In silico discovery of 3 novel quercetin derivatives against papain-like protease, spike protein, and 3C-like protease of SARS-CoV-2.
The derivatives of quercetin is known for their immune-modulating antiviral, anti-blood clotting, antioxidant, and also for its anti-inflammatory efficacy. The current study was therefore conducted to examine the noted novel derivatives of quercetin present in plant sources as an immune modulator and as an antiviral molecule in the COVID-19 disease and also to study their affinity of binding with potential three targets reported for coronavirus, i.e., papain-like protease, spike protein receptor-binding domain, and 3C-like protease. Based on the high-positive drug-likeness score, the reported derivatives of quercetin obtained from an open-source database were further filtered. Compounds with positive and high drug-likeness scores were further predicted for their potential targets using DIGEP-Pred software, and STRING was used to evaluate the interaction between modulated proteins. The associated pathways were recorded based on the Kyoto Encyclopedia of Genes and Genomes pathway database. Docking was performed finally using PyRx having AutoDock Vina to identify the efficacy of binding between quercetin derivatives with papain-like protease, spike protein receptor-binding domain, and 3C-like protease. The ligand that scored minimum binding energy was chosen to visualize the interaction between protein and ligand. Normal mode analysis in internal coordinates was done with normal mode analysis to evaluate the physical movement and stability of the best protein-ligand complexes using the iMODS server. Forty bioactive compounds with the highest positive drug-likeness scores were identified. These 40 bioactives were responsible for regulating different pathways associated with antiviral activity and modulation of immunity. Finally, three lead molecules were identified based on the molecular docking and dynamics simulation studies with the highest anti-COVID-19 and immunomodulatory potentials. Standard antiviral drug remdesivir on docking showed a binding affinity of - 5.8 kcal/mol with PLpro, - 6.4 kcal/mol with 3CLpro, and - 8.6 kcal/mol with spike protein receptor-binding domain of SARS-CoV-2, the discovered hit molecules quercetin 3-O-arabinoside 7-O-rhamnoside showed binding affinity of - 8.2 kcal/mol with PLpro, whereas quercetin 3-[rhamnosyl-(1- > 2)-alpha-L-arabinopyranoside] and quercetin-3-neohesperidoside-7-rhamnoside was predicted to have a binding affinity of - 8.5 kcal/mol and - 8.8 kcal/mol with spike protein receptor-binding domain and 3CLpro respectively CONCLUSION: Docking study revealed quercetin 3-O-arabinoside 7-O-rhamnoside to possess the highest binding affinity with papain-like protease, quercetin 3-[rhamnosyl-(1- > 2)-alpha-L-arabinopyranoside] with spike protein receptor-binding domain, and quercetin-3-neohesperidoside-7-rhamnoside with 3C-like protease and all the protein-ligand complexes were found to be stable after performing the normal mode analysis of the complexes in internal coordinates.


Condensing osteitis in oral region.
Condensing osteitis is defined as pathologic growth of maxillomandibular bones characterized by mild clinical symptoms. The bone thickening reflects the impaired bone rearrangement in response to mild infection of dental pulp. This clinical study describes case reports of patients sent to us with radiological findings and clinical examination that failed to lead to definitive diagnosis. On differential diagnosis, all bone tissue tumors were considered. Based on clinical and radiological findings (bone density and trabeculation of the bone) we settled on the diagnosis of osteitis condensans, which allowed us to remain in conservative therapy in terms of observing the patient (Fig. 3, Ref. 26). Full Text (Free, PDF) www.bmj.sk.


Soluble aggregates of the amyloid-beta protein selectively stimulate permeability in human brain microvascular endothelial monolayers.
Cerebral amyloid angiopathy associated with Alzheimer's disease is characterized by cerebrovascular deposition of the amyloid-beta protein (Abeta). Abeta elicits a number of morphological and biochemical alterations in the cerebral microvasculature, which culminate in hemorrhagic stroke. Among these changes, compromise of the blood-brain barrier has been described in Alzheimer's disease brain, transgenic animal models of Alzheimer's disease, and cell culture experiments. In the current study, presented data illustrates that isolated soluble Abeta(1-40) aggregates, but not unaggregated monomer or mature fibril, enhance permeability in human brain microvascular endothelial monolayers. Abeta(1-40)-induced changes in permeability are paralleled by both a decrease in transendothelial electrical resistance and a re-localization of the tight junction-associated protein zonula occludin-1 away from cell borders and into the cytoplasm. Small soluble Abeta(1-40) aggregates are confirmed to be the most potent stimulators of endothelial monolayer permeability by establishing an inverse relationship between average aggregate size and stimulated changes in diffusional permeability coefficients. These results support previous findings demonstrating that small soluble Abeta(1-40) aggregates are also primarily responsible for endothelial activation, suggesting that these same species may elicit other changes in the cerebrovasculature associated with cerebral amyloid angiopathy and Alzheimer's disease.


Cell cycle kinetics of human anagen scalp hair bulbs in thyroid disorders determined by DNA flow cytometry.
In both, 6 hyperthyroid and 6 hypothyroid patients as well as 10 healthy volunteers, cell cycle kinetics of dissected anagen scalp hair bulbs were determined by means of DNA flow cytometry (DNA-FCM). Compared with the healthy control group in patients with thyroid disorders striking differences of cell kinetic data were evaluated. In hyperthyroidism a significant increase (30%) and in hypothyroidism a significant decrease (15%) of S and G2+M phase cell percentages was found. The proliferation index (S+G2+M %) calculated revealed similar results. A correlation between the height of S phase percentages and plasma T3 levels was recognizable but could not be proven statistically. By means of DNA-FCM the study demonstrates for the first time the influence of thyroid hormones on in vivo cell cycle kinetics of human scalp hair bulbs.


[Improved nitric acid digestion method for detecting diatom in autopsy tissue].
To investigate the advantages of nitric acid digestion method and its differences with the traditional method. Ethanol was used to fully fix the testing sample. About 80-100 g of the testing samples were cut into pieces and digested with nitric acid. It was then centrifuged and washed to remove organic components. Smears were prepared and examined under the light microscope. The diatom had been identified with clear striations, counted conveniently and classified easily. The improved nitric acid digestion method is not only simple with a higher successful rate of detection, but also can prevent interference from contamination. It can improve the stability of the experimental results, avoid harm to human and environment, and provide higher safety in the course of experiment.


The risk of malignancy associated with psoriasis.
To measure the incidence of cancer in patients with psoriasis, stratified by the severity of their disease. A cohort study. Administrative claims records obtained from Medicaid programs in 3 US states. All individuals in the claims database who qualified for 1 of the 5 following groups: severe psoriasis as defined by treatment with systemic medication, less severe psoriasis, severe eczema, history of organ transplantation, and hypertension. A diagnosis of cancer. Individuals with severe psoriasis were more likely to develop a malignancy than those with hypertension (risk ratio, 1.78; 95% confidence interval [CI], 1.32-2.40). The risk of malignancy in the severe psoriasis group approaches that in patients with organ transplants (risk ratio, 2.12; 95% CI, 1.80-2.50). Most of these cancers were nonmelanoma skin cancers and lymphoproliferative malignancies. Those with less severe psoriasis were only slightly more likely to develop a new malignancy than those with hypertension (risk ratio, 1.13; 95% CI, 1.03-1.25). Patients with psoriasis are at an increased risk of developing a malignancy compared with patients with hypertension. The increased risk is greatest for those with severe disease (ie, patients with psoriasis treated with systemic agents) and minimal (if an increased risk at all) for those with less severe disease compared with those in the hypertension group. The increased risk is mainly for lymphoproliferative cancers and nonmelanoma skin cancers.


Bleeding peptic ulcers and presence of Helicobacter pylori by various tests: a case-control study.
Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with bleeding peptic ulcers (BPU). To determine whether H. pylori and/or the cytotoxin-associated gene (cagA) can increase the risk of bleeding in peptic ulcers. Sixty-seven patients were studied. Thirty had BPU, 20 had non-bleeding peptic ulcers (NBPU), and 17 were control subjects (NPU). The prevalence of H. pylori was assessed by the urease fast test, histological examination, serology, and 16S ribosomal RNA and cagA gene amplification by polymerase chain reaction (PCR). Histology and PCR showed greater sensitivity for diagnosis of H. pylori under bleeding circumstances when compared with other tests. Association of H. pylori was greater in the NBPU group (odds ratio [OR] 4.91, P = 0.06) than in the BPU group (OR 1.27, P = NS) when compared with the control group. When the BPU and NBPU groups were compared, H. pylori was found more often in the NBPU group (OR 0.26, P < 0.10 ). The cagA-positive gene showed a similar distribution in the three groups. The titres for anti-CagA immunoglobulin A (IgA) antibodies were higher in NBPU patients (83%) than in BPU or control patients. Furthermore, anti-urease immunoglobulin G (IgG) was detected more frequently among BPU and NBPU patients. NBPU patients had the highest prevalence of H. pylori by PCR. It seems unlikely that either H. pylori or the cagA-positive gene act as significant risk factors for bleeding in peptic ulcers. The lower prevalence of the microorganism among patients who bleed cannot be explained as an artificial finding.


Principles for quality undergraduate education in psychology.
The principles for undergraduate education in psychology presented here are designed for creating a world-class educational system that provides students with the workplace skills needed in this information age; a solid academic background that prepares them for advanced study in a wide range of fields; and the knowledge, skills, and abilities that will enhance their personal lives. A quality undergraduate education is designed to produce psychologically literate citizens who apply the principles of psychological science at work and at home. The American Psychological Association (APA) urges all stakeholders in undergraduate education in psychology to incorporate these principles in establishing goals and objectives that fit their specific institutional needs and missions.


Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression.
The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene (Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, and selected the cells that overexpressed Pdx1 by 150-fold compared with control. The cells were examined for differentiation into enteroendocrine cells by immunocytochemical and electron microscopic analyses. Transfected cells cultured on micropore filters formed a trabecular network piled up on monolayer cells. These trabecular cells showed nuclear localization of Pdx1 protein and contained well-developed rough endoplasmic reticulum as well as many secretory granules of pleomorphic shape in the cytoplasm. Antibodies against chromogranin A, serotonin, cholecystokinin, gastrin, and somatostatin stained these secretory granules in the cytoplasm. Furthermore, immunofluorescence double staining analysis showed that different hormones were produced within a cell. These results provide the evidence that immature intestinal epithelial cells can differentiate into multiple hormone-producing enteroendocrine cells in response to overexpression of Pdx1.


