Highly efficient debromination of 4,4'-dibrominated diphenyl ether by organic palygorskite-supported Pd/Fe nanoparticles.
Organic palygorskite (OP)-supported Pd/Fe nanoparticles composite (OP-Pd/Fe) was prepared by stepwise reduction method. The removal capacity of 4,4'-dibrominated diphenyl ether (BDE15) by OP-Pd/Fe was compared with other various materials. For better understanding the possible mechanism, the synthesized and reacted OP-Pd/Fe materials were characterized by TEM, SEM, XRD, and XPS, respectively. The effects of major influencing parameters on the degradation of BDE15 were also studied. Benefit from the synergistic effect of the carrier and bimetallic nanoparticles, BDE15 could be completely debrominated into diphenyl ether (DE) under suitable conditions. A two-stage adsorption/debromination removal mechanism was proposed. The degradation of BDE15 with OP-Pd/Fe was mainly stepwise debromination reaction, and hydrogen transfer mode was assumed as the dominated debromination mechanism. The removal process fitted well to the pseudo first-order kinetic equation. The observed rate constants increased with increasing Pd loading and OP-Pd/Fe dosage while decreased with increasing initial BDE15 concentration, the tetrahydrofuran/water ratio, and the initial pH of the solution. The work provides a new approach for the treatment of PBDEs pollution.


Catalase overexpression impairs TNF-alpha induced NF-kappaB activation and sensitizes MCF-7 cells against TNF-alpha.
The pleiotropic cytokine tumor necrosis factor alpha (TNF-alpha) can induce apoptosis but also supports cell survival pathways. Among the possible anti-apoptotic mechanisms of TNF-alpha is the activation of the transcription factor NF-kappaB. Since reactive oxygen species (ROS) are assumed to contribute to TNF-alpha mediated cytotoxicity but can also facilitate NF-kappaB activation this study investigates the relationship between TNF-alpha treatment, NF-kappaB activation and the expression of the anti-oxidative enzyme catalase. TNF-alpha treatment caused downregulation of catalase expression in MCF-7, Caco-2 and Hct-116 cancer cell lines. Overexpression of catalase in MCF-7 cells, resulting in lower intracellular ROS levels upon challenge with H(2)O(2), caused a transient nuclear p65 translocation upon TNF-alpha treatment as compared to the sustained NF-kappaB activation in wild type cells. This was due to a lack of sufficient H(2)O(2) to co-stimulate NF-kappaB activation as demonstrated by the observation that addition of exogenous H(2)O(2) led to a second increase of NF-kappaB activity. The rapid decline of nuclear translocation of NF-kappaB in the catalase overexpressing cells resulted in a slower increase of NF-kappaB mediated reporter gene expression. These results indicate that TNF-alpha mediated downregulation of catalase expression and accordingly sufficient H(2)O(2) is required for appropriate function of the NF-kappaB dependent survival pathway.


Health-related quality of life and impact of haemangiomas on children and their parents.
Haemangiomas are the most common tumours of infancy, they are often present on the face and can lead to disfigurement. The aim of our study was to assess the health-related quality of life (HRQoL) of children aged 1-15 years with a haemangioma and their parents in comparison with healthy children, and to assess the impact on their life. Furthermore, we investigated if visibility and a complicated course of the haemangioma had influence on these outcomes. Age-specific validated HRQoL and haemangioma-specific questionnaires were sent to all children seen at the AMC in Amsterdam at the plastic surgery or dermatology departments. Two hundred and one parents of children with a haemangioma returned the questionnaire (85%). The majority of parents and patients with a haemangioma are not negatively affected by it. Concerning HRQoL, parents of children aged 8 to 11 years reported their children to have more negative emotions. Children aged 12 to 15 reported a better HRQoL for physical symptoms, and positive emotions. No differences were found in the HRQoL questionnaires between visibility and complicated course. Significant differences occur in the specific haemangioma questionnaire. High scores on feelings of disbelief and panic during the growing phase are given by parents and patients agree with the statement on whether their life would be different without a haemangioma, especially when the haemangioma was visible and/or had a complicated course. This is the first study to describe the HRQoL of children with haemangiomas. The psychosocial consequences of a haemangioma are feared by physicians and parents. The most important finding of this study is that the majority of children of all ages and their parents feel children with haemangiomas can live a good life. There is reason, however, to believe that having a haemangioma, especially one with a complicated course or a visible location, could result in psychosocial problems later in life, mostly related to physical appearance.


Improvement of osseointegration by recruiting stem cells to titanium implants fabricated with 3D printing.
Slow and incomplete osseointegration and loss of osseointegration are major problems in dental and bone implants. We designed implants with interconnected 3D-tubulous structures and hypothesized that such interconnecting 3D (I3D) structures would serve as a repository for chemoattractants to recruit stem cells to promote osseointegration. A concept Laser Mlab-cusing-R laser-powder-bed-fusion (LPBF) 3D printing system was used to produce titanium implants with designed features. The implants were loaded (coated) with stromal cell-derived factor-1 alpha (SDF-1α), and subjected to stem cell recruitment. Implants were then surgically transplanted into the rabbit skull bone. After 12 weeks, osseointegration was analyzed by reverse-torque test and the implants were examined for calcium deposition by Alizarin Red staining. The I3D implants attracted significantly more stem cells than solid implants when coated (loaded) with SDF-1α. Greater torque force was needed to extract the I3D implants with 200 and 300 µm I3D structures than to extract solid implants from the skull. Generally, more calcium deposition was observed on the I3D implants than on the solid counterparts. LPBF 3D printing can be used to fabricate implants with complex structures. I3D-tubulous structures of implants can retain chemoattractant for recruitment of stem cells to enhance osseointegration.


Comparison of two methods for detecting intrathecal synthesis of Borrelia burgdorferi-specific antibodies and PCR for diagnosis of Lyme neuroborreliosis.
An indirect immunofluorescence assay (IFA), a commercial capture enzyme-linked immunosorbent assay (ELISA), and PCR were compared for the diagnosis of Lyme neuroborreliosis in 16 individuals. Borrelia burgdorferi-specific intrathecal immunoglobulin G was found in 10 of 16 patients by IFA and in 8 of 12 patients by capture ELISA. PCRs performed on cerebrospinal fluid samples stored at -70 degrees C were positive for one of eight children and one of four adults with intrathecal antibody production and negative for all four adults without intrathecal antibody production. For two children with facial palsy following erythema chronicum migrans, neither IFA nor capture ELISA detected specific intrathecal antibodies and PCR was also negative. We conclude that both clinical manifestations and laboratory parameters are important for the diagnosis of Lyme neuroborreliosis.


Biparental genetic mapping reveals that CmCLAVATA3 (CmCLV3) is responsible for the variation in carpel number in melon (Cucumis melo L.).
Genetic analysis revealed that CmCLV3 is a candidate gene for the variation in melon carpel number. Carpel number (CN) is an important trait in melon. Three-CN melon fruit is oval, while 5-CN melon fruit has a round or flat shape. Herein, a genetic analysis of a population in which the CN locus was segregated indicated that 3-CN is controlled by a major dominant effective gene. Bulked segregant analysis and initial linkage mapping placed the CN locus in a 6.67 Mb region on chromosome 12, and it was narrowed to 882.19 kb with molecular markers and recombinant plants. Fine mapping with a large F2 population containing 1026 individuals further narrowed the locus to an 83.98 kb region harboring five annotated genes. Gene structure alignment between the parental lines revealed MELO3C035640.2 (annotated as CLAVATA3, CmCLV3) as the best candidate gene for the CN trait. CmCLV3 was more highly expressed in 3- than 5-CN lines and specifically expressed in terminal buds rather than in young leaves, hypocotyls, and roots. The CmCLV3 coding region was cloned from eight 3- or 5-CN melon accessions, and a nonsynonymous SNP site was highly correlated with CN variation. This SNP site was also related to CN variations among 40 melon lines according to their resequencing data, causing a helix alteration in the CmCLV3 protein. Promoter region sequence alignment and activity analysis showed that, unlike in cucumber and tomato, CmCLV3 promoter variation and activity were not the main reasons for CN alteration. Overall, this study provides a genetic resource for melon fruit development research and molecular breeding tools for melon CN improvement.


Regulation of Cl- Electrolyte Permeability in Epithelia by Active Traditional Chinese Medicine Monomers for Diarrhea.
The epithelial layer, lining the inner surface of the mammalian alveolar, kidney, brain and colon, is a typical electrolyte transporting tissue. Large quantities of salt and fluid are actively moved from the mucosal side toward the blood vessel. Transepithelial salt re-absorption in epithelial tissues plays an important role in maintaining fluid homeostasis. In absorptive epithelium, fluid and salt flux is controlled by the machinery mainly composed of epithelial sodium channel, cystic fibrosis transmembrane conductance regulator, Na+-K+-2Cl- cotransporter, Na+/H+ exchanger, and Na+/K+-ATPase. Dysregulation of salt permeability across epithelium contributes to the pathogenesis of organ edema. In numerous ion transporters, epithelial Cl- transportation plays an important role in water secretion across epithelial tissues and regulation of body fluid content. Many traditional Chinese medicines treat diarrhea by regulating the Cl- electrolyte transport. We systematically summarized the recent progress regarding the traditional Chinese medicine on Cl- electrolyte transport in the intestinal epithelial tissues. The pharmaceutical relevance of developing advanced strategies to mitigate edematous disorders is also implicated. In conclusion, the crosstalk between Cl- electrolyte transport and active traditional Chinese medicine monomers may lead to the development of new strategies for diarrhea by manipulating the function and expression of ion channels.


Gene network biological validity based on gene-gene interaction relevance.
In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.


