Socioeconomic disadvantage and child development.
Recent research consistently reports that persistent poverty has more detrimental effects on IQ, school achievement, and socioemotional functioning than transitory poverty, with children experiencing both types of poverty generally doing less well than never-poor children. Higher rates of perinatal complications, reduced access to resources that buffer the negative effects of perinatal complications, increased exposure to lead, and less home-based cognitive stimulation partly account for diminished cognitive functioning in poor children. These factors, along with lower teacher expectancies and poorer academic-readiness skills, also appear to contribute to lower levels of school achievement among poor children. The link between socioeconomic disadvantage and children's socioemotional functioning appears to be mediated partly by harsh, inconsistent parenting and elevated exposure to acute and chronic stressors. The implications of research findings for practice and policy are considered.


Dissolving microneedle patch for transdermal delivery of human growth hormone.
The clinical impact of biotechnology has been constrained by the limitations of traditional hypodermic injection of biopharmaceuticals. Microneedle patches have been proposed as a minimally invasive alternative. In this study, the translation of a dissolving microneedle patch designed for simple, painless self-administration of biopharmacetucials that generates no sharp biohazardous waste is assessed. To study the pharmacokinetics and safety of this approach, human growth hormone (hGH) was encapsulated in 600 μm-long dissolving microneedles composed of carboxymethylcellulose and trehalose using an aqueous, moderate-temperature process that maintained complete hGH activity after encapsulation and retained most activity after storage for up to 15 months at room temperature and humidity. After manual insertion into the skin of hairless rats, hGH pharmacokinetics were similar to conventional subcutaneous injection. After patch removal, the microneedles had almost completely dissolved, leaving behind only blunt stubs. The dissolving microneedle patch was well tolerated, causing only slight, transient erythema. This study suggests that a dissolving microneedle patch can deliver hGH and other biopharmaceuticals in a manner suitable for self-administration without sharp biohazardous waste.


T2-weighted prostate MRI at 7 Tesla using a simplified external transmit-receive coil array: correlation with radical prostatectomy findings in two prostate cancer patients.
To report design of a simplified external transmit-receive coil array for 7 Tesla (T) prostate MRI, including demonstration of the array for tumor localization using T2-weighted imaging (T2WI) at 7T before prostatectomy. Following simulations of transmitter designs not requiring parallel transmission or radiofrequency-shimming, a coil array was constructed using loop elements, with anterior and posterior rows comprising one transmit-receive element and three receive-only elements. This coil structure was optimized using a whole-body phantom. In vivo sequence optimization was performed to optimize achieved flip angle (FA) and signal to noise ratio (SNR) in prostate. The system was evaluated in a healthy volunteer at 3T and 7T. The 7T T2WI was performed in two prostate cancer patients before prostatectomy, and localization of dominant tumors was subjectively compared with histopathological findings. Image quality was compared between 3T and 7T in these patients. Simulations of the B1(+) field in prostate using two-loop design showed good magnitude (B1(+) of 0.245 A/m/w(1/2)) and uniformity (nonuniformity [SD/mean] of 10.4%). In the volunteer, 90° FA was achieved in prostate using 225 v 1 ms hard-pulse (indicating good efficiency), FA maps confirmed good uniformity (14.1% nonuniformity), and SNR maps showed SNR gain of 2.1 at 7T versus 3T. In patients, 7T T2WI showed excellent visual correspondence with prostatectomy findings. 7T images demonstrated higher estimated SNR (eSNR) in benign peripheral zone (PZ) and tumor compared with 3T, but lower eSNR in fat and slight decreases in tumor-to-PZ contrast and PZ-homogeneity. We have demonstrated feasibility of a simplified external coil array for high-resolution T2-weighted prostate MRI at 7T.


Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells.
Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over an eight-month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth, indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed increased expression of cancer stem cell markers in tobacco treated cells. In addition, tobacco exposed cells showed the Oxidative Phosphorylation (OXPHOS) phenotype with decreased expression of enzymes associated with glycolytic pathway and increased expression of a large number of mitochondrial proteins involved in electron transport chain as well as enzymes of the tricarboxylic acid (TCA) cycle. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we propose that chronic exposure of esophageal epithelial cells to tobacco leads to cancer stem cell-like phenotype. These cells show the characteristic OXPHOS phenotype, which can be potentially targeted as a therapeutic strategy.


Optical tweezing and binding at high irradiation powers on black-Si.
Nowadays, optical tweezers have undergone explosive developments in accordance with a great progress of lasers. In the last decade, a breakthrough brought optical tweezers into the nano-world, overcoming the diffraction limit. This is called plasmonic optical tweezers (POT). POT are powerful tools used to manipulate nanomaterials. However, POT has several practical issues that need to be overcome. First, it is rather difficult to fabricate plasmonic nanogap structures regularly and rapidly at low cost. Second, in many cases, POT suffers from thermal effects (Marangoni convection and thermophoresis). Here, we propose an alternative approach using a nano-structured material that can enhance the optical force and be applied to optical tweezers. This material is metal-free black silicon (MFBS), the plasma etched nano-textured Si. We demonstrate that MFBS-based optical tweezers can efficiently manipulate small particles by trapping and binding. The advantages of MFBS-based optical tweezers are: (1) simple fabrication with high uniformity over wafer-sized areas, (2) free from thermal effects detrimental for trapping, (3) switchable trapping between one and two - dimensions, (4) tight trapping because of no detrimental thermal forces. This is the NON-PLASMONIC optical tweezers.


[Therapeutic uses for Asian yellow-flowered crowfoot, genus Ranunculus: the case of Blastoestimulina].
Asian yellow-flower crowfoot is a plant which has been used for therapeutic purposes for more than 3000 years. Its main active ingredients are asiaticóside and madecasóside which give it a cicatrizing action as well as being a tonic for the blood. At present time, Asian yellow-flower crowfoot extract is indicated to treat ulcers, sores, scabs, and some types of burns. It is also used as a secondary helping agent to treat surgical wounds and to help skin grafts take root. Its use in the form of vaginal ovules make it be an appropriate treatment for some vaginal diseases. This extract is currently found in diverse medical preparations under the trade name "Blastoestimulina". Numerous studies are underway in the scientific field with the objective of discovering new therapeutic uses for this plant.


Can HPV-16 genotyping provide a benchmark for cervical biopsy specimen interpretation?
Human papillomavirus (HPV) detection is an objective quality assurance benchmark for cervical cytology. There is no comparable metric for cervical biopsies despite biopsies having similar interobserver variability. Because HPV-16 positivity increases with the severity of cervical abnormality, we explored whether HPV-16 detection might be a useful metric for distinguishing a diagnosis of less than cervical intraepithelial neoplasia (CIN) 2 from CIN 2 or worse (representing the clinical threshold for treatment). By using Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion Triage Study data, we compared biopsy diagnoses of the 10 clinical center (CC) pathologists with the quality control (QC) group. Although the percentage of HPV-16 correlated with severity of diagnoses, there was great variability between the rates for each individual CC pathologist. Agreement between individual CC pathologists and the QC group on the percentage of CIN 2 or worse containing HPV-16 correlated weakly with agreement on whether the diagnosis was less than CIN 2 or CIN 2 or worse. Thus the HPV-16 fraction was not found to be broadly useful as a quality assurance metric for biopsy diagnosis in this analysis.


Spider movement, UV reflectance and size, but not spider crypsis, affect the response of honeybees to Australian crab spiders.
According to the crypsis hypothesis, the ability of female crab spiders to change body colour and match the colour of flowers has been selected because flower visitors are less likely to detect spiders that match the colour of the flowers used as hunting platform. However, recent findings suggest that spider crypsis plays a minor role in predator detection and some studies even showed that pollinators can become attracted to flowers harbouring Australian crab spider when the UV contrast between spider and flower increases. Here we studied the response of Apis mellifera honeybees to the presence of white or yellow Thomisus spectabilis Australian crab spiders sitting on Bidens alba inflorescences and also the response of honeybees to crab spiders that we made easily detectable painting blue their forelimbs or abdomen. To account for the visual systems of crab spider's prey, we measured the reflectance properties of the spiders and inflorescences used for the experiments. We found that honeybees did not respond to the degree of matching between spiders and inflorescences (either chromatic or achromatic contrast): they responded similarly to white and yellow spiders, to control and painted spiders. However spider UV reflection, spider size and spider movement determined honeybee behaviour: the probability that honeybees landed on spider-harbouring inflorescences was greatest when the spiders were large and had high UV reflectance or when spiders were small and reflected little UV, and honeybees were more likely to reject inflorescences if spiders moved as the bee approached the inflorescence. Our study suggests that only the large, but not the small Australian crab spiders deceive their preys by reflecting UV light, and highlights the importance of other cues that elicited an anti-predator response in honeybees.


Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage.
Polymeric medical devices widely used in orthopedic surgery play key roles in fracture fixation and orthopedic implant design. Topographical modification and surface micro-roughness of these devices regulate cellular adhesion, a process fundamental in the initiation of osteoinduction and osteogenesis. Advances in fabrication techniques have evolved the field of surface modification; in particular, nanotechnology has allowed the development of nanoscale substrates for the investigation into cell-nanofeature interactions. In this study human osteoblasts (HOBs) were cultured on ordered nanoscale pits and random nano "craters" and "islands". Adhesion subtypes were quantified by immunofluorescent microscopy and cell-substrate interactions investigated via immuno-scanning electron microscopy. To investigate the effects of these substrates on cellular function 1.7 k microarray analysis was used to establish gene profiles of enriched STRO-1+ progenitor cell populations cultured on these nanotopographies. Nanotopographies affected the formation of adhesions on experimental substrates. Adhesion formation was prominent on planar control substrates and reduced on nanocrater and nanoisland topographies; nanopits, however, were shown to inhibit directly the formation of large adhesions. STRO-1+ progenitor cells cultured on experimental substrates revealed significant changes in genetic expression. This study implicates nanotopographical modification as a significant modulator of osteoblast adhesion and cellular function in mesenchymal populations.


Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta.
The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.


Simulator for evaluating shoulder motion as a command source for FES grasp restoration systems.
A simulator has been developed to evaluate the command channels through which a quadriplegic patient controls an upper limb neural prosthesis. The simulator consists of an animated grasping task implemented on a video screen. The patient controls the motion of an animated hand on the screen by moving his or her own hand while the animated hand opens and closes under control of the tested command channel. Experiments were performed using both able-bodied and quadriplegic subjects to evaluate shoulder motion as a command-channel source. The results demonstrated that optimal combinations of shoulder command-channel parameters are subject specific, which suggests using the simulator in the prescription of upper limb neural prostheses and in training quadriplegic persons who use them. Additionally, the experimental results quantified the reduction in performance that came from using ipsilateral vs contralateral shoulder control and the enhancement in performance realized when using substitute sensory force-feedback displays.


Multiple endocrine neoplasia, type IIb. Report of a case.
Multiple endocrine neoplasia, type IIb, is a rare syndrome characterized by mucosal neuromas, medullary thyroid carcinoma (MTC), pheochromocytoma and somatic abnormalities. A case of a 10-year-old girl with multiple mucosal neuromas and bilateral MTC is reported. The presumptive diagnosis of MTC was made on the basis of abnormal basal values of calcitonin and increased calcitonin secretion after pentagastrin injection. The manifestations of the syndrome are summarized, and the importance of repeated evaluation of thyroidal C-cell and adrenal medullary function in patients with the characteristic aspect of the syndrome is emphasized.


Repression of major histocompatibility complex I-A beta gene expression by dbpA and dbpB (mYB-1) proteins.
The induction of major histocompatibility complex class II gene expression is mediated by three DNA elements in the promoters of these genes (W, X, and Y boxes). The Y box contains an inverted CCAAT box sequence, and the binding activity to the CAAT box is mediated by factor NF-Y, which is composed of subunits NF-YA and NF-YB. We have found that transfection of either dbpA or dbpB (mYB-1) or both inhibits I-A beta gene expression. Although the genes for some members of the Y-box family of binding proteins have been isolated by screening an expression library using the Y-box sequence, under our conditions no binding of dbpA or dbpB to the Y box of the I-A beta or I-E alpha promoter was detected. This suggested that repression of I-A beta gene expression by dbpA and dbpB was not due to competition for binding to the Y-box sequence. The results suggest two other mechanisms by which dbpA and dbpB can inhibit transcription from the I-A beta promoter. When dbpA was added, the binding of NF-YA to DNA increased, which could be explained by interaction between these two proteins whose purpose is to increase the binding affinity of NF-YA for DNA. However, this complex was unable to stimulate transcription from the I-A beta promoter. Thus, dbpA competed for the interaction between NF-YA and NF-YB by binding to NF-YA. When dbpB factor was added together with NF-YA and NF-YB, the binding of the NF-YA--NF-YB complex was reduced. This suggested that dbpB may complete with NF-YB for interaction with NF-YA. These results provide an example of how dbpA and dbpB may regulate transcription of promoters that utilize NF-Y as a transcription factor.


Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain.
To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Male Sprague-Dawley (250-300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P < 0.001]) decreased VMR compared with the control group. Metamizole 200 mg/kg did not change responses but dose of 400 and 600 mg/kg metamizole reduced VMR. Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P < 0.05]). Metamizole, dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain.


Stacking-Controlled Growth of rBN Crystalline Films with High Nonlinear Optical Conversion Efficiency up to 1.
Nonlinear optical crystals lie at the core of ultrafast laser science and quantum communication technology. The emergence of two-dimensional (2D) materials provides a revolutionary potential for nonlinear optical crystals due to their exceptionally high nonlinear coefficients. However, uncontrolled stacking orders generally induce the destructive nonlinear response due to the optical phase deviation in different 2D layers. Therefore, conversion efficiency of 2D nonlinear crystals is typically limited to less than 0.01% (far below the practical criterion of >1%). Here, we controllably synthesize crystalline films of rhombohedral boron nitride (rBN) with parallel stacked layers. This success is realized by the utilization of vicinal FeNi (111) single crystal, where both the unidirectional arrangement of BN grains into a single-crystal monolayer and the continuous precipitation of (B, N) source for thick layers are guaranteed. The preserved in-plane inversion asymmetry in rBN films keeps the in-phase second harmonic generation field in every layer and leads to a record-high conversion efficiency of 1% in the whole family of 2D materials within the coherence thickness of only 1.6 μm. Our work provides a route for designing ultrathin nonlinear optical crystals from 2D materials, and will promote the on-demand fabrication of integrated photonic and compact quantum optical devices. This article is protected by copyright. All rights reserved.


[Flow analysis by phase modulation of NMR signals].
Time modulated field-gradient-sequences able to selectively phase encode spatial location or flow velocity in NMR signals are described. The specific phase modulation discriminates between stationary and mobile protons. The method is presented in the one dimensional case and has the following advantages: it is sensitive to flow direction and unaffected by the relaxation times.


Evolution of taxanes in the treatment of metastatic breast cancer.
Taxanes have become effective therapies for patients with metastatic breast cancer (MBC); however, understanding the differences among them is important. Each of the taxanes currently approved for treating MBC has a unique formulation, which translates to differences in toxicity profiles and administration considerations. In this article, the rationale for the development of the taxanes paclitaxel, docetaxel, and nab-paclitaxel is reviewed from a historical perspective. The mechanisms of action, formulations, and indications of taxanes also are discussed. The impact of their formulations on clinical practice and patient care, particularly solvent-based versus novel solvent-free formulations, will be reviewed from the nursing perspective.


Echocardiography in the evaluation of cardiac sources of emboli: the role of transthoracic echocardiography.
Cardioembolism is responsible for a significant number of systemic emboli including approximately 15% of all ischemic strokes. Transthoracic echocardiography has contributed to the understanding of cardioembolism and has been used to detect specific and potential cardiac sources of systemic emboli and risk stratify patients with specific clinical findings for subsequent cardiovascular events. Findings from transthoracic echocardiography indicate that stasis is an important prerequisite for intracardiac thrombosis while reversal of stasis and thrombolysis appear operative in embolism of existing thrombus. Transthoracic echocardiography allows a sensitive and specific noninvasive means to detect left ventricular thrombus, valvular vegetation, and intracardiac tumor, lesions that are directly responsible for cardioembolism. Transthoracic echocardiography can also detect lesions that could potentially contribute to cardioembolism but are not specific causes. Examples of these potential lesions include mitral valve prolapse, patent foramen ovale, and interatrial septal aneurysm. Finally, population-based studies and prospective clinical trials have indicated that the results of transthoracic echocardiography have predictive value for subsequent cardiovascular events and hence provide a means for stratification of patients at risk for cardioembolism. The latter is most notable for the group of patients with nonvalvular atrial fibrillation where left ventricular dysfunction and increased left atrial size are independent predictors for subsequent stroke.


Multi-scaled drivers of ecosystem state: quantifying the importance of the regional spatial scale.
The regional spatial scale is a vital linkage for the informed extrapolation of results from local to continental scales to address broad-scale environmental problems. Among-region variation in ecosystem state is commonly accounted for by using a regionalization framework, such as an ecoregion classification. Rarely have alternative regionalization frameworks been tested for variables measuring ecosystem state, nor have the underlying relationships with the variables that are used to define them been assessed. In this study, we asked two questions: (1) How much among-region variation is there for ecosystems and does it differ by regionalization framework? (2) What are the likely causes of this among-region variation? We present a case study using a large data set of lake water chemistry, uni- and multi-scaled hydrogeomorphic and anthropogenic driver variables that likely influence lake chemistry at the subcontinental scale, and seven existing regionalization frameworks. We used multilevel models to quantify and explain within- and among-region variation in lake water chemistry. Our models account for local driver variables of ecosystem variation within regions, differences in regional mean ecosystem state (i.e., random intercepts in multilevel models), and differences in relationships between local drivers and ecosystem state by region (i.e., random slopes in multilevel models). Using one of the best performing regionalization frameworks (Ecological Drainage Units), we found that for lake phosphorus and alkalinity: (1) a majority of all the variation in water chemistry among the studied lakes occurred among regions, (2) very few regional-scale landscape driver variables were required to explain among-region variation in lake water chemistry, (3) a much higher proportion of the total variation among lakes was explained at the regional scale than at the local scale, and (4) some relationships between local-scale driver variables and lake water chemistry varied by region. Our results demonstrate the importance of considering the regional spatial scale for broad-scale research and ecosystem management and conservation. Our quantitative approach can be easily applied to other response variables, ecosystem types, geographic areas, and spatial extents to inform ecosystem responses to global environmental stressors.