Administration of low-dose resveratrol attenuated hepatic inflammation and lipid accumulation in high cholesterol-fructose diet-induced rat model of nonalcoholic fatty liver disease.
Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1β, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.


Childhood abuse in adults in primary care: Empirical findings and clinical implications.
In the healthcare setting, adult patients with histories of childhood abuse are of significant concern and are frequently encountered in the primary care setting. However, there is a dearth of studies investigating the relationships between psychopathology, overall health, healthcare utilization, physician ratings of patient difficulty, and childhood abuse. The present study examines these relationships in primary care patients with (N = 45) and without (N = 129) histories of childhood abuse (physical, sexual, and both). Findings revealed that adult patients with histories of childhood abuse generally scored significantly higher on measures of psychopathology, emergency room use, and doctor-patient relationship difficulty, and lower on a measure of mental and physician-rated physical health. In a multiple regression analysis, income and a history of childhood sexual abuse significantly predicted overall mental health. In a second multiple regression analysis, income, depression, somatization, borderline personality disorder, and difficult doctor-patient relationship ratings significantly predicted physician-rated physical health. Overall, these findings suggest that a history of childhood abuse is associated with a host of negative health outcomes. Findings also suggest that negative feelings about a patient may help physicians identify patients with histories of childhood abuse. It is especially important for physicians to routinely include an assessment of childhood abuse during the psychosocial portion of the medical interview or through screening instruments.


Qualitative neuropsychological measures: normative data on executive functioning tests from the Framingham offspring study.
BACKGROUND/STUDY CONTEXT: Studies have found that executive functioning is affected early in the pathophysiological processes associated with Alzheimer's disease and vascular dementia. There also exists a range of functioning on executive tasks during normal aging. Although qualitative data are commonly utilized in clinical practice for evaluating subtle changes in cognitive functioning and diagnostic discernment, it is not clear whether error responses used in clinical practice are also evident as normative behavior. As part of an extensive battery of neuropsychological tests, executive functioning measures (i.e., Trail Making Test Part B, Similarities and Verbal Fluency tests) were administered via standardized administration prescript. Regression analyses were used to determine associations between vascular aging indices and qualitative performance measures. Descriptive statistics are included for 1907 cognitively normal individuals. Results suggest that although qualitative errors do occur, they are relatively infrequent within a presumably cognitively normal sample. Error commission rates on executive functioning tests are significantly associated with both age and education. Provided is a baseline profile of errors committed on tests of executive function across a range of age and educational levels. The normative data sets are included, stratified by age and educational achievement, for which to compare qualitative test performance of clinical and research populations.


What do artificial neural networks tell us about the genetic structure of populations? The example of European pig populations.
General and genetic statistical methods are commonly used to deal with microsatellite data (highly variable neutral genetic markers). In this paper, the self-organizing map (SOM) that belongs to the unsupervised artificial neural networks (ANNs) was applied to analyse the structure of 58 European and two Chinese pig populations (Sus scrofa) including commercial lines, local breeds and cosmopolitan breeds. Results were compared with other unsupervised classification or ordination methods such as factorial correspondence analysis, hierarchical clustering from an allele sharing distance and the Bayesian genetic model and with principal components analysis and neighbour joining from allelic frequencies and genetic distances between populations. Like other methods, SOMs were able to classify individuals according to their breed origin and to visualize similarities between breeds. They provided additional information on the within- and between-population diversity, allowed differences between similar populations to be highlighted and helped differentiate different groups of populations.


Nodular lung disease with five year survival and unilateral pleural effusion in AL amyloidosis.
A 67-year-old female patient with biopsy proven AL systemic amyloidosis developed rapidly progressive dyspnea. Chest roentgenogram and CT scan revealed a large right pleural effusion in addition to nodular lesions with bilateral hilar lymphadenopathy. The patient's serum showed IgG lambda type monoclonal gammopathy and she also had Bence Jones proteinuria. The pleural effusion was an exudate that contained many mononuclear cells and a high concentration of protein. Cardiac function was not seriously disturbed. Except for amyloidosis, no other causes for the severe pleural effusion were found. This patient was treated with chemical pleurodesis using Picibanil and a low dose of prednisolone. Eighteen months after this treatment, her right pleural effusion did not recur. Bronchopulmonary tissues are known to be frequently involved by AL systemic amyloidosis, but a nodular pattern of pulmonary amyloid deposition and a unilateral large pleural effusion are rare clinical manifestations in this disease.


"Pure" Suprasellar Schwannoma Presented with Communicating Hydrocephalus: A Case Report.
Schwannoma is a benign peripheral nerve sheath tumor originating from Schwann cells. Most intracranial schwannomas arise from vestibular nerve and schwannoma in the suprasellar region is extremely rare. A 64-year-old man presented with walking disturbance and blurred vision for three months. Lateral hemianopsia in the left eye and brachybasia were observed. Magnetic resonance imaging revealed a suprasellar tumor with strong contrast enhancement associated with communicating hydrocephalus. The cerebrospinal fluid tap test improved gait disturbance. Hypothalamic stimulation test revealed hypo-reaction of GH, FSH and LH. After ventriculo-peritoneal shunting, the tumor was totally removed via a bilateral front-basal approach with a clinical diagnosis of craniopharyngioma. No adhesion was observed between the tumor and surrounding structures such as meninges and brain. The histopathological diagnosis was schwannoma. Here we report a case of suprasellar schwannoma associated with communicating hydrocephalus that has not ever been previously reported, with special reference to its pathogenesis.


Perinatal outcome of pregnancies following in vitro fertilization and ovulation induction.
To investigate pregnancy outcome in patient who conceived by assisted reproductive techniques. A retrospective population-based study was conducted, comparing obstetrical complications and neonatal outcomes of singleton pregnancies conceived by in vitro fertilization (IVF; n = 1296) and ovulation induction (n = 1988) as compared to singleton pregnancies conceived spontaneously (n = 172 288). Multivariable models were constructed to control for confounders. A significant linear association (using the chi-square test for trends) was documented among the three groups in adverse outcomes such as gestational diabetes mellitus (17.3% in the IVF, 14.2% in the ovulation induction, 6.6% in the comparison group, p < 0.001), severe preeclampsia (2.7% in the IVF, 1.8% in the ovulation induction, 1.1% in the comparison group, p < 0.001) and perinatal mortality (3.3% in the IVF, 2.1% in the ovulation induction, 1.3% in the comparison group, p < 0.001). In vitro fertilization and ovulation induction treatments were found to be independent risk factors for gestational diabetes mellitus, using two different multiple logistic regression models controlling for confounders such as maternal age (adjusted OR = 1.77, 95% CI:1.52-2.07, p < 0.001 and adjusted OR = 1.93, 95% CI:1.69-2.21, p < 0.001; respectively). Pregnancies conceiving following assisted reproductive techniques are at an increased risk for adverse obstetrics outcomes. The risk is higher for pregnancies following IVF compared with these conceived following ovulation induction.


Expression of intercellular adhesion molecule 1 (ICAM-1) on human articular cartilage chondrocytes.
Monoclonal antibodies have been used to demonstrate the induction of intercellular adhesion molecule 1 (ICAM-1) on chondrocytes in human articular cartilage. ICAM-1 was found not to be constitutively expressed but could be induced by exogenous interleukin 1 alpha(IL1- alpha) at concentrations ranging from 0.01 to 20 ng/ml during in vitro culture. Maximum expression was observed with 2-5ng/ml. In time-course experiments ICAM-1 was not expressed after 4h in culture with IL1 alpha. Expression was induced by 16h and was sustained for a minimum of 6 days in the continued presence of the cytokine. The endothelial leukocyte adhesion molecule (ELAM-1) was not expressed on chondrocytes and was not induced by IL1-alpha.


Smear correction of highly variable, frame-transfer CCD images with application to polarimetry.
Image smear, produced by the shutterless operation of frame-transfer CCD detectors, can be detrimental for many imaging applications. Existing algorithms used to numerically remove smear do not contemplate cases where intensity levels change considerably between consecutive frame exposures. In this report, we reformulate the smearing model to include specific variations of the sensor illumination. The corresponding desmearing expression and its noise properties are also presented and demonstrated in the context of fast imaging polarimetry.


Caregivers' treatment-seeking behaviors and predictors of whether a child received an appropriate antimalarial treatment: a household survey in rural Uganda.
This study responds to a rural community's concern that, despite national initiatives, malaria management in young children falls short of national guidelines in their district. This study aimed to: (1) describe caregivers' treatment-seeking behaviors in the rural district of Butaleja, (2) estimate the percentage of children who received an appropriate antimalarial, and (3) determine factors that maximized the likelihood of receiving an appropriate antimalarial. Appropriate antimalarial in this study is defined as having received only the Uganda's age-specific first-line malaria treatment for uncomplicated and severe malaria during the course of the febrile illness. A household survey design was used in 2011 to interview 424 caregivers with a child aged five and under who had fever within the two weeks preceding the survey. The survey evaluated factors that included: knowledge about malaria and its treatment, management practices, decision-making, and access to artemisinin combination therapy (ACT) and information sources. Bivariate analysis, followed by logistic regression, was used to determine predictors of the likelihood of receiving an appropriate antimalarial. Home management was the most common first action, with most children requiring a subsequent action to manage their fever. Overall, 20.9 % of children received a blood test, 68.4 % received an antimalarial, and 41.0 % received an ACT. But closer inspection showed that only 31.6 % received an appropriate antimalarial. These results confirm that ACT usage and receipt of an appropriate antimalarial in Butaleja remain well below the 2010/2015 target of 85 %. While nine survey items differentiated significantly whether a child had or had not received an appropriate antimalarial, our logistic regression model identified four items as independent predictors of likelihood that a child would receive an appropriate antimalarial: obtaining antimalarials from regulated outlets (OR = 14.99); keeping ACT in the home for future use (OR = 6.36); reporting they would select ACT given the choice (OR = 2.31); and child's age older than four months (OR = 5.67). Few children in Butaleja received malaria treatment in accordance with national guidelines. This study highlighted the importance of engaging the full spectrum of stakeholders in the management of malaria in young children - including licensed and unlicensed providers, caregivers, and family members.


