Assessment of the presence and dynamics of fungi in drinking water sources using cultural and molecular methods.
A comparison of different isolation techniques and culture media for detection of filamentous fungi and yeasts in the aquatic environment revealed that the use of membrane filtration with the media dichloran rose bengal chloramphenicol (DRBC) optimized fungi detection in terms of abundance and variety in three untreated water sources with very different characteristics (surface water, spring water, and groundwater). The diversity of the fungi population captured by direct DNA extraction of fungi collected by membrane filtration was compared with the isolates obtained after selective growth using different culture media through amplification of the internal transcribed spacer gene and denaturing gradient gel electrophoresis (DGGE). The Czapek-Dox agar, Sabouraud dextrose agar, and DRBC media showed closer similarities to those obtained by the uncultured biomass for the different water sources. Based on these data and the best enumeration results, DRBC is recommended for the assessment of fungi in water sources using culture-based methods. DGGE was also used to monitor temporal variations in the fungal population structure and showed that each water matrix possessed a distinct population profile as well as that changes in the fungal community can be expected in the different matrices throughout the year.


Competition effects in the dynamics of tumor cords.
A general feature of cancer growth is the cellular competition for available nutrients. This is also the case for tumor cords, neoplasms forming cylindrical structures around blood vessels. Experimental data show that, in their avascular phase, cords grow up to a limit radius of about 100 microm, reaching a quasi-steady-state characterized by a necrotized area separating the tumor from the surrounding healthy tissue. Here we use a set of rules to formulate a model that describes how the dynamics of cord growth is controlled by the competition of tumor cells among themselves and with healthy cells for the acquisition of essential nutrients. The model takes into account the mechanical effects resulting from the interaction between the multiplying cancer cells and the surrounding tissue. We explore the influence of the relevant parameters on the tumor growth and on its final state. The model is also applied to investigate cord deformation in a region containing multiple nutrient sources and to predict the further complex growth of the tumor.


Infant feeding in Queensland, Australia: long-term trends.
Infant feeding practices were retrospectively ascertained in a random cohort of parous women (mean age 54.8 years) from Brisbane, Australia. Reported proportions of infants who were ever breast-fed fell from around 90% before 1960 to around 70% in the early 1970s, with some subsequent increase. Similar but stronger trends were reported in proportions of infants breast- but not bottle-fed. Few maternal characteristics were associated with feeding practices, but women with more education appear to have led both the early retreat from and the later return to breast-feeding.


Modeling the paramyxovirus hemagglutinin-neuraminidase protein.
The paramyxovirus hemagglutinin-neuraminidase (HN) protein exhibits neuraminidase activity and has an active site functionally similar to that in influenza neuraminidases. Earlier work identified conserved amino acids among HN sequences and proposed similarity between HN and influenza neuraminidase sequences. In this work we identify the three-dimensional fold and develop a more detailed model for the HN protein, in the process we examine a variety of protein structure prediction methods. We use the known structures of viral and bacterial neuraminidases as controls in testing the success of protein structure prediction and modeling methods, including knowledge-based threading, discrete three-dimensional environmental profiles, hidden Markov models, neural network secondary structure prediction, pattern matching, and hydropathy plots. The results from threading show that the HN protein sequence has a 6 beta-sheet propellor fold and enable us to assign the locations of the individual beta-strands. The three-dimensional environmental profile and hidden Markov model methods were not successful in this work. The model developed in this work helps to understand better the biological function of the HN protein and design inhibitors of the enzyme and serves as an assessment of some protein structure prediction methods, especially after the x-ray crystallographic solution of its structure.


Gamma-glutamyltranspeptidase and alkaline phosphatase serum activities: their relation to the outcome of Graves' disease.
Gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP) were assayed in the sera of 27 patients affected with Graves' disease prior to conventional (12-18 months) methimazole (30-5 mg/day) treatment, who were subsequently followed up over 36 +/- 1.5 months (m +/- SEM). Twelve patients underwent recurrence of thyrotoxicosis (relapsers) at variable intervals from withdrawal of treatment, whereas the remaining 12 remained euthyroid (nonrelapsers). In the study group as a whole, both GGT and ALP serum levels were significantly (p less than 0.001) increased with respect to 24 sex- and age-matched euthyroid controls (31.8 +/- 3.6 vs. 11.5 +/- 1.2 U/l and 203 +/- 13.8 vs. 110 +/- 7.3 U/l, m +/- SEM). Prevalence of GGT and ALP elevations was 56% (15/27) and 58% (15/26), respectively. Serum GGT activity was age dependent (r = 0.466, p less than 0.05) and inversely related to log2 microsomal antibody initial titer (r = 0.499, p less than 0.05) in the whole series. There was no difference in mean pretreatment thyroxine (T4) or triiodothyronine (T3) between the groups with supranormal enzyme and normal enzyme levels. However, in the group with enhanced enzyme levels, relapsed patients had higher initial T4 (20.3 +/- 0.8 vs. 17.1 +/- 0.7 micrograms/dl, p less than 0.01) and lower both initial T3 (452 +/- 31.1 vs. 551 +/- 57.8 ng/dl, p less than 0.02) than the nonrelapsed patients. Only in this group, initial T3:T4 ratio was a valuable indicator of the outcome of the disease, since it was below 30 in 7/7 (100%) relapsers vs. 2/8 (25%) nonrelapsers, but above 30 only in 6 subjects who remitted.


A new species of earth snake (Dipsadidae, Geophis) from Mexico.
A new species of the Geophis dubius group is described from the mountains of the Sierra Zongolica in west-central Veracruz and the Sierra de Quimixtlán in central-east Puebla. The new species is most similar to Geophis duellmani and Geophis turbidus, which are endemic to the mountains of northern Oaxaca and the Sierra Madre Oriental of Puebla and Hidalgo, respectively. However, the new species differs from Geophis duellmani by the presence of postocular and supraocular scales and from Geophis turbidus by having a bicolor dorsum. With the description of the new species, the species number in the genus increases to 50 and to 12 in the Geophis dubius group. Additionally, a key to the species of the Geophis dubius group is provided.


The Influence of Pain, Weakness and Rheumatoid Factor Status on Depression Incidence Among Iranian Patients With Rheumatoid Arthritis.
Increased prevalence of depression among patients with Rheumatoid arthritis (RA) has been described previously. However, the impact of depression among Iranian patients has not yet been investigated. Here, the prevalence of depression was assessed and the effect of disease-related characteristics including pain, weakness and rheumatoid factor (RF) status on incidence of depression was evaluated. Patients with RA, who were referred to rheumatology clinics of Kermanshah University of Medical Sciences and healthy subjects from the general population of Kermanshah participated in this investigation. Depression was assessed using Beck's depression inventory II (BDI II). Pain and weakness were assessed subjectively by patients' self-report. Data was collected during a year between 2012 and 2013. Chi-square test and independent t-test were used. One hundred and seventy-one patients with RA and 198 healthy individuals participated in this investigation. In the RA group, depressive mood was detected in 45.7% of patients, which was significantly higher than healthy subjects (P = 0.008). Depression was more common in elderly patients (> 50 years old) in comparison with healthy subjects at a similar age (P = 0.03). Pain and weakness had no influence on depression incidence (P = 0.14 and 0.19, respectively) whereas patients with negative RF status were significantly more susceptible to severe depression (P: 0.001). Depression is more common among Iranian patients with RA (45%) than healthy subjects regardless of gender. Depression has a significant association with older age. Negative RF status may predict future risk of depression.


Multinozzle low-temperature deposition system for construction of gradient tissue engineering scaffolds.
Tissue engineering is a technology that enables us to construct complicated hominine organs composed of many different types of cells. One of the key points to achieve this goal is to control the material composition and porous structure of the scaffold accurately. A disposable syringe based volume-driven injecting (VDI) nozzle was proposed and designed to extrude both natural derived and synthetic polymers. A multinozzle low-temperature deposition and manufacturing (M-LDM) system is proposed to fabricate scaffolds with heterogeneous materials and gradient hierarchical porous structures. PLGA, collagen, gelatin, chitosan can be extruded without leaking to form hierarchical porous scaffolds for primary study. Composite scaffolds with two kinds of materials were fabricated via two different nozzles to get both hydrophilic and mechanical properties. The results from scanning electron microscopy (SEM) demonstrated that the natural-derived biomaterials were strongly absorbed onto the synthetic biomaterials to form a stable network. Several gradient PLGA/TCP scaffolds were also fabricated to supply several samples.