The mean visible labial length of maxillary and mandibular anterior teeth at rest.
To determine the mean visible labial length of maxillary and mandibular anterior teeth at rest. Cross-sectional study. Department of Prosthodontics, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Karachi, from October 2012 to March 2013. A total of 200 subjects were included. Measurements were carried out using digital caliper from the border of the lip to the incisal edges of incisor and to the cusp tip for the canines. The length of the upper lip was measured from subnasale to stomion. Statistical analyses were performed by Mann Whitney-U test and Kruskal Walli's test. The age of the participant ranged between 20 and 65 years. At rest, females significantly displayed more of the maxillary central incisor (2.93 ± 1.57 mm; p=0.003), lateral incisor (1.87 ± 1.12 mm; p=0.005) and canine (0.59 ± 0.62 mm; p=0.031). With increasing age, the amount of maxillary anterior teeth visible at rest significantly decreased (p < 0.001), and increased for the mandibular teeth (p < 0.001). Subjects with shorter upper lips significantly displayed more maxillary anterior incisor structure than subjects with longer upper lip (p < 0.001). Females displayed significantly more labial length of the maxillary anterior teeth. The mean visible labial length of maxillary anterior teeth significantly decreased with increasing age and increased for the mandibular teeth. As the upper lip length increased, the mean visible labial length of maxillary anterior teeth significantly decreased.


Expression of CYP71B7, a cytochrome P450 expressed sequence Tag from Arabidopsis thaliana.
The systematic sequencing of anonymous cDNA clones (expressed sequence tags or ESTs) from the plant Arabidopsis thaliana has identified a number of cDNAs with similarity to known cytochrome P450 sequences. The partial sequence of one of these cDNAs, 5G6, indicated that it was likely to encode a full-length cytochrome P450 monooxygenase (cyt P450) sequence. In this paper we describe the complete sequence of this clone, which has been designated CYP71B7 in accordance with the nomenclature for the cyt P450 gene superfamily. The cDNA was used to determine the pattern of expression of the corresponding gene in A. thaliana. Northern hybridization analysis indicated that maximal expression of CYP71B7 occurred in rosette leaves. Weaker hybridizing bands were also detected by Northern analysis of RNA from roots, leaves, flowers, and siliques. No expression could be detected in stem tissue. Southern analysis indicated that the CYP71B7 gene was likely to exist as a single copy in the genome of A. thaliana. CYP71B7 was expressed episomally in yeast, and microsomes prepared from transgenic yeast exhibited a carbon monoxide difference spectrum characteristic of cyt P450. Microsomes from yeast expressing CYP71B7 were assayed for enzymatic activity with synthetic model cyt P450 substrates. Microsomes from yeast cells expressing CYP71B7 or those from control cells exhibited no detectable NADPH-supported 7-ethoxycoumarin or 7-ethoxyresorufin deethylase activities. However, in the presence of cumene hydroperoxide, activity was observed with microsomes from cells expressing CYP71B7 with 7-ethoxycoumarin as substrate. Organic hydroperoxides are well known to support cyt P450 catalysis in the absence of electrons from NADPH. The yeast microsomes contained high levels of endogenous NADPH-ferricytochrome P450 reductase (CPR) activity. The data suggest that this A. thaliana cyt P450, although expressed in an active form, is incapable of accepting electrons from the endogenous yeast CPR protein.


Aldosterone response to adrenocorticotrophin and furosemide in primary aldosteronism after prolonged spironolactone treatment.
We evaluated the effects of prolonged spironolactone treatment on aldosterone secretion in patients with primary aldosteronism. The patients were hospitalized and underwent a furosemide test with or without dexamethasone, as well as an adrenocorticotrophin (ACTH) test. In untreated patients, neither plasma renin activity (PRA) nor plasma aldosterone showed a response in the furosemide test. In patients receiving spironolactone, furosemide increased significantly both the PRA and the plasma aldosterone concentration (from 2.6 +/- 0.8 to 7.0 +/- 2.0 micrograms.l-1.h-1 (p < 0.05) and from 345.6 +/- 55.8 to 492.7 +/- 76.8 ng/l (p < 0.05), mean +/- SEM, respectively). Dexamethasone administration had no effect on the results of the furosemide test (p > 0.1). However, dexamethasone tended to decrease the basal plasma aldosterone concentration in the untreated patients, but not in the patients receiving spironolactone. In the ACTH test, the plasma aldosterone concentration increased significantly in the untreated patients (from 549.0 +/- 69.8 to 1169.3 +/- 165.5 ng/l, p < 0.01), but there was no significant aldosterone response in the spironolactone-treated patients (from 885.5 +/- 204.9 to 1260.3 +/- 289.2 ng/l, p > 0.1). We conclude that aldosterone secretion is mainly dependent on ACTH in the untreated patients with primary aldosteronism and is more strongly regulated by the renin-angiotensin system during spironolactone treatment.


Model of spatio-temporal propagation of action potentials in the Schaffer collateral pathway of the CA1 area of the rat hippocampus.
There is a sharp contrast between the profuse in vivo axonal arborization of CA3 pyramidal cells in the CA1 area and the low probability of finding pairs of connected CA3-CA1 pyramidal cells in vitro. These anatomical differences contribute to a connectivity argument for discrepancies between electrophysiological data recorded in vitro and in vivo. In order to investigate this issue, we have developed a realistic computer model of the Schaffer collateral pathway of the hippocampus and analyzed the spatio-temporal distribution of action potentials along this pathway following three different types of electrical test stimulus. Direct activation of mossy fibers, CA3 pyramidal cells and focal stimulation of CA1 stratum radiatum were investigated. The parameters of the model were selected from available biological data. Spikes in Schaffer collaterals were followed from their onset in the CA3 pyramidal cell initial segment to the last order branches of their axonal tree in two types of configuration: the whole hippocampus and the slice configuration. The anatomical and electropysiological characteristics of the mossy fibre and Schaffer collateral pathways were found to impose strong constraints on the spatio-temporal distribution of action potentials in the CA1 area. Specific projection zones are determined by the spatial localization of the emitting CA3 pyramidal cells. Their position also defines precise time windows during which some CA1 projection zones receive a large number of correlated signals. Moreover, the variability of the delay at the mossy fibre/CA3 pyramidal cell synapse seems to provide the CA1 projection zones with a background level of excitation. Finally, we show how the patterns of activation obtained in the whole hippocampus are different from those obtained in the slice.


Mesenchymal stromal cells from female donors enhance breast cancer cell proliferation in vitro.
The interplay between tumor stroma and breast cancer cells (BCCs) is thought to play a significant role in breast cancer. The current knowledge of human mesenchymal stromal cell (MSC) and BCC interaction is contradictory, and the donor sex issue is not addressed at all. We hypothesized that donor sex could have an effect on proliferation of MSCs or BCCs in co-culture in vitro. Three estrogen receptor-negative BCC lines, 19 primary human MSCs and breast tissue-derived fibroblasts from 4 donors were used. MSCs from female donors enhanced BCC proliferation (p = 0.005). The change in BCC proliferation was only partly due to soluble factors excreted by MSCs. The highly aggressive BCC line MDA-MB- 231 induced the proliferation of MSCs (p < 0.001) and fibroblasts (p = 0.037) in co-culture experiments. The magnitude in proliferation change was cell line dependent and partly sex dependent.


EPIDEMIOLOGY OF HONEYBEE STING CASES IN THE STATE OF CEARÁ, NORTHEASTERN BRAZIL.
In the American continent, honeybee envenomation is a public health problem due to the high incidence and severity of the cases. Despite its medical importance, there is a lack of epidemiological studies on this topic in Brazil, especially referring to the Northeastern states. The present study has aimed to describe the epidemiological features of honeybee envenomation cases in the state of the Ceará, Northeastern Brazil, from 2007 to 2013. Data were collected from the Injury Notification Information System database of the Health Department of Ceará. A total of 1,307 cases were analyzed. Cases were shown to be distributed in all the months of the studied years, reaching higher frequencies in August. The majority of cases occurred in urban areas and involved men aged between 20 and 29 years. Victims were mainly stung on the head and torso, and they received medical assistance predominantly within 3 hours after being stung. Local manifestations were more frequent than systemic ones. Most cases were classified as mild and progressed to cure. The high number of honeybee sting cases shows that Ceará may be an important risk area for such injuries. Moreover, the current study provides data for the development of strategies to promote control and prevention of bee stings in this area.


Landscape beauty: A wicked problem in sustainable ecosystem management?
Recent discourses on sustainable ecosystem management have increasingly emphasized the importance of bundling relationships and interactions among multiple ecosystem services supported by similar natural and anthropogenic mechanisms within the total environment. Yet, the aesthetic benefits of ecosystems, playing critical role in management of both wild and anthropogenic landscapes, have been under-represented in these discussions. This disregard contributes to the disconnection between environmental science and practice and limits our understanding of ecological and societal implications of management decisions that either generate aesthetic benefits or impact them while targeting other ecosystem services. This discussion reviews several "wicked problems" that arise due to such limited understanding, focusing on three recognized challenges in present-day ecosystem management: replacement of natural ecosystem functions, spatial decoupling of service beneficiaries from its environmental consequences and increasing inequalities in access to services. Strategies towards solutions to such wicked challenges are also discussed, capitalizing on the potential of innovative landscape design, cross-disciplinary research and collaboration, and emerging economic and policy instruments.


Optic disk edema associated with sudden-onset anterior uveitis.
To describe the clinical characteristics and course of optic disk edema (ODE) associated with isolated sudden-onset anterior uveitis. Interventional, noncomparative retrospective case series. Review of patients with sudden-onset anterior uveitis and concomitant ODE seen in an academic uveitis referral center or a general ophthalmology clinic between August 2001 and November 2002. A total of eleven eyes of seven patients were included. Optic nerve function was intact in all. Cranial magnetic resonance imaging was normal in four of five and revealed an abnormality not felt to be responsible for the ODE in one. Resolution of anterior uveitis occurred over a mean of 36 days while ODE resolution lagged by a mean of 20 days. Resolution of ODE trailed that of the anterior uveitis by up to 6 weeks. No abnormalities responsible for ODE were found on cranial imaging.


