Central projections from the skin of the hand in squirrel monkeys.
Central termination patterns of afferents from the hands of squirrel monkeys were studied after subdermal injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) or cholera toxin subunit B conjugated to HRP (BHRP). WGA-HRP more effectively labeled axons terminating in the superficial dorsal horn of the spinal cord, while BHRP more effectively labeled axons terminating in the deeper layers. Injections of both tracers, when restricted to parts of glabrous digits, palm, or dorsal hand, revealed somatotopic patterns in the spinal cord and pars rotunda of the cuneate nucleus that were, in some respects, similar and, in other respects, quite different from those previously reported for macaque monkey (Florence et al., J. Comp. Neurol. 286:48-70, '89). As in macaques, injections in digits 1-5 produced a rostrocaudal sequence of foci of terminations in the cervical spinal cord. However, inputs from the palm were located medial to those from the digits, whereas the palm is represented lateral to the digits in macaque monkeys. Since inputs from the palm is also medial in the dorsal horn in cats (Nyberg and Blomqvist, J. Comp. Neurol. 242:28-39, '85), the condition in squirrel monkeys may be similar to the generalized state. In the cuneate nucleus, single injections in the hand produced dense label in the pars rotunda, and sparse label in the rostral and caudal poles. As in macaque monkeys, inputs from specific parts of the hand related to rostrocaudal clusters of cells that are cytochrome oxidase dense. The representation of the digits differed from macaques in that the digits were represented dorsal to the palm, rather that ventral to the palm as in macaques. Again, comparisons with cats suggest that squirrel monkeys have the more generalized pattern. Finally, inputs from the hair, dorsal surfaces of the digits terminated on the same clusters as the inputs from the glabrous, ventral surfaces, apparently overlapping somewhat. The proximity of these terminations from dorsal and ventral surfaces of the digits may be related to observations that cortical representations of the glabrous surfaces of digits become responsive to dorsal surfaces of the same digits when inputs from glabrous skin are chronically deactivated (e.g., Merzenich et al., Neuroscience 3:33-55, '83).


Therapeutic strategies for the treatment of multiple myeloma.
The outcome of patients with myeloma has improved significantly in the past decade with the incorporation of the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor, bortezomib. Considering nearly all patients relapse, myeloma remains an active area of investigation. There are several promising classes of agents including next generation immunomodulatory agents, proteasome inhibitors, antibody and antitumor immunotherapy approaches that are being evaluated. This article provides an overview on the therapeutic strategies in the treatment of multiple myeloma.


Leu-arylamidase activity levels during the estrous cycle and pregnancy in several extrahypothalamic areas of the rat brain.
A wide variety of behavioral changes in the female rat have been associated with the estrous cycle, pregnancy, and the postpartum period and their accompanying hormonal fluctuations. Since aminopeptidase activity, that presumably controls the activity of several neuroactive peptides, has been implicated in the control of these hormonal changes, the present study examined the tissue levels of Leu-arylamidase activity (Leu-ArA) in the cortices (frontal, parietal and occipital), striatum, hippocampus, amygdala, pineal gland and medulla oblongata during the estrous cycle, different stages of pregnancy (2nd, 7th, 14th and 20th postinsemination day) and the postpartum day. In the estrous cycle, Leu-ArA was significantly increased during the afternoon of the proestrous in the occipital cortex, amygdala and medulla oblongata. In general, higher enzyme levels were found during the middle stages of pregnancy. There is a significant rise after parturition in the occipital cortex, and clear but insignificant increases in the striatum and medulla. It is suggested that several extrahypothalamic areas may mediate several effects on Gn-RH secretion from the hypothalamus, and that Leu-ArA could be implicated.


Expression of Inhibitor of Differentiation-1 and Its Effects on Angiogenesis in Gastric Cancer.
To explore the effects of recombinant human endostatin (endostar, ES) and cisplatin on the growth of gastric cancer-transplanted tumor in nude mice and the expression of microvessel density (MVD). Human gastric cancer SGC-7901 cells were subcutaneously injected into the armpit of nude mice to prepare cancer-bearing nude mice. A total of 32 cancer-bearing nude mice were divided into four groups (each group with 8 mice). The four groups included control group and other three groups in which mice were treated with 5 mg/kg of ES (group E), 5 mg/kg of cisplatin (group Ci), and 5 mg/kg of ES combined with 5 mg/kg of cisplatin (group C), respectively. MVD was determined by immunohistochemistry, and the expressions of mRNA and protein of inhibitor of differentiation-1 (ID1) and vascular endothelial growth factor (VEGF) were detected with reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively. Apoptosis was observed with transmission electron microscope. Compared with control group, the sizes and weights of tumors were significantly decreased in other three groups (all p < 0.05). MVD was significantly lower in groups E, Ci, and C than in control group, and in groups E and C than in group Ci (all p < 0.05). Compared with control group, the expressions of mRNA and protein of ID1 and VEGF significantly decreased in groups E and C (all p < 0.05). There were no significant differences in the expressions of mRNA and protein of ID1 and VEGF between group Ci and control group. There was apoptosis in groups E and C, but no apoptosis was found in group Ci and control group. ES can inhibit the growth of gastric cancer cells through suppressing angiogenesis and promoting apoptosis of tumor cell. This study provides a new idea for the treatment of gastric cancer.


Cathodic electrochemical detection of sonochemical radical products.
This paper reports on an electrochemical technique for the detection of oxidizing radical species, produced as the result of cavitation induced by ultrasound. A study of two example reactions is reported: the Weissler reaction and the Fricke reaction. In both cases, redox-active materials trap oxidative radicals. Electrochemical detection within a flow cell system is then used to sense redox-active products of the reactions between a chosen trapping agent and radicals produced within an ultrasonically irradiated aqueous solution. A demonstration of the sensitivity of electrochemical detection of radical products is presented. An equivalent dose of the ultrasonic reactor is reported.


High-Brilliance Ultranarrow-Band X Rays via Electron Radiation in Colliding Laser Pulses.
A setup of a unique x-ray source is put forward employing a relativistic electron beam interacting with two counterpropagating laser pulses in the nonlinear few-photon regime. In contrast to Compton scattering sources, the envisaged x-ray source exhibits an extremely narrow relative bandwidth of the order of 10^{-4}, comparable with an x-ray free-electron laser. The brilliance of the x rays can be an order of magnitude higher than that of a state-of-the-art Compton source. By tuning the laser intensities and the electron energy, one can realize either a single peak or a comblike x-ray source of around keV energy. The laser intensity and the electron energy in the suggested setup are rather moderate, rendering this scheme compact and tabletop size, as opposed to x-ray free-electron laser and synchrotron infrastructures.


Study of discrepancies between recorded and actual blood flow in hemodialysis patients.
Adequate blood flow (Qb) is necessary for effective hemodialysis (HD). Aim of the study was to examine relationship between the actually delivered Qb (dQb) and reported Qb (rQb) with dialysis machine. One hundred HD patients with arteriovenous fistula were enrolled. Delivered Qb was measured at the beginning and end of each HD session. dQb/rQb < 1 indicated a discrepancy between actual dQb and rQb reported using a dialysis machine. In addition, dQb/rQb was examined in HD patients using needles of different gauges during treatment. The average levels of dQb/rQb at start and end of HD session were 1.01 ± 0.04 and 0.98 ± 0.05, respectively. In the 16 gauge and 17 gauge needle groups, the percentage of patients with dQb/rQb < 1 increased in accordance with the increase in rQb or as the HD session progressed. In the 15 gauge needle group, the percentage of patients with dQb/rQb < 1 was <50% at any level of rQb. Selection of needle gauge is important factors for determining actual dQb in HD patients.


Gene regulatory networks on transfer entropy (GRNTE): a novel approach to reconstruct gene regulatory interactions applied to a case study for the plant pathogen Phytophthora infestans.
The increasing amounts of genomics data have helped in the understanding of the molecular dynamics of complex systems such as plant and animal diseases. However, transcriptional regulation, although playing a central role in the decision-making process of cellular systems, is still poorly understood. In this study, we linked expression data with mathematical models to infer gene regulatory networks (GRN). We present a simple yet effective method to estimate transcription factors' GRNs from transcriptional data. We defined interactions between pairs of genes (edges in the GRN) as the partial mutual information between these genes that takes into account time and possible lags in time from one gene in relation to another. We call this method Gene Regulatory Networks on Transfer Entropy (GRNTE) and it corresponds to Granger causality for Gaussian variables in an autoregressive model. To evaluate the reconstruction accuracy of our method, we generated several sub-networks from the GRN of the eukaryotic yeast model, Saccharomyces cerevisae. Then, we applied this method using experimental data of the plant pathogen Phytophthora infestans. We evaluated the transcriptional expression levels of 48 transcription factors of P. infestans during its interaction with one moderately resistant and one susceptible cultivar of yellow potato (Solanum tuberosum group Phureja), using RT-qPCR. With these data, we reconstructed the regulatory network of P. infestans during its interaction with these hosts. We first evaluated the performance of our method, based on the transfer entropy (GRNTE), on eukaryotic datasets from the GRNs of the yeast S. cerevisae. Results suggest that GRNTE is comparable with the state-of-the-art methods when the parameters for edge detection are properly tuned. In the case of P. infestans, most of the genes considered in this study, showed a significant change in expression from the onset of the interaction (0 h post inoculum - hpi) to the later time-points post inoculation. Hierarchical clustering of the expression data discriminated two distinct periods during the infection: from 12 to 36 hpi and from 48 to 72 hpi for both the moderately resistant and susceptible cultivars. These distinct periods could be associated with two phases of the life cycle of the pathogen when infecting the host plant: the biotrophic and necrotrophic phases. Here we presented an algorithmic solution to the problem of network reconstruction in time series data. This analytical perspective makes use of the dynamic nature of time series data as it relates to intrinsically dynamic processes such as transcription regulation, were multiple elements of the cell (e.g., transcription factors) act simultaneously and change over time. We applied the algorithm to study the regulatory network of P. infestans during its interaction with two hosts which differ in their level of resistance to the pathogen. Although the gene expression analysis did not show differences between the two hosts, the results of the GRN analyses evidenced rewiring of the genes' interactions according to the resistance level of the host. This suggests that different regulatory processes are activated in response to different environmental cues. Applications of our methodology showed that it could reliably predict where to place edges in the transcriptional networks and sub-networks. The experimental approach used here can help provide insights on the biological role of these interactions on complex processes such as pathogenicity. The code used is available at https://github.com/jccastrog/GRNTE under GNU general public license 3.0.