A Bayesian Nonlinear Mixed-Effects Regression Model for the Characterization of Early Bactericidal Activity of Tuberculosis Drugs.
Trials of the early bactericidal activity (EBA) of tuberculosis (TB) treatments assess the decline, during the first few days to weeks of treatment, in colony forming unit (CFU) count of Mycobacterium tuberculosis in the sputum of patients with smear-microscopy-positive pulmonary TB. Profiles over time of CFU data have conventionally been modeled using linear, bilinear, or bi-exponential regression. We propose a new biphasic nonlinear regression model for CFU data that comprises linear and bilinear regression models as special cases and is more flexible than bi-exponential regression models. A Bayesian nonlinear mixed-effects (NLME) regression model is fitted jointly to the data of all patients from a trial, and statistical inference about the mean EBA of TB treatments is based on the Bayesian NLME regression model. The posterior predictive distribution of relevant slope parameters of the Bayesian NLME regression model provides insight into the nature of the EBA of TB treatments; specifically, the posterior predictive distribution allows one to judge whether treatments are associated with monolinear or bilinear decline of log(CFU) count, and whether CFU count initially decreases fast, followed by a slower rate of decrease, or vice versa.


Radiation Esophagitis in a Patient with Oral Carcinoma and Bone Metastasis.
Radiation esophagitis requiring endoscopic evaluation occurs quite rarely, affecting <1% of patients undergoing radiation treatment. Acute radiation esophagitis develops within 3 weeks of radiation therapy. We describe herein a case of radiation esophagitis in a patient with oral carcinoma with multiple general bone metastases. Cisplatin, fluorouracil, and cetuximab were given for 3 cycles. Radiation therapy (30 Gy) to the thoracic vertebrae and lumbar vertebrae was prescribed to prevent worsening of bone metastases and relieve pain. Neutropenia was also observed due to chemotherapy. After the end of radiation therapy, the patient experienced chest pain, heartburn, and dysphagia. Upper gastrointestinal endoscopy revealed severe radiation esophagitis of endoscopic Fukui Acute Radiation Esophagitis grade 4. Oral food was discontinued and an intravenous proton-pump inhibitor was administered. After 3 weeks, upper gastrointestinal endoscopy showed improvement of radiation esophagitis, with scars. The symptoms of chest pain, heartburn, and dysphagia had also disappeared. This is the first case to be reported of acute radiation esophagitis in a patient with oral carcinoma with bone metastasis who experienced dramatic improvement of endoscopic findings. Neutropenia appears to be associated with more severe acute radiation esophagitis.


Alpha1,3-L-fucosyltransferase expression in developing human myeloid cells. Antigenic, enzymatic, and mRNA analyses.
In an attempt to correlate the cell surface expression of Lex and sialyl-Lex structures in immature and mature myeloid cells with the genes expressing alpha1,3-fucosyltransferase(s) we have examined: 1) the properties of the cellular alpha1,3-fucosyltransferases and the mRNA transcripts corresponding to the five cloned genes, Fuc-TIII, Fuc-TIV, Fuc-TV, Fuc-TVI, and Fuc-TVII, in mature granulocytes and in the myeloid cell line HL-60, before and after dimethyl sulfoxide-induced differentiation and 2) the properties of the alpha1,3-fucosyltransferases expressed in COS-7 cells transfected with plasmids containing Fuc-TIV and Fuc-TVII cDNAs. The previously shown increase in cell surface expression of sialyl-Lex on differentiation of HL-60 cells (Skacel P. O., Edwards A. J., Harrison C. T., and Watkins W. M. (1991) Blood 78, 1452-1460) is accompanied by a sharp fall in expression of Fuc-TIV mRNA and a persistence of expression of Fuc-TVII mRNA. The properties of the alpha1,3-fucosyltransferase expressed in COS-7 cells transfected with Fuc-TIV are consistent with this being the major gene responsible for the expression of Lex in the immature myeloid cells. In Northern blot analyses, no transcripts of Fuc-TIII, Fuc-TV, or Fuc-TVI were detected in total RNA from mature granulocytes or mRNA from HL-60 cells before or after differentiation. In total RNA from mature granulocytes, Fuc-TIV transcripts were only faintly visible, whereas Fuc-TVII transcripts were quite definitely expressed. The specificity properties of Fuc-TVII expressed in COS-7 cells are consistent with this gene being the major candidate alpha1, 3-fucosyltransferase controlling the expression of sialyl-Lex on mature cells. However, Lex continues to be expressed on the surface of mature granulocytes and cell extracts retain the capacity to transfer fucose to non-sialylated acceptor substrates. The question therefore remains as to whether these properties result from the weakly expressed Fuc-TIV gene or whether another alpha1, 3-fucosyltransferase gene remains to be identified.


A Novel Ventilatory Technique in Refractory Hypoxemic Respiratory Failure Secondary to Therapeutic Thoracentesis and Paracentesis.
BACKGROUND MetaNeb® is a respiratory therapy modality that aims to effect clearance of airway secretions through chest physiotherapy. It typically is used in critically ill patients with bronchiectasis or copious secretions. However, it also expands lungs through a continuous positive expiratory pressure and continuous high-frequency oscillation, which has the benefit of increasing lung recruitment and improving oxygenation. CASE REPORT A 61-year-old male who had re-expansion pulmonary edema following a paracentesis and thoracentesis for cirrhosis, which caused a large unilateral pleural effusion. He required intubation and his hypoxemia was refractory to standard maximum ventilatory measures. A trial of continuous MetaNeb® acted as a noninvasive extracorporeal membrane oxygenation method, dramatically improving oxygenation and hypoxemia, normalizing the patient's blood gas, and thus stabilizing him. CONCLUSIONS MetaNeb® could potentially be used in other community hospitals that lack the capability for advanced ventilatory modes or in patients who are too unstable for transfer.


The incidence of exercise-induced bronchospasm in competitive figure skaters.
Pediatric commitment to competitive sports is on the rise. Previous reports of the incidence of exercise-induced bronchospasm (EIB) have investigated high school, college, and Olympic athletes in traditional sports. The purpose of this study was to investigate the incidence of EIB in competitive figure skating, a high-intensity, cold-weather sport performed by young athletes. To investigate the incidence of EIB in skaters, 100 competitive skaters from five Mid-Atlantic rinks completed rinkside pulmonary function tests. Results showed an overall incidence of 30%, signaling the need for education and screening for EIB in youth participating in physically demanding, cold-weather sports.


Analysis of cocaine, benzoylecgonine, and cocaethylene in urine by HPLC with diode array detection.
A solid phase extraction method was developed for the isolation of cocaine, benzoylecgonine, and cocaethylene from urine followed by high-performance liquid chromatography/diode array detection. The application of a new solid hybrid phase extraction technology produced much cleaner extracts than conventional extraction procedures and made the selective extraction of substances with different polarities possible. Two internal standards with great structural resemblance to benzoylecgonine (a carboxylic acid) and to the two esters, cocaine and cocaethylene, respectively, were synthesized. A linear response over a broad concentration range was obtained. The sensitivity, specificity, and accuracy were satisfactory for each analyte. Hydrolysis of cocaine and cocaethylene to benzoylecgonine during extraction and analysis was less than 0.5%. The method described can be used to corroborate cocaine use, to establish cocaine overdoses, and to study pharmacological effects of cocaine and its metabolites.