Hematological responses of the grey carpet shark (Chiloscyllium punctatum) and the epaulette shark (Hemiscyllium ocellatum) to anoxia and re-oxygenation.
We compared the hematological responses of wild and captive populations of two closely related sharks to a standardized anoxic challenge and during a 12 hr recovery period in normoxia: the epaulette shark (Hemiscyllium ocellatum, Bonnaterre, 1788) and the grey carpet shark (Chiloscyllium punctatum, Müller and Henle, 1838). Compared to normoxic controls, a significant increase in hematocrit (captive 22.3%; wild 35.9%) coupled with a decline in mean corpuscular hemoglobin concentration occurred in epaulette sharks indicating erythrocyte swelling in response to anoxia. However, the grey carpet shark had a significantly increased hematocrit (captive 27.2%; wild 29.3%), erythrocyte count (captive 37.6%; wild 46.3%) and hemoglobin concentration (captive 31.9%; wild 31.5%), suggesting a release of erythrocytes into the circulation and/or hemoconcentration in response to anoxia. Plasma glucose concentrations were maintained in both wild and captive epaulette sharks and in wild grey carpet sharks during anoxia but increased significantly after 2 hr of re-oxygenation (epaulette: captive 55.8%; wild 50.1%; grey carpet shark: wild 70.3%) and remained elevated for 12 hr. Captive grey carpet sharks had an immediate increase in plasma glucose concentrations after anoxia (96.4%), which was sustained for 12 hr of re-oxygenation. Lactate concentrations significantly increased in captive and wild animals of both species after anoxia, reaching a peak at 2 hr of re-oxygenation. Both species showed significant, yet divergent, hematological changes in response to anoxia and re-oxygenation, which may not only prolong their survival and assist in recovery but also reflect their respective ecophysiological adaptations to the extreme environments that they inhabit.


Optimization of a Soft Ensemble Vote Classifier for the Prediction of Chimeric Virus-Like Particle Solubility and Other Biophysical Properties.
Chimeric virus-like particles (cVLPs) are protein-based nanostructures applied as investigational vaccines against infectious diseases, cancer, and immunological disorders. Low solubility of cVLP vaccine candidates is a challenge that can prevent development of these very substances. Solubility of cVLPs is typically assessed empirically, leading to high time and material requirements. Prediction of cVLP solubility in silico can aid in reducing this effort. Protein aggregation by hydrophobic interaction is an important factor driving protein insolubility. In this article, a recently developed soft ensemble vote classifier (sEVC) for the prediction of cVLP solubility was used based on 91 literature amino acid hydrophobicity scales. Optimization algorithms were developed to boost model performance, and the model was redesigned as a regression tool for ammonium sulfate concentration required for cVLP precipitation. The present dataset consists of 568 cVLPs, created by insertion of 71 different peptide sequences using eight different insertion strategies. Two optimization algorithms were developed that (I) modified the sEVC with regard to systematic misclassification based on the different insertion strategies, and (II) modified the amino acid hydrophobicity scale tables to improve classification. The second algorithm was additionally used to synthesize scales from random vectors. Compared to the unmodified model, Matthew's Correlation Coefficient (MCC), and accuracy of the test set predictions could be elevated from 0.63 and 0.81 to 0.77 and 0.88, respectively, for the best models. This improved performance compared to literature scales was suggested to be due to a decreased correlation between synthesized scales. In these, tryptophan was identified as the most hydrophobic amino acid, i.e., the amino acid most problematic for cVLP solubility, supported by previous literature findings. As a case study, the sEVC was redesigned as a regression tool and applied to determine ammonium sulfate concentrations for the precipitation of cVLPs. This was evaluated with a small dataset of ten cVLPs resulting in an R 2 of 0.69. In summary, we propose optimization algorithms that improve sEVC model performance for the prediction of cVLP solubility, allow for the synthesis of amino acid scale tables, and further evaluate the sEVC as regression tool to predict cVLP-precipitating ammonium sulfate concentrations.


Initial experience with a direct antithrombin, Hirulog, in unstable angina. Anticoagulant, antithrombotic, and clinical effects.
Currently available antithrombotic therapy for unstable angina is unwieldy and occasionally ineffective. This study was designed to investigate the potential of Hirulog, a new synthetic specific antithrombin agent, for the management of this condition. A total of 55 patients in the acute phase of unstable angina received intravenous Hirulog according to one of two protocols. In an acute dose-escalating study, 0.02, 0.05, 0.1, 0.25, and 0.5 mg.kg-1 x h-1, each for 30 minutes, were infused in 15 patients. Prolongation of activated partial thromboplastin time (aPTT) (r = .95), fibrinopeptide A inhibition (r = .96), and Hirulog plasma levels (r = .91) correlated closely with the dose infused, with significant changes compared with baseline appearing at doses of 0.25 mg.kg-1 x h-1 and higher. The purposes of the second protocol were to determine whether the anticoagulant and antithrombotic effects of the drug were sustained during a 72-hour infusion and to assess whether such treatment prevented the complications of unstable angina. Based on the initial study, we planned to give a dose of 0.25 mg.kg-1 x h-1 to each patient until 2 patients failed therapy, then successively higher doses until a 95% success rate was achieved or adverse effects intervened, increasing the dose after two failures had occurred at each level. Five patients received the 0.25-mg.kg-1 x h-1 dose and 14 the 0.5-mg.kg-1 x h-1 dose before two failures occurred. Failure was observed in only one of 21 patients at the dose of 1 mg.kg-1 x h-1. aPTT (+/- SEM) levels increased to 62 +/- 5, 76 +/- 2, and 98 +/- 3 seconds at the three doses, with minimal intraindividual variation, and Hirulog plasma levels to 1050, 2100, and 4200 mg/mL, respectively. Fibrinopeptide A plasma levels decreased at all doses but more consistently at the dose of 1 mg.kg-1 x h-1. The overall clinical success rate was 87.5%: 60% (3/5) at the low dose, 86% (12/14) at the intermediate dose, and 95% (20/21) at the high dose. No deaths, myocardial infarctions, or bleeding complications occurred. In unstable angina patients, Hirulog infusions quickly and reproducibly yield stable, dose-dependent anticoagulant and antithrombotic effects with a favorable clinical efficacy profile.


Well-organized spheroids as a new platform to examine cell interaction and behaviour during organ development.
We present an experimental method allowing the production of three-dimensional organ-like structures, namely microtissues (MTs), in vitro without the need for exogenous extracellular matrix (ECM) or growth factors. Submandibular salivary glands (embryonic day ED14), kidneys (ED13) and lungs (ED13) were harvested from mouse embryos and dissociated into single cells by enzyme treatment. Single cells were seeded into special hanging drop culture plates (InSphero) and cultured for up to 14 days to obtain MTs. This strategy permitted full control of the quantity of seeded cells. The development of the MTs into organs was followed histologically and immunohistochemically. Well-organized epithelial structures surrounded by a basal lamina were formed, as confirmed by transmission electron microscopy. Expression of E-cadherin, vimentin, fibronectin and α-SMA was compared in organs and corresponding MTs by real-time quantitative polymerase chain reaction. Branching morphogenesis was induced in MTs (as shown by histology and immunostaining for fibronectin and perlecan) and was conserved even after 14 days of culture. MTs continued their development and their epithelial structures were comparable with those of the physiological organ at postnatal day 2 (PN2). Expression of aquaporins was investigated to obtain better support for the functional differentiation of epithelial cells. Histogenesis proceeded and led to the start of organogenesis. This experimental model might improve our knowledge of epithelial-mesenchymal histogenesis and can be employed to study development or cellular organization during the embryonic formation of organs.


Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents.
Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common in overweight adolescents. The purpose of this study was to determine the relation between NAFLD and insulin sensitivity in liver and skeletal muscle by studying overweight adolescents with a normal or high intrahepatic triglyceride (IHTG) content, who were matched for age, sex, body mass index (BMI; in kg/m(2)), and Tanner stage. Stable-isotope-labeled tracer infusion and the hyperinsulinemic-euglycemic clamp procedure were used to assess skeletal muscle and hepatic insulin sensitivity, and magnetic resonance spectroscopy was used to assess the IHTG content in 10 overweight (BMI = 35.9 +/- 1.3) adolescents with NAFLD (IHTG = 28.4 +/- 3.4%) and 10 overweight (BMI = 36.6 +/- 1.5) adolescents with a normal IHTG content (3.3 +/- 0.5%). The baseline plasma glucose concentration and the rate of appearance of glucose in plasma were the same in subjects with a normal (87.1 +/- 1.2 mg/dL, 16.2 +/- 1.1 micromol . kg fat-free mass(-1) . min(-1)) or high (89.2 +/- 2.5 mg/dL, 16.3 +/- 1.2 micromol . kg fat-free mass(-1) . min(-1)) IHTG content. However, compared with subjects who had a normal IHTG content, subjects with NAFLD had a lower hepatic insulin sensitivity index, based on baseline glucose kinetics and insulin concentrations (4.0 +/- 0.5 compared with 2.4 +/- 0.4; P < 0.05) and an impaired increase in glucose uptake during insulin infusion (169 +/- 28.1% compared with 67 +/- 9.6% above baseline; P < 0.01). In addition, the plasma triglyceride concentration was greater and the plasma HDL-cholesterol concentration was lower in subjects with NAFLD than in those with a normal IHTG content. An elevated IHTG content in overweight adolescents is associated with dyslipidemia and with insulin-resistant glucose metabolism in both liver and skeletal muscle.


1-hexyl-2-cyanoacrylate compound (Neucrylate) bactericidal properties.
The need for medical grade tissue adhesives both in surgery and to treat trauma has become well established. Such a device has been developed and preliminary toxicity testing completed on a compounded cyanoacrylate (Neucrylate), and its properties have been modified so it may be used as an intravascular embolic agent. Given the high incidence of iatrogenic infections in hospital, it would be desirable to have such an implantable device that inhibits dangerous bacteria. Seven separate cultures of common bacteria were grown and exposed to Neucrylate. The impact on the exposed microorganisms was analyzed visually as well as by means of fluorescence and optical microscopy. The device produced high degrees of antibacterial effect when exposed to gram positive bacteria whereas it had modest impact on gram negative bacteria.


