Bifurcation dynamics of natural drainage networks.
As water erodes a landscape, streams form and channellize the surficial flow. In time, streams become highly ramified networks that can extend over a continent. Here, we combine physical reasoning, mathematical analysis and field observations to understand a basic feature of network growth: the bifurcation of a growing stream. We suggest a deterministic bifurcation rule arising from a relationship between the position of the tip in the network and the local shape of the water table. Next, we show that, when a stream bifurcates, competition between the stream and branches selects a special bifurcation angle α=2π/5. We confirm this prediction by measuring several thousand bifurcation angles in a kilometre-scale network fed by groundwater. In addition to providing insight into the growth of river networks, this result presents river networks as a physical manifestation of a classical mathematical problem: interface growth in a harmonic field. In the final sections, we combine these results to develop and explore a one-parameter model of network growth. The model predicts the development of logarithmic spirals. We find similar features in the kilometre-scale network.


Two-stage revision of hip prosthesis infection using a hip spacer with stabilising proximal cementation.
Two-stage revision hip arthroplasty for infection using an antibiotic-loaded cement spacer has been used frequently with good results. However, spacer instability is also frequent. Proximal cementation of the spacer could avoid spacer dislocation. We retrospectively assessed 35 patients in whom a 2-stage revision hip arthroplasty for infection was carried out using an antibiotic-loaded cement spacer with gentamicin (Spacer-G) in which the spacer was proximally cemented in 16 patients. The mean follow-up was 32 months. We assessed spacer stability and infection elimination. There were 8 spacer dislocations (22.9%), 5 in hips without proximal cementation and 2 in hips with proximal cementation (p>0.05). There was no fracture in any hip. Reinfection occurred in 5 hips (14.3%), in 3 with the same microorganism, while 2 had a different microorganism. Our results indicate that the proximal cementation of the spacer prevents its dislocation. Infection was eliminated in 86% of the hips.


The cardiotoxicology of anthracycline chemotherapeutics: translating molecular mechanism into preventative medicine.
Anthracyclines remain a mainstay of chemotherapy in spite of their well-recognized cardiotoxicity. Recent experience with trastuzumab (Herceptin) and anthracycline therapy has prompted a detailed analysis of the function of erbB2 in the heart. These studies demonstrate a cardioprotective effect of neuregulin, the endogenous ligand for the erbB4/erbB2 heterodimeric receptor complex. Although the mechanisms of cytoprotection remain incompletely understood, these studies have triggered the question of whether physiological manipulation of cardioprotective pathways that involve erbB can be used to improve outcome in patients treated with anthracyclines. The local activation of cardioprotection by cardiovascular exercise may be such a manipulation and warrants further investigation.


Comparison processes in category learning: from theory to behavior.
Recent studies stressed the importance of comparing exemplars both for improving performance by artificial classifiers as well as for explaining human category-learning strategies. In this report we provide a theoretical analysis for the usability of exemplar comparison for category-learning. We distinguish between two types of comparison -- comparison of exemplars identified to belong to the same category vs. comparison of exemplars identified to belong to two different categories. Our analysis suggests that these two types of comparison differ both qualitatively and quantitatively. In particular, in most everyday life scenarios, comparison of same-class exemplars will be far more informative than comparison of different-class exemplars. We also present behavioral findings suggesting that these properties of the two types of comparison shape the category-learning strategies that people implement. The predisposition for use of one strategy in preference to the other often results in a significant gap between the actual information content provided, and the way this information is eventually employed. These findings may further suggest under which conditions the reported category-learning biases may be overcome.


Mechanical properties and microstructures of cast Ti-Cu alloys.
This study evaluated the mechanical properties of cast Ti-Cu alloys with the hope of developing an alloy for dental casting with better mechanical properties than unalloyed titanium. Ti-Cu alloys with five concentrations of copper (0.5, 1.0, 2.0, 5.0 and 10.0 mass%) were made in an argon-arc melting furnace. The alloys were cast into magnesia-based molds using a centrifugal casting machine. The microstructure, microhardness profile of the specimen cross section, tensile strength, yield strength, and elongation were determined for the castings. Scanning electron microscope fractography was undertaken for the fractured surfaces after tensile testing. XRD was performed on the polished specimens. Results were analyzed using one-way ANOVA and the Student-Newman-Keuls tests. The mean tensile strengths of all the cast Ti-Cu alloys were significantly (p<0.05) higher than for cast commercially pure titanium (CP Ti). Of the Ti-Cu alloys tested, the 5 and 10% Cu alloys had significantly higher strength than the rest. The 10% Cu alloy exhibited the lowest mean elongation. CP Ti and the 0.5 and 1% Cu alloys showed higher ductility. The bulk hardness of all the cast Ti-Cu alloys, except for the 10% Cu alloy, and CP Ti was approximately the same. By alloying with copper, the cast titanium became stronger. Increases in the tensile strength (30%) and yield strength (40%) over CP Ti were obtained for the 5% Cu alloy. Elongation was approximately 3%, which was similar to cast Ti-6Al-4V. Ti-Cu alloys, such as the 5% Cu alloy, could be used for prosthetic dental applications if other properties necessary for dental castings are obtained.


A Novel Computer-Based Set-Up to Study Movement Coordination in Human Ensembles.
Existing experimental works on movement coordination in human ensembles mostly investigate situations where each subject is connected to all the others through direct visual and auditory coupling, so that unavoidable social interaction affects their coordination level. Here, we present a novel computer-based set-up to study movement coordination in human groups so as to minimize the influence of social interaction among participants and implement different visual pairings between them. In so doing, players can only take into consideration the motion of a designated subset of the others. This allows the evaluation of the exclusive effects on coordination of the structure of interconnections among the players in the group and their own dynamics. In addition, our set-up enables the deployment of virtual computer players to investigate dyadic interaction between a human and a virtual agent, as well as group synchronization in mixed teams of human and virtual agents. We show how this novel set-up can be employed to study coordination both in dyads and in groups over different structures of interconnections, in the presence as well as in the absence of virtual agents acting as followers or leaders. Finally, in order to illustrate the capabilities of the architecture, we describe some preliminary results. The platform is available to any researcher who wishes to unfold the mechanisms underlying group synchronization in human ensembles and shed light on its socio-psychological aspects.


Second malignancy after treatment of childhood non-Hodgkin lymphoma.
The objective of this report was to determine the cumulative incidence of and risk factors for second malignancy and the competing risk of death due to any other cause among patients who were treated for childhood non-Hodgkin lymphoma (NHL). The authors retrospectively reviewed a cohort of 497 patients with NHL who were treated at St. Jude Children's Research Hospital between 1970 and 1997. A second malignancy developed in 16 patients (9 patients with solid tumors and 7 patients with secondary acute myeloid leukemia [AML]). This number was 10.8-fold (95% confidence interval, 6.1-16.9) higher than the 1.48 patients projected for the general population by SEER Cancer Statistics. The estimated cumulative incidence rate of second malignancy was 2.1% +/- 0.7% at 10 years after diagnosis of NHL and increased to 4.8% +/- 1.3% at 20 years after diagnosis. The cumulative incidence rate of second malignancy was least among patients with small noncleaved cell lymphoma (0.5% +/- 0.5% at 20 years), higher among patients with large cell lymphoma (5.8% +/- 3.3% at 20 years), and highest among patients with lymphoblastic lymphoma (10.9% +/- 3.6% at 20 years; P = 0.002 for overall comparison). Exposure to epipodophyllotoxins was a risk factor for the development of secondary AML (P < 0.001). The cumulative incidence rate of death due to other causes was significantly less for patients who were treated after June 1978 (19.9% +/- 2.2% at 10 years) compared with patients who were treated earlier (55.6% +/- 4.2% at 10 years; P < 0.001), whereas the risk of second malignancy was similar for these two eras. Survivors of childhood NHL, especially those with lymphoblastic histology, are at a greater risk of developing a second malignancy compared with the general population. The incidence rate of second malignancy has remained unchanged despite a recent decline in the risk of death related to primary NHL or earlier treatment complications.


ReTrust: attack-resistant and lightweight trust management for medical sensor networks.
Wireless medical sensor networks (MSNs) enable ubiquitous health monitoring of users during their everyday lives, at health sites, without restricting their freedom. Establishing trust among distributed network entities has been recognized as a powerful tool to improve the security and performance of distributed networks such as mobile ad hoc networks and sensor networks. However, most existing trust systems are not well suited for MSNs due to the unique operational and security requirements of MSNs. Moreover, similar to most security schemes, trust management methods themselves can be vulnerable to attacks. Unfortunately, this issue is often ignored in existing trust systems. In this paper, we identify the security and performance challenges facing a sensor network for wireless medical monitoring and suggest it should follow a two-tier architecture. Based on such an architecture, we develop an attack-resistant and lightweight trust management scheme named ReTrust. This paper also reports the experimental results of the Collection Tree Protocol using our proposed system in a network of TelosB motes, which show that ReTrust not only can efficiently detect malicious/faulty behaviors, but can also significantly improve the network performance in practice.


[Development of a nutritional assessment tool for home care centers].
The purpose of this study was to develop a tool for nutritional assessment, so that home care nurses can make early assessment of patients' nutritional status. The study was done in two parts: first a tool was developed to assess nutrition, and second the content validity and clinical validity of the categories and indices were verified. The results of this study are summarized in two ways. First, the nutritional assessment tool was classified into 3 areas, physical measurement, nutritional survey and clinical survey, and into 11 categories with 22 indices. Second, when 5 of the 11 categories were positive, nutritional status was considered to be poor. By developing a clinically useful nutritional assessment tool for patients receiving home care, which was developed in this study, the quality of life for these patients will improve and contribution to the development of a more effective clinical home nursing practice will occur.


Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances.
Monoamine oxidase inhibitors (MAOI) in clinical use have an irreversible action on MAO, and this persists until the enzyme has been resynthesized. The effects of small daily doses of MAOI are therefore cumulative. The biochemical effects of these drugs will involve several substrates of MAO, e.g. dopamine, tyramine, serotonin and, to a lesser extent, noradrenaline and adrenaline.MAO probably regulates the metabolism of catecholamines and serotonin in tissues, while catechol-O-methyltransferase is responsible for the metabolism of circulating noradrenaline and adrenaline.Certain pharmacological effects of MAOI are related to the accumulation of monoamines in various tissues that follows the decrease of intraneuronal deamination. Among these effects are reversal of the reserpine syndrome in animals and augmentation of the pharmacological action of monoamines. Other effects are unrelated to the inhibition of MAO, e.g. immediate desynchronization of EEG and initial pressor effects.MAOI may potentiate or change the action of several other drugs and even certain foods. The mechanisms involved are usually reasonably predictable from animal experiments. Substrates of MAO, e.g. dopamine and tyramine, evoke augmented and prolonged effects in patients treated with MAOI. This is partly due to an impaired metabolism of the circulating amines. In addition, inhibition of intestinal and hepatic MAO largely increases the absorption of tryamine from cheeses and other foods. Usually innocuous amounts of tyramine may therefore cause hypertensive reactions in patients treated with MAOI. Indirectly acting sympathomimetic amines, such as amphetamines, ephedrine and MAOI with amphetamine-like properties, can be potentiated, because they may release increased amounts of nor-adrenaline from sympathetic nerve endings after MAO inhibition. The effects of any amine, whether a substrate of MAO or not, may be enhanced by MAO inhibitors producing postganglionic block. This is due to ;denervation' supersensitivity of adrenergic receptors.Harmful pharmacological interaction is also possible between MAO inhibitors and agents which release (reserpine) or replete (amine precursors, e.g. L-DOPA in broad beans) monoamines centrally and peripherally. Drugs that sensitize adrenergic and tryptaminergic receptors to the action of monoamines, e.g. imipramine-like compounds, may be greatly potentiated by MAO inhibitors. The anti-hypertensive effects of thiazides and ganglion-blocking agents may be enhanced by MAOI. A few drugs are known to exert prolonged effects in occasional patients treated with MAOI, e.g. pethidine, phenothiazines and pentobarbital. MAOI may possibly decelerate the metabolism of these compounds by a nonspecific inhibition of liver microsomal enzymes. Finally, a great number of agents have been found empirically to evoke augmented effects after inhibition of MAO, e.g. insulin and anti-Parkinson drugs.


Stimulatory and inhibitory actions of lysophosphatidylcholine, depending on its fatty acid residue, on the phospholipase C/Ca2+ system in HL-60 leukaemia cells.
We examined the mechanism of action of lysophosphatidylcholine (LPC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflammatory disorders, in HL-60 leukaemia cells. Extracellular 1-palmitoyl LPC increased the intracellular Ca2+ concentration in association with production of inositol phosphate. These actions of LPC were markedly inhibited by treatment of the cells with pertussis toxin and U73122, a phospholipase C inhibitor. The lipid-induced stimulation of the phospholipase C/Ca2+ system was also attenuated in the dibutyryl cAMP-induced differentiated (neutrophil-like) cells, in which phospholipase C activation induced by NaF or formyl-Met-Leu-Phe was enhanced. In contrast with the stimulatory action of 1-palmitoyl LPC, 1-stearoyl LPC was inhibitory for the phospholipase C/Ca2+ system stimulated by NaF as well as by 1-palmitoyl LPC or other Ca2+-mobilizing agonists. In a cell-free system, only an inhibitory effect on phospholipase C activity was observed even by 1-palmitoyl LPC; 1-stearoyl LPC was more inhibitive than 1-palmitoyl LPC. Taken together, these results suggest that atherogenic and inflammatory LPC exerts both stimulatory and inhibitory actions on the phospholipase C/Ca2+ system depending on the species of fatty acid residue of the lipid; the stimulatory effect is possibly mediated through G-protein-coupled receptors; the inhibitory effect might be caused by dysfunction of the components involved in the enzyme system owing to the amphiphilic nature of the lipid. 1-Palmitoyl LPC prefers the former receptor stimulation at least in intact cells, but 1-stearoyl LPC preferentially exerts the latter inhibitory action.


Crash injury risk behavior in adolescent latino males: the power of friends and relational connections.
The adolescent Latino male mortality profile is an anomaly when compared to an otherwise more favorable overall U.S. Latino population mortality profile. Motor vehicle crash fatalities bear a considerable proportion of mortality burden in this vulnerable population. Friend influence and relational connection are two contextual domains that may mediate crash injury risk behavior in these adolescents. Our study goal was to assess the role of friend influence over time and relational connections associated with crash injury risk behavior (CIRB) in adolescent Latino males. Waves I and II data from the National Longitudinal Study of Adolescent Health were used. Scale of CIRB, and three relational connections; school connectedness, parent connectedness, and expectation of academic success were developed and tested. Friend nomination data were available and the index student responses were linked to friend responses. Linear regression was used to assess the relationship of relational connections and friend CIRB on index student CIRB at wave I and II. Longitudinal analysis did not show significant evidence for friend influence among adolescent Latino males on CIRB. The best predictor of CIRB at wave II for adolescent Latino males was their CIRB at wave I. Relational connections were important yet exaggerated cross-sectionally but their effect was substantially attenuated longitudinally. The lack of friend influence on CIRB for adolescent Latino males may be specific to this demographic group or characteristic of the sample studied. Prevention strategies that focus on modulating friend influence in adolescent Latino males may not yield the desired prevention effects on CIRB.


The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study.
Recurrent cellulitis is an important clinical issue but the optimal strategy for prophylaxis is not determined. Intramuscular benzathine penicillin at a 4-week interval had been adopted in our hospital and the study was conducted to evaluate the efficacy. From January 1, 2009 to May 31, 2013, all patients aged ≥ 18 year, with a history of recurrent cellulitis and having received at least three shots of intramuscular benzathine penicillin for prophylaxis were retrospectively recruited for analysis. Two treatment periods (prophylaxis period and nonprophylaxis period) were defined. The effects of benzathine penicillin prophylaxis and patient characteristics on the incidence rate of recurrent cellulitis were analyzed using Poisson regression model. A total of 72 patients were enrolled, including 26 (36.1%) men. The most common underlying conditions were past surgery at the proximal side of the affected limb (38, 52.8%), malignancy (31, 43.1%), and diabetes mellitus (24, 33.3%). The incidence rate of recurrent cellulitis in the prophylaxis period was 0.73 episode/patient-year, significantly lower than that of 1.25 episodes/patient-year in the nonprophylaxis period (p < 0.001). Tinea pedis was a significant factor associated with increasing incidence of recurrent cellulitis in our cohort. Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.


Selection bias as an explanation for the observed protective association of childhood adiposity with breast cancer.
Recalled childhood adiposity is inversely associated with breast cancer observationally, including in Mendelian randomization (MR) studies. Breast cancer studies recruited in adulthood only include survivors of childhood adiposity and breast cancer or a competing risk. We assessed recalled childhood adiposity on participant reported sibling and maternal breast cancer to ensure ascertainment of nonsurvivors. We obtained independent strong genetic predictors of recalled childhood adiposity for women and their associations with participant reported own, sibling and maternal breast cancer from UK Biobank genome wide association studies. Recalled childhood adiposity in women was inversely associated with own breast cancer using Mendelian randomization inverse variance weighting (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.52-0.84) but less clearly related to participant reported sibling (OR 0.89, 95% CI 0.69-1.14) or maternal breast cancer (OR 0.84, 95% CI 0.67-1.05). Weaker inverse associations of recalled childhood adiposity with breast cancer with more comprehensive ascertainment of cases before recruitment suggests the inverse association of recalled childhood adiposity with breast cancer could be partly selection bias from preferential selection of survivors. Greater consideration of survival bias in public health relevant causal inferences would be helpful.


Vascularization of the ovine amnion and chorion: a morphometric characterization of the surface area of the intramembranous pathway.
The purpose of this study was to characterize the vascularization of the ovine amnion, allantois, and chorion. A white silicone vascular casting material was infused into both umbilical arteries of nine fetal sheep ranging in age from 58 to 142 days' gestation. A morphometric analysis of photomicrographs of the membranes was then performed with computerized image analysis techniques. After removal of the uterus, the fetus was surrounded by a layer of white silicone-filled microvessels in the chorion. The amniotic membrane after separation from the chorion was covered by a fine mesh of microvessels, whereas the allantois was avascular. The amniotic membrane readily separated into an outer vascularized layer and an inner, avascular layer containing the amnion. Approximately 50% of the surface of the chorionic membrane was covered by microvessels; this appeared independent of gestational age. At midgestation 30% of the surface of the amnion was covered by microvessels, and this decreased to 17% at 142 days. Relative to fetal weight, the amniotic and chorionic vascular surface areas decreased from 6 to 0.3 and from 15 to 1.5 cm2/gm fetal weight, respectively, over the last half of gestation. There is an extensive network of microscopic fetal blood vessels within the ovine chorion and covering the outer surface of the amnion. These vessels appear to be ideally situated to facilitate a direct exchange of water and solutes between amniotic or allantoic fluids and fetal blood through the intramembranous pathway.