440 Consecutive immediate, implant-based, single-surgeon breast reconstructions in 281 patients: a comparison of early outcomes and costs between SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices.
A 2010 nationwide survey of plastic and reconstructive surgeons indicated that approximately 83 percent performed predominantly implant-based breast reconstruction, with acellular dermal matrix used by approximately half of those practitioners. Although the medical literature documents well over 2000 cases of breast reconstruction with matrices, relatively few cases using other than human cadaveric acellular dermal matrices have been reported. The author compared complications and costs using SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices. A retrospective review of a single surgeon's 5-year experience was performed for consecutive, nonrandomized immediate breast reconstructions with acellular dermal matrix from 2005 to 2010. Two hundred eighty-one patients had 440 implant-based reconstructions using SurgiMend [222 patients (79.0 percent)] or AlloDerm [59 patients (21.0 percent)]. No significant differences in complication rates were observed between SurgiMend and AlloDerm for hematoma, infection, major skin necrosis, or breast implant removal. Seroma was the most prevalent complication; the seroma rate for AlloDerm (15.7 percent) was significantly greater than that for SurgiMend (8.3 percent). Using recent product costs for equivalently sized AlloDerm and SurgiMend units, the cost of SurgiMend was $1024 less per breast than AlloDerm. SurgiMend fetal bovine and AlloDerm human cadaveric acellular dermal matrices demonstrate similar rates of major early complications in breast reconstruction in this study. This similarity in complication rates between SurgiMend and AlloDerm and the cost savings seen with the use of SurgiMend are factors for the surgeon to consider in choosing a matrix for breast reconstruction. : Therapeutic, III.


EXPLICIT LEAST-DEGREE BOUNDARY FILTERS FOR DISCONTINUOUS GALERKIN.
Convolving the output of Discontinuous Galerkin (DG) computations using spline filters can improve both smoothness and accuracy of the output. At domain boundaries, these filters have to be one-sided for non-periodic boundary conditions. Recently, position-dependent smoothness-increasing accuracy-preserving (PSIAC) filters were shown to be a superset of the well-known one-sided RLKV and SRV filters. Since PSIAC filters can be formulated symbolically, PSIAC filtering amounts to forming linear products with local DG output and so offers a more stable and efficient implementation. The paper introduces a new class of PSIAC filters NP0 that have small support and are piecewise constant. Extensive numerical experiments for the canonical hyperbolic test equation show NP0 filters outperform the more complex known boundary filters. NP0 filters typically reduce the L∞ error in the boundary region below that of the interior where optimally superconvergent symmetric filters of the same support are applied. NP0 filtering can be implemented as forming linear combinations of the data with short rational weights. Exact derivatives of the convolved output are easy to compute.


End piece: reflections on the treatment of anger.
Research on the nature of anger and how it differs from other emotions is reviewed. Dimensions that differentiate disturbed from normal anger are also discussed. Based on the research and results of several reviews of anger treatment, an ideal treatment package for the treatment of anger is presented. The components include: (i) addressing motivation; (ii) cultivating the therapeutic alliance; (iii) managing physiological arousal; (iv) fostering cognitive change; (v) implementing behavior change; (vi) providing environmental supports for change; (vii) teaching relapse-prevention skills; and (viii) initiating restitution and reintegration. Also, the articles describing experiential, self psychology, cognitive-behavioral, Buddhist, and systems approaches to anger are compared and contrasted. Each of these treatment approaches is compared with the ideal treatment components.


Development and Implementation of Societal Influences Survey Questionnaire (SISQ) for Peoples during COVID-19 Pandemic: A Validity and Reliability Analysis.
The emergence of Coronavirus disease 2019 (COVID-19) had rapidly spread since FEB/MAR 2020. Policy to prevent transmission of COVDI-19 resulted in multi-dimensional impact on social interaction. We aimed to develop a beneficial survey tool with favorable quality and availability, the Societal Influences Survey Questionnaire (SISQ), to evaluate social influences on people during this pandemic. The SISQ was developed with 15 items and 4-point Likert scales consisting of five factors. These include social distance, social anxiety, social desirability, social information, and social adaptation. Construct validity and reliability were performed to verify the SISQ. A total of 1912 Taiwanese were recruited. The results demonstrated that the SISQ has acceptable reliability, with Cronbach's alphas ranging between 0.57 and 0.76. The SISQ accounted for 58.86% and satisfied the requirement of Kaiser-Mayer-Olkinvalues (0.78) and significant Bartlett's Test of sphericity. Moreover, the confirmatory factor analysis fit indices also indicated the adequacy of the model. As for multiple comparison, females scored higher than males in factor of social distance. Unemployed participants and those without partners scored higher in several domains of factors. The survey method and survey instrument prove reliable and valuable, also providing different categories of assessment results regarding social influences and their impacts. Further studies are warranted to extend the applicability of SISQ.


Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications.
Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as a potential pharmacotherapy for a number of psychiatric diseases, including anxiety and depression. Most of the mGluR5 NAM clinical candidates can be characterized by the central acetylenic moiety that connects the terminal pharmacophores. Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by optimization provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore. Optimization of the core and aryl appendages was performed by scanning and matrix libraries synthesized by the multiple parallel synthesis approach. Biological evaluation of matrix libraries provided a number of potent, metabolically stable, and in vivo active compounds. One of these compounds, 25 showed high efficacy and safety in preclinical in vivo models; this allowed its nomination as a novel, nonacetylenic mGluR5 NAM clinical candidate. Compound 25 was advanced to first-in-man trials for the treatment of psychiatric conditions.


Association between antipsychotics and body mass index when treating patients with tics.
Treatment with antipsychotics can be associated with weight gain, and second-generation (atypical) antipsychotics (SGAs) can increase the risk for diabetes and dyslipidemia. These risks have not been assessed in patients with tics, who receive lower doses than those used to treat psychosis. The objective of this study is to investigate the relationship between antipsychotic use and weight in tic patients and compare the effects of SGAs to first-generation (typical) antipsychotics (FGAs). We studied the association between antipsychotic use and body mass index (BMI) in consecutive patients with tics seen in a specialty Movement Disorders clinic. Height and weight were recorded on 198 patients, average age 19.9 years+/-14.0 years, 128 treated and 70 not treated with antipsychotics. Standardized measures of BMI were significantly higher in the antipsychotic-treated patients compared to the untreated patients (0.56+/-1.10) treated vs. untreated (-0.31+/-0.82). This difference remained significant after controlling for age, gender, stimulant medications, and co-morbidities such as attention-deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Concomitant medications did not independently influence weight, and there was no difference between FGAs and SGAs. Antipsychotic dose, expressed in chlorpromazine (CPZ) equivalents, and treatment duration did not influence weight. Patients with tics on either FGAs or SGAs have higher BMI values compared to patients on no antipsychotics. Better knowledge of this risk should guide physician decision making when treating patients with tics.


[Low temperature oxygen plasma sterilization effect on pseudomonas aeruginosa].
Low temperature oxygen plasma was used to sterilize the Pseudomonas aeruginosa samples on the polyethylene terephthalate (PET) sheets in a self-designed reactor that included the discharge area, afterglow area and remote area. Before and after plasma treatment, the cell morphology was studied by scanning electron microscopy (SEM). The cell wall or cell membrane cracking was testified to determine the content of protein by using coomassie light blue technique. Besides, double Langmuir probe and electron spin resonance spectroscopy were used to determine the temperature of electrons (ions) and the concentration of free radicals, respectively. Under the treatment time of 30 s,the germicidal effects were 4.2, 3.8 and 2.6 respectively in the three areas. SEM observations showed that the plasma activity cracks the cell wall and cell membrane, resulting in cellular content leakage. In addition,the results from electron spin resonance spectroscopy and double Langmuir electron probe showed that electrons, ions and oxygen free radicals played important roles in sterilization in the discharge area, but only oxygen free radicals acted to sterilize the bacteria in the afterglow area and the remote area. The active species can be separated effectively in this reaction equipment, and we further elucidated the mechanisms of plasma sterilization in the remote plasma field.


An autopsy report of graft-versus-host disease (GVHD) following blood transfusion.
A case of graft-versus-host disease (GVHD) associated with blood transfusion in a 71-year-old man is reported. The patient received transfusions (irradiation red cells M.A.P 14 units, fresh frozen plasma 11 units) and developed features of GVHD including fever, a skin rash, diarrhea, liver dysfunction, hypoplastic bone marrow, and pancytopenia. He died on day 32 posttransfusion. Pathologically, lymphocyte infiltration of skin and liver lesions, degeneration of small bile ducts, crypt cell necrosis in the gastrointestinal tract, and bone marrow hypoplasia were observed. Immunohistochemically, infiltrating lymphocytes were CD8+ T type, the result suggesting that they role a part in posttransfusion GVHD.