Changes in catecholamine-induced lipolysis in isolated human fat cells during the first year of life.
Catecholamine-induced lipolysis in isolated human adipocytes during the first year of life was investigated. During this period fat cell size increased markedly. Basal and catecholamine-induced glycerol release were positively correlated with age when lipolysis was expressed per cell. However, when lipolysis was expressed per unit of cell surface area (micrometer squared), this correlation was observed only for noradrenaline. Basal lipolysis and the effect of the pure beta-agonist, isoprenaline, were identical in infants and adults. From 0 to 2 mo of age noradrenaline had very little lipolytic effect. The addition of the alpha-2-adrenoceptor antagonist, yohimbine, to noradrenaline equalized lipolysis per micrometer squared in infants and adults and the alpha-2-adrenoceptor sensitivity was significantly enhanced in infants. In both groups the lipolytic adrenoceptor was of the beta-1 type. In conclusion, adipocytes from infants have a poor lipolytic response to noradrenaline partly because of the small fat cells but mainly because of an enhanced alpha-2-adrenoceptor activity.


Occurrence and fate of selected anticancer, antimicrobial, and psychotropic pharmaceuticals in an urban river in a subcatchment of the Yodo River basin, Japan.
Pollution status of six anticancer agents in the river water and effluents of sewage treatment plants (STPs) in Japan was surveyed with comparative analysis of the levels of four microbial and one psychotropic pharmaceuticals widely used for therapeutic medication. The area of survey is located in the Kanzaki-Ai River basin which is a major subcatchment of the Yodo River basin and is centered on a highly populated area that includes the middle and downstream reaches of the Yodo River. Selected cancer agents were bicalutamide, capecitabine, cyclophosphamide, doxifluridine, tamoxifen, and tegafur. A combination of strong anion solid-phase extraction cartridge under pH 11 for adsorption and optimization of liquid chromatography-tandem mass spectroscopy (LC-MS/MS) system was necessary to ensure high recovery rates (63-124% for river water and 52-115% for STP effluent). The year-round survey of these compounds in four seasons showed that all anticancer compounds were detected at median concentrations ranged from not detected to 32 ng/L in the river water and from not detected to 245 ng/L in the effluents of sewage treatment plants not using ozonation. In the case of bicalutamide (an active antiandrogen used to treat prostate cancer), the maximum concentration detected was 254 ng/L in river water and 1032 ng/L in non-ozonated sewage treatment plant effluents. Based on the mass balance, sewage treatment plants were the primary sources of anticancer compounds as well as the other pharmaceuticals in the river, and the attenuation effect of the river water was small. Ozonation at sewage treatment plants was effective in removing these compounds. To the best of our knowledge, this study is the first to report the existence of bicalutamide, doxifluridine, and tegafur in the river environment.


FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study.
FIRST (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study) aimed to determine the optimal minimum lumen area (MLA) by intravascular ultrasound (IVUS) that correlates with fractional flow reserve (FFR) and to assess the correlation between virtual histology IVUS and FFR for intermediate coronary lesions. FFR is considered the gold standard for assessing intermediate coronary lesions. Measurements of ≤0.8 are considered clinically significant and indicative of physiological ischemia. FIRST is a multicenter, prospective, international registry of patients with intermediate coronary lesions, defined as 40% to 80% stenosis by angiography. In total, 350 patients (367 lesions) were enrolled at 10 U.S. and European sites. Patients were followed through hospital discharge. Overall, an MLA <3.07 mm(2) (64.0% sensitivity, 64.9% specificity, area under curve [AUC] = 0.65) was the best threshold value for identifying FFR <0.8. The accuracy improved when reference vessel-specific analyses were performed. An MLA <2.4 mm(2) (AUC = 0.66) was best for reference vessel diameters <3.0 mm, an MLA <2.7 mm(2) (AUC = 0.71) for reference vessel diameters of 3.0 to 3.5 mm, and an MLA <3.6 mm(2) (AUC = 0.68) for reference vessel diameters >3.5 mm. FFR correlated with plaque burden (r = -0.220, p < 0.001) but not with other plaque morphology. Anatomic measurements by IVUS show a moderate correlation with the FFR values. The optimal cutoff for an MLA to FFR <0.8 is vessel dependent. Plaque morphology characteristics do not correlate with FFR. The utility of IVUS MLA as an alternative to FFR to guide intervention in intermediate lesions may be limited in accuracy and should be tested clinically. (Fractional Flow Reserve and Intravascular Ultrasound Relationship Study [FIRST]; NCT01153555).


Prostaglandins: localization in subcellular particles of rat cerebral cortex.
Homogenates of rat cerebral cortex contain material corresponding to prostaglandins E(1), E(2), F(1)alpha, and F(2)alpha which are concentrated mainly in the light microsomal and mitochondrial fractions. Only the former fraction exhibits significant ability to synthesize prostaglandins E(1) and F(1)alpha from bis-homo-gamma-linolenic acid. After subfractionation of the crude mitochondrial fraction, prostaglandin E and F material is found mainly in the cholinergic and noncholinergic nerve endings. We conclude that the nerve endings are a storage site, whereas the light microsomes are the site of synthesis.


Role of vitamin D in cardiovascular health.
Observational studies strongly associate vitamin D deficiency with a variety of cardiovascular diseases beyond defects in bone and calcium metabolism. Vitamin D has multiple mechanisms that potentially may affect cardiovascular health. Because vitamin D deficiency is common, therapies directed at the replacement of vitamin D may be beneficial. To date however, studies evaluating vitamin D supplementation are few and have not consistently shown benefit. It is possible that the lack of benefit in these studies may have arisen from suboptimal levels of vitamin D supplementation or other unknown factors. Nevertheless, the growing body of observational data and consistent findings of relatively high rates of low vitamin D serum levels warrant further well-designed studies to investigate the relation between vitamin D and cardiovascular health. In conclusion, vitamin D is now recognized as important for cardiovascular health and its deficiency as a potential risk factor for several cardiovascular disease processes.


Lean Mass and Fat Mass as Mediators of the Relationship Between Physical Activity and Bone Mineral Density in Postmenopausal Women.
The relationship between physical activity (PA) and bone health is well known, but the role of lean mass (LM) and fat mass (FM) in this relationship remains uncertain. Therefore, the aim of this study was to examine the mediating effect of LM and FM on the relationship between PA and bone mineral density (BMD) in postmenopausal women. This cross-sectional study involved 282 postmenopausal women aged between 50 and 65 year, who were randomly selected from Hongqi community of Harbin City in China. PA was measured using an International PA Questionnaire. Body composition, BMD of the lumbar spine, hip, and total body were measured using dual-energy X-ray absorptiometry. Mediation analysis was performed to investigate the mediating effect of LM and FM on the relationship between PA and BMD. In partial correlation analysis, PA, LM, and FM were positively related to BMD. Positive correlation was found between PA and LM. There were significant differences in BMD between different categories of PA, but the differences disappeared after adjusting for LM. Mediation analysis showed that LM and FM played a mediating role in the relationship between PA and BMD. LM appeared to mediate the effect of BMD in the spine, hip, and total body by 26.91%, 19.55% and 47.98%, respectively; and FM was 22.23%, 27.97%, and 33.02%, respectively. LM and FM affected the relationship between PA and BMD as mediator. Postmenopausal women with high LM and FM had more BMD.


Coarse graining of star-polymer--colloid nanocomposites.
We consider mixtures of self-avoiding multiarm star polymers with hard colloids that are smaller than the star polymer size. By employing computer simulations, and by extending previous theoretical approaches, developed for the opposite limit of small star polymers [A. Jusufi et al., J. Phys.: Condens. Matter 13, 6177 (2001)], we coarse-grain the mixture by deriving an effective cross-interaction between the unlike species. The excellent agreement between theory and simulation for all size ratios examined demonstrates that the theoretical approaches developed for the colloidal limit can be successfully modified to maintain their validity also for the present case of the protein limit, in contrast to the situation for mixtures of colloids and linear polymers. We further analyze, on the basis of the derived interactions, the non-additivity parameter of the mixture as a function of size ratio and star functionality and delineate the regions in which we expect mixing as opposed to demixing behavior. Our results are relevant for the study of star-colloid nanocomposites and pave the way for further investigations of the structure and thermodynamics of the same.


Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling.
The causes and clinical course of acute rejection vary, and it is not possible to predict graft outcome reliably on the basis of available clinical, pathological, and genetic markers. We hypothesized that previously unrecognized molecular heterogeneity might underlie some of the variability in the clinical course of acute renal allograft rejection and in its response to treatment. We used DNA microarrays in a systematic study of gene-expression patterns in biopsy samples from normal and dysfunctional renal allografts. A combination of exploratory and supervised bioinformatic methods was used to analyze these profiles. We found consistent differences among the gene-expression patterns associated with acute rejection, nephrotoxic effects of drugs, chronic allograft nephropathy, and normal kidneys. The gene-expression patterns associated with acute rejection suggested at least three possible distinct subtypes of acute rejection that, although indistinguishable by light microscopy, were marked by differences in immune activation and cellular proliferation. Since the gene-expression patterns pointed to substantial variation in the composition of immune infiltrates, we used immunohistochemical staining to define these subtypes further. This analysis revealed a striking association between dense CD20+ B-cell infiltrates and both clinical glucocorticoid resistance (P=0.01) and graft loss (P<0.001). Systematic analysis of gene-expression patterns provides a window on the biology and pathogenesis of renal allograft rejection. Biopsy samples from patients with acute rejection that are indistinguishable on conventional histologic analysis reveal extensive differences in gene expression, which are associated with differences in immunologic and cellular features and clinical course. The presence of dense clusters of B cells in a biopsy sample was strongly associated with severe graft rejection, suggesting a pivotal role of infiltrating B cells in acute rejection.


Natural infection of pregnant cows with Schmallenberg virus--a follow-up study.
Schmallenberg virus (SBV), an orthobunyavirus discovered in European livestock in late 2011 for the first time, causes premature or stillbirth and severe fetal malformation when cows and ewes are infected during pregnancy. Therefore, cattle of two holdings in the initially most affected area in Germany were closely monitored to describe the consequence for fetuses and newborn calves. Seventy-one calves whose mothers were naturally infected during the first five months of pregnancy were clinically, virologically, and serologically examined. One calve showed typical malformation, another one, born without visible abnormalities, was dead. Two cows aborted during the studied period; spleen and brain samples or meconium swabs were tested by real-time PCR, in none of the fetuses SBV-specific RNA was detectable and the tested fetal sera were negative in a commercially available antibody ELISA. In contrast, in nine clinically healthy calves high SBV-antibody titers were measurable before colostrum intake, and in meconium swabs of six of these animals viral RNA was present as well. The mothers of all nine seropositive calves were presumably infected between days 47 and 162 of gestation, which is within the critical timeframe for fetal infection suggested for SBV and related viruses.


Characterization of immunodominant surface antigens of Haemophilus somnus.
An immunodominant Haemophilus somnus outer membrane protein with an apparent molecular mass of 40 kDa on Western blots (immunoblots) of gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels was characterized because a monospecific antibody against this antigen was protective. This monospecific antibody was used for immunoaffinity purification of the antigen. The immunoaffinity-purified antigen reacted with a polyclonal antibody to the 40-kDa antigen but not with a monoclonal antibody (3G9) which reacted with the 40-kDa antigen in gradient gels. On 8 or 10% gels, the approximately 40-kDa antigen was resolved as two bands, a 40-kDa band which reacted with the protective monospecific polyclonal antibody (p40) and a band of lower molecular mass which reacted with monoclonal antibody 3G9. The latter antigen was designated p39. Both antigens were conserved in all H. somnus isolates tested. The specific antibodies were also used to detect cross-reacting antigens in other gram-negative bacteria. Antibody to p40 reacted with proteins of 55 to 28 kDa, with the greatest intensity shown among proteins from other members of the family Pasteurellaceae. Antibody to p40 was reduced by absorption with live H. somnus or other members of the family Pasteurellaceae, so the antigen appears to be surface exposed. Antibody to p39 only cross-reacted with a broad band (38 to 40 kDa) in Haemophilus agni. Since H. agni is not a bovine pathogen and since convalescent-phase serum from H. somnus-infected animals did recognize p39, the latter may be a good immunodiagnostic antigen, if the lack of cross-reactivity with antigens in other gram-negative bacteria is confirmed with a polyclonal antibody to p39. The cross-reactivity of antiserum to p40 with antigens of members of the family Pasteurellaceae and the ability of this antiserum to protect against H. somnus pneumonia indicate that p40 may be a useful vaccine antigen for H. somnus disease and perhaps even diseases caused by other members of the family Pasteurellaceae.


Multiparametric spectroscopic photoacoustic imaging of breast cancer development in a transgenic mouse model.
To evaluate the potential of multiparametric spectroscopic photoacoustic imaging using oxygen saturation, total hemoglobin, and lipid content to differentiate among four different breast histologies (normal, hyperplasia, ductal carcinoma in situ (DCIS), and invasive breast carcinoma) in a transgenic mouse model of breast cancer development. Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mammary glands (n=251) of a transgenic mouse model of breast cancer development (FVB/N-Tg(MMTV-PyMT)634Mul) were imaged using B-mode ultrasound and spectroscopic photoacoustic imaging, analyzed for oxygen saturation, total hemoglobin, and lipid content, and processed for histological analysis. Statistical analysis was performed using one-way ANOVA, two-sample t-tests, logistic regression, and ROC analysis. Eighty-two normal, 12 hyperplastic, 96 DCIS, and 61 invasive breast carcinoma mammary glands were analyzed. Based on spectroscopic photoacoustic imaging, the oxygen saturation of hyperplasia (50.6%), DCIS (43.0%), and invasive carcinoma (46.2%) significantly increased compared to normal glands (35.5%, P <0.0001), while both total hemoglobin (P<0.01), and lipid content (P<0.0008) significantly decreased with advancing histology. In differentiating normal and hyperplasia from DCIS and invasive breast carcinoma, multiparametric imaging of oxygen saturation, lipid content, and raw photoacoustic signal at 750 nm provided an AUC value of 0.770. Multiparametric spectroscopic photoacoustic imaging is feasible and allows detection of differences in concentration of tissue chromophores among different histologies in a transgenic mouse model of breast cancer development.


Permeability of Gemcitabine and PBPK Modeling to Assess Oral Administration.
Gemcitabine is a nucleoside analog effective against several solid tumors. Standard treatment consists of an intravenous infusion over 30 min. This is an invasive, uncomfortable and often painful method, involving recurring visits to the hospital and costs associated with medical staff and equipment. Gemcitabine's activity is significantly limited by numerous factors, including metabolic inactivation, rapid systemic clearance of gemcitabine and transporter deficiency-associated resistance. As such, there have been research efforts to improve gemcitabine-based therapy efficacy, as well as strategies to enhance its oral bioavailability. In this work, gemcitabine in vitro and clinical data were analyzed and in silico tools were used to study the pharmacokinetics of gemcitabine after oral administration following different regimens. Several physiologically based pharmacokinetic (PBPK) models were developed using simulation software GastroPlus™, predicting the PK parameters and plasma concentration-time profiles. The integrative biomedical data analyses presented here are promising, with some regimens of oral administration reaching higher AUC in comparison to the traditional IV infusion, supporting this route of administration as a viable alternative to IV infusions. This study further contributes to personalized health care based on potential new formulations for oral administration of gemcitabine, as well nanotechnology-based drug delivery systems.


Evidence for the hook supercoiling mechanism of the bacterial flagellum.
The bacterial flagellar hook is a short, highly curved tubular structure connecting the basal body as a rotary motor and the filament as a helical propeller to function as a universal joint to transmit motor torque to the filament regardless of its orientation. This highly curved form is known to be part of a supercoil as observed in the polyhook structure. The subunit packing interactions in the Salmonella hook structure solved in the straight form gave clear insights into the mechanisms of its bending flexibility and twisting rigidity. Salmonella FlgE consists of four domains, D0, Dc, D1 and D2, arranged from inside to outside of the tube, and an atomic model of the supercoiled hook built to simulate the hook shape observed in the native flagellum suggested that the supercoiled form is stabilized by near-axial interactions of the D2 domains on the inner surface of the supercoil. Here we show that the deletion of domain D2 from FlgE makes the hook straight, providing evidence to support the proposed hook supercoiling mechanism that it is the near-axial interactions between the D2 domains that stabilize the highly curved hook structure.


Errors in ozone risk assessment using standard conditions for converting ozone concentrations obtained by passive samplers in mountain regions.
Passive samplers are often employed to measure ozone concentrations in remote areas such as mountain forests. The potential ozone risk for vegetation is then assessed by calculating the AOT40 exposure index (accumulated hourly ozone concentration exceedances above 40 ppb, i.e. AOT40 = Σ([O(3)] - 40)Δt for any hourly ozone concentration [O(3)] > 40 ppb). AOT40 is customary calculated on the basis of ozone concentrations expressed as a volumetric mixing ratio, while lab sheets normally report ozone concentrations from passive samplers in mass units per cubic metre. Concentrations are usually converted from mass units to ppb using a standard conversion factor taking SATP (Standard Ambient Temperature and Pressure) conditions into account. These conditions, however, can vary considerably with elevation. As a consequence, the blanket application of a standard conversion factor may lead to substantial errors in reporting and mapping ozone concentrations and therefore in assessing potential ozone risk in mountain regions. In this paper we carry out a sensitivity analysis of the effects of uncertainties in estimations of air temperature (T) and atmospheric pressure (P) on the concentration conversion factor, and present two examples from two monitoring and mapping exercises carried out in the Italian Alps. We derived P and T at each site from adiabatic lapse rates for temperature and pressure and analysed the magnitude of error in concentration estimations. Results show that the concentration conversion is much more sensitive to uncertainties in P gradient estimation than to air temperature errors. The concentration conversion factor (cf) deviates 5% from the standard transformation at an elevation of 500 m asl. As a consequence, the standard estimated AOT40 at this elevation is about 13% less than the actual value. AOT40 was found to be underestimated by an average between 25% and 34% at typical elevations of mountain forest stands in the Italian Alps when a correct conversion factor for transforming ozone concentrations from μg m(-3) to ppb is not applied.


How can we possibly resolve the planet's nitrogen dilemma?
Nitrogen is the most crucial element in the production of nutritious feeds and foods. The production of reactive nitrogen by means of fossil fuel has thus far been able to guarantee the protein supply for the world population. Yet, the production and massive use of fertilizer nitrogen constitute a major threat in terms of environmental health and sustainability. It is crucial to promote consumer acceptance and awareness towards proteins produced by highly effective microorganisms, and their potential to replace proteins obtained with poor nitrogen efficiencies from plants and animals. The fact that reactive fertilizer nitrogen, produced by the Haber Bosch process, consumes a significant amount of fossil fuel worldwide is of concern. Moreover, recently, the prices of fossil fuels have increased the cost of reactive nitrogen by a factor of 3 to 5 times, while international policies are fostering the transition towards a more sustainable agro-ecology by reducing mineral fertilizers inputs and increasing organic farming. The combination of these pressures and challenges opens opportunities to use the reactive nitrogen nutrient more carefully. Time has come to effectively recover used nitrogen from secondary resources and to upgrade it to a legal status of fertilizer. Organic nitrogen is a slow-release fertilizer, it has a factor of 2.5 or higher economic value per unit nitrogen as fertilizer and thus adequate technologies to produce it, for instance by implementing photobiological processes, are promising. Finally, it appears wise to start the integration in our overall feed and food supply chains of the exceptional potential of biological nitrogen fixation. Nitrogen produced by the nitrogenase enzyme, either in the soil or in novel biotechnology reactor systems, deserves to have a 'renaissance' in the context of planetary governance in general and the increasing number of people who desire to be fed in a sustainable way in particular.


SxsA, a novel surface protein mediating cell aggregation and adhesive biofilm formation of Staphylococcus xylosus.
Biofilm formation of staphylococci has been an emerging field of research for many years. However, the underlying molecular mechanisms are still not fully understood and vary widely between species and strains. The aim of this study was to identify new effectors impacting biofilm formation of two Staphylococcus xylosus strains. We identified a novel surface protein conferring cell aggregation, adherence to abiotic surfaces, and biofilm formation. The S. xylosus surface protein A (SxsA) is a large protein occurring in variable sizes. It lacks sequence similarity to other staphylococcal surface proteins but shows similar structural domain organization and functional features. Upon deletion of sxsA, adherence of S. xylosus strain TMW 2.1523 to abiotic surfaces was completely abolished and significantly reduced in TMW 2.1023. Macro- and microscopic aggregation assays further showed that TMW 2.1523 sxsA mutants exhibit reduced cell aggregation compared with the wildtype. Comparative genomic analysis revealed that sxsA is part of the core genome of S. xylosus, Staphylococcus paraxylosus, and Staphylococcus nepalensis and additionally encoded in a small group of Staphylococcus cohnii and Staphylococcus saprophyticus strains. This study provides insights into protein-mediated biofilm formation of S. xylosus and identifies a new cell wall-associated protein influencing cell aggregation and biofilm formation.


Inflammatory mechanisms: the molecular basis of inflammation and disease.
Inflammation participates importantly in host defenses against infectious agents and injury, but it also contributes to the pathophysiology of many chronic diseases. Interactions of cells in the innate immune system, adaptive immune system, and inflammatory mediators orchestrate aspects of the acute and chronic inflammation that underlie diseases of many organs. A coordinated series of common effector mechanisms of inflammation contribute to tissue injury, oxidative stress, remodeling of the extracellular matrix, angiogenesis, and fibrosis in diverse target tissues. Atherosclerosis provides an example of a chronic disease that involves inflammatory mechanisms. Recruitment of blood leukocytes characterizes the initiation of this disease. Its progression involves many inflammatory mediators, modulated by cells of both innate and adaptive immunity. The complications of established atheroma, including plaque disruption and thrombosis, also intimately involve inflammation. Mastery of the inflammatory response should aid the development of novel strategies to predict disease susceptibility, target and monitor therapies, and ultimately develop new approaches to the prevention and treatment of chronic diseases associated with aging, such as atherosclerosis.


[The participation of the striatum in the central regulation of gonadal hormonal function].
Intrastriatal corticotrophin-releasing hormone (CRH) was shown to induce a decrease in the plasma tectosterone concentration. Besides, the 6-OHDA pre-treatment completely prevented the suppression of plasma testosterone in response to intrastriatal CRH administration. The findings suggest that the striatum is involved in the extrahypothalamic regulation of the gonadal endocrine function.


Paeoniflorin regulates the hypothalamic-pituitary-adrenal axis negative feedback in a rat model of post-traumatic stress disorder.
To investigate the effects of paeoniflorin (PEF) on the hypothalamic-pituitary-adrenal (HPA) axis feedback function of post-traumatic stress disorder (PTSD). Single-prolonged stress (SPS) was used to establish a PTSD-like rat model. The contents of plasma corticosterone (CORT), adrenocorticotropin hormone (ACTH) and corticotropin-releasing hormone (CRH) were measured by ELISA. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR), adrenocorticotropic hormone-releasing factor I receptor (CRF1R), and adrenocorticotropic hormone-releasing factor II receptor (CRF2R) in the hippocampus and amygdala were measured by RT-PCR and immunohistochemistry. The results showed that on day 8 after SPS, model rats showed enhanced HPA axis negative feedback lasting to day 29. On day 29, plasma CORT levels increased in model rats, while plasma CRH levels had no significant difference on days 8, 22, and 29. The expression of GR and MR of model rats significantly increased in the hippocampus, while the expression of GR, MR, and CRF1R significantly decreased in the amygdala. After 14 days of continuous administration of PEF, the enhanced negative feedback was inhibited, and the plasma CORT level significantly reduced after 21 days of administration. Moreover, PEF could significantly decrease the expression of GR and MR in the hippocampus, and increase the expression of GR, MR, and CRF1R significantly in the amygdala. PEF could regulate HPA axis dysfunction in a rat model of PTSD, which may be related to regulating expression of GR and MR in the hippocampus and amygdala and regulating expression of CRF1R in the amygdala.


Spectrum of cancer risk late after AIDS onset in the United States.
Persons living with AIDS today remain at elevated cancer risk. Highly active antiretroviral therapy (HAART), widely available since 1996, prolongs life, but immune function is not fully restored. We conducted this study to assess long-term cancer risk among persons with AIDS relative to the general population and the impact of HAART on cancer incidence. Records of 263 254 adults and adolescents with AIDS (1980-2004) from 15 US regions were matched to cancer registries to capture incident cancers during years 3 through 5 and 6 through 10 after AIDS onset. Standardized incidence ratios (SIRs) were used to assess risks relative to the general population. Rate ratios (RRs) were used to compare cancer incidence before and after 1996 to assess the impact of availability of HAART. Risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin lymphoma (SIRs, 32 and 15). Incidence of both malignancies declined in the HAART era (1996-2006). Risk was elevated for all non-AIDS-defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively) and for the following specific non-AIDS-defining cancers: Hodgkin lymphoma and cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung and/or bronchus, and penis. Anal cancer incidence increased between 1990-1995 and 1996-2006 (RR, 2.9; 95% confidence interval [CI], 2.1-4.0), as did that of Hodgkin lymphoma (RR, 2.0; 95% CI, 1.3-2.9). Among people who survived for several years or more after an AIDS diagnosis, we observed high risks of AIDS-defining cancers and increasing incidence of anal cancer and Hodgkin lymphoma.


Effect of Weather on the Die-Off of Escherichia coli and Attenuated Salmonella enterica Serovar Typhimurium on Preharvest Leafy Greens following Irrigation with Contaminated Water.
The Food Safety Modernization Act (FSMA) includes a time-to-harvest interval following the application of noncompliant water to preharvest produce to allow for microbial die-off. However, additional scientific evidence is needed to support this rule. This study aimed to determine the impact of weather on the die-off rate of Escherichia coli and Salmonella on spinach and lettuce under field conditions. Standardized, replicated field trials were conducted in California, New York, and Spain over 2 years. Baby spinach and lettuce were grown and inoculated with an ∼104-CFU/ml cocktail of E. coli and attenuated Salmonella Leaf samples were collected at 7 time points (0 to 96 h) following inoculation; E. coli and Salmonella were enumerated. The associations of die-off with study design factors (location, produce type, and bacteria) and weather were assessed using log-linear and biphasic segmented log-linear regression. A segmented log-linear model best fit die-off on inoculated leaves in most cases, with a greater variation in the segment 1 die-off rate across trials (-0.46 [95% confidence interval {95% CI}, -0.52, -0.41] to -6.99 [95% CI, -7.38, -6.59] log10 die-off/day) than in the segment 2 die-off rate (0.28 [95% CI, -0.20, 0.77] to -1.00 [95% CI, -1.16, -0.85] log10 die-off/day). A lower relative humidity was associated with a faster segment 1 die-off and an earlier breakpoint (the time when segment 1 die-off rate switches to the segment 2 rate). Relative humidity was also found to be associated with whether die-off would comply with FSMA's specified die-off rate of -0.5 log10 die-off/day.IMPORTANCE The log-linear die-off rate proposed by FSMA is not always appropriate, as the die-off rates of foodborne bacterial pathogens and specified agricultural water quality indicator organisms appear to commonly follow a biphasic pattern with an initial rapid decline followed by a period of tailing. While we observed substantial variation in the net culturable population levels of Salmonella and E. coli at each time point, die-off rate and FSMA compliance (i.e., at least a 2 log10 die-off over 4 days) appear to be impacted by produce type, bacteria, and weather; die-off on lettuce tended to be faster than that on spinach, die-off of E. coli tended to be faster than that of attenuated Salmonella, and die-off tended to become faster as relative humidity decreased. Thus, the use of a single die-off rate for estimating time-to-harvest intervals across different weather conditions, produce types, and bacteria should be revised.


Posterior tibial slope after medial opening wedge high tibial osteotomy of the varus degenerative knee.
This study examined whether medial opening wedge osteotomy inadvertently changes posterior tibial slope and whether this change affects range of motion and functional outcomes. Lateral radiographs of 82 knees with varus arthrosis were reviewed to measure posterior tibial slope before and after medial opening wedge high tibial osteotomy. Anterior or posterior cruciate ligament-deficient knees were excluded. Twenty-one osteotomies were performed using distraction osteogenesis/medial external fixator, 26 using acute distraction/Arthrex plate fixation, and 35 using acute distraction/EBI plate fixation. Preoperative and postoperative Lysholm scores and range of motion were recorded. Posterior slope increased from a mean of 12.5 degrees preoperatively to 16.5 degrees postoperatively (P<.01). Fixation types revealed no difference in posterior slope change. Large slope changes had less preoperative knee flexion than did small changes (123 versus 131; P=.012). No significant correlation existed between posterior slope change and postoperative Lysholm scores (r=0.047, P>.05). We found that medial opening wedge osteotomy may alter sagittal alignment by increasing posterior tibial slope.


[A massive hernia of the bladder into the scrotum. A report of a case].
The hernia of the bladder in the scrotum is a highly uncommon observation. From the clinical standpoint the usual manifestation is a two-stroke voiding. The recommended urological examinations to reach a diagnosis are ultrasound, endovenous urography, retrograde urethrocystography and cystoscopy. Management includes the de-obstruction of the lower urinary tract, if present, resection of associated peritoneum, resection or reduction of the vesical hernia and repairment of inguinal path. The case contributed corresponds to a vesical hernia in a 72-year-old patient, with no obstructive cause, that was treated surgically by resection of the herniated bladder, with good morphological and functional results.


Nanostructure of wet-chemically prepared, polymer-stabilized silver-gold nanoalloys (6 nm) over the entire composition range.
Bimetallic silver-gold nanoparticles were prepared by co-reduction using citrate and tannic acid in aqueous solution and colloidally stabilized with poly(N-vinylpyrrolidone) (PVP). The full composition range of silver : gold from 0 : 100 to 100 : 0 (n : n) was prepared with steps of 10 mol%. The nanoparticles were spherical, monodispersed, and had a diameter of ∼6 nm, except for Ag : Au 90 : 10 nanoparticles and pure Ag nanoparticles which were slightly larger. The size of the nanoalloys was determined by differential centrifugal sedimentation (DCS) and transmission electron microscopy (TEM). By means of X-ray powder diffraction (XRD) together with Rietveld refinement, precise lattice parameters, crystallite size and microstrain were determined. Scanning transmission electron microscopy (STEM) combined with energy-dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS) showed that the particles consisted of a gold-rich core and a silver-rich shell. XRD and DCS indicated that the nanoparticles were not twinned, except for pure Ag and Ag : Au 90 : 10, although different domains were visible in the TEM. A remarkable negative deviation from Vegard's linear rule of alloy mixtures was observed (isotropic contraction of the cubic unit cell with a minimum at a 50 : 50 composition). This effect was also found for Ag:Au bulk alloys, but it was much more pronounced for the nanoalloys. Notably, it was much less pronounced for pure silver and gold nanoparticles. The microstrain was increased along with the contraction of the unit cell with a broad maximum at a 50 : 50 composition. The synthesis is based on aqueous solvents and can be easily scaled up to a yield of several mg of a well dispersed nanoalloy with application potential due to its tuneable antibacterial action (silver) and its optical properties for bioimaging.


A Genetic Screen for Pre-mRNA Splicing Mutants of Arabidopsis thaliana Identifies Putative U1 snRNP Components RBM25 and PRP39a.
In a genetic screen for mutants showing modified splicing of an alternatively spliced GFP reporter gene in Arabidopsis thaliana, we identified mutations in genes encoding the putative U1 small nuclear ribonucleoprotein (snRNP) factors RBM25 and PRP39a. The latter has not yet been studied for its role in pre-messenger RNA (pre-mRNA) splicing in plants. Both proteins contain predicted RNA-binding domains and have been implicated in 5' splice site selection in yeast and metazoan cells. In rbm25 mutants, splicing efficiency of GFP pre-mRNA was reduced and GFP protein levels lowered relative to wild-type plants. By contrast, prp39a mutants exhibited preferential splicing of a U2-type AT-AC intron in GFP pre-mRNA and elevated levels of GFP protein. These opposing findings indicate that impaired function of either RBM25 or PRP39a can differentially affect the same pre-mRNA substrate. Given a prior genome-wide analysis of alternative splicing in rbm25 mutants, we focused on examining the alternative splicing landscape in prp39a mutants. RNA-seq experiments performed using two independent prp39a alleles revealed hundreds of common genes undergoing changes in alternative splicing, including PRP39a itself, a second putative U1 snRNP component PRP40b, and genes encoding a number of general transcription-related proteins. The prp39a mutants displayed somewhat delayed flowering, shorter stature, and reduced seed set but no other obvious common defects under normal conditions. Mutations in PRP39b, the paralog of PRP39a, did not visibly alter GFP expression, indicating the paralogs are not functionally equivalent in this system. Our study provides new information on the contribution of PRP39a to alternative splicing and expands knowledge of plant splicing factors.


Investigating theoretical and experimental cross sections for elastic electron scattering from isoflurane.
We present a comprehensive analysis of elastic electron scattering from isoflurane in the intermediate energy range of 50-300 eV. This research is motivated by the significant impact of this molecule on global warming effects. We conducted this investigation through experimental measurements using a crossed-beam apparatus and covering a wide angular range from 25 to 125 degrees. Relative differential cross sections (DCSs) were obtained and subsequently normalized on an absolute scale by using the relative flow technique, with argon as the reference gas. These DCS values were then extrapolated and integrated to determine the experimental integral cross sections (ICSs). Additionally, we employed the independent atom model and the screening corrected additivity rule with incorporated Interference effects (IAM-SCAR+I) to calculate the theoretical differential and integral cross-sections. Remarkably, the calculated cross sections align closely with the experimental measurements across the entire energy and angular range. Furthermore, this study involved a comparison of the DCSs for isoflurane with previously published DCS values for two other volatile anesthetics, sevoflurane and halothane.


Trauma in the elderly: a bilateral rectus sheath haematoma.
Life expectancy has more than doubled in the last century, and a new cohort of elderly and increasingly frail patients is presenting to emergency departments with new clinical challenges. When this patient cohort presents after injury, all aspects of clinical practice have to be recalibrated to provide safe and appropriate care. The prevalence of chronic disease, levels of organ failure, multiple comorbidities, greater use of anticoagulation and incidence of recurrent low- and high-impact trauma may delay and obscure diagnosis and, ultimately, increase mortality.Older age is a risk factor for rectus sheath haematoma (RSH), which is haemorrhage into the potential space surrounding the rectus abdominis muscle/s. It is a rare presentation following trauma but can provide diagnostic challenges and be fatal. Even more rare is bilateral RSH with only 12 reported in the literature since 1981.This case report describes bilateral RSH presenting in an elderly woman following a fall and the consequences of seemingly minor trauma in the elderly.


Purines and pyrimidines in malarial parasites.
In order for the plasmodium malarial parasite to replicate in the human erythrocyte it requires metabolic pathways which are not operative in the host erythrocyte. Thus, the malarial parasite not only synthesizes enzymes for purine salvage and interconversion, for the pyrimidine biosynthetic pathway de novo, and for the folate cycle, but it also alters the host erythrocyte membrane in respect to the transport of purines. Several of the plasmodium enzymes from these pathways have been cloned and these appear to be highly homologous to the corresponding human enzymes. However, enzymes which have been purified from Plasmodium, have demonstrated physicochemical and kinetic differences and may be potential targets for chemotherapy. Inhibition of individual enzymes, such as the dihydroorotate dehydrogenase (DHO-DHase), and inhibition of the inserted pathway from IMP to AMP and IMP to GMP hold considerable promise as chemotherapeutic targets. An entirely new approach in inhibiting malarial growth involves the altered nucleoside transporter in the infected cell membrane through which cytotoxic compounds may be selectively targeted into only the infected cell.


Streptococcal pyrogenic exotoxin B-induced apoptosis in a549 cells is mediated by a receptor- and mitochondrion-dependent pathway.
It has been shown that streptococcal pyrogenic exotoxin B (SPE B) can induce cells to undergo apoptosis. The present study is to dissect the role of SPE B protease and SPE B protein in the apoptotic process of A549 cells and to elucidate the SPE B-induced apoptotic pathway. Recombinant SPE B (rSPE B) and C192S, a mutant of SPE B without protease activity, were expressed in Escherichia coli and purified by using an affinity column. The apoptosis of A549 cells was assayed by propidium iodide staining, followed by flow cytometry analysis. Our results showed that SPE B induced apoptosis in a dose-dependent manner, whereas C192S did not. When cells were pretreated with rSPE B (2 mug/ml) for as briefly as 5 min and then incubated with C192S of 28 kDa, an apoptosis that is proportional to the period of pretreatment was observed but not with C192S of 42 kDa. These results suggest that the extracellular protease activity of rSPE B is required for the initiation of apoptosis and that the size of SPE B is important for an effective induction of apoptosis. The time course analysis revealed that molecules activated in apoptosis were in the following order: caspase-8 (1.5 h), t-Bid (2.5 h), Bax (3 h), cytochrome c release (6 h), caspase-9 (7 h), and caspase-3 (8 h). The overexpression of Bcl-2 inhibited depolarization of mitochondrial membrane, cytochrome c release, and apoptosis. The results of the present study suggest that SPE B-induced apoptosis is mediated through a receptor-like mechanism and a mitochondrion-dependent pathway.


Mechanism of ultraviolet-induced mutagenesis: extent and fidelity of in vitro DNA synthesis on irradiated templates.
The effect of UV irradiation on the extent and fidelity of DNA synthesis in vitro was studied by using homopolymers and primed single-stranded varphiX174 phage DNA as substrates. Unfractionated and fractionated cell-free extracts from Escherichia coli pol(+) and polA1 mutants as well as purified DNA polymerase I were used as sources of enzymatic activity. (DNA polymerases, as used here, refer to deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 184.108.40.206.) The extent of inhibition of DNA synthesis on UV-irradiated varphiX174 DNA suggested that pyrimidine dimers act as an absolute block for chain elongation by DNA polymerases I and III. Experiments with an irradiated poly(dC) template failed to detect incorporation of noncomplementary bases due to pyrimidine dimers. A large increase in the turnover of nucleoside triphosphates to free monophosphates during synthesis by DNA polymerase I on irradiated varphiX174 DNA has been observed. We propose that this nucleotide turnover is due to idling by DNA polymerase (i.e., incorporation and subsequent excision of nucleotides opposite UV photolesions, by the 3'-->5' "proofreading" exonuclease) thus preventing replication past pyrimidine dimers and the potentially mutagenic event that should result. In support of this hypothesis, DNA synthesis by DNA polymerase from avian myeloblastosis virus and by mammalian DNA polymerase alpha, both of which are devoid of any exonuclease activity, was found to be only partially inhibited, but not blocked, by UV irradiation of the template and accompanied by an increased incorporation of noncomplementary nucleotides. It is suggested that UV mutagenesis in bacteria requires an induced modification of the cellular DNA replication machinery, possibly an inhibition of the 3'-->5' exonuclease activity associated with DNA polymerases.


Prognostic implications of left ventricular global longitudinal strain in patients with bicuspid aortic valve disease and preserved left ventricular ejection fraction.
In patients with bicuspid aortic valve (BAV) and preserved left ventricular (LV) ejection fraction (EF), the frequency of impaired LV global longitudinal strain (GLS) and its prognostic implications are unknown. The present study evaluated the proportion and prognostic value of impaired LV GLS in patients with BAV and preserved LVEF. Five hundred and thirteen patients (68% men; mean age 44 ± 18 years) with BAV and preserved LVEF (>50%) were divided into five groups according to the type of BAV dysfunction: (i) normal function BAV, (ii) mild aortic stenosis (AS) or aortic regurgitation (AR), (iii) ≥moderate isolated AS, (iv) ≥moderate isolated AR, and (v) ≥moderate mixed AS and AR. LV systolic dysfunction based on 2D speckle-tracking echocardiography was defined as a cut-off value of LVGLS (-13.6%). The primary outcome was aortic valve intervention or all-cause mortality. The proportion of patients with LVGLS ≤-13.6% was the highest in the normal BAV group (97%) and the lowest in the group with moderate and severe mixed AS and AR (79%). During a median follow-up of 10 years, 210 (41%) patients underwent aortic valve replacement and 17 (3%) died. Patients with preserved LV systolic function (LVGLS ≤ -13.6%) had significantly better event-free survival compared to those with impaired LV systolic function (LVGLS > -13.6%). LVGLS was independently associated with increased risk of events (mainly aortic valve replacement): hazard ratio 1.09; P < 0.001. Impaired LVGLS in BAV with preserved LVEF is not infrequent and was independently associated with increased risk of events (mainly aortic valve replacement events).


Retained foreign bodies after emergent trauma surgery: incidence after 2526 cavitary explorations.
Trauma patients are thought to be at high risk for iatrogenic retained foreign bodies (RFBs). The objective of this study was to evaluate this incidence. All cases of RFB after cavitary trauma surgery were identified by review of Morbidity and Mortality reports at a Level 1 trauma center from January 1998 to December 2005 and confirmed by the Octagon Risk Management System. Over 8 years, 10,053 trauma operations were performed (2075 laparotomies, 377 thoracotomies, and 74 sternotomies). Three cases (0.1%) of RFB (all sponges) occurred during one single-stage and two damage control laparotomies. The counts were correct before definitive closure in two of three cases. No postoperative x-rays were obtained in any of the cases. RFB diagnosis occurred between days 3 and 9, one on a routine chest x-ray and the other two on abdominal computed tomography scans during a septic workup. Four-month to 8-year follow up documented one pleural effusion and one abscess resulting from the RFB. Iatrogenic RFBs after emergent cavitary trauma surgery occur at a rate of 0.12 per cent and are associated with significant morbidity. In addition to standard preventive strategies, in emergent cases with risk factors such as requiring damage control, before final cavity closure, even with a correct sponge count, radiographic evaluation is warranted.


Triplet state promoted reaction of SO2 with H2O by competition between proton coupled electron transfer (pcet) and hydrogen atom transfer (hat) processes.
The SO2 + H2O reaction is proposed to be the starting process for the oxidation of sulfur dioxide to sulfate in liquid water, although the thermal reaction displays a high activation barrier. Recent studies have suggested that the reaction can be promoted by light absorption in the near UV. We report ab initio calculations showing that the SO2 excited triplet state is unstable in water, as it immediately reacts with H2O through a water-assisted proton coupled electron transfer mechanism forming OH and HOSO radicals. The work provides new insights for a general class of excited-state promoted reactions of related YXY compounds with water, where Y is a chalcogen atom and X is either an atom or a functional group, which opens up interesting chemical perspectives in technological applications of photoinduced H-transfer.


Does adiposity affect muscle function during walking in children?
The biomechanical mechanisms responsible for the altered gait in obese children are not well understood, particularly as they relate to increases in adipose tissue. The purpose of this study was to test the hypotheses that as body-fat percentage (BF%) increased: (1) knee flexion during stance would decrease while pelvic obliquity would increase; (2) peak muscle forces normalized to lean-weight would increase for gluteus medius, gastrocnemius, and soleus, but decrease for the vasti; and (3) the individual muscle contributions to center of mass (COM) acceleration in the direction of their primary function(s) would not change for gluteus medius, gastrocnemius, and soleus, but decrease for the vasti. We scaled a musculoskeletal model to the anthropometrics of each participant (n=14, 8-12 years old, BF%: 16-41%) and estimated individual muscle forces and their contributions to COM acceleration. BF% was correlated with average knee flexion angle during stance (r=-0.54, p=0.024) and pelvic obliquity range of motion (r=0.78, p<0.001), as well as with relative vasti (r=-0.60, p=0.023), gluteus medius (r=0.65, p=0.012) and soleus (r=0.59, p=0.026) force production. Contributions to COM acceleration from the vasti were negatively correlated to BF% (vertical-- r=-0.75, p=0.002, posterior-- r=-0.68, p=0.008), but there were no correlation between BF% and COM accelerations produced by the gastrocnemius, soleus and gluteus medius. Therefore, we accept our first, partially accept our second, and accept our third hypotheses. The functional demands and relative force requirements of the hip abductors during walking in pediatric obesity may contribute to altered gait kinematics.


Bretylium Tosylate; adverse effects in acute myocardial infarction.
The effects of bretylium tosylate in managing acute myocardial infarction were studied in 16 patients within 24 hours from the onset of symptoms and were compared to those of lidocaine in a comparable group of 15 patients. Both drugs were equally effective in preventing cardiac arrhythmias during the 48 hours of trial. No deleterious hemodynamic effects were associated with lidocaine treatment. However, marked supine hypotension developed in seven patients treated with bretylium. No changes occurred simultaneously in heart rate, left ventricular ejection time, or central venous pressure. The occurrence of hypotension correlated with a poor initial hemodynamic state. The substantial and unpredictable circulatory effects of bretylium in acute myocardial infarction contraindicates its routine use in the prevention of infarction arrhythmias.


Fracture resistance of endodontically treated teeth: effect of tooth coloured post material and surface conditioning.
This in vitro study evaluated the effects of the different endodontic posts and surface conditioning on the fracture resistance and fracture modes of endodontically treated teeth. The experimental groups consisted of zirconia ceramic post with a glasss-ceramic core [A], zirconia ceramic post with a composite core [B], glass fiber composite post (FRC) with a composite core [C], and titanium post with a composite core [D]. All posts in these groups were cemented with self-adhesive resin cement (Rely X Unicem Aplicap) combination with tribochemical silica coating (TSC). Groups E, F, G and H comprised the same post-and-core materials as the first 4 groups but cemented with the same resin cement without TSC. Specimens were subjected to thermal cycling between 5 degrees C and 55 degrees C for a total of 5000 cycles with 30s per cycle. Static load was applied to the palatal surface of each specimen until they were fractured. Statistical analysis was conducted using analysis of variance (ANOVA) followed by post-hoc comparisons (Tukey). The fracture resistance was significantly affected by the post material (P < 0.001) and surface conditioning (P < 0.001; two-way ANOVA). The application of TSC to post surface decreased the fracture resistance of zirconia ceramic post with composite core (p=0.002; Tukey) and glass FRC post with composite core (p=0.029; Tukey). No catastrophic failure was observed for groups B, C, D, E, F and G. Under the testing conditions used, the titanium post/composite core that had been silicoated exhibited the highest fracture resistance.


Stimulation of bradykinin B(1) receptors induces vasodilation in conductance and resistance coronary vessels in conscious dogs: comparison with B(2) receptor stimulation.
Constitutive bradykinin B(1) receptors have been identified in dogs; however, their physiological implications involving the coronary circulation remain to be determined. This study examined, in conscious dogs, the coronary response to des-Arg(9)-bradykinin (a B(1) receptor agonist) and the mechanisms involved. Eleven dogs were instrumented with a left ventricular micromanometer, a circumflex coronary catheter, a cuff occluder, a Doppler flow probe, and ultrasonic crystals to measure coronary blood flow velocity (CBFv) and coronary diameter (CD). Intracoronary des-Arg(9)-bradykinin (3 to 100 ng/kg) and bradykinin (0.1 to 10 ng/kg) did not modify systemic hemodynamics but dose-dependently increased CBFv and CD. Des-Arg(9)-bradykinin was less potent than bradykinin. Hoe 140 (a B(2) antagonist, 10 microg/kg) abolished the effects of bradykinin but did not influence the effects of des-Arg(9)-bradykinin. When CBFv increase was prevented by the cuff occluder, CD responses to bradykinin and des-Arg(9)-bradykinin were maintained. Intracoronary lisinopril (0. 75 mg) increased the CD response to bradykinin, with only minimal effect on CBFv, and extended the duration of the effect. Lisinopril did not alter des-Arg(9)-bradykinin responses. Intracoronary N(omega)-nitro-L-arginine (2 mg/kg) decreased the CD effect of bradykinin and prevented the CBFv and CD effects of des-Arg(9)-bradykinin. The relaxing effect of des-Arg(9)-bradykinin on isolated coronary rings was prevented by des-Arg(9), [Leu(8)]-bradykinin. In the conscious dog, B(1) receptors are present in coronary vessels, and their stimulation produces vasodilation in conductance and resistance vessels, which is mediated essentially by NO but not modulated by angiotensin-converting enzyme. However, the coronary vasodilation induced by B(1) receptor stimulation is not as great as that produced by B(2) receptor stimulation.


Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA.
Like most retroviruses and retrotransposons, the retrotransposon Ty3 expresses its pol gene analog (POL3) as a translational fusion to the upstream gag analog (GAG3). The Gag3-Pol3 fusion occurs by frameshifting during translation of the mRNA that encodes the two separate but overlapping ORFs. We showed previously that the shift occurs by out-of-frame binding of a normal aminoacyl-tRNA in the ribosomal A site caused by an aberrant codonoanticodon interaction in the P site. This event is unlike all previously described programmed translational frameshifts because it does not require tRNA slippage between cognate or near-cognate codons in the mRNA. A sequence of 15 nt distal to the frameshift site stimulates frameshifting 7.5-fold. Here we show that the Ty3 stimulator acts as an unstructured region to stimulate frameshifting. Its function depends on strict spacing from the site of frameshifting. Finally, the stimulator increases frameshifting dependent on sense codon-induced pausing, but has no effect on frameshifting dependent on pauses induced by nonsense codons. Complementarity between the stimulator and a portion of the accuracy center of the ribosome, Helix 18, implies that the stimulator may directly disrupt error correction by the ribosome.


Nutritional intake and dietary patterns in pregnancy: a longitudinal study of women with lifetime eating disorders.
There is limited knowledge about dietary patterns and nutrient/food intake during pregnancy in women with lifetime eating disorders (ED). The objective of the present study was to determine patterns of food and nutrient intake in women with lifetime ED as part of an existing longitudinal population-based cohort: the Avon Longitudinal Study of Parents and Children. Women with singleton pregnancies and no lifetime psychiatric disorders other than ED (n 9723) were compared with women who reported lifetime (ever) ED: (anorexia nervosa (AN, n 151), bulimia nervosa (BN, n 186) or both (AN+BN, n 77)). Women reported usual food consumption using a FFQ at 32 weeks of gestation. Nutrient intakes, frequency of consumption of food groups and overall dietary patterns were examined. Women with lifetime ED were compared with control women using linear regression and logistic regression (as appropriate) after adjustment for relevant covariates, and for multiple comparisons. Women with lifetime ED scored higher on the 'vegetarian' dietary pattern; they had a lower intake of meat, which was compensated by a higher consumption of soya products and pulses compared with the controls. Lifetime AN increased the risk for a high ( ≥ 2500 g/week) caffeine consumption in pregnancy. No deficiencies in mineral and vitamin intake were evident across the groups, although small differences were observed in macronutrient intakes. In conclusion, despite some differences in food group consumption, women with lifetime ED had similar patterns of nutrient intake to healthy controls. Important differences in relation to meat eating and vegetarianism were highlighted, as well as high caffeine consumption. These differences might have an important impact on fetal development.


MicroRNA-193a Downregulates HMGB1 to Alleviate Diabetic Neuropathic Pain in a Mouse Model.
Diabetic neuropathy is a serious complication for diabetic patients involving the nervous system. This disease is a quiet but painful condition caused by chronically high blood glucose levels. It is reported that high mobility group box 1 protein (HMGB1) participates in the development of neuropathic pain. This study aimed to explore the role of microRNA (miR)-193a in diabetic neuropathic pain through the regulation of HMGB1. A diabetic mouse model was established through the injection of streptozocin (STZ). Neuropathic pain development was shown by paw withdrawal thresholds and paw withdrawal latency. Expression levels of relative genes or miR were analyzed by qRT-PCR, while Western blot was employed to assess the protein levels. The interaction between miR-193a and HMGB1 mRNA 3'-UTR region was shown by luciferase assay. The levels of inflammation cytokines were measured by ELISA kits. miR-193a expression was decreased and HMGB1 expression was upregulated in the lumbar spinal dorsal horn of STZ-induced diabetic mice. miR-193a inhibited HMGB1 expression in the lumbar spinal dorsal horn. Overexpression of miR-193a alleviated neuropathic pain in STZ-induced diabetic mice. Peripheral neuroinflammation in diabetic mice was suppressed by miR-193a overexpression. This research illustrates that miR-193a alleviates diabetic neuropathic pain in a mouse model through the inhibition of HMGB1 expression.


Accidental intravenous infusion of a large dose of magnesium sulphate during labor: A case report.
During labor and child delivery, a wide range of drugs are administered. Most of these medications are high-alert medications, which can cause significant harm to the patient due to its inadvertent use. Errors could be caused due to unfamiliarity with safe dosage ranges, confusion between similar looking drugs, mislabeling of drugs, equipment misuse, or malfunction and communication errors. We report a case of inadvertent infusion of a large dose of magnesium sulphate in a pregnant woman.


PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization.
Fluorescence in situ hybridization (FISH) is the most widely used method for detecting unbalanced chromosome rearrangements in preimplantation embryos but it is known to have several technical limitations. We describe the clinical application of a molecular-based assay, array comparative genomic hybridization (array-CGH), to simultaneously screen for unbalanced translocation derivatives and aneuploidy of all 24 chromosomes. Cell biopsy was carried out on cleavage-stage embryos (Day 3). Single cells were first lysed and DNA amplified by whole-genome amplification (WGA). WGA products were then processed by array-CGH using 24sure + arrays, BlueGnome. Balanced/normal euploid embryos were then selected for transfer on Day 5 of the same cycle. Twenty-eight consecutive cycles of preimplantation genetic diagnosis were carried out for 24 couples carrying 18 different balanced translocations. Overall, 187/200 (93.5%) embryos were successfully diagnosed. Embryos suitable for transfer were identified in 17 cycles (60.7%), with transfer of 22 embryos (mean 1.3 ± 0.5). Twelve couples achieved a clinical pregnancy (70.6% per embryo transfer), with a total of 14 embryos implanted (63.6% per transferred embryo). Three patients delivered three healthy babies, during writing, the other pregnancies (two twins and seven singletons) are ongoing beyond 20 weeks of gestation. The data obtained demonstrate that array-CGH can detect chromosome imbalances in embryos, also providing the added benefit of simultaneous aneuploidy screening of all 24 chromosomes. Array-CGH has the potential to overcome several inherent limitations of FISH-based tests, providing improvements in terms of test performance, automation, sensitivity and reliability.


An update and ecological perspective on certain sentinel helminth endoparasites within the Mediterranean Sea.
The Mediterranean Sea is recognized as a marine biodiversity hotspot. This enclosed basin is facing several anthropogenic-driven threats, such as seawater warming, pollution, overfishing, bycatch, intense maritime transport and invasion by alien species. The present review focuses on the diversity and ecology of specific marine trophically transmitted helminth endoparasites (TTHs) of the Mediterranean ecosystems, aiming to elucidate their potential effectiveness as 'sentinels' of anthropogenic disturbances in the marine environment. The chosen TTHs comprise cestodes and nematodes sharing complex life cycles, involving organisms from coastal and marine mid/upper-trophic levels as definitive hosts. Anthropogenic disturbances directly impacting the free-living stages of the parasites and their host population demographies can significantly alter the distribution, infection levels and intraspecific genetic variability of these TTHs. Estimating these parameters in TTHs can provide valuable information to assess the stability of marine trophic food webs. Changes in the distribution of particular TTHs species can also serve as indicators of sea temperature variations in the Mediterranean Sea, as well as the bioaccumulation of pollutants. The contribution of the chosen TTHs to monitor anthropogenic-driven changes in the Mediterranean Sea, using their measurable attributes at both spatial and temporal scales, is proposed.


Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.
Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), urea, and creatinine increased significantly in the DPN and diabetic rats without peripheral neuropathy (PN) compared with control group. The treatment of DNP with gabapentin induced significant increases in ALAT and ASAT activities but LLLT treatment induced significant decreases in ALAT and ASAT activities as compared with DNP group. Neither gabapentin nor LLLT could improve the elevated levels of serum urea and creatinine in the DNP. It could be concluded that LLLT is more safe and effective than gabapentin in the management of neuropathy in diabetic rats.


Touch to learn: Multisensory input supports word learning and processing.
Infants experience language in rich multisensory environments. For example, they may first be exposed to the word applesauce while touching, tasting, smelling, and seeing applesauce. In three experiments using different methods we asked whether the number of distinct senses linked with the semantic features of objects would impact word recognition and learning. Specifically, in Experiment 1 we asked whether words linked with more multisensory experiences were learned earlier than words linked fewer multisensory experiences. In Experiment 2, we asked whether 2-year-olds' known words linked with more multisensory experiences were better recognized than those linked with fewer. Finally, in Experiment 3, we taught 2-year-olds labels for novel objects that were linked with either just visual or visual and tactile experiences and asked whether this impacted their ability to learn the new label-to-object mappings. Results converge to support an account in which richer multisensory experiences better support word learning. We discuss two pathways through which rich multisensory experiences might support word learning.