The mental health of officials who regularly examine child sexual abuse material: strategies for harm mitigation.
The current study aims to better understand the mental health and subjective well-being of investigators and forensic examiners exposed to child sexual abuse material (CSAM) by examining which components of this work are associated with elevated mental health conditions and decreased well-being, as well as the intra-personal and organizational variables that may mitigate harm and improve well-being. Police investigators, forensic examiners, and others connected with the criminal justice system from across the United States who were exposed to CSAM as part of their professions (N = 500) completed an anonymous online survey. Participants were recruited through connections with the National Criminal Justice Training Center. Duration, frequency, amount, and content of CSAM exposure was not related to poorer mental health with the exception of exposure to violent CSAM which was related to elevated post-traumatic stress symptoms. Several agency-level practices and policies, such as the availability of an Officer Wellness Program and more frequently knowing the final case resolution, were related to better mental health and well-being. Harm mitigation strategies, such as talking to other officers investigating the case and taking breaks from the material being viewed, were also related to better mental health. Findings indicate that police agencies have options for implementing agency-level procedures and practices that have the potential to reduce the negative impact of CSAM investigations. Additionally, many investigators use strategies that are correlated with greater well-being, suggesting opportunities for improving training programs.


Efficacy of a training intervention on the quality of practitioners' decision support for patients deciding about place of care at the end of life: A randomized control trial: Study protocol.
Most people prefer home palliation but die in an institution. Some experience decisional conflict when weighing options regarding place of care. Clinicians can identify patients' decisional needs and provide decision support, yet generally lack skills and confidence in doing so. This study aims to determine whether the quality of clinicians' decision support can be improved with a brief, theory-based, skills-building intervention. The Ottawa Decision Support Framework (ODSF) guides an evidence based, practical approach to assist clinicians in providing high-quality decision support. The ODSF proposes that decisional needs [personal uncertainty, knowledge, values clarity, support, personal characteristics] strongly influence the quality of decisions patients make. Clinicians can improve decision quality by providing decision support to address decisional needs [clarify decisional needs, provide facts and probabilities, clarify values, support/guide deliberation, monitor/facilitate progress]. The efficacy of a brief education intervention will be assessed in a two-phase study. In phase one a focused needs assessment will be conducted with key informants. Phase two is a randomized control trial where clinicians will be randomly allocated to an intervention or control group. The intervention, informed by the needs assessment, knowledge transfer best practices and the ODSF, comprises an online tutorial; an interactive skills building workshop; a decision support protocol; performance feedback, and educational outreach. Participants will be assessed: a) at baseline (quality of decision support); b) after the tutorial (knowledge); and c) four weeks after the other interventions (quality of decision support, intention to incorporate decision support into practice and perceived usefulness of intervention components). Between group differences in the primary outcome (quality of decision support scores) will be analyzed using ANOVA. Few studies have investigated the efficacy of an evidence-based, theory guided intervention aimed at assisting clinicians to strengthen their patient decision support skills. Expanding our understanding of how clinicians can best support palliative patients' decision-making will help to inform best practices in patient-centered palliative care. There is potential transferability of lessons learned to other care situations such as chronic condition management, advance directives and anticipatory care planning. Should the efficacy evaluation reveal clear improvements in the quality of decision support provided by clinicians who received the intervention, a larger scale implementation and effectiveness trial will be considered. This study is registered as NCT00614003.


Tower of London versus real life analogue planning in schizophrenia with disorganization and psychomotor poverty symptoms.
Neuropsychological models propose qualitatively distinct planning impairments in the psychomotor poverty and disorganization syndromes in schizophrenia. It was proposed that poor plan initiation in psychomotor poverty would lead to longer initial planning times, while poor plan execution in disorganization would lead to greater inefficiency. Participants with psychomotor poverty (n = 30) and disorganization (n = 29) symptoms were contrasted with healthy controls (n = 28) to elucidate distinct planning impairments. Planning was compared in the Tower of London task versus real life analogue performance in the form of a board-game style diary planning task. The specificity of planning impairments was investigated by controlling for current IQ. The disorganization group demonstrated inefficient planning across both tasks, with poor performance on the Tower of London but not on the real life analogue task remaining after intelligence levels were taken into account. Initial planning times did not differ between groups. Previous associations between poor planning and symptoms may have been driven by poor planning with disorganization symptoms and associated lower order impairments in executive function or the semantic system. Targeting these impairments in people with disorganization symptoms may lead to a greater chance of success in promoting generalization to the real world.


Phylogenetic relationships of Sparassis inferred from nuclear and mitochondrial ribosomal DNA and RNA polymerase sequences.
Sparassis species show extensive morphological variation, especially when materials from eastern Asia and Australia are compared with collections from North America and Europe. We have been studying the taxonomy of Sparassis from eastern Asia, North America, Australia and Europe, using both morphological and molecular data. DNA was extracted from 32 recent collections of Sparassis from Australia, Canada, China, Finland, France, Germany, Japan, Switzerland, Thailand, the United Kingdom and the United States. The report of a Sparassis taxon from Australia is the first report of this genus from the Southern Hemisphere. Sequences of nuclear and mitochondrial rDNA and the gene encoding RNA polymerase subunit II (RPB2) were used to examine relationships both within the genus Sparassis and between Sparassis species and other members of the polyporoid clade. Equally weighted parsimony analyses and Bayesian analyses were performed using independent datasets and combined datasets of sequences from different regions. Our results suggest that: (i) Polyporoid fungi producing a brown rot may form a clade; (ii) as suggested in a previous study, Sparassis and Phaeolus form a monophyletic group, which is united by the production of a brown rot, the presence of a bipolar mating system and the frequent habit of growing as a root and butt rot on living trees; (iii) at least seven lineages are within Sparassis, represented by S. spathulata, S. brevipes, S. crispa, S. radicata and three taxa that have not been described, which can be distinguished on the basis of fruiting body structure, presence or absence of clamp connections, presence or absence of cystidia and spore size.


Alternatively spliced tissue factor. A crippled protein in coagulation or a key player in non-haemostatic processes?
Full-length tissue factor (flTF) initiates coagulation, but also exerts non-hemostatic functions such as inflammation and angiogenesis through protease activated receptors (PARs). In 2003 a soluble variant of flTF was described which results from alternative splicing. Since its discovery the role of alternatively spliced tissue factor (asTF) in coagulation has been debated. asTF may have pro-coagulant properties but due to structural differences when compared to flTF, asTF coagulant function may be relatively low. Nevertheless, similar to flTF, asTF appears to have non-hemostatic properties; asTF expression in tumors correlates with increased tumor size, vessel number and poor survival in some cancer types, and drives tumor growth in animal models. Interestingly, unlike flTF, asTF does not promote angiogenesis through activating PARs but rather via integrin ligation. flTF is a critical determinant in cardiovascular disease but little is known about asTF in cardiovascular disease. asTF is produced by monocytes and macrophages, thus macrophage-derived asTF may contribute to atherosclerotic disease. In conclusion, unraveling asTF's non-hemostatic properties may generate new insights in the pathophysiology and diagnostics of cancer and cardiovascular disease.


Evaluation of bioenergy crop growth and the impacts of bioenergy crops on streamflow, tile drain flow and nutrient losses in an extensively tile-drained watershed using SWAT.
Large quantities of biofuel production are expected from bioenergy crops at a national scale to meet US biofuel goals. It is important to study biomass production of bioenergy crops and the impacts of these crops on water quantity and quality to identify environment-friendly and productive biofeedstock systems. SWAT2012 with a new tile drainage routine and improved perennial grass and tree growth simulation was used to model long-term annual biomass yields, streamflow, tile flow, sediment load, and nutrient losses under various bioenergy scenarios in an extensively agricultural watershed in the Midwestern US. Simulated results from bioenergy crop scenarios were compared with those from the baseline. The results showed that simulated annual crop yields were similar to observed county level values for corn and soybeans, and were reasonable for Miscanthus, switchgrass and hybrid poplar. Removal of 38% of corn stover (3.74Mg/ha/yr) with Miscanthus production on highly erodible areas and marginal land (17.49Mg/ha/yr) provided the highest biofeedstock production (279,000Mg/yr). Streamflow, tile flow, erosion and nutrient losses were reduced under bioenergy crop scenarios of bioenergy crops on highly erodible areas and marginal land. Corn stover removal did not result in significant water quality changes. The increase in sediment and nutrient losses under corn stover removal could be offset with the combination of other bioenergy crops. Potential areas for bioenergy crop production when meeting the criteria above were small (10.88km2), thus the ability to produce biomass and improve water quality was not substantial. The study showed that corn stover removal with bioenergy crops both on highly erodible areas and marginal land could provide more biofuel production relative to the baseline, and was beneficial to water quality at the watershed scale, providing guidance for further research on evaluation of bioenergy crop scenarios in a typical extensively tile-drained watershed in the Midwestern U.S.


Synthesis of organic salts with large second-order optical nonlinearities.
A series of organic salts, in which the cation has been designed to have a large molecular hyperpolarizability, has been prepared. Variation of the counterion (anion) in many cases leads to materials with large powder second harmonic generation efficiencies, the highest of which is roughly 1000 times that of a urea reference.