Health insurance, primary care, and preventable hospitalization of children in a large state.
To analyze variations in the admission rate to hospitals of children with ambulatory care-sensitive (ACS) conditions and to test the relationship of ACS admission rates to insurance coverage, health maintenance organization (HMO) enrollment, availability of primary care, severity of illness, distance to hospital, and a number of other factors. Hypotheses were derived from basic considerations about demand and use of primary care and preventive services and then were tested with a weighted linear regression model of the ACS admission rate for children residing in each county. The principal data were all hospital discharges for New York resident children admitted to hospitals in New York, Pennsylvania, New Jersey, or Connecticut in 1994. The data and methodology were noteworthy for including out-of-area hospital admissions. There was a substantial negative association of the ACS rate with private HMO coverage. There also were sizable negative effects of the availability of primary care services in physician offices and the distance traveled. Large differences related to racial and ethnic composition of the population were found independent of other determinants. There was a positive association with the proportion of all admissions (admissions for all conditions) covered by Medicaid or self-pay. Severity of illness and use of emergency departments were controlled. There was no independent effect of a location in New York City. The results are consistent with smaller-scale studies suggesting that improved health insurance for children could reduce hospital admissions. Contracting with HMOs also appears to be beneficial. Independently, programs to increase the availability of primary and preventive services could substantially reduce ACS admissions.


Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial.
While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration.


High fat feeding promotes obesity and renal inflammation and protects against post cardiopulmonary bypass acute kidney injury in swine.
Obesity confers a survival advantage in the critically ill and in patients undergoing cardiac surgery. We explored whether an obesogenic high fat diet could confer protection against post cardiopulmonary bypass (CPB) acute kidney injury (AKI) in a swine model. In this study, 28 anaesthetised adult female Landrace White swine (55 to 70 kg) were allocated into a 4 group design to either 2.5 hours of CPB or Sham operation with or without pre-procedural high fat (HF) feeding containing 15% lard, 1.5% cholesterol and 1% cholic acid for 12-weeks (Groups: Sham, CPB, CPB + HF and Sham + HF). Our primary endpoint was creatinine clearance measured at 1.5 and 24 hours post intervention. This is a validated index of the glomerular filtration rate (GFR) in swine and an endpoint used in our clinical studies. Secondary endpoints included measures of systemic and renal inflammation, endothelial homeostasis, tubular injury and dysfunction, and inflammatory cell signalling. Differences between groups were calculated using analysis of variance with adjustment for baseline differences for repeated measures. CPB in pigs fed a normal chow diet resulted in AKI. This was characterised by reductions in GFR sustained for up to 24 hours post injury relative to Sham operated pigs fed a normal diet; mean difference 50.2 ml/min (95% CI 5.9 to 94.4). Post CPB AKI was also characterised by renal inflammation, parallel activation of both pro-inflammatory (NF-kB, iNOS) and pro-survival pathways (pAkt, p70s6k, HIF-1α) and apoptosis. Pigs fed a 12-week high fat diet developed obesity and hyperlipidaemia. This was associated with increased redox sensitive pro-inflammatory and anti-apoptotic signalling, and tubular epithelial cell proliferation. High fat feeding also protected swine against post CPB AKI; mean difference in creatinine clearance CPB - CPB + HF -65.3 ml/min (95% CI -106.9 to -23.7), by preserving endothelial homeostasis and function, and preventing the reductions in GFR, loss of ATP and tubular apoptosis that characterise the extension phase of AKI in swine at 24 hours post injury. Reno-protection was not attributed to pAkt signaling. A high fat diet promoted obesity and renal inflammation and prevented post CPB AKI in swine. This study provides insights into the obesity paradox and the failure of anti-inflammatory interventions to improve clinical outcomes in patients at risk of post cardiac surgery AKI.


Role of vascular angiotensin converting enzyme in hypertension.
The possible role of vascular angiotensin converting enzyme (ACE) in the maintenance of one-kidney, one clip (1-K,1C) hypertensive rats was studied in comparison with age-matched, one-kidney (1-K) normotensive rats. Mean blood pressure was elevated after partial occlusion of the left renal artery with unilateral nephrectomy, and the high blood pressure persisted for at least 11 weeks, whereas no significant changes in mean blood pressure were observed in 1-K rats. Plasma and vascular renin activities and plasma ACE activity did not differ between the two groups of rats, both 5 and 11 weeks after operation. In contrast, ACE activity in lung and mesenteric arteries in 1-K,1C hypertensive rats was significantly elevated 11 weeks after operation, but not 5 weeks after operation, compared with the matched 1-K normotensive rats. In addition, the decreases in mean blood pressure induced by ACE inhibition were significantly greater in 1-K,1C rats than those in 1-K rats. These results indicate that the elevation of vascular ACE activity may play an important role in the maintenance of high blood pressure and may result in hypotension in response to ACE inhibitors in the chronic stage of 1-K,1C hypertension.


Uterine receptivity in the baboon: modulation by chorionic gonadotropin.
Embryonic signals not only rescue the corpus luteum but also modulate the uterine environment in preparation for implantation. Chorionic gonadotropin (CG), an early embryonic signal, is one such molecule. In vivo studies in the baboon show that CG alters the morphology and biochemical activity of the uterus, especially with respect to the three major cell types: luminal epithelium, glandular epithelium, and stromal fibroblasts. Further, CG and progesterone have a synergistic effect on the receptive endometrium. CG action on the endometrial cells is transduced via a seven transmembrane G protein-coupled receptor. Possible signaling pathways involved are discussed.


Preferential Photosynthetic Uptake of Exogenous HCO(3) in the Marine Macroalga Chondrus crispus.
The rate of HCO(3) (-) uptake by the red macroalga Chondrus crispus has been investigated. Unbalanced concentrations of free CO(2) and HCO(3) (-), generated by the photosynthetic activity, were detected in steady state conditions by using an exchange column apparatus linked to an assimilation chamber. Observing the variations of this gradient as influenced by the time of seawater transit from the assimilation chamber towards the column allowed an experimental determination of: (a) the actual gradient created by the photosynthetic activity, (b) the rate constant of the chemical conversion of free CO(2) to HCO(3) (-). With a value of 0.115 per second at pH 8.92, this rate constant was in good agreement with a previous estimation. By using a simple model, we show that the photosynthetic rate of HCO(3) (-) consumption can be estimated by the product of the actual gradient and the rate constant. In the conditions of the experiments reported here, this rate represented more than 90% of the whole photosynthetic flux.


[The effects of teacher stimulation on student learning motivation].
The purpose of this study was to compare the effects of two types of teacher stimulation on 1) learning motivation of students who were poor in mathematics and 2) the students' impression of the teachers. One type of teacher stimulation was the encouragement of students who were poor in mathematics to make more effort because they had good ability but their ability was not yet realized. The other type of teacher stimulation was the encouragement of the students to exert themselves because of their previous lack of effort. A questionnaire, including the scenario describing the two types of teacher stimulation and several questions about the students' motivation and impression of the teachers, was administered to 378 elementary school, junior high school, and college students. The former type of teacher stimulation was partially more effective in the motivation of students and also fully more effective in the students' impression of the teachers than the latter type of teacher stimulation.


Cadmium-induced adaptive response in cells of Chinese hamster ovary cell lines with varying DNA repair capacity.
The combined exposure to environmental toxicants such as heavy metals and radiation is an important research area in health protection. The aim of this study was to investigate the role of DNA repair and the phosphatidylinositol 3-kinase (PI3K) family in the cadmium-induced adaptive response to toxicants or radiation. Using cells of three Chinese hamster ovary (CHO) cell lines with different capacities to repair DNA damage, we found that pre-exposure to cadmium at a nonlethal concentration could induce an adaptive response to a subsequent challenge with cadmium or radiation in all the cell lines. The magnitude of the adaptive response in adapted cells was dependent on several factors, including DNA repair capacity, the priming dose of cadmium, and the challenging dose of cadmium or radiation. When the cells were challenged with 50 microM CdCl2, the adaptive response was less evident in XRCC1-defective EM-C11 cells than in cells of the other two cell lines. Moreover, treatment of cells with wortmannin or KU-55933 eliminated the adaptive response in all the cell lines. Our data suggest that the triggering of a cadmium-induced adaptive response was independent of DNA repair capacity. Single-strand break (SSB) repair or base excision repair (BER) rather than double-strand break (DSB) repair was mainly involved in the adaptive response. This response of cells to a further challenge with cadmium or radiation may be mediated through the ataxia telangiectasia mutated (ATM) pathway.


Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer.
The low rate of pelvic node metastasis in most contemporary series of patients undergoing radical prostatectomy for carcinoma of the prostate has been attributed to earlier and better patient selection than historical series. Alternatively, it has been suggested that the limited dissection commonly performed misses nodal metastasis in a substantial number of patients. To assess the value of an extended node dissection in detecting nodal metastasis, we performed a randomized prospective study. A total of 123 patients undergoing radical prostatectomy were randomized to an extended node dissection on the right versus the left side of the pelvis with the other side being a limited dissection. The extended dissection included removal of all external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. The limited dissection included only the nodes along the external iliac vein and obturator nerve. Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p = 0.08). Extended node dissection in contemporary series of patients undergoing radical prostatectomy identifies few with nodal metastases not found by a more limited dissection. A trend toward an increased risk of complications attributable to the lymphadenectomy occurs with an extended dissection.


Conformational diseases: structural studies of aggregation of polyglutamine proteins.
Protein misfolding and aggregation into insoluble amyloid deposits are often associated with neurodegenerative disorders. In particular, the polyglutamine (polyQ) diseases are inherited disorders triggered by the expansion of the polyQ tract over its physiological length in the involved protein. The molecular mechanism of aggregation from the native protein into amyloids involves several steps including protein misfolding, aggregation into oligomers, which seems to be the most toxic species, and, finally rearrangements into mature fibrils. In the present contribution, we review studies, integrating computational and experimental approaches, of polyQ proteins, as well as of the details of the complicate aggregation mechanisms in which aberrant form of polyQ proteins are involved. These aspects are of crucial relevance for a complete understanding of the onset of polyQ conformational diseases and can also shed light on putative therapeutic targets and future development of aggregation inhibitors.


Peroxisome proliferator activated receptor alpha inhibits hepatocarcinogenesis through mediating NF-κB signaling pathway.
Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been reported to suppress cancer growth. However, the role of PPARα in hepatocarcinogenesis remains unclear. We investigated the functional significance of PPARα in HCC. PPARα-knockout (PPARα-/-) mice were more susceptible to diethylnitrosamine (DEN)-induced HCC at 6 months compared with wild-type (WT) littermates (80% versus 43%, P < 0.05). In resected HCCs, TUNEL-positive apoptotic cells were significantly less in PPARα-/- mice than in WT mice (P < 0.01), commensurate with a reduction in cleaved caspase-3 and caspase-7 protein expression. Ki-67 staining showed increased cell proliferation in PPARα-/- mice (P < 0.01), with concomitant up-regulation of cyclin-D1 and down-regulation of p15. Moreover, ectopic expression of PPARα in HCC cells significantly suppressed cell proliferation and induced apoptosis. The anti-tumorigenic function of PPARα was mediated via NF-κB as evidenced by inhibition of NF-κB promoter activity, diminution of phosphor-p65, phosphor-p50 and BCL2 levels, and enhancing IkBα protein. Chromatin immunoprecipitation analysis confirmed PPARαdirectly binds to the IkBα promoter. In conclusion, PPARα deficiency enhances susceptibility to DEN-initiated HCC. PPARα suppresses tumor cell growth by inhibiting cell proliferation and inducing cell apoptosis via direct targeting IκBα and NF-κB signaling pathway.


Intraoral excision of arteriovenous malformation of lower lip.
Vascular malformations can be categorized into low-flow lesions and high-flow lesions according to blood flow volume. Arterial lesions such as arteriovenous malformations (AVMs) are generally high-flow lesions. Arteriovenous malformations are high-flow vascular anomalies consisting of a nidus or a network of abnormal vascular channels between feeding arteries and draining veins. Arteriovenous malformations become destructive progressively by compression or erosion of surrounding tissue by itself. Angiography is the most important diagnostic technique for determination of location and flow characteristics of vascular lesions. Embolization is used preoperatively to decrease the size of AVM and reduce the extent of surgical excision. The modern treatment of AVM requires multidisciplinary study between the surgeon and vascular radiologist. We reported an early diagnosed AVM at the lower lip, and it was resected totally intraorally without any complication and morbidity.


Managing medicaid.
Medicaid beneficiaries in the Lower Rio Grande Valley and rural Texas who have little or no experience with HMOs soon will become closely acquainted with them. Under Senate Bill 7, which passed in this summer's special session, the Texas Legislature mandated statewide Medicaid managed care, which previously was limited to large urban areas. The move is one of dozens of cost-cutting initiatives included in SB 7.


Improvement of renal functions after embolization of renal AVF in a patient who had been on dialysis for 5 years.
Recently, ultrasound-guided percutaneous renal biopsy has been used in the diagnosis of renal diseases. Development of an arteriovenous fistula (AVF), which is one of the post-biopsy complications, is not frequently encountered. AVFs are usually asymptomatic; however, they may lead to serious outcomes. We report a 21-year-old patient, who had been on dialysis for 5 years. Due to high blood pressure (230/160 mmHg) and a thrill in the lumbar area detected on physical examination, Doppler examination was performed and a renal AVF was detected. Because the patient had a history of renal biopsy 5 years previously, the fistula was thought to be secondary to the biopsy. After embolization of the AVF, renal functions improved enough to terminate dialysis treatment.


Terminal alkyne addition to diazodicarboxylates: synthesis of hydrazide linked alkynes (ynehydrazides).
A new route to form C(sp)-N bonds has been developed via addition of in situ generated lithium acetylides to sterically hindered diazodicarboxylates. The reaction provides straightforward access to a previously unexplored ynehydrazide class of stable N-linked alkynes directly from commercially available precursors. Preliminary results show that alkynyl hydrazides are useful reagents for the selective installation of nitrogen functional groups and as precursors to pharmaceutically relevant heterocycles using metal catalyzed cycloadditions and condensations.


Angiographic follow-up of cerebral aneurysms treated with Guglielmi detachable coils: an analysis of 162 cases with 173 aneurysms.
The endovascular approach, with the use of Guglielmi detachable coils (GDC), has been increasingly used to treat ruptured and unruptured cerebral aneurysms in recent years. Our objective was to assess the mid- to long-term radiologic outcome of cerebral aneurysms treated with GDC embolization. One hundred and sixty-two patients with a total of 173 aneurysms embolized with GDCs underwent angiographic follow-up 1 to 54 months after the procedure and were reviewed retrospectively. Each angiogram was reviewed by 2 neuroradiologists and 1 neurosurgeon, each of whom made a comparison between the initial and follow-up angiograms. Morphologic outcomes were scored as follows: unchanged, progressive thrombosis, and reopening or regrowth. Of the 173 aneurysms with GDC embolization, 142 had total or nearly total occlusion, 23 subtotal occlusion, and 8 partial occlusion on the initial angiograms. The incidence of reopening was 17.1% (13/76) in less than 3 months and 6.2% (6/97) between 3 and 6 months after the procedure. Four aneurysms (2.3%) were found to be recurrent in the second follow-up angiography within 1 year after the procedure. The 1-year cumulative recurrent rate was 13.3%. Among 56 aneurysms with a third follow-up angiography in the period of 12 to 54 months after the procedure, 4 (7.1%) displayed a slight enlargement; the long-term cumulative recurrent rate was 20.4%. The direct and primary causes for aneurysmal recurrence are incomplete and loose packing. The first angiographic follow-up is recommended to be performed at 3 months or earlier for incompletely occluded aneurysms and at 6 months for totally or nearly totally occluded aneurysms. In case of total or nearly total occlusion that remains stable at follow-up, the interval for monitoring should be prolonged appropriately. Retreatment with balloon- or stent-assisted coil embolization is recommended for reopened aneurysms.


Relaxin-2 Prevents Erectile Dysfunction by Cavernous Nerve, Endothelial and Histopathological Protection Effects in Rats with Bilateral Cavernous Nerve Injury.
Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.