Hyperspectral Imaging to Determine the Properties and Homogeneity of Renewable Carbon Materials.
Hyperspectral imaging within the near infrared (NIR) region offers a fast and reliable way for determining the properties of renewable carbon materials. The chemical information provided by a spectrum combined with the spatial information of an image allows mathematical operations that can be performed in both the spectral and spatial domains. Here, we show that hyperspectral NIR imaging can be successfully used to determine the properties of hydrothermally prepared carbon on the material and pixel levels. Materials produced from different feedstocks or prepared under different temperatures can also be distinguished, and their homogeneity can be evaluated. As hyperspectral imaging within the NIR region is non-destructive and requires very little sample preparation, it can be used for controlling the quality of renewable carbon materials destined for a wide range of different applications.


Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases.
Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland. The samples were taken before and 3 months after curative resection. Increased concentrations of CEA (>5 µg/L) and hCGβ (>1 pmol/L) 3 months after liver resection correlated with recurrence and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired overall survival, but postoperative TATI was not prognostic. Preoperatively elevated CEA and CA19-9 correlated with impaired overall survival, but not with recurrence. Neither preoperative hCGβ nor TATI was prognostic. In conclusion, CEA is a useful prognostic marker, when measured 3 months after resection of colorectal liver metastases. CA19-9 also has prognostic significance and may have additional value.


One-way transmission of 10 Gbps data through a silicon optical diode based on nonreciprocal resonance reshaping.
The reduced optical bandwidth associated with resonance enhancement poses a significant challenge for resonators to process wide-bandwidth optical data. We report one-way transmission of 10 giga-bit-per-second optical data through a silicon optical diode based on both the resonance-enhanced optical nonlinear effects and resonance reshaping. The diode is operated with a forward-only or backward-only input. In the backward direction, the diode corrupts the data through the strong dispersion and attenuation associated with the resonance of a microring. In the forward direction, the data pass through the diode with negligible distortions because the resonance is red-shifted from the carrier wavelength. In this experimental context the finite bandwidth associated with the optical resonance may be considered beneficial, since the phase response makes an additional contribution to transmission nonreciprocity beyond what is seen with unmodulated light.


Theoretical assumptions and psychometric characteristics of the sense of personal control at work questionnaire.
Personal control is a very important determinant of stress experienced at work. This variable is taken into account in different models of stress, and its role in the relationship between stress and stress effects has been studied in many research projects. But there is still lack of in-depth theoretical considerations on various definitions of control, which would allow to develop precise operationalization of this phenomenon. The following issues are discussed in this paper: 1) theoretical assumptions important for proper construction of the Sense of Personal Control at Work (SPCW); 2) the origins of SPCW Questionnaire; 3) the results of empirical study on psychometric characteristics of the SPCW Questionnaire. A group of 160 subjects participated in the study; the SPCW Questionnaire was administered twice with a 2-week interval; at the first stage, it was used together with other instruments, such as Maslach Burnout Inventory, Stress at Work Questionnaire, Work Satisfaction Scale, general Health Questionnaire-28. Reliability coefficients: Cronbach alpha = 0.81; r(tt) = 0.69. correlation coefficients between personal control and work satisfaction r = 0.44; stress at work r = -0.33; emotional exhaustion r = -0.28; personal accomplishment r = 0.25; depersonalisation r = 4.26; mental health r = -0.19. Exploratory factors analysis have not confirmed theoretical structure of the SPCW Questionnaire.


Removal of cadmium from contaminated Lentinula edodes by optimized complexation and coagulation.
Heavy metal pollution is a serious problem for Lentinula edodes; however, the treatment of contaminated L. edodes has seldom been studied. This study investigated the removal of cadmium (Cd) from contaminated L. edodes and its lentinan by complexation and coagulation. Some influencing factors, such as pH, medical dosage, and preoxidation were examined. Cd complexation from contaminated L. edodes was shown to be more efficient under acidic conditions (pH 5.0), with a clearance rate of 80.47% in 25 mmol/L EDTA and 78.45% in 25 mmol/L sodium citrate. The Cd content in the lentinan of the contaminated L. edodes was markedly lower than that in the powdered mushroom (2.77 mg/kg vs. 19.49 mg/kg) and was easier to remove. The maximum Cd clearance rate (96.3%) for lentinan was obtained using an optimized process that involved preoxidation with 0.5 mg/L KMnO4, complexing with 25 mmol/L EDTA and 25 mmol/L sodium citrate, and coagulation with 50 mg/L activated carbon (AC) at pH 10.0.


Ultrasonic assessment of gastric emptying in the preterm infant.
The study of gastric emptying in the preterm infant has been hampered by the absence of a suitable, valid technique. We have evaluated gastric antral clearance using serial ultrasonic measurement of the antral cross sectional area (ACSA). The study was easy to perform, providing successful results in 15 of 17 low birth-weight infants, with feed volumes of 8-31 ml/kg. ACSA was closely related to intragastric volume (mean (range) r = 0.96 (0.89-0.99)). Measurements were reproducible: mean (SE) coefficient of variation was 7.7% (1.1). Gastric antral clearance was observed as a fall in ACSA that began shortly after completion of the feed and returned to prefeed values at a variable rate. The pattern of gastric antral transit was entirely consistent with recognised patterns of gastric emptying and half gastric antral clearance times ranged from 20-63 minutes. Ultrasonic measurement of gastric antral clearance is a new technique allowing the study of gastric emptying in the preterm infant.


Bend-insensitive bismuth-doped P2O5-SiO2 glass core fiber for a compact O-band amplifier.
For the first time, we report on the fabrication of a bend-insensitive single-mode bismuth (Bi)-doped $ {{\rm P}_2}{{\rm O}_5} {-} {{\rm SiO}_2} $P2O5-SiO2 fiber having a depressed cladding design and study its gain characteristics at a spectral region of 1.3-1.4 µm. It was shown that the obtained Bi-doped fiber can efficiently operate in the spectral band even at a bend radius of 1.5 cm. In addition, it was shown that this type of fiber has a smaller mode-field diameter in comparison with a step-index single-mode Bi-doped $ {{\rm P}_2}{{\rm O}_5} {-} {{\rm SiO}_2} $P2O5-SiO2 fiber with $ \Delta {n} \approx 0.006 $Δn≈0.006 that resulted in a decrease of saturation power and, as a consequence, in a reduction of the total pump power required to a high-level-gain operation. The laser and gain experiments show the possibility of the construction of a compact high-performance optical amplifier for O-band based on the depressed-cladding Bi-doped fiber.


Reassessing the labor market effects of California's minimum nurse staffing regulations.
California implemented hospital-unit level licensed nurse minimum staffing regulations in 2004, with more stringent regulations applying for certain units in 2005 and 2008. All analyses agree that there were significant increases in Registered Nurse (RN) staffing levels, especially in hospitals with lower preregulation staffing. Analyses of the labor market effects of the regulations, however, come to mixed conclusions. I revisit the labor market effects of the regulations using different data and a different analytical model for RN wages. For the analysis of growth of RN employment, I use information from the National Sample Survey of Registered Nurses, the largest and most complete source of information on nurse employment, and find that RN employment grew significantly faster in California than in other states after the regulations were implemented. For the analysis of changes in RN wages, I apply a panel difference-in-difference-in-difference model to wage averages in Metropolitan Statistical Areas, controlling for MSA-, occupation-, and time-fixed effects, and all their two-way interactions. Analysis of changes in the differential between RN wages and wages in four other selected occupations indicates significant growth in RN wages after the regulations were implemented.


Regulatory effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the levels of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 in primary cultures of human extravillous cytotrophoblasts.
An intricate balance between the production of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), modulates the overall proteolytic activity of trophoblasts during human implantation. In these studies we have examined the ability of classical GnRH I and the second form of this hormone (GnRH II) to regulate MMP-2, MMP-9, and TIMP-1 mRNA and protein levels in extravillous cytotrophoblasts propagated from explants of first trimester chorionic villi. GnRH I and GnRH II were found to increase MMP-2 and MMP-9 mRNA and protein levels in these primary cell cultures in a dose- and time-dependent manner using quantitative competitive-PCR and ELISA. In contrast, these two hormones decreased trophoblastic TIMP-1 mRNA and protein levels. Cetrorelix, a GnRH receptor antagonist, inhibited the regulatory effects of GnRH I, but not GnRH II, on MMP-2, MMP-9, and TIMP-1 expression in these cells. Collectively, these observations suggest that GnRH I and GnRH II differentially regulate MMP-2, MMP-9, and TIMP-1 expression in human trophoblasts, possibly via distinct receptor-mediated intracellular signaling pathways.


Seroprevalence of Mycoplasma synoviae in Dutch commercial poultry farms.
Before the year 2000, Mycoplasma synoviae was associated mainly with subclinical respiratory infections in broilers in the Netherlands and was considered to have low clinical and economic impact. The subsequent occurrence of M. synoviae arthritis and amyloid arthropathy, and of eggshell apex abnormalities, has resulted in an increasing demand for M. synoviae-free poultry. Therefore, a cross-sectional seroprevalence study was carried out over a 12-month period during 2005 and 2006. Ten blood samples per farm were generally used because M. synoviae was expected to spread quickly. However, for grandparent and layer breeder stock, 24 to 60 blood samples per house were available from a voluntary M. synoviae monitoring programme. Sera were tested by means of the rapid plate agglutination test (agglutination at dilution > or =1:8 was considered positive). The numbers of farms sampled out of the national total were: broiler grandparent, 53/53; broiler parent rearing, 34/150; broiler parent, 114/300; broiler, 185/800; layer grandparent, 13/13; layer parent, 40/50; layer, 173/1250; and meat turkey, 50/75. The seroprevalence of M. synoviae in commercial poultry was high, especially in commercial layers where it was 73% (95% confidence interval (CI)=67 to 80); in layer and broiler grandparent stock, the seroprevalence was 0% and 10%, respectively, based on sample sizes equal to the population size. In layer and broiler parent farms, the seroprevalence was 25% (95% CI=19 to 31) and 35% (95% CI=28 to 44); in both broiler parent rearing and broiler farms it was 6% (95% CI=0 to 13 and 95% CI=3 to 9); and in meat turkey, the seroprevalence was 16% (95% CI=10 to 22).