Understanding rural practice: implications for occupational therapy education in Canada.
Currently Canadians living in rural communities tend to have a poorer health status than those living in urban settings. This is contributed to by the shortage of health professionals choosing work in rural and remote areas. Over the past decade there has been much research into the recruitment and retention of rural health professionals. However little has been done to identify the actual nature of rural practice and whether graduates have been adequately prepared for the diversity of rural work. The present study sought to identify the rewards and challenges of rural occupational therapy practice in western Canada. Participants' were also asked about their preparedness for rural practice after graduation, and specifically about the usefulness of course work and practical skills taught as undergraduates. Participants were occupational therapists working in rural communities in the Canadian provinces of Alberta and Saskatchewan. The quantitative approach employed a self-administered survey with closed- and open-ended questions. Data were entered into SPSS v14 (http://www.spss.com.au) for frequency data and percentages. The participants (n = 59) worked mainly in full-time community healthcare positions with clients who had physical health issues. More than half worked in sole therapy positions. The average length of time in their current position was 5 years. Most participants reported that they were receiving informal professional support, with some receiving a formal support as well. Participants more frequently identified the rewards of rural practice (n = 214) than its challenges (n = 112). Perceived rewards included team work, autonomy, diversity and flexible work schedule, increased client contact, job satisfaction, experiences gained and the rural lifestyle. The most frequently mentioned challenges included staff shortages, the generalist nature of rural occupational therapy practice, excess time spent travelling, coping with inappropriate referrals and the need for more professional support. Regarding participants' perceptions about the course work and practical skills taught during their training that best prepared them for actual practice, some highlighted additional valuable resources such as actual hands-on experience during rural fieldwork placement, personal characteristics, working in an urban setting prior to embarking on a rural career, coming from a rural background and locating a mentor prior to working rurally. Some recommended increasing management and organisational skills content in the curriculum because these were considered essential skills for effective rural practice. The return of unanswered questionnaires by participants who did not consider themselves to be rural therapists because of access to online and telehealth resources suggests further research is warranted into the changing nature of rural practice. Characteristics of current rural occupational therapy practice in western Canada were identified. Overall, rural occupational therapy practice appeared to be rewarding, and few had difficulty in accessing professional support. While on the whole the participants believed their training prepared them adequately for rural practice, the acquisition of increased management and organisational skills during training was seen as necessary to effectively manage their typically large and diverse caseloads. Participants' access to online and telehealth resources appears to have markedly changed the nature of rural practice and further research is recommended to determine the impact of such technologies.


Antibiotics and efflux: combined spectrofluorimetry and mass spectrometry to evaluate the involvement of concentration and efflux activity in antibiotic intracellular accumulation.
In Gram-negative bacteria, passing through the double membrane barrier to reach the inhibitory concentration inside the bacterium is a pivotal step for antibiotic activity. Spectrofluorimetry has been developed to follow fluoroquinolone accumulation inside bacteria using intrinsic bacterial fluorescence as an internal standard. However, adaptation for non-fluorescent antibiotics is needed; quantitative methods based on MS offer the possibility of expanding the detection range obtained by spectrofluorimetry. To validate, with spectrofluorimetry, the use of MS to measure antibiotic accumulation in cells and to determine the relationship between antibiotic concentrations and the amount of intrabacterial accumulation in different efflux backgrounds on the same batch of molecules. Spectrofluorimetry was performed in parallel with MS on the same samples to measure the ciprofloxacin and fleroxacin accumulation in cells expressing various efflux pump levels. A microplate protocol was set up to determine the antibiotic accumulation as a function of external antibiotic concentrations. A correlation existed between the data obtained with spectrofluorimetry and MS, whatever the efflux pump or tested antibiotic. The results highlighted different dynamics of uptake between ciprofloxacin and fleroxacin as well as the relationship between the level of efflux activity and antibiotic accumulation. We have developed a microplate protocol and cross-validated two complementary methods: spectrofluorimetry, which contains a reliable internal standard; and MS, which allows detection of low antibiotic amounts. These assays allow study of the dose effect and the efflux impact on the intrabacterial accumulation of antibiotics.


Detection of Nonvolatile Inorganic Oxidizer-Based Explosives from Wipe Collections by Infrared Thermal Desorption-Direct Analysis in Real Time Mass Spectrometry.
Infrared thermal desorption (IRTD) was coupled with direct analysis in real time mass spectrometry (DART-MS) for the detection of both inorganic and organic explosives from wipe collected samples. This platform generated discrete and rapid heating rates that allowed volatile and semivolatile organic explosives to thermally desorb at relatively lower temperatures, while still achieving elevated temperatures required to desorb nonvolatile inorganic oxidizer-based explosives. IRTD-DART-MS demonstrated the thermal desorption and detection of refractory potassium chlorate and potassium perchlorate oxidizers, compounds difficult to desorb with traditional moderate-temperature resistance-based thermal desorbers. Nanogram to sub-nanogram sensitivities were established for analysis of a range of organic and inorganic oxidizer-based explosive compounds, with further enhancement limited by the thermal properties of the most common commercial wipe materials. Detailed investigations and high-speed visualization revealed conduction from the heated glass-mica base plate as the dominant process for heating of the wipe and analyte materials, resulting in thermal desorption through boiling, aerosolization, and vaporization of samples. The thermal desorption and ionization characteristics of the IRTD-DART technique resulted in optimal sensitivity for the formation of nitrate adducts with both organic and inorganic species. The IRTD-DART-MS coupling and IRTD in general offer promising explosive detection capabilities to the defense, security, and law enforcement arenas.


A feasibility study of the in vivo measurement of aluminium in peripheral bone.
In summary, it is feasible to construct a neutron source, using the 3H(1H,n)3He reaction and the Dynamitron accelerator, which is suitable for the measurement of aluminium in vivo. It is useful to compare this system with other published data for in vivo aluminium measurement. The important parameters are presented in table 2 where MDL represents the minimum detectable level for the stated local dose. The figures in table 2 are very encouraging since the system described in this paper is at a very early stage of development. Significant improvements in sensitivity (detected 28Al counts per unit dose) should be expected from the combined effects of: (i) Increased NaI detector sizes. (ii) Neutron transport calculations to optimise the irradiation cavity. (iii) Experiments to determine the optimum source energy more precisely. (iv) Better dose delivery (giving the same dose in a shorter time). (v) More sophisticated spectroscopic data reduction. Published data on the amounts of aluminium typically found in hands of patients with renal disease (Ellis and Kelleher 1987) show that aluminium levels are likely to be in the 0.3 to about 15 mg range. Any improvements in system performance could largely be used to reduce the patient dose since the measurement sensitivity reported here is already close to that required for meaningful clinical measurements.


A rapid method for determining kinetic parameters of enzymes exhibiting nonlinear thermal inactivation behavior.
A rapid method is developed to analyze the kinetics of thermal inactivation of enzymes that exhibit a nonlinear biphasic log(activity)-time relationship. Thermal destruction experiments on alcohol dehydrogenase from baker's yeast demonstrate the applicability of the method. The method is based on physical considerations (as opposed to mathematical curve fitting/regression methods) and also serves as a quick check of results obtained using nonlinear regression. It is superior to fitting nonlinear enzyme inactivation data by first-order kinetics or taking the initial and final slopes of the inactivation data. In fact, the method is of general validity and can be applied to any decay process that can be represented by a sum of exponentials.


GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa.
Phytochemical investigation of the lipids extracted from seeds of Cannabis sativa by GC-MS showed 43 cannabinoids, 16 of which are new. The extract is dominated by Δ9-tetrahydrocannabinolic acid (A) and its neutral derivative trans-Δ9-tetrahydrocannabinol-C5 (THC) Cis and trans-Δ9-tetrahydrocannabinol-C7 isomers with an ethyl-pentyl branched chain together with minor amounts of trans-Δ9-tetrahydrocannabinol with a methyl-pentyl C6 branched side chain were identified as new natural compounds. Four cannabichromene isomers with a C5 side chain are postulated to be derived from the double bond migration at the terminal isoprenyl unit. C7 cannabichromene together with the neutral and acidic forms of cannabinol-C7 were also detected. The mass spectrum of these homologues as trimethylsilyl (TMS) derivatives are presented, and the fragmentation patterns are discussed.


NaGaSe2: A Water-Loving Multifunctional Non-van der Waals Layered Selenogallate.
A missing member of well-known ternary chalcometallates, a sodium selenogallate, NaGaSe2, has been synthesized by employing a polyselenide flux and stoichiometric reaction. Crystal structure analysis using X-ray diffraction techniques reveals that it contains supertetrahedral adamantane-type Ga4Se10 secondary building units. These Ga4Se10 secondary building units are further connected via corners to form two-dimensional (2D) [GaSe2]∞- layers stacked along the c-axis of the unit cell, and the Na ions reside in the interlayer space. The compound has an unusual ability to absorb water molecules from the atmosphere or a nonanhydrous solvent to form distinct hydrated phases, NaGaSe2·xH2O (where x can be 1 and 2), with an expanded interlayer space, as verified by X-ray diffraction (XRD), thermogravimetric-differential scanning calorimetry (TG-DSC), desorption, and Fourier transform infrared spectroscopy (FT-IR) studies. The in situ thermodiffractogram indicates the emergence of an anhydrous phase before 300 °C with the decrease of interlayer spacings and reverting to the hydrated phase within a minute of re-exposure to the environment, supporting the reversibility of such a process. Structural transformation induced through water absorption results in an increase of Na ionic conductivity by 2 orders of magnitude compared to that of the pristine anhydrous phase, as verified by impedance spectroscopy. Na ions from NaGaSe2 can be exchanged in the solid-state route with other alkali and alkaline earth metals in a topotactic or nontopotactic way, leading to 2D isostructural and three-dimensional networks, respectively. Optical band gap measurements show a band gap of ∼3 eV for the hydrated phase, NaGaSe2·xH2O, which is in good agreement with the calculated band gap using a density functional theory (DFT)-based method. Sorption studies further confirm the selective absorption of water over MeOH, EtOH, and CH3CN with a maximum water uptake of 6 molecules/formula unit at a relative pressure, P/P0, of 0.9.


[Status of elemental diets in the therapy of Crohn disease in childhood].
Since the seventieth low molecular weight formulas, "elemental diets", are applied in acute Crohn's disease in addition to drug therapy. In small bowel involvement, therapeutic efficiency in active disease is as good as salazosulfapyridine combined with corticosteroids. Physiological changes under elemental diet have been reported: decrease of gastric and pancreatic secretion, changes of bacterial bowel flora and in patients with Crohn's disease decreased fecal bile acid excretion and decreased intestinal losses of lymphocytes were described. Further, the absence of allergens in the formula and the quick and complete resorption are discussed to be important to clinical improvement in Crohn's disease. Indications for elemental diet are acute small bowel disease, intestinal obstruction, malnourishment and growth retardation. Further studies are needed to examine if elemental diets are effective in gastrointestinal fistulas and extraintestinal symptoms in Crohn's disease.