Encapsulation of silica nanoparticles by redox-initiated graft polymerization from the surface of silica nanoparticles.
This study describes a facile and versatile method for preparing polymer-encapsulated silica particles by 'grafting from' polymerization initiated by a redox system comprising ceric ion (Ce(4+)) as an oxidant and an organic reductant immobilized on the surface of silica nanoparticles. The silica nanoparticles were firstly modified by 3-aminopropyltriethoxysilane, then reacted with poly(ethylene glycol) acrylate through the Michael addition reaction, so that hydroxyl-terminated poly(ethylene glycol) (PEG) were covalently attached onto the nanoparticle surface and worked as the reductant. Poly(methyl methacrylate) (PMMA), a common hydrophobic polymer, and poly(N-isopropylacrylamide) (PNIPAAm), a thermosensitive polymer, were successfully grafted onto the surface of silica nanoparticles by 'grafting from' polymerization initiated by the redox reaction of Ce(4+) with PEG on the silica surface in acid aqueous solutions. The polymer-encapsulated silica nanoparticles (referred to as silica@PMMA and silica@PNIPAAm, respectively) were characterized by infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy. On the contrary, graft polymerization did not occur on bare silica nanoparticles. In addition, during polymerization, sediments were observed for PMMA and for PNIPAAm at a polymerization temperature above its low critical solution temperature (LCST). But the silica@PNIPAAm particles obtained at a polymerization temperature below the LCST can suspend stably in water throughout the polymerization process.


Isolation of a strain-specific Entamoeba histolytica cDNA clone.
Entamoeba histolytica is an intestinal parasite causing significant morbidity and mortality worldwide. More tools are needed to understand the epidemiology and molecular pathogenesis of amebiasis. A cDNA library was constructed by using poly(A)+ RNA isolated from an axenic strain of E. histolytica, HM1:IMSS, which expresses a pathogenic isoenzyme pattern (zymodeme). Differential screening of the library yielded a strain-specific 3' polyadenylated cDNA clone, C2, possessing nine 26-nucleotide tandem repeats. RNA and DNA transfer blot analysis of four axenic strains of E. histolytica possessing the same pathogenic zymodeme revealed that the gene is present and expressed in pathogenic E. histolytica HM1:IMSS and 200:NIH but is not present in pathogenic strains HK-9 and Rahman. In addition, Southern blot analysis using the C2 clone showed heterogeneity of genomic organization between HM1:IMSS and 200:NIH. DNA dot blot hybridization analysis demonstrated that cDNA clone C2 was also able to distinguish axenically cultured E. histolytica strains possessing pathogenic zymodemes from those possessing nonpathogenic zymodemes and could detect as few as 100 amebic trophozoites. We conclude that C2 is a strain-specific E. histolytica cDNA clone that, in conjunction with other E. histolytica-specific probes, could serve as a useful epidemiologic tool.


Chronic disseminated intravascular coagulation presenting as renal mass.
Disseminated intravascular coagulation (DIC) is a complex clinical syndrome, described as a sequential activation of the coagulation and fibrinolytic system. Trauma and sepsis are some of the known precipitating factors. We report a case of nonovert disseminated intravascular coagulation presenting as a huge renal mass in a 3-year-old child, suspected to be a Wilms' tumor. On imaging studies, it was found to be a renal hematoma. Laboratory investigations revealed an underlying chronic disseminated intravascular coagulation caused by sepsis. The child recovered with conservative treatment; follow up investigations showed resolution of renal hematoma with renal function returning to base line. Clinical presentation of Chronic DIC is variable. Laboratory investigations usually help to diagnose the condition and also to monitor the progress of the treatment. The treatment of the triggering cause is the cornerstone of the management of this condition.


Liposomes Decorated with 2-(4'-Aminophenyl)benzothiazole Effectively Inhibit Aβ1-42 Fibril Formation and Exhibit in Vitro Brain-Targeting Potential.
The potential of 2-benzothiazolyl-decorated liposomes as theragnostic systems for Alzheimer's disease was evaluated in vitro, using PEGylated liposomes that were decorated with two types of 2-benzothiazoles: (i) the unsubstituted 2-benzothiazole (BTH) and (ii) the 2-(4-aminophenyl)benzothiazole (AP-BTH). The lipid derivatives of both BTH-lipid and AP-BTH-lipid were synthesized, for insertion in liposome membranes. Liposomes (LIP) containing three different concentrations of benzothiazoles (5, 10, and 20%) were formulated, and their stability, integrity in the presence of serum proteins, and their ability to inhibit β-amyloid (1-42) (Αβ42) peptide aggregation (by circular dichroism (CD) and thioflavin T (ThT) assay), were evaluated. Additionally, the interaction of some LIP with an in vitro model of the blood-brain barrier (BBB) was studied. All liposome types ranged between 92 and 105 nm, with the exception of the 20% AP-BTH-LIP that were larger (180 nm). The 5 and 10% AP-BTH-LIP were stable when stored at 4 °C for 40 days and demonstrated high integrity in the presence of serum proteins for 7 days at 37 °C. Interestingly, CD experiments revealed that the AP-BTH-LIP substantially interacted with Αβ42 peptides and inhibited fibril formation, as verified by ThT assay, in contrast with the BTH-LIP, which had no effect. The 5 and 10% AP-BTH-LIP were the most effective in inhibiting Αβ42 fibril formation. Surprisingly, the AP-BTH-LIP, especially the 5% ones, demonstrated high interaction with brain endothelial cells and high capability to be transported across the BBB model. Taken together, the current results reveal that the 5% AP-BTH-LIP are of high interest as novel targeted theragnostic systems against AD, justifying further in vitro and in vivo exploitation.


Effects and mechanisms of CTRP3 overexpression in secondary brain injury following intracerebral hemorrhage in rats.
C1q/TNF-related protein-3 (CTRP3) is a novel adipokine that serves an important role in oxidative stress, anti-apoptosis, anti-inflammation and immune regulation. The aim of the present study was to investigate the protective role of CTRP3 against intracerebral hemorrhage (ICH)-induced brain injury. A model of autologous arterial blood-induced ICH was constructed in rats. Intracerebral infusion of a lentivirus carrying the CTRP3 gene was used to induce CTRP3 overexpression in the brain. The effects and mechanisms of CTRP3 overexpression on brain injury were investigated by detecting brain edema, blood-brain barrier (BBB) integrity, neurological function and inflammatory-associated factors 3 days after ICH. The present results demonstrated that CTRP3 overexpression ameliorated ICH-induced neurological dysfunction, decreased brain edema, maintained BBB integrity and attenuated inflammation. The protective effect of CTRP3 overexpression was associated with increased activation of silent information regulator 1 (SIRT1). In conclusion, the present study demonstrated that CTRP3 overexpression protected against ICH-induced brain injury in rats, potentially via activating the SIRT1 signaling pathway.


[The effect of ventricular fibrillation time and NYHA classification on defibrillation in intensive care unit patients].
To investigate whether the sequence of defibrillation (DF) and cardiopulmonary resuscitation (CPR), duration of ventricular fibrillation (VF), and New York Heart Association (NYHA) classification would affect DF result in intensive care unit. Ninety-three cases needing instantaneous DF were divided into three groups according to VF lasting time: <4 minute group (n=53), 4 - 8 minute group (n=24), >8 minute group (n=16), and each group was randomly divided into two sub-groups according to time sequence: the prior DF group or the prior CPR for five cycles followed by DF group (prior CPR group). The effect of VF time, the sequence of DF and CPR, and NYHA classification on success rate of DF were observed. With prolonging VF time, success rate of DF obviously lowered [success rate of DF for VF<4 minute, 4 - 8 minute, and >8 minute groups were 83.0% (44/53), 62.5% (15/24), and 25.0% (4/16), respectively, all P<0.01]. When VF time lasted less than 4 minutes, success rate of DF in the prior DF group was obviously higher than that in the prior CPR group [88.9% (24/27) vs. 76.9% (20/26), P<0.05]. When VF time lasted for 4 - 8 minutes, the prior DF group had slightly higher success rate of DF compared with the prior CPR group [66.7% (8/12) vs. 58.3% (7/12), P=0.09]. When VF time lasted longer than 8 minutes, the success rate of DF in the prior CPR group was obviously higher than that in the prior DF group [37.5% (3/8) vs. 12.5% (1/8), P<0.01]. The success rate of DF was lowered in higher NYHA classification [success rate of DF for NYHA classification I-IV was 96.4% (27/28), 80.0% (20/25), 47.8% (11/23), 29.4% (5/17), respectively, P<0.05 or P<0.01]. VF lasting time and NYHA classification are key factors to success rate of DF, and the choice of sequence of DF and CPR depends on the lasting time of VF. For cases with the high NYHA classification, we should make some judgement beforehand and prepare some preventive measures.


A new approach for estimating the labile aluminium fraction in soil solutions, through batch experiments, using cationic (Amberlite IR 120) or non ionic (Amberlite XAD 2) resins.
Aluminium fractionation was tested on two types of resin. The first approach was based on the selective sorption of cationic forms on a strong cation exchange resin (Amberlite IR 120) which is commonly used. Using a defined contact time (1 hour) between solution and resin (batch technique) it was possible to obtain separation between different aluminium species. The second approach was based on the sorption of organic matter, especially complexes between organic matter and aluminium, onto a non ionic resin (Amberlite XAD 2), batch reactors containing the solution and the resin were stirred for 16 hours. Some tests were carried out to compare the different techniques using samples containing various complexing molecules (salicylic acid and purified commercial humic acid). Aluminium fractionation was then carried out on different soil solutions with the two different types of resin. Horizons A and S from acid brown soil under chestnut and Douglas fir were used in order to compare the influence of the type and the content of organic matter on the released aluminium forms. It appears that A layers release more total aluminium than the S ones but only a small part is in cationic forms. The S layer presents Al essentially under reactive cationic forms.