Neonatal herpes simplex virus infections.
Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.


Helicobacter pylori Found Incidentally During Upper Endoscopy Performed for Diagnosis of Common Pediatric Gastrointestinal Diseases.
Helicobacter pylori ( H. pylori ) gastritis may be an incidental finding during upper endoscopy performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE). We aimed to describe the incidence of H. pylori in children undergoing endoscopy for CeD, IBD and EoE and determine the indications for treatment. A retrospective, single-center study based on the review of endoscopy reports of pediatric patients, diagnosed with CeD, IBD and EoE, between January 2017 and December 2021. Data collected included; age, gender, hematologic parameters, endoscopic, histologic and H. pylori culture results, and information on eradication treatment. H. pylori gastritis was diagnosed in 120 of 558 (21.5%) children [72 (60%) female, mean age 10.6 years] during gastroscopy performed for the diagnosis of other GI diseases. H. pylori was present in 87 of 404 (21.5%) CeD, 27 of 113 (23.9%) IBD and 6 of 41 (14.6%) EOE patients ( P = 0.46). The main indication for treatment was the presence of ulcers, in 4 of 120 (3.3%), and erosions in 17 of 120 (14.2%). Eradication treatment was recommended in 22 of 120 (18.3%) patients, 8 of 87 (9.2%) CeD, 10 of 27 (37%) IBD and 4 of 6 (66.7%) EoE patients, P < 0.001. Four independent positive treatment predictors were identified; age above 10 years {odds ratio (OR) = 10.57 [95% confidence interval (CI) 1.88-59.36], P = 0.007} the presence of nodular gastritis (OR = 5.03 [95% CI 1.09-23.15], P = 0.38), erosions [OR = 49.21 (95% CI 8.19-295.83), P < 0.000] and ulcers [OR = 22.69 (95% CI 1.25-410.22), P = 0.035]. CeD was a strong negative predictor for treatment [OR = 0.23 (95% CI 0.002-0.241), P = 0.002]. H. pylori gastritis is a common incidental finding during endoscopy. The indications for treatment are not well defined and should be further investigated.


Direct costs of adult chronic rhinosinusitis by using 4 methods of estimation: Results of the US Medical Expenditure Panel Survey.
Chronic rhinosinusitis (CRS) is an inflammatory disease that affects 2% to 16% of the US population. Despite its increasing prevalence, there are currently limited data in the literature evaluating the economic burden of this disease. This study aimed to determine the direct health care costs of CRS from the perspective of the US government. A prevalence-based approach was used to estimate cost of illness for CRS from the 2011 Medical Expenditure Panel Survey database by using a 4-part model: (1) an estimated sum of all health care expenditures, (2) an attribution model for disease-specific estimation of expenditures, (3) an estimation based on a propensity score model, and (4) estimated disease-specific expenditure by using a linear regression-based approach. A disease prevalence of 3.5% was used. The mean CRS-specific annual expenditure was $5955 (95% CI, $5087-$6823) by using method 1 compared with $5560 (95% CI, $4689-$6431) by using method 2 and $5560 (95% CI, $4653-$6467) by using method 3. The annual expenditure, as estimated by using method 4, was $5589 (95% CI, $4986-$6192). Ambulatory expenses accounted for the largest proportion of expenditures, followed by prescription and in-hospital expenses. This study provided a range of estimates of the direct medical expenditures associated with CRS. We demonstrated that the economic burden attributable to this disease was an estimated $60.2 to $64.5 billion US dollars in 2011, with a wide variation in the total and incremental direct expenditures depending on the type of estimation model used and the prevalence assumed.


Diversity of Ig V gene segments found in anti-DNA autoantibodies from a single (NZB x NZW)F1 mouse.
We have studied 18 anti-DNA secreting hybridomas derived from a single, nephritic NZB/NZW mouse. The antibodies were analyzed for the expression of idiotypic families that are enriched in the antibodies to DNA from diseased animals (IdGN2 and IdX), and for the expression of VH and V kappa gene segment subfamilies. Most of the mAb have characteristics similar to those that may be pathogenic because they 1) bound to native DNA, 2) were of the IgG2a or IgG2b isotype, and 3) expressed idiotopes associated with glomerulonephritis in NZB/NZW mice and human lupus. Among the 18 mAb, at least six VH subfamilies and six V kappa subfamilies were expressed. A majority of the antibodies utilized a VH gene segment from the large J558 subfamily. Slot blot analyses of total spleen cell RNA revealed that as NZB/NZW mice aged and developed nephritis, they expressed progressively higher quantities of Ig transcripts. The proportion of these transcripts derived from the VH J558 subfamily also increased. Our results indicate that a diversity of B cell clones participate in the anti-DNA response of a single NZB/NZW mouse. There was no preferential utilization of 3' Ig V gene segment subfamilies. Furthermore, there was no marked difference in the pattern of VH and V kappa gene segment expression in antibodies defined by their isotypes or idiotopes.


Inhibition of cytochrome P450 3A4 by a pyrimidineimidazole: Evidence for complex heme interactions.
PH-302 inhibits the inducible form of nitric oxide synthase (iNOS) by coordinating with the heme of the monomeric form and preventing formation of the active dimer. Inherent with the mechanism of pharmacology for this compound was the inhibition of cytochrome P450 3A4 (P450 3A4), observed from early ADME screening. Further investigation showed that PH-302 inhibited P450 3A4 competitively with a Ki of approximately 2.0 microM against both midazolam and testosterone hydroxylation in human liver microsomes. As expected, spectral binding analysis demonstrated that inhibition was a result of type II coordination to the P450 heme with the imidazole moiety of PH-302, although only 72% of the maximal absorbance difference was achievable with PH-302 compared to that of the smaller ligand imidazole. Time-dependent inhibition of P450 3A4 by PH-302 was also observed because of metabolite-inhibitory (MI) complex formation via metabolism of the methylenedioxyphenyl group. The profile for time-dependent inhibition in recombinant P450 3A4 was biphasic, and was kinetically characterized by a kinact of 0.08 min-1 and a Ki of 1.2 microM for the first phase (0-1.5 min) and a kinact of 0.06 min-1 and a Ki of 23.8 microM for the second phase (1.5-10 min). Spectral characterization of the PH-302 MI complex demonstrated that formation began to plateau within 3 min, consistent with the kinetic profile of inactivation by PH-302. Meanwhile, spectral evidence for the imidazole-derived type II difference spectrum of PH-302 was captured simultaneously with the formation of the MI complex. The presence of simultaneously operable type II coordination and rapidly saturable MI complex formation with heme by PH-302 indicates the presence of complex heme interactions with this unique molecule. Information from these mechanistic studies adds to our understanding of the nature of P450 3A4 inhibition by PH-302 and provides a potentially useful tool compound for future studies investigating binding interactions in this important drug-metabolizing enzyme.


The acquisition and analysis of polarized total internal reflection fluorescence microscopy (polTIRFM) data.
Polarized total internal reflection fluorescence microscopy (polTIRFM) can be used to detect the spatial orientation and rotational dynamics of single molecules. polTIRFM determines the three-dimensional angular orientation and the extent of wobble of a fluorescent probe bound to the macromolecule of interest. This protocol describes how to acquire polTIRFM data and then calibrate the setup. Calibration corrects for any systematic variations in beam intensity and unequal detector sensitivities and is performed for each slide after experimental data are recorded. To convert the intensities into angles, one set of (θ, ϕ, δ(s), δ(f), κ) is then determined from one complete cycle of the incident intensities. This process is repeated for every cycle in the trace to measure the time dependence of rotational motions. The collection and analysis of data is similar for the processive motility assay for myosin V and for the twirling filament assay, in which a sparsely labeled actin filament is translocated by a field of unlabeled myosin V.


Short communication: insoluble fibres in supplemental pre-weaning diets affect behaviour of suckling piglets.
We investigated the effect of offering supplementary dietary fibres to suckling piglets on their behaviour and performance before weaning. From 5 to 22 days of age, suckling piglets were offered a high-fibre diet (HF; 5% cellulose; n=5 litters), or a control low-fibre diet (n=5 litters). Piglets were housed with the sows in individual farrowing pens, and had access to maternal milk until weaning, at 23 days of age. Behaviours of six focal piglets per pen were scored at 6, 16 and 21 days of age. All piglets were individually weighed at 5, 15 and 20 days of age and feed intake was measured daily at the pen level. Piglets on the HF diet were more active than controls (P=0.05), and spent more time suckling or massaging the udder (P=0.01) and interacting with pen mates (P=0.008). Time spent manipulating pen mates, which may reflect re-directed foraging activity in the absence of substrate, accounted for most of the time spent interacting with pen mates (⩾73% of total time spent interacting). Dietary fibres had no effect on BW and feed intake. In conclusion, inclusion of cellulose in the supplemental diet of suckling piglets affects behaviour, with no deleterious effects on performance before weaning.


Bone and cartilage differentiation of a single stem cell population driven by material interface.
Adult stem cells, such as mesenchymal stem cells, are a multipotent cell source able to differentiate towards multiple cell types. While used widely in tissue engineering and biomaterials research, they present inherent donor variability and functionalities. In addition, their potential to form multiple tissues is rarely exploited. Here, we combine an osteogenic nanotopography and a chondrogenic hyaluronan hydrogel with the hypothesis that we can make a complex tissue from a single multipotent cell source with the exemplar of creating a three-dimensional bone-cartilage boundary environment. Marrow stromal cells were seeded onto the topographical surface and the temperature gelling hydrogel laid on top. Cells that remained on the nanotopography spread and formed osteoblast-like cells, while those that were seeded into or migrated into the gel remained rounded and expressed chondrogenic markers. This novel, simple interfacial environment provides a platform for anisotropic differentiation of cells from a single source, which could ultimately be exploited to sort osteogenic and chondrogenic progenitor cells from a marrow stromal cell population and to develop a tissue engineered interface.