Effects of verapamil in models of ischemic acute renal failure in the rat.
This study was designed to determine whether verapamil protects renal function in experimental ischemia in the rat and, if so, whether the protection is mediated by verapamil's vasodilatory action or by an effect on renal cells independent of vascular perfusion. Inulin clearance (CIn) was examined for 3 h subsequent to 40 min of unilateral intrarenal infusion of norepinephrine (0.75 microgram X kg-1 X min-1) and 3 and 48 h subsequent to 40 min of unilateral renal pedicle clamp. In norepinephrine-induced ischemia CIn fell to 0.8 +/- 0.4% of preischemic values in saline-treated kidneys and 0.5 +/- 0.3% in verapamil post-treated kidneys. By contrast, CIn fell only to 52.3 +/- 6.5% of preischemic values in verapamil-pretreated kidneys. Verapamil pretreatment significantly counteracted the intrarenal vasoconstriction produced by norepinephrine, sustaining renal blood flow during the norepinephrine infusion. In pedicle clamp-induced ischemia verapamil pre- and posttreatment had no beneficial effect on preservation of glomerular filtration rate, whereas mannitol pretreatment was beneficial. Parallel studies in the isolated perfused rat kidney confirmed the in vivo observations. In conclusion, verapamil exerts no protective effect on renal function at 3 or 48 h when ischemia is induced by renal pedicle clamp. Likewise, verapamil administration subsequent to norepinephrine-induced ischemia is ineffective in preserving renal function. Verapamil pretreatment in norepinephrine-induced ischemia preserves renal function probably by attenuating the vasoconstrictive ischemic insult due to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients.
Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) is a rare inborn error of the immune system characterized by impaired antigen presentation and combined immunodeficiency. It causes severe and unremitting infections leading to progressive liver and lung dysfunctions and death during childhood. As in other combined immunodeficiency disorders, bone marrow transplantation (BMT) is considered the treatment of choice for MHC class II deficiency. We analyzed the files of 19 patients who have undergone BMT in our center. Of the 7 patients who underwent HLA-identical BMT, 3 died in the immediate posttransplant period of severe viral infections, whereas the remaining 4 were cured, with recovery of normal immune functions. Of the 12 patients who underwent HLA-haplo-identical BMT, 3 were cured, 1 was improved by partial engraftment, 7 died of infectious complications due to graft failure or rejection, and 1 is still immunodeficient because of engraftment failure. A favorable outcome in the HLA-non-identical BMT group was associated with an age of less than 2 years at the time of transplantation. All the patients with stable long-term engraftment had persistently low CD4 counts after transplantation (105 to 650/microL at last follow up), but no clear susceptibility to opportunistic infections despite persisting MHC class II deficiency on thymic epithelium and other nonhematopoietic cells. We conclude that HLA-identical and -haploidentical BMT can cure MHC class II deficiency, although the success rate of haploidentical BMT is lower than that in other combined immunodeficiency syndromes. HLA-haploidentical BMT should preferably be performed in the first 2 years of life, before the acquisition of chronic virus carriage and sequelae of infections.


Basement membrane component changes in nerve allografts and isografts.
This study describes immunocytochemical changes in laminin, which is an integral basement membrane (BM) component, during axonal regeneration through antigenic nerve allografts and nonantigenic nerve isografts. In normal rat nerve, laminin was localized in the BM of Schwann cells and the perineurium. During nerve allograft rejection, the perineurium and Schwann cells disappeared. However, the Schwann cell BMs persisted and became distorted and collapsed. In isografted nerves, the perineurium and Schwann cells were present, and only a few Schwann cell BMs appeared to be distorted; however, the staining for laminin was faint, indicating a possible BM breakdown. A new BM appeared as small rings around the Schwann cells after they had become associated with regenerated axons. Because only a limited axonal regeneration occurred in allografts as compared to isografts, it is concluded that the viable Schwann cells, and their BM architecture, are essential for regeneration through long nerve grafts.


Living donor liver transplantation: complications in donors and interventional management.
To evaluate the incidence of postoperative complications in liver donors and the efficacy of interventional management for treating these complications. The study included 386 consecutive donors: 219 donors underwent right lobectomy or segmentectomy and 167 donors underwent left lobectomy or segmentectomy. Postoperative status, laboratory data, and radiologic images were reviewed for postoperative complications. Interventional management consisted of percutaneous drainage, ultrasonographic (US)-guided aspiration, percutaneous transhepatic biliary drainage (PTBD) and balloon dilation, transcatheter arterial embolization, or portal vein stent placement. Technical success, clinical improvement, and complications were documented following intervention. In 52 (13.5%) donors, 56 postoperative complications were encountered, including pleural effusion (n = 9), biliary leakage (n = 6), biliary obstruction (n = 5), intraperitoneal abscess (n = 5), active bleeding (n = 5), portal vein stenosis or kink (n = 3), biloma (n = 2), and other complications (n = 21). Complications occurred in 41 (18.9%) right lobe and 11 (7.0%) left lobe donors (P <.001). Twenty-seven (48%) complications were treated with interventional management (percutaneous drainage, n = 10; US-guided aspiration, n = 6; PTBD and balloon dilation, n = 4; transcatheter arterial embolization, n = 4; and stent placement, n = 3) and resolved completely. No procedure-related complications occurred. In one donor with venous oozing, arteriographic images did not show an active bleeding focus; thus, bleeding control with interventional management failed. The remaining 29 complications were treated using medical (n = 27) or surgical (n = 2) management. One donor with acute renal failure has thus far been treated with hemodialysis. Although complications from liver donation are not uncommon, most are minor and, with medical or interventional management, have no long-term sequelae. Interventional management seems useful in the treatment of postoperative complications of liver donation.


DNA barcoding of pear psyllids (Hemiptera: Psylloidea: Psyllidae), a tale of continued misidentifications.
Pear psyllids (Hemiptera: Psylloidea: Psyllidae: Cacopsylla spp.) belong to the most serious pests of pear (Pyrus spp.). They damage pear trees by excessive removal of phloem sap, by soiling the fruits with honeydew which, in turn, provides a substrate for sooty mould, and by transmission of Candidatus Phytoplasma spp., the causal agents of the pear decline disease. The morphological similarity, the presence of seasonal dimorphism that affects adult colour, size and wing morphology and uncritical use of species names, led to much confusion in the taxonomy of pear psyllids. As a result, pear psyllids have been frequently misidentified. Many of the entries attributed to Cacopsylla pyricola and other species in the GenBank are misidentifications which led to additional, unnecessary confusion. Here we analysed DNA barcodes of 11 pear psyllid species from eastern Asia, Europe and Iran using four mitochondrial gene fragments (COI 658 bp, COI 403 bp, COI-tRNAleu-COII 580 bp and 16S rDNA 452 bp). The efficiency of identification was notably high and considerable barcoding gaps were observed in all markers. Our results confirm the synonymies of the seasonal forms of Cacopsylla jukyungi ( = C. cinereosignata, winter form) and C. maculatili ( = C. qiuzili, summer form) previously suggested based on morphology. Some previous misidentifications (C. chinensis from China, Japan and Korea = misidentification of C. jukyungi; C. pyricola and C. pyrisuga from East Asia = misidentification of C. jukyungi and C. burckhardti, respectively; C. pyricola from Iran = misidentification of C. bidens, C. pyri and Cacopsylla sp.) are also corrected. There is no evidence for the presence of European pear psyllid species in East Asia.


ITO Work Function Tunability by Polarizable Chromophore Monolayers.
The ability to tune the electronic properties of oxide-bearing semiconductors such as Si/SiO2 or transparent metal oxides such as indium-tin oxide (ITO) is of great importance in both electronic and optoelectronic device applications. In this work, we describe a process that was conducted on n-type Si/SiO2 and ITO to induce changes in the substrate work function (WF). The substrates were modified by a two-step synthesis comprising a covalent attachment of coupling agents' monolayer followed by in situ anchoring reactions of polarizable chromophores. The coupling agents and chromophores were chosen with opposite dipole orientations, which enabled the tunability of the substrates' WF. In the first step, two coupling agents with opposite molecular dipole were assembled. The coupling agent with a negative dipole induced a decrease in WF of modified substrates, while the coupling agent with a positive dipole produced an increase in WFs of both ITO and Si substrates. The second modification step consisted of in situ anchoring reaction of polarizable chromophores with opposite dipoles to the coupling layer. This modification led to an additional change in the WFs of both Si/SiO2 and ITO substrates. The WF was measured by contact potential difference and modeled by density functional theory-based theoretical calculations of the WF for each of the assembly steps. A good fit was obtained between the calculated and experimental trends. This ability to design and tune the WF of ITO substrates was implemented in an organic electronic device with improved I- V characteristics in comparison to a bare ITO-based device.


Helping Others and Long-term Sobriety: Who Should I Help to Stay Sober?
Examination of the change strategies associated with successful long-term sobriety remains an understudied area in addiction research. The following study recruited individuals with long-term sobriety (range 16-25 years continuous abstinence). Subjects (n = 11 were surveyed on demographic information, problem history, Alcoholics Anonymous (AA) affiliation, and helping behaviors within several life domains over the course of sobriety. General helping behaviors increased from lower levels in the month prior to getting sober, to moderate levels at 1 year of sobriety, but did not continue to increase with additional years of sobriety. Levels of general help to others at home, work, and 12-step programs were similar at varying lengths of sobriety. Whereas overall levels of general help given to others were similar across settings, helping other alcoholics, as opposed to helping others at home or work, was rated as contributing the most to staying sober. Across time, alcoholics increased participation in helping behaviors specific to 12-step programs. The utility of helping others as a behavioral strategy to maintain successful addictive behavioral change is discussed.


Effect of initial cell density on the bioavailability and toxicity of copper in microalgal bioassays.
Algal toxicity tests based on growth inhibition over 72 h have been extensively used to assess the toxicity of contaminants in natural waters. However, these laboratory tests use high cell densities compared to those found in aquatic systems in order to obtain a measurable algal response. The high cell densities and test duration can result in changes in chemical speciation, bioavailability, and toxicity of contaminants throughout the test. With the recent application of flow cytometry to ecotoxicology, it is now possible to use lower initial cell densities to minimize chemical speciation changes. The speciation and toxicity of copper in static bioassays with the tropical freshwater alga Chlorella sp. and the temperate species Selenastrum capricornutum (Pseudokirchneriella subcapitata) were investigated at a range of initial cell densities (10(2)-10(5) cells/ml). Copper toxicity decreased with increasing initial cell density. Copper concentrations required to inhibit growth (cell division) rate by 50% (72-h median effective concentration [EC50]) increased from 4.6 to 16 microg/L for Chlorella sp. and from 6.6 to 17 microg/L for S. capricornutum as the initial cell density increased from 10(2) to 10(5) cells/ml. Measurements of anodic stripping voltammetry-labile, extracellular, and intracellular copper confirmed that at higher initial cell densities, less copper was bound to the cells, resulting in less copper uptake and lower toxicity. Chemical measurements indicated that reduced copper toxicity was due primarily to depletion of dissolved copper in solution, with solution speciation changes due to algal exudates and pH playing a minor role. These findings suggest that standard static laboratory bioassays using 10(4) to 10(5) algal cells/ml may seriously underestimate metal toxicity in natural waters.


Identification of sequence elements in the human cytomegalovirus DNA polymerase gene promoter required for activation by viral gene products.
To determine the mechanisms involved in the regulation of human cytomegalovirus early gene expression, we have examined the gene that encodes the viral DNA polymerase (UL54, pol). Our previous studies demonstrated that sequences required for activation of the pol promoter by immediate-early proteins are contained within a region from -128 to +20 and that cellular proteins can bind to this activation domain. In this study, we demonstrate by competition analysis that binding of cellular proteins to pol is associated with an 18-bp region containing a single copy of a novel inverted repeat, IR1. Time course analysis indicated that viral infection increased the level of protein binding to IR1, concurrent with the activation of the pol promoter. Mutation of the IR1 element abrogated binding of cellular factors to the pol promoter and reduced by threefold the activation by immediate-early proteins. Similarly, mutation of IR1 rendered the promoter poorly responsive to activation by viral infection. Mutation of additional sequence elements in the pol promoter had little effect, indicating that IR1 plays the major role in pol promoter regulation. These studies demonstrate that the interaction between cellular factors and IR1 is important for the regulation of expression of the polymerase gene by viral proteins.


COVID-19 and Heart: From Clinical Features to Pharmacological Implications.
A highly pathogenic human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized in Wuhan, China, as the cause of the coronavirus disease 2019 (COVID-19) outbreak which has spread rapidly from China to other countries in the world, causing a pandemic with alarming morbidity and mortality. The emerging epidemiological data about COVID-19 patients suggest an association between cardiovascular diseases (CVD) and SARS-CoV-2 infection, in term of clinical features at hospital admission and prognosis for disease severity. The aim of our review is to describe the cardiological features of COVID-19 patients at admission, the acute cardiac presentation, the clinical outcome for patients with underlying CVD and the pharmacological implications for disease management.


On a fast calculation of structure factors at a subatomic resolution.
In the last decade, the progress of protein crystallography allowed several protein structures to be solved at a resolution higher than 0.9 A. Such studies provide researchers with important new information reflecting very fine structural details. The signal from these details is very weak with respect to that corresponding to the whole structure. Its analysis requires high-quality data, which previously were available only for crystals of small molecules, and a high accuracy of calculations. The calculation of structure factors using direct formulae, traditional for 'small-molecule' crystallography, allows a relatively simple accuracy control. For macromolecular crystals, diffraction data sets at a subatomic resolution contain hundreds of thousands of reflections, and the number of parameters used to describe the corresponding models may reach the same order. Therefore, the direct way of calculating structure factors becomes very time expensive when applied to large molecules. These problems of high accuracy and computational efficiency require a re-examination of computer tools and algorithms. The calculation of model structure factors through an intermediate generation of an electron density [Sayre (1951). Acta Cryst. 4, 362-367; Ten Eyck (1977). Acta Cryst. A33, 486-492] may be much more computationally efficient, but contains some parameters (grid step, 'effective' atom radii etc.) whose influence on the accuracy of the calculation is not straightforward. At the same time, the choice of parameters within safety margins that largely ensure a sufficient accuracy may result in a significant loss of the CPU time, making it close to the time for the direct-formulae calculations. The impact of the different parameters on the computer efficiency of structure-factor calculation is studied. It is shown that an appropriate choice of these parameters allows the structure factors to be obtained with a high accuracy and in a significantly shorter time than that required when using the direct formulae. Practical algorithms for the optimal choice of the parameters are suggested.


Biocompatibility of tungsten disulfide inorganic nanotubes and fullerene-like nanoparticles with salivary gland cells.
Impaired salivary gland (SG) function leading to oral diseases is relatively common with no adequate solution. Previously, tissue engineering of SG had been proposed to overcome this morbidity, however, not yet clinically available. Multiwall inorganic (tungsten disulfide [WS2]) nanotubes (INT-WS2) and fullerene-like nanoparticles (IF-WS2) have many potential medical applications. A yet unexplored venue application is their interaction with SG, and therefore, our aim was to test the biocompatibility of INT/IF-WS2 with the A5 and rat submandibular cells (RSC) SG cells. The cells were cultured and subjected after 1 day to different concentrations of INT-WS2 and were compared to control groups. Growth curves, trypan blue viability test, and carboxyfluorescein succinimidyl ester (CFSE) proliferation assay were obtained. Furthermore, cells morphology and interaction with the nanoparticles were observed by light microscopy, scanning electron microscopy and transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy. The results showed no significant differences in growth curves, proliferation kinetics, and viability between the groups compared. Moreover, no alterations were observed in the cell morphology. Interestingly, TEM images indicated that the nanoparticles are uptaken by the cells and accumulate in cytoplasmic vesicles. These results suggest promising future medical applications for these nanoparticles.


Patient-related risk factors associated with poorer outcomes following total ankle arthroplasty.
This scoping review aims to identify patient-related factors associated with a poorer outcome following total ankle arthroplasty (TAA). A scoping review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer-based literature search was performed in PubMed, Embase, Cochrane trials, and Web of Science. Two reviewers independently performed title/abstract and full-text screening according to predetermined selection criteria. English-language original research studies reporting patient-related factors associated with a poorer outcome following TAA were included. Outcomes were defined as patient-reported outcome measures (PROMs), perioperative complications, and failure. A total of 94 studies reporting 101,552 cases of TAA in 101,177 patients were included. The most common patient-related risk factor associated with poorer outcomes were younger age (21 studies), rheumatoid arthritis (17 studies), and diabetes (16 studies). Of the studies using multivariable regression specifically, the most frequently described risk factors were younger age (12 studies), rheumatoid arthritis (eight studies), diabetes (eight studies), and high BMI (eight studies). When controlling for confounding factors, the most commonly reported risk factors for poor outcome are younger age, rheumatoid arthritis, and comorbidities such as diabetes and increased BMI. These patient-related risk factors reported may be used to facilitate the refinement of patient selection criteria for TAA and inform patient expectations.


Cell type-specific expression of beta-carotene 9',10'-monooxygenase in human tissues.
The symmetrically cleaving beta-carotene 15,15'-monooxygenase (BCO1) catalyzes the first step in the conversion of provitamin A carotenoids to vitamin A in the mucosa of the small intestine. This enzyme is also expressed in epithelia in a variety of extraintestinal tissues. The newly discovered beta-carotene 9',10'-monooxygenase (BCO2) catalyzes asymmetric cleavage of carotenoids. To gain some insight into the physiological role of BCO2, we determined the expression pattern of BCO2 mRNA and protein in human tissues. By immunohistochemical analysis it was revealed that BCO2 was detected in cell types that are known to express BCO1, such as epithelial cells in the mucosa of small intestine and stomach, parenchymal cells in liver, Leydig and Sertoli cells in testis, kidney tubules, adrenal gland, exocrine pancreas, and retinal pigment epithelium and ciliary body pigment epithelia in the eye. BCO2 was uniquely detected in cardiac and skeletal muscle cells, prostate and endometrial connective tissue, and endocrine pancreas. The finding that the BCO2 enzyme was expressed in some tissues and cell types that are not sensitive to vitamin A deficiency and where no BCO1 has been detected suggests that BCO2 may also be involved in biological processes other than vitamin A synthesis.


Target-independent regulation of a novel growth associated protein in the visual system of the chicken.
Using an immunosuppression technique, the monoclonal antibody 2A1 has been generated specific for a 140 x 10(3) Mr cytoplasmic-membrane-associated protein as shown by subcellular fractionation and Western blot analysis. The antigen is initially confined to perikarya of postmitotic migratory ganglion cells of the embryonic chick retina as revealed by bromodeoxyuridine labeling. During the subsequent period of axon outgrowth, the antigen becomes restricted to ganglion cell axons but disappears during the innervation of the tectum opticum, suggesting a tectal inhibition of antigen expression in retinal axons. To analyse whether the tectum suppresses 2A1-antigen expression, optic nerves of chick embryos were severed to prevent tectal innervation. 2A1-immunoreactivity was determined in deflected axons in comparison to control axons. In addition, retinal axons were grown in vitro on a substratum consisting of alternating stripes of laminin and tectal membranes, in order to investigate whether retinal axons become devoid of the 2A1-antigen once they cross from laminin to tectal membranes. However, neither prevention of target innervation by optic nerve transection in vivo nor exposure of retinal axons to soluble or particulate tectal components in vitro modify 2A1-antigen regulation in ganglion cell axons, suggesting a retina inherent-control of gene expression. Antigen expression is essentially restricted to the period of axonal outgrowth and therefore the 2A1-protein is likely to be involved in processes essential for neurite extension, independent of the synaptic target.


Implications of Social and Material Deprivation for Changes in Health of Older People.
Objective: We use the panel structure of the Survey of Health, Ageing and Retirement in Europe (SHARE) data for 14 countries to examine the implications of material and social deprivation for health deterioration in old age and mortality. Method: To minimize the potential endogeneity bias, we examine the relationship between deprivation and changes in health rather than levels of health. We include a substantial set of fixed "initial conditions," and extend the controls with health measures, as observed at the initial period. Results: The results of the probit regression suggest a strong and statistically significant relationship between measures of material and social deprivation and changes in physical and mental health. Mortality is only affected by the social dimension of deprivation. Discussion: Treating material and social deprivation separately rather than as a single social exclusion indicator allows for more specific identification of the role of the two dimensions, which might be important for policy decisions.


Research productivity of staff in NHS mental health trusts: comparison using the Leiden method.
Aims and method To examine research productivity of staff working across 57 National Health Service (NHS) mental health trusts in England. We examined research productivity between 2010 and 2012, including funded portfolio studies and all research (funded and unfunded). Results Across 57 trusts there were 1297 National Institute for Health Research (NIHR) studies in 2011/2012, involving 46 140 participants and in the same year staff in these trusts published 1334 articles (an average of only 23.4 per trust per annum). After correcting for trust size and budget, the South London and Maudsley NHS Foundation Trust was the most productive. In terms of funded portfolio studies, Manchester Mental Health and Social Care Trust as well as South London and Maudsley NHS Foundation Trust, Oxford Health NHS Foundation Trust and Cambridgeshire and Peterborough NHS Foundation Trust had the strongest performance in 2011/2012. Clinical implications Trusts should aim to capitalise on valuable staff resources and expertise and better support and encourage research in the NHS to help improve clinical services.


An Experimental and Numerical Investigation to Characterize an Aerospace Composite Material with Open-Hole Using Non-Destructive Techniques.
In this study, the open-hole quasi-static tensile and fatigue loading behavior of a multidirectional CFRP thick laminate, representative of laminates used in the aerospace industry, is studied. Non-destructive techniques such as infrared thermographic (IRT) and digital image correlation (DIC) are used to analyze the behavior of this material. We aim at characterizing the influence of the manufacturing defects and the stress concentrator through the temperature variation and strain distribution during fatigue and quasi-static tests. On the one hand, the fatigue specimens were tested in two main perpendicular directions of the laminate. The results revealed that manufacturing defects such as fiber waviness can have a major impact than open-hole stress concentrator on raising the material temperature and causing fracture. In addition, the number of plies with fibers oriented in the load direction can drastically reduce the temperature increment in the laminate. On the other hand, the quasi-static tensile tests showed that the strain distribution around the hole is able to predict the crack initiation and progression in the external plies. Finally, the experimental quasi-static tests were numerically simulated using the finite element method showing good agreement between the numerical and experimental results.


Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen.
An increase in oxygen tension is an important factor in decreasing pulmonary vascular resistance (PVR) at birth. Birth asphyxia results in acidosis and increased PVR. We determined the effect of resuscitation with 21 vs. 100% O(2) on pulmonary hemodynamics, pulmonary arterial (PA) reactivity, and oxidant stress in a lamb model of in utero asphyxia. Term fetal lambs were acutely asphyxiated by intrauterine umbilical cord occlusion for 10 min resulting in acidosis (pH 6.96 ± 0.05 and Pco(2) 103 ± 5 Torr), bradycardia, systemic hypotension, and increased PVR. Lambs were treated with 30 min of resuscitation with 21% or 100% O(2) (n = 6 each). Pa(O(2)) was significantly elevated with 100% O(2) resuscitation compared with 21% O(2) (430 ± 38 vs. 64 ± 8 Torr), but changes in pH and Pa(CO(2)) were similar. The 100% O(2) induced greater increase in pulmonary blood flow and decrease in PVR at 1 min of life, but subsequent values were similar to 21% O(2) group between 2 and 30 min of life. Oxygen uptake from the lung and systemic oxygen extraction was similar between the two groups. Pulmonary arteries showed increased staining for superoxide anions and increased contractility to norepinephrine following resuscitation with 100% O(2). The increased PA contractility induced by 100% O(2) was reversed by scavenging superoxide anions with superoxide dismutase and catalase. We conclude that resuscitation of asphyxiated lambs with 100% O(2) increases Pa(O(2)) but does not improve lung oxygen uptake, decrease PVR at 30 min, or increase systemic oxygen extraction ratios. Furthermore, 100% O(2) also induces oxidative stress and increases PA contractility. These findings support the new neonatal resuscitation guidelines recommending 21% O(2) for initial resuscitation of asphyxiated neonates.


The effect of sucrose content in high and low carbohydrate diets on plasma glucose, insulin, and lipid responses in hypertriglyceridemic humans.
To further understand the effect of high carbohydrate (CHO)-low fat diets and the role of variations in dietary sucrose on CHO and lipid metabolism, 10 patients with hypertriglyceridemia were fed 2 isocaloric, typical American diets, containing 40% and 60% CHO, for 15 days in random sequence. Each patient was their own control, and they were divided into 2 groups of 5 patients each. In one group, sucrose was held constant at 13% of total calories (40-13% and 60-13%), whereas the sucrose content was 9% of the total calories on a 40% CHO diet (40-9%), and 15% of total calories on a 60% CHO diet (60-15%) in the other group. Fasting and postprandial blood samples were analyzed for plasma glucose, insulin, cholesterol (Chol), and triglycerides (TG), as well as for Chol and TG in chylomicrons, very low density, low density, and high density lipoproteins (HDL). Fasting plasma TG levels were significantly increased in both groups on the 60% CHO diet, primarily due to increases in very low density-TG concentration. The magnitude of the elevation was attenuated when sucrose content was kept constant. Postprandial TG responses were qualitatively similar. There were no significant changes in plasma Chol concentrations, except for a modest fall in plasma HDL-Chol level after the 60-13% diet period (P less than 0.05). No significant differences were found in fasting plasma glucose or insulin concentration. However, postprandial glucose and insulin responses were increased on both high CHO diets. The results of these studies demonstrate that high CHO-low fat diets, in general, tend to elevate plasma glucose, insulin, and TG concentrations and reduce HDL-Chol concentration in patients with endogenous hypertriglyceridemia. In addition, these data illustrate the important role that small variations in dietary sucrose can play in modulation of CHO and lipid metabolism.


Interferon-gamma and tumor necrosis factor-alpha enhance p60src expression in human macrophages and myelomonocytic cell lines.
We investigated modulation of p60src expression in human mononuclear phagocytes. By analysis of [35S]methionine-labelled cells we found that synthesis of p60src is higher in human monocytes compared to macrophages derived from in vitro cultivation of monocytes. Western blot analysis showed that expression of p60src in monocyte-derived macrophages can be enhanced if monocytes are differentiated into macrophages in the presence of interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha). Enhanced p60src expression caused by IFN-gamma or TNF-alpha correlated with an enhanced autophosphorylating kinase activity assayed in anti-p60src immune precipitates. In vivo phosphorylation of p60src and analysis of phosphopeptides by tryptic digestion showed that treatment with cytokines did not affect the pattern of phosphorylation of distinct phosphopeptides. The human monocytic cell lines, U937 and HL-60, induced to differentiate along the monocytic pathway by IFN-gamma, or a combination of IFN-gamma and TNF-alpha, expressed higher amounts of the p60src, but not of the p59fyn or p62yes, kinase activity. These findings show that p60src is modulated in the course of differentiation of human monocytes to macrophages, and that macrophage-activating cytokines increase p60src expression in human monocyte-derived macrophages.


Impact of cervicovaginal microbiome on the risk of cervical abnormalities development.
The vaginal microbiome has emerged as potentially influencing the natural history of Human Papillomavirus (HPV) infections and their clinical impact. We aimed to characterize the vaginal microbiome in samples from 807 high-risk HPVs (Hr-HPV) positive women with a mean age of 41.45 ± 10.79 years who participated in the Regional Cervical Cancer Screening Program from the Northern Region of Portugal. Microbiome analysis was performed with commercial kits for the detection of 21 microorganisms. The most frequent microorganisms were Ureaplasma parvum (52.5%), Gardnerella vaginalis (GV) (34.5%), Atopobium vaginae (AV) (32.6%), Lacto (30.7%), and Mycoplasma hominis (MH) (23.5%). The distribution according to age reveals that MH, Mega1, GV, BVab2, AV, and Mob were more prevalent in women older than 41 years of age (p < 0.050), while Lacto is significantly decreased in this group (23.5% vs. 39.4%, p < 0.001; RR = 0.47). The risk analysis showed that Hr-HPV-16/-18 and Hr-HPV-9val genotypes are associated with an increased risk of developing cervical abnormalities, while Lacto (p < 0.001; odd ratio [OR] = 0.33), GV (p = 0.0111; OR = 0.41), AV (p = 0.033; OR = 0.53) and Mob (p = 0.022; OR = 0.29) are associated with protection. Similar results were found for the risk of development atypical squamous cells cannot exclude HSIL/high-grade squamous intraepithelial lesion. Overall, the multivariate analysis confirmed that lactobacillus and bacteria associated with bacterial vaginosis (GV, AV, and Mob) are associated with protection against the development of cervical abnormalities. This study provides important data to be included in the future management of risk stratification for Hr-HPV-positive women.


Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism.
Circadian rhythms coordinate an organism's activities and biological processes to the optimal time in the 24-h daylight cycle. We previously demonstrated that male C57BL/6 mice develop sepsis more rapidly when the disease is induced in the nighttime versus the daytime. In this report, we elucidate the mechanism of this diurnal difference. Sepsis was induced via cecal ligation and puncture (CLP) at zeitgeber time (ZT)-19 (2 am) or ZT-7 (2 pm). Like the males used in our prior study, female C57BL/6 mice had a worse outcome when CLP was induced at ZT-19 versus ZT-7, and these effects persisted when we pooled the data from both sexes. In contrast, mice with a mutated Period 2 (Per2) gene had a similar outcome when CLP was induced at ZT-19 versus ZT-7. Bone marrow chimeras reconstituted with C57BL/6 immune cells exhibited a worse outcome when sepsis was induced at ZT-19 versus ZT-7, whereas chimeras with Per2-mutated immune cells did not. Next, murine macrophages were subjected to serum shock to synchronize circadian rhythms and exposed to bacteria cultured from the mouse cecum at 4-h intervals for 48 h. We observed that IL-6 production oscillated with a 24-h period in C57BL/6 cells exposed to cecal bacteria. Interestingly, we observed a similar pattern when cells were exposed to the TLR2 agonist lipoteichoic acid. Furthermore, TLR2-knockout mice exhibited a similar sepsis phenotype when CLP was induced at ZT-19 versus ZT-7. Together, these data suggest that circadian rhythms in immune cells mediate diurnal variations in murine sepsis severity via a TLR2-dependent mechanism.


Women's and care providers' perspectives of quality prenatal care: a qualitative descriptive study.
Much attention has been given to the adequacy of prenatal care use in promoting healthy outcomes for women and their infants. Adequacy of use takes into account the timing of initiation of prenatal care and the number of visits. However, there is emerging evidence that the quality of prenatal care may be more important than adequacy of use. The purpose of our study was to explore women's and care providers' perspectives of quality prenatal care to inform the development of items for a new instrument, the Quality of Prenatal Care Questionnaire. We report on the derivation of themes resulting from this first step of questionnaire development. A qualitative descriptive approach was used. Semi-structured interviews were conducted with 40 pregnant women and 40 prenatal care providers recruited from five urban centres across Canada. Data were analyzed using inductive open and then pattern coding. The final step of analysis used a deductive approach to assign the emergent themes to broader categories reflective of the study's conceptual framework. The three main categories informed by Donabedian's model of quality health care were structure of care, clinical care processes, and interpersonal care processes. Structure of care themes included access, physical setting, and staff and care provider characteristics. Themes under clinical care processes were health promotion and illness prevention, screening and assessment, information sharing, continuity of care, non-medicalization of pregnancy, and women-centredness. Interpersonal care processes themes were respectful attitude, emotional support, approachable interaction style, and taking time. A recurrent theme woven throughout the data reflected the importance of a meaningful relationship between a woman and her prenatal care provider that was characterized by trust. While certain aspects of structure of care were identified as being key dimensions of quality prenatal care, clinical and interpersonal care processes emerged as being most essential to quality care. These processes are important as they have a role in mitigating adverse outcomes, promoting involvement of women in their own care, and keeping women engaged in care. The findings suggest key considerations for the planning, delivery, and evaluation of prenatal care. Most notably, care should be woman-centred and embrace shared decision making as an essential element.


Academic achievement following childhood brain disease: implications for the concept of learning disabilities.
The present study examined three hypotheses regarding the consequences of early brain damage for academic achievement: First, early brain insults will have a negative impact on achievement, even in children with normal intelligence. Second, underachievement in these children will be at least partially independent of IQ (i.e., not fully accounted for by a lowering of IQ within the average range). Third, normally intelligent children with histories of brain insult will also manifest selective cognitive dysfunctions. To test these hypotheses, we compared two groups of children who had recovered from Haemophilus influenzae type b meningitis. The "complicated" group consisted of children who, as a consequence of having sustained neurologic complications during their illness, were more likely to have had brain insults. Children in the "uncomplicated" group did not have complications with their illness and were regarded as having escaped significant central nervous system (CNS) pathology. Only children with normal hearing and a prorated Full Scale IQ of at least 80 (WISC-R) were considered. Group differences on the Wide Range Achievement Test-Revised were consistent with the first two hypotheses. Although the two groups had similar Verbal IQs, the complicated group also had a lower mean Performance IQ and performed less well on perceptually demanding neuropsychological tasks. Findings suggest that learning disabilities may have selective, brain-related cognitive antecedents; but they challenge the practice of using IQ criteria for clinical diagnosis.


Tissue reaction induced by implanted venous access ports in adult patients after infection of the implantation site.
Implantable long-term central venous port systems (CVPS) are widely used as a permanent means of accessing the vascular system for intravenous delivery of drugs, parenteral nutrition, blood transfusion, and blood sampling. These systems allow easy and repetitive puncture without causing much damage to the vessels. However, the body foreign surface of CVPS induces an inflammatory response with varying intensity (depending on the implant materials) that leads to formation of a fibrous tissue capsule around the implant. This study was designed to investigate the influence of bacterial infection on the tissue reaction induced by implanted CVPS in adult patients. 20 patients (9 women, 11 men, 58 ± 14 yrs of age) were included in this study. These patients received explantation of a polysulfone based CVPS (ChemoSite™, Covidien, Mansfield, USA) due to port related infections (patients with bacterial infections at the implantation site: group A, 5 men, 1 women) or to other reasons such as termination of treatment, thrombosis, or CVPS dysfunction (patients without bacterial infections, group B, 6 men, 8 women) 299.9 ± 261.2 days after CVPS implantation. A sample of the encapsulating tissue covering the CVPS together with surrounding tissue (at least 1 × 1 cm2) was placed in a small container with fixing agent, a buffered neutral 4% formalin solution (pH 7). Histological sections of the samples were prepared for light microscopic analysis after paraffin embedding. Sections of 3 μm were cut and stained with haematoxylin and eosin, Weigert's elastic stain, and Heidenhain's azan stain. There was no difference in thickness, collagen and elastin content, or cell and capillary density of the fibrous capsule between both groups. Due to the wound healing reaction involving angiogenesis and fibroblast activation cell density and number of capillaries in the capsule tissue of all patients showed a positive correlation (r = 0.45, p < 0.05). However, the study demonstrated that at the end of the foreign body reaction the artificial tissue layer which covers the CVPS after implantation due to foreign body reaction shows only low reactivity towards infections.


How to construct an optimal interim report: What the data monitoring committee does and doesn't need to know.
Data monitoring committees for randomized clinical trials have the responsibility of safeguarding interests of trial participants. To do so, the data monitoring committee must receive reports on safety and efficacy to assess risk/benefit and on trial conduct to ensure that the study can achieve its goals. This article outlines the key components of reports to the data monitoring committee and the important role of the unblinded statistician in preparing those reports. Most data monitoring committee meetings include open and closed sessions. For each session, there is a report of interim results. The open session is attended by the sponsor and lead investigators, including the statistician(s) responsible for the trial design. These investigators are blinded to the interim treatment comparisons. The closed session is attended by the data monitoring committee members and by the statistician(s) who prepared the closed report. These individuals are unblinded to interim treatment comparisons and therefore are not involved in study design changes. The optimal content of data monitoring committee reports and qualifications of the unblinded statistician(s) are discussed. Open reports should include responses to data monitoring committee recommendations, a synopsis of the protocol, a review of the protocol history and amendments, and information on enrollment, baseline characteristics, completeness of follow-up, and data quality. The open report is also a vehicle through which the sponsor and investigators should inform the data monitoring committee of relevant external information. Data in the open report are pooled over the treatment groups. The open report should not include data summaries by treatment group. The closed report should include a written summary with references to key tables and figures and methods used to prepare them. Tables and figures should summarize baseline characteristics, follow-up completeness, treatment adherence, and major safety and efficacy outcomes by treatment group. Text summaries should accompany the tables and figures. The data monitoring committee monitoring history (e.g. treatment differences at previous meetings) should be summarized. The unblinded statistician preparing the closed report should be familiar with the protocol and data collection plan and be capable of customizing the report to the current stage of the trial. This includes anticipating questions that may arise during the data monitoring committee review and pro-actively including data summaries to address these questions. There is considerable variation in the quality of open and closed data monitoring committee reports. Open and closed data monitoring committee reports should be concise, up to date, and informative. To achieve this, unblinded statisticians responsible for preparing closed data monitoring committee reports should be familiar with the statistical methods, the trial protocol, and the data collection plan. They should be capable of anticipating questions from the data monitoring committee and responding to requests for additional analyses.


Genistein inhibits invasion and migration of colon cancer cells by recovering WIF1 expression.
Colon cancer is characterized by invasion and migration. DNA methylation of CpG islands in tumor suppressor genes is considered to be an epigenetic mechanism underlying cancer development. Epigenetic silencing of a gene may be reversed by drugs, including genistein. The present study aimed to determine the effect of genistein on Wnt inhibitory factor 1 (WIF1) and invasion, and migration of colon cancer cells. The viability of HT29 colon cancer cells was suppressed by genistein in a dose dependent manner. Following 72 h of treatment with 10, 20 and 60 µmol/l genistein, increased demethylation of WIF1 was induced in a dose‑dependent manner. Additionally, the invasive/migratory abilities of cells treated with genistein decreased in a dose‑dependent manner. Reverse transcription‑quantitative polymerase chain reaction and western blot analyses were performed to identify the mRNA and protein expression levels of invasion/migration‑associated factors. Following treatment with genistein, matrix metalloproteinase (MMP) 2 and MMP9 expression levels decreased, whereas the expression of metalloproteinase inhibitor 1 and E‑cadherin increased significantly. In addition, the expression levels of proto‑oncogene Wnt‑1 (Wnt‑1)/β‑catenin pathway‑associated factors, β‑catenin, c‑Myc proto‑oncogene protein and cyclin D1 decreased in a dose‑dependent manner following treatment with genistein. The invasive/migratory abilities of cells transfected with WIF1‑small interfering (si) RNA, and those transfected with WIF1‑siRNA and treated with genistein, increased notably compared with the control group. The present study demonstrated that genistein was able to inhibit the cell invasion and migration of colon cancer cells by inducing demethylation, and recovering the activity of WIF1 by altering the expression of invasion‑associated factors, and components of the Wnt signaling pathway.