Macrophage control of Brucella abortus: role of reactive oxygen intermediates and nitric oxide.
Macrophages infected with Brucella abortus are able to kill intracellular brucellae over the first 12 to 24 hr following infection. Thereafter, the surviving brucellae replicate. We have shown previously that macrophages activated with interferon-gamma (IFN-gamma) have enhanced brucellacidal and brucellastatic activities. In studies reported here, treatment of macrophages with methylene blue, an electron carrier, enhanced the initial killing of intracellular brucellae, indicating their susceptibility to reactive oxygen intermediates. In addition, inhibitors of reactive oxygen intermediates partially blocked the antibrucella activities exhibited by both non-cytokine-treated and IFN-gamma-activated macrophages. In contrast, addition of up to 5 mM NG-monomethyl-L-arginine, to block generation of nitric oxide, resulted in minor but significant levels of blocking of macrophage antibrucella activities only when macrophages were not maximally activated even though maximally activated macrophages produced nitric oxide as indicated by accumulation of nitrite in culture supernatants. In addition, while the J774A.1 macrophage cell line had antibrucella activities which were enhanced by IFN-gamma activation, it did not produce nitric oxide when activated with IFN-gamma and infected with B. abortus. Finally, the IFN-gamma-induced enhancement of antibrucella activities by peritoneal macrophages was inhibited by addition of antitumor necrosis factor-alpha (TNF-alpha) antibodies to the cultures, indicating that TNF-alpha is necessary for full expression of the macrophage antibrucella activities.


Effect of mouthwashes on the microhardness of aesthetic composite restorative materials.
Mouthwashes are increasingly being used worldwide. However, these preparations are known to have a negative impact on composite resin dental restorations. In this study, we aim to evaluate the effect of mouthwashes on the microhardness of such restorations. Thirty specimens of Tetric N-Ceram composite were prepared. Each composite specimen was cured for 40 seconds and kept in saline solution for 24 hours at 37 °C. Baseline microhardness of each specimen was recorded using an Innovatest Vickers Micro Hardness Tester. Composite specimens were randomly placed in 20 mL of the selected mouthwashes (Colgate® Plax, Listerine® Teeth & Gum Defence, and Closeup® Antibacterial Mouthwash Cool Breeze) and stored in an incubator for 24 hours at 37 °C. Next, microhardness values were rechecked. pH measurements were recorded for each type of mouthwash using a digital pH meter. Due to the acidic nature of Colgate® and Listerine®, the microhardness of the restorations decreased with these mouthwashes; Listerine® caused the greatest decrease in microhardness and had the lowest pH reading (4.34). For Closeup®, with a neutral pH (7.02), no negative effect on microhardness was found; on the contrary, due to the presence of zinc in this latter mouthwash, an increase of the microhardness was found. We confirm the negative effect of acidic mouthwashes on the microhardness of composite dental restorations.


50 grams glucose challenge test for screening of gestational diabetes mellitus in each trimester in potential diabetic pregnancy.
To evaluate the cutoff value of the 50 grams glucose challenge test (GCT) for screening of gestational diabetes mellitus (GDM) in each trimester in potential diabetic pregnancy and to determine the prevalence of GDM. Retrospective descriptive study (Diagnostic test). Section of Obstetrics and Gynecology, Taksin Hospital. Two thousand and ten potential diabetic pregnant women who attended the antenatal care clinic at Taksin Hospital between August 2004 and December 2005 were identified and recruited based on risk indicators. A GCT was performed If GCT was positive, 100 grams oral glucose tolerance test (OGTT) was done to confirm the GDM. All relevant data including demographic information, GCT and OGTT results were collected The receiver operating characteristic (ROC) curve was used to identify the cutoff value of GCT for screening of GDM. The cutoff value of GCT for screening of GDM in each trimester by using ROC curve. The cutoff values of GCT in 1st, 2nd, 3rd, and all trimesters were 179, 177, 184, and 179 mg/dl respectively The authors recommended 177 mg/dl as the cutoff value of GCT for screening of GDM in potential diabetic pregnancy in each trimester The prevalence of GDM in 1st, 2nd, 3rd, and all trimesters were 14.22, 13.04, 11.96, and 13.2% respectively. The threshold of 177 mg/dl was recommended as the cutoff value of GCT for screening of GDM in each trimester in potential diabetic pregnancy. The prevalence was 13.2%.


Vigorous physical activity among high school students--United States, 1990.
Vigorous physical activity can improve the health of both adults and children. Among adults, regular physical activity can reduce risk for chronic diseases such as coronary heart disease, hypertension, noninsulin-dependent diabetes mellitus, colon cancer, and depression, as well as lower all-cause death rates (1,2). Among children, regular physical activity can reduce chronic disease risk factors such as obesity, elevated cholesterol, and hypertension (3). Physical activity patterns established during childhood may extend into adulthood (4). This report examines the prevalence of vigorous physical activity among U.S. students in grades 9-12.


Reliability estimation in a multilevel confirmatory factor analysis framework.
Scales with varying degrees of measurement reliability are often used in the context of multistage sampling, where variance exists at multiple levels of analysis (e.g., individual and group). Because methodological guidance on assessing and reporting reliability at multiple levels of analysis is currently lacking, we discuss the importance of examining level-specific reliability. We present a simulation study and an applied example showing different methods for estimating multilevel reliability using multilevel confirmatory factor analysis and provide supporting Mplus program code. We conclude that (a) single-level estimates will not reflect a scale's actual reliability unless reliability is identical at each level of analysis, (b) 2-level alpha and composite reliability (omega) perform relatively well in most settings, (c) estimates of maximal reliability (H) were more biased when estimated using multilevel data than either alpha or omega, and (d) small cluster size can lead to overestimates of reliability at the between level of analysis. We also show that Monte Carlo confidence intervals and Bayesian credible intervals closely reflect the sampling distribution of reliability estimates under most conditions. We discuss the estimation of credible intervals using Mplus and provide R code for computing Monte Carlo confidence intervals.


Endothelial nitric oxide synthase genotypes in the etiology of retinopathy of prematurity in premature infants.
Retinopathy of Prematurity (ROP) is a vasoproliferative disorder affecting preterm infants leading to visual impairment. ROP is more common in Caucasians than African Americans. Very low birth weight infants have immature retinas and are susceptible to ROP. Because of differences in individual responses to the treatment, various genetic factors have been looked into to understand the etiology of ROP. Endothelial nitric oxide (eNO) serves as a vasodilator, relaxes smooth muscle, prevents platelet aggregation, and facilitates improved blood flow and vascular tonicity. Mutant eNO synthase (eNOS) genotypes result in reduced nitric oxide levels by decreasing enzyme activity. Since eNO affects vasculature and ROP is a vascular disease, the present investigation was aimed at studying the association of genotypes with ROP. Two eNOS gene single nucleotide polymorphisms (SNPs) (T-786C, and G894T) were studied by microplate-Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP PCR) method. Genotypes were studied in 146 premature infants. The present data showed significant differences in the baseline gene frequencies between Caucasians and African Americans. ROP patients displayed 3-fold higher frequencies of mutant -786C and 894T alleles in both ethnicities compared to respective controls. The present data suggest ethnic stratification of genotypes. Mutant -786C and 894T alleles are significant risk factors in the development of ROP, and suggest a strong association between eNOS polymorphisms and the disease. It is interesting to know if a larger dataset of ROP patients can confirm our initial findings.


Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite.
Vegetables are the cheapest and most available sources of important proteins, minerals, vitamins, and essential amino protein. These vegetables are commonly used in Africa for the treatment of illness. This study evaluated the protective effects of Amaranthus caudatus and A. hybridus against sodium arsenite-induced toxicity in rats. The effects of sodium arsenite and/or the plant extracts were assessed using bone marrow micronucleus assay and by measuring the activities of tumour maker enzymes such as gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) in white albino Wister rats. The study showed that sodium arsenite significantly (P < 0.05) induced the formation of micronucleated polychromatic erythrocytes and the activities of ALP and GGT when compared with control. The levels of white blood cell, hemoglobin, and lymphocyte count were altered in sodium arsenite fed rats and were reverted back to near normal levels in rats pretreated with the plant extracts. A. caudatus and A. hybridus showed significant role in protecting the detoxifying enzymes; also, A. caudatus has a more protective effect on reducing the micronuclei formation when compared with A. hybridus. This study suggests that A. caudatus and A. hybridus possess anticarcinogenic effect.


Differences in the Association Between Oral Glucocorticoids and Risk of Preterm Birth by Data Source: Reconciling the Results.
To investigate causes of discrepancies in the association between early pregnancy oral glucocorticoid (OGC) use and preterm birth risk among women with rheumatoid arthritis (RA) in health care utilization data from California Medicaid (Medi-Cal) and the prospective cohort MotherToBaby Pregnancy Studies. Separately, we estimated risk ratios (RRs) between OGC exposure before gestational day 140 and preterm birth risk in data from Medi-Cal (2007-2013; n = 844) and MotherToBaby (2003-2014; n = 528). We explored differences in socioeconomic status, OGC dose distribution, exposure misclassification, and confounding by RA severity across the data sources. Preterm birth risk in women without OGC was 17.3% in Medi-Cal and was 9.7% in MotherToBaby. There was no association between OGC and preterm birth in Medi-Cal (adjusted RR 1.00 [95% confidence interval (95% CI) 0.71, 1.42]), and a 1.85-fold (95% CI 1.20, 2.84) increased preterm birth risk in MotherToBaby. When restricting each sample to women with a high-school diploma or less, preterm birth risk following no OGC exposure was 15.9% in Medi-Cal and 16.7% in MotherToBaby; adjusted RRs were 1.16 (95% CI 0.74, 1.80) in Medi-Cal and 0.81 (95% CI 0.25, 2.64) in MotherToBaby. Cumulative OGC dose was higher in MotherToBaby (median 684 mg) than in Medi-Cal (median 300 mg). An OGC dose of ≤300 mg was not associated with increased preterm birth risk. Exposure misclassification and confounding by RA severity were unlikely explanations of differences. Higher baseline preterm birth risk and lower OGC dose distribution in Medi-Cal may explain the discrepancies. Studies are needed to understand the effects of autoimmune disease severity and undertreatment on preterm birth risk in low-income populations.