Root uptake and shoot accumulation of cadmium by lettuce at various Cd:Zn ratios in nutrient solution.
Cadmium (Cd) is toxic to animals and humans after it accumulates over decades in the kidney cortex. Food crops grown in Cd-contaminated soils are the primary sources of excessive Cd entry into humans. Although plant available Zn concentration in soil is an important factor which can greatly reduce Cd uptake by plant roots and its translocation into the edible parts, Cd:Zn ratio is suggested to be a more important factor in comparison with Zn concentration alone in determining Cd uptake by plants. In the present study, the physiological mechanisms of Cd absorption by roots and its translocation to leaves of lettuce (Lactuca sativa L.) at various Cd:Zn ratios in the rooting media were investigated. For this purpose, seedlings of hydroponically-grown lettuce were exposed to combinations of four Zn (0, 12.5, 50 and 100μM) and four Cd (0, 0.5, 1 and 10μM) concentrations providing different ratios of Cd:Zn. At each level of Cd, decreasing the Cd:Zn ratio by increasing Zn concentration in the nutrient solution caused significant reduction of root symplastic Cd and also reduced Cd loading into the xylem and Cd transport to and accumulation in leaves. The highest root symplastic Cd (1087mg/kg-1 Dry Weight [DW]) and shoot Cd concentrations (64mg/kg-1 DW) were observed at the highest Cd:Zn ratio of = 0.8 (Zn = 12.5, Cd = 10). At the Cd:Zn ratios of ≤ 0.01, shoot Cd concentration was less than the Detection Limit (< 0.02mg/kg DW). Decreasing Cd:Zn ratio in nutrient solution was accompanied with significant increase in root apoplastic Cd and decrease in the root symplastic Cd. According to the obtained results, at the Cd:Zn ratio equal to 0.01 and less, Cd concentration in lettuce shoots decreased to < 0.02mg/kg.


Phenotypes to remember: Evolutionary developmental memory capacity and robustness.
There is increased awareness of the possibility of developmental memories resulting from evolutionary learning. Genetic regulatory and neural networks can be modelled by analogous formalism raising the important question of productive analogies in principles, processes and performance. We investigate the formation and persistence of various developmental memories of past phenotypes asking how the number of remembered past phenotypes scales with network size, to what extent memories stored form by Hebbian-like rules, and how robust these developmental "devo-engrams" are against networks perturbations (graceful degradation). The analogy between neural and genetic regulatory networks is not superficial in that it allows knowledge transfer between fields that used to be developed separately from each other. Known examples of spectacular phenotypic radiations could partly be accounted for in such terms.


Stepwise photocatalytic dissociation of methanol and water on TiO2(110).
We have investigated the photocatalysis of partially deuterated methanol (CD(3)OH) and H(2)O on TiO(2)(110) at 400 nm using a newly developed photocatalysis apparatus in combination with theoretical calculations. Photocatalyzed products, CD(2)O on Ti(5c) sites, and H and D atoms on bridge-bonded oxygen (BBO) sites from CD(3)OH have been clearly detected, while no evidence of H(2)O photocatalysis was found. The experimental results show that dissociation of CD(3)OH on TiO(2)(110) occurs in a stepwise manner in which the O-H dissociation proceeds first and is then followed by C-D dissociation. Theoretical calculations indicate that the high reverse barrier to C-D recombination and the facile desorption of CD(2)O make photocatalytic methanol dissociation on TiO(2)(110) proceed efficiently. Theoretical results also reveal that the reverse reactions, i.e, O-H recombination after H(2)O photocatalytic dissociation on TiO(2)(110), may occur easily, thus inhibiting efficient photocatalytic water splitting.


Complex disorder in beta-NH(4)Fe(2)(PO(4))(2): deciphering from a five-dimensional formalism.
A new mixed-valent iron ammonium phosphate, beta-NH(4)Fe(2)(PO(4))(2), has been synthesized. The diffuse scattering observed on the diffraction patterns implies complex disorder phenomena and prevents a direct structure resolution. The latter can be solved by generating an artificially ordered orthorhombic structure, using a five-dimensional approach and performing partial integration of the diffuse streaks. In the artificially ordered structure, hexagonal tunnels, delimited by FeO(6) octahedra, perpendicular to the directions [011] and [01(over)1] can then be seen; they are filled either by [FeP(2)O(10)](infinity) zigzag ribbons or by NH(4)(+) cations. It is shown that the disordering originates from the shifting of adjacent (100) tunnel slices of the structure with respect to each other along [011], allowing the formation of either new commensurate (superstructure) or incommensurate modulations, or even complete disorder along a. The close relationships with the ordered monoclinic form alpha-NH(4)Fe(2)(PO(4))(2) are also explained by this description.


Identification of community flour mills as the source of lead poisoning in West Bank Arabs.
Following the discovery of severe lead poisoning in members of several households in a West Bank village, studies were carried out to establish the magnitude of the problem in the community and to identify the source of lead poisoning. Forty-three patients with Centers for Disease Control risk group IV lead poisoning were identified and treated in three villages within a radius of about 10 km of each other. The prevalence of increased lead burden among 563 schoolchildren aged 10 to 18 years was 19% for Centers for Disease Control risk groups I and II and 11% for groups III and IV. A survey of potential sources excluded all items, except for locally ground flour, which was heavily contaminated in all affected households. Examination of community flour mills revealed that, in contrast to unprocessed grain, freshly ground flour contained large amounts of lead originating from lead fillings employed to fasten the housing of the driveshafts to the millstones. Systematic screening of 146 community stone mills in 92 West Bank villages showed significant lead contamination of flour in 33 mills (23%). In all cases, the source of lead contamination was identical. As methods of milling in the area are similar, a prompt investigation of this potential source of lead poisoning in other near-Eastern countries is indicated.


Fatty acid and energy metabolism in broiler chickens fed diets containing either beef tallow or an oil blend.
The hypothesis tested was that the feeding of n-6 polyunsaturated fatty acids (PUFA) results in more whole-body fatty acid oxidation than the feeding of saturated fatty acids (SFA). It was reasoned that the increased fatty acid oxidation would be associated with enhanced whole-body energy expenditure and stimulated de novo fatty acid synthesis. To put the hypothesis to the test, broiler chickens were fed diets containing either beef tallow as source of SFA or an oil blend as source of n-6 PUFA. The broilers either had free access to their diet or were fed a restricted amount. Seven-day-old, male broiler chickens were used; they were kept individually in cages from 1 to 4 weeks of age. In the birds fed ad libitum, the n-6 PUFA diet reduced average daily feed intake (ADFI), but did not significantly affect average daily weight gain (ADG) and the feed:conversion ratio (FCR). The lower ADFI on the n-6 PUFA diet was associated with a higher apparent digestibility of total fatty acids. The ratio of deposition in the body to intake of digestible total PUFA, which reflected n-6 PUFA, was significantly decreased by the n-6 PUFA diet, pointing at preferentially increased n-6 PUFA oxidation on the n-6 PUFA diet. The ratio for n-9 monounsaturated fatty acids (MUFA) was higher than 1.0, which agrees with net de novo synthesis, but the n-6 PUFA diet induced a lower value than did the SFA diet. Feeding either the n-6 PUFA or SFA diet did not influence energy expenditure expressed as percentage of energy intake. This study supports the idea that dietary n-6 PUFA instead of SFA are preferentially oxidized, but no proof was obtained for enhanced energy expenditure and contrary to the hypothesis put forward, the n-6 PUFA diet depressed de-novo fatty acid synthesis.


Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth.
Aldosterone-producing adenomas with somatic mutations in the KCNJ5 G-protein-coupled inwardly rectifying potassium channel are a cause of primary aldosteronism. These mutations drive aldosterone excess, but their role in cell growth is undefined. Our objective was to determine the role of KCNJ5 mutations in adrenal cell proliferation and apoptosis. The Ki67 proliferative index was positively correlated with adenoma diameter in aldosterone-producing adenomas with a KCNJ5 mutation (r=0.435, P=0.007), a negative correlation was noted in adenomas with no mutation detected (r=-0.548, P=0.023). Human adrenocortical cell lines were established with stable expression of cumate-inducible wild-type or mutated KCNJ5. Increased cell proliferation was induced by low-level induction of KCNJ5-T158A expression compared with control cells (P=0.009), but increased induction ablated this difference. KCNJ5-G151R displayed no apparent proliferative effect, but KCNJ5-G151E and L168R mutations each resulted in decreased cell proliferation (difference P<0.0001 from control cells, both comparisons). Under conditions tested, T158A had no effect on apoptosis, but apoptosis increased with expression of G151R (P<0.0001), G151E (P=0.008), and L168R (P<0.0001). We generated a specific KCNJ5 monoclonal antibody which was used in immunohistochemistry to demonstrate strong KCNJ5 expression in adenomas without a KCNJ5 mutation and in the zona glomerulosa adjacent to adenomas irrespective of genotype as well as in aldosterone-producing cell clusters. Double immunofluorescence staining for KCNJ5 and CYP11B2 (aldosterone synthase) showed markedly decreased KCNJ5 immunostaining in CYP11B2-positive cells compared with CYP11B2-negative cells in aldosterone-producing adenomas with a KCNJ5 mutation. Together, these findings support the concept that cell growth effects of KCNJ5 mutations are determined by the expression level of the mutated channel.


Local superficial radiotherapy in the management of minimal stage IA cutaneous T-cell lymphoma (Mycosis Fungoides).
To evaluate the impact of local superficial radiotherapy with respect to local control, survival, and toxicity for patients with "minimal" stage IA cutaneous T-cell lymphoma (Mycosis Fungoides). Between 1954 and 1996 a total of 21 patients were identified as receiving curative local superficial radiation (LSR) for minimal stage IA Mycosis Fungoides. All patients had pathologic documentation at diagnosis and at the time of suspected recurrences and no patient received prior radiation. Ten patients were treated with 100-280 Kv (A1), and 11 with 4-12 Mev electrons. Nine patients had failed prior therapies (steroids: 4; PUVA: 3; BCNU: 1; UVB: 1) and six received adjuvant therapy after completion of LSR (PUVA: 5; steroids: 1). Minimum follow-up was 1 year. The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All patients were Caucasian, and 11 were male. A total of 32 lesions were identified in 21 patients; 13 patients had unilesional disease, 5 patients had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107 cm2 (11-785). The median surface dose was 20 Gy (6-40), with 17 patients receiving a dose > or = 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all patients were alive at last evaluation. All failures were cutaneous. One patient had persistent disease (treated with 6 Gy), and three failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy). None of these patients received adjuvant therapy. Two patients failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64%, respectively, with local control of 75% at both time intervals. For the 13 patients with unilesional disease, the DFS was 85% at 10 years. For those treated with doses > or = 20 Gy, the DFS was 91% as was local control (no distant failures). Toxicity included mild erythema and dry desquamation acutely. Chronic toxicity included dermatitis [2], and telangiectasia [1]. No second cutaneous malignancies or hematologic toxicity was noted. Patients with minimal Stage IA Mycosis Fungoides may be managed effectively with local superficial radiation alone without adjuvant therapy. Distant failure is unusual and patients should receive a minimum surface dose of 20 Gy, which offers excellent local control. Sequalae of therapy are minimal.