[Poking reduction cannulated screw for the treatment of SandersⅡ calcaneal fracture].
To evaluate clinical effect of poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture. From October 2014 to December 2017, 28 patients with Sanders Ⅱ calcaneal fracture were treated with poking reduction cannulated screw guided by Pingle orthopedic muscle-bone interoperability balance theory, including 20 males and 8 females, aged from 24 to 55 years old with an average of (37.2±3.9) years old. Calcaneal width, Bhler angle, and Gissane angle were measured before and after operation, and Maryland Score before and 6 months after operation were compared. All patients were followed up from 12 to 16 months with an average of (13.7±1.3) months. All fractures healed normally, and healing time ranged from 9 to 12 weeks with an average of (10.2±1.3) weeks. No postoperative wound infection, cortical necrosis, or osteomyelitis occurred. The width of the calcaneus decreased from (34.15±2.58) mm before surgery to (30.49±2.37) mm after surgery, Bhler angle increased from (14.16±3.27)° before operation to (31.95±3.07)°after operation, Gissane angle decreased from (128.45±9.04)° before operation to (120.83±8.15)° after operation. Maryland Score was 15.68±4.73 before operation, and was improved to 88.32±2.65 at 6 months after operation;19 patients got excellent result, 6 good, 2 fair and 1 poor. Poking reduction cannulated screw based on Pingle orthopedic muscle-bone interoperability balance theory in treating Sanders Ⅱ calcaneal fracture has certain clinical effects, high acceptation of patient, and without special demand for soft tissue around fracture. But it should avoid choosing severe comminuted Sanders Ⅲand Ⅳcalcaneal fracture.


Effectiveness of early chemotherapy treatment in anaplastic astrocytoma patients.
There are limited data in the literature concerning chemotherapy trials for the treatment of anaplastic astrocytomas. Forty-one anaplastic astrocytoma patients, operated on during the period 1988 to 1993 at the Neurological institute of Milan, received 4-5 cycles of chemotherapy (BCNU + cisplatin), subsequently radiotherapy (median dose 56.5 Gy), and finally a second-line chemotherapy protocol at recurrence (procarbazine, vincristine, lomustine). The aim of the study was to evaluate the effectiveness of the planned protocol, considering the time to tumor progression and the survival time. The group of anaplastic astrocytoma patients was compared with a homogeneous group of 39 anaplastic astrocytoma patients treated only with radiotherapy after surgery. The median time to tumor progression of patients on the protocol was 24.5 months. The median survival time for anaplastic astrocytoma patients treated with our scheduled protocol or only with radiotherapy was 38.8 and 21 months, respectively. However, our data need to be confirmed by large randomized clinical studies.


Prenatal diagnosis of fetal complete atrioventricular block with QT prolongation and alternating ventricular pacemakers using multi-channel magnetocardiography and current-arrow maps.
We report a case of fetal complete atrioventricular block (CAVB) with QT prolongation and alternating ventricular pacemakers diagnosed by magentocardiography (MCG). Fetal bradyarrhythmia of around 60 bpm was detected at 30 weeks of gestation. Ultrasonography revealed fetal CAVB without structural cardiac anomalies. MCG was recorded at 30 weeks of gestation using a 64-channel superconducting quantum interference device (MC-6400, Hitachi, Japan). The averaged MCG revealed QT prolongation, and the current-arrow maps generated by MCG revealed alternating ventricular pacemakers. The diagnosis was confirmed by electrocardiogram after birth. A permanent pacemaker was implanted during the early neonatal period, and the infant was healthy at 6 months of follow-up. MCG may be a useful diagnostic tool for fetal CAVB with QT prolongation and alternating ventricular pacemakers.


[Electroacupuncture at "Zusanli" (ST 36) Alleviates Myocardium Damage in Intestinal Ischemia-reperfusion Rats by Up-regulating Periphery Dopamine Level].
To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36) on myocardium ischemic damage following intestinal ischemia-reperfusion (I/R) in rats. Thirty SD rats were randomly divided into five groups:sham, I/R-1 h, I/R-4 h, EA-I/R-1 h and EA-I/R-4 h (n=6 in each group). The intestinal I/R model was established by occlusion of the superior mesenteric artery. EA (2 Hz/100 Hz, 2-3 mA) was applied to bilateral ST 36 for 30 min. In rats of the sham group, only the stomach was opened. Plasma dopamine (DA) and tumor necrosis factor (TNF)-α contents, and myocardial myeloperoxidase (MPO) activity and methane dicarboxylic aldehyde (MDA) content were assayed using ELISA, and plasma creastine kinase isoenzyme (CK-MB) and lactate dehydrogenese (LDH) activities were detected using a fully biochemical analyser. Myocardial pathological changes were observed under microscope after H.E. staining. Compared with the sham group, plasma DA content was significantly decreased in both I/R-1 h and I/R-4 h groups, while plasma TNF-α content and CK-MB and LDH activities, and myocardial MPO activity and MDA content in both I/R-1 h and I/R-4 h groups were obviously increased (P<0.05). After EA, the decreased plasma DA and the increased plasma TNF-α contents and the increased plasma CK-MB and LDH and myocardial MPO activities and MDA contents in the EA-I/R-1 h and EA-I/R-4 h groups were reversed (P<0.05). The inhibitory rates of EA on myocardial MDA content and MPO activity were 9% and 13% in the EA-I/R-1 h group and 30% and 15% in the EA-I/R-4 h group, respectively, suggesting a better protective effect of EA intervention on myocardium in the EA-I/R-4 h group. EA of ST 36 has a better protective action on myocardium in intestinal I/R injury rats, which may be related to its effects in up-regulating plasma DA level and down-regulating circulating pro-inflammatory factor TNF-α content, and reducing myocardial oxygen free radicals.


Cytotoxic, trypanocidal, and antifungal activities of Eugenia jambolana L.
Chagas' disease, caused by Trypanosoma cruzi, is considered a public health problem. Nowadays, chemotherapy is the only available treatment for this disease, and the drugs currently used, nifurtimox and benzonidazole, present high toxicity levels. Alternatives for replacing these drugs are natural extracts from Eugenia jambolana, a plant used in traditional medicine because of its antimicrobial and biological activities. An ethanol extract from E. jambolana was prepared. To research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1×10(5)/mL in 200 μL of tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used. To examine antifungal activity, Candida albicans, Candida tropicalis, and Candida krusei were used. This is the first record of trypanocide activity for E. jambolana. The effective concentration capable of killing 50% of the parasites was 56.42 μg/mL. The minimum inhibitory concentration was ≤1,024 μg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with the ethanol extract of E. jambolana. Thus our results indicate that E. jambolana could be a source of plant-derived natural products with anti-epimastigote and antifungal modifying activity with moderate toxicity.


Parallel coil resonators for time-domain radiofrequency electron paramagnetic resonance imaging of biological objects.
Resonators suitable for time-domain electron paramagnetic resonance spectroscopy and imaging at a radiofrequency capable of accommodating experimental animals such as mice are described. Design considerations included B(1) field homogeneity, optimal Q, spectral bandwidth, resonator ring-down, and sensitivity. Typically, a resonator with 25-mm diameter and 25-mm length was constructed by coupling 11 single loops in parallel with a separation of 2.5 mm. To minimize the resonator ring-down time and provide the necessary spectral bandwidth for in vivo imaging experiments, the Q was reduced predominantly by overcoupling. Capacitative coupling was utilized to minimize microphonic effects. The B(1) field in the resonator was mapped both radially and axially and found to be uniform and adequate for imaging studies. Imaging studies with phantom objects containing a narrow-line spin probe as well as in vivo objects administered with the spin probe show the suitability of these resonators for valid reproduction of the spin probe distribution in three dimensions. The fabrication of such resonators is simple and can be scaled up with relative ease to accommodate larger objects as well.


[Overwhelming Postsplenectomy Infection after Cardiac Surgery in a Patient with Immune Thrombocytopenia;Report of a Case].
Splenectomy for immune thrombocytopenia (ITP) can increase the number of platelets. However, patients without functioning spleen become vulnerable to bacteria. Overwhelming post-splenectomy infection( OPSI), its most fulminant form, is rapidly progressive and is highly fatal. A 76-year-old male, who had undergone splenectomy for refractory ITP and taken a vaccination for treptococcus pneumoniae 4 years previously, was admitted to undergo cardiac surgery for severe aortic regurgitation and coronary disease. Prior to operation, high dose intravenous immunoglobulin therapy (400 mg/kg/day) for 5 days successfully increased platelet count. Surgery and early postoperative course were satisfactory. However, on 6th postoperative day, the patient had sudden high fever and became septic. After adequate antibiotic treatment for OPSI, the patient recovered well. Blood culture yielded methicillin-susceptible Staphylococcus aureus (MSSA). The patient discharged in good condition 30 days after the operation.


