Characteristics of Pediatric Pheochromocytoma/paraganglioma.
The "rule of 10" used to describe pheochromocytoma/paragangliomas (PCC/PGLs) has been challenged. However, recent studies suggested that pediatric PCC/PGLs may follow a pattern. Hence, we reviewed the available literature to verify the same. We searched PubMed, Scopus, ProQuest, and Google Scholar for studies describing the genotype and/or phenotype characteristics of pediatric PCC/PGL cohorts published after 2000 in English language and those with sample size more than 35 were included in this review. Pediatric PCC/PGLs were malignant in 10%, synchronous bilateral in 20%, extra-adrenal in 30%, among which, 30% were extra-abdominal and familial in 40%. PCC/PGL diagnosed during pediatric age recurs in 50% by 30 years of follow-up and 60% cases occur in boys. Seventy percent of children with PCC/PGL are likely to have sustained hypertension. Germline mutations could be identified in 80% of children with PCC/PGL and 90% are secretory. The review concludes that pediatric PCC/PGLs follow a pattern, which we call "10%-90% rule." This new rule will help easily remember the characteristics of pediatric PCC/PGLs.


Depression and prospection.
Prospection, the mental representation of possible futures, is usually adaptive. When it goes awry, however, it disrupts emotion and motivation. A negative view of the future is typically seen as one symptom of depression, but we suggest that such negative prospection is the core causal element of depression. Here, we describe the empirical evidence supporting this framework, and we explore the implications for clinical interventions. We integrate several literatures: Using the database PsycInfo, we retrieved empirical studies with the keywords prospection, prediction, expectation, pessimism, mental simulation, future-thinking, future-directed thinking, foresight, and/or mental time travel, in conjunction with depression, depressed, or depressive. Three kinds of faulty prospection, taken together, could drive depression: Poor generation of possible futures, poor evaluation of possible futures, and negative beliefs about the future. Depressed mood and poor functioning, in turn, may maintain faulty prospection and feed a vicious cycle. Future-oriented treatment strategies drawn from cognitive-behavioural therapy help to fix poor prospection, and they deserve to be developed further. Prospection-based techniques may lead to transdiagnostic treatment strategies for depression and other disorders.


Evaluation of Biopolymer Materials and Synthesis Techniques to Develop a Rod-Shaped Biopolymer Surrogate for Legionella pneumophila.
Biopolymer microparticles have been developed for applications that require biocompatibility and biodegradability, such as drug delivery. In this study, we assessed the production of microparticles using carnauba wax, κ-carrageenan, alginate, and poly (lactic-co-glycolic acid) (PLGA) with the aim of developing a novel, DNA-tracer-loaded, biopolymer surrogate with a size, shape, surface charge, and relative hydrophobicity similar to stationary-phase Legionella pneumophila to mimic the bacteria's mobility and persistence in engineered water systems. We found that the type and concentration of biopolymer, reaction conditions, and synthesis methods affected the morphology, surface charge, relative hydrophobicity, and DNA tracer loading efficiency of the biopolymer microparticles produced. Carnauba wax, κ-carrageenan, and alginate (Protanal®, and low and medium viscosity) produced highly polydisperse microspheres. In contrast, PLGA and alginate-CaCO3 produced uniform microspheres and rod-shaped microparticles, respectively, with high DNA tracer loading efficiencies (PLGA 70% and alginate-CaCO3 95.2 ± 5.7%) and high reproducibilities. Their synthesis reproducibility was relatively high. The relative hydrophobicity of PLGA microspheres closely matched the cell surface hydrophobicity of L. pneumophila but not the bacterial morphology, whereas the polyelectrolyte layer-by-layer assembly was required to enhance the relative hydrophobicity of alginate-CaCO3 microparticles. Following this surface modification, alginate-CaCO3 microparticles represented the best match to L. pneumophila in size, morphology, surface charge, and relative hydrophobicity. This new biopolymer surrogate has the potential to be used as a mimic to study the mobility and persistence of L. pneumophila in water systems where the use of the pathogen is impractical and unsafe.


The Nd:YAG laser in neurosurgery. Part 1. Laboratory investigations: dose-related biological response of neural tissue.
The biological response of normal cat brain to Nd:YAG laser light was studied both in vitro and in vivo to evaluate the potential safety of this laser for coagulation in brain tissue. Transmission studies revealed a blood:brain absorption ratio of 100:1 indicating the selective absorption of Nd:YAG light by hemoglobin and enabling Nd:YAG light to selectively heat blood vessels compared to brain tissue. In vivo temperature recordings and pathological evaluation demonstrated a remarkable ability of the brain to dissipate the thermal energy produced by Nd:YAG light with only a small amount of structural damage. Powers of 10 W applied for 8 seconds using a 1.2-mm focused probe resulted in a penetration depth in normal brain of only 2 mm. Thermal recordings also revealed that blood is heated to 90% of its maximum temperature within 3 seconds, while the brain temperature increases linearly as the duration of the laser pulse is increased. In addition, the localized heating of brain tissue was cooled rapidly within seconds following cessation of the laser pulse. These findings indicate that by using short, intermittent pulses of light focused upon blood vessels, damage to the surrounding tissue can be minimized, and the Nd:YAG laser can be used safely as an adjunctive measure for hemostasis in many neurosurgical procedures.


Girls' perception of physical environmental factors and transportation: reliability and association with physical activity and active transport to school.
Preliminary evidence suggests that the physical environment and transportation are associated with youth physical activity levels. Only a few studies have examined the association of physical environmental factors on walking and bicycling to school. Therefore, the purpose of this study was (1) to examine the test-retest reliability of a survey designed for youth to assess perceptions of physical environmental factors (e.g. safety, aesthetics, facilities near the home) and transportation, and (2) to describe the associations of these perceptions with both physical activity and active transport to school. Test and retest surveys, administered a median of 12 days later, were conducted with 480 sixth- and eighth-grade girls in or near six U.S. communities. The instrument consisted of 24 questions on safety and aesthetics of the perceived environment and transportation and related facilities. Additionally, girls were asked if they were aware of 14 different recreational facilities offering structured and unstructured activities, and if so, whether they would visit these facilities and the ease with which they could access them. Test-retest reliability was determined using kappa coefficients, overall and separately by grade. Associations with physical activity and active transport to school were examined using mixed model logistic regression (n = 610), adjusting for grade, race/ethnicity, and site. Item-specific reliabilities for questions assessing perceived safety and aesthetics of the neighborhood ranged from 0.31 to 0.52. Reliabilities of items assessing awareness of and interest in going to the 14 recreational facilities ranged from 0.47 to 0.64. Reliabilities of items assessing transportation ranged from 0.34 to 0.58. Some items on girls' perceptions of perceived safety, aesthetics of the environment, facilities, and transportation were important correlates of physical activity and, in some cases, active transport to school. This study provides some psychometric support for the use of the questionnaire on physical environmental factors and transportation for studying physical activity and active transport to school among adolescent girls. Further work can continue to improve reliability of these self-report items and examine their association of these factors with objectively measured physical activity.


Evaluation of Differential Sensitivity for Frequency, Intensity, and Duration around the Tinnitus Frequency in Adults with Tonal Tinnitus.
The perceptual characteristics of tinnitus are usually assessed by a matching procedure, where loudness and pitch of an external sound are matched to those of the tinnitus percept. The duration discrimination test (DDT), differential limen for intensity (DLI) and differential limen for frequency (DLF) are relatively simple psychoacoustic methods of measuring differential sensitivity. 15 participants with normal or minimal hearing loss with tinnitus in the age range of 18 to 40 years were enrolled in the present study. Pure tone audiometry (PTA), immittance audiometry and otoacoustic emissions were done to diagnose the degree of hearing loss. Duration discrimination test (DDT), differential limen for intensity (DLI) and differential limen for frequency (DLF) was administered on all the participants using MATLAB software (MLP toolbox) at the matched tinnitus frequency, half an octave below - above the frequency. The results show that there was a significant increase in DDT, DLI and DLF thresholds at the tinnitus frequency compared to half an octave above and below the matched frequency. The result suggests that differential sensitivity abilities regarding frequency, intensity, and duration are affected at the tinnitus frequency in individuals with tinnitus. The results of the study suggest that the differential sensitivity ability is affected in individuals with tinnitus especially at the frequency of tinnitus.