The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi.
Here, we report an inhibitory effect of a sesquiterpene lactone dehydroleucodine (DhL) on the growth of Trypanosoma cruzi in culture. At concentrations of the drug between 5 and 10 microg/ml in the medium,the parasites remained alive for at least 4 days. Higher concentrations of DhL were lethal for the parasites within a few hours. The effect of DhL is irreversible. Morphological changes induced by DhL were also observed in the parasites. The effect of DhL was blocked by the presence of reducing substrates such as glutathione or dithiothreitol, but these agents were not able to reverse the effect of DhL if added 2 days after the start of drug exposure.


Using concept mapping to explore why patients become lost to follow up from an antiretroviral therapy program in the Zomba District of Malawi.
Retention in antiretroviral therapy (ART) programmes remains a challenge in many settings including Malawi, in part due to high numbers of losses to follow-up. Concept Mapping (CM), a mix-method participatory approach, was used to explore why patients on ART are lost to follow-up (LTFU) by identifying: 1) factors that influence patient losses to follow-up and 2) barriers to effective and efficient tracing in Zomba, Malawi. CM sessions (brainstorming, sorting and rating, interpretation) were conducted in urban and rural settings in Zomba, Malawi. Participants included ART patients, ART providers, Health Surveillance Assistants, and health managers from the Zomba District Health Office. In brainstorming, participants generated statements in response to "A specific reason why an individual on ART becomes lost to follow-up is…" Participants then sorted and rated the consolidated list of brainstormed items. Analysis included inductive qualitative methods for grouping of data and quantitative cluster identification to produce visual maps which were then interpreted by participants. In total, 90 individuals brainstormed 371 statements, 64 consolidated statements were sorted (participant n = 46), and rated on importance and feasibility (participant n = 69). A nine-cluster concept map was generated and included both patient- and healthcare-related clusters such as: Stigma and Fears, Beliefs, Acceptance and Knowledge of ART, Access to ART, Poor Documentation, Social and Financial Support Issues, Health Worker Attitudes, Resources Needed for Effective Tracing, and Health Worker Issues Related to Tracing. Strategies to respond to the clusters were generated in Interpretation. Multiple patient- and healthcare focused factors influence why patients become LTFU. Findings have implications particularly for programs with limited resources struggling with the retention of ART patients.


Web query-based surveillance in Sweden during the influenza A(H1N1)2009 pandemic, April 2009 to February 2010.
At the Swedish Institute for Communicable Disease Control, statistical models based on queries submitted to a Swedish medical website are used as a complement to the regular influenza surveillance. The models have previously been shown to perform well for seasonal influenza. The purpose of the present study was to evaluate the performance of the statistical models in the context of the influenza A(H1N1)2009 pandemic, a period when many factors, for example the media, could have influenced people's search behaviour on the Internet and consequently the performance of the models. Our evaluation indicates consistent good reliability for the statistical models also during the pandemic. When compared to Google Flu Trends for Sweden, they were at least equivalent in terms of estimating the influenza activity, and even seemed to be more precise in estimating the peak incidence of the influenza pandemic.


Inhibition of lactose transport in E. coli by N-ethylmaleimide-beta-galactoside, N-ethylsuccinimide-beta-galactoside and N-ethylmaleimide.
N-ethylmaleimide (NEM) inhibits lactose uptake in E. coli by reacting with the M protein component of the lac permease system. In an attempt to estimate the distance between the NEM reactive site and the substrate binding site, we have synthesized a beta-galactoside with NEM as the aglycon moiety (NEM-gal). NEM-gal was a more effective inhibitor of lactose transport than was NEM. Part of the inhibition by NEM-gal was caused by competition with lactose for the substrate binding site. To estimate this part of the inhibition, we synthesized the saturated and thus the unreactive N-ethylsuccinimide (NES) analog of NEM-gal. Nes-gal was a competitive inhibitor of lactose uptake. The remainder of the inhibition by NEM-gal followed first-order kinetics with the same rate constant as NEM. In addition, the protective effect of thiodigalactoside against the inhibition of transport by NEM was also observed against irreversible inhibition by NEM-gal. We suggest that the reactivity of NEM was unaltered by bringing it near the beta-galactoside binding site by way of covalent attachment to galactose. We conclude that the distance between the NEM reactive site and the position of the glycosidic oxygen of beta-galactosides bound to the lactose site is greater than 8 A.


[Fast technique to quantify liver steatosis at 3T: principles, parametric imaging and applications].
The purpose of this article is to present a fast and clinically usable technique for quantification of liver steatosis. This technique, based on a triple-echo gradient-echo sequence (in-phase, opposed-phase, in-phase), has recently been validated with excellent correlation and accuracy compared to proton MR spectroscopy. The theoretical principles are reviewed, with emphasis on the need to correct for the T2* decay inherent to the use of in-phase and opposed-phase sequences. T1 decay also is negligible due to the use of a low flip angle (20 degrees). The advantage of this technique is that it can generate a parametric representation (map) of liver steatosis, after fast and simple post-processing, based on measurements from standard images (addition, subtraction, division, multiplication) available on the MR scanning console. This parametric method allows quantification of steatosis in focal lesions. The main limitation of the technique relates to its ambiguity with lipid content over 50%, a phenomenon that does not occur with liver steatosis.


Roles of ionic residues of the C1 domain in protein kinase C-alpha activation and the origin of phosphatidylserine specificity.
On the basis of extensive structure-function studies of protein kinase C-alpha (PKC-alpha), we have proposed an activation mechanism for conventional PKCs in which the C2 domain and the C1 domain interact sequentially with membranes (Medkova, M., and Cho, W. (1999) J. Biol. Chem. 274, 19852-19861). To further elucidate the interactions between the C1 and C2 domains during PKC activation and the origin of phosphatidylserine specificity, we mutated several charged residues in two C1 domains (C1a and C1b) of PKC-alpha. We then measured the membrane binding affinities, activities, and monolayer penetration of these mutants. Results indicate that cationic residues of the C1a domain, most notably Arg(77), interact nonspecifically with anionic phospholipids prior to the membrane penetration of hydrophobic residues. The mutation of a single aspartate (Asp(55)) in the C1a domain to Ala or Lys resulted in dramatically reduced phosphatidylserine specificity in vesicle binding, activity, and monolayer penetration. In particular, D55A showed much higher vesicle affinity, activity, and monolayer penetration power than wild type under nonactivating conditions, i.e. with phosphatidylglycerol and in the absence of Ca(2+), indicating that Asp(55) is involved in the tethering of the C1a domain to another part of PKC-alpha, which keeps it in an inactive conformation at the resting state. Based on these results, we propose a refined model for the activation of conventional PKC, in which phosphatidylserine specifically disrupts the C1a domain tethering by competing with Asp(55), which then leads to membrane penetration and diacylglycerol binding of the C1a domain and PKC activation.


Kinesin family member 18B: A contributor and facilitator in the proliferation and metastasis of cutaneous melanoma.
Melanoma is the most aggressive type of cutaneous tumor and the occurrence of metastasis makes it resistant to almost all available treatment and becomes incorrigible. Hence, identifying metastasis-related biomarkers and effective therapeutic targets will assist in preventing metastasis and ameliorating cutaneous melanoma. In our present study, we reported kinesin family member 18B (KIF18B) as a novel contributor in cutaneous melanoma proliferation and metastasis, and it was found to be of great significance in predicting the prognosis of cutaneous melanoma patients. Bioinformatics analysis based on ONCOMINE, The Cancer Genome Atlas, and Genotype-Tissue Expression database revealed that KIF18B was highly expressed in cutaneous melanoma and remarkably correlated with unfavorable clinical outcomes. Consistently, the results of the quantitative real-time polymerase chain reaction exhibited that the expression of KIF18B was significantly higher in cutaneous melanoma cell lines than that in normal cells. In vitro, biological assays found that knockdown of KIF18B in cutaneous melanoma cells noticeably repressed cell proliferation, migration, and invasion, while inducing cell apoptosis. Moreover, the protein expression of E-cadherin was enhanced while the expression of N-cadherin, vimentin, and Snail was decreased in M14 cells after knocking down KIF18B. In addition, the phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular-signal-regulated kinase (ERK) was significantly suppressed in M14 cells with silenced KIF18B. Above all, our results indicated that the repression of cutaneous melanoma cell migration and proliferation caused by KIF18B depletion suggested an oncogenic role of KIF18B in cutaneous melanoma, which acts through modulating epithelial-mesenchymal transition and ERK/PI3K pathway.