Changes in the segmental pattern of sensory neuron projections in the chick hindlimb under conditions of altered cell adhesion molecule function.
In the developing chick hindlimb, pathfinding by sensory axons is affected by their interactions with other axons entering the limb. Cell adhesion molecules (CAMs) expressed on the growing axons are likely to influence these interactions. Accordingly, to elucidate how CAMs affect sensory axon pathfinding, we injected antibodies that block the functions of NCAM, G4/L1, or N-cadherin into the hindlimb, starting at St. 25, when all motoneuron axons but only a few sensory axons had entered the plexus. In each case, the segmental pattern of projections was assessed 2-3 days later by retrogradely labeling individual peripheral nerves. With all perturbations, the gross anatomical nerve pattern developed normally; that is, some sensory axons formed cutaneous nerves while other sensory axons projected to muscles. However, the segmental pattern of sensory projections was changed when either G4/L1 or N-cadherin function was blocked in that fewer sensory axons crossed the anterior-posterior axis of the plexus. A likely reason for this effect is that anti-G4/L1 and anti-N-cadherin each decreased the amount of fasciculation and that sensory axons are less able to travel across the plexus when they are defasciculated. Anti-G4/L1 affected both cutaneous and muscle sensory projections while anti-N-cadherin affected cutaneous but not muscle sensory projections, in accord with known differences in the expression of these two CAMs on sensory and motoneuron axons. Although anti-NCAM did not appear to alter sensory projections, when polysialic acid (PSA) was enzymatically removed from NCAM, there was a marked increase in cutaneous projections from the most proximate DRG, although muscle sensory projections were unchanged. PSA removal may cause an increase in fasciculation that forces sensory axons to track along neighboring axons. Thus, without PSA, cutaneous axons project more in accord with the relative anterior-posterior positions they had as they entered the plexus. Taken together, these studies suggest that axonal fasciculation mediated by CAMs and regulated by PSA influences the ability of sensory growth cones to navigate through the plexus and project along the correct peripheral nerves.


Primary adenocarcinoma of the appendix in an inguinal hernia.
Primary adenocarcinoma of the appendix and primary carcinomata within hernial sacs are both uncommon clinical problems. A previously undescribed presentation of primary adenocarcinoma of the appendix in a right sided sliding inguinal hernia is presented and discussed. It is important to follow up patients with carcinoma of the appendix in order to exclude other colonic lesions. The St Vincent's Hospital (Melbourne) experience in this condition is limited but parallels that of major series elsewhere.


Amphotericin B, alone or followed by itraconazole therapy, is effective in the control of experimental disseminated sporotrichosis by Sporothrix brasiliensis.
Sporothrix brasiliensis is a highly virulent member of the S. schenckii complex, which is responsible for the emergence of the epidemic sporotrichosis in southeastern Brazil over the last two decades. There are no in vivo studies on the sensitivity of S. brasiliensis to the therapeutic regimens used to treat sporotrichosis. Here, we evaluated the efficacy and safety of antifungal treatments against S. brasiliensis using a murine model of disseminated sporotrichosis. In vitro, S. brasiliensis yeasts were sensitive to low concentrations of amphotericin B-deoxycholate (AMB-d) and itraconazole (ITZ), the latter having greater selectivity toward the fungus. The following treatment regimens were tested in vivo: intravenous AMB-d for 7 days post-infection (p.i.), oral ITZ for up to 30 days p.i., and AMB-d followed by ITZ (AMB-d/ITZ). AMB-d and AMB-d/ITZ led to 100% survival of infected mice at the end of the 45-day experimental period. Although all treatments extended mice survival, only AMB-d and AMB-d/ITZ significantly reduced fungal load in all organs, but AMB-d/ITZ led to a more consistent decrease in overall fungal burden. No treatment increased the levels of serum toxicity biomarkers. Taken together, our results indicate that AMB-d/ITZ is the best therapeutic option for controlling disseminated sporotrichosis caused by S. brasiliensis.


Marketing-oriented organizations: an integrated approach.
Organizations can be oriented toward marketing from a production, product, sales, or marketing perspective. Strategies, structures, and cultures, which reflect a company's basic orientation, must be integrated to ensure that marketing efforts communicate a clear corporate position. In a study of 31 hospitals, the Center for Health Services Education Research, St. Louis University, found that no hospital's organization fit neatly into a single category. For example, a hospital may have some service lines that were marketing oriented while other lines were production oriented. The majority of hospitals, however, were product oriented, focusing on productivity and financial performance rather than on market factors. The most effective sales orientation was observed in the for-profits. Their selling efforts, however, tended to be internally focused, with product development activities divorced from the planning and marketing functions. Only the for-profit hospitals showed the beginning of a marketing orientation. Developing a marketing orientation, especially in line divisions, requires a careful, well-orchestrated effort and the presence of several key factors: Access to capital and an emphasis on long-range planning and strategic spending The availability of hospital-specific market research. Key distribution channels. Talented middle managers. Up-to-date systems and structures equipped to serve new values and strategies. Leaders capable of communicating to the organization a vision of its role in the community.


Submaximal predischarge exercise testing after myocardial infarction: prognostic value and limitations.
The prognostic value of abnormalities resulting from predischarge submaximal treadmill exercise testing was evaluated in 222 patients after myocardial infarction. The presence of the following variables--ST segment depression and elevation, an abnormal blood pressure response, limited exercise duration, angina pectoris, ventricular arrhythmias--were predictive of subsequent cardiac events (P less than 0.001) among the 154 patients with one or more of these abnormalities. When the presence or absence of specific variables was assessed, only an abnormal blood pressure response, limited exercise duration (P less than 0.001), and ST segment elevation and shift (P less than 0.05), were significantly associated with cardiac death. Exercise-induced angina was predictive only of the development of subsequent angina (P less than 0.05), and ST depression was associated only with future coronary surgery (P less than 0.01). Ventricular arrhythmias had no independent prognostic value. Markers of left ventricular dysfunction elicited by submaximal exercise testing are therefore valuable in identifying patients at high risk of death after infarction. Hallmarks of residual reversible myocardial ischaemia are of limited prognostic importance. The test result may be useful in selecting patients for coronary angiography.


Quantitation of antibody binding to erythrocytes in LISS.
The amount of antibody bound to cells in a low ionic strength solution (LISS) has been quantitated for several antibodies including anti-D, anti-c, anti-Kell, anti-Fya, and anti-Jka. With the exception of the Kell antibodies there was an enhancement of the rate of antibody uptake in LISS. For Rh antibodies the amount bound after a 5-min LISS incubation is comparable to that bound after 45 min in saline. For Kell antibodies a smaller amount was bound in LISS than in saline. The effect of the ratio of serum to cells was also studied, and with several antibodies there was an increase in the amount of antibody bound with a higher serum to cell ratio irrespective of suspending medium. For Kell antibodies this ratio appears to be of greater importance than the ionic strength for antibody detection. A modification to the LISS method to increase the serum to cell ratio is, therefore, presented.


Creatinine reference values in ELBW infants: impact of quantification by Jaffe or enzymatic method.
Serum creatinine (Scr) reflects to a certain extent glomerular filtration rate in neonates, but postnatal observations also depends on the technique used to quantify Scr (Jaffe colorimetry or enzymatic quantification). In an attempt to quantify differences between these techniques, we compared postnatal Scr trends in two consecutive cohorts of extremely low birth-weight (ELBW) neonates before and following a switch from uncompensated Jaffe to enzymatic Scr quantification. Postnatal Scr (Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 14, 21, 28, and 42) in 151 ELBW neonates (uncompensated Jaffe) was compared to 116 more recently admitted ELBW neonates (enzymatic). Although clinical characteristics were similar between both cohorts, median postnatal Jaffe Scr values were significantly higher compared to enzymatic quantification (all days, at least p < 0.001) throughout postnatal life. While both cohorts displayed a similar trend with an initial increase with a Scr peak on Days 3 and 4 and a subsequent decrease, the difference in within-day median values fluctuated between 11 and 24 mmol.L(-1). There is neither fixed nor relative difference in Scr between both techniques. When using Scr to estimate renal function in ELBW neonates, clinicians should in addition to the postnatal changes and other covariates of renal function, also consider the technique applied. We provide reference values and comparison between both techniques.