Evaluation of the Impact of Different Natural Zeolite Treatments on the Capacity of Eliminating/Reducing Odors and Toxic Compounds.
Unlike odorants that mask odors, natural zeolite acts as a molecular sieve that captures and eliminates odors. Different treatment methods can be applied to influence the properties of the natural zeolites. To enhance the odor adsorption capacities of the natural zeolite two types of treatment methods were applied: chemical (acid, basic) and thermal. The initial natural zeolites and the activated one were characterized using X-ray diffraction (XRD) and scanning electron microscope (SEM-EDX). Two experiments were performed to establish the odor adsorption capacity of the activated natural zeolites. The best zeolite for the adsorption of humidity, ammonia and hydrogen sulfide was the 1-3 mm zeolite activated through thermal treatment. For the adsorption of PAHs, the best zeolite was the one activated through basic treatment, with an adsorption capacity of 89.6 ng/g.


A retrospective study of the prevalence of anaemia in pregnancy at booking in Niger Delta, Nigeria.
We reviewed the records of antenatal clinic attendees over a period of 9 years to determine the prevalence of anaemia at booking. The laboratory records of 8751 out of a total of 37,506 pregnant women who booked for antenatal care between 2004 and 2013 at the BMSH were reviewed. The effects of maternal age, educational status, parity, gestational age, haemoglobin genotype and infections on the prevalence of anaemia were investigated. The prevalence of anaemia at booking was 69.6%, most of whom had moderate anaemia. Anaemia was significantly prevalent in the 10-19 year age group, and in women with secondary education, in their 2nd trimester and with SS genotype. Anaemia also increased with gestational age, this however was not statistically significant. There was no statistical difference between those who are human immunodeficiency virus (HIV) positive and had anaemia and those who are HIV negative who also had anaemia. This study shows that anaemia in pregnant women is still unacceptably high considering the consequences and despite interventions on the ground to reduce prevalence. There is a need to review the intervention measures with emphasis on programmes that would increase awareness among pregnant women and the general public.


[Percutaneously introduced bile duct prostheses as primary measure in obstructive jaundice (author's transl)].
The simplest measure for overcoming obstructive jaundice, and the one with the least complications, is percutaneous transhepatic bile duct drainage, which we have carried out on 38 patients. We have abandoned the catheter technique with combined external and internal drainage and instead use primary implantation of a bile duct prosthesis by the transhepatic route in cases of obstructive jaundice. The results are better, and the procedure is easier for the patient. Our experience with twelve implants in nine patients is described.


(Rad 8)Caffeine prophylaxis to improve intermittent hypoxaemia in infants born late preterm: a randomised controlled dosage trial (Latte Dosage Trial).
Infants born late preterm (34+0 to 36+6 weeks' gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term neurodevelopmental outcomes in infants born very preterm and may have similar effects in late preterm infants. Clearance of caffeine citrate increases with gestational age and late preterm infants are likely to need a higher dose than very preterm infants. Our aim is to determine the most effective and best-tolerated dose of caffeine citrate to reduce transient intermittent hypoxaemia events in late preterm infants. A phase IIB, double-blind, five-arm, parallel, randomised controlled trial to compare the effect of four doses of oral caffeine citrate versus placebo on the frequency of intermittent hypoxaemia. Late preterm infants will be enrolled within 72 hours of birth and randomised to receive 5, 10, 15 or 20 mg/kg/day caffeine citrate or matching placebo daily until term corrected age. The frequency of intermittent hypoxaemia (events/hour where oxygen saturation concentration is ≥10% below baseline for ≤2 min) will be assessed with overnight oximetry at baseline, 2 weeks after randomisation (primary outcome) and at term corrected age. Growth will be measured at these timepoints, and effects on feeding and sleeping will be assessed by parental report. Data will be analysed using generalised linear mixed models. This trial has been approved by the Health and Disability Ethics Committees of New Zealand (reference 18/NTA/129) and the local institutional research review committees. Findings will be disseminated to peer-reviewed journals to clinicians and researchers at local and international conferences and to the public. The findings of the trial will inform the design of a large multicentre trial of prophylactic caffeine in late preterm infants, by indicating the most appropriate dose to use and providing information on feasibility. ACTRN12618001745235; Pre-results.


Online teaching of undergraduates in pathology during COVID-19 pandemic: An opportunity to grab or dismiss?
Covid 19 pandemic has brought human life one on one with the pace of growth. The indispensable lockdown and social distancing norms have posed challenges to continue education in various fields. Distance learning via online teaching has emerged as a savior in the pandemic. In the current scenario, it is very important to keep learners in the loop and obtain feedback from students at the end of online teaching, for understanding its strength and weaknesses which will eventually assist in developing strategies to improve its quality. We intend to share our experience with the online teaching. The study was conducted from March 2020 to Feb 2021, which includes 8 months of online teaching classes and practicals, one online examination (mid term exam), and 1 offline examination (final professional exam). The marks obtained by the students who attended online classes (batch II) in 2020-21 session was compared with previous batch i.e 2019-20 (batch I). Also the marks obtained by batch I during online exam (mid-term exam) were compared with their marks during offline exam (final professional exam). Results: Batch II scored higher marks than batch I in theory and practical (p-value < 0.05). However, the marks of viva for both batches were equitable. We feel that the online teaching is a reasonable alternative to conventional teaching in the current scenario.


Synthesis and Characterization of Hydrophilic Trityl Radical TFO for Biomedical and Biophysical Applications.
Tetrathiatriarylmethyl (TAM, trityl) radicals have found wide applications as spin probes/labels for EPR spectroscopy and imaging, and as polarizing agents for dynamic nuclear polarization. The high hydrophilicity of TAM radicals is essential for their biomedical applications. However, the synthesis of hydrophilic TAM radicals (e.g., OX063) is extremely challenging and has only been reported in the patent literature, to date. Herein, an efficient synthesis of a highly water-soluble TAM radical bis(8-carboxyl-2,2,6,6-tetramethylbenzo[1,2-d:4,5-d']bis([1,3]dithiol-4-yl)-mono-(8-carboxyl-2,2,6,6-tetrakis(2-hydroxyethyl)benzo[1,2-d:4,5-d']bis([1,3]dithiol-4-yl)methyl (TFO), which contains four additional hydroxylethyl groups, relative to the Finland trityl radical CT-03, is reported. Similar to OX063, TFO exhibits excellent properties, including high water solubility in phosphate buffer, low log P, low pKa , long relaxation times, and negligible binding with bovine serum albumin. On the other hand, TFO has a sharper EPR line and higher O2 sensitivity than those of OX063. Therefore, in combination with its facile synthesis, TFO should find wide applications in magnetic resonance related fields and this synthetic approach would shed new light on the synthesis of other hydrophilic TAM radicals.


Artifactual pyrosequencing reads in multiple-displacement-amplified sediment metagenomes from the Red Sea.
The Multiple Displacement Amplification (MDA) protocol is reported to introduce different artifacts into DNA samples with impurities. In this study, we report an artifactual effect of MDA with sediment DNA samples from a deep-sea brine basin in the Red Sea. In the metagenomes, we showed the presence of abundant artifactual 454 pyrosequencing reads over sizes of 50 to 220 bp. Gene fragments translocated from neighboring gene regions were identified in these reads. Occasionally, the translocation occurred between the gene fragments from different species. Reads containing these gene fragments could form a strong stem-loop structure. More than 60% of the artifactual reads could fit the structural models. MDA amplification is probably responsible for the massive generation of the artifactual reads with the secondary structure in the metagenomes. Possible sources of the translocations and structures are discussed.


Computational elucidation of the transition state shape selectivity phenomenon.
The most commonly cited example of a transition state shape selective reaction, m-xylene disproportionation in zeolites, is examined to determine if the local spatial environment of a reaction can significantly alter selectivity. In the studied reaction, ZPE-corrected rate limiting energy barriers are 136 kJ/mol for the methoxide-mediated pathway and 109 to 145 kJ/mol for the diphenylmethane-mediated pathway. Both pathways are likely to contribute to selectivity and disfavor one product isomer (1,3,5-trimethylbenzene), but relative selectivity to the other two isomers varies with pore geometry, mechanistic pathway, and inclusion of entropic effects. Most importantly, study of one pathway in three different common zeolite framework types (FAU, MFI, and MOR) allows explicit and practically oriented consideration of pore shape. Variation of the environment shape at the critical transition states is thus shown to affect the course of reaction. Barrier height shifts on the order of 10-20 kJ/mol are achievable. Observed selectivities do not agree with the transition state characteristics calculated here and, hence, are most likely due to product shape selectivity. Further examination of the pathways highlights the importance of mechanistic steps that do not result in isomer-defining bonds and leads to a more robust definition of transition state shape selectivity.


[Surgery of asymmetry].
Endeavoring to present, within a few pages, an exhaustive work of all the surgical proposals, regarding the multitude of ethiopathogeneses, is quite utopic. The author considers the evaluation of the asymmetrical patient and underlines in the complementary examinations the advantage of 3D tomodensitometry. A chapter is devoted to presurgical orthodontic preparation aimed at counteracting the compensations, which affect the maxillary and mandibular alveolar support. The therapeutic strategy calls upon "combined" programs. A "range" of osteotomies is suggested within the framework of the most frequent dysmorphoses. Two more complex pathologies, which may be met by the orthodontist, are evoked: condylar hyperplasia and temporomandibular ankylosis related to inflammatory affections and traumatisms. Glossoplasty is the rule in some hemihypertrophies. Relapses, hindering the stability of the result, can be thwarted by overcorrections, different means of splinting and postoperative kinesitherapy. Iconography and clinical observations illustrate both the orthodontist's and the surgeon's approach: they heighten the reader's awareness of the various problems linked with asymmetry.


Purification and characterization of an aminopeptidase A from Staphylococcus chromogenes and its use for the synthesis of amino-acid derivatives and dipeptides.
An aminopeptidase with original specificity was purified 3800-fold to homogeneity from a cellular extract of Staphylococcus chromogenes. The enzyme was specific for acidic amino acids (Asp and Glu) at the N-terminus of peptides and thus can be classified as an aminopeptidase A. However, its specificity was not restricted to acidic amino acids: alpha-hydroxy acids such as L-malic and L-lactic acids were also accepted in position P1. The enzyme had a broad specificity for the residue at position P' 1, accepting all types of amino acids, including Pro, in this position. The optimal conditions for the hydrolysis of Asp-Phe-NH2 were pH 9.5 and 60 degrees C. The enzyme was inhibited by chelating agents and serine-protease inhibitors. The activity lost by treatment with chelating agents could be restored by Mn2+ or Zn2+ which also stimulated the native enzyme. This suggests that it is a metalloprotease with a serine residue essential for the activity. The native enzyme had an apparent molecular mass of 430 kDa on gradient-gel electrophoresis and subunits of 43 kDa as determined by SDS/PAGE. The enzyme catalyzed the synthesis of peptide and amino acid derivatives such as Asp-Phe-OMe (Aspartame) and malyl-Tyr-OEt from L-Asp and L-malic acid as acyl donors and L-Phe-OMe and L-Tyr-OEt as nucleophiles, respectively. The use of the enzyme as a reagent in protease-catalyzed peptide synthesis, N-terminal protection and subsequent deprotection, is described.


Proteinase Inhibitor-inducing Factor in Plant Leaves: A Phylogenetic Survey.
Thirty-nine plant species representing 20 families from the four major divisions of plants were surveyed for the presence of proteinase inhibitor-inducing factor activity in leaves or other tissues. Tissue juices were assayed for their capacity to induce accumulation of proteinase inhibitor I in excised tomato (Lycopersico esculentum) leaves. In tissues of only 2 of the 39 species was proteinase inhibitor-inducing factor-like activity not found. The activity was absent in cabbage leaves and celery stalks. Fruiting bodies from one of three fungi genera assayed contained exceptionally large quantities of proteinase inhibitor-inducing factor-like activity. Extracts from Agraricus campestris fruiting bodies contained over 20 times more activity than tomato leaf juice. The survey confirms that substances with proteinase inhibitor-inducing factor-like activity are widespread in the plant kingdom.


Differential effects of cultivated and wild barley 5H chromosomes on heading characters in wheat-barley chromosome addition lines.
Wheat (Triticum aestivum L.)-barley (Hordeum vulgare L.) chromosome addition lines are possible vehicles for transferring barley genes into wheat. The barley 5H chromosome has genetic effects on the heading characters in wheat-barley addition lines: accelerating narrow-sense earliness, decreasing vernalization requirement and/or increasing photoperiodic sensitivity. To elucidate the effects of different 5H chromosomes under an identical wheat genetic background, two wheat-barley addition lines, i.e. cultivated barley 'New Golden' 5H chromosome added to 'Shinchunaga' wheat (Shi-NG5H) and wild barley H. vulgare ssp. spontaneum 5H chromosome added to 'Shinchunaga' wheat (Shi-Spn5H), were examined for their heading characters. The addition line Shi-NG5H showed a significantly lower vernalization requirement in comparison with 'Shinchunaga' wheat, whereas Shi-Spn5H did not. Furthermore, both NG5H and Spn5H chromosomes shortened narrow-sense earliness and increased photoperiodic sensitivity in wheat, but the effects of Spn5H were weaker than those of NG5H. The fact that NG5H and Spn5H showed differential effects on heading characters in wheat demonstrated that the heading characters were altered by the function of the barley genes located on 5H chromosomes, not merely by the aneuploid effect alone.


Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels, Metastatic Progression, and Survival in Osteosarcoma.
Overall survival of patients with osteosarcoma (OS) has improved little in the past three decades, and better models for study are needed. OS is common in large dog breeds and is genetically inducible in mice, making the disease ideal for comparative genomic analyses across species. Understanding the level of conservation of intertumor transcriptional variation across species and how it is associated with progression to metastasis will enable us to more efficiently develop effective strategies to manage OS and to improve therapy. In this study, transcriptional profiles of OS tumors and cell lines derived from humans (n = 49), mice (n = 103), and dogs (n = 34) were generated using RNA sequencing. Conserved intertumor transcriptional variation was present in tumor sets from all three species and comprised gene clusters associated with cell cycle and mitosis and with the presence or absence of immune cells. Further, we developed a novel gene cluster expression summary score (GCESS) to quantify intertumor transcriptional variation and demonstrated that these GCESS values associated with patient outcome. Human OS tumors with GCESS values suggesting decreased immune cell presence were associated with metastasis and poor survival. We validated these results in an independent human OS tumor cohort and in 15 different tumor data sets obtained from The Cancer Genome Atlas. Our results suggest that quantification of immune cell absence and tumor cell proliferation may better inform therapeutic decisions and improve overall survival for OS patients.Significance: This study offers new tools to quantify tumor heterogeneity in osteosarcoma, identifying potentially useful prognostic biomarkers for metastatic progression and survival in patients. Cancer Res; 78(2); 326-37. ©2017 AACR.


Cuprous oxidase activity of CueO from Escherichia coli.
We have found CueO from Escherichia coli to have a robust cuprous oxidase activity, severalfold higher than any homologue. These data suggest that a functional role for CueO in protecting against copper toxicity in vivo includes the removal of Cu(I).


High-dose methotrexate: a critical reappraisal.
High-dose methotrexate (HDMTX) with leucovorin (LV) rescue has been used as a therapeutic strategy in oncology for more than a decade. Administration of HDMTX results in tumoricidal plasma concentrations of the drug without significant host toxicity, provided that plasma MTX levels are monitored and LV rescue is properly administered. The original premise of LV rescue was that the provision of reduced folate to normal cells would circumvent the metabolic block produced by MTX and allow resumption of DNA synthesis, although the presumed therapeutic selectivity of leucovorin has not yet been adequately explained. Despite a strong pharmacologic rationale and a vast clinical experience, HDMTX with leucovorin rescue has not been shown to be unequivocally superior to conventional doses of MTX in any clinical situation except, perhaps, for treatment of osteogenic sarcoma and childhood acute leukemia. While HDMTX is an important component of effective treatment regimens for these diseases, its precise contribution to the success of these regimens remains undefined. Although HDMTX can theoretically overcome all known mechanisms of MTX resistance, no data exist to suggest that this can be accomplished in the clinic. Thus, this well-known but poorly understood treatment regimen must remain a subject of clinical investigation rather than a part of routine clinical practice.


Histopathologic effects of neoadjuvant therapies for advanced squamous cell carcinoma of the esophagus: multivariate analysis of predictive factors and p53 overexpression.
In 97 patients (60, chemotherapy; 22, chemoradiotherapy; 15, radiotherapy), histopathologic effects were evaluated microscopically, and histologic response rates were compared among three neoadjuvant treatment modalities. Predictive factors for neoadjuvant therapies were analyzed by logistic regression, including the results of p53 immunohistochemical staining. In the chemoradiotherapy group, the pathologic response rate was 86.4%, and was significantly higher than that for chemotherapy (P < 0.0001) or for radiotherapy (P = 0.0031). In patients with normal p53 protein expression, the histopathologic response rate to chemotherapy was 20.0%, a higher rate than that for patients with abnormal p53 overexpression. In the chemoradiotherapy or radiotherapy group, however, the response rates were almost the same, irrespective of p53 oncoprotein status. From multivariate analysis, the neoadjuvant treatment modality itself was identified as the most powerful predictive factor for the effect. Chemoradiotherapy had the most powerful effect on advanced esophageal cancer, and p53 status did not influence the clinical outcome in this group.


Detection of generalized tonic-clonic seizures using short length accelerometry signal.
Epileptic seizures are characterized by the excessive and abrupt electrical discharge in the brain. This asynchronous firing of neurons causes unprovoked convulsions which can be a cause of sudden unexpected death in epilepsy (SUDEP). Remote monitoring of epileptic patients can help prevent SUDEP. Systems based on wearable accelerometer sensors have shown to be effective in ambulatory monitoring of epileptic patients. However, these systems have a trade-off between seizure duration and the false alarm rate (FAR). The FAR of the system decreases as we increase the seizure duration. Further, multiple sensors are used in conjugation to improve the overall performance of the detection system. In this study, we propose a system based on single wrist-worn accelerometer sensor capable of detecting seizures with short duration (≥ 10s). Seizure detection was performed by employing machine learning approach such as kernelized support vector data description (SVDD). The proposed approach is validated on data collected from 12 patients, corresponding to approximately 966h of recording under video-telemetry unit. The algorithm resulted in a seizure detection sensitivity of 95.23% with a mean FAR of 0.72=24h.


A comparison of the MMPI-2-RF and PAI overreporting indicators in a civil forensic sample with emphasis on the Response Bias Scale (RBS) and the Cognitive Bias Scale (CBS).
The Cognitive Bias Scale (CBS; Gaasedelen, Whiteside, Altmaier, Welch, & Basso, 2019) was developed as a Personality Assessment Inventory (PAI) indicator of poor performance on Performance Validity Tests (PVTs) in a neuropsychological context. The current study aimed to investigate the effectiveness of the CBS in a forensic disability sample through a series of analyses by comparing it to other PAI validity scales and the Minnesota Multiphasic Personality Inventory (MMPI)-2-RF overreporting scales with an emphasis on the Response Bias Scale (RBS), which guided the development of the CBS. The participants in this study were drawn from an archival dataset containing 588 consecutive civil disability claimants. Findings showed the RBS and the CBS yielded similar patterns of negative correlations to PVTs, with RBS effect sizes being somewhat larger in most comparisons. Results of ANOVAs showed that the RBS produced the largest effect sizes in distinguishing between incentive only versus probable/definite malingered neurocognitive dysfunction (MND) groups, followed by the CBS. Estimates of sensitivity and specificity were comparable between the RBS and CBS at liberal cut scores, but the RBS was more specific to detecting Probable/Definite MND at more conservative cutoffs. Hierarchical logistic regression analyses showed that RBS accounted for 6% variance over CBS in the probable/definite MND classification, whereas the CBS accounted for 2% variance beyond the RBS. Overall, the results of this study support the utility of the CBS as the most effective PAI validity scale for detecting MND in a civil disability sample, and the RBS generally outperformed the CBS to some degree in all analyses. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Host restrictions of avian influenza viruses: in silico analysis of H13 and H16 specific signatures in the internal proteins.
Gulls are the primary hosts of H13 and H16 avian influenza viruses (AIVs). The molecular basis for this host restriction is only partially understood. In this study, amino acid sequences from Eurasian gull H13 and H16 AIVs and Eurasian AIVs (non H13 and H16) were compared to determine if specific signatures are present only in the internal proteins of H13 and H16 AIVs, using a bioinformatics approach. Amino acids identified in an initial analysis performed on 15 selected sequences were checked against a comprehensive set of AIV sequences retrieved from Genbank to verify them as H13 and H16 specific signatures. Analysis of protein similarities and prediction of subcellular localization signals were performed to search for possible functions associated with the confirmed signatures. H13 and H16 AIV specific signatures were found in all the internal proteins examined, but most were found in the non-structural protein 1 (NS1) and in the nucleoprotein. A putative functional signature was predicted to be present in the nuclear export protein. Moreover, it was predicted that the NS1 of H13 and H16 AIVs lack one of the nuclear localization signals present in NS1 of other AIV subtypes. These findings suggest that the signatures found in the internal proteins of H13 and H16 viruses are possibly related to host restriction.