The successful uptake and sustainability of rapid infectious disease and antimicrobial resistance point-of-care testing requires a complex 'mix-and-match' implementation package.
The emergence and spread of antimicrobial resistance is one of the major global issues currently threatening the health and wealth of nations, with effective guidelines and intervention strategies urgently required. Such guidelines and interventions should ideally be targeted at individuals, communities, and nations, requiring international coordination for maximum effect. In this respect, the European Joint Programming Initiative on Antimicrobial Resistance Transnational Working Group 'Antimicrobial Resistance - Rapid Diagnostic Tests' (JPIAMR AMR-RDT) is proposing to consider a 'mix-and-match' package for the implementation of point-of-care testing (PoCT), which is described in this publication. The working group was established with the remit of identifying barriers and solutions to the development and implementation of rapid infectious disease PoCT for combatting the global spread of antimicrobial resistance. It constitutes a multi-sectoral collaboration between medical, technological, and industrial opinion leaders involved in in vitro diagnostics development, medical microbiology, and clinical infectious diseases. The mix-and-match implementation package is designed to encourage the implementation of rapid infectious disease and antimicrobial resistance PoCT in transnational medical environments for use in the fight against increasing antimicrobial resistance.


Factors Associated With Waiting Time to Deceased Donor Kidney Transplantation in Transplant Candidates.
Although a nationwide activation system has been developed to increase deceased donor kidney transplantation (DDKT), there is still enormous discrepancy between transplant need and deceased donor supply in Korea, and therefore waiting time to DDKT is still long. We need to determine the current status of waiting time and the risk factors for long waiting time. We retrospectively analyzed the medical records of the patients on the wait list for DDKT at the Seoul National University Hospital from 2000 to 2017. Among 2,211 wait-listed patients, 606 (27.5%) received DDKT and mean waiting time to DDKT was 45 months. Among them, blood type A was most prevalent (35.6%) and type AB was the least (14.0%). Panel-reactive assay (PRA) was positive in 59 (11.0%) in the first transplant group and 25 (35.0%) in retransplant group. Waiting time in PRA-positive recipients was 63 and 66 months in the first transplant group and retransplant group, respectively. However, waiting time for patients with negative PRA was 42.8 months. Waiting time was shorter in blood type AB (39 months) than other types (46 months). Waiting time was the shortest in children and adolescents. Among patients who were still on the wait list, retransplantation candidates, especially with PRA higher than 50%, had longer waiting time than first transplant candidates. In conclusion, non-AB blood type, positive PRA, and adult age were significantly associated with long waiting time. Therefore, it is necessary to establish a management strategy such as tailored desensitization for highly sensitized patients on the wait list to reduce their waiting time.


The burden of influenza and the role of influenza vaccination in adults aged 50-64 years: A summary of available evidence.
Influenza is a vaccine-preventable disease and a global public health problem. Although most national influenza vaccination recommendations focus on subjects aged ≥65 years, an extensive burden of influenza has also been reported in those aged ≥50 years and is exacerbated by immune system aging. The main purpose of this review is to provide an overview of the burden of influenza and its potential prevention within the 50-64 age-group. These subjects account for a large proportion of the workforce, and play a central economic and social role. Individuals aged 50-64 years had a 3-times higher rate of hospitalization and a 9-fold higher mortality rate attributable to influenza than those aged 18-49-years, generating higher influenza-related hospitalization costs. Available data suggest that including healthy subjects aged 50-64 years in influenza vaccination recommendations would allow a broader population to be reached, reducing the economic and social burden of influenza.


Radiographic position of the hyoid bone in children with atypical deglutition.
The persistence of childlike deglutition after the replacement of deciduous teeth is described as atypical deglutition. This condition has been attributed to sucking action without nutritive purposes, use of a feeding bottle, oral respiration, and anatomical abnormalities. Among the possible anatomical alterations, the hyoid bone, as a result of being the origin or the insertion of several muscles involved in swallowing, may have its position altered in cases of atypical deglutition. The aim of the present study was to evaluate the position of the hyoid bone using lateral teleradiographs, among patients with atypical deglutition during the stage of mixed dentition. Using cephalometric analysis on lateral teleradiographs, the distances of H-MP (hyoid to mandibular plane) and H-T (hyoid to tuber) were measured in two groups: the experimental group with atypical deglutition and the control group normal deglutition. Both groups included subjects in mixed dentition stage. Measurements from the groups were compared using Mann-Whitney U-test and a P-value <0.05 was considered as an indication of statistical significance. The average distance of the H-MP variable was 11.69 mm for the control group and 16.14 mm for the experimental group, with a statistically significant difference (P = 0.016). The average distance of the H-T variable was 2.26 mm for the control group and -5.89 mm for the experimental group, with significant difference (P < 0.001). There was no correlation among the variables studied. Cephalometric analysis of the H-MP distance revealed a mean difference of approximately 5 mm between the two groups, and the difference was more than 7 mm for H-T distance. Distances of H-MP and H-T based on radiographic measurements were greater in individuals with atypical deglutition than in control group and there was no correlation between these two parameters.


Regional distribution of prostaglandin-metabolizing enzymes in the mucosa of the human upper gastrointestinal tract.
The occurrence of three enzymes of prostaglandin metabolism, 15-hydroxy-prostaglandin-dehydrogenase, delta13 -reductase and prostaglandin E-9-keto-reductase was investigated in gastroscopically obtained biopsy specimens of human upper gastrointestinal mucosa. All three enzymes could be found in the mucosa of oesophagus, gastric fundus, corpus and antrum and duodenum. While the specific activity of 15-hydroxy-prostaglandin-dehydrogenase was highest and the specific activity of prostaglandin E-9-keto-reductase was lowest in all regions studied, differences of the specific activities of the enzymes between the regions are remarkably small. These results are discussed with respect to possible functions of endogenous prostaglandins in human gastrointestinal mucosa.


An evaluation of warning habits and beliefs across the adult life span.
Beliefs about warnings and habits associated with reading them were assessed for 863 individuals of various ages. Information gathered for various common household products included (a) how frequently people attend to warning information, (b) the degree of risk they believe is involved during product usage, and (c) how important they believe warnings are for different product types. Also assessed were perceived helpfulness and comprehension for symbols commonly found on product labels or on signs in the environment. Respondents 55 years and older reported reading product warnings more frequently than did younger adults, although they generally perceived warnings as less important. However, no overall age-related differences were found for perceived level of risk involved in using different product types. Although older adults generally perceived symbols to be very helpful when using a particular product, their comprehension levels were poorer than those of younger adults for half of the symbols. Overall, these data suggest that adults of all ages do read warnings on a variety of product types and that they believe warning information is important. This research illustrates the importance of including older adults in usability studies during the development of warning systems, given age-related effects may be associated with some aspects of the warning processing but not others.


Essential Thrombocythaemia with Concomitant Waldenström Macroglobulinaemia: Case Report and Literature Review.
Essential thrombocythaemia (ET) and Waldenström macroglobulinaemia (WM) are two distinct disorders. Studies have reported several cases of myeloproliferative neoplasms (MPNs) with concomitant plasma cell dyscrasia. However, there were no reported cases of ET with concomitant WM to date. Here, we present a 55-year-old Chinese man with thrombocytosis and raised immunoglobulin level. Further investigations led to a diagnosis of ET and coexistent WM. Next-generation sequencing (NGS) of his bone marrow identified 3 mutated genes: JAK2 V617F, MYD88 L265P, and ATM F1036L. After being treated with pegylated interferon and low-dose aspirin, his platelet count normalized and immunoglobulin M (IgM) level reduced. To the best of our knowledge, this is the first reported case of dual pathology ET with WM.


Use of an immunoperoxidase stain for the demonstration of bovine viral diarrhea virus by light and electron microscopies.
Bovine viral diarrhea (BVD) virus-specific antiserum eluted from an immunoabsorbent column was conjugated with horseradish peroxidase. The immunoperoxidase (IP) conjugate was used to stain BVD virus-inoculated and control tissue cultures processed for light and electron microscopies. Infected cells (in the inoculated cultures) viewed by light microscopy had diffuse staining of the cytoplasm of nonvacuolated cells and a more predominant staining associated with vacuoles as vacuolation occurred. The peroxidase label as demonstrated by electron microscopy was associated primarily with nonenveloped and membrane-associated viral particles. Viral particles 20 to greater than 100 nm (diam) were observed. Some of the particles which were greater than 30 mm in diameter contained multiple nuclear cores. The most intensely stained viral particles were outside of the cells.


Independence of buoyant cell density and growth rate in Escherichia coli.
The relationship between growth rate and buoyant density was determined for cells from exponential-phase cultures of Escherichia coli B/r NC32 by equilibrium centrifugation in Percoll gradients at growth rates ranging from 0.15 to 2.3 doublings per h. The mean buoyant density did not change significantly with growth rate in any of three sets of experiments in which different gradient conditions were used. In addition, when cultures were allowed to enter the stationary phase of growth, mean cell volumes and buoyant densities usually remained unchanged for extended periods. These and earlier results support the existence of a highly regulated, discrete state of buoyant density during steady-state growth of E. coli and other cells that divide by equatorial fission.


Use of the polymerase chain reaction to screen cell banks for retroviruses.
The polymerase chain reaction (PCR) may be used to increase the sensitivity for detecting nucleic acids of specific adventitious agents. PCR can be used in combination with other assays such as infectivity or co-cultivation to increase the sensitivity of detecting adventitious agents or to identify a particular adventitious agent present in the test sample. In addition, PCR is useful for confirming the results of other assays such as reverse transcriptase or electron microscopy. Sources of the test sample, passage history and raw materials added to the test sample are considered when deciding upon the appropriate screening procedures and the adventitious agents for which to screen. In developing a PCR assay, the experiments should be designed to address specificity, sensitivity and reproducibility. Assay development issues include design of primers for the particular retroviruses in question, determination of quantity of sample to test, potential levels of interference, and appropriate positive and negative controls. Validation of a PCR assay is necessary to prove reproducibility for detecting the retrovirus. Data are presented on the qualification of a primate master cell bank to assure the absence of simian immunodeficiency viruses.