Trigger-oriented HIV testing at Internal Medicine hospital Departments in Northern Italy: an observational study (Fo.C.S. Study).
Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD). Patients admitted to IMD of a General University Hospital in Italy in March-June 2013 were interviewed using a structured questionnaire investigating the presence of triggers for HIV testing, including patient's characteristics, symptoms and conditions associated with HIV infection. HIV tests performed during hospitalisation were recorded. HIV testing was performed in 73 (6.6%) out of 1113 hospitalisations (1072 patients), providing positive results in three cases (4.1%). All of them presented ≥1 triggers. Conversely, 853 triggers were identified in 528 hospitalisations with at least one trigger (47.4%). The proportion of hospitalisations where an HIV testing was prescribed was 3.1%, 9.5% and 16.0% in the presence of zero, one-to-two or more triggers, respectively. Age <70 years, female gender, length of hospital stay, haematological disease, HBV infection, multiple sexual partners and lymphadenopathy were predictors of HIV testing by logistic regression analysis. Although chances of an HIV test being performed in patients hospitalised in IMD increases along with the number of triggers, the number of tests being performed in people presenting with triggers is unacceptably low and requires educational interventions in order to obtain individual and public health advantages.


Case of undiagnosed pneumocystis pneumonia (PCP).
Pneumocystis pneumonia (PCP) is an opportunistic fungal infection that is usually seen in immunocompromised patients, especially those with HIV, malignancies, organ transplants and on drug therapies like chemotherapy and steroids. PCP has subacute presentation in patients with AIDS which if left untreated gets worse and is a significant cause of morbidity and mortality. Here we present a case of PCP went undiagnosed, partially due to the patient being unaware of his HIV positive status and partially because no organism could be found under the microscope.


[A case of amaurosis fugax with anomalous origin of the ophthalmic artery and atheromatous stenosis of the external carotid artery].
Amaurosis fugax associated with anomalous origin of the ophthalmic artery without occlusion of internal carotid artery is very rare. We are reporting such a case of amaurosis fugax with anomalous origin of the ophthalmic artery and atheromatous stenosis of the external carotid artery. A 49-year-old-man was referred to our neurosurgical clinic because of transient monocular blindness. The patient was diagnosed as carotid TIA and was treated within aspirin and dipyridamole. In spite of this treatment, he experienced further transient dimness of vision in the right eye, several times during a period of one month. On admission, general, physical and neurological examinations disclosed no abnormality except for a bruit over the right carotid artery. Platelet adhesiveness and aggregation were slightly elevated. Right common carotid angiogram showed marked stenosis of the origin of the external carotid artery and small "sail-like" plaque in the internal carotid sinus. The angiogram also demonstrated that the right ophthalmic artery was originated from the middle meningeal artery through the superior orbital fissure. Since choroid crescent was observed, all the branches of the ophthalmic artery including the central retinal artery were filled by the external carotid system. The right ophthalmic artery was never visualized by the selective internal carotid angiography. Subsequently right carotid endarterectomy was performed without complication. One year later he remains asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)


Right ventricular regional wall curvedness and area strain in patients with repaired tetralogy of Fallot.
A quantitative understanding of right ventricular (RV) remodeling in repaired tetralogy of Fallot (rTOF) is crucial for patient management. The objective of this study is to quantify the regional curvatures and area strain based on three-dimensional (3-D) reconstructions of the RV using cardiac magnetic resonance imaging (MRI). Fourteen (14) rTOF patients and nine (9) normal subjects underwent cardiac MRI scan. 3-D RV endocardial surface models were reconstructed from manually delineated contours and correspondence between end-diastole (ED) and end systole (ES) was determined. Regional curvedness (C) and surface area at ED and ES were calculated as well as the area strain. The RV shape and deformation in rTOF patients differed from normal subjects in several respects. Firstly, the curvedness at ED (mean for 13 segments, 0.030 ± 0.0076 vs. 0.029 ± 0.0065 mm(-1); P < 0.05) and ES (mean for 13 segments, 0.040 ± 0.012 vs. 0.034 ± 0.0072 mm(-1); P < 0.001) was decreased by chronic pulmonary regurgitation. Secondly, the surface area increased significantly at ED (mean for 13 segments, 982 ± 192 vs. 1,397 ± 387 mm(2); P < 0.001) and ES (mean for 13 segments, 576 ± 130 vs. 1,012 ± 302 mm(2); P < 0.001). In particular, rTOF patients had significantly larger surface area than that in normal subjects in the free wall but not for the septal wall. Thirdly, area strain was significantly decreased (mean for 13 segments, 56 ± 6 vs. 34 ± 7%; P < 0.0001) in rTOF patients. Fourthly, there were increases in surface area at ED (5,726 ± 969 vs. 6,605 ± 1,122 mm(2); P < 0.05) and ES (4,280 ± 758 vs. 5,569 ± 1,112 mm(2); P < 0.01) and decrease in area strain (29 ± 8 vs. 18 ± 8%; P < 0.001) for RV outflow tract. These findings suggest significant geometric and strain differences between rTOF and normal subjects that may help guide therapeutic treatment.


Minimally invasive follicular thyroid carcinoma.
Infiltration of the capsule, vascular invasion, and/or neoplastic extension into the adjacent parenchyma are regarded as prerequisites for the diagnosis of follicular carcinoma. In modern practice, most of these tumors fall into the category of follicular carcinoma, minimally invasive (FCMI) characterized by evidence of limited capsular or vascular invasion with an excellent long-term prognosis and a good patient outcome. Notwithstanding the wide acceptance of the diagnostic criteria established by the World Health Organization for the classification of follicular carcinomas in particular, they have been difficult to apply and have led to a great deal of confusion. This confusion is compounded when applied to "low-grade" or "minimally invasive" follicular carcinoma because of the poor reproducibility of the classification and the variable results reported in the literature. Our surgical colleagues face a similar lack of a standardized treatment for low-grade follicular carcinomas, which leads to unnecessary surgical treatment. Standardization of histologic criteria is necessary to promote confidence and uniformity in the therapeutic approach of these tumors. We believe that a FCMI is defined as an encapsulated follicular tumor (not papillary), with only small to medium vessel invasion within or immediately adjacent to the tumor capsule and/or up to full-thickness capsular transgression without accompanying extension into the thyroid parenchyma with intervening fibrosis. By using these criteria, patients can be managed with conservative surgical excision to yield an excellent long-term patient outcome.


Depletion of minichromosome maintenance protein 7 inhibits glioblastoma multiforme tumor growth in vivo.
Minichromosome maintenance (MCM) proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication in eukaryotes. Consistent with their roles in initiating DNA replication, overexpression of MCM family members has been observed in several malignancies. Through bioinformatic analysis of The Cancer Genome Atlas's data on glioblastoma multiforme (GBM), we found that the genomic region containing MCM7 gene was amplified in more than 80% of the present cases. To validate this finding and to identify the possible contribution of the remaining members of the MCM family to GBM progression, we used quantitative real-time PCR to analyze the gene expression profiles of all MCM family members in Grade IV (GBM) tissue samples and observed a significant upregulation in GBM samples compared with normal white matter tissues. In addition, we compared the observed gene expression profiles with those of Grade II and Grade III astrocytoma samples and determined that the observed upregulation was restricted and specific to Grade IV. MCM7 was the most upregulated gene in the gene set we analyzed, and therefore we wanted to identify the role of MCM7 in GBM progression. We determined that siRNA-mediated knockdown of MCM7 expression reduced GBM cell proliferation and also inhibited tumor growth in both xenograft and orthotopic mouse models of GBM. Taken together, our data suggest that MCM7 can be a potential prognostic marker and a novel therapeutic target in GBM therapy.


Photoaffinity labelling of central-nervous-system myelin. Evidence for an endogenous type I cyclic AMP-dependent kinase phosphorylating the larger subunit of 2',3'-cyclic nucleotide 3'-phosphodiesterase.
Endogenous cyclic AMