsbB proteins assemble onto a ssDNA molecule differs from that observed with the SsbA and SsbEc proteins. These results represent the first analysis of paralogous SSB proteins from any bacterial species and provide a foundation for further investigations into the biological roles of these proteins.


Nonlinear mechanical modeling of cell adhesion.
Cell adhesion, which is mediated by the receptor-ligand bonds, plays an essential role in various biological processes. Previous studies often described the force-extension relationship of receptor-ligand bond with linear assumption. However, the force-extension relationship of the bond is intrinsically nonlinear, which should have significant influence on the mechanical behavior of cell adhesion. In this work, a nonlinear mechanical model for cell adhesion is developed, and the adhesive strength was studied at various bond distributions. We find that the nonlinear mechanical behavior of the receptor-ligand bonds is crucial to the adhesive strength and stability. This nonlinear behavior allows more bonds to achieve large bond force simultaneously, and therefore the adhesive strength becomes less sensitive to the change of bond density at the outmost periphery of the adhesive area. In this way, the strength and stability of cell adhesion are soundly enhanced. The nonlinear model describes the cell detachment behavior better than the linear model.


Progestins and estrogens and Alzheimer's disease.
Sex-specific incidence rates for Alzheimer's disease (AD) are higher in women than men. Many fundamental researches and some clinical investigations have reported therapeutic and preventive effects of estrogens on AD. But WHIMS [S.A. Shumaker, C. Legault, S.R. Rapp, L. Thal, R.B. Wallace, J.K. Ockene, S.L. Hendrix, B.N. Jones IIIrd, A.R. Assaf, R.D. Jackson, J.M. Kotchen, S. Wabertheil-Smoller, J. Wactawsk-Wende, WHIMS investigators, Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The women's health initiative memory study: a randomized controlled trial, JAMA 289 (2003) 2651-2662], which used daily continuous hormone replacement therapy (HRT), reported that the hazard ratio of the HRT for probable dementia was 2.05. Effect of progestins, and continuous (not cyclically) HRT, even only with estrogen should be reconsidered. In our clinical study, conjugated equine estrogen (CEE) alone showed good changes of psychiatric tests for AD on the 3rd week, but addition of medroxyprogesterone acetate (MPA) or norethindrone since 4th week suppressed these tests. Using human umbilical vein epithelial cell (HUVEC), levonorgestrel (LNG), norethindrone acetate (NETA), MPA increased intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-secretin but dienogest (DNG) showed no effect. In vitro flow system, estradiol (E2), suppressed adhesion of white cell, but LNG, NETA, MPA increased the adhesions. DNG showed less effect. Non-feminizing estrogen J 861, which has delta8,9 double bond and straight in its structure and has less effect on sexual organs. J 861 has shown ameliorative effects on central nervous system (CNS) (increasing of cholineacetyltransferase immunoreactive cells in substantia innominata (SI), etc.) like E2. More investigations about progestins and estrogens and AD should be done.


[Kidney and liver support therapies: state-of-the-art methods].
Today, worldwide approximately 1.5 million uremic patients owe their lives to hemodialysis. This figure will increase further by a growth rate of 6% annually reflecting a necessary increasing high interest in innovative technologies as well as in individualized therapies in this area. The main focus of developmental efforts, today and in the future, is to adapt the therapy to the specific physiological conditions of kidney patients, e.g., by means of a precise control of body water and its removal. This can be precisely monitored by bioimpedance analyses. Liver patients also benefit from the experiences with extracorporeal blood circuits. In contrast to hemodialysis, protein-permeable membranes are applied which allow for the removal of albumin-bound toxins. Albumin is then cleansed in the secondary circuit by adsorber cartridges and then readministered to the patient leading to improved recovery. This short review summarizes the state-of-the-art of blood purification methods in hemodialysis and liver support therapies.


Enhanced oxidative stress in hypertrophic cardiomyopathy.
Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated with enhanced oxidative stress. We enrolled 54 HCM patients with sinus rhythm, including 21 subjects with a left ventricular outflow tract (LVOT) obstruction (gradient >/= 30 mmHg), and 54 age- and sex-matched controls without cardiovascular diseases. Serum levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a stable marker of oxidative stress, were determined. Serum 8-iso-PGF(2alpha) levels were elevated in HCM patients compared with controls (35.4 +/- 10.2 vs. 29.9 +/- 9.9 pg/ml, p < 0.001). Patients with obstructive HCM displayed higher 8-iso-PGF(2alpha) levels compared with the non-obstructive HCM subgroup (41.6 +/- 12.7 vs. 31.4 +/- 5.4 pg/ml, p < 0.0001). Both anatomic (mitral-septal distance) and hemodynamic (subaortic gradient) indexes of LVOT obstruction, but not other echocardiographic variables, correlated with 8-iso-PGF(2alpha) levels (r = -0.43; p < 0.05 and r = 0.39; p < 0.05, respectively). This study is the first to show that HCM is characterized by enhanced oxidative stress as evidenced by higher 8-iso-PGF(2alpha), which achieves its highest values in the presence of LVOT obstruction in HCM patients.


PAF receptor and PAF acetylhydrolase expression in the endosalpinx of the human Fallopian tube: possible role of embryo-derived PAF in the control of embryo transport to the uterus.
Prostaglandin-E(2) and platelet-activating factor (PAF) are embryonic-derived signals that time embryo passage into the uterus in the mare and hamster respectively. PAF-like activity is detectable in the spent media of preimplantation human embryos and it has been suggested that PAF may be the embryonic signal that controls embryo transport to the uterus in our species. The actions of PAF are regulated at the level of its synthesis and degradation as well as the expression of a specific cell surface receptor (PAFr). The enzyme PAF acetylhydrolase (PAF-AH) degrades PAF. This study was undertaken to examine whether or not PAFr and PAF-AH are expressed in the human Fallopian tube and to identify the cell types in which they are expressed. The presence of PAFr mRNA in tissue extracts was investigated using reverse transcription-polymerase chain reaction. We amplified the predicted amplicon for PAFr mRNA from RNA samples extracted from Fallopian tubes. The expression of PAF-AH was detected by Western blot and the localization of PAFr and PAF-AH proteins was detected by immunohistochemistry. Utilizing antibodies against PAFr and PAF-AH, co-localization of the two proteins in the epithelium and stromal cells were demonstrated. These observations show that the human Fallopian tube expresses PAFr and PAF-AH at a location compatible with the proposed paracrine role of early embryo-derived PAF.


[The effect of a combined transplant on reparative osteogenesis in experimental bone defects of the jaw (the immediate results)].
A combined transplant consisting of bone flour plus the sorption-antimicrobial complex polymethylsiloxane + furazolidone + metronidazole is proposed to be grafted into the bone periodontal pockets in patients with generalized parodontitis. Effects were studied of the above transplant on the experimental defects of the lower jaw--of albino rats (n = 36). Morphologic changes in the immediate periods of follow-up (at day 7, 14, and 21) were characterized by a poorly manifest and short-term reactive inflammatory process in the paratransplant tissues as well as by an earlier development of the osteoid tissue and early formation of the bone regenerate.


Health care system redesign: a strategic management framework.
The current health care environment can best be characterized as uncertain, unfamiliar, ambiguous, unexpected, untraveled, and amorphous. All administrators and managers are facing a tremendous challenge in managing available human, technological, materiel, and fiscal resources to accomplish their organization's mission. They must be able to assess organizational environments, identify strategies to align the organization and the environment, implement these strategies, and continuously evaluate the outcomes of those strategies. Therefore, health care administrators and managers must adopt a management perspective that is responsive, dynamic, comprehensive, systematic, and both process and outcome oriented. Such a perspective is strategic management.


Early benefit of implantable cardioverter defibrillator therapy in patients waiting for cardiac transplantation.
The ICD can effectively recognize and treat ventricular arrhythmias that can lead to sudden death. Sudden death is a major problem in patients awaiting heart transplantation. We reviewed our experience with the ICD in patients with malignant ventricular arrhythmias waiting for cardiac transplantation. Nineteen patients were included. Seventeen were men, mean age was 54 +/- 11 years (range 17-66) and the left ventricular ejection fraction was 22% +/- 10% (range 9%-46%). After a mean follow-up of 6 +/- 5 months (range 1-20 months), 17 patients reached heart transplantation. One patient died and the other is waiting for a transplant. Before transplantation 71% of patients received an appropriate discharge. The mean time to the first appropriate discharge was 2 +/- 2 months (range < 1-6 months), which was significantly shorter than the mean time to first discharge in the other patients (n = 182) receiving a defibrillator in our center (11 +/- 10 months; range 1-58 months) (P < 0.0004). In conclusion, cardiac transplantation candidates with life-threatening ventricular arrhythmias can effectively be protected against sudden arrhythmic death by ICD. These patients have a high incidence of appropriate shocks occurring very early after implantation.


Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain.
To date no nucleic acid has been found in the purified infectious agent which causes the spongiform encephalopathy known as scrapie. In an attempt to identify a unique scrapie virus-associated messenger RNA in tissues of infected animals, we have synthesized an oligonucleotide probe complementary to the mRNA sequence corresponding to the amino-acid sequence of the prion protein, PrP27-30 (ref. 1). We report here that, with this probe, a complementary DNA clone representing PrP27-30 was obtained from scrapie-infected mouse brain; the DNA sequence of this clone could be translated into a protein that matches exactly the published sequence of PrP27-30. The cDNA clone hybridized to a single 2.4-2.5-kilobase (kb) mRNA from both normal and scrapie-infected brain. Thus, the PrP27-30 mRNA is not uniquely associated with scrapie infectivity, suggesting that PrP27-30 may be a normal component of mouse and hamster brain.


A predictive tool for the self-management of diabetes (Librae): evaluation using a continuous glucose monitoring system.
Diabetes self-management involves a difficult balancing act between insulin, food and exercise. The challenge is to develop innovative, validated algorithms to aid patient decision-making and optimize glycaemic control. 'Librae' is a computerized diabetes simulator in diary format, developed as an educational predictive tool for patients, reducing 'trial and error' by allowing patients to simulate and experiment with dietary or insulin adjustments on a 'body double'. We have evaluated the predictive ability of Librae using continuous blood glucose monitoring (CGMS). Patients with Type 1 Diabetes attending the Paediatric Clinic were invited to use 'Librae' for 1 week and were then fitted with a CGMS for 72 h. The predictive ability of 'Librae' was compared with concurrent data obtained from the CGMS. Seven thousand nine hundred and sixty paired blood glucose values were obtained from the 11 patients who completed the study. 'Librae' underestimated the measured CGMS values, the error having a positive mean of 0.35 mmol/l (95% confidence interval 0.22-0.48 mmol/l). However, Librae tended to overestimate at low levels of blood glucose readings, and underestimate at high levels of blood glucose readings. The modelled values of 'Librae' correlated well with the CGMS data, but clinically unacceptable errors occurred at extremes of blood glucose levels. Concurrent CGMS recordings have provided a large data set to modify and improve the existing Librae model and patient feedback has led to improvements in its usability. Librae may provide a useful tool to improve diabetes self-management education and optimize glycaemic control.


Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia.
This study investigated the impact of SLCO1B1 genotype on pravastatin systemic exposure in children and adolescents with hypercholesterolemia. Participants (8-20 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 15; 521CC, n = 2) and wild-type controls (521TT, n = 15) completed a single oral dose pharmacokinetic study. Interindividual variability of pravastatin acid (PVA) exposure within SLCO1B1 genotype groups exceeded the approximately twofold difference in mean PVA exposure observed between SLCO1B1 genotype groups (P > 0.05, q > 0.10). The 3'α-iso-pravastatin acid and lactone isomer formation in the acidic environment of the stomach prior to absorption also was variable and affected PVA exposure in all genotype groups. The SLCO1B1 c.521 gene variant contributing to variability in systemic exposure to PVA in our pediatric cohort was comparable to previous studies in adults. However, other demographic and physicochemical factors seem to also contribute to interindividual variability in the dose-exposure relationship.


Prevention and Amelioration of Rodent Ventilation-Induced Lung Injury with Either Prophylactic or Therapeutic feG Administration.
Mechanical ventilation is a well-established therapy for patients with acute respiratory failure. However, up to 35% of mortality in acute respiratory distress syndrome may be attributed to ventilation-induced lung injury (VILI). We previously demonstrated the efficacy of the synthetic tripeptide feG for preventing and ameliorating acute pancreatitis-associated lung injury. However, as the mechanisms of induction of injury during mechanical ventilation may differ, we aimed to investigate the effect of feG in a rodent model of VILI, with or without secondary challenge, as a preventative treatment when administered before injury (prophylactic), or as a therapeutic treatment administered following initiation of injury (therapeutic). Lung injury was assessed following prophylactic or therapeutic intratracheal feG administration in a rodent model of ventilation-induced lung injury, with or without secondary intratracheal lipopolysaccharide challenge. Prophylactic feG administration resulted in significant improvements in arterial blood oxygenation and respiratory mechanics, and decreased lung oedema, bronchoalveolar lavage protein concentration, histological tissue injury scores, blood vessel activation, bronchoalveolar lavage cell infiltration and lung myeloperoxidase activity in VILI, both with and without lipopolysaccharide. Therapeutic feG administration similarly ameliorated the severity of tissue damage and encouraged the resolution of injury. feG associated decreases in endothelial adhesion molecules may indicate a mechanism for these effects. This study supports the potential for feG as a pharmacological agent in the prevention or treatment of lung injury associated with mechanical ventilation.


Impact of chirality on the Glass Forming Ability and the crystallization from the amorphous state of 5-ethyl-5-methylhydantoin, a chiral poor glass former.
The investigation of the glassy state of 5-ethyl-5-methylhydantoin (i.e. 12H, a chiral Active Pharmaceutical Ingredient) was attempted by Differential Scanning Calorimetry (DSC) and Fast Scanning Calorimetry (FSC). This compound exhibits a high crystallization propensity for every enantiomeric composition. Nevertheless, glassy states of pure enantiomer or mixtures between enantiomers were successfully reached by FSC at cooling rates of: 1000 °C/s and 300 °C/s respectively, even though limitations on the sampling reproducibility were evidenced due to FSC sample size. The Glass Forming Ability (GFA) was proven to increase with the counter-enantiomer content. From the glassy state, pure enantiomer displayed a more pronounced crystallogenic character (with a crystallization occurring 36 °C below Tg during ageing) than that of the mixture between enantiomers. Ageing of amorphous 12H promotes a strong nucleation behavior in both samples but enantiopure 12H crystallizes upon ageing while scalemic 12H evolves towards the metastable equilibrium. Finally, potential new phase equilibria (previously not reported) in the enantiomeric phase diagram could have been highlighted by FSC by recrystallization from the amorphous state.


Electronic and magnetic properties of pristine and chemically functionalized germanene nanoribbons.
We perform a spin polarized density-functional theory (DFT) study of the electronic and magnetic properties of pristine and chemically doped germanene nanoribbons (GeNRs) with different widths. It is found that the Ge atom at the ribbon edge always prefers to be substituted by an impurity atom. Our study reveals that a single N or B atom substitution induces a semiconducting-metal transition in armchair oriented germanene nanoribbons (AGeNRs) as evidenced by the appearance of a half-filled band with less dispersion; however, N and B co-doping at the ribbon edges only modifies their band gaps, due to the accomplishment of an effective charge compensation. A single N or B atom substitution usually turns antiferromagnetic (AFM) semiconducting zigzag germanene nanoribbons (ZGeNRs) into ferromagnetic (FM) semiconductors. This AFM-FM transition is attributed mainly to the perturbation of π and π states localized at the doped edge. Double atom substitutions (regardless of N-N, B-B or N-B configurations) at the edges of ZGeNRs removes the spin-polarization at both edges and transforms them into non-magnetic (NM) semiconductors. Moreover, it is interesting that some single atom doped ZGeNRs can exhibit a FM half-metallic character with 100% spin-polarization at the Fermi level. Our results suggest that doped AGeNRs and ZGeNRs have potential applications in Ge-based nanoelectronics, such as field effect transistors (FETs), negative differential resistance (NDR) and spin filter (SF) devices.


Molecular cloning and nucleotide sequence of the pectin methyl esterase gene of Erwinia chrysanthemi B374.
The gene encoding pectin methyl esterase (pme) has been cloned from Erwinia chrysanthemi B374. Expression of pme in Escherichia coli allowed the enzyme to be characterized. Pectin methyl esterase (PME) was found to have an apparent molecular weight of 36,000 Daltons and an isoelectric point of approximately 9.9. The structural gene was sequenced and consists of a 1098-bp open reading frame encoding a polypeptide of 39,318 Daltons, which includes an amino-terminal signal peptide. The isolation of the Erwinia gene provides a simple method for the production of PME free from depolymerizing pectinases thereby extending its potential uses.


Torsade de pointes in a case of pheochromocytoma--an unusual presentation of an uncommon disease.
We report the case of a middle aged lady with dilated cardiomyopathy, presenting with recurrent syncope due to torsade de pointes. Further evaluation revealed that she had a pheochromocytoma which caused the arrhythmia.


"Sticky" brains and sticky encounters in a U.S. pediatric pain clinic.
In the U.S. multidisciplinary pediatric pain clinic where I conducted 18 months of fieldwork, a widely held explanatory model tied the neurobiology of intractable pain to certain features of pervasive developmental disorders (PDD) such as concrete thinking, an interest in details, and hyper-attentiveness. Clinicians used terms such as "sticky brains" and "sticky neurons" to describe the perseverative thoughts and quirky behavior that characterized a sizable subset of the program's chronic pain patients who were believed to show signs of PDD, and consequently, did not respond well to treatment. Drawing on observations of clinical consultations, team meetings, and interviews with clinicians and families, I examine the meta-discursive processes by which clinical difficulties were inscribed onto difficult patients. Specifically, I demonstrate how discourse on sticky brains worked to re-classify challenging patients as psychologically abnormal, rationalizing their failed response to standard treatment. I argue that 'stickiness' provides an appropriate metaphor not only for a particular neurobiological configuration, but also for challenging clinical encounters. By illuminating the interactional processes through which clinical difficulties are managed, interpreted, and explained, the paper advances anthropological theorizing on the performative work of diagnosis and institutionalized misrecognition.


Divining sugar substrates.


Digitalis: dead or alive?
Over 200 years age, William Withering described the advantages which might be gained by the considered use of extracts of the foxglove, digitalis purpurea, in patients with congestive heart failure, particularly if the rhythm was irregular. In the subsequent years many patients undoubtedly benefited from the use of this drug. The introduction of diuretics in the present century provided an alternative, more effective and safer treatment for heart failure. More recently, angiotensin-converting enzyme inhibitors have become available. The use of digoxin in the treatment of heart failure is now indicated almost solely for the control of a fast heart rate in patients with atrial fibrillation.


Assessment of Teeth Prepared by Senior Dental Students for CAD/CAM Restorations.
The aim of this study was to evaluate teeth prepared for computer-aided design/computer-aided manufacturing (CAD/CAM) restorations by senior dental students using recently developed rubrics. The rubrics used evaluation criteria based on four factors: retention or resistance form; marginal or internal adaption or manufacturing process; biology, esthetics, or durability of restorative material; and intraoral scanner impression. In academic year 2018-19, four faculty members used the rubrics to assess 111 first maxillary right premolars (tooth no. 4) prepared for lithium disilicate crowns and 223 second maxillary right premolars (tooth no. 5) and first maxillary right molars (tooth no. 3) prepared for monolithic zirconia partial fixed dental prostheses. The preparations had been performed on typodont teeth. The most common errors identified for tooth preparations were in the finish line quality (136 errors in 223 prostheses), a criterion that is crucial for quality CAD/CAM restorations. To prevent poorly fit CAD/CAM restoration preparations that result from an unacceptable finish line quality, students need to understand the rationale used to develop detailed rubrics and adhere to the defined critera.


Modeling analysis of [11C]flumazenil kinetics studied by PET: application to a critical study of the equilibrium approaches.
The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function. The experimental protocol consisted of four injections of labeled and/or unlabeled ligand. This protocol allows the evaluation, from a single experiment, of the five model parameters in various regions of interest. For example, in the temporal cortex, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (Kd) were estimated to be 70 +/- 15 pmol/ml and 15.8 +/- 2.2 nM, respectively. The validity of the equilibrium approach, which is the most often used quantitation method, has been studied from simulated data calculated using these model parameters. The equilibrium approaches consist of reproducing in PET studies the experimental conditions that permit the use of the usual in vitro methods such as Scatchard analysis. These approaches are often open to criticism because of the difficulty of defining the notion of equilibrium in in vivo studies. However, it appears that the basic relation of Scatchard analysis is valid over a broader range of conditions than those normally used, such as the requirement of a constant bound/free ratio. Simulations showed that the values of the receptor concentration (B'max) and the equilibrium dissociation constant (Kd) found using Scatchard analysis are always underestimated. These simulations also suggest an explanation concerning the dependency of B'max and Kd on the time point employed for the Scatchard analysis, a phenomenon found by several authors. To conclude, we propose new protocols that allow the estimation of the B'max and Kd parameters using a Scatchard analysis but based on a protocol including only one or two injections. These protocols being entirely noninvasive, it thus becomes possible to investigate possible changes in receptor density and/or affinity in patients.


Breathing during sleep in menopause: a randomized, controlled, crossover trial with estrogen therapy.
To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P <.05. The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P =.047) and frequency (P =.049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.


Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease.
The microtubule-affinity regulating kinase (MARK) family consists of four highly conserved members that have been implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer's disease (AD). Understanding of roles by individual MARK isoform in phosphorylating tau has been limited due to lack of antibodies selective for each MARK isoform. In this study, we first applied the proximity ligation assay on cells to select antibodies specific for each MARK isoform. In cells, a CagA peptide specifically and significantly inhibited tau phosphorylation at Ser²⁶² mediated by MARK4 but not other MARK isoforms. We then used these antibodies to study expression levels of MARK isoforms and interactions between tau and individual MARK isoforms in postmortem human brains. We found a strong and significant elevation of MARK4 expression and MARK4-tau interactions in AD brains, correlating with the Braak stages of the disease. These results suggest the MARK4-tau interactions are of functional importance in the progression of AD and the results also identify MARK4 as a promising target for AD therapy.


Quality of life after restorative proctocolectomy with pelvic ileal reservoir.
Fifty-five patients who had undergone restorative proctocolectomy with a pelvic ileal reservoir between 3 and 82 months previously were sent a detailed questionnaire to assess their quality of life. All patients had experienced an ileostomy at some time. Fifty-one (94 per cent) returned completed questionnaires. The average frequency of evacuation from the reservoir was four times per 24 hours. Antidiarrhoeal medication was required by 14 (27.4 per cent). Continence was normal in 32 (62.7 per cent) and only 3 (5.9 per cent) had troublesome faecal leakage. Twenty-two (43.1 per cent) evacuated stool spontaneously, while 24 (47.1 per cent) needed to catheterize the reservoir for each evacuation. Four patients who had had the reservoir removed were added to the 51 responders to give a total number of 55 whose quality of life was considered in this study. The reservoir was preferred to an ileostomy with regard to confidence (87 per cent), cleanliness (89 per cent), sexual self-image (87 per cent), social (85 per cent) and sport activity (87 per cent), and ease of carrying out work (84 per cent). The overall preference was 87 per cent. Thirty-four (66.7 per cent) felt there was no significant disadvantage associated with the reservoir, while 10 (19.6 per cent) saw the long convalescent period and 9 (17.6 per cent) the requirement for catheterization as drawbacks.


Pharmacological interventions for sleepiness and sleep disturbances caused by shift work.
Are pharmacological interventions associated with better-quality sleep and alertness in shift workers? Low-quality evidence shows that melatonin is associated with 24 minutes longer daytime sleep after the shift but not with faster falling asleep compared with placebo. There is no association between hypnotics, such as zopiclone, and sleep outcomes, alertness, or harms. The alertness-promoting medications armodafinil and modafinil are associated with improved alertness during shift work but are also associated with headache and nausea.


The association of serum insulin-like growth factor-I with mortality, cardiovascular disease, and cancer in the elderly: a population-based study.
Numerous studies have investigated the effect of serum IGF-I concentration on aging and different aging-related diseases, e.g. cardiovascular disease (CVD) and cancer. Decreased as well as increased levels have been reported to be associated with reduced life expectancy in humans. This study investigates the association of serum IGF-I concentration with all-cause and cause-specific mortality of community-dwelling older persons and the development of CVD and cancer. Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing multidisciplinary cohort study in the general Dutch population of older persons (≥65 yr old) where serum IGF-I was measured (n = 1273). The mortality information was ascertained using the International Classification of Diseases, 10th revision, and the presence or absence of CVD and cancer by self-reports with a follow-up of 11.6 yr. We measured all-cause, CVD, and cancer mortality and nonfatal CVD and cancer. Fully adjusted Cox proportional hazards models demonstrated an increased risk of all-cause mortality for older persons with IGF-I values in the lowest quintile as compared to the middle quintile [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.63]. A more than 2-fold increased risk of CVD mortality was revealed for both low-normal (HR, 2.39; 95% CI, 1.22-4.66) and high-normal (HR, 2.03; 95% CI, 1.02-4.06) IGF-I values. Significant associations of serum IGF-I with nonfatal CVD and fatal and nonfatal cancer were not observed. Results suggest a U-shaped relationship between IGF-I level and mortality, with fatal CVD as the most critical outcome in community-dwelling older persons.


Single-center experience with an inner branched arch endograft.
Whereas open repair is the "gold standard" for most aortic arch diseases, a subgroup of patients might benefit from an endovascular approach. The introduction of branched stent grafts with dedicated design to address the challenges of the ascending aorta and the aortic arch has opened an entirely new area of treatment for these patients. We investigated the early outcomes of branched thoracic endovascular aortic repair (b-TEVAR) in various types of disease of the aortic arch. A retrospective analysis was conducted of prospectively collected data from a single center of all consecutive patients treated with b-TEVAR. The indication for elective endovascular repair was consented in an interdisciplinary case conference. All patients were treated with a custom-made inner branched arch endograft with two internal branches (Cook Medical, Bloomington, Ind) and left-sided carotid-subclavian bypass. Study end points were technical success, 30-day mortality, and complications as well as late complications and reinterventions. Between 2012 and 2017, there were 54 patients (38 male; median age, 71 years) treated with diseases of the aortic arch. Indications for therapy involved degenerative aortic arch or proximal descending aortic aneurysms requiring arch repair (n = 24), dissection with or without false lumen aneurysms (n = 26), and penetrating aortic ulcers (n = 4). Forty-three cases (80%) were performed electively and 11 urgently for contained ruptures (n = 3) or symptomatic aneurysms (n = 8) with endografts already available for the patient or with grafts of other patients with similar anatomy. Technical success was achieved in 53 cases (98%). The 30-day mortality and major stroke incidence were 5.5% (3/54) and 5.5% (3/54), respectively; in-hospital mortality was 7.4% (n = 4), and minor strokes (including asymptomatic new cerebral lesions) occurred in 5.5% (n = 3). There were two cases of transient spinal cord ischemia with complete recovery and one of paraplegia. No retrograde type A dissections or cardiac injuries were observed. Three early stent graft-related reinterventions were necessary to correct proximal endograft kinking with type IA endoleak in one patient, a bridging stent graft stenosis in another patient, and false lumen persistent perfusion from dissected supra-aortic vessels in the last patient. Mean in-hospital stay was 14 ± 8 days. During a mean follow-up of 12 ± 9 months, three nonaorta-related deaths and one aorta-related death distal to the arch repair were observed. Treatment of aortic arch diseases with b-TEVAR is feasible and safe with acceptable mortality and stroke rates.


Recreational noise exposure and its effects on the hearing of adolescents. Part II: development of hearing disorders.
Part II, continuation of a previous paper, describes the significant hearing threshold shift found during the third year of the long-term study, which continued to be present in the fourth year, in a number of adolescents classified as Subgroup 2, who showed a higher mean HTL in the middle and especially in the high frequency ranges than the rest of the studied adolescents, classified as Subgroup 1. In both subgroups, the subjects showed high participation in recreational activities; nevertheless, the adolescents in Subgroup 2 showed higher participation in some of them in the last year of the study. From the beginning of the study, the mean HTL of the adolescents in Subgroup 2 was higher than the mean HTL of the adolescents in Subgroup 1. The exposure to high sound levels during leisure activities can be a cause of permanent hearing damage among young people with 'tender ears'.


Central nervous system dysfunction as the first manifestation of multiple organ dysfunction syndrome in stem cell transplant patients.
Development of CNS dysfunction in the setting of hematopoietic stem cell transplant (HSCT) has been previously shown to predict for subsequent second organ dysfunction and death. In this paper, we describe the characteristics of this isolated CNS dysfunction, and its relationship to multiple organ dysfunction syndrome (MODS) after HSCT. Twenty-one of 186 patients undergoing HSCT developed CNS dysfunction as their first organ dysfunction a mean of 22.8 +/- 0.9 days after the start of the preparative regimen. Compared with 137 patients who developed no organ dysfunction, patients presenting with CNS dysfunction were more likely to have undergone allogeneic HSCT (P = 0.001) and to have received a total body irradiation-based regimen (P = 0.001), and were less likely to have been transplanted for lymphoma (P = 0.008). Patients who developed CNS dysfunction were more likely to die than those with no organ dysfunction (P < 0. 001). Of the 21 patients who developed CNS dysfunction, 48% resolved their dysfunction by a mean of 4.6 days later without progression to second organ dysfunction, and 90% of these patients survived to day 100. Fifty-two percent of patients with CNS dysfunction progressed to second organ dysfunction (pulmonary or hepatic) a mean of 5.5 days later, and only 36% survived to day 100 (P = 0.02). The patients who progressed to second organ dysfunction and those who did not were not different in terms of type of HSCT (allogeneic vs autologous), stem cell source (blood vs bone marrow), age, diagnosis or preparative regimen. Development of CNS dysfunction in the setting of HSCT, as with other organ dysfunctions (such as hepatic veno-occlusive disease), probably represents an early manifestation of a systemic disorder predisposing for MODS, increasing the risk of transplant-related mortality. Early systemic therapies directed at modulating this systemic disorder are probably indicated. Bone Marrow Transplantation (2000) 25, 79-83.


Anticholinergic toxicity associated with lupine seeds as a home remedy for diabetes mellitus.
We describe a case of sparteine intoxication associated with using a preparation from lupine seeds. A female patient of Portuguese origin presented to the emergency department with classic anticholinergic signs after ingestion of a lupine seed extract. She took the preparation with the belief it represented a cure for her recently diagnosed diabetes. Analysis of the patient's lupine bean extract identified the preponderant compound as oxo-sparteine by gas chromatography/mass spectrometry. Intoxication by lupine seeds rarely occurs in human beings. To our knowledge, no medical or toxicologic evidence supports a belief that lupine extract could lower serum glucose levels. This case highlights the need for emergency care providers to be aware of the health hazards that can be associated with the use of such home remedies.


Mechanistic and kinetic study on the catalytic hydrolysis of COS in small clusters of sulfuric acid.
The catalytic hydrolysis of carbonyl sulfide (COS) and the effect of small clusters of H2O and H2SO4 have been studied by theoretical calculations. The addition of H2SO4 could increase the enthalpy change (ΔH<0) and decrease relative energy of products (relative energy<0), resulting in hydrolysis reaction changed from an endothermic reaction to an exothermic reaction. Further, H2SO4 decreases the energy barrier by 5.25 kcal/mol, and it enhances the catalytic hydrolysis through the hydrogen transfer effect. The (COS + H2SO4-H2O) reaction has the lowest energy barrier of 29.97 kcal/mol. Although an excess addition of H2O and H2SO4 increases the energy barrier, decreases the catalytic hydrolysis, which is consistent with experimental observations. The order of the energy barriers for the three reactions from low to high are as follows: COS + H2SO4-H2O < COS + H2O + H2SO4-H2O < COS + H2O+(H2SO4)2. Kinetic simulations show that the addition of H2SO4 can increase the reaction rate constants. Consequently, adding an appropriate amount of sulfuric acid promotes the catalytic hydrolysis of COS both kinetically and thermodynamically.


Crystal structure of a plant ribonuclease, RNase LE.
Ribonuclease LE (RNase LE) from cultured tomato (Lycopersicon esculentum) cells is a member of the RNase T(2) family showing broad base specificity. The crystal structure of RNase LE has been determined at 1.65 A resolution. The structure consists of seven alpha-helices and seven beta-strands, belonging to an alpha+beta type structure. Comparison of the structure of RNase LE with that of RNase Rh, a microbial RNase belonging to the RNase T(2) family, reveals that while the overall folding topologies are similar to each other, major insertions and deletions are found at the N-terminal regions. The structural comparison, an amino acid sequence alignment of the RNase T(2) enzymes, and comparison of the disulfide-bonding pattern of these enzymes show that the structure of RNase LE shown here is the basic framework of the animal/plant subfamily of RNase T(2) enzymes (including a self-incompatibility protein called S-RNase), and the structure of RNase Rh is that of the fungal subfamily of RNase T(2) enzymes (including RNase T(2)). Subsequently, we superposed the active-site of the RNase LE with that of RNase Rh and found that (1) His39, Trp42, His92, Glu93, Lys96, and His97 of RNase LE coincided exactly with His46, Trp49, His104, Glu105, Lys108, and His109, respectively, of RNase Rh, and (2) two conserved water molecules were found at the putative P(1) sites of both enzymes. These facts suggest that plant RNase LE has a very similar hydrolysis mechanism to that of fungal RNase Rh, and almost all the RNase T(2) enzymes widely distributed in various species share a common catalytic mechanism. A cluster of hydrophobic residues was found on the active-site face of the RNase LE molecule and two large hydrophobic pockets exist. These hydrophobic pockets appear to be base binding sites mainly by hydrophobic interactions and are responsible for the base non-specificity of RNase LE.


Imaging of en bloc renal transplants: normal and abnormal postoperative findings.
Cadaveric kidneys from donors less than 5 years old, previously considered inferior graft material, are now being successfully transplanted en bloc into children and adults. On the basis of our experience with 132 patients, we describe the general principles of the procedure and review the spectrum of normal and abnormal imaging findings in patients who have undergone this promising transplantation procedure. Paired cadaveric kidneys obtained from donors less than 5 years old (mean age, 24 months) were transplanted en bloc to 132 patients (mean age, 37 years) at our institution between 1981 and 1991. All available medical, surgical, pathologic, and imaging records were retrospectively reviewed to define the surgical technique, 1-year survival rate of the graft, appearance of the transplant on postoperative imaging studies, and the prevalence of and imaging findings caused by vascular, urinary, infectious, and neoplastic complications after transplantation. Complications were confirmed by a definitive imaging study, surgical exploration, or study of a pathologic specimen. Paired donor kidneys were transplanted en bloc extraperitoneally into the recipient's right or left iliac fossa, with intact portions of the donor aorta and inferior vena cava anastomosed to the recipient's external iliac artery and vein. One-year graft survival was 70% during the first 8 years of the study and 78% during the last 2 years. Postoperative imaging, particularly sonography and scintigraphy, clearly depicted the normal individual kidneys, urinary collecting systems, and en bloc vasculature. Postoperative complications were vascular (arterial stenoses and thromboses, venous thromboses, and pseudoaneurysms) in 18%, urinary (obstruction and anastomotic leak) in 11%, infectious (caliceal fungal balls) in 1%, and neoplastic (posttransplant lymphoma) in 1%. The complications involved one kidney in 60% of the patients and both kidneys in 40%. The imaging findings caused by these complications were similar to those caused by complications occurring after transplantation of single cadaveric kidneys; however, their detection was more difficult because of the complexity of the en bloc graft. Because of the shortage of available donor organs, en bloc renal transplantation will most likely become increasingly popular. Familiarity with the imaging appearance of the normal transplant and of posttransplantation complications will allow radiologists to perform effective postoperative imaging evaluations.


Integration and persistence of an investigational human living skin equivalent (ICX-SKN) in human surgical wounds.
To present the first human clinical data on an investigational living skin graft replacement that is being designed for application where tissue has been lost through surgery, disease or trauma. The ICX-SKN skin graft replacement is composed of an autosynthesized human collagen-based extracellular matrix and human dermal fibroblasts. In a first study to examine integration and persistence, full-thickness excisional wounds were made in six healthy human female volunteers and the ICX-SKN skin graft replacement applied and dressed. The surgical wounds were examined for up to 28 days post-application and the graft excised from each volunteer. Pre-excision gross examination revealed that the ICX-SKN skin graft replacement had integrated well in each of the six wounds and that re-epithelialization had occurred in each case. Histological analysis revealed that the ICX-SKN skin graft replacement remained in place and had become vascularized and provided a continuous wound closure. No serious adverse events were reported and no gross scarring or wound contracture was evident in the healed wounds. This is the first report of preliminary evidence indicating the persistence of an autosynthesized, tissue-engineered, living human skin substitute in healed acute wounds in humans.


Prevalence of symptoms of asthma, rhinitis, and atopic eczema in Brazilian adolescents related to exposure to gaseous air pollutants and socioeconomic status.
To evaluate the relationship between exposure to gaseous air pollutants (ozone [O3], carbon monoxide [CO], nitrogen dioxide [NO2], and sulfur dioxide [SO2]) socioeconomic status and the prevalence of symptoms of asthma, rhinitis and atopic eczema in adolescents. A sample of 16 209 adolescents from São Paulo West (SPW), São Paulo South (SPS), Santo André (SA), Curitiba (CR), and Porto Alegre (PoA) were enrolled. Data on air pollutants and socioeconomic status were compared to prevalence of symptoms with the Spearman correlation coefficient. Socioeconomic status was quite similar in all cities. The levels of O3 in SPW, SPS, and SA, and of CO in SA were higher than the acceptable ones. In relation to O3 and CO exposures, adolescents from SPW and SA had a significant risk of current wheezing, whereas living in SPW was associated with a high risk of rhinoconjunctivitis, eczema, and flexural eczema and living in CR to rhinitis. Exposure to NO2 was associated with a high risk of current wheezing in SPW and SA, and of severe asthma in SPW and PoA. Exposure to SO2 was associated with a high risk of current wheezing in SPW and SA, severe asthma in SPW and PoA, and nighttime cough, eczema, flexural eczema and severe eczema in SPW. Living in SPW, CR, or PoA was associated with a high risk of rhinitis, rhinoconjunctivitis, and severe rhinitis. Although we did not detect a characteristic pattern for all symptoms evaluated or a specific air pollutant, our data suggest a relationship between higher exposure to photochemical pollutants and high prevalence or risk of symptoms of asthma, rhinitis, and atopic eczema.


Risk--what is it?
Risk has been defined by the World Health Organization International Program on Chemical Safety as "the probability of an adverse effect in an organism, system or (sub) population caused under specified circumstances by exposure to an agent". This article addresses some of the key components of this definition. Determining risk is dependent on expert judgement of the overall body of evidence relating to adverse effects or hazards. Such evidence can come from a range of experimental and observational studies and reports. Ideally determining risk to humans would be based upon evidence from humans rather than from experimental animals but this is generally not feasible. Even when epidemiological studies are available there can be difficulties in ascribing a disease to a causal chemical agent, and there are inevitable limitations in assessing exposure. Whilst probability refers to a mathematical or statistical quantification of the proportion of a population at risk of adverse effects, it is more common to compare point estimates of exposure with health-based guidance values.