Homoplasious colony morphology and mito-nuclear phylogenetic discordance among Eastern Pacific octocorals.
Octocorals are a diverse and ecologically important group of cnidarians. However, the phylogenetic relationships of many octocoral groups are not well understood and are based mostly on mitochondrial sequence data. In addition, the discovery and description of new gorgonian species displaying unusual or intermediate morphologies and uncertain phylogenetic affinities further complicates the study of octocoral systematics and raises questions about the role played by processes such as plasticity, crypsis, and convergence in the evolution of this group of organisms. Here, we use nuclear (i.e. 28S rDNA) and mitochondrial (mtMutS) markers and a sample of Eastern Pacific gorgonians thought to be remarkable from a morphological point of view to shed light on the morphological diversification among these organisms. Our study reveals the loss of the anastomosed colony morphology in two unrelated lineages of the seafan genus Pacifigorgia and offers strong evidence for the independent evolution of a whip-like morphology in two lineages of Eastern Pacific Leptogorgia. Additionally, our data revealed one instance of mito-nuclear discordance in the genera Leptogorgia and Eugorgia, which may be the results of incomplete lineage sorting or ancient hybridization-introgression events. Our study stresses the importance of comprehensive taxonomic sampling and the use of independent sources of evidence to address the phylogenetic relationships and clarifying the evolution of octocorals.


A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis.
Ketoconazole (KET) and zinc pyrithione (ZPT) are compounds active against the Malassezia spp. yeasts, which are believed to play a major role in dandruff and seborrheic dermatitis. We compared the efficacy and safety of KET 2% and ZPT 1% in shampoo formulations for the alleviation of severe dandruff and seborrheic dermatitis. This open randomized, parallel-group trial began with a 2-week run-in phase during which subjects applied a neutral non-antidandruff shampoo. It was followed by a 4-week randomized treatment phase and a subsequent 4-week follow-up phase without treatment. Shampooing during the treatment period was carried out twice weekly for the KET group and at least twice weekly for the ZPT group in accordance with the label instructions. A total of 343 subjects were recruited to enter the trial. Of the 331 eligible volunteers, 171 were randomized to KET 2% and 160 to ZPT 1%. Clinical assessments were performed. Beneficial effects were evidenced for both medicated shampoos, but the effect was significantly better for KET 2%, which achieved a 73% improvement in the total dandruff severity score compared with 67% for ZPT 1% at week 4 (p < 0.02). The recurrence rate of the disease was also significantly lower following KET 2% treatment than following ZPT 1% treatment. As a consequence, the overall clearing of the skin condition at the end of treatment and follow-up phase was in favor of the KET 2% formulation (p = 0.004). Side effects were minimal. It is concluded that after a 4-week treatment, KET 2% shampoo was significantly superior to ZPT 1% shampoo in the treatment of subjects with severe dandruff or seborrheic dermatitis of the scalp. It is our assumption that this difference is noticeable for the patient and as a consequence relevant. Both formulations were well tolerated.


Decoupling scattering and absorption of turbid samples using a simple empirical relation between coefficients of the Kubelka-Munk and radiative transfer theories.
Efforts are underway to better understand the absorption properties of micro- and nano-sized particles due to their potential in various photonic applications. However, most of these particles exhibit strong scattering in the spectral regions of interest in addition to absorption. Due to strong interference from scattering, the absorption of these turbid samples cannot be directly measured using conventional spectroscopy techniques. The optical properties of these particles are also different from that of the bulk due to quantum confinement and plasmon resonance effects and cannot be inferred from their bulk properties. By measuring the total transmittance and total reflectance (diffuse and collimated) of turbid samples and using an empirical relation between the coefficients of the Kubelka-Munk and radiative transfer theories, we have demonstrated a method to calculate the absorption and reduced scattering coefficients of turbid samples. This method is capable of extracting the absorption coefficient of turbid samples with an error of 2%. Using this method, we have decoupled the specific absorption and specific reduced scattering coefficients of commercially available micro-sized iron oxide particles. The current method can be used to measure the optical properties of irregularly shaped particle dispersions, which are otherwise difficult to estimate theoretically.


Nonideal Transport and Extended Elution Tailing of PFOS in Soil.
The objective of this research was to examine the influence of nonideal sorption/desorption on the transport of polyfluorinated alkyl substances (PFASs) in soil, with a specific focus on characterizing and quantifying potential extended, mass-transfer-limited elution behavior. Perfluorooctane sulfonic acid (PFOS) was used as a representative PFAS, and miscible-displacement experiments were conducted with two soils comprising contrasting geochemical properties. The influence of nonlinear, rate-limited, hysteretic, and irreversible sorption/desorption on transport was investigated through experiments and model simulations. The breakthrough curves measured for PFOS transport in the two soils were asymmetrical and exhibited extensive elution tailing, indicating that sorption/desorption was significantly nonideal. The widely used two-domain sorption kinetics model could not fully simulate the observed transport behavior, whereas a multirate model employing a continuous distribution of sorption domains was successful. The overall results indicated that sorption/desorption was significantly rate-limited and that nonlinear, hysteretic, and irreversible sorption/desorption had minimal impact on PFOS transport. Comparison of PFOS transport data to data reported for two hydrophobic organic contaminants (HOCs) showed that the HOCs exhibited much more extensive elution tailing, likely reflecting differences in sorption/desorption mechanisms. The projected influence of rate-limited sorption/desorption on PFOS transport at the field scale was investigated through simulation. The results of the study suggest that rate-limited sorption/desorption may affect the field-scale transport of PFOS and other PFAS for systems influenced by transient or short-residence-time conditions and in some cases could possibly increase the amount of flushing required to reduce PFOS concentrations to levels below those associated with human-health concerns.


Colloidal particles for the delivery of steroid glycosides.
Water insoluble bioactive molecules with very high melting temperature and low solubility in water are difficult to formulate in food products. We demonstrate the synthesis of nanoscale particles from steroid glycosides using a facile liquid antisolvent precipitation method in the presence of various food grade stabilizers. Colloidal particles with sizes well below 200 nm are prepared from steroid glycosides containing extracts, as well as mixtures with phytosterol. In the mixtures, the formation of the typical for the phytosterol rod-like particles is suppressed. Particle size and structure are investigated by electron microscopy and dynamic light scattering. Due to the presence of surface charge and steric stabilization, colloidal particles do not display aggregation and are stable for a period of longer than one year. The results of this study are important for the formulation and delivery of steroid glycoside and phytosterol bioactive molecules in the fields of food, nutraceuticals, and medical applications.


Redundant expression of canonical Wnt ligands in human breast cancer cell lines.
Human breast cancer displays nuclear accumulation of beta-catenin and induction of cyclin D1 expression, which suggests that canonical Wnt/beta-catenin signaling is activated. In other cancers, the activation of canonical wnt/beta-catenin signaling is associated with APC, CTNNB1 or AXIN1 mutations. However, these mutations are rare or absent in breast cancer. In search of alternative mechanisms, we performed comprehensive expression analysis of Wnt signaling molecules, including 19 Wnt ligands, ten Frizzled receptors, two co-receptors and four Lef/TCF transcription factors in immortalized normal human mammary epithelial cells (HMEC) and six breast cancer cell lines. HMEC expressed all Frizzled receptors except FZD9 and FZD10. They also expressed LRP5 and LRP6 co-receptors, as well as four Lef/TCF transcription factors. HMEC cells also expressed many Wnt ligands, including WNT1, WNT2B, WNT3, WNT5A, WNT5B, WNT7B, WNT9A, WNT10B and WNT16. Redundant expression of Wnt ligands, Frizzled receptors, co-receptors and Lef/TCF transcription factors was maintained in breast cancer cell lines with some exceptions. The most important changes in cancer cell lines concerned Wnt ligand expression. We noticed that most breast cancer cell lines overexpressed WNT3A, WNT4, WNT6, WNT8B, WNT9A and WNT10B. In contrast, the expression of WNT5A, WNT5B and WNT16 was usually down-regulated. It is noteworthy that all six Wnt ligands that are overexpressed in malignant cell lines are known to signal through the canonical Wnt/beta-catenin signaling pathway, whereas down-regulated WNT5A and WNT5B ligands signal via the non-canonical pathway. The expression of both canonical Wnt ligands and most Frizzled receptors in breast cancer cell lines suggests that canonical Wnt/beta-catenin signaling is activated in these cell lines by an autocrine/paracrine mechanism. In support of this prediction, we observed nuclear beta-catenin accumulation and cyclin D1 induction in breast cancer cell lines, but not in HMEC. These results imply that ligand-dependent canonical Wnt/beta-catenin signaling is active in human breast cancer.


A multi-part matching strategy for mapping LOINC with laboratory terminologies.
To address the problem of mapping local laboratory terminologies to Logical Observation Identifiers Names and Codes (LOINC). To study different ontology matching algorithms and investigate how the probability of term combinations in LOINC helps to increase match quality and reduce manual effort. We proposed two matching strategies: full name and multi-part. The multi-part approach also considers the occurrence probability of combined concept parts. It can further recommend possible combinations of concept parts to allow more local terms to be mapped. Three real-world laboratory databases from Taiwanese hospitals were used to validate the proposed strategies with respect to different quality measures and execution run time. A comparison with the commonly used tool, Regenstrief LOINC Mapping Assistant (RELMA) Lab Auto Mapper (LAM), was also carried out. The new multi-part strategy yields the best match quality, with F-measure values between 89% and 96%. It can automatically match 70-85% of the laboratory terminologies to LOINC. The recommendation step can further propose mapping to (proposed) LOINC concepts for 9-20% of the local terminology concepts. On average, 91% of the local terminology concepts can be correctly mapped to existing or newly proposed LOINC concepts. The mapping quality of the multi-part strategy is significantly better than that of LAM. It enables domain experts to perform LOINC matching with little manual work. The probability of term combinations proved to be a valuable strategy for increasing the quality of match results, providing recommendations for proposed LOINC conepts, and decreasing the run time for match processing.


Chromosome landing at the bacterial blight resistance gene Xa4 locus using a deep coverage rice BAC library.
Xa4 is a dominantly inherited rice gene that confers resistance to Philippine race 1 of the bacterial blight pathogen Xanthomonas oryzae pv. oryzae in rice. In order to isolate the gene by positional cloning, a bacterial artificial chromosome (BAC) library was constructed from genomic DNA isolated from an Xa4-harboring accession, IRBB56. The library contains 55,296 clones with an average insert size of 132 kb, providing 14 rice genome equivalents. Three DNA markers closely linked to Xa4 were used to screen the library. The marker RS13, a resistance gene analogue that co-segregates with Xa4, identified 18 clones, of which four and six, respectively, were simultaneously detected by the other two markers, G181 and L1044. Fingerprinting and Southern analysis indicated that these clones overlapped and define an interval spanning 420 kb. In an F2 population derived from an indica variety, IR24, and its Xa4-containing near isogenic line (NIL), IRBB4, the susceptible plants were screened in order to map the Xa4 gene genetically and physically. Out of 24 insert ends isolated from the BACs in the contig, three revealed polymorphisms between IR24 and IRBB4. Two insert ends, 56M22F and 26D24R, flanked Xa4 on each side. Based on the overlap of the BACs, six overlapping clones were considered to include the Xa4 allele, one of which, 106P13, was chosen for further investigation.


Translation and validation of the German version of the Bournemouth Questionnaire for Neck Pain.
Clinical outcome measures are important tools to monitor patient improvement during treatment as well as to document changes for research purposes. The short-form Bournemouth questionnaire for neck pain patients (BQN) was developed from the biopsychosocial model and measures pain, disability, cognitive and affective domains. It has been shown to be a valid and reliable outcome measure in English, French and Dutch and more sensitive to change compared to other questionnaires. The purpose of this study was to translate and validate a German version of the Bournemouth questionnaire for neck pain patients. German translation and back translation into English of the BQN was done independently by four persons and overseen by an expert committee. Face validity of the German BQN was tested on 30 neck pain patients in a single chiropractic practice. Test-retest reliability was evaluated on 31 medical students and chiropractors before and after a lecture. The German BQN was then assessed on 102 first time neck pain patients at two chiropractic practices for internal consistency, external construct validity, external longitudinal construct validity and sensitivity to change compared to the German versions of the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD). Face validity testing lead to minor changes to the German BQN. The Intraclass Correlation Coefficient for the test-retest reliability was 0.99. The internal consistency was strong for all 7 items of the BQN with Cronbach α's of .79 and .80 for the pre and post-treatment total scores. External construct validity and external longitudinal construct validity using Pearson's correlation coefficient showed statistically significant correlations for all 7 scales of the BQN with the other questionnaires. The German BQN showed greater responsiveness compared to the other questionnaires for all scales. The German BQN is a valid and reliable outcome measure that has been successfully translated and culturally adapted. It is shorter, easier to use, and more responsive to change than the NDI and NPAD.


Hypokalemia.
Hypokalemia is an electrolyte imbalance that can have serious effects on the patient if not detected early. Therefore, it is important for the nurse to: (1) be aware of those patients at risk for excess potassium loss, (2) monitor those patients' ECG to observe for any changes indicative of hypokalemia, and (3) assess for physical signs and symptoms indicative of hypokalemia. Early detection of hypokalemia and early intervention will prevent potential catastrophic events.


Comparative ecology of North Atlantic shores: do differences in players matter for process?
The contrasting histories of the western and eastern shores of the North Atlantic Ocean provide an excellent opportunity to consider the implications of past events for present ecological processes and the functioning of marine ecosystems. Similarities and differences in assemblage composition have been driven by large-scale events, such as the trans-Arctic interchange, which has shaped the species pool, and cycles of glaciation, which have determined phases of local or regional extinction and colonization. More recently, anthropogenically induced invasions and local extinctions have significantly altered biogeographic distributions. Here we consider for both hard and soft substrata how the presence or absence of key taxa influences the outcomes of trophic and other biological interactions, and evaluate the consequences for community structure and ecosystem functioning. On intertidal hard substratum shores, biodiversity of epilithic microphagous grazers differs across latitudinal and longitudinal scales. Diversity is high in southern Europe but declines to the north and across the Atlantic. Lower diversity and the absence of patellid limpets in Iceland and the northwest Atlantic compared to Europe result in differences in consumer pressure, and an apparent contrast in the importance of herbivory vs. competitive interactions and predation pressure as community structuring processes. Interestingly, despite differences in "process," community patterns are remarkably similar between the east and west. On soft sediment shores, there are conspicuous geographic differences in importance of bioturbators and large digging predators. Hemichordates can be abundant and important infaunal bioturbators in the western Atlantic, but they generally play a much reduced role in the eastern Atlantic. In addition, the number and diversity of digging predators on western Atlantic shores is high; the horseshoe crab, swimming portunid crabs, large whelks, excavating waterfowl, and an abundance of skates and rays exert intense predation pressure and associated biogenic disturbance to sediments. In Europe, except for excavating waterfowl these taxa are rare or absent. Thus, the importance of large, biological agents of disturbance is lower on European shores as a consequence of both recent anthropogenic pressure and natural processes over larger time scales. Consideration of key structuring taxa over the Atlantic shows that human-mediated transport has had considerable influence. Faunas on both sides of the Atlantic are becoming more similar to the point that some of the key differences in assemblage composition and hence community organization have blurred. Recent introductions as well as planned experimental manipulations provide the opportunity to understand the role of species identity in determining community structure and ecosystem functioning over large spatial scales; the North Atlantic may be an ideal test system to explore these areas.


Sludge reduction by direct addition of chlorine dioxide into a sequencing batch reactor under operational mode of repeatedly alternating aeration/non-aeration.
The effect of direct addition of chlorine dioxide (ClO2) into a repeatedly alternating aeration/non-aeration sequencing batch reactor (SBR) on its sludge reduction and process performance was investigated. The experimental results showed that the sludge reduction efficiency was 32.9% and the observed growth yield (Yobs) of SBR was 0.11 kg VSS (volatile suspended solids) /kg COD (chemical oxygen demand) for 80 days' operation at the optimum ClO2 dosage of 2.0 mg/g TSS (total suspended solids). It was speculated that cell lysis and cryptic growth, uncoupled metabolism and endogenous metabolism were jointly responsible for the sludge reduction in this study. COD, NH3-N, total nitrogen (TN) and total phosphorus (TP) in the effluent increased on average 29.47, 4.44, 1.97 and 0.05 mg/L, respectively. However, the effluent quality still satisfied the first-class B discharge standards for municipal wastewater treatment plants in China. In that case, the sludge maintained fine viability with the specific oxygen uptake rate (SOUR) being 14.47 mg O2/(g VSS·h) and demonstrated good settleability with the sludge volume index (SVI) being 116 mL/g. The extra cost of sludge reduction at the optimum ClO2 dosage was estimated to be 2.24 CNY (or 0.36 dollar)/kg dry sludge.


Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity.
Hepatic involvement is commonly observed in arenavirus infections, but the viral determinants of liver disease are only partially understood. Here we exploited newly developed reverse-genetic techniques with Lymphocytic choriomeningitis virus (LCMV), the prototype arenavirus, to address specifically the contribution of the viral glycoprotein (GP) to liver pathogenicity. It is well established that strain WE, but not ARM, causes hepatitis in mice. We found that this property correlated with the superior capacity of WE to propagate in cultured macrophages and hepatocyte-derived cells. In mice, the ability to establish prolonged viraemia allowed the virus to propagate from initially infected Kupffer cells in the liver to neighbouring hepatocytes that underwent apoptosis. Reverse-genetic replacement of the GP in strain ARM with WE-GP resulted in only a very modest increase in liver pathogenicity, if any. Yet, an ARM-derived variant virus with a mutated polymerase gene caused severe liver disease when engineered to display WE-GP but considerably less when expressing ARM-GP. This reverse-genetic approach to an animal model of arenaviral hepatitis reveals a previously underestimated contributory role of the GP that alone is, however, insufficient to cause disease.


Optimization of green fluorescent protein expression vectors for in vitro and in vivo detection of Listeria monocytogenes.
The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is a useful reporter molecule for monitoring in vivo gene expression in eukaryotic and prokaryotic cells. We constructed a series of GFP vectors for in situ detection of the intracellular pathogen Listeria monocytogenes. The gfp-mutl gene, which encodes a red-shifted GFP, was transcriptionally fused to a strong L. monocytogenes promoter and inserted into various Escherichia coli-Listeria shuttle vectors: i) the integrative monocopy plasmid pAT113; ii) the low copy number plasmid pTCV-Exl; iii) the high copy number plasmid pAT18. Listeria cells harboring pNF6 and pNF7, constructed from pAT113 and pTCV-Exl, respectively, gave low fluorescence intensities, and were optically detected in cultured macrophages, but not in tissue sections. The fluorescence of Listeria with the pAT18 derivative pNF8 was about 40 times greater than that with pNF6 and 15 times greater than that with pNF7. Listeria cells harboring pNF8 were readily detected in both cultured macrophages and tissue sections. Constructed GFP vectors did not affect the virulence of L. monocytogenes in a murine model of infection.


Pharmacological agents (anti-inflammatory and analgesic) for managing symptoms in people with cystic fibrosis-related arthritis.
Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Date of most recent search: September 2007. Randomised controlled trials which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis. Studies should also better define the two conditions. A study has recently been conducted in CFA and may help fill this gap when analysed and published.


A mobile field-work data collection system for the wireless era of health surveillance.
In many countries or regions the capacity of health care resources is below the needs of the population and new approaches for health surveillance are needed. Innovative projects, utilizing wireless communication technology, contribute to reliable methods for field-work data collection and reporting to databases. The objective was to describe a new version of a wireless IT-support system for field-work data collection and administration. The system requirements were drawn from the design objective and translated to system functions. The system architecture was based on fieldwork experiences and administrative requirements. The Smartphone devices were HTC Touch Diamond2s, while the system was based on a platform with Microsoft .NET components, and a SQL Server 2005 with Microsoft Windows Server 2003 operating system. The user interfaces were based on .NET programming, and Microsoft Windows Mobile operating system. A synchronization module enabled download of field data to the database, via a General Packet Radio Services (GPRS) to a Local Area Network (LAN) interface. The field-workers considered the here-described applications user-friendly and almost self-instructing. The office administrators considered that the back-office interface facilitated retrieval of health reports and invoice distribution. The current IT-support system facilitates short lead times from fieldwork data registration to analysis, and is suitable for various applications. The advantages of wireless technology, and paper-free data administration need to be increasingly emphasized in development programs, in order to facilitate reliable and transparent use of limited resources.


Walls talk: Microbial biogeography of homes spanning urbanization.
Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households' increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes-which could increase transmission of potential pathogens-and decrease exposure to the environmental microbes with which humans have coevolved.


Does Homeostatic Sleep Pressure Buildup Explain Objective Excessive Daytime Sleepiness in Adults With ADHD? An Exploratory Study.
Background: Excessive daytime sleepiness (EDS) is central in Attention deficit hyperactivity disorder (ADHD) but its causes remain unclear. The aim of this study was to explore objective EDS and homeostatic sleep pressure buildup, evaluated by power theta-alpha frequency (PTAF), in drug-free sleepy adults with ADHD and controls. Methods: Participants were placed during a 36-h period of extended wakefulness under constant routine protocol to strictly control sleep time, sleep duration, and circadian zeitgebers. Results: Eight drug-free sleepy patients with ADHD and 7 matched controls were included. The ADHD group had significantly shorter sleep latency on the Maintenance of Wakefulness Test (MWT) throughout extended wakefulness than the control group. There was no significant difference between the groups in PTAF evolution during extended wakefulness and in kinetic sleep pressure buildup, evaluated by the time constant of saturating exponential function. Limitations: The sample was small, so the findings cannot be generalized. Moreover, psychiatric comorbidities and circadian regulation should be taken into account in future studies. Conclusion: In very controlled conditions, mean sleep latency on the MWT during the whole extended wakefulness was significantly shorter in sleepy patients with ADHD than in control subjects. However, the difficulty to remain awake during soporific circumstances observed in these patients with ADHD cannot be explained by changes in the kinetic of sleep pressure buildup. Clinical Trials Registration: www.clinicaltrials.gov/, Identifier: NCT02217371.


A proposed approach to accelerate evidence generation for genomic-based technologies in the context of a learning health system.
Genomic technologies should demonstrate analytical and clinical validity and clinical utility prior to wider adoption in clinical practice. However, the question of clinical utility remains unanswered for many genomic technologies. In this paper, we propose three building blocks for rapid generation of evidence on clinical utility of promising genomic technologies that underpin clinical and policy decisions. We define promising genomic tests as those that have proven analytical and clinical validity. First, risk-sharing agreements could be implemented between payers and manufacturers to enable temporary coverage that would help incorporate promising technologies into routine clinical care. Second, existing data networks, such as the Sentinel Initiative and the National Patient-Centered Clinical Research Network (PCORnet) could be leveraged, augmented with genomic information to track the use of genomic technologies and monitor clinical outcomes in millions of people. Third, endorsement and engagement from key stakeholders will be needed to establish this collaborative model for rapid evidence generation; all stakeholders will benefit from better information regarding the clinical utility of these technologies. This collaborative model can create a multipurpose and reusable national resource that generates knowledge from data gathered as part of routine care to drive evidence-based clinical practice and health system changes.


Recognising falls risk in older adult mental health patients and acknowledging the difference from the general older adult population.
Older adults admitted to inpatient mental health units present with complex mental health care needs which are often compounded by the challenges of living with physical co-morbidities. They are a mobile population and a high risk group for falling during hospitalisation. To address quality and safety concerns around the increased risk for falls, a qualitative research study was completed to obtain an improved understanding of the factors that increase the risk of falling in this patient cohort. Focus groups were conducted with mental health professionals working across older adult mental health services in metropolitan Western Australia. Data were analysed using content analysis and three themes emerged that were significant concepts relevant to falls risk in this patient group. These themes were (1) limitations of using generic falls risk assessment and management tools, (2) assessment of falls risk not currently captured on standardised tools, and (3) population specific causes of falls. The findings demonstrate that older adult mental health patients are a highly mobile group that experience frequent changes in cognition, behaviour and mental state. The mix of patients with organic or functional psychiatric disorders within the same environment also presents complex and unique care challenges and multi-disciplinary collaboration is central to reduce the risk of falls. As this group of patients are also frequently admitted to both general inpatient and aged care settings, the findings are relevant to the assessment and management of falls risk across all health care settings.


Pieces-of-parts for supervoxel segmentation with global context: Application to DCE-MRI tumour delineation.
Rectal tumour segmentation in dynamic contrast-enhanced MRI (DCE-MRI) is a challenging task, and an automated and consistent method would be highly desirable to improve the modelling and prediction of patient outcomes from tissue contrast enhancement characteristics - particularly in routine clinical practice. A framework is developed to automate DCE-MRI tumour segmentation, by introducing: perfusion-supervoxels to over-segment and classify DCE-MRI volumes using the dynamic contrast enhancement characteristics; and the pieces-of-parts graphical model, which adds global (anatomic) constraints that further refine the supervoxel components that comprise the tumour. The framework was evaluated on 23 DCE-MRI scans of patients with rectal adenocarcinomas, and achieved a voxelwise area-under the receiver operating characteristic curve (AUC) of 0.97 compared to expert delineations. Creating a binary tumour segmentation, 21 of the 23 cases were segmented correctly with a median Dice similarity coefficient (DSC) of 0.63, which is close to the inter-rater variability of this challenging task. A second study is also included to demonstrate the method's generalisability and achieved a DSC of 0.71. The framework achieves promising results for the underexplored area of rectal tumour segmentation in DCE-MRI, and the methods have potential to be applied to other DCE-MRI and supervoxel segmentation problems.


The emergence of the volume transmission concept.
Interneuronal communication in the central nervous system (CNS) have always been of basic importance for theories on the cerebral morphofunctional architecture. Our group has proposed that intercellular communication in the brain can be grouped into 2 broad classes based on some general features of the transmission: wiring (WT) and volume (VT) transmission. WT occurs via a relatively constrained cellular chain (wire), while VT consists of 3-dimensional diffusion of signals in the extracellular fluid (ECF) for distances larger than the synaptic cleft. Both morphological and functional evidence indicates that dopamine (DA) synapses in striatum are 'open' synapses, i.e., synapses which favor diffusion of the transmitter into the surrounding ECF and observations are compatible with the view that DA varicosities can synthesize, store and release DA for VT. The DAergic mesostriatal transmission has, therefore, been examined by several groups to give experimental support to VT. Moreover, due to its minor structural requirements, VT may become prevalent under some pathological conditions, e. g. Parkinson's disease. In animal models of DAergic pathway degeneration, it has been shown that a compensatory activation of surviving DA terminals may lead to a preferential potentiation of VT. WT and VT favor different and complementary types of computation. VT is markedly slower and less safe than WT, but has minor spatial constraints and allows the reach of a large number of targets. Models of neuronal systems integrating classical neuronal circuits and diffusible signals begin to show how WT and VT may interact in the neural tissue.


A novel, immortal, and multipotent human neural stem cell line generating functional neurons and oligodendrocytes.
The discovery and study of neural stem cells have revolutionized our understanding of the neurogenetic process, and their inherent ability to adopt expansive growth behavior in vitro is of paramount importance for the development of novel therapeutics based on neural cell replacement. Recent advances in high-throughput assays for drug development and gene discovery dictate the need for rapid, reproducible, long-term expansion of human neural stem cells (hNSCs). In this view, the complement of wild-type cell lines currently available is insufficient. Here we report the establishment of a stable human neural stem cell line (immortalized human NSCs [IhNSCs]) by v-myc-mediated immortalization of previously derived wild-type hNSCs. These cells demonstrate three- to fourfold faster proliferation than wild-type cells in response to growth factors but retain rather similar properties, including multipotentiality. By molecular biology, biochemistry, immunocytochemistry, fluorescence microscopy, and electrophysiology, we show that upon growth factor removal, IhNSCs completely downregulate v-myc expression, cease proliferation, and differentiate terminally into three major neural lineages: astrocytes, oligodendrocytes, and neurons. The latter are functional, mature cells displaying clear-cut morphological and physiological features of terminally differentiated neurons, encompassing mostly the GABAergic, glutamatergic, and cholinergic phenotypes. Finally, IhNSCs produce bona fide oligodendrocytes in fractions up to 20% of total cell number. This is in contrast to the negligible propensity of hNSCs to generate oligodendroglia reported so far. Thus, we describe an immortalized hNSC line endowed with the properties of normal hNSCs and suitable for developing the novel, reliable assays and reproducible high-throughput gene and drug screening that are essential in both diagnostics and cell therapy studies.


Defining and measuring the patient-centered medical home.
The patient-centered medical home (PCMH) is four things: 1) the fundamental tenets of primary care: first contact access, comprehensiveness, integration/coordination, and relationships involving sustained partnership; 2) new ways of organizing practice; 3) development of practices' internal capabilities, and 4) related health care system and reimbursement changes. All of these are focused on improving the health of whole people, families, communities and populations, and on increasing the value of healthcare. The value of the fundamental tenets of primary care is well established. This value includes higher health care quality, better whole-person and population health, lower cost and reduced inequalities compared to healthcare systems not based on primary care. The needed practice organizational and health care system change aspects of the PCMH are still evolving in highly related ways. The PCMH will continue to evolve as evidence comes in from hundreds of demonstrations and experiments ongoing around the country, and as the local and larger healthcare systems change. Measuring the PCMH involves the following: Giving primacy to the core tenets of primary care. Assessing practice and system changes that are hypothesized to provide added value Assessing development of practices' core processes and adaptive reserve. Assessing integration with more functional healthcare system and community resources. Evaluating the potential for unintended negative consequences from valuing the more easily measured instrumental features of the PCMH over the fundamental relationship and whole system aspects. Recognizing that since a fundamental benefit of primary care is its adaptability to diverse people, populations and systems, functional PCMHs will look different in different settings. Efforts to transform practice to patient-centered medical homes must recognize, assess and value the fundamental features of primary care that provide personalized, equitable health care and foster individual and population health.


Six novel deleterious and three neutral mutations in the gene encoding the alpha-subunit of hexosaminidase A in non-Jewish individuals.
Initial investigations demonstrated that only 3/34 "Tay-Sachs chromosomes" in 22 unrelated, non-Jewish patients or carriers of some form of GM2-gangliosidosis (7 black and 15 non-Jewish Caucasian) had either of the two mutations commonly found in the Jewish population. To determine the nature and incidence of the alterations in this non-Jewish population we have utilized PCR, single-strand conformation polymorphism analysis and sequencing to detect new mutations in genomic DNA. Fourteen primer sets have been utilized to analyze 80% of the coding region and 23/26 splice sites of the gene coding for the alpha chain of hexosaminidase A. Presumed deleterious mutations were discovered in 17/34 chromosomes believed to be carrying a beta-hexosaminidase A alpha-subunit gene mutation. Ten had abnormalities which have been described previously. In the remaining 24 Tay-Sachs disease alleles, six novel mutations predicted to be deleterious were discovered. These include two small deletions (a single-base frameshift and a three-base deletion removing an amino acid), two different nonsense mutations, an initiation codon mutation (ATG----GTG), and a missense mutation (Arg499Cys) in a highly conserved residue. In addition, three presumed nondeleterious mutations were found.


Removal and recovery of phosphate from municipal wastewaters using a polymeric anion exchanger bound with hydrated ferric oxide nanoparticles.
A new type of ion exchange media which is highly selective for phosphate, and can be easily regenerated has been investigated. The media consists of hydrated ferric oxide nanoparticles dispersed within the pore structures of polymeric anion exchanger beads. The media combines the durability and mechanical strength of ion exchange resins with the high sorption capacity of ferric oxide for phosphate. The media was trialled in fixed bed mini column experiments with real final effluent from two UK sewage treatment works, one with treatment based on chemical precipitation with iron chloride salts into an activated sludge process (population >250,000), and one based on trickling filter treatment with no specific phosphorus removal process (population <10,000). Results show that the media has high capacity for removing phosphate, reaching capacity at 4000 and 1300 bed volumes for the chemical precipitation and trickling filter works respectively, with performance greatly exceeding that of a standard anion exchanger, Amberlite IRA-410. Also trialled was the media's ability to elute the phosphorus after breakthrough, with the aim of recovering and processing it into a useful product. A one step regenerative process using a single solution containing 4% NaOH and 2% NaCl was passed through the resin bed and the phosphorus concentration of each bed volume leaving the column analysed. 80% of the phosphorus was eluted in the first bed volume. Subsequent tests investigated the performance of the media after successive partial regenerations of one bed volume of the NaOH/NaCl solution. There was no loss of performance observed after ten regeneration cycles, and levels of eluted phosphate were consistently high. These results suggest that the media has high potential for the removal and recovery of phosphate from wastewater streams. Additionally, the small volume of regenerant required translates to a very small operational footprint.


Drawing experts have better visual memory while drawing.
Drawing involves frequent shifts of gaze between the original and the drawing and visual memory helps compare the original object and the drawing across these gaze shifts while creating and correcting the drawing. It remains unclear whether this memory encodes all of the object or only the features around the current drawing position and whether both the original and the copy are equally well represented. To address these questions, we designed a "drawing" experiment coupled with a change detection task. A polygon was displayed on one screen and participants had to copy it on another, with the original and the drawing presented in alternation. At unpredictable moments during the copying process, modifications were made on the drawing and the original figure (while they were not in view). Participants had to correct their drawing every time they perceived a change so that their drawing always matched the current original figure. Our results show a better memory representation of the original figure than of the drawing, with locations relevant to the current production most accurately represented. Critically, experts showed better memory for both the original and the drawing than did novices, suggesting that experts have specialized advantages for encoding visual shapes.


The Hamilton scales and the Hopkins Symptom Checklist (SCL-90). A cross-national validity study in patients with panic disorders.
The HRSD, HRSA, SCL-90 scales were psychometrically investigated in a cross-national sample of patients with varieties of non-psychotic symptoms of anxiety and depression. Across the cultural backgrounds the scores obtained from the original versions of these scales are not sufficient statistics. However, latent structure analysis has identified homogeneous subscales for depression (the HRSD) and for discomfort (an SCL subscale). High concurrent validity was found between the subscales of depression, anxiety and discomfort. In international research, inhomogeneity among scale items can be confounded with group differences which are usually ascribed to drug differences.


Impact of Indian Total Sanitation Campaign on latrine coverage and use: a cross-sectional study in Orissa three years following programme implementation.
Faced with a massive shortfall in meeting sanitation targets, some governments have implemented campaigns that use subsidies focused on latrine construction to overcome income constraints and rapidly expand coverage. In settings like rural India where open defecation is common, this may result in sub-optimal compliance (use), thereby continuing to leave the population exposed to human excreta. We conducted a cross-sectional study to investigate latrine coverage and use among 20 villages (447 households, 1933 individuals) in Orissa, India where the Government of India's Total Sanitation Campaign had been implemented at least three years previously. We defined coverage as the proportion of households that had a latrine; for use we identified the proportion of households with at least one reported user and among those, the extent of reported use by each member of the household. Mean latrine coverage among the villages was 72% (compared to <10% in comparable villages in the same district where the Total Sanitation Campaign had not yet been implemented), though three of the villages had less than 50% coverage. Among these households with latrines, more than a third (39%) were not being used by any member of the household. Well over a third (37%) of the members of households with latrines reported never defecating in their latrines. Less than half (47%) of the members of such households reported using their latrines at all times for defecation. Combined with the 28% of households that did not have latrines, it appears that most defecation events in these communities are still practiced in the open. A large-scale campaign to implement sanitation has achieved substantial gains in latrine coverage in this population. Nevertheless, gaps in coverage and widespread continuation of open defecation will result in continued exposure to human excreta, reducing the potential for health gains.


Ellagitannin-rich bioactive extracts of Tuberaria lignosa: insights into the radiation-induced effects in the recovery of high added-value compounds.
Ellagitannins are polyphenols responsible for a number of bioactivities and health-promoting effects. These industrially important molecules can be affected by post-harvest treatments and recovery processes, but little is known about the irradiation-induced effects on their integrity, bioactivity and extractability. Herein, the impact of gamma radiation on the production of ellagitannin-rich extracts was investigated using Tuberaria lignosa as a case study. These effects were compared with those induced in flavonoids and organic acids. The extracts were particularly rich in hydrophilic antioxidants (measured by in vitro assays). The recovery of different phytochemicals was favoured by longer extraction times. Ellagitannins (mainly punicalagin derivatives) were extracted better from samples irradiated at 5 kGy and were not significantly affected by the 10 kGy dose. However, the total contents of flavonoids and organic acids were decreased by the consequent increase in irradiation dose. Therefore, this study supports the use of gamma radiation for processing T. lignosa, aiming to obtain ellagitannin-rich bioactive extracts.


Forecasting Effusive Dynamics and Decompression Rates by Magmastatic Model at Open-vent Volcanoes.
Effusive eruptions at open-conduit volcanoes are interpreted as reactions to a disequilibrium induced by the increase in magma supply. By comparing four of the most recent effusive eruptions at Stromboli volcano (Italy), we show how the volumes of lava discharged during each eruption are linearly correlated to the topographic positions of the effusive vents. This correlation cannot be explained by an excess of pressure within a deep magma chamber and raises questions about the actual contributions of deep magma dynamics. We derive a general model based on the discharge of a shallow reservoir and the magmastatic crustal load above the vent, to explain the linear link. In addition, we show how the drastic transition from effusive to violent explosions can be related to different decompression rates. We suggest that a gravity-driven model can shed light on similar cases of lateral effusive eruptions in other volcanic systems and can provide evidence of the roles of slow decompression rates in triggering violent paroxysmal explosive eruptions, which occasionally punctuate the effusive phases at basaltic volcanoes.


Hybrid Nanocellulose-Copper (II) Oxide as Engine Oil Additives for Tribological Behavior Improvement.
Friction and wear are the main factors in the failure of the piston in automobile engines. The objective of this work was to improve the tribological behaviour and lubricant properties using hybrid Cellulose Nanocrystal (CNC) and Copper (II) oxide nanoparticles blended with SAE 40 as a base fluid. The two-step method was used in the hybrid nanofluid preparation. Three different concentrations were prepared in a range of 0.1% to 0.5%. Kinematic viscosity and viscosity index were also identified. The friction and wear behavior were evaluated using a tribometer based on ASTM G181. The CNC-CuO nano lubricant shows a significant improvement in term of viscosity index by 44.3-47.12% while for friction, the coefficient of friction (COF) decreases by 1.5%, respectively, during high and low-speed loads (boundary regime), and 30.95% during a high-speed, and low load (mixed regime). The wear morphologies results also show that a smoother surface was obtained after using CNC-CuO nano lubricant compared to SAE 40.


Catabolism of neurotensin in the epithelial layer of porcine small intestine.
The mammalian small intestine is both a source and a site of degradation of neurotensin. Metabolites produced by incubation of the peptide with dispersed enterocytes from porcine small intestine were isolated by high-performance liquid chromatography and identified by amino-acid analysis. The principal sites of cleavage were at the Tyr-11-Ile-12 bond, generating neurotensin-(1-11), and at the Pro-10-Tyr-11 bond, generating neurotensin-(1-10). The corresponding COOH-terminal fragments, neurotensin-(11-13) and -(12-13) were metabolized further. Formation of neurotensin-(1-11) and -(1-10) was completely inhibited by phosphoramidon (Ki = 6 nM), an inhibitor of endopeptidase 24.11, but not by captopril, an inhibitor of peptidyl dipeptidase A. Incubation of neurotensin with purified endopeptidase 24.11 from pig stomach also resulted in cleavage of the Tyr-11-Ile-12 and Pro-10-Tyr-11 bonds. A minor pathway of cell-surface-mediated degradation was the phosphoramidon-insensitive cleavage of the Tyr-3-Glu-4 bond, generating neurotensin-(1-3) and neurotensin-(4-13). No evidence for specific binding sites (putative receptors) for neurotensin was found either on the intact enterocyte or on vesicles prepared from the basolateral membranes of the cells. Neurotensin-(1-8), the major circulating metabolite, was not formed when neurotensin(1-13) was incubated with cells, but represented a major metabolite (together with neurotensin-(1-10] when neurotensin-(1-11) was used as substrate. The study has shown that degradation of neurotensin in the epithelial layer of the small intestine is mediated principally through the action of endopeptidase 24.11, but this enzyme is probably not responsible for the production of the neurotensin fragments detected in the circulation.


The Relationship Between Parental Affective Temperament Traits and Disruptive Behavior Disorders Symptoms in Children With ADHD.
This study investigated the relationship between parental affective temperaments and the oppositional defiant disorder (ODD) and conduct disorder (CD) symptoms of children with ADHD. The sample consisted of 542 treatment-naive children with ADHD and their biological parents. Children were assessed via both parent- and teacher-rated behavioral disorder scales. Parental affective temperament and ADHD symptoms were measured by self-report inventories. The relationships between psychiatric variables were evaluated using structural equation modeling. According to parent-rated behavioral disorder scales, paternal cyclothymic and maternal irritable temperaments were associated with ODD scores, and maternal depressive temperament was associated with CD scores. In terms of teacher-rated behavioral disorder scales, maternal anxious temperament was associated with ODD scores, and paternal cyclothymic and maternal depressive temperaments were associated with CD scores. These results suggest that certain parental affective temperaments are related to an increase in symptoms of disruptive behavioral disorders in children with ADHD.


Hydrophilic and Functionalized Nanographene Oxide Incorporated Faster Dissolving Megestrol Acetate.
The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37 °C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T50 and T80, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T50 did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.


Pharmacological interventions for cognitive decline in people with Down syndrome.
People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear. To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome. In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies. Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment. Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary. Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures. Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.


Alternative Ultrasound-Assisted Method for the Extraction of the Bioactive Compounds Present in Myrtle (Myrtus communis L.).
The bioactive compounds in myrtle berries, such as phenolic compounds and anthocyanins, have shown a potentially positive effect on human health. Efficient extraction methods are to be used to obtain maximum amounts of such beneficial compounds from myrtle. For that reason, this study evaluates the effectiveness of a rapid ultrasound-assisted method (UAE) to extract anthocyanins and phenolic compounds from myrtle berries. The influence of solvent composition, as well as pH, temperature, ultrasound amplitude, cycle and solvent-sample ratio on the total phenolic compounds and anthocyanins content in the extracts obtained were evaluated. The response variables were optimized by means of a Box-Behnken design. It was found that the double interaction of the methanol composition and the cycle, the interaction between methanol composition and temperature, and the interaction between the cycle and solvent-sample ratio were the most influential variables on the extraction of total phenolic compounds (92.8% methanol in water, 0.2 s of cycle, 60 °C and 10:0.5 mL:g). The methanol composition and the interaction between methanol composition and pH were the most influential variables on the extraction of anthocyanins (74.1% methanol in water at pH 7). The methods that have been developed presented high repeatability and intermediate precision (RSD < 5%) and the bioactive compounds show a high recovery with short extraction times. Both methods were used to analyze the composition of the bioactive compounds in myrtle berries collected from different locations in the province of Cadiz (Spain). The results obtained by UAE were compared to those achieved in a previous study where microwave-assisted extraction (MAE) methods were employed. Similar extraction yields were obtained for phenolic compounds and anthocyanins by MAE and UAE under optimal conditions. However, UAE presents the advantage of using milder conditions for the extraction of anthocyanins from myrtle, which makes of this a more suitable method for the extraction of these degradable compounds.


PI-RADS v2: Current standing and future outlook.
The Prostate Imaging-Reporting and Data System (PI-RADS) was created in 2012 to establish standardization in prostate multiparametric magnetic resonance imaging (mpMRI) acquisition, interpretation, and reporting. In hopes of improving upon some of the PI-RADS v1 shortcomings, the PI-RADS Steering Committee released PI-RADS v2 in 2015. This paper reviews the accuracy, interobserver agreement, and clinical outcomes of PI-RADS v2 and comments on the limitations of the current literature. Overall, PI-RADS v2 shows improved sensitivity and similar specificity compared to PI-RADS v1. However, concerns exist regarding interobserver agreement and the heterogeneity of the study methodology.


Effect of L-glutamic acid N,N-diacetic acid on the availability of dietary zinc in broiler chickens.
Chelating agents can be used to improve the nutritional availability of trace minerals within the gastrointestinal tract. This study was conducted to determine the effect of a novel chelating agents, L-glutamic acid N,N-diacetic acid (GLDA), a biodegradable alternative to ethylenediaminetetraacetic acid on the nutritional bioavailability of zinc in broilers. Twelve dietary treatments were allocated to 96 pens in a randomized block design. Pens contained 10 Ross 308 male broilers in a factorial design with 6 incremental zinc levels (40, 45, 50, 60, 80, and 120 ppm of total Zn), with and without inclusion of GLDA (0 and 100 ppm) as respective factors. Experimental diets were supplied from day 7 to 21/22 and serum, liver and tibia Zn content were determined in 3 birds per pen. Growth performance and liver characteristics were not affected by dietary treatments, but both supplemental Zn and GLDA enhanced tibia and serum zinc concentration. The positive effect of GLDA was observed at all levels of the dietary Zn addition. The amount of zinc needed to reach 95% of the asymptotic Zn response was determined using nonlinear regression. When GLDA was included in the diet, based on tibia Zn, the same Zn status was achieved with a 19 ppm smaller Zn dose while based on serum Zn this was 27 ppm less Zn. Dietary GLDA reduces supplemental Zn needs to fulfill nutritional demands as defined by tibia Zn and serum Zn response. Considering the positive effect on the nutritional availability of Zn in broilers, GLDA presents an opportunity as biodegradable additive, to reduce Zn supplementation to livestock and thereby reducing Zn excretion into the environment, while fulfilling the nutrition Zn needs of farmed animals.


Clinical spectrum of reversible posterior leukoencephalopathy syndrome.
Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by neuroimaging findings of reversible vasogenic subcortical edema without infarction. The clinical syndrome of RPLS typically involves headache, encephalopathy, visual symptoms, and seizures. To retrospectively identify patients with RPLS with a characteristic clinical presentation and neuroimaging abnormalities and documented improvement on repeated neuroimaging. Retrospective. Mayo Clinic. Thirty-six patients with RPLS. Associated comorbid medical conditions, presenting clinical symptoms, duration of clinical symptoms, diagnostic test results (magnetic resonance imaging, electroencephalography, and lumbar puncture), and time to clinical and neuroimaging recovery. We identified 38 episodes of RPLS in 36 patients (20 females and 16 males) with a mean age of 44.7 years. Comorbid conditions included hypertension (53%), renal disease (45%), dialysis dependency (21%), malignancy (32%), and transplantation (24%). Presenting symptoms included clinical seizures (87%), encephalopathy (92%), visual symptoms (39%), and headache (53%). Mean peak systolic blood pressure at presentation was 187 mm Hg. Clinical symptoms resolved after a mean of 5.3 days. Atypical neuroimaging features included significant frontal involvement in 22 episodes (58%), gray matter lesions in 16 (42%), unilateral lesions in 2 (5%), hemorrhage in 2 (5%), recurrent RPLS in 2 (5%), confluent lesions in 2 (5%), and foci of permanent injury in 10 (26%). Twenty-two episodes (58%) had brainstem/cerebellar involvement on neuroimaging. This is the largest clinical series to date of RPLS with confirmed neuroimaging improvement. Clinical recovery occurred in most patients within days. The condition was rarely isolated to the parieto-occipital white matter, and atypical neuroimaging features were frequent.


Distribution of serotypes of human rotavirus in different populations.
Serotyping is a useful tool to study the epidemiologic characteristics of rotaviruses in large populations and to assess the need for a vaccine to protect against all strains. By using an enzyme immunoassay with serotype-specific monoclonal antibodies to the four most common rotavirus serotypes, we analyzed 1,183 rotavirus-positive specimens from 16 stool collections in eight countries on four continents that were obtained from 1978 to 1989. Of the 926 strains (78%) that could be serotyped, 48% were serotype 1, 8% were serotype 2, 15% were serotype 3, and 7% were serotype 4. Twenty-two percent had insufficient numbers of double-shelled virus particles to react with the monoclonal antibody of the VP4 rotavirus protein and therefore could not be serotyped. Our results indicate that vaccines being developed must provide the greatest coverage against serotype 1 and that the serotype distribution cannot be predicted currently by the geographic area or prevalence in the preceding year.


Selective increases in antibody isotypes and immunoglobulin G subclass responses to secreted antigens in tuberculosis patients and healthy household contacts of the patients.
Mycobacterium tuberculosis-specific antibodies (immunoglobulin M [IgM], IgE, IgG, and IgG subclasses) were determined in 164 tuberculosis patients (pulmonary involvement, n = 135; lymph node involvement, n = 29), 59 healthy household contacts (HC), and 51 healthy endemic donors (EC) by a quantitative enzyme-linked immunosorbent assay for reactivity with culture filtrate. Among the isotypes, significant differences between tuberculosis patient groups with either pulmonary or lymph node involvement and healthy control groups (HC and EC) were detected only for IgG (P < 0.001) and IgG1 (P < 0.001) antibodies. Pulmonary patients also showed a significant difference with IgM (P < 0.01) and IgE (P < 0.05) antibodies. HC showed elevation of only IgM antibodies compared with EC, indicating that IgM antibodies may be an indicator of recent infection with M. tuberculosis. These results suggest that the switching of IgM antibody response to IgG1 is a critical event in disease progression. Polyclonal IgG1, IgG3, and IgE antibodies also showed significant elevation (P < 0.05) in patients compared with EC. A strong correlation (rho = 0.254; P < 0.003) was observed between M. tuberculosis-specific IgG1 and polyclonal IgG1 in patients, suggesting that activations of antigen-specific and polyclonal antibodies are related events. No correlation was found between IgG1 antibodies and purified protein derivative skin test results. Since IgG1 antibody responses to culture filtrate are present only after disease establishment, IgG1 responses could provide a useful diagnostic marker of disease.


Reassessment of the effect of fluoridation on cost of dental treatment among Scottish schoolchildren.
The present study, which is a repeat of a 1980 study, compares the dental treatment needs of 5, 10, and 15-yr-old life-time residents of a fluoridated town (Stranraer) and non-fluoridated town (Annan). Although fluoridation ceased in July 1983, the cost of all dental treatment in 1986 was 57% lower for 5-yr-olds in the fluoride area compared with the non-fluoride one. The corresponding differences in costs for 10- and 15-yr-old groups were 36% and 63%, respectively. Comparison with the 1980 results showed a 21% drop in the cost of all treatment for 5-yr-olds in Annan and a 4% drop in 10-yr-olds. The corresponding comparison for Stranraer 5-yr-olds showed a 43% reduction in the cost of all treatment. The 10-yr-old group in Stranraer showed a 21% increase in the cost of all treatment and a 115% increase in the cost of restorations for caries. The implications of these findings and the possible link with the cessation of water fluoridation are discussed.


Chemical characterization of sunscreens composition and its related potential adverse health effects.
Although the sun is very beneficial and essential for life, exposing ourselves too much to sunlight might lead to detrimental health effects such as skin cancer. Eight percent of the total different electromagnetic radiation that regularly irradiates the earth is classified as ultraviolet (UV) radiation. The ozone layer absorbs the most energetic UV rays; consequently, UV-A and UV-B reach the earth surface. UV-A rays heavily contribute to both premature skin aging and skin cancer, while UV-B rays cause sunburn. Hence, the use of sunscreen is strongly encouraged by many healthcare practitioners in order to minimize or possibly eradicate the harmful effects of UV rays on our skin, keeping in mind, that about 90% of all skin cancers are associated with exposure to the sun's harmful radiation. Unfortunately, inaccurate information is currently roaming the media and the Internet regarding the safety, toxicity, and acute side effects of the active ingredients currently used in sunscreens, therefore discouraging people from using sunscreens. In this review article, it is concluded based on the scientific published literature that the sunscreen ingredients are safe and there are no related potential hazardous health risks associated with their use. In addition, at present, sunscreens are very useful in preventing sunburn and probably skin cancer and photoaging and their regular use can have a positive and a significant impact on public health as means or instruments implemented to reduce exposure to UV radiation.


Interactions of vitamin D analogue CB1093, TNFalpha and ceramide on breast cancer cell apoptosis.
Mechanisms by which vitamin D analogues promote apoptosis in tumour cells are unclear. In this study we have examined possible interactions between the synthetic vitamin D analogue CB1093 and two other known mediators of apoptosis, TNFalpha and ceramide, in MCF-7, T47D and Hs578T breast cancer cells. These studies indicated that cytosolic phospholipase A(2) (cPLA(2)) is involved in CB1093 as well as TNFalpha-mediated cell death. CB1093 promoted both TNFalpha and ceramide-induced c-PLA(2) activation, which was inversely related to loss of cell viability in MCF-7 and Hs578T cells. TNFalpha alone (5-20 ng/ml) failed to induce cytotoxicity and activation of cPLA(2) in T47D cells. However, pretreatment of these cells with CB1093 potentiated C(2)-ceramide-induced cPLA(2) activation and cell death. Treatment with CB1093 alone induced loss of cell viability and DNA fragmentation in all three cell lines by 5 days and these effects were accompanied by activation of cPLA(2). Furthermore, co-treatment with the cPLA(2) inhibitor AACOCF(3) led to partial protection against loss of cell viability induced by CB1093 in Hs578T and T47D cells as well as MCF-7 cells. The broad-spectrum caspase inhibitor z-VAD-fmk prevented TNFalpha but not C(2)-ceramide and CB1093-mediated release of arachidonic acid and cell death in MCF-7 cells. These results indicate that CB1093 potentiates responsiveness of breast cancer cells to TNFalpha and suggest that ceramide and/or cPLA(2) might be involved as downstream effectors in vitamin D-mediated caspase-independent cell death.


Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.
Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI). Systematic review and four meta-analyses conducted using random-effects modelling. Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017. Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics. Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10). High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women.


Long-term outcomes of childhood sexual abuse: an umbrella review.
Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4 089 547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. Wellcome Trust.


Differences between children and adolescents who commit suicide and their peers: A psychological autopsy of suicide victims compared to accident victims and a community sample.
The purpose of this study was to gain knowledge about the circumstances related to suicide among children and adolescents 15 years and younger. We conducted a psychological autopsy, collecting information from parents, hospital records and police reports on persons below the age of 16 who had committed suicide in Norway during a 12-year period (1993-2004) (n = 41). Those who committed suicide were compared with children and adolescents who were killed in accidents during the same time period (n = 43) and with a community sample. Among the suicides 25% met the criteria for a psychiatric diagnosis and 30% had depressive symptoms at the time of death. Furthermore, 60% of the parents of the suicide victims reported the child experienced some kind of stressful conflict prior to death, whereas only 12% of the parents of the accident victims reported such conflicts. One in four suicide victims fulfilled the criteria for a psychiatric diagnosis. The level of sub-threshold depression and of stressful conflict experienced by youths who committed suicide did not appear to differ substantially from that of their peers, and therefore did not raise sufficient concern for referral to professional help.


MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma.
To measure oxidative reduction potential (ORP) in semen and seminal plasma and to establish their reference levels. ORP levels were measured in semen and seminal plasma. Tertiary hospital. Twenty-six controls and 33 infertile men. None. Static ORP (sORP) and capacitance ORP (cORP) were measured in semen and seminal plasma at time 0 and 120 minutes. Correlation of ORP was assessed between [1] semen and seminal plasma and [2] time 0 and 120 minutes. The association with sperm parameters was studied in (a) controls and (b) infertile patients, and a receiver operating characteristic curve was generated to establish the sORP cutoff. Semen sORP and cORP levels were associated with seminal plasma levels at time 0 and time 120 minutes. In controls and infertile patients, an inverse relationship of sORP levels was established with concentration and total sperm count in semen as well as seminal plasma at time 0 and 120 minutes. Classification of subjects based on sperm motility showed that subjects with abnormal motility present with poor concentration, total count, morphology, and elevated levels of semen and seminal plasma sORP at time 120 minutes. The sORP cutoff of 1.48 in semen and 2.09 in seminal plasma based on motility was able to distinguish subjects with normal semen quality from those with abnormal semen quality. The MiOXSYS System can reliably measure ORP levels in semen and seminal plasma. ORP levels are not affected by semen age, making this new technology easy to employ in a clinical setting.


Factors associated with shift work disorder in nurses working with rapid-rotation schedules in Japan: the nurses' sleep health project.
Workers who meet the criteria for shift work disorder (SWD) have elevated levels of risk for various health and behavioral problems. However, the impact of having SWD on shiftworkers engaged in rapid-rotation schedules is unknown. Moreover, the risk factors for the occurrence of SWD remain unclear. To clarify these issues, we conducted a questionnaire-based, cross-sectional survey on a sample of shiftworking nurses. Responses were obtained from 1202 nurses working at university hospitals in Tokyo, Japan, including 727 two-shift workers and 315 three-shift workers. The questionnaire included items relevant to age, gender, family structure, work environment, health-related quality of life (QOL), diurnal type, depressive symptoms, and SWD. Participants who reported insomnia and/or excessive sleepiness for at least 1 mo that was subjectively relevant to their shiftwork schedules were categorized as having SWD. The prevalence of SWD in the sampled shiftworking nurses was 24.4%; shiftworking nurses with SWD showed lower health-related QOL and more severe depressive symptoms, with greater rates of both actual accidents/errors and near misses, than those without SWD. The results of logistic regression analyses showed that more time spent working at night, frequent missing of nap opportunities during night work, and having an eveningness-oriented chronotype were significantly associated with SWD. The present study indicated that SWD might be associated with reduced health-related QOL and decreased work performance in shiftworking nurses on rapid-rotation schedules. The results also suggested that missing napping opportunities during night work, long nighttime working hours, and the delay of circadian rhythms are associated with the occurrence of SWD among shiftworking nurses on rapid-rotation schedules.


Repeated treatment with cholecystokinin octapeptide improves maze performance in aged Fischer 344 rats.
Previous studies have shown that sulfated cholecystokinin octapeptide (CCK-8S) can improve learning in adult rodents when administered systemically or into the central nucleus of amygdala. Here we analyzed the effect of repeated intraperitoneal (i.p.) injection of CCK-8S on the performance of 26-month-old Fischer 344 rats in different versions of the Morris water maze and in a rota-rod test of motor coordination. Old rats were injected daily with different doses of CCK-8S (0.32 to 8.0 microg/kg; IP) 10 min before the behavioral tests. Control groups included vehicle-injected old and adult (3-month-old) F 344 rats. To control for a possible development of tolerance to the behavioral effects of repeated CCK-8S administration, groups of aged rats were included which were subjected to an acute rather than a repeated CCK injection schedule. The repeated administration of CCK-8S did not influence the performance of the old rats in the hidden-platform version of the maze. In addition, the acute treatment with CCK-8S failed to modify navigation performance in this task, suggesting that drug-tolerance may not account for the lack of behavioral effects seen after repeated CCK-8S injection. During the "probe trial", the percentage of animals per group, which swam exactly across the former platform site, was markedly increased in aged rats treated repeatedly with 1.6 microg/kg CCK-8S. This might be indicative of improved retention of the prior platform location and/or a higher resistance of the learned escape response to extinction. The specificity of the effect of CCK-8S on processes related to spatial learning and memory is supported by the lack of effect on motor performance.


Regulation of small GTPases by GEFs, GAPs, and GDIs.
Small GTPases use GDP/GTP alternation to actuate a variety of functional switches that are pivotal for cell dynamics. The GTPase switch is turned on by GEFs, which stimulate dissociation of the tightly bound GDP, and turned off by GAPs, which accelerate the intrinsically sluggish hydrolysis of GTP. For Ras, Rho, and Rab GTPases, this switch incorporates a membrane/cytosol alternation regulated by GDIs and GDI-like proteins. The structures and core mechanisms of representative members of small GTPase regulators from most families have now been elucidated, illuminating their general traits combined with scores of unique features. Recent studies reveal that small GTPase regulators have themselves unexpectedly sophisticated regulatory mechanisms, by which they process cellular signals and build up specific cell responses. These mechanisms include multilayered autoinhibition with stepwise release, feedback loops mediated by the activated GTPase, feed-forward signaling flow between regulators and effectors, and a phosphorylation code for RhoGDIs. The flipside of these highly integrated functions is that they make small GTPase regulators susceptible to biochemical abnormalities that are directly correlated with diseases, notably a striking number of missense mutations in congenital diseases, and susceptible to bacterial mimics of GEFs, GAPs, and GDIs that take command of small GTPases in infections. This review presents an overview of the current knowledge of these many facets of small GTPase regulation.