[Interaction effects in the lateral visual field: an extension of Bouma's (1970) approach].
The recognizability of a letter is impaired by the presence of additional letters. This phenomenon is called lateral masking. Proceeding on the assumption of Bouma (1970) lateral masking can be described in terms of retinal eccentricity of the target letter and the distance between target and flanking stimuli. In this paper, we will address to the question if these kinds of parameters are adequate for describing lateral masking effects. For this purpose, characteristics of the string like its length and its homogenity are varied. The subject's task is to identify the central letter of a tachistoscopically presented string. The targets in the string are flanked both by only x and by different randomly selected letters. Additionally, we varied the length of the string. The data show that these variations influence the strength of the masking effect. It is concluded that a pure sensorical approach is not sufficient for an explanation of lateral masking effects.


Synchronization of the factors critical for diabetic teratogenesis: an in vitro model.
Our goal was to determine the relationship between critical factors and conditions such as gestational age and exposure time to elevated glucose levels in diabetic embryopathy. A postimplantation rat embryo culture was used as a model for investigation. The effect of various factors on embryonic development was studied. Experiments were conducted with increasing glucose concentrations (150 to 905 mg/dl, n = 186), at various gestational ages (10 to 12 days, n = 169), and for varying durations of exposure (30 to 180 minutes, n = 169). Gross morphologic characteristics of the yolk sac and embryo were assessed. Embryopathy was induced by hyperglycemia in a dose-related fashion: a 20% rate at two times control glucose concentration, almost a 50% rate at four times control, and approximately a 100% abnormality rate at more than six times control. A critical window in gestational age, days 10 to 11, and a minimum exposure time to hyperglycemia of 2 hours were necessary to induce teratogenesis. Diabetic teratogenesis occurs in a dose-related fashion and requires a minimum exposure time and critical gestational age. Only synchronization of these critical conditions induces embryonic maldevelopment. Furthermore, nonsynchronized aberrant conditions may result in apparently normal embryonic development.


Highly efficient asymmetric construction of quaternary carbon-containing homoallylic and homopropargylic amines.
A highly efficient method for the asymmetric synthesis of chiral quaternary carbon-containing homoallylic and homopropargylic amines under mild conditions was achieved with good yields and high diastereoselectivities.


Increased chemokinetic and chemotactic responses of eosinophils in asthmatic patients.
The aim of the present study was to investigate the migratory responses of eosinophil and neutrophil granulocytes from asthmatic patients compared with granulocytes from healthy individuals. Twenty-three patients with unstable and severe asthma and blood eosinophilia (greater than 400 x 10(6) cells/l) were selected for the study. Eosinophil and neutrophil chemotactic and chemokinetic responses were tested twice, at the beginning and end of a 5 week treatment period. Lung function was followed by daily measurements of PEF. The eosinophils of the asthmatics demonstrated increased chemokinetic responses to albumin, autologous serum, and normal human serum (NHS), and an increased chemotactic response to NHS at the beginning of the treatment period compared with eosinophils from the references. At the end of the period the eosinophil chemokinetic responses to albumin, autologous serum and NHS were still increased and so was the chemotactic response to zymosan-activated serum (ZAS). The neutrophil migratory responses were not increased compared with those of the references, except for the chemokinetic response to autologous serum, which was increased both at the beginning and end of the treatment period. Patients in whom the eosinophil migratory responses, to most of the agents used, decreased over the treatment period, demonstrated a significantly greater improvement of their lung function at the end of the period compared with patients in whom the eosinophil migratory responses increased. However, no direct relationship between eosinophil migratory responses and lung function of the patients was found. In conclusion, the present investigation demonstrated increased migratory responses of eosinophils from asthmatic patients. This enhanced responsiveness is proposed to be due to priming of the eosinophils in vivo, and might be one mechanism behind the selective recruitment of eosinophils to the lungs of asthmatics.


FM 'in fashion' now and for the future.
With estates and facilities "very much in fashion" given that patients now increasingly put cleanliness and the "general environment" at the top of their agenda, estates personnel now have an opportunity to be "right at the heart of health", said Health Facilities Scotland (HFS) director Paul Kingsmore, keynote speaker at the recent 2009 Healthcare Facilities Consortium conference in Oxford. However, achieving this goal would, he said, require not only developing firm goals and a strong, skilled workforce for today, but equally for the next decade and beyond. Jonathan Baillie reports.


Paraventricular thalamus: Gateway to feeding, appetitive motivation, and drug addiction.
This chapter reviews the anatomical and functional evidence demonstrating the contribution of the paraventricular thalamic nucleus (PVT) to appetitive motivation, food intake control, and drug-seeking behaviors. We first consider the anatomical properties of the PVT to highlight its relevance in the control of appetitive motivation, feeding, and drug seeking. This is followed by a review of the available literature on PVT neurocircuitry, PVT involvement in food intake control, animal models of drug self-administration, withdrawal, and relapse. We show that PVT occupies a strategic position as a major thalamic interface between hindbrain and hypothalamic regions for viscerosensation and energy states; and between amygdala, cortical, and ventral striatal regions for motivation, reward, and learning. Understanding the precise anatomical and functional organization of these trans-PVT pathways remains a key challenge. Nonetheless, we show that PVT may be profitably viewed as the thalamic gateway to appetitive motivation, feeding, and drug addiction allowing both bottom-up (from brainstem and hypothalamus) and top-down (from cortex) control over reward and motivation.


Acute left main coronary arterial thrombosis - a case series.
Acute left main coronary artery thrombosis is an uncommon, but important clinical entity. We report 6 consecutive cases of acute left main thrombosis that highlight the spectrum in clinical presentation of this entity, and the potential of an initial medical approach in managing a subset of these patients.


Identification of the Expression Patterns and Potential Prognostic Role of 5-Methylcytosine Regulators in Hepatocellular Carcinoma.
Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. 5-methylcytosine (m5C) modification plays a nonnegligible role in tumor pathogenesis and progression. However, little is known about the role of m5C regulators in HCC. Methods: Based on 9 m5C regulators, the m5C modification patterns of HCC samples extracted from public databases were systematically evaluated and correlated with tumor immune and prognosis characteristics. An integrated model called the "m5Cscore" was constructed using principal component analysis, and its prognostic value was evaluated. Results: Almost all m5C regulators were differentially expressed between HCC and normal tissues. Through unsupervised clustering, three different m5Cclusters were ultimately uncovered; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m5Cscore was constructed to quantify the m5C modifications of individual patients. Subsequent analysis revealed that the m5Cscore was an independent prognostic factor of HCC and could be a novel indicator to predict the prognosis of HCC. Conclusion: This study comprehensively explored and systematically profiled the features of m5C modification in HCC. m5C modification patterns play a crucial role in the tumor immune microenvironment (TIME) and prognosis of HCC. The m5Cscore provides a more holistic understanding of m5C modification in HCC and provides a practical tool for predicting the prognosis of HCC. This study will help clinicians identify effective indicators of HCC to improve the poor prognosis of this disease.


The relationship among the polymorphisms of SULT1A1, 1A2 and different types of cancers in Taiwanese.
Sulfotransferase (SULT) enzymes play an important role in the detoxification, metabolism and bioactivation of numerous xenobiotics, many dietary and environmental mutagens, drugs, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in the level of enzyme activities as well as variations of biochemical and physical properties. We developed a PCR-RFLP method to analyze the frequencies of SULT1A1 and SULT1A2 alleles among cancerous patients and normal controls in Taiwan. The results showed that SULT1A1*1 and SULT1A2*1 were in positive linkage disequilibrium. Neither SULT1A1*3 nor SULT1A2*3 were found in this study. The frequencies of SULT1A1*2 and SULT1A2*2 for hepatic, colon, lung, oral, gastric, renal and cervical cancerous patients were 3.95, 5.56, 4.92, 3.84, 2.70, 7.41 and 4.50%, respectively. No statistical significance was found for these cancer patients after comparison with normal controls (4.0%) for the allelic frequencies of SULT1A1*2 and SULT1A2*2.


Functional disability and mental impairment as predictors of mortality in community-dwelling elderly Puerto Ricans.
This is a prospective study that explores the role of functional impairment as predictor of one-year mortality in the elderly of rural Puerto Rico. Between September, 1987 and June 1988, 1901 elderly were interviewed at their place of residence. Besides obtaining social and demographic information, assessment of functional status using a modified Katz scale and determination of mental status using the Short Portable Mental Status questionnaire were performed. During the one-year follow-up period 43 participants died. Multiple logistic regression analysis showed that the presence of functional (OR = 5.31) and mental impairment (OR = 2.22) were independent predictors of mortality when adjusted for age, education, gender and income. These findings are consistent with those of other studies, where the presence of functional and mental impairment, detected on admission to a hospital or while living in the community, were associated to a higher mortality.


The lateral paramedian: revisiting a forgotten incision.
Incisional hernia is a potential complication of all abdominal incisions and still remains a significant problem financially and medically. Presently, there is a lack of general consensus among surgeons in regard to the optimal treatment. The midline incision is the most common used abdominal incision and it carries a high incidence of incisional hernia (up to 15%). The paramedian incision was known to lead to a small incidence of incisional hernias. This discussion is meant to bring the paramedian incision back to the picture as a hope to decrease the incidence of incisional hernia.