Effect of Different Local Vibration Frequencies on the Multiscale Regularity of Plantar Skin Blood Flow.
Local vibration has shown promise in improving skin blood flow (SBF). However, there is no consensus on the selection of the best vibration frequency. An important reason may be that previous studies utilized time- and frequency-domain parameters to characterize vibration-induced SBF responses. These parameters are unable to characterize the structural features of the SBF response to local vibrations, thus contributing to the inconsistent findings seen in vibration research. The objective of this study was to provide evidence that nonlinear dynamics of SBF responses would be an important aspect for assessing the effect of local vibration on SBF. Local vibrations at 100 Hz, 35 Hz, and 0 Hz (sham vibration) with an amplitude of 1 mm were randomly applied to the right first metatarsal head of 12 healthy participants for 10 min. SBF at the same site was measured for 10 min before and after local vibration. The degree of regularity of SBF was quantified using a multiscale sample entropy algorithm. The results showed that 100 Hz vibration significantly increased multiscale regularity of SBF but 35 Hz and 0 Hz (sham vibration) did not. The significant increase of regularity of SBF after 100 Hz vibration was mainly attributed to increased regularity of SBF oscillations within the frequency interval at 0.0095-0.15 Hz. These findings support the use of multiscale regularity to assess effectiveness of local vibration on improving skin blood flow.


Disruption of neural systems of visual attention in schizophrenia.
Patients with schizophrenia show attention deficits. The frontal P2a and posterior N2b event-related potential components are early indices of activity in neural systems supporting attention and they are reduced in schizophrenia in auditory tasks. However, the auditory P300 is reduced as well. Thus, the P2a and N2b reductions may simply reflect a general event-related potential amplitude reduction. The visual P300, however, is often spared in schizophrenia. If neural systems supporting attention are specifically disrupted in schizophrenia, the attention-sensitive P2a and N2b should be differentially reduced in patients, compared with the P300, in a visual attention task. We analyzed 64-channel event-related potentials from 14 schizophrenic patients and 14 control subjects in a visual object-spatial attention task. We examined the amplitude of the P2a, N2b, and P300 components in the target minus standard difference wave to see if there was a differential reduction of the P2a and N2b compared with the P300. Both the P2a and N2b waveforms were reduced in the patient group (81% [control mean, 1.99 microV; patient mean, 0.38 microV] and 95% [control mean, 0.55 microV; patient mean, 0.03 microV], respectively) while the P300 was not reduced. Measured at the peak of the frontal P2a, the N2b was larger dorsally in the spatial task and larger ventrally in the object task in the control group. The spatial distribution of the P2a and N2b was consistent with activity in the prefrontal cortex and modality-specific posterior cortex, respectively. The differential reduction of the P2a and N2b waveforms supports the hypothesis of specific disruption in neural systems of visual attention in schizophrenia.


Creative Dance Practice Improves Postural Control in a Child With Cerebral Palsy.
To investigate the effect of creative dance instruction on postural control and balance in an 11-year-old with spastic triplegic cerebral palsy, Gross Motor Function Classification Scale level II. We conducted 1-hour dance interventions twice weekly for 8 weeks, with a focus on somatosensory awareness and movement in all planes of motion. Computerized dynamic posturography using the SMART Balance Master/EquiTest (NeuroCom) was used to assess postural control and balance reactions before the first class and following the final class. Gains in standing stability, balance recovery, directional control, and endpoint excursion of movement were found. Participation in creative dance lessons appears to improve somatosensory effectiveness and postural control in a child with cerebral palsy. Dance is a fun way to improve balance and coordination. These interventions could be easily implemented into programs for children with cerebral palsy.


[Flea allergy and proligestone].
In a small animal practice, 126 cats were given combined treatment with proligestone and an ectoparasitic agent for flea allergy during a period of ten months. Complete recovery (81%) or very marked improvement (10%) were observed in 91% of the cases.


An SCN2A mutation in a family with infantile seizures from Madagascar reveals an increased subthreshold Na(+) current.
Missense mutations in SCN2A, encoding the brain sodium channel NaV 1.2, have been described in benign familial neonatal-infantile seizures (BFNIS), a self-limiting disorder, whereas several SCN2A de novo nonsense mutations have been found in patients with more severe phenotypes including epileptic encephalopathy. We report a family with BFNIS originating from Madagascar. Onset extended from 3 to 9 months of age. Interictal EEGs were normal. In two patients, ictal electroencephalography (EEG) studies showed partial seizure patterns with secondary generalization in one. Seizures remitted before 18 months of age, with or without medication. Intellectual development was normal. A novel missense mutation of SCN2A, c.4766A>G/p.Tyr1589Cys, was found in a highly conserved region of NaV 1.2 (D4/S2-S3). Functional studies using heterologous expression in tsA201 cells and whole-cell patch clamping revealed a depolarizing shift of steady-state inactivation, increased persistent Na(+) current, a slowing of fast inactivation and an acceleration of its recovery, thus a gain-of-function. Using an action potential waveform in a voltage-clamp experiment we indicated an increased inward Na(+) current at subthreshold voltages, which can explain a neuronal hyperexcitability. Our results suggest that this mutation induces neuronal hyperexcitability, resulting in infantile epilepsy with favorable outcome.


Effect of extrinsic denervation on muscarinic neurotransmission in the canine ileocolonic region.
To explore the hypothesis that denervation hypersensitivity increases ileocolonic motor activity after extrinsic denervation, we compared muscarinic neurotransmission in canine ileocolonic loops that were isolated and either extrinsically innervated or extrinsically denervated. We recorded ileal, ileocolonic sphincter (ICS) and colonic pressures, and colonic tone, compliance and relaxation during ileal distention. Muscarinic effects were probed by neostigmine, and minimally effective doses of muscarinic receptor antagonists. Denervation augmented ileal, ICS and colonic contractile activity; colonic high-amplitude propagating contractions (HAPCs) were also augmented; colonic relaxation during ileal distention was abolished. Neostigmine induced HAPCs in both loop preparations. Pirenzipine (M1 antagonist) reduced ileal contractile activity in all loops and reduced colonic relaxation during ileal distention in innervated loops. Pirenzipine also reduced colonic tone and colonic HAPCs, more in denervated loops. Darifenacin (M3 antagonist) reduced ileocolonic contractile activity and tone more than did AF-DX 116 (M2 antagonist) in all loops. Cholinergic receptor subtypes modulate different facets of ileocolonic motor activity in the canine ileocolonic region. Increased sensitivity at M1 muscarinic receptors may partly account for the effects of extrinsic denervation.


Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis.
Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs for treating advanced stages of breast cancers, women eventually develop resistance. One of the approaches to control breast cancer is prevention through diet, which inhibits one or more neoplastic events and reduces cancer risk. In this study, we have used human breast cancer cells, MCF-7 and MDA-MB-231, and primary human mammary epithelial cells as an in vitro model to assess the efficacy of bitter melon (Momordica charantia) extract (BME) as an anticancer agent. BME treatment of breast cancer cells resulted in a significant decrease in cell proliferation and induced apoptotic cell death. Apoptosis of breast cancer cells was accompanied by increased poly(ADP-ribose) polymerase cleavage and caspase activation. Subsequent studies showed that BME treatment of breast cancer cells inhibited survivin and claspin expression. Fluorescence-activated cell sorting analysis suggested that MCF-7 cells treated with BME accumulated during the G2-M phase of the cell cycle. Further studies revealed that BME treatment enhanced p53, p21, and pChk1/2 and inhibited cyclin B1 and cyclin D1 expression, suggesting an additional mechanism involving cell cycle regulation. Together, these results show that BME modulates signal transduction pathways for inhibition of breast cancer cell growth and can be used as a dietary supplement for prevention of breast cancer.


Design of annulene-within-an-annulene systems by the altanisation approach. A study of altan-[n]annulenes.
The altanisation strategy, devised to design molecules with large and paratropic perimeter circulations, is applied to the family of [n]annulenes to give, altan-[n]annulenes, i.e. [n,5]coronenes. Analytical expressions are obtained for the eigenvalues of the Hückel Hamiltonian for altan-[n]annulenes, and used in conjunction with selection rules derived from the ipsocentric approach to predict patterns of global ring current in these systems. Density-functional calculations performed on seven altan-[n]annulenes, three neutral and four charged, give current-density maps in essential agreement with the predictions obtained at the unperturbed Hückel level. All but one of the systems show patterns with the tropicities expected for isolated annulenes, in line with the altanisation concept. The apparent exception is altan-[11]annulene-, the only singlet system with a well defined open-shell character in the studied set. The key role of open-shell character can be accommodated by appropriate choice of the occupation numbers of the initial Hückel molecular orbitals, where the anion altan-[11]annulene- is considered as an [11]annulene inside the [22]annulene anion.


Comparison of open and percutaneous lumbar pedicle screw revision rate using 3-D image guidance and intraoperative CT.
Complications arising from a malpositioned screw can be both devastating and costly. The incidence of neurologic injury secondary to a malpositioned screw is reported to be as high as 7% to 12%. The advancement of image-guided technology has allowed surgeons to place screws more accurately and confirm correct placement prior to leaving the operating room. Only a small number of studies have examined image-guided pedicle screw accuracy in terms of intraoperative revision and reoperation rates. The purpose of this study was to determine the intraoperative revision and return to surgery rates for navigated lumbar pedicle screws and to compare navigated open and percutaneous techniques. The authors reviewed 199 cases of 3-dimensional image-guided lumbar pedicle screw instrumentation from November 2006 to December 2011. Screw or K-wire removal, repositioning, or eventual abandonment of insertion were noted. Chi-square test was used to determine statistical significance in rates between the 2 groups (alpha=0.05). The authors also noted return to surgery secondary to complications from a malpositioned screw. The overall intraoperative revision rate of navigated lumbar pedicle screws was 4.6%. There were significantly more revisions in the percutaneously inserted screws (7.5%) than with the open technique (2.7%) (P=.0004). If K-wire revisions are excluded, there was no statistically significant difference in intraoperative revision rates between the percutaneous and open groups (2.1% vs 2.7%, respectively) (P=.0004). No patients underwent reoperation for a malpositioned screw. This technology has virtually eliminated the need for reoperation for screw malposition. It may suggest a more cost-effective way of preventing neurovascular injuries and revision surgeries.


Novel phloretin-based combinations targeting glucose metabolism in hepatocellular carcinoma through GLUT2/PEPCK axis of action: in silico molecular modelling and in vivo studies.
Hepatocellular carcinoma (HCC) is commonly associated with disturbances in glucose metabolism and enhanced glycolysis. However, a controversial role for gluconeogenesis was reported to be tumor-promoting and tumor-suppressive. We investigated novel anti-HCC treatments through either the simultaneous inhibition of glycolysis and gluconeogenesis by "phloretin" and "sodium meta-arsenite", respectively (Combination 1); or the concurrent inhibition of glycolysis and induction of gluconeogenesis by phloretin and dexamethasone, respectively, (combination 2). A total of 110 Swiss albino mice were divided into eleven groups, HCC was induced by N, N-dimethyl-4-aminoazobenzene. We have measured the expression of the glucose transporter 2 (GLUT2), Phosphoenolpyruvate carboxykinases (PEPCK), Caspase-3, Beclin 1, Cyclin D1, and cytokeratin 18 genes; blood glucose and ATP levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Furthermore, in silico molecular docking was performed to investigate the potential drug-receptor interactions. Histologically, the phloretin-based combinations resulted in a significant regression of malignant tissue compared to various treatments. GLUT2 and PEPCK mRNA analysis indicated successful off/on modulation of glycolysis and gluconeogenesis. Docking confirmed the potent binding between phloretin, sodium meta-arsenite, and dexamethasone with GLUT2, PEPCK, and Retinoid X Receptor Alpha, respectively. Molecularly, Combination 2 resulted in the highest reduction in cyclin D1, cytokeratin 18, and Beclin 1 expression contemporaneously with the upregulation in Caspase-3 levels. Biochemically, both combinations caused a significant reduction in ATP levels, ALT, and AST activity compared to the other groups. In conclusion, we propose two novel phloretin-based combinations that can be used in treating HCC through the regulation of glucose metabolism and ATP production.


A Primer on Bayesian Analysis for Experimental Psychopathologists.
The principal goals of experimental psychopathology (EPP) research are to offer insights into the pathogenic mechanisms of mental disorders and to provide a stable ground for the development of clinical interventions. The main message of the present article is that those goals are better served by the adoption of Bayesian statistics than by the continued use of null-hypothesis significance testing (NHST). In the first part of the article we list the main disadvantages of NHST and explain why those disadvantages limit the conclusions that can be drawn from EPP research. Next, we highlight the advantages of Bayesian statistics. To illustrate, we then pit NHST and Bayesian analysis against each other using an experimental data set from our lab. Finally, we discuss some challenges when adopting Bayesian statistics. We hope that the present article will encourage experimental psychopathologists to embrace Bayesian statistics, which could strengthen the conclusions drawn from EPP research.


Which environmental factors are associated with performance when controlling for capacity?
To determine which environmental factors are associated with performance when controlling for capacity, using the International Classification of Functioning, Disability and Health (ICF). A psychometric study using a sample of 296 persons with musculoskeletal health conditions as a case in point. The following steps were carried out: (i) Rasch analyses created 2 interval measurement scales, capacity and performance, based on 22 Activities and Participation ICF categories that had been rated as capacity and performance. Capacity and performance scores, ranging from 0 (low level) to 100 (high level) were calculated; (ii) group lasso regression was used to identify the environmental factors associated with a person's performance when controlling for capacity. Gender, age and health condition were forced to remain in the model. A capacity scale based on 16 ICF categories (rated as capacity) and a performance scale based on 18 categories (rated as performance) were created. Thirteen environmental factors ICF categories covering the physical, social, attitudinal and political environment were identified as highly associated with patient's performance. Using an exclusively statistical approach this study identified environmental factors associated with a person's performance.


Dislocation-pipe diffusion in nitride superlattices observed in direct atomic resolution.
Device failure from diffusion short circuits in microelectronic components occurs via thermally induced migration of atoms along high-diffusivity paths: dislocations, grain boundaries, and free surfaces. Even well-annealed single-grain metallic films contain dislocation densities of about 1014 m-2; hence dislocation-pipe diffusion (DPD) becomes a major contribution at working temperatures. While its theoretical concept was established already in the 1950s and its contribution is commonly measured using indirect tracer, spectroscopy, or electrical methods, no direct observation of DPD at the atomic level has been reported. We present atomically-resolved electron microscopy images of the onset and progression of diffusion along threading dislocations in sequentially annealed nitride metal/semiconductor superlattices, and show that this type of diffusion can be independent of concentration gradients in the system but governed by the reduction of strain fields in the lattice.


A proteomic perspective on the changes in milk proteins due to high somatic cell count.
Although cows with subclinical mastitis have no difference in the appearance of their milk, milk composition and milk quality are altered because of the inflammation. To know the changes in milk quality with different somatic cell count (SCC) levels, 5 pooled bovine milk samples with SCC from 10(5) to 10(6) cells/mL were analyzed qualitatively and quantitatively using both one-dimension sodium dodecyl sulfate PAGE and filter-aided sample preparation coupled with dimethyl labeling, both followed by liquid chromatography tandem mass spectrometry. Minor differences were found on the qualitative level in the proteome from milk with different SCC levels, whereas the concentration of milk proteins showed remarkable changes. Not only immune-related proteins (cathelicidins, IGK protein, CD59 molecule, complement regulatory protein, lactadherin), but also proteins with other biological functions (e.g., lipid metabolism: platelet glycoprotein 4, butyrophilin subfamily 1 member A1, perilipin-2) were significantly different in milk from cows with high SCC level compared with low SCC level. The increased concentration of protease inhibitors in the milk with higher SCC levels may suggest a protective role in the mammary gland against protease activity. Prostaglandin-H2 D-isomerase showed a linear relation with SCC, which was confirmed with an ELISA. However, the correlation coefficient was lower in individual cows compared with bulk milk. These results indicate that prostaglandin-H2 D-isomerase may be used as an indicator to evaluate bulk milk quality and thereby reduce the economic loss in the dairy industry. The results from this study reflect the biological phenomena occurring during subclinical mastitis and in addition provide a potential indicator for the detection of bulk milk with high SCC.


Determinants of successful vitamin A supplementation coverage among children aged 6-59 months in thirteen sub-Saharan African countries.
Vitamin A supplementation (VAS) for children aged 6-59 months occurs regularly in most sub-Saharan African countries. The present study aimed to explore child, household and delivery platform factors associated with VAS coverage and identify barriers to compliance in thirteen African countries. We pooled data (n ~60 000) from forty-four household coverage surveys and used bivariate and multivariable regression analyses to assess the effects of supplementation strategy, rural v. urban residence, child sex, child age, caregiver education and campaign awareness on child VAS status. Setting/Subjects Primary caregivers of children aged 6-59 months in thirteen countries. Door-to-door distribution resulted in higher VAS coverage than fixed-site plus outreach approaches (91 v. 63 %) and was a significant predictor of supplementation in the adjusted model (OR=19·0; 95 % CI 17·2, 21·1; P<0·001). Having been informed about the campaign was the main predictor of VAS in the door-to-door (OR=6·8; 95 % CI 5·8, 7·9; P<0·001) and fixed-site plus outreach (OR=72·5; 95 % CI 66·6, 78·8; P<0·001) groups. Door-to-door provision of VAS may achieve higher coverage than fixed-site models in the African context. However, the phase-out of door-to-door polio immunization campaigns in most sub-Saharan African countries threatens the main distribution vehicle for VAS. Our findings suggest well-informed communities are key to attaining higher coverage using fixed-site delivery alternatives.


Mining the accident causes of railway dangerous goods transportation: A Logistics-DT-TFP based approach.
Accurately and quickly mining the hidden information in railway dangerous goods transportation (RDGT) accident reports has great significance for its safety management. In this paper, a data mining method Logistics-DT-TFP is proposed for analysing the causes of RDGT accidents. Firstly, analyse the transportation process, extract the cause of the accident, and classify the severity of the accident. Then, using ordered multi-classification Logistic regression for correlation calculation, qualitatively judge and quantitatively analyse the relationship between each cause and the severity of the accident. The feature tags of the Decision Tree (DT) are screened, the C5.0 algorithm is used to obtain the accident coupling rules. Next, the FP-Growth algorithm is used to mine frequent itemsets, and TOP-K is used to improve it and output effective association rules with the degree of lift as the indicator, which avoids repeated traversal of the database, shortens the time complexity, and reduces the impact of the minimum support setting on the calculation results. The degree of lift among the causes in the coupling chain is calculated as a complement to the extraction of coupling rules. Finally, based on the analysis and mining results of case study, the management strategies for railway dangerous goods are proposed.


Vitamin A fortification of wheat flour: considerations and current recommendations.
Vitamin A deficiency is a major public health nutrition problem, affecting an estimated 190 million preschool-aged children and 19 million pregnant and lactating women globally, and 83 million adolescents in Southeast Asia alone. Its consequences (disorders) include xerophthalmia (the leading cause of early childhood blindness), increased severity of infection, anemia, and death. Because vitamin A deficiency is largely due to chronic dietary insufficiency of preformed vitamin A and proactive carotenoids, food fortification can offer an effective approach to prevention. To provide guidance on fortifying wheat and maize flour milled in industrial rollers for national fortification programs in countries where vitamin A deficiency is considered a public health problem. Critical review of the literature on the dietary gap in vitamin A intake and levels of wheat flour intake among risk groups as a basis for determining vitamin A fortificant levels. Additional review of efficacy evidence, safety and cost considerations, and country experiences related to wheat-flour fortification with vitamin A. Mill-rolled wheat flour is a technically fortifiable, centrally processed food vehicle that, where routinely and adequately consumed by target groups, should be considered a candidate for fortification. Vitamin A can be stable in flour under typical, ambient conditions, with processing losses estimated at approximately 30%, depending on source and premix conditions. Factors to guide a decision to fortify flour with vitamin A include the extent of deficiency, availability of other food vehicle options, the centrality of milling, market reach and population intake distributions of the flour products, the dietary vitamin A intake required, and associated costs. Large gaps persist in knowledge of these factors, which are needed to enable evidence-based fortification in most countries, leaving most decisions to fortify guided by assumptions. Where flour can and should be fortified, guidelines are given for providing nearly 25% of the Recommended Dietary Allowance for vitamin A to vulnerable groups consuming varying ranges of flour products. The costs will vary according to the level of fortification.


Care integration within and outside health system boundaries.
Examine care integration-efforts to unify disparate parts of health care organizations to generate synergy across activities occurring within and between them-to understand whether and at which organizational level health systems impact care quality and staff experience. Surveys administered to one practice manager (56/59) and up to 26 staff (828/1360) in 59 practice sites within 24 physician organizations within 17 health systems in four states (2017-2019). We developed manager and staff surveys to collect data on organizational, social, and clinical process integration, at four organizational levels: practice site, physician organization, health system, and outside health systems. We analyzed data using descriptive statistics and regression. Managers and staff perceived opportunity for improvement across most types of care integration and organizational levels. Managers/staff perceived little variation in care integration across health systems. They perceived better care integration within practice sites than within physician organizations, health systems, and outside health systems-up to 38 percentage points (pp) lower (P < .001) outside health systems compared to within practice sites. Of nine clinical process integration measures, one standard deviation (SD) (7.2-pp) increase in use of evidence-based care related to 6.4-pp and 8.9-pp increases in perceived quality of care by practice sites and health systems, respectively, and a 4.5-pp increase in staff job satisfaction; one SD (9.7-pp) increase in integration of social services and community resources related to a 7.0-pp increase in perceived quality of care by health systems; one SD (6.9-pp) increase in patient engagement related to a 6.4-pp increase in job satisfaction and a 4.6-pp decrease in burnout; and one SD (10.6-pp) increase in integration of diabetic eye examinations related to a 5.5-pp increase in job satisfaction (all P < .05). Measures of clinical process integration related to higher staff ratings of quality and experience. Action is needed to improve care integration within and outside health systems.


[Differential diagnosis of proteinuria].
Normally, protein secretion in the urine is less than 150 mg/day or less than 100 mg/g creatinine. Orthostatic proteinuria, proteinuria in the presence of fever, and effort proteinuria are benign forms. In cases of persistent proteinuria, prerenal or overflow proteinuria are distinguished from renal and post-renal proteinuria. Renal forms can be differentiated into glomerular and tubular as well as mixed forms. The urine dipstick is of only low sensitivity, and is therefore unsuitable as a screening test for diabetic microalbuminuria. In addition, it cannot detect immunoglobulin light chains in Bence Jones proteinuria. For the differentiation between glomerular and tubular forms of proteinuria, the determination of marker proteins in the urine, for example, alpha1 microglobulin, albumin and IgG, has proven utility.


Modulation of masseter exteroceptive suppression by non-nociceptive upper limb afferent activation in humans.
The effects induced by non-noxious electrical stimulation of upper limb nerves on exteroceptive suppression (ES) of masseter muscle EMG activity were studied in 15 healthy subjects. EMG activity of masseter muscles was recorded bilaterally and great care was taken to minimise the activation of afferents other than the stimulated ones. Masseter ES was elicited by applying a non-noxious electrical stimulus to the skin above the mental nerve (Mt) of one side, during a voluntary contraction of masseter muscles at a prescribed steady clenching level. Onset and offset latencies and duration of early and late components of masseter ES (ES1 and ES2, respectively) were evaluated in control conditions and compared to those obtained when a non-noxious electrical stimulation was delivered separately to Med or Rad or simultaneously to both nerves (Med-Rad) of one side. Upper limb nerve stimulation could be simultaneous or it could precede or follow Mt stimulation by various time intervals. In control conditions, ES1 latency onset and duration values (mean +/- SD) were 11.3+/-2.9 ms and 16.9+/-2.1 ms, respectively, and ES2 latency onset and duration values were 44.5+/-6.0 ms and 28.6+/-11.1 ms, respectively. No significant differences were observed which were related to the side being recorded. Two types of effects, opposite in nature, were shown on masseter ES, depending on the time intervals between Mt and upper limb nerve stimulation. The first effect, which was facilitatory, consisted of a significant increase in ES1 and ES2 duration. A maximal increase in ES1 duration (134-155% compared to control value) occurred when upper limb nerve stimulation preceded that of Mt by 18-30 ms. Maximal ES2 lengthening (115-145%) was observed when upper limb nerve stimulation followed that of the Mt by 10 ms. The second effect was inhibitory and affected only ES2, which appeared completely eliminated when Med stimulation preceded that of Mt by 40-80 ms. By contrast, ES1 was never suppressed at any interstimulus interval. These data might reflect the different action of the central outflow, following the upper limb-induced effects, on the different neuronal circuits mediating ES1 and ES2.


Dual-template molecularly imprinted polymers for dispersive solid-phase extraction of fluoroquinolones in water samples coupled with high performance liquid chromatography.
Novel dual-template molecularly imprinted polymers (dt-MIPs) were prepared by simple and facile precipitation polymerization using norfloxacin (NOR) and enrofloxacin (ENR) as templates for simultaneous selective recognition and extraction of the two fluoroquinolones (FQs). The as-prepared dt-MIPs exhibited high adsorption capacity and excellent selectivity towards NOR and ENR. Several main parameters affecting the efficiency of dt-MIP based dispersive solid-phase extraction (DSPE) were systematically investigated, coupled with high performance liquid chromatography determination. Consequently, high enrichment factors of 71 and 61 were obtained for NOR and ENR respectively, and good linearity in the range of 1-200 μg L-1 was observed, with correlation coefficients (r) above 0.9977. The limits of detection and quantification for NOR were 0.22 and 0.67 μg L-1, respectively, and 0.36 and 0.98 μg L-1 for ENR. Satisfactory recoveries of the two FQs from spiked lake, sea and tap water samples at three concentration levels were attained in the range of 80.9-101.0% with relative standard deviations of 0.9-6.9%. The present study not only has great potential for applications in FQ determination, but will also enrich research into dual/multi-template imprinting.


Managed care operations and plan design.
Plan design has come a long way from the days when all one had to do was figure out the right deductible, coinsurance and out-of-pocket amounts and consider some questions about competitive practice and employee perception. Today one must also consider systems capabilities, strategic fit, provider requirements and consistency of the logic supporting each payment decision.


Changes in foliar spectral reflectance and chlorophyll fluorescence of four temperate species following branch cutting.
Spectral reflectance and chlorophyll fluorescence are rapid non-invasive methods that can be used to quantify plant stress. Because variation in ambient light (e.g., diurnal patterns of solar radiation) may have a confounding effect on these measurements, branches are often excised in the field and then measured under controlled conditions in the laboratory. We studied four temperate tree species (Abies balsamea (L.) Mill. (balsam fir), Betula papyrifera var. cordifolia (Regel) Fern. (paper birch), Picea rubens Sarg. (red spruce) and Sorbus americana Marsh. (mountain-ash)) to determine how quickly reflectance and fluorescence change following branch cutting. We hypothesized that conifer species, which have tough xeromorphic foliage, would exhibit changes more slowly than broadleaf species. Furthermore, we hypothesized that keeping broadleaf samples cool and moist would delay the onset of reflectance and fluorescence changes. In one set of experiments, we did not use any treatments to maintain the freshness of cut branches. During the first 12 h following cutting, changes in reflectance and fluorescence were slight for all species. Two or 3 days after branch cutting, the two conifers still showed only small changes in the ratio of variable to maximum fluorescence (Fv/Fm) and most reflectance indices, whereas paper birch and mountain-ash showed larger and more rapid declines in Fv/Fm and most reflectance indices. We attribute these declines to loss of water. As a consequence of xeromorphic leaf structure, the conifers were better able to minimize water loss than the two broadleaf species. In another experiment, paper birch that had been kept cool and moist after cutting showed only slight changes in fluorescence and reflectance, even after 3 days, indicating that with careful handling the time interval between collection and measurement of reflectance and fluorescence of many broadleaf specimens can be extended to several days. We conclude that measurements of reflectance and fluorescence need not be made in situ to be accurate and reliable.


Anti-Semaphorin 3A neutralization monoclonal antibody prevents sepsis development in lipopolysaccharide-treated mice.
Semaphorin 3A (Sema3A), originally identified as a potent growth cone collapsing factor in developing sensory neurons, is now recognized as a key player in immune, cardiovascular, bone metabolism and neurological systems. Here we established an anti-Sema3A monoclonal antibody that neutralizes the effects of Sema3A both in vitro and in vivo. The anti-Sema3A neutralization chick IgM antibodies were screened by combining an autonomously diversifying library selection system and an in vitro growth cone collapse assay. We further developed function-blocking chick-mouse chimeric and humanized anti-Sema3A antibodies. We found that our anti-Sema3A antibodies were effective for improving the survival rate in lipopolysaccharide-induced sepsis in mice. Our antibody is a potential therapeutic agent that may prevent the onset of or alleviate symptoms of human diseases associated with Sema3A.


Effect of erythritol and xylitol on dental caries prevention in children.
The aim of this study was to test the efficacy of long-term, daily intake of erythritol and xylitol candy, compared with sorbitol candy, on the development of enamel and dentin caries lesions. The study was a double-blind randomized controlled prospective clinical trial. Altogether 485 primary school children, first- and second-graders at baseline, from southeastern Estonia participated in this 3-year intervention. Each child consumed four erythritol, xylitol or sorbitol (control) candies three times per school day. The daily intake of polyol was about 7.5 g. The International Caries Detection and Assessment System (ICDAS) was used in the clinical examinations by four calibrated examiners at baseline and at 12, 24 and 36 months. The annual examination analyses and the follow-up analyses confirmed that the number of dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months follow-up was significantly lower in the mixed dentition in the erythritol group than in the xylitol or control group. Time of enamel/dentin caries lesions to develop and of dentin caries lesions to progress was significantly longer in the erythritol group compared to the sorbitol and xylitol groups. Also the increase in caries score was lower in the erythritol group than in the other groups. In the follow-up examinations, a lower number of dentin caries teeth and surfaces was found in the erythritol group than in the xylitol or control groups. Time to the development of caries lesions was longest in the erythritol group. ClinicalTrials.gov Identifier NCT01062633.


Characteristics and aluminum reuse of textile sludge incineration residues after acidification.
The chemical composition and aluminum speciation of sludge incineration residue (SIR) were determined. Cementation of aluminum from sulfuric acid solution using SIR was studied. The results showed that acid-soluble inorganic aluminum was the predominant component in the sludge, and the total leached aluminum increased from 62.2% to 92.9% after incineration. Sulfuric acid dosage and reaction time were found to affect aluminum recovery positively. Conversely, the increase in temperature significantly inhibited recovery reactions. The optimized leaching condition was 1.66 g sulfuric acid per gram of SIR with a reaction time of 3 hr at 20 degrees C, resulting in the highest aluminum leaching rate of 96.7%. Compared to commercial aluminum sulfate solution coagulants, the leaching solution demonstrated higher COD(Cr), turbidity and color removal efficiency for textile wastewater.


Definition of unique traits of human CD4-CD8- alpha beta T cells.
We have studied the nature of human CD4-CD8- (double negative) alpha beta T cells to determine whether they possess unique characteristics which could further differentiate them from conventional CD4+ or CD8+ (single positive) T cells. We observed that double negative TCR alpha beta+ T cells differ from single positive T cells in the following respects: (i) their T cell receptor (TCR) repertoire is different, as revealed by the analysis of 47 clones derived from three individuals and by analysis of peripheral blood lymphocytes (PBL) prior to in vitro manipulation; (ii) their in vivo CD3:TCR expression is lower before in vitro manipulation and expansion; (iii) their direct proliferative response to IL-3, which is not mediated by secondary release of other T cell growth factors. These characteristics have also been recently ascribed to murine double negative alpha beta T cells, which develop extrathymically and are considered to be a distinct T cell lineage. Our data suggest that, like their murine counterparts, human double negative alpha beta T cells may represent a distinct T cell lineage which might develop extrathymically.


Transient in vivo selection of transduced peripheral blood cells using antifolate drug selection in rhesus macaques that received transplants with hematopoietic stem cells expressing dihydrofolate reductase vectors.
One of the main obstacles for effective human gene therapy for hematopoietic disorders remains the achievement of an adequate number of genetically corrected blood cells. One approach to this goal is to incorporate drug resistance genes into vectors to enable in vivo selection of hematopoietic stem cells (HSCs). Although a number of drug resistance vectors enable HSC selection in murine systems, little is known about these systems in large animal models. To address this issue, we transplanted cells transduced with dihydrofolate resistance vectors into 6 rhesus macaques and studied whether selection of vector-expressing cells occurred following drug treatment with trimetrexate and nitrobenzylmercaptopurineriboside-phosphate. In some of the 10 administered drug treatment courses, substantial increases in the levels of transduced peripheral blood cells were noted; however, numbers returned to baseline levels within 17 days. Attempts to induce stem cell cycling with stem cell factor and granulocyte-colony stimulating factor prior to drug treatment did not lead to sustained enrichment for transduced cells. These data highlight an important species-specific difference between murine and nonhuman primate models for assessing in vivo HSC selection strategies and emphasize the importance of using drugs capable of inducing selective pressure at the level of HSCs.


The effects of skin-to-skin contact, application site washing, and sunscreen use on the pharmacokinetics of estradiol from a metered-dose transdermal spray.
This study evaluated the transfer of estradiol by skin-to-skin contact and the influence of washing and sunscreen use on the absorption of estradiol from a transdermal spray. Studies were conducted in the same group of 20 healthy postmenopausal women over a period of 18 days. The women were dosed with three sprays of study medication once daily (a total daily dose of 4.59 mg). To evaluate skin-to-skin transfer, estradiol levels in 20 untreated men were evaluated before and after direct skin-to-skin contact with the application sites of 20 treated women after application of study medication on study days 1 to 3. To examine the effect of washing the application site, estradiol absorption was evaluated when the application site was washed 1 hour after application compared with the unwashed site on study days 10 to 12. To examine the effects of sunscreen use, estradiol pharmacokinetic profiles were evaluated when sunscreen was applied before and after study drug application on study days 14 to 17. The 90% CI of the ratios of the areas under the serum estradiol-time curves (AUC0-24) in untreated men before and after contact with treated women was 1.00 to 1.07, which was within the prespecified equivalence range (0.8-1.25). The 90% CI of the AUC0-24 ratios with and without application site washing was 0.92 to 1.15. Application of sunscreen 1 hour after study drug resulted in a 90% CI of AUC0-24 ratios of 0.76 to 1.08. Application of sunscreen 1 hour before study drug resulted in a 90% CI of AUC0-24 ratios of 0.86 to 1.23. The use of a transdermal estradiol spray did not result in a significant transfer of estradiol by skin-to-skin contact. Washing the application site did not significantly affect absorption of estradiol. Estradiol absorption was slightly decreased due to the application of sunscreen after study drug application, but was unaffected when sunscreen was applied before study drug.


Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients.
To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities. We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences. Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001). Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.


PGE2 promotes Ca2+-mediated epithelial barrier disruption through EP1 and EP4 receptors in Caco-2 cell monolayers.
We recently demonstrated that PGE(2) induces the disruption of the intestinal epithelial barrier function. In the present study, our objectives were to study the role of PGE(2) receptors (EP(1)-EP(4)) and the signaling pathways involved in this event. Paracellular permeability (PP) was assessed in differentiated Caco-2 cell cultures from d-mannitol fluxes and transepithelial electrical resistance (TER) in the presence of different PGE(2) receptor agonists (carbacyclin, sulprostone, butaprost, ONO-AE1-259, ONO-AE-248, GR63799, and ONO-AE1-329) and antagonists (ONO-8711, SC-19220, AH-6809, ONO-AE3-240, ONO-AE3-208, and AH-23848). The results indicate that EP(1) and EP(4) but not EP(2) and EP(3) might be involved in PP regulation. These effects were mediated through PLC-inositol trisphosphate (IP(3))-Ca(2+) and cAMP-PKA signaling pathways, respectively. We also observed an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) strengthened by cAMP formation indicating a cross talk interaction of these two pathways. Moreover, the participation of a conventional PKC isoform was shown. The results also indicate that the increase in PP may be correlated with the redistribution of occludin, zona occludens 1 (ZO-1), and the perijunctional actin ring together with an increase in myosin light chain kinase activity. Although the disruption of epithelial barrier function observed in inflammatory bowel disease (IBD) patients has been traditionally attributed to cytokines, the present study focused on the role of PGE(2) in PP regulation, as mucosal levels of this eicosanoid are also increased in these inflammatory processes.


Female Sexual Function following Sling Surgery: A Prospective Parallel Cohort, Multi-Center Study of the Solyx™ Single Incision Sling System versus the Obtryx™ II Sling System.
Limited data exist regarding sexual function after single incision sling (SIS) surgery. We compared sexual function 36 months postoperatively between patients undergoing SIS and transobturator sling (TMUS) for treatment of stress urinary incontinence. Assessment of sexual function was a planned secondary objective of this prospective, multi-center study that enrolled women to Solyx SIS or Obtryx II TMUS. The primary study aim was to compare efficacy and safety using non-inferiority design at 36 months. Patient-reported outcomes of sexual function were assessed at baseline and 6, 12, 18, 24 and 36 months using Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Changes in sexual function were analyzed within and between groups. Outcomes for patients requiring surgical retreatment were determined. Baseline characteristics were balanced using propensity score stratification (N=141 SIS, N=140 TMUS). Groups were similar in age, body mass index and concomitant surgery performed. Average length of followup was 30 months. Baseline sexual activity was similar (123/141 SIS, 114/140 TMUS, p=0.18). Severity of urinary incontinence did not correlate with baseline sexual activity. Mean PISQ-12 scores increased significantly from baseline to 36 months for both groups, indicating better sexual function at each visit. There were no significant differences in PISQ-12 scores between groups except at 36 months, where the difference was small (-2.5, 95% CI [-4.7, 0.2]). Among patients undergoing surgical retreatment (9/281, 3%), improvement in sexual function was maintained. De novo dyspareunia was rare following both treatments (SIS 1/141, TMUS 0/140, p=1.00). Patients have significant improvement in sexual function after SIS and TMUS. De novo sexual pain is low after sling surgery.


Bleeding from cerebral arteriovenous malformations as part of their natural history.
The case records of 191 patients with a cerebral arteriovenous malformation (AVM) were reviewed to determine bleeding characteristics of these lesions. Possible influences of age, sex, the location and size of the AVM, type of initial hemorrhage, and condition of the patients were analyzed. Of these 191 patients, 102 had a single hemorrhage, 32 had a recurrent hemorrhage, and 57 never bled. The follow-up period for patients with an unruptured AVM was a mean of 4.8 years and a maximum of 31 years; for those with a ruptured AVM, the mean was 2 years, and the maximum 37 years. Size of the AVM was significantly related to the risk of first hemorrhage. The average yearly risk for first hemorrhage was between 2% and 3%. Bleeding occurred most frequently in the 11- to 35-year-old age group. The risk of rebleeding increased with advancing age. Among 93 patients followed after their AVM had ruptured, the risk of rebleeding was 6% in 1 year. After the first year, the average rebleeding rate was about 2% per year up to 20 years.


Successful haematopoietic stem cell transplantation in 44 children from healthy siblings conceived after preimplantation HLA matching.
Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic option for many acquired and inherited paediatric haematological disorders. Unfortunately, the probability of finding an HLA matched donor is limited. An alternative technique is PGD combined with HLA matching, which offers the possibility of selecting unaffected embryos that are HLA compatible with the sick child, with the aim of possible use of stem cells from the resulting baby in future. Since the first successful report for Fanconi anaemia a decade ago, the therapeutic success of this technique was reported in a few cases and for a limited number of disorders. Here, we report full recovery of 44 sick children who received HSCT from healthy infants conceived after pre-implantation HLA matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, Glanzmann's thrombasthaenia, Diamond-Blackfan anaemia, X-linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious complications were observed among recipients and donors. Graft failure occurred in four children with beta-thalassaemia where a second HSCT was planned. Preimplantation HLA matching is a reliable technique and provides a realistic option for couples seeking treatment for an affected child when no HLA-matched donor is available.


Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?
Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.


The research-practice relationship in ergonomics and human factors--surveying and bridging the gap.
Significant discord has been aired regarding the widening research-practice gap in several disciplines (e.g. psychology, healthcare), especially with reference to research published in academic journals. The research-practice gap has profound and wide-ranging implications for the adequacy of ergonomics and human factors (E/HF) research and the implementation of research findings into practice. However, no substantive research on this issue has been identified in E/HF. Using an online questionnaire, practitioners were asked about their application of scientific research findings published in peer-reviewed journals and to suggest ways to improve research application in practice. A total of 587 usable responses were collected, spanning 46 countries. This article describes some of the key differences and correlations concerning reading, usefulness and barriers to application among respondents, who varied in terms of organisational type, percentage of work time devoted to application vs. research, society membership and experience. Various solutions proposed by the survey respondents on ways to bridge the research-practice gap are discussed. STATEMENT OF RELEVANCE: The relationship between research and practice in E/HF has long been a subject of discussion, with commentators pointing to tension and possible implications for the adequacy of the discipline. Findings from a cross-sectional survey provide ergonomics practitioners' views on research, leading to discussion of strategies for achieving better integration.


[Quality of life in chronic renal disease patients submitted to hemodialysis evaluated with SF-36 instrument].
Quality of life is a new concept in the health area and controversies exist about its application to clinical practice. Studies carried out in Brazil in the nephrology area have indicated the need for further investigations. To analyze the quality of life of patients with different times of hemodialysis. The study consisted of application of the questionnare SF-36, collection of demographic, socioeconomic and biochemical data, as well as of the clinical characteristics. The study was conducted on 184 patients, 63% of them males, aged 46 15 years (X SD), with a hemodialysis time of 30 36 months; 48% had up to 4 years of schooling and 53% belonged to the economic-social classes D and E. Impairment of the different dimensions analyzed was observed, with the poorest results being obtained for Physical Aspects and Vitality. A negative correlation was detected between Age and Functional Capacity, Physical Aspects, Pain, and Vitality, and between Hemodialysis Time and Emotional Aspects. A positive correlation was observed between Schooling and Emotional Aspects and between Hemoglobin and Vitality. We observed that diabetic patients were older than non-diabetic patients and presented lower values for the Functional Capacity and General Health condition dimensions. SF-36 proved to be a good instrument for the assessment of the quality of life of hemodialysis patients. The presence of a chronic disease, the need for continuous treatment over a long period of time, advanced age, and the presence of co-morbidities were factors that might interfere with the quality of life of this population.


A label-free fluorescence sensing strategy based on GlaI-assisted EXPAR for rapid and accurate quantification of human methyltranferase activity.
DNA methylation plays an important role in epigenetic modification. DNA methyltransferase (DNMT) is essential in the DNA methylation process, and its abnormal expression is closely related to cancer. In this study, we propose a novel biosensor platform (DS-GlaI-EXPAR) that combines hemi-methylated double-stranded DNA (dsDNA) as the substrate for DNMT1 with GlaI-assisted isothermal exponential amplification reaction (EXPAR) for rapid, simple, and sensitive detection of DNMT1 activity. The hemi-methylated dsDNA is fully methylated by DNMT1, and GlaI recognizes and cleaves the fully methylated sequence, generating terminal fragments that trigger EXPAR for efficient signal amplification. Whereas hemi-methylated dsDNA without DNMT1 will keep intact and cannot initiate EXPAR. DNMT1 activity can therefore be sensitively quantified by the real-time fluorescence signal of the DS-GlaI-EXPAR platform. The high-efficiency amplification of EXPAR and the recognition of GlaI enable the platform to overcome the inherent cumbersome and time-consuming shortcomings of traditional methods while meeting specificity and sensitivity. This DS-GlaI-EXPAR platform offers an impressively low limit of detection of 0.86 pg/μL and the entire detection process can be completed in a short time of 2.5 h in a single tube. Furthermore, DNMT1 activity detected by this platform in MCF-7 cells was significantly higher than that of HEK293 cells, and the inhibition of Apt. #9 was verified. This DNMT1 activity detection platform is very convenient and effective for the discovery of inhibitors and early cancer diagnosis.


Unexpected diagnosis of fetal abnormality: women's encounters with caregivers.
It is acknowledged that health professionals have difficulty with breaking bad news. However, relatively little research has been conducted on the experiences of women who have had a fetal anomaly detected at the routine pregnancy ultrasound examination. The study objective was to explore women's experiences of encounters with caregivers after the diagnosis of fetal anomaly at the routine second trimester ultrasound scan. The theoretical perspective of symbolic interactionism guided this study design. A purposive sample of 38 women, at low risk of fetal abnormality, who received a diagnosis of a fetal abnormality in a tertiary referral center in Ireland, were recruited to participate. An in-depth interview was conducted within 4-6 weeks of the diagnosis. Data were collected between April 2004 and August 2005 and analyzed using the constant comparative method. Six categories in relation to women's encounters with caregivers emerged: information sharing, timing of referral, getting to see the expert, describing the anomaly, availability of written information, and continuity of caregiver. Once an anomaly was suspected, women wanted information quickly, including prompt referral to the fetal medicine specialist for confirmation of the diagnosis. Supplementary written information was seen as essential to enhance understanding and to assist women in informing significant others. Continuity of caregiver and empathy from staff were valued strongly. The way in which adverse diagnoses are communicated to parents leaves room for improvement. Health professionals should receive specific education on how to break bad news sensitively to a vulnerable population. A specialist midwifery or nursing role to provide support for parents after diagnosis is recommended.


A cardiac implantable device infection by Raoultella planticola in an immunocompromized patient.
Introduction. Infection of cardiac implantable electronic devices is a severe condition associated with high mortality, particularly in patients who are dependent upon heart-pacing devices. Staphylococci are found in 70 % of reported cases. Case presentation. We report the case of a cardiac-pacemaker infection in a 79-year-old man, cumulating a history of rheumatoid arthritis treated by corticosteroids and methotrexate by a recently identified micro-organism: Raoultella planticola. He presented local signs of infection on his VVI pacemaker implantation site and underwent urgent pocket device replacement under cefamandole antibioprophylaxis. On incision thick pus oozed out. It was necessary to perform a complete hardware extraction comprising the pulse generator and the ancient lead. Pus was inoculated into aerobic and anaerobic culture vials and Gram staining unveiled Gram-negative rods. Microbiology analysis identified the organism as R. planticola. A new pacing device was inserted on the contrlateral pectoral region. Ciprofloxacin enabled full recovery. A literature review concerning this pathogen revealed that it is involved in severe infections such as bloodstream infections, peritonitis, cellulitis, pneumonia and lung abscesses, and urinary tract infections. In these case reports, underlying co-morbidities were identified such as solid active neoplasia, recent chemotherapy, corticosteroids, solid-organ-recipient patients and recent open surgery. Conclusion.R. planticola is a serious emerging pathogen and contributes to the burden of various infectious conditions. Its pathogenicity and occurrence should be known by clinicians and a high level of awareness is necessary to precisely identify it provide the correct antibiotic regimen.


Factors affecting smile esthetics in adults with different types of anterior overjet malocclusion.
This study aimed to quantitatively assess the relationship of smile esthetic variables with various types of malocclusion, and identify the cephalometric factors affecting smile measurements. This retrospective study included 106 patients who were treated with retention at the orthodontic department of Taipei Medical University Hospital. Hard-tissue variables were measured using lateral cephalographic tracings, and nine smile esthetic variables were measured using facial photographs. The patients were divided into three groups according to their overjet (< 0, 0-4, and > 4 mm). An analysis of variance was conducted to compare the pretreatment cephalometric variables and smile esthetic variables among the three groups. Multiple linear regression analysis was performed to identify the cephalometric factors affecting the smile measurements in each group. Except the upper midline and buccal corridor ratio, all of the smile measurements differed significantly among the three groups before orthodontic treatment. Some of the smile characteristics were correlated with the cephalometric measurements in different types of malocclusion. The overjet was the major factor influencing the smile pattern in all three types of malocclusion. Smile characteristics differ between different types of malocclusion; the smile may be influenced by skeletal pattern, dental procumbency, or facial type. These findings indicate that establishment of an optimal horizontal anterior teeth relationship is the key to improving the smile characteristics in different types of malocclusion.