[Effects of gosha-jinki-gan on urinary bladder contraction in dogs].
The effects of Gosha-Jinki-Gan on the urinary bladder contraction in anesthetized dogs were studied to elucidate the mode of action. The bladder contraction was induced by electrical stimulation of the left distal end of the pelvic nerve under the bilateral pelvic nerve and hypogastric nerve transections, or by the infusion of acetylcholine (200 micrograms) in to the abdominal aorta. The bladder contraction induced by pelvic nerve stimulation was significantly inhibited by 10 and 100 mg/kg of intravenous Gosha-Jinki-Gan administration. A similar phenomenon was observed by the administration of atropine sulfate (0.1 mg). The acetylcholine-induced contraction was significantly inhibited by administration of 100 mg/kg of Gosha-Jinki-Gan. These findings suggested that Gosha-Jinki-Gan inhibits the urinary bladder contraction induced by the stimulation of cholinergic nerve.


Clinical use of atrial pacing test in angina pectoris.
Atrial pacing can be used as a safe test in the assessment of patients with angina pectoris. The results are useful in clinical judgements, and this method of investigation may be indicated for patients in whom the diagnosis of angina pectoris is in doubt or who are being considered for surgical treatment of ischaemic heart disease.


The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species.
Uvomorulin belongs to the group of Ca2+-dependent cell adhesion molecules, which are integral membrane proteins with several structural features in common. In particular, the cytoplasmic part of these proteins is highly conserved in different species, suggesting a common biological function. To test this assumption we transfected a uvomorulin full-length cDNA into uvomorulin-negative mouse NIH 3T3 and L cells. Immunoprecipitations with anti-uvomorulin antibodies detected, in addition to uvomorulin, three independent proteins of 102, 88 and 80 kd which are of host origin and which form complexes with uvomorulin. Using cDNA constructs coding for uvomorulin with cytoplasmic or extracellular deletions it is shown that the 102, 88 and 80 kd proteins complex with the cytoplasmic domain of uvomorulin. Peptide pattern analysis revealed that these three proteins are identical in different mouse cells. When uvomorulin cDNA was introduced into cell lines from other species, such as human HeLa and avian fibroblasts, the expressed uvomorulin was also associated with endogenous 102, 88 and 80 kd proteins and, moreover, each of these proteins showed structural similarities to the respective mouse molecule. A panel of antibodies specific for known cytoplasmic proteins of mol. wts similar to those of the three proteins did not react with any of the described components. This suggests that the 102, 88 and 80 kd proteins constitute a new group of proteins for which we propose the nomenclature of catenin alpha, beta and gamma respectively. The characterization of these proteins provides a first molecular basis for a possible cytoplasmic anchorage of uvomorulin to the cytoskeleton.


Isolation of porcine reproductive and respiratory syndrome (PRRS) virus in a Danish swine herd and experimental infection of pregnant gilts with the virus.
The first case of porcine reproductive and respiratory syndrome (PRRS) in Denmark was diagnosed in March 1992 by the detection of specific antibodies against PRRS virus in serum samples originating from sows in a herd located on the island of Als. Subsequently, PRRS virus was isolated from a 200-sow farrow-to-finish herd with clinical signs consistent with PRRS. The virus was isolated by inoculation of pleural fluid from a stillborn piglet onto porcine pulmonary alveolar macrophages. The isolate was identified as PRRS virus by staining with a specific antiserum. By electron microscopy, the virus particle was found to be spherical and enveloped, measuring 45-55 nm in diameter and containing a 30-35 nm nucleocapsid. Only minor antigenic differences were found between the Danish and a Dutch isolate. Following intranasal inoculation of 3 pregnant gilts with the Danish isolate transplacental infection was demonstrated by the re-isolation of PRRS virus from approximately 45% of the piglets from the experimentally infected gilts. However, the experimental infection produced no significant reproductive disorders or other clinical signs. At autopsy, histopathological examination revealed slight interstitial pneumonia in a few piglets.


BCc1 Nanomedicine Therapeutic Effects in Streptozotocin and High-Fat Diet Induced Diabetic Kidney Disease.
One common feature of chronic diseases, such as cancer, diabetes and chronic kidney disease (CKD), is the disruption of iron metabolism and increase in labile iron pool, which can result in excessive production of harmful oxidative stress. The proper management of iron metabolism in this situation can be a valuable tool to ameliorate pathological events. In the previous studies, the anti-neoplastic effects of BCc1, a nanochelating-based nanomedicine with iron-chelating property, were demonstrated in cell culture, animal models and clinical trials. In the present study, the therapeutic effects of BCc1 in animal model of diabetic kidney disease (DKD), induced by streptozotocin injection (35 mg/kg) and high-fat diet consumption, were evaluated. The results showed that BCc1 significantly decreased HOMA-IR index, uric acid, blood urea nitrogen, malondialdehyde and 8-isoprostane. In addition, it reduced urinary albumin excretion rate and albumin-to-creatinine ratio in comparison to DKD control rats. This nanomedicine had no negative impact on liver iron content, hemoglobin level, red blood cell count, hematocrit and mean corpuscular volume, while it significantly decreased aspartate aminotransferase and alanine aminotransferase compared to DKD control group. Moreover, the histopathological assessment indicated that lesser glomerular basement membrane and wrinkling, mesangial matrix expansion and pathological changes in proximal cortical tubules were seen in the kidney samples of BCc1-treated rats. In conclusion, BCc1 as an iron-chelating agent shows promising impacts in DKD animal model, which can ameliorate biochemical and pathological events of this disease.


The putative polyketide cyclase MSMEG_0129 from Mycobacterium smegmatis: purification, crystallization and X-ray crystallographic analysis.
Mycobacterium tuberculosis Rv0164 has previously been identified as a human T-cell antigen that induces significant production of IFN-γ in human peripheral blood mononuclear cells. M. smegmatis MSMEG_0129 shares 59% sequence identity with Rv0164. Based on sequence alignment, both proteins are predicted to be members of the cyclase/dehydrase family, which is part of a large group of enzymes referred to as type II polyketide synthases (PKSs). In biosynthetic pathways mediated by type II PKSs, cyclases catalyze the conversion of linear poly-β-ketones to cyclized intermediates. To date, no mycobacterial type II PKSs have been reported. Here, the goal is to determine whether these proteins adopt similar folds to reported cyclase structures, and to this end MSMEG_0129 was cloned, expressed, purified and crystallized. An X-ray diffraction data set was collected to 1.95 Å resolution from a crystal belonging to space group P62, with unit-cell parameters a = 109.76, b = 109.76, c = 56.5 Å, α = 90, β = 90, γ = 120°. Further crystallographic analysis should establish a basis for investigating the structure and function of this putative mycobacterial type II PKS enzyme.


Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A.
We describe here N-phenylpyrrolidine-based inhibitors of HCV NS5A with excellent potency, metabolic stability, and pharmacokinetics. Compounds with 2S,5S stereochemistry at the pyrrolidine ring provided improved genotype 1 (GT1) potency compared to the 2R,5R analogues. Furthermore, the attachment of substituents at the 4-position of the central N-phenyl group resulted in compounds with improved potency. Substitution with tert-butyl, as in compound 38 (ABT-267), provided compounds with low-picomolar EC50 values and superior pharmacokinetics. It was discovered that compound 38 was a pan-genotypic HCV inhibitor, with an EC50 range of 1.7-19.3 pM against GT1a, -1b, -2a, -2b, -3a, -4a, and -5a and 366 pM against GT6a. Compound 38 decreased HCV RNA up to 3.10 log10 IU/mL during 3-day monotherapy in treatment-naive HCV GT1-infected subjects and is currently in phase 3 clinical trials in combination with an NS3 protease inhibitor with ritonavir (r) (ABT-450/r) and an NS5B non-nucleoside polymerase inhibitor (ABT-333), with and without ribavirin.


Acute lithium effects on rat brain glucose metabolism - in vivo.
Administration of LiCl to rats was found to affect brain glucose metabolism in the following ways. The concentrations of brain glucose, brain lactate and brain glycogen were increased, and the concentration of brain glutamate was decreased. The incorporation of (14)C from U-(14)C D-glucose, administered intraperitoneally to the rats, was increased in brain glucose and brain lactate, and decreased in brain glutamate. The results were explained by a lithium-induced increase in brain glucose uptake and an increased rate of glycolysis, and a slight inhibition of the oxidative decarboxylation of the Krebs cycle.


Genetic and biochemical evidence for a critical role of Janus kinase (JAK)-3 in mast cell-mediated type I hypersensitivity reactions.
We investigated the role of JAK3 in IgE receptor/FcepsilonRI-mediated mast cell responses. IgE/antigen induced degranulation and mediator release were substantially reduced with Jak3-/- mast cells from JAK3-null mice that were generated by targeted disruption of Jak3 gene in embryonic stem cells. Further, treatment of mast cells with 3'bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154), a potent inhibitor of JAK3, inhibited degranulation and proinflammatory mediator release after IgE receptor/ FcepsilonRI crosslinking. Thus, JAK3 plays a pivotal role in IgE receptor/ FcepsilonRI-mediated mast cell responses and targeting JAK3 may provide the basis for new and effective treatment as well as prevention programs for mast cell-mediated allergic reactions.


Traumatic macular hole.
A traumatic macular hole has never been seen immediately after the causal accident. We examined a case of macular hole within half an hour of the injury and photographed it within three hours. We comment on the genesis of traumatic macular edema.


An economic evaluation of home care for children with newly diagnosed diabetes: results from a randomized controlled trial.
This study was undertaken to determine the health and cost effects of using home care to treat newly diagnosed Type I diabetic children rather than traditional inpatient hospital care. There had been no well-designed evaluations of home care for such children, and very few for children with other health conditions. Sixty-three children seen at the Montreal Children's Hospital were randomly assigned at diagnosis to home care or traditional inpatient care. The children in the former group were discharged once their metabolic condition stabilized; insulin adjustments and teaching were done in their homes by a trained nurse. The children in the latter group remained hospitalized for insulin adjustments and teaching. All were followed for 24 months. The cost effects were estimated using hospital and parental data. Social costs were only $48 higher with home care. It had little effect on social costs, because the increased costs of health care services with home care ($768) were largely offset by parental cost savings ($720). Home care improved the children's metabolic outcomes without adversely affecting their psychosocial outcomes. Using home care to reduce hospital stays for children with newly diagnosed Type I diabetes improved the children's health outcomes without significantly increasing social costs.


Development of a simple hollow fibre supported liquid membrane extraction method to extract and preconcentrate dinitrophenols in environmental samples at ng L(-1) level by liquid chromatography.
An easy and rapid hollow-fibre supported liquid membrane method (HFSLM) has been developed to extract and determinate the total concentration of four dinitrophenols in environmental water at ng L(-1) level. This extraction method provides a high selectivity, short extraction time and very low cost for real samples. It is a three-phase system, aqueous-organic-aqueous, where the organic solvent is held into the fibre pores, being in contact with the two other phases. The organic phase is formed by two different organic solvents, with two different polarities, n-undecane and toluene (1:1). The optimization step was performed using a three-variable Doehler design, involving three factors, stirring speed, fibre length and sample volume. The organic phase composition, as well as the pH of the acceptor and donor phases was also optimized. The extraction equilibrium was reached after 30 min, after which essentially the total amount (90-80%) of the four dinitrophenolic compounds were extracted from the sample. Better repeatability and reproducibility at the expense of lower enrichment factors was obtained compared with other methods, employing incomplete extraction during a fixed time. The matrix effect was tested by performing extractions from leachate water and river water. This method is linear in the range 0.1-100 microgL(-1) in different matrices, with detection limit around 100 ng L(-1), after extraction of 6 mL of sample and using high performance liquid chromatography for final analysis.


Carboxypeptidase E is a prognostic biomarker co-expressed with osteoblastic genes in osteosarcoma.
Osteosarcoma (OS) is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. The identification of prognostic genes lags far behind advancements in treatment. In this study, we identified differential genes using mRNA microarray analysis of five paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain insight into the pathway alterations of OS. Prognostic genes were screened using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, then overlapped with the differential gene dataset. The carboxypeptidase E (CPE) gene, found to be an independent risk factor, was further validated using RT-PCR and Gene Expression Omnibus (GEO) datasets. Additionally, we explored the specific expression of CPE in OS tissues by reanalyzing single-cell genomics. Interestingly, CPE was found to be co-expressed with osteoblast lineage cell clusters that expressed RUNX2, SP7, SPP1, and IBSP marker genes in OS. These results suggest that CPE could serve as a prognostic factor in osteoblastic OS and should be further investigated as a potential therapeutic target.


A penalized likelihood approach for bivariate conditional normal models for dynamic co-expression analysis.
Gene co-expressions have been widely used in the analysis of microarray gene expression data. However, the co-expression patterns between two genes can be mediated by cellular states, as reflected by expression of other genes, single nucleotide polymorphisms, and activity of protein kinases. In this article, we introduce a bivariate conditional normal model for identifying the variables that can mediate the co-expression patterns between two genes. Based on this model, we introduce a likelihood ratio (LR) test and a penalized likelihood procedure for identifying the mediators that affect gene co-expression patterns. We propose an efficient computational algorithm based on iterative reweighted least squares and cyclic coordinate descent and have shown that when the tuning parameter in the penalized likelihood is appropriately selected, such a procedure has the oracle property in selecting the variables. We present simulation results to compare with existing methods and show that the LR-based approach can perform similarly or better than the existing method of liquid association and the penalized likelihood procedure can be quite effective in selecting the mediators. We apply the proposed method to yeast gene expression data in order to identify the kinases or single nucleotide polymorphisms that mediate the co-expression patterns between genes.


Fatal intoxication due to tramadol alone: case report and review of the literature.
Poisoning may also lead to both coma and multiple organ failure, also in youngsters without a known major medical history. As not all toxic agents are routinely screened when a poisoning is suspected, it is useful to consider less frequently encountered poisons in certain cases. We describe the occurrence of asystole and multiple organ failure which occurred in a young man after a suspected tramadol overdose. The tramadol concentration on admission in the ICU was indeed 8 microg/ml (mg/l), far above the therapeutic range. Subsequently, the patient developed severe acute liver failure, finally leading to death. Post-mortem toxicology did not reveal any other poison responsible for this unfavourable course as only very high serum and tissue tramadol and desmethyltramadol concentrations were found. Only a few fatal poisonings attributable to tramadol alone, as observed in our case, have been reported. An overview of these cases is presented.


Comparing electronic structure predictions for the ground state dissociation of vinoxy radicals.
This paper reports a series of electronic structure calculations performed on the dissociation pathways of the vinoxy radical (CH(2)CHO). We use coupled-cluster with single, double, and perturbative triple excitations (CCSD(T)), complete active space self-consistent field (CASSCF), multireference configuration interaction (MRCI), and MRCI with the Davidson correction (MRCI+Q) to calculate the barrier heights of the two unimolecular dissociation pathways of this radical. The effect of state averaging on the barrier heights is investigated at the CASSCF, MRCI, and MRCI+Q levels. The change in mixing angle along the reaction path is calculated as a measure of derivative coupling and found to be insufficient to suggest nonadiabatic recrossing. We also present a new analysis of previous experimental data on the unimolecular dissociation of ground state vinoxy. In particular, an error in the internal energy distribution of vinoxy radicals reported in a previous paper is corrected and a new analysis of the experimental sensitivity to the onset energy (barrier height) for the isomerization reaction is given. Combining these studies, a final "worst case" analysis of the product branching ratio is given and a statistical model using each of the calculated transition states is found to be unable to correctly reproduce the experimental data.


RNA sequencing analysis of the human retina and associated ocular tissues.
The retina is a stratified layer of sensory neurons lining the posterior portion of the eye. In humans, fine detail and color vision are enabled by the macula, a central region of the retina dense in cone photoreceptors (PRs). Achromatic low light and peripheral vision are facilitated by rod PRs found with increasing density outside the macula in the peripheral retina. The outer retina is nourished by choroidal blood flow regulated by a single layer of intervening retinal pigment epithelial (RPE) cells. Existing human retinal transcriptome projects have been critical for studying aspects of retinal development and disease however, there are currently no publicly available data sets accurately describing the aging human central retina, peripheral retina, and supporting RPE/choroid. Here we used Illumina RNA sequencing (RNA-seq) analysis to characterize the mRNA transcriptome of rod and cone PR-enriched human retina as well as supporting macular RPE/choroid tissue. These data will be valuable to the vision research community for characterizing global changes in gene expression in clinically relevant ocular tissues.


Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.
Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing TH1 cells or interleukin (IL)-17-producing TH17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of TH17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.


[Living epidermal and dermal substitutes for treatment of severely burned patients].
Epidermal and dermal cells can be multiplied in vitro using different techniques. Under particular conditions, the structure and the function of the original tissues are partly recreated. Autologous epidermal substitutes for wound coverage in deep burns are prepared in less than three weeks. Bilayered skin equivalents containing a dermal component are obtained by growing epidermal cells on a reconstructed dermal substitute or by juxtaposing stratified cultures of keratinocytes and fibroblasts. New technologies are required to optimise the nutrition of three-dimensional cultures of skin cells, which should lead to further progress in the area of skin reconstruction.


Trade-offs between burst performance and maximal exertion capacity in a wild amphibian, Xenopus tropicalis.
Trade-offs are thought to impose barriers to phenotypic diversification and may limit the evolutionary responses of organisms to environmental changes. In particular, locomotor trade-offs between endurance or maximal exertion capacity and burst performance capacity have been observed in some species and may constrain the ability of organisms to disperse. Here, we tested for the presence of locomotor trade-offs between maximal exertion and burst performance capacity in an aquatic frog, the tropical clawed frog (Xenopus tropicalis). Given the importance of overland dispersal for this species, we focused on terrestrial exertion capacity (time and distance jumped until exhaustion) and tested whether it trades-off with aquatic burst performance capacity (maximum instantaneous velocity and acceleration), which is likely to be relevant in the context of predator escape and prey capture. Our data show that in both sexes, individuals with longer hindlimbs display higher endurance. Additionally, in females forelimb length was positively correlated with aquatic burst performance capacity and negatively correlated with terrestrial exertion. Trade-offs between endurance and burst performance capacity were detected, but were significant in males only. Finally, males and females differ in morphology and performance. Our data suggest that trade-offs are not universal and may be driven by sex-dependent selection on locomotor capacity. Moreover, our results suggest that locomotor trade-offs may result in sex-biased dispersal under selection for improved endurance capacity as is expected under habitat fragmentation scenarios.


The use of corticosteroids for COVID-19 infection.
The SARS-CoV-2 pandemic is continuing relentlessly in many parts of the world and has resulted in the outpouring of literature on various aspects of the infection, including studies and recommendations regarding the optimal treatment of infected patients. Not surprisingly, the use of corticosteroids in the management of such patients has featured prominently in many of these publications. There is considerable debate in the literature as to the likely benefits, as well as the potential detrimental effects of corticosteroid therapy in general viral respiratory infections and, in particular, COVID-19 infections. While the definitive answer may need to await the results of ongoing randomised, controlled trials recent studies suggest that corticosteroid use in COVID-19 cases with hypoxaemia may benefit from low-dose corticosteroid therapy.


The platelet hyporeactivity of extremely low birth weight neonates is age-dependent.
We have previously demonstrated that, as compared to adults, the platelets of extremely low birth weight (ELBW) neonates are markedly hyporeactive on day 0-1 of life. The purpose of this study was to examine the age dependency of this hyporeactivity. On days 0-1, 3-4, and 10-14, peripheral blood was collected from 14 stable ELBW neonates and compared to peripheral blood from normal adults run in parallel. Whole blood flow cytometry was used to examine the activation-dependent increase in platelet surface P-selectin (reflecting degranulation) and platelet surface binding of factor V/Va (reflecting platelet surface procoagulant activity) and decrease in platelet surface glycoprotein (GP) Ib (the von Willebrand factor receptor). In the physiologic milieu of whole blood, ELBW neonatal platelets on days 0-1 and 3-4 were markedly less reactive than adult platelets. However, by day 10-14, the platelet function of ELBW neonates improved significantly, although not completely to adult levels. The age-dependent platelet hyporeactivity of ELBW neonates demonstrated in this study may be a contributing factor to the similar age-dependent propensity of ELBW neonates to intraventricular hemorrhage.


Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy.
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth. However, a high proportion of patients is resistant or acquires resistance to these therapeutic strategies. The latter findings may reflect, at least in some cases, the inability of the immunotherapeutic strategies used to eradicate CICs. The CICs that escape immune recognition and destruction may give rise to new tumors in the same organ site or through the metastatic colonization in other anatomic sites. Identification of novel therapeutic approaches that can eradicate CICs is a major challenge in the cancer therapy area. An improved understanding of the interactions of CICs with immune system and with tumor microenvironment may contribute to optimize the available therapies and to design novel combination treatments for cancer therapy. ALDH, aldehyde dehydrogenase; APC, antigen-presenting cells; APM, antigen-processing machinery; CAR: chimeric antigen receptor; CHK1, checkpoint serine/threonine protein kinase; CIC, cancer-initiating cell; CRC, colorectal cancer; CTLA-4, cytotoxic T lymphocyte antigen-4; GBM, glioblastoma multiforme; GDF-15, growth differentiation factor-15; CSPG4: chondroitin sulfate proteoglycan-4; IFN, interferon; IL-4, interleukin-4; IL-10, interleukin-10; IL-13, interleukin-13; IL-13α2, α2 chain of IL-13 receptor; mAb, monoclonal antibody; MDSC, myeloid-derived suppressor cell; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1 programmed death ligand-1; PDK, 3-phosphoinositide-dependent protein kinase-1; PGE2, prostaglandin E2; STAT3, signal transducer and activator of transcription 3; TGFB-1, transforming growth factor beta-1; Treg, T regulatory cell.


Diabetic foot ulcers in Cameroon: can microflora prevalence inform probabilistic antibiotic treatment?
To determine the clinical features, regularly associated microorganisms and their susceptibility to antibiotics, and the clinical outcomes of foot ulcers in patients with diabetes at the Yaoundé Central Hospital, Cameroon. A retrospective analysis of routinely collected hospital data, and data validation by survey of clinical notes was conducted from November 1999 to October 2002 for adult diabetic patients with foot ulcers. Clinical data were recorded for each patient, followed by a record of microbiological investigations where available. Of 503 patients with diabetes admitted during the study period, 54 (10.7%) had foot ulcers. Male subject represented 66.7% of this population. The mean age of the study population was 59.66 +/- 1.52 years. The foot ulcer led to the diagnosis of diabetes in six patients in whom the condition was previously unidentified. Of the 54 patients with foot ulcers, nine (16.7%) were selected for surgery and the remaining 45 were managed conservatively. Microbiological investigations were available for 21 patients. Proteus mirabilis was the most frequent microorganism yielded, and was regularly associated with Staphylococcus aureus. All the microorganisms isolated showed high sensitivity to second-generation quinolone antibiotics and were regularly sensitive to aminoglycoside antibiotics. Nine (16.7%) patients died and seven (13%) were discharged at their own request. The mortality rate among our diabetic patients with foot ulcers is high and the combination of second-generation quinolone and aminoglycoside antibiotics can be proposed as a probabilistic antibiotic approach to treating foot infection.


Evaluation of three combinations of anesthetics for use in free-ranging alpine marmots (Marmota marmota).
From April 1998 to September 2000, 241 free-ranging alpine marmots (Marmota marmota) were anesthetized in the course of a field project using either xylazine plus ketamine (XK), medetomidine plus ketamine (MK), or xylazine plus a 1:1 mixture of zolazepam and tiletamine (XZT). For each of the combinations, the respective doses for short term and long-term surgery were established and seasonal variations in the amount of drugs needed were assessed. No fatalities occurred, and doses for efficient and safe anesthesia in spring were as follows (XK, MK, and XZT, respectively, in mg/kg body mass): short term surgery 3 + 40, 0.25 + 35, and 3 + 15; long term surgery 20 + 80, 0.5 + 70, and 10 + 20. In late summer/autumn, higher doses (20 + 60, 0.2 + 60, and 10 + 15 for short term surgery) had to be administered, probably due to increase of marmots' body fat content. Heart rate, respiratory rate, rectal temperature, palpebral reflex, muscle relaxation, and analgesia were monitored to evaluate the animals' responses to each of the drug combinations. Hypothermia was induced by all combinations and heart rate significantly decreased during anesthesia, especially in marmots receiving MK. Respiratory rate was highly variable and no significant differences between the drugs were found. Muscle relaxation was rather poor in marmots anesthetized with XK. The XZT combination tended to have a longer induction period but was found to subsequently depress the palpebral reflex and induce muscle relaxation and analgesia very efficiently. We conclude that, regardless of the anesthetics used, doses should always be adjusted to the planned manipulations, the marmots' nutritional state, and to the time of year. Furthermore, close monitoring of physiologic parameters, especially body temperature, should be guaranteed. On the basis of physiologic and behavioral responses, XZT is the most effective drug combination for anesthetizing alpine marmots, especially for long term, potentially painful procedures.


Time-dependent density functional theory investigation of the electronic spectra of hexanuclear chalcohalide rhenium(III) clusters.
The UV-vis spectra of the hexanuclear chalcohalide rhenium(III) clusters of formula [Re(6)S(8)X(6)](4-) (X(-) = Cl(-), Br(-), I(-)) were investigated at the time-dependent density functional theory (TD-DFT) level employing B3LYP, PBE1PBE, and the double-hybrid B2PLYP functional in combination with the LANL2DZ basis set. We were able to reproduce the red shift experimentally observed when the halide changes from chloride to iodide. However, some discrepancies between experimental results and theory were found. First, we did not observe a remarkable dependence of the experimental ill-resolved bands on the solvent. Indeed, similar spectra were obtained taken CH(2)Cl(2) or CH(3)CN as solvents into account. Second, all calculations explained the origin of the band peaked at the low-energy region in contraposition with the one experimentally assumed by R. Long et al. (J. Am. Chem. Soc. 1996, 118, 4603), and theoretically made available by Arratia-Pérez et al. (J. Chem. Phys. 1999, 110, 2529). These authors have proposed a ligand-to-cluster charge transfer (LCCT) for all title complexes. Our findings undoubtedly allow such origin to be discarded. While the HGGA functionals lead to a cluster-to-halide ligand charge transfer (CLCT), an intracluster charge transfer (ICCT) has been considered by employing B2PLYP. This contribution showed B2PLYP in the presence of the solvent to be the best performer in studying the UV-vis spectra of large complexes of rhenium(III) containing the Re-S bond. We strongly recommended the use of the double-hybrid B2PLYP in studying UV-vis spectrum of rhenium complexes of size making the computational cost affordable. We expect that our work stimulates new experimental and theoretical investigations of the title complexes to confirm our assignment.


[Cranial surgery without shaving: practice and results in our hospital].
Hair removal or shaving, even if partial, increases mental anguish of patients, especially in female. Several reports demonstrating successful cranial surgery without hair removal led us to start cranial surgery with completely preserving hair. The purpose of this study was to demonstrate our methods and tips of cranial surgery without hair removal and to evaluate the rate of postoperative infection in these patients. We performed 82 procedures without shaving, including craniotomy for brain tumors, trauma, intracranial aneurysms and so on (n = 70), ventriculo-peritoneal shunt placement (n = 5), and other miscellaneous procedures (n = 7). All the patients were highly satisfied with the cosmetic results keeping their hair. We observed 5 patients whose wounds took relatively long time to be cured (6.1%), and 2 patients whose wounds were infected (2.4%). All infections were superficial and cured by the application of antibiotic ointment. There was no significant difference between the rate of wound complication in patients whose heads were shaven (5/82) and the rate in those whose head were not shaven (7/82). So we suggest that neurosurgery without shaving is safe, and does not increase the risk of severe wound infection. In addition, it helps patients to look normal and to start their routine earlier.


Beta2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD.
COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the beta2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta2-agonists; however, the effects of these polymorphisms on responses to beta2-agonists in patients with COPD is unknown. To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta2-agonists in patients with COPD. A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. The presence of the Arg16 allele was associated with lower BDRs to beta2-agonist inhalation. The mean (+/-SD) log (postbronchodilator FEV1-prebronchodilator FEV1) values of Gly16 homozygotes (n=65), Arg16Gly16 heterozygotes (n=106), and Arg16 homozygotes (n=75) were 2.19+/-0.43, 2.09+/-0.42, and 2.01+/-0.42, respectively (p<0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p<0.01). The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting beta2-agonists in patients with COPD.


[Therapy of consumption coagulopathies].
The terms "consumption coagulopathy" and "disseminated intravascular coagulation" are used synonymously, though the former expression refers to the process of consuming the haemostatic potential, whereas the latter is based upon the generalized formation of microthrombi. Both terms apply to an acquired disturbance of blood clotting leading to an increased turnover of coagulation factors and platelets by which the production sites are being exhausted. Such a process is triggered off by generalized activation of the haemostatic system: after a period of hypercoagulability, haemostasis changes into hypocoagulability with subsequent haemorrhagic diathesis. Additionally, the generalized activation of the haemostatic system leads to a formation of microthrombi in the microcirculation. Since consumption coagulopathies are bound to be secondary disorders, any underlying disease prone to lead to disseminated intravascular coagulation, should be treated as early and as intensively as possible. Solely by this and by restoring circulatory functions impaired by the underlying disease, it is possible in the majority of cases to stop the consumptive coagulopathy and to repair its sequelae. The shock frequently going along with a consumption coagulopathy requires immediate therapy: correction of hypothermia, treatment of acid-base and electrolyte disorders as well as fighting against hypovalaemia, anuria, and uraemia. Dextran does not serve only as plasma expander, but also corrects hypercoagulability and improves the rheological qualities of circulating blood. If these measures fail to stop the consumptive reaction of blood coagulation and/or fail to restore microcirculation in vital organs, indication for the use of anticoagulants or fibrinolytic drugs is given.(ABSTRACT TRUNCATED AT 250 WORDS)


Transfer Latent SVM for Joint Recognition and Localization of Actions in Videos.
In this paper, we develop a novel transfer latent support vector machine for joint recognition and localization of actions by using Web images and weakly annotated training videos. The model takes training videos which are only annotated with action labels as input for alleviating the laborious and time-consuming manual annotations of action locations. Since the ground-truth of action locations in videos are not available, the locations are modeled as latent variables in our method and are inferred during both training and testing phrases. For the purpose of improving the localization accuracy with some prior information of action locations, we collect a number of Web images which are annotated with both action labels and action locations to learn a discriminative model by enforcing the local similarities between videos and Web images. A structural transformation based on randomized clustering forest is used to map the Web images to videos for handling the heterogeneous features of Web images and videos. Experiments on two public action datasets demonstrate the effectiveness of the proposed model for both action localization and action recognition.


[Calculating the Human Eye - The Evolution of Biometry for Cataract Surgery].
Optical biometry is the standard diagnostic tool and essential basis for IOL calculation prior to cataract surgery today. Our article will provide a short overview of the historical development of biometry of the human eye and the formulas used for IOL calculation. Selective literature search in books and journal articles via PubMed, Google Scholar and Google as well as close cooperation with IOLCon at Saarland University, Homburg/Saar (Germany). For first measurements of the eye, ultrasound was applied invasively. Today, ultrasound is mostly restricted to cases where optical biometry cannot be performed due to opaque optical media. However, today, most of the modern biometers are working with OCT non-invasively. Along with this technical evolution, numerous formulas have been developed for calculating the optical power of each respective IOL. Intraocular lenses can be calculated with different strategies: with empirical formulas, the IOL power is derived from a series of biometric data without any anatomical or physical background. With the theoretical-optical formulas, which are most commonly used today, the IOL power is extracted from a paraxial optical model which simplifies the eye to linear Gaussian optics. With modern raytracing settings, the Snell's law is applied at each refracting surface within the eye and the best focus position is compared with the position of the fovea. Today, an increasing number of eyes that underwent refractive surgery previously are facing cataract surgery. Maybe even more important than adequate biometry of the human eye will be using appropriate calculation schemes in order to enhance post-cataract refractive outcomes or predictability.


The novel gene HA117 promotes in vitro and in vivo drug resistance in mouse colon tumor cells.
In this study, we characterized the role of HA117, a novel gene we previously identified, in drug resistance in vitro and in vivo. Briefly, CT26 cells expressing HA117 were obtained by infection with a recombinant adenovirus, and tested for drug sensitivity by methyl thiazolyl tetrazolium assay. In addition, the effect of HA117 on drug sensitivity was assessed in CT26 colon tumors transplanted into nude mice. In vitro, expression of HA117 increased the resistance of CT26 cells to 5-fluorouracil 2.75 times (P<0.05). Similarly, expression of HA117 in subcutaneously xenografted CT26 colon cancer significantly lowered its sensitivity to 5-fluorouracil (P<0.05). Collectively, the results suggest that HA117 regulates the development of drug resistance in CT26 cells in vitro and in vivo.


Functional analysis of BPSS2242 reveals its detoxification role in Burkholderia pseudomallei under salt stress.
A bpss2242 gene, encoding a putative short-chain dehydrogenase/oxidoreductase (SDR) in Burkholderia pseudomallei, was identified and its expression was up-regulated by ten-fold when B. pseudomallei was cultured under high salt concentration. Previous study suggested that BPSS2242 plays important roles in adaptation to salt stress and pathogenesis; however, its biological functions are still unknown. Herein, we report the biochemical properties and functional characterization of BPSS2242 from B. pseudomallei. BPSS2242 exhibited NADPH-dependent reductase activity toward diacetyl and methylglyoxal, toxic electrophilic dicarbonyls. The conserved catalytic triad was identified and found to play critical roles in catalysis and cofactor binding. Tyr162 and Lys166 are involved in NADPH binding and mutation of Lys166 causes a conformational change, altering protein structure. Overexpression of BPSS2242 in Escherichia coli increased bacterial survival upon exposure to diacetyl and methylglyoxal. Importantly, the viability of B. pseudomallei encountered dicarbonyl toxicity was enhanced when cultured under high salt concentration as a result of BPSS2242 overexpression. This is the first study demonstrating that BPSS2242 is responsible for detoxification of toxic metabolites, constituting a protective system against reactive carbonyl compounds in B. pseudomallei..


I choose health (Elijo Salud: impacting youth through parish nursing.
The 2009-2010 National Health and Nutritional Examination Survey (NHANES) found that 34% of adolescents are overweight and 18% obese. The chance of an overweight/obese adolescent becoming an overweight/obese adult by age 35 is 60%. Hispanic youth are at risk for becoming obese related to eating habits. This paper describes an intervention, I Choose Health (Elijo Salud), with Hispanic church youth.


Biomarkers of calcineurin inhibitor nephrotoxicity in transplantation.
Over 35 years of use has demonstrated the revolutionary therapeutic benefits of calcineurin inhibitors (CNI) in not only preventing transplant rejection, but also the renal and nonrenal toxicity of CNI. Acute reversible and insidious irreversible forms of CNI nephrotoxicity have been identified, with ischemia from an imbalance between vasoconstrictors and vasodilators playing an important role. The ongoing search to define toxicity pathways has been enriched by 'Omics' studies. Changes in proteins including those involved in activation of pro-inflammatory responses, oxidative stress, ER stress and the unfolded protein response have been identified, and these may serve as biomarkers of toxicity. However, the current standard of CNI toxicity, histology, lacks specificity, which creates challenges for biomarker validation. This review focuses on progress in nephrotoxic pathway identification of CNI and biomarker validation.


Cloning of avian Delta-like 1 homolog gene: the biallelic expression of Delta-like 1 homolog in avian species.
Delta-like 1 homolog (Dlk1) is a paternally expressed imprinted gene in mammals, regulating development and differentiation of adipose and muscle. The Dlk1 genes of the quail and turkey were cloned and analyzed in their properties of amino acid sequences, alternative splicing, and genetic distances from other species. In addition, because Dlk1 is located in the cluster of up to 10 imprinted genes in mammals, the genomic structure of the cluster was investigated in the chicken. Furthermore, the imprinting status of the avian Dlk1 gene was also determined here. The numbers of coding sequences of the quail and turkey Dlk1 were the same as chicken Dlk1 in nucleotide (1,161 bp) and amino acid (386 amino acids) sequences. The amino acid similarities were more than 96% with predicted conserved domains including the signal sequence, 6 epidermal growth factor-like domains, and a transmembrane domain. As in the chicken, the alternative splicing of Dlk1 transcripts was not observed in the turkey and quail. Phylogenetic analysis revealed that the chicken and turkey Dlk1 were closer than the chicken and quail. Comparative analysis of the gene clusters containing the Dlk1 gene revealed that Yy1, Wars, Wdr25, Begain, Dlk1, Dio3, and Ppp2r5c were found in the cluster of the chicken genome, but 3 genes (Meg3, Rtl1, and Meg8) between Dlk1 and deiodinase, iodothyronine, type III (Dio3) were not found. Several SNP in the genomic DNA sequences of the fifth exon were identified in chickens and quail. Sequencing analysis of reverse transcription-PCR products of Dlk1 revealed that adipose and muscle from chickens and quail heterozygous for these SNP produce Dlk1 transcripts from both alleles, demonstrating biallelic expression of Dlk1 in the avian species. These results clearly demonstrate that avian Dlk1 is not imprinted and its expression might be regulated in a different manner from mammals.


[Effect of attenuation by the cranium on quantitative SPECT measurements of cerebral blood flow and a correction method].
Attenuation correction for cerebral blood flow SPECT image reconstruction is usually performed by considering the head as a whole to be equivalent to water, and the effects of differences in attenuation between subjects produced by the cranium have not been taken into account. We determined the differences in attenuation between subjects and assessed a method of correcting quantitative cerebral blood flow values. Attenuations by head on the right and left sides were measured before intravenous injection of 123I-IMP, and water-converted diameters of both sides (Ta) were calculated from the measurements obtained. After acquiring SPECT images, attenuation correction was conducted according to the method of Sorenson, and images were reconstructed. The diameters of the right and left sides in the same position as the Ta (Tt) were calculated from the contours determined by threshold values. Using Ts given by 2Ts = Ta - Tt, the correction factor gamma = exp (mu(1)Ts) was calculated and multiplied as the correction factor when rCBF was determined. The results revealed significant differences between Tt and Ta. Although no gender differences were observed in Tt, they were seen in both Ta and Ts. Thus, interindividual differences in attenuation by the cranium were found to have an influence that cannot be ignored. Inter-subject correlation is needed to obtain accurate quantitative values.