Electron density modulation of a metallic GeSb monolayer by pnictogen doping for excellent hydrogen evolution.
The catalyst assisted water-splitting method as an eco-friendly and cleaner pathway for energy generation has gained much interest in recent times. In this regard, numerous two-dimensional electrocatalysts such as mono/binary compounds synthesized from group IV, III-V and V elements with compatible activity towards hydrogen evolution, oxygen evolution, oxygen reduction and CO2 reduction have been reported. Motivated by the novel approach of material design and the need for better and cheaper electrocatalytic materials, we have investigated the ground state properties of the GeSb monolayer using state-of-the-art density functional theory. The computed electronic properties reveal the metallic nature of the pristine GeSb monolayer, indicating its potential for utilization as an electrocatalyst. The site-dependent catalytic response of the GeSb monolayer indicates that the Sb-site is more sensitive towards hydrogen adsorption amongst the considered sites. The computed adsorption and Gibbs free energies follow the trend of E < E < E. Finally, we have investigated the role of arsenic (As) and bismuth (Bi) doping on the catalytic activity of the GeSb monolayer. We notice that the electron density modulation occurs at the Sb-site due to incorporation of substitutional doping which results in a 72% enhancement in the catalytic activity of the monolayer on As substitution. The present study envisages that the electron density modulation can be utilized as a pathway for tailoring the catalytic activity of a system for the hydrogen evolution reaction.


Seroprevalence and risk factors for Campylobacter jejuni seropositivity in Jordan.
This is the first large-scale cross-sectional study to examine Campylobacter jejuni seropositivity in Jordan. A total of 368 serum samples from nine governorates of Jordan were tested for IgA and IgG antibodies using enzyme-linked immunosorbent assay along with data collection to determine and rank possible risk factors by logistic regression analyses. The results showed that the rate of seroprevalence is 13.9%. Using chi-square test, six factors were significantly associated with C. jejuni seropositivity (p ≤ .05) including age, drinking raw milk, drinking spring lake water, small ruminant ownership, and dairy cow ownership; meanwhile, drinking filtered water was a protective factor. Chi-square test showed that people ≤19 years old and ≥60 years old had significantly higher seropositivity than other age groups. The multivariate logistic regression model showed that people drinking raw milk had higher odds (adjusted OR= 4.6, 95% CI 2.4-8.8, p-value <.001) for positivity compared with people who do not drink raw milk. Meanwhile, people who own a small ruminant had higher odds (adjusted OR= 1.9, 95% CI 1.0-3.8, p-value = .05) when compared with people who do not own a small ruminant. This study concludes that raw milk consumption and ruminant ownership are risk factors of campylobacter infection in Jordan. Thus, awareness regarding the adverse health consequences from raw milk consumption should be addressed, and campylobacteriosis should also be considered in the differential diagnosis of diarrhoea cases in farmers and their children. Further investigation of Campylobacter infection among younger age groups is recommended.


Analyzing Femorotibial Cartilage Thickness Using Anatomically Standardized Maps: Reproducibility and Reference Data.
Alterations in cartilage thickness (CTh) are a hallmark of knee osteoarthritis, which remain difficult to characterize at high resolution, even with modern magnetic resonance imaging (MRI), due to a paucity of standardization tools. This study aimed to assess a computational anatomy method producing standardized two-dimensional femorotibial CTh maps. The method was assessed with twenty knees, processed following three common experimental scenarios. Cartilage thickness maps were obtained for the femorotibial cartilages by reconstructing bone and cartilage mesh models in tree-dimension, calculating three-dimensional CTh maps, and anatomically standardizing the maps. The intra-operator accuracy (median (interquartile range, IQR) of -0.006 (0.045) mm), precision (0.152 (0.070) mm), entropy (7.02 (0.71) and agreement (0.975 (0.020))) results suggested that the method is adequate to capture the spatial variations in CTh and compare knees at varying osteoarthritis stages. The lower inter-operator precision (0.496 (0.132) mm) and agreement (0.808 (0.108)) indicate a possible loss of sensitivity to detect differences in a setting with multiple operators. The results confirmed the promising potential of anatomically standardized maps, with the lower inter-operator reproducibility stressing the need to coordinate operators. This study also provided essential reference data and indications for future research using CTh maps.


Atopic diathesis in patients with Kawasaki disease.
To determine the association between Kawasaki disease (KD) and atopic diathesis (atopic dermatitis [AD], allergic rhinitis, and asthma) in children younger than 5 years of age. In this nationwide study, we aimed to analyze the association and temporal relationship between KD and atopic diathesis. Data were obtained from the National Health Insurance Research Database of Taiwan from 1997 to 2010. In total, 200 patients with KD younger than 5 years of age and 800 age- and sex-matched control subjects were enrolled. In the whole study population, an increased risk of any concomitant atopic diseases was observed in patients with KD (OR 1.61, 95% CI 1.15-2.26). The risk of AD was increased in male patients between 1 and 5 years of age (OR 3.02, 95% CI 1.22-7.50). More than 60% of the patients developed atopic diseases after the diagnosis of KD. There appears to be an association between KD and risk of AD. Most of the atopic diseases occurred after the episode of KD.


Sweat testing in hypomelanosis of Ito: divergent results reflecting genetic heterogeneity.
Sweat testing using a modified version of the method described by Minor was performed in 5 children affected with hypomelanosis of Ito. In 4 cases the areas of hypopigmentation were arranged in patterns following the lines of Blaschko, whereas in one case a phylloid pattern was observed. In 4 cases the hypomelanotic areas were shown to be anhidrotic. In one case of hypomelanosis following Blaschko's lines, sweat testing was normal and did not reveal any functional difference between the normally pigmented and the hypopigmented areas. These results provide a clinical illustration of the fact that hypomelanosis of Ito is not an entity but constitutes a cutaneous manifestation of various states of mosaicism.


Pretreated Butterfly Wings for Tuning the Selective Vapor Sensing.
Photonic nanoarchitectures occurring in the scales of Blue butterflies are responsible for their vivid blue wing coloration. These nanoarchitectures are quasi-ordered nanocomposites which are constituted from a chitin matrix with embedded air holes. Therefore, they can act as chemically selective sensors due to their color changes when mixing volatile vapors in the surrounding atmosphere which condensate into the nanoarchitecture through capillary condensation. Using a home-built vapor-mixing setup, the spectral changes caused by the different air + vapor mixtures were efficiently characterized. It was found that the spectral shift is vapor-specific and proportional with the vapor concentration. We showed that the conformal modification of the scale surface by atomic layer deposition and by ethanol pretreatment can significantly alter the optical response and chemical selectivity, which points the way to the efficient production of sensor arrays based on the knowledge obtained through the investigation of modified butterfly wings.


The impact of Prevention of mother to Child Transmission of HIV programme in the Federal Capital Territory, Abuja.
Human Immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) is spreading rapidly among the world's children especially in Sub-Saharan Africa. Mother-to-child transmission (MTCT) is the major route of acquired this disease in children. Prevention of mother-to-child transmission (PMTCT) of HIV programme is aimed at reducing HIV/AIDS in children to its barest minimum. The aim of the present study is to determine the impact of PMTCT programme on HIV exposed infants in the Federal Capital Territory (FCT), Abuja. A six month prospective study of 160 HIV exposed infants attending Paediatric Outpatient Special Treatment Clinic (POSTC) of the University of Abuja Teaching Hospital (UATH) was carried out. Exposed infants were categorized based on their participation in the PMTCT programme. Deoxyribonucleic acid (DNA) Polymerase Chain Reaction (PCR) test was used for early diagnosis of HIV infection in the study infants. Overall transmission rate of HIV infection among the study subjects was 33.7%. Transmission was found to occur in 6.7% of infants who participated in PMTCT programme and in 68.6% of those not involved in the programme, P < 0.001. For infants in the full programme, transmission occurred in 2.7% of cases and in 25.0% among those involved partially, P < 0.05. The study shows that transmission of HIV infection to exposed infants is high in FCT, Abuja. Transmission was however found to be significantly lower in infants who participated in PMTCT programme and even much lower in those involved in the full programme. It is therefore recommended that there is an urgent need to establish full PMTCT programme in many health care facilities across the nation as a major way of reducing paediatric HIV/AIDS in the country.


Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study.
Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.


Brain tumor risk in children in relation to use of electric blankets and water bed heaters. Results from the United States West Coast Childhood Brain Tumor Study.
The possible relation between the occurrence of brain tumors in children and exposure to electric blankets or electrically heated water beds was investigated in a multicenter, population-based case-control study conducted on the West Coast of the United States. Information on maternal exposure during pregnancy or direct exposure to the subject child was collected by in-person interview from the mothers of 540 case children and 801 control children. Cases were 19 years of age or younger and were diagnosed between 1984 and 1991. Controls were recruited using a random digit dialing procedure. The risk of brain tumor occurrence from in utero exposure to either electric blankets (odds ratio (OR) = 0.9, 95% confidence interval (Cl) 0.6-1.2) or heated water beds (OR = 0.9, 95% Cl 0.6-1.3) was not elevated. Brain cancer risk did not vary by use in any trimester of pregnancy, and children with mothers who reported use throughout their pregnancy had no increased risk. Similar results were observed for exposure to the child, in that no association between brain cancer and use of electric blankets (OR = 1.0, 95% Cl 0.6-1.7) or heated water beds (OR = 1.2, 95% Cl 0.7-2.0) was observed. Risks did not vary significantly by age, sex, race, socioeconomic status, or histologic category for either in utero exposure or child's exposure. This study provides no evidence to support the hypothesis that there is a relation between brain cancer occurrence in children and 50-/60-Hz magnetic field exposure from the use of electric blankets and heated water beds.


The carboxyl-terminal region of erythroid-specific 5-aminolevulinate synthase acts as an intrinsic modifier for its catalytic activity and protein stability.
Erythroid-specific 5-aminolevulinate synthase (ALAS2) is essential for hemoglobin production, and a loss-of-function mutation of ALAS2 gene causes X-linked sideroblastic anemia. Human ALAS2 protein consists of 587 amino acids and its carboxyl(C)-terminal region of 33 amino acids is conserved in higher eukaryotes, but is not present in prokaryotic ALAS. We explored the role of this C-terminal region in the pathogenesis of X-linked sideroblastic anemia. In vitro enzymatic activity was measured using bacterially expressed recombinant proteins. In vivo catalytic activity was evaluated by comparing the accumulation of porphyrins in eukaryotic cells stably expressing each mutant ALAS2 tagged with FLAG, and the half-life of each FLAG-tagged ALAS2 protein was determined by Western blot analysis. Two novel mutations (Val562Ala and Met567Ile) were identified in patients with X-linked sideroblastic anemia. Val562Ala showed the higher catalytic activity in vitro, but a shorter half-life in vivo compared to those of wild-type ALAS2 (WT). In contrast, the in vitro activity of Met567Ile mutant was about 25% of WT, while its half-life was longer than that of WT. However, in vivo catalytic activity of each mutant was lower than that of WT. In addition, the deletion of 33 amino acids at C-terminal end resulted in higher catalytic activity both in vitro and in vivo with the longer half-life compared to WT. In conclusion, the C-terminal region of ALAS2 protein may function as an intrinsic modifier that suppresses catalytic activity and increases the degradation of its protein, each function of which is enhanced by the Met567Ile mutation and the Val562Ala mutation, respectively.


Post-traumatic stress disorder in children and adolescents: epidemiology, diagnosis and treatment options.
Post-traumatic stress disorder (PTSD) is a common psychiatric condition in childhood and adolescence. Rates vary widely depending upon the type of trauma exposure. Interpersonal traumas, such as rape or physical abuse, are more likely to result in PTSD than exposure to natural or technological disaster. Clinical presentations are exceedingly complex and children with PTSD are at increased risk of having comorbid psychiatric diagnoses. Because of its complexity and frequent occurrence with other disorders, assessment of PTSD necessitates a broad-based evaluation utilizing multiple informations and structured instruments specific to the symptoms of PTSD in youth. Cognitive-behavioral therapy (CBT) is the treatment of first choice. Pharmacological agents for PTSD treatment have received little empirical investigation in childhood. Pharmacological treatment is used to target disabling symptoms of the disorder, which limit psychotherapy or life functioning, by helping children to tolerate working through distressful material in therapy and life. Pharmacological treatment should be based on a stepwise approach utilizing broad spectrum medications such as the selective serotonin reuptake inhibitors as first-line agents. Comorbid conditions should be identified and treated with appropriate medication or psychosocial interventions. Treatment algorithms are provided to guide rational medication strategies for children and adolescents with PTSD, subsyndromal PTSD, and in PTSD that is comorbid with other psychiatric conditions of childhood. Reduction in even one debilitating symptom of PTSD can improve a child's overall functioning across multiple domains.


An integrative modular approach to systematically predict gene-phenotype associations.
Complex human diseases are often caused by multiple mutations, each of which contributes only a minor effect to the disease phenotype. To study the basis for these complex phenotypes, we developed a network-based approach to identify coexpression modules specifically activated in particular phenotypes. We integrated these modules, protein-protein interaction data, Gene Ontology annotations, and our database of gene-phenotype associations derived from literature to predict novel human gene-phenotype associations. Our systematic predictions provide us with the opportunity to perform a global analysis of human gene pleiotropy and its underlying regulatory mechanisms. We applied this method to 338 microarray datasets, covering 178 phenotype classes, and identified 193,145 phenotype-specific coexpression modules. We trained random forest classifiers for each phenotype and predicted a total of 6,558 gene-phenotype associations. We showed that 40.9% genes are pleiotropic, highlighting that pleiotropy is more prevalent than previously expected. We collected 77 ChIP-chip datasets studying 69 transcription factors binding over 16,000 targets under various phenotypic conditions. Utilizing this unique data source, we confirmed that dynamic transcriptional regulation is an important force driving the formation of phenotype specific gene modules. We created a genome-wide gene to phenotype mapping that has many potential implications, including providing potential new drug targets and uncovering the basis for human disease phenotypes. Our analysis of these phenotype-specific coexpression modules reveals a high prevalence of gene pleiotropy, and suggests that phenotype-specific transcription factor binding may contribute to phenotypic diversity. All resources from our study are made freely available on our online Phenotype Prediction Database.


[Adenocarcinomas of the ethmoid sinuses. Epidemiological data].
The relationship between adenocarcinomas of the ethmoid (ADKE) and wood-dust exposure has been well established. Sino-nasal cancer in wood-workers has been added to the list of occupational disorders in France, as prescribed disease number 47-Bq. Our data set consisted of 207 cases with sino-nasal cancer (from January 1985 to January 2001). Among these cases, 67.1% were adenocarcinoma. A wood dust exposure has been reported in 96.4% cases. The mean duration of wood dust exposure was 30 years. The mean latency between the end of the exposure and the diagnostic was 10.6 years. Our epidemiological data confirmed those from the biomedical literature. The occupations at greatest risk are furniture workers, sawmill workers, carpentry workers, and other wood product workers. Two components of exposure - duration and average level - contributed independently to the overall elevated risk. The risk is greater among men who were employed in jobs with the highest wood dust exposure and increases with the duration of exposure. The preinvasive stages of ADKE (mucostasis/cuboïd metaplasia/dysplasia) are still an unverified hypothesis. ADKE were observed in workers who use "hard" woods. The chemical nature of the carcinogenic factor(s) in wood dust is not known. The factors responsible for induction of ADKE in hard wood-workers probably exist in the wood-dust itself. Tannins were suggested as possible contributing agents to induction of ADKE. In addition to wood dust, exposures may include formaldehyde. Given these facts, it should be possible to define preventive measures, so that incidence of ADKE in professional wood and leather workers should decrease.


Low-loss high-confinement waveguides and microring resonators in AlGaAs-on-insulator.
AlGaAs is a promising material for integrated nonlinear photonics due to its intrinsic high nonlinearity. However, the challenging fabrication of deep etched AlGaAs devices makes it difficult to realize high-performance devices such as low-loss dispersion engineered waveguides and high-quality microring resonators. Here, we report a process to make high-quality AlGaAs-on-insulator (AlGaAsOI) wafers where high confinement waveguides can be realized. Using optimized patterning processes, we fabricated AlGaAsOI waveguides with propagation losses as low as 1 dB/cm and microring resonators with quality factors up to 350,000 at telecom wavelengths. Our demonstration opens new prospects for AlGaAs devices in integrated nonlinear photonics.


Diaqua-bis-(pyridine-2-carboxyl-ato-κN,O)manganese(II) dimethyl-formamide hemisolvate.
There are two crystallographically independent complex mol-ecules with very similar geometries in the unit cell of the title compound, [Mn(C(6)H(4)NO(2))(2)(H(2)O)(2)]·0.5C(3)H(7)NO. The central ion is situated in a distorted octa-hedral environment of two N- and four O-donor atoms from two pyridine-2-carboxyl-ate ligands and two cis-disposed water mol-ecules. The carboxyl-ate ligands are coordinated in a chelate fashion with the formation of two five-membered rings. In the crystal, the complex mol-ecules are connected by O-H⋯O hydrogen bonds between the coordinated water mol-ecules and the uncoordinated carboxyl-ate O atoms, thus forming hydrogen-bonded walls disposed perpendicularly to the bc plane.


A laboratory evaluation of the antibacterial and cytotoxic effect of Liquorice when used as root canal medicament.
To evaluate the antibacterial and cytotoxic effects of Liquorice as a root canal medicament and to compare its action to the commonly used root canal medicament calcium hydroxide Ca(OH)(2). The antibacterial effect of Liquorice and Ca(OH)(2) either separately or in combination was investigated against Enterococcus faecalis. Agar-well diffusion methods, broth microdilution tests and biofilm susceptibility assays were used to determine the antibacterial activity. Human periodontal ligament fibroblast tissue culture was used to assess the cytotoxicity of the preparations under investigation. Liquorice extract either by itself or in combination with Ca(OH)(2) had a significant inhibitory effect against Enterococcus faecalis compared with that of Ca(OH)(2) alone. The use of Liquorice extract followed by Liquorice/Ca(OH)(2) mixture retained significantly more viable periodontal ligament cells than Ca(OH)(2) , which had a strong lethal effect on the cells. Liquorice extract either separately or as Liquorice/Ca(OH)(2) mixture had a potent bactericidal effect against Enterococcus faecalis and retained compatibility with fibroblasts in tissue culture compared to the commonly used root canal medicament Ca(OH)(2).


Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, on lactate metabolism and muscle high energy phosphates during endotoxic shock in rats.
Overproduction of NO by an inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. In such situations, NOS inhibition might be of therapeutic value, although detrimental side effects possibly related to inhibition of constitutive NOS have been reported. The use of L-canavanine, a selective inhibitor of iNOS, might be more suitable. The aim of the study was to compare in a rodent endotoxic shock the effects of saline (2 mL/h), N(G)-methyl-L-arginine(L-NMMA) (10 mg/kg/h) and L-canavanine (100 mg/kg/h) on muscle intracellular pH (pHi) and intracellular bioenergetic patterns (ATP, phosphocreatine/inorganic phosphate ratio) using in vivo 31P magnetic resonance spectroscopy (31P MRS). Three groups of anesthetized, mechanically ventilated and paralyzed rats received an intravenous infusion of 15 mg/kg of endotoxin. A fourth time-matched control group (n = 8) received 2 mL/h of saline. Mean arterial pressure, femoral blood flow, arterial blood gases, lactate, nitrate level, and 31P nuclear magnetic resonance (31P MRS) measurements were acquired at onset (T = 0), 90 min (T = 90), and 180 min (T180) after the endotoxin challenge. Femoral oxygen delivery was calculated as the product of femoral blood flow (mL/min) and arterial oxygen content. Endotoxin induced a marked decrease in arterial pressure and femoral oxygen delivery and an increase in lactate level. Intracellular pH and phosphocreatine/inorganic phosphate ratio decreased. ATP level did not change. Both L-NMMA and L-canavanine reversed the endotoxin-induced decrease in arterial pressure. L-NMMA attenuated the decrease in femoral oxygen delivery and the increase in lactate level while these were corrected by L-canavanine. Considering 31P MRS derived bioenergetic indices, the endotoxin-induced decrease in pHi and Pcr/Pi was attenuated by L-NMMA and corrected by L-canavanine. In conclusion, in a rodent model of endotoxinic shock, the continuous infusion of L-canavanine, a selective iNOS inhibitor, improved the systemic hemodynamic parameters and the intracellular bio-energetic patterns estimated by in vivo 31P MRS. To the contrary, the continuous infusion of both constitutive and inducible NOS inhibitor L-NMMA was not followed by the same achievement.


Plexiform ameloblastoma of the mandible.
Ameloblastoma is a common and aggressive odontogenic epithelial tumor. It has an aggressive behavior and recurrent course, and is rarely metastatic. Ameloblastoma represents 1% of all tumors and cysts that involve the maxillomandibular area and about 10% of the odontogenic tumors. It is primarily seen in adults in the third to fifth decade of life, with equal sex predilection. Radiographically, it appears as an expansile radiolucent, with thinned and perforated cortices, and is known to cause root resorption. As it shares common radiographic features with other lesions such as the giant cell tumor, aneurismal bone cyst, and renal cell carcinoma metastasis, a definitive diagnosis can only be made with histopathology. We present an extensive case of plexiform ameloblastoma of the mandible in a 42-year-old female patient.


Can behavioural differences in Platypus cylindrus (Coleoptera: Platypodinae) from Portugal and Tunisia be explained by genetic and morphological traits?
Platypus cylindrus is an important wood borer of cork oak trees (Quercus suber) in the Mediterranean region, namely Portugal, Morocco and Algeria where its presence has drastically increased in the past few decades. On the contrary, the insect is not a relevant pest in Tunisia. The aim of this work is to analyze morphological and genetic differences among Tunisian and Portuguese populations in order to understand their role in the diverse population dynamics (e.g., aggressiveness) of the insect. The information could be used as a novel tool to implement protective measures. Insects were collected from cork oak stands in Tunisia (Ain Beya, Babouch and Mzara) and Portugal (Chamusca and Crato). Morphological traits of female and male mycangial pits were determined, using scanning electron microscopy but no significant differences were found. Genetic differences were analyzed using nuclear (internal simple sequence repeat polymerase chain reaction) and mitochondrial (cytochrome oxidase I (COI)) molecular markers. The results showed a very low level of intraspecific polymorphism and genetic diversity. The alignment of COI sequences showed high percentage of identical sites (99%) indicating a very low variation in nucleotide composition. Other variables related with the ecology of the insect and its associated fungi must be studied for a better understanding of the differences in the insect population's dynamic in Mediterranean countries.


Taraxasterol attenuates melanoma progression via inactivation of reactive oxygen species-mediated PI3K/Akt signaling pathway.
Background: Taraxasterol (TX), a pentacyclic triterpene, is one of the main active constituents isolated from Taraxacum officinale. A growing number of studies have reported that TX exhibits a wide range of biological activities such as anti-oxidative, anti-inflammatory, and neuro-protective effects. Recently, TX has been demonstrated to be a potential drug candidate for treatment of some types of cancers. However, the specific role of TX in melanoma remains unclear.Purpose: In this study, we aimed at exploration of the effect of TX on melanoma cell viability, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the underlying mechanisms.Research design: A375 and SK-MEL-28 cells were treated with various concentrations of TX for different times. Cell viability was measured using CCK-8 assay. Cell apoptosis was determined by flow cytometry. Transwell assays were performed to measure cell migration and invasion. The expression of E-cadherin, α-catenin, N-cadherin, vimentin, p-PI3K, PI3K, p-Akt and Akt was detected using western blot.Results: The study showed that TX induced A375 and SK-MEL-28 cell apoptosis. Furthermore, exposure to TX inhibited A375 and SK-MEL-28 cell migration and invasion. Besides, the EMT process was reversed in A375 and SK-MEL-28 cells after TX treatment. We also observed that TX reduced the protein expression of p-PI3K and p-Akt; thus, inhibiting activity of the PI3K/Akt pathway in A375 and SK-MEL-28 cells. In addition, TX treatment increased the levels of reactive oxygen species (ROS) in A375 and SK-MEL-28 cells, and treatment with the ROS scavenger NAC significantly rescued TX-induced down-regulation of p-PI3K and p-Akt in A375 and SK-MEL-28 cells.Conclusions: In conclusion, our study demonstrated that TX induced ROS accumulation followed by inactivation of the PI3K/Akt pathway and subsequently attenuated melanoma progression, suggesting that TX may be a potential candidate for treatment of melanoma.


Development of a competing risk nomogram for the prediction of cause-specific mortality in patients with thymoma: a population-based analysis.
This study was developed to assess the odds of cause-specific mortality and other types of mortality in thymoma patients. In addition, these analyses were leveraged to develop a comprehensive competing risk model-based nomogram capable of predicting cause-specific mortality as a result of thymoma. Thymoma patients included within the Surveillance, Epidemiology, and End Results (SEER) database from 2004-2016 were identified, and the odds of cause-specific mortality due to thymoma and other forms of mortality for these patients were estimated. In addition, Fine and Gray's proportional subdistribution hazard model was constructed, and a competing risk nomogram was developed using this model that was capable of predicting the odds of 3-, 5-, and 10-year cause-specific mortality in thymoma patients. In total, 1,591 relevant cases in the SEER database were selected for analysis. In this patient cohort, the respective 5-year cumulative incidence rates for cause-specific mortality and mortality attributable to other causes were 12.4% and 8.2%. Variables significantly associated with cause-specific mortality included age, chemotherapy, surgery, and Masaoka stage. Additionally, the odds of other-cause-specific mortality rose with increasing patient age, and chemotherapy was correlated with other-cause-specific mortality. The competing risk nomogram that was developed exhibited good discriminative ability as a means of predicting cause-specific mortality, as evidenced by a concordance index (C-index) value of 0.84. Calibration curves further revealed excellent consistency between predicted and actual mortality when using this nomogram. In summary, we herein assessed the odds of cause-specific and other-cause-specific mortality among thymoma patients, and we designed a novel nomogram capable of predicting cause-specific mortality for thymoma, providing a promising tool that may be of value in the context of individualized patient prognostic evaluation.


Effects of Exercise on Nutritional Status in People with Cystic Fibrosis: A Systematic Review.
Physical exercise is an important part of regular care for people with cystic fibrosis (CF). It is unknown whether such exercise has beneficial or detrimental effects on nutritional status (body composition). Thus, the objective of this review was to evaluate the effect of exercise on measures of nutritional status in children and adults with CF. Standardized reporting guidelines for systematic reviews were followed and the protocol was prospectively registered. Multiple databases were utilized (e.g., PubMed, Scopus, and CINHAL). Two reviewers independently reviewed titles/abstracts and then the full text for selected studies. In total, 924 articles were originally identified; data were extracted from 4 eligible studies. These four studies included only children; pulmonary function ranged from severe to normal, and the majority of participants were at or below their recommended weight. Exercise training did not worsen nutritional status in any study; two studies that included resistance exercise reported an increase in fat-free mass. Three of the four studies also reported increased aerobic capacity and/or muscle strength. Exercise training can produce positive physiologic changes in children with CF without impairing their nutritional status. In fact, resistance exercise can help improve body mass. Much less is known about how exercise may affect adults or those who are overweight.


Exploring effectiveness of different health financing mechanisms in Nigeria; what needs to change and how can it happen?
Various attempts to examine health financing mechanisms in Nigeria highlight the fact that there is no single mechanism that fits all contexts and people. This paper sets out findings of an in-depth assessment of different health financing mechanisms in Nigeria. The study was undertaken in the Federal Capital territory of Nigeria and two States (Niger and Kaduna). Data were collected through review of government documents, and in-depth interviews of purposively selected respondents. Data analysis was guided by a conceptual framework which draws from various approaches for assessing health financing mechanisms. Data was examined for current practices, what needs to change and how the change can happen. Health financing mechanisms in Nigeria do not operate optimally. Allocation and use of resources are neither evidence-based nor results-driven. Resources are not allocated equitably or in a manner that minimizes wastage and improves efficiency. None of the mechanisms effectively protects individuals/households from catastrophic health expenditure. Issues with social health insurance cut across legal frameworks and use of Health Maintenance Organisations (HMOs) as purchasers. The concomitant effect is that attainment of Universal Health Coverage is greatly compromised. In order to improve efficiency of health financing mechanisms, government needs to allocate more funds for purchasing health services; this spending must be based on evidence (strategic), and appropriately tracked. The legislation that established National Health Insurance Scheme should be amended such that social health insurance becomes mandatory for all citizens. Implementation of the latter should be complemented by revision of benefit package, strict oversight and regulation of HMOs. In order to improve health financing in the country, legal and regulatory frameworks need to be revised. Efficient utilization of resources could be improved through strategic purchasing arrangements and strict oversight.


Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells.
Oxidative stress-induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)-induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.


Brain morphology and response to nortriptyline in geriatric depression.
In geriatric patients with major depression (N=15), the authors compared response to treatment with nortriptyline as it relates to brain morphology assessed by computed tomography. There was a significant negative association between ventricle-brain ratio and response to nortriptyline (rs=-0.63; P=0.015).


Adopting the qualitative paradigm to understanding children's perspectives of illness: barrier or facilitator?
Reliance on the traditional quantitative paradigm has been the norm for exploring the phenomenon of children's illness experiences. Although it provides valuable information on the psychosocial sequelae of children in response to illness, an account of children's perspectives of the illness experience is missing. Accordingly, researchers since the early 1980s have been advocating the need to adopt the qualitative paradigm in the study of children's illness experiences. Nonetheless, even though there is a call for more qualitative research, the majority of research being conducted today still supports the quantitative paradigm. This report examines why researchers may be reluctant to adopt the qualitative paradigm. Specifically, the author proposes that this reluctance may stem from researchers' perceiving children as being less competent and social than adults, which would explain the need to research children solely from an objective, impersonal stance. Primary philosophical principles of the qualitative paradigm may be seen as barriers to accessing children's thoughts. The author suggests, however, that when children are viewed from an alternative perspective, the major principles of the qualitative paradigm may actually serve as facilitators to apprehending their thoughts and feelings. The following key principles of the qualitative research paradigm are examined: (a) realities are constructed by human beings who are viewed as active agents making sense out of the realities they encounter; (b) realities are multiple and must be perceived holistically and from various vantage points; and (c) realities are shared and mutually shaped by the researcher and research participants. Key strategies that promote successful use of the qualitative paradigm in the study of children's illness experiences are also discussed.


Potential Ameliorative Effects of Qing Ye Dan Against Cadmium Induced Prostatic Deficits via Regulating Nrf-2/HO-1 and TGF-β1/Smad Pathways.
Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways.


Can we improve delirium prevention and treatment in the emergency department? A systematic review.
This systematic review was conducted to evaluate any interventions to prevent incident delirium, or shorten the duration of prevalent delirium, in older adults presenting to the emergency department (ED). Health sciences librarian designed electronic searches were conducted from database inception through September 2021. Two authors reviewed studies, and included studies that evaluated interventions for the prevention and/or treatment of delirium and excluded non-ED studies. The risk of bias (ROB) was evaluated by the Cochrane ROB tool or the Newcastle-Ottawa (NOS) scale. Meta-analysis was conducted to estimate a pooled effect of multifactorial programs on delirium prevention. Our search strategy yielded 11,900 studies of which 10 met study inclusion criteria. Two RCTs evaluated pharmacologic interventions for delirium prevention; three non-RCTs employed a multi-factorial delirium prevention program; three non-RCTs evaluated regional anesthesia for hip fractures; and one study evaluated the use of Foley catheter, medication exposure, and risk of delirium. Only four studies demonstrated a significant impact on delirium incidence or duration of delirium-one RCT of melatonin reduced the incidence of delirium (OR 0.19, 95% CI 0.06 to 0.62), one non-RCT study on a multi-factorial program decreased inpatient delirium prevalence (41% to 19%) and the other reduced incident delirium (RR 0.37, 95% CI 0.22 to 0.61). One case-control study on the use of ED Foley catheters in the ED increased the duration of delirium (proportional OR 3.1, 95% CI 1.3 to 7.4). A pooled odds ratio for three multifactorial programs on delirium prevention was 0.46 (95% CI 0.31-0.68, I2 = 0). Few interventions initiated in the ED were found to consistently reduce the incidence or duration of delirium. Delirium prevention and treatment trials in the ED are still rare and should be prioritized for future research.


Technological innovations in surgical approach for thyroid cancer.
Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options.


Copper oxide-based model of persistent free radical formation on combustion-derived particulate matter.
We have found that environmentally persistent free radicals (PFRs) are formed by adsorption of substituted aromatic molecular precursors on the surface of cupric oxide-containing particles at temperatures between 100 and 400 degrees C. This temperature range corresponds to the conditions in the postflame, cool zone of combustion, and thermal processes. Depending upon the nature of the precursor and the adsorption temperature, both substituted phenoxyl and semiquinone radicals are formed. The PFRs are formed through a mechanism of initial physisorption, followed by chemisorption via elimination of water or hydrogen chloride, and electron transfer resulting in the simultaneous reduction of Cu(II) to Cu(I) and formation of the PFR. The PFRs are still observable by electron paramagnetic resonance (EPR) after exposure to air for more than a day. Their lifetimes under vacuum appear to be infinite. Other redox-active transition metals such as iron are expected to also mediate or catalyze the formation of PFRs. The properties of the observed radicals are consistent with radicals previously observed on airborne and combustion-generated particulate matter. We propose a catalytic biochemical cycle for both the particle-associated semiquinone and phenoxyl PFRs that result in the formation of hydroxyl radical and other reactive oxygen species (ROS). This suggests that combustion-generated, particle-associated PFRs may be responsible for the oxidative stress resulting in cardiopulmonary disease and probably cancer that has been attributed to exposure to airborne fine particles.


Suture laterofixation of the vocal fold for bilateral vocal fold immobility.
To review the recent published literature on the subject of suture laterofixation for bilateral vocal fold immobility, to evaluate outcomes, and to assess advances and modifications of the procedure during the review period. Suture laterofixation offers potential benefits over other surgical procedures employed in the treatment of bilateral vocal fold immobility. The procedure is potentially reversible, avoids long-term consequences of ablative procedures such as arytenoidectomy, and can be accomplished under jet ventilation without the need for tracheostomy. Modifications to the technique such as increasing suture size and utilizing a dual suture technique may decrease the risk of injury to the vocal fold mucosa. The advantages of suture laterofixation have argued for closer scrutiny as a potential treatment for pediatric patients. Suture laterofixation is an important option in the treatment of bilateral vocal fold immobility. Laryngologists should be aware of the potential advantages over other procedures, particularly those that necessitate surgical ablation of the arytenoid or vocal fold.


Patient-centered placement matching of alcohol-dependent patients based on a standardized intake assessment: process evaluation within an exploratory randomized controlled trial.
In the implementation of placement matching guidelines, feasibility has been concerned in previous research. Objectives of this process evaluation were to investigate whether the patient-centered matching guidelines (PCPM) are consistently applied in referral decision-making from an inpatient qualified withdrawal program to a level of care in aftercare, which factors affect whether patients actually receive matched aftercare according to PCPM, and whether its use is feasible and accepted by clinic staff. The study was conducted as process evaluation within an exploratory randomized controlled trial in four German psychiatric clinics offering a 7-to-21 day qualified withdrawal program for patients suffering from alcohol dependence, and with measurements taken during detoxification treatment and six months after the initial assessment. PCPM were used with patients in the intervention group by feeding back to them a recommendation for a level of care in aftercare that had been calculated from Measurements in the Addictions for Triage and Evaluation (MATE) and discussed with the staff on the treatment unit. As measurements, The MATE, the Client Socio-Demographic and Service Receipt Inventory-European Version, a documentation form, the Control Preference Scale, and the Motivation for Treatment Scale were administered. A workshop for the staff at the participating trial sites was conducted after data collection was finished. Among 250 patients participating in the study, 165 were interviewed at follow-up, and 125 had received aftercare. Although consistency in the application of PCPM was moderate to substantial within the qualified withdrawal program (Cohen's kappa ≥ .41), it was fair from discharge to follow-up. In multifactorial multinomial regression, the number of foregoing substance abuse treatments predicted whether patients received more likely undermatched (Odds Ratio=1.27; p=.018) or overmatched (Odds Ratio=0.78; p=.054) treatment. While the implementation process during the study was evaluated critically by the staff, they stated a potential of quality assurance, more transparency and patient-centeredness in the use of PCPM. While the use of PCPM has the potential to enhance the quality of referral decision making within treatment, it may not be sufficient to determine referral decisions for aftercare. German Clinical Trials Register DRKS00005035 . Registered 03/06/2013.


β-lactam antibiotics residues analysis in bovine milk by LC-ESI-MS/MS: a simple and fast liquid-liquid extraction method.
This study presents the development and validation of a simple method for the detection and quantification of six β-lactam antibiotics residues (ceftiofur, penicillin G, penicillin V, oxacillin, cloxacillin and dicloxacillin) in bovine milk using a fast liquid-liquid extraction (LLE) for sample preparation, followed by liquid chromatography-electrospray-tandem mass spectrometry (LC-MS/MS). LLE consisted of the addition of acetonitrile to the sample, followed by addition of sodium chloride, centrifugation and direct injection of an aliquot into the LC-MS/MS system. Separation was performed in a C(18) column, using acetonitrile and water, both with 0.1% of formic acid, as mobile phase. Method validation was performed according to the criteria of Commission Decision 2002/657/EC. Limits of detection ranged from 0.4 (penicillin G and penicillin V) to 10.0 ng ml(-1) (ceftiofur), and linearity was achieved. The decision limit (CCα), detection capability (CCβ), accuracy, inter- and intra-day repeatability of the method are reported.


[A pediatric case of Schoenlein-Henoch purpura with clinical, serologic and electrocardiographic signs of myocardial damage].
The Schoenlein-Henoch purpura is a vascular disease that affects blood vessels and/or capillaries. It usually occurs in children, particulary male, between 2 and 8 years of age. The clinical presentation is characterized by purple spots on the skin, joint pain, gastrointestinal symptoms, and kidney disorders. Occasionally, it may affect the lungs, testicles, heart, and central neervous system. Interestingly, heart involvement appears as myocarditis or arrythmia due to vascular damage of coronary arteries and tiny intramyocardial capillaries. We here describe a case of Schoenlein-Henoch purpura with clinical, electrocardiographic and serologic signs of myocardial ischemia, likely due to capillary vasculitis associated with streptococcus infection.


Bio-efficacy of deltamethrin based durable wall lining against wild populations of Anopheles gambiae s.l. in Northern Tanzania.
Indoor residual spraying (IRS) is one of the preferred tools used for control of malaria in many settings in the world. However, this control tool still faces challenges that include lack of long lasting active ingredient, limited number of well-trained personal, and need of repeated treatment which increases operational costs and reduces acceptability by residents. As a result there is need to develop and validate other methods which can complement the existing controls. The current study compared the bio-efficacy of durable wall lining (DL) (treated with deltamethrin 265 mg/m2) and IRS (with deltamethrin 5% WP at 20 mg/m2) on indoor mosquitoes densities and biting behaviour of mosquitoes in comparison with control houses without either DL or IRS. A study with two treatment arms and a control was conducted in Magugu ward, Northern Tanzania. Overall, a total of 60 houses were selected for the study with 20 houses per treatment arm and control. From each arm and control five houses were selected for mosquitoes trapping. Mosquitoes were sampled from 18:00 to 07:00 hourly every month for a period of 6 months. Mosquitoes were sampled using CDC miniature light traps. A total of 14,400 female wild mosquitoes were used for contact bioassays in the control arm. 20 houses were sprayed, additionally walls of 20 houses were installed with wall liners, and walls of 20 unsprayed houses were used as control. Also, a total of 946 mosquitoes were sampled with traps in 60 houses during the hourly sampling for 6 months. A total of 3000 unfed females of An. gambiae s.l. wild population raised from larvae were collected from natural habitats in the same village for bioassays. The decline in indoor mosquitoes densities observed in this study did not lead to a shift in the biting cycles (P = 0.712). The number of mosquitoes caught indoors in houses with DL and IRS was significantly lower (P < 0.001) compared to control houses. When the comparisons were done between DL and IRS houses, the densities were significantly lower in DL houses compared to IRS houses (P = 0.021). In the DL installed houses, indoor mosquito density declined notably and sustained throughout the 6 months of the study. However, in those houses sprayed with deltamethrin 5% WP (PALI™5 WP), the density noted to start to increase within four months after spraying(do you mean to say that the densities declined up to 4 months post spraying and thereafter increased. Considering the efficacy duration of DL against IRS with deltamethrin 5% WP on mosquito densities decline indoors. The results of this study suggest that DL is more effective in malaria control as its efficacy lasted more than that of IRS.


Changes in the Invasion Rate of Prosopis juliflora and Its Impact on Depletion of Groundwater in the Northern Part of the United Arab Emirates.
Prosopis species were introduced to the United Arab Emirates (UAE) region for desert greening. However, the species now pose a great threat to the native plant diversity. This study used high-resolution satellite imagery (1990-2019) to understand the history and current distribution of Prosopis species and their impact on fresh groundwater. The results show that the Prosopis invasion in the study area reached its maximum expansion rate in 2019 and covered an area of about 16 km2 compared to 0.2 km2 in 1990. The areas near Sharjah Airport, Umm Fannan, and Al Talla, located at a lower elevation of the sand dune area, are heavily invaded. Prosopis groundwater requirement derived using evapotranspiration shows that groundwater consumption has changed drastically after 2010 and consumed about 22.22 million m3 of groundwater in 2019, which is about a 7372% increase in groundwater consumption from the year 1990 to 2019. The results can be useful for setting up a management plan for the sustainable use of this species in the UAE region in particular and other similar countries in the arid land regions that are suffering from freshwater depletion because of Prosopis invasion.


A sensitive and high-throughput LC-ESI-MS/MS method to detect budesonide in human plasma: application to an evaluation of pharmacokinetics of budesonide intranasal formulations with and without charcoal-block in healthy volunteers.
Budesonide is one of the intranasal corticosteroids, referred as first-line therapy for allergic rhinitis. Its determination is a challenging task due to its extremely low plasma levels, which limits the progress in the investigation of pharmacokinetics and quality control of preparations. In this study, a sensitive and high-throughput method to determine budesonide in human plasma using budesonide-d8 as the internal standard was developed and validated. A small volume of plasma sample (0.2 mL) was diluted with 0.2 mL water, followed by a solid-phase extraction using Cleanert PEP-2 products. Extracted samples were analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Chromatographic separation of analytes was performed on an InertSustain AQ-C18 HP column (3 µm, 2.1 × 50 mm) under the reversed-phase condition with gradient elution. With the assay, linear calibration curves were obtained over the concentration range of 10-1200 pg/mL for budesonide, with considerable extraction recoveries (84.7-89.4%), and negligible matrix effects (<4.1). Moreover, the newly developed method was successfully applied to the evaluation of pharmacokinetics of two budesonide intranasal formulations with and without charcoal block in healthy volunteers.


Simultaneous on-line size and chemical analysis of gas phase and particulate phase of cigarette mainstream smoke.
This paper describes the combined set-up of on-line chemical analysis of gas phase by single-photon ionisation/resonance enhanced multiphoton ionisation-time-of-flight mass spectrometry (SPI/REMPI-TOFMS) and on-line particle size analysis by differential electrical mobility particle spectrometry (DMS 500) for the investigation of fresh cigarette mainstream smoke. SPI is well suited for the investigation of a great variety of organic species, whereas REMPI is highly sensitive for aromatic compounds. Gas phase measurements of filtered and unfiltered smoke are possible with the SPI/REMPI-TOFMS in order to determine the influence of the presence of particles on the chemical composition of the gas phase. Initial results are shown for the characterisation and comparison of three pure Virginia tobacco research cigarettes having filter ventilations of 0%, i.e. no filter ventilation, 35% and 70% ventilation. The three cigarette types are smoked under two different smoking regimes, a standard regime using puff parameters equivalent to the conventional International Standard Organisation regime and a more intense smoking regime. For the gas phase, qualitative puff-by-puff resolved yields of three selected compounds (acetaldehyde, phenol and styrene) are shown and compared. For particulate matter, particle number, count median diameter and total surface area are illustrated on a puff-by-puff basis. Yields of the chemicals analysed, puff number and surface area are in good agreement with the intensity of the smoking regime and the dilution of smoke by filter ventilation. However, gaseous compounds are influenced differently, depending whether an absolute particle filter is present or not, i.e. they can be totally removed (phenol), partially removed (styrene) or not affected (acetaldehyde). For particle analysis, the count median diameter decreases from puff to puff and is strongly dependent on the smoking regime and ventilation rate. Thereby, 0% ventilated cigarettes smoked under the intense regime result in the smallest count median diameters of ca. 180 nm, whereas 70% ventilated cigarettes smoked with a standard regime lead to the largest values of up to 280 nm. As particle diameter increases, particle number decreases as a consequence of increasing time for particle coagulation.


Turcot syndrome in an elderly adult.
A 67-year-old woman presented with hematochezia and an episode of transient expressive dysphasia. She was found to have multiple colonic polyps with adenocarcinomatous changes. Computed tomography brain scan and computed tomography-guided biopsy revealed a left frontoparietal glioblastoma multiforme. This case illustrates the rare presentation of Turcot syndrome-a hereditary colorectal polyposis syndrome-in an older adult.


Activity and viability of methanogens in anaerobic digestion of unsaturated and saturated long-chain fatty acids.
Lipids can be anaerobically digested to methane, but methanogens are often considered to be highly sensitive to the long-chain fatty acids (LCFA) deriving from lipids hydrolysis. In this study, the effect of unsaturated (oleate [C18:1]) and saturated (stearate [C18:0] and palmitate [C16:0]) LCFA toward methanogenic archaea was studied in batch enrichments and in pure cultures. Overall, oleate had a more stringent effect on methanogens than saturated LCFA, and the degree of tolerance to LCFA was different among distinct species of methanogens. Methanobacterium formicicum was able to grow in both oleate- and palmitate-degrading enrichments (OM and PM cultures, respectively), whereas Methanospirillum hungatei only survived in a PM culture. The two acetoclastic methanogens tested, Methanosarcina mazei and Methanosaeta concilii, could be detected in both enrichment cultures, with better survival in PM cultures than in OM cultures. Viability tests using live/dead staining further confirmed that exponential growth-phase cultures of M. hungatei are more sensitive to oleate than are M. formicicum cultures; exposure to 0.5 mM oleate damaged 99% ± 1% of the cell membranes of M. hungatei and 53% ± 10% of the cell membranes of M. formicicum. In terms of methanogenic activity, M. hungatei was inhibited for 50% by 0.3, 0.4, and 1 mM oleate, stearate, and palmitate, respectively. M. formicicum was more resilient, since 1 mM oleate and >4 mM stearate or palmitate was needed to cause 50% inhibition on methanogenic activity.


Neonatal outcomes in immediate versus delayed conceptions after spontaneous abortion: a retrospective case series.
This study was undertaken to determine differences in neonatal outcomes between successful pregnancies conceived immediately after a spontaneous abortion (SAB) and successful pregnancies conceived after two menstrual cycles or at least 100 days from the spontaneous abortion. This study was a retrospective case series. Deliveries were identified from the University of California-San Francisco Perinatal Database among patients with a history of one SAB. Medical records of 268 patients were reviewed. Sixty-four patients fulfilled study criteria, with 19 in the immediate conception group and 45 in the delayed conception group. Categorical variables were analyzed using chi(2) tests and Fisher exact tests for variables with expected values of <5, whereas continuous variables were analyzed using Student t tests. Neonatal outcomes for the 2 groups were similar, although neonates in the delayed conception group were more likely to have at least one of the following: low birth weight, an Apgar score <7 at 5 minutes, or admission to the neonatal intensive care unit. In this small retrospective case series, there was no evidence of adverse neonatal outcomes associated with conception immediately after a SAB.


Cell surface antigens of Bordetella pertussis.
Cell surface-specific radiolabelling techniques, monoclonal antibody analyses, and chemical and physical isolation of cell fractions were used to study the surface of B. pertussis cells. Four surface specific proteins were identified by radioiodination and monoclonal antibody techniques. These included the filamentous hemagglutinin (FHA), and three outer membrane proteins-OMP91, OMP18 and OMP15. Membrane blebs were isolated from culture supernatants and shown to contain LPSII, pertussis toxin (PT), FHA, OMP91, and OMP18, but not OMP15. The level of LPS I in blebs appeared to be reduced from the level in cell envelopes. Bleb fractions contained enzymatically active adenylate cyclase (AC), and biologically active dermonecrotic toxin (DNT) and PT. Blebs were also toxic for mice, even when heated to 80 degrees C for 30 minutes. To explain these data, we propose that membrane blebs comprise an effective toxin delivery system, and that the cell surface of B. pertussis is composed of at least two domains.


Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?
Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity.


Vancomycin-resistant enterococcus outbreak in a pediatric intensive care unit: report of successful interventions for control and prevention.
The objective of this study is to retrospectively report the results of interventions for controlling a vancomycin-resistant enterococcus (VRE) outbreak in a tertiary-care pediatric intensive care unit (PICU) of a University Hospital. After identification of the outbreak, interventions were made at the following levels: patient care, microbiological surveillance, and medical and nursing staff training. Data were collected from computer-based databases and from the electronic prescription system. Vancomycin use progressively increased after March 2008, peaking in August 2009. Five cases of VRE infection were identified, with 3 deaths. After the interventions, we noted a significant reduction in vancomycin prescription and use (75% reduction), and the last case of VRE infection was identified 4 months later. The survivors remained colonized until hospital discharge. After interventions there was a transient increase in PICU length-of-stay and mortality. Since then, the use of vancomycin has remained relatively constant and strict, no other cases of VRE infection or colonization have been identified and length-of-stay and mortality returned to baseline. In conclusion, we showed that a bundle intervention aiming at a strict control of vancomycin use and full compliance with the Hospital Infection Control Practices Advisory Committee guidelines, along with contact precautions and hand-hygiene promotion, can be effective in reducing vancomycin use and the emergence and spread of vancomycin-resistant bacteria in a tertiary-care PICU.


Use of N-Bromoacetyl-l-ornithine to Study l-Ornithine and l-Arginine Biosynthesis in Soybean (Glycine max L.) Cell Cultures.
The effect of the inhibitor N(2)-bromoacetyl-l-ornithine (NBAO) on the biosynthesis of ornithine in higher plants, was investigated using soybean cells (Glycine max L. var Mandarin), grown in suspension culture. The NBAO was found to reduce the specific activity of the enzyme N(2)-acetyl-l-ornithine: l-glutamate N-acetyltransferase (EC 184.108.40.206). In contrast, the specific activity of the enzyme acetyl coenzyme A:L-glutamate N-acetyltransferase (EC 188.8.131.52), which is also involved in N-acetylglutamate biosynthesis, was not significantly changed. Estimation of the concentrations of free amino acids in the soluble fraction of the cells showed that while ornithine levels were decreased, glutamic acid levels were increased in the presence of NBAO. While arginine levels initially increased in the presence of NBAO, they finally decreased near the end of the growth period. Evidence was obtained that the initial increase in arginine levels was due to the inhibition of arginase (EC 126.96.36.199) by N(2)-bromoacetyl l-ornithine. We conclude that the reaction catalyzed by N(2)-acetyl-l-ornithine:l-glutamate N-acetyl transferase is a rate limiting reaction in vivo.


Theophylline dose prediction.
Two methods of predicting the optimal dose of theophylline in children aged 2 to 13 years were assessed. The observed plasma concentration was within 95% confidence limits of that predicted on eight of 14 occasions using a traditional multiple point pharmacokinetic method. Using a nomogram derived from the plasma concentration 6 hours after dosing and the logarithm of the calculated dose, which were significantly correlated, there was a significant relation between the dose predicted and the actual dose required to produce a concentration of 55 mumol/l.


MRCP Versus ERCP in the Evaluation of Chronic Pancreatitis in Children: Which Is the Better Choice?
To evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) in the detection of chronic pancreatitis (CP)-specific changes in the pediatric population. The study included 48 children with pancreatic disorders subjected to both endoscopic retrograde cholangiopancreatography (ERCP) and MRCP within a 1- to 4-month interval. The sensitivity, specificity, positive predictive value, and negative predictive value of MRCP in the detection of CP-specific changes were determined using ERCP as a diagnostic standard. Diagnostic ERCP pancreatograms were obtained in 41 (85.4%) of 48 patients and diagnostic MRCP images in all 48 children. The sensitivity and positive predictive value of MRCP were 77.1% and 90%, respectively, and its specificity and negative predictive value amounted to 50% and 27.3%, respectively. The patients with consistent results of MRCP and ERCP (ie, true-positive and true-negative cases) and individuals with incompatible results of the tests (ie, false-positive and false-negative cases) differed in terms of their median age at MRCP (14.17 vs 10.33 years) and median CP stage according to the Cambridge Scale (4 vs 2). Magnetic resonance cholangiopancreatography provides diagnostic information equivalent to ERCP in a large percentage of pediatric patients with CP and should be used as the imaging method of choice, especially if the likelihood of therapeutic intervention is low.


Dimethyl 2,6-dimethyl-4-(2-nitro-phen-yl)pyridine-3,5-dicarboxyl-ate.
The title compound, C(17)H(16)N(2)O(6), is a decomposition product of the hypertension drug nifedipine [systematic name: dimethyl 2,6-dimethyl-4-(2-nitro-phen-yl)-1,4-dihydro-pyridine-3,5-dicarboxyl-ate]. The dihedral angle between the nitro-sophenyl ring and the pyridine ring is 67.1 (5)°.


Nitric oxide and changes of iron metabolism in exercise.
Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed.


Immunohistochemical detection of HER-2/neu expression in spontaneous feline mammary tumours.
Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER-2/neu protooncogene encodes a 185-kDa transmembrane tyrosine receptor kinase protein. Approximately 25-30% of human MGT demonstrate HER-2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis. No reports have been published, to date, investigating the expression of Her-2/neu in cats or cats with spontaneous mammary tumours. Based on the increased percentage of malignant mammary cancers in cats, compared to that in dogs, and the correlation of an increased malignancy and a decreased prognosis with Her-2 overexpression in human mammary cancer, we hypothesized that cats with spontaneous malignant mammary adenocarcinoma overexpress Her-2/neu in the neoplastic mammary epithelial cells. Thirty cats with MGT were assayed for Her-2/neu immunohistochemical expression. The median percentage of cells from feline MGT expressing Her-2/neu by utilizing the Dako polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her-2/neu expression intensity grades 2 and 3 consistent with the overexpression by utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90 and 76.7% of cats with MGT, respectively. The level of overexpression concordance across the two antibodies was 70%. The results from this study suggest that Her-2/neu overexpression is common in cats with spontaneous MGT, and therefore appears to represent an excellent model for Her-2/neu-overexpressing human breast cancer.


Human natural antibodies to Culex quinquefasciatus: age-dependent occurrence.
The titer of anti-Culex quinquefasciatus antibodies which were mostly of IgG and IgE isotypes was determined in humans living in Wuchereria bancrofti endemic regions. A progressive increase in the titer of antibodies was observed with age. In contrast, sera from people living in regions where the Cx. quinquefasciatus is of low prevalence were found to have markedly reduced IgG and almost zero IgE levels.


Epigenetics of neurological cancers.
Epigenetic mechanisms involving DNA methylation, histone modifications and noncoding RNAs regulate and maintain gene-expression states. Similar to genetic mutations, alterations in epigenetic regulation can lead to uncontrolled cell division, tumor initiation and growth, invasiveness and metastasis. Research in brain cancer, particularly gliomas, has uncovered global and gene-specific DNA hypomethylation, local DNA hypermethylation of gene promoters and the de-regulation of microRNA expression. Understanding epigenetic dysregulation in brain cancers has provided new tools for prognostication, as well as suggesting new approaches to therapy. There is significant interest in new sequencing-based technologies that map genetic and epigenetic alterations comprehensively and at high resolution. These methods are being applied to brain tumors, and will better define the contribution of epigenetic defects to tumorigenesis.


A new earthworm cellulase and its possible role in the innate immunity.
A new endogenous cellulase (Ean-EG) from the earthworm, Eisenia andrei and its expression pattern are demonstrated. Based on a deduced amino acid sequence, the open reading frame (ORF) of Ean-EG consisted of 1368 bps corresponding to a polypeptide of 456 amino acid residues in which is contained the conserved region specific to GHF9 that has the essential amino acid residues for enzyme activity. In multiple alignments and phylogenetic analysis, the deduced amino acid sequence of Ean- EG showed the highest sequence similarity (about 79%) to that of an annelid (Pheretima hilgendorfi) and could be clustered together with other GHF9 cellulases, indicating that Ean-EG could be categorized as a member of the GHF9 to which most animal cellulases belong. The histological expression pattern of Ean-EG mRNA using in situ hybridization revealed that the most distinct expression was observed in epithelial cells with positive hybridization signal in epidermis, chloragogen tissue cells, coelomic cell-aggregate, and even blood vessel, which could strongly support the fact that at least in the earthworm, Eisenia andrei, cellulase function must not be limited to digestive process but be possibly extended to the innate immunity.


Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction.
Research over the past four decades has highlighted the importance of certain brain cells, called glial cells, and has moved the neurocentric vision of structure, function, and pathology of the nervous system toward a more holistic perspective. In this view, the demand for technologies that are able to target and both selectively monitor and control glial cells is emerging as a challenge across neuroscience, engineering, chemistry, and material science. Frequently neglected or marginally considered as a barrier to be overcome between neural implants and neuronal targets, glial cells, and in particular astrocytes, are increasingly considered as active players in determining the outcomes of device implantation. This review provides a concise overview not only of the previously established but also of the emerging physiological and pathological roles of astrocytes. It also critically discusses the most recent advances in biomaterial interfaces and devices that interact with glial cells and thus have enabled scientists to reach unprecedented insights into the role of astroglial cells in brain function and dysfunction. This work proposes glial interfaces and glial engineering as multidisciplinary fields that have the potential to enable significant advancement of knowledge surrounding cognitive function and acute and chronic neuropathologies.


Singlet oxygen photosensitisation by GFP mutants: oxygen accessibility to the chromophore.
Aiming at the rational development of genetically-encoded photosensitisers, the production of singlet oxygen has been assessed for a number of class-2 Green Fluorescent Protein (GFP) mutants by means of time-resolved near-infrared luminescence detection. The accessibility of molecular oxygen to the chromophore seems to play a major role in the ability of GFPs to photosensitise singlet oxygen and this can be modulated by introducing specific mutations such as replacement of His148 by a less bulky amino acid. GFPs are also good singlet oxygen quenchers, hence further developments in this area should also seek to eliminate those amino acids with the highest quenching ability, particularly those at the protein surface and in the vicinity of the chromophore.


Up-regulatory impact of boron on vitamin D function -- does it reflect inhibition of 24-hydroxylase?
Nutritional intakes of boron have been shown to lessen the adverse consequences of vitamin D deficiency in rodents. Pilot clinical studies suggest that this effect may be mediated, in whole or in part, by an increase in serum 25-hydroxyvitamin D. We propose that, in concentrations achievable with good diets, boron suppresses the activity of the microsomal enzyme 24-hydroxylase, chiefly responsible for catabolism of this steroid. This inhibition may reflect a direct interaction with the enzyme, or perhaps boron's ability to form a covalent complex with the product of its activity, 24,25-dihydroxyvitamin D. An up-regulatory impact of boron on 25-hydroxyvitamin D is potentially beneficial in light of the fact that the vitamin D status of many individuals is poor during winter months, and traditional supplemental doses of this vitamin are often too low to correct this problem. There is growing evidence that good vitamin D status -- as reflected by 25-hydroxyvitamin D levels -- may reduce risk for a host of prominent disorders; thus, boron may have the ability to potentiate this protection. Clinical studies also suggest that nutritional boron can up-regulate 17beta-estradiol levels in women, including postmenopausal women receiving hormone replacement therapy. The catabolism of this hormone is achieved by microsomal enzymes catalyzing vicinal hydroxylations -- a description that also applies to 24-hydroxylase. This suggests the more general hypothesis that nutritional boron can inhibit a range of microsomal enzymes which insert hydroxyl groups vicinal to existing hydroxyls in steroids -- including the enzymes which catabolize estradiol and 25-hydroxyvitamin D.


Polar solvation dynamics in water and methanol: search for molecularity.
Time-dependent Stokes shifts (TDSS) were measured for diverse polarity probes in water, heavy water, methanol, and benzonitrile, by broadband fluorescence up-conversion with 85 fs time resolution. In water the spectral dynamics is solute-independent and quantitatively described by simple dielectric continuum theory of solvation. In methanol the slower part of the TDSS is solute-dependent. A correlation with anisotropy decay suggests that methanol solvation dynamics is modulated by orientational solute diffusion. An empirical power law which links the solvation relaxation function of a mobile solute to that of an immobile solute is experimentally verified. Activation energies for the average relaxation rate are also given. Solvation dynamics in H(2)O and D(2)O are identical at and above 20 °C but diverge below.


Muscle activity response to external moment during single-leg drop landing in young basketball players: the importance of biceps femoris in reducing internal rotation of knee during landing.
Internal tibial rotation with the knee close to full extension combined with valgus collapse during drop landing generally results in non-contact anterior cruciate ligament (ACL) injury. The purpose of this study was to investigate the relationship between internal rotation of the knee and muscle activity from internal and external rotator muscles, and between the internal rotation of knee and externally applied loads on the knee during landing in collegiate basketball players. Our hypothesis was that the activity of biceps femoris muscle would be an important factor reducing internal knee rotation during landing. The subjects were 10 collegiate basketball students: 5 females and 5 males. The subjects performed a single-leg drop landing from a 25-cm height. Femoral and tibial kinematics were measured using a 3D optoelectronic tracking system during the drop landings, and then the knee angular motions were determined. Ground reaction forces and muscle activation patterns (lateral hamstring and medial hamstring) were simultaneously measured and computed. Results indicated that lower peak internal tibial rotation angle at the time of landing was associated with greater lateral hamstring activity (r = -0.623, p < 0.001). When gender was considered, the statistically significant correlation remained only in females. There was no association between the peak internal tibial rotation angle and the knee internal rotation moment. Control of muscle activity in the lateral to medial hamstring would be an important factor in generating sufficient force to inhibit excessive internal rotation during landing. Strengthening the biceps femoris might mitigate the higher incidence of non-contact ACL injury in female athletes. Key pointsLower activity of the external rotator muscle of the knee, which inhibits internal rotation of the knee, may be the reason why females tend to show a large internal rotation of the knee during drop landing.Externally applied internal rotation moment of the knee during landing would not be expected to explain why female athletes tend to show excessive internal knee rotation.Biceps femoris strength training might help decrease the incidence of non-contact ACL injury in female athletes.


Corrosion behavior and surface characterization of Ti-20Cr alloy in a solution containing fluoride.
The purpose of this study was to investigate the correlation between corrosion resistance and surface composition of an experimental Ti-20 mass% Cr casting alloy in a saline solution containing fluoride. The alloy had a greater resistance to corrosion in a fluoride-containing saline solution than did commercially pure titanium. However, with confirmed dissolution of titanium and chromium, it meant that the fluoride in the saline solution corroded the alloy slightly. X-ray photoelectron spectroscopy analysis revealed that the surface composition of the alloy consisted of titanium and chromium oxides containing hydroxide. The [Ti]/([Ti] + [Cr]) ratio in the surface oxide film decreased when immersed in fluoride-containing saline solution, that is, the surface oxide film became chromium-rich oxide. Therefore, the alloy obtained good corrosion resistance to fluoride due to formation of a chromium-rich oxide film.


The role of intersensory redundancy in the emergence of social referencing in 5½-month-old infants.
Early evidence of social referencing was examined in 5½-month-old infants. Infants were habituated to 2 films of moving toys, one toy eliciting a woman's positive emotional expression and the other eliciting a negative expression under conditions of bimodal (audiovisual) or unimodal visual (silent) speech. It was predicted that intersensory redundancy provided by audiovisual (but not available in unimodal visual) events would enhance detection of the relation between emotional expressions and the corresponding toy. Consistent with predictions, only infants who received bimodal, audiovisual events detected a change in the affect-object relations, showing increased looking during a switch test in which the toy-affect pairing was reversed. Moreover, in a subsequent live preference test, they preferentially touched the 3-dimensional toy previously paired with the positive expression. These findings suggest social referencing emerges by 5½ months in the context of intersensory redundancy provided by dynamic multimodal stimulation and that even 5½-month-old infants demonstrate preferences for 3-dimensional objects on the basis of affective information depicted in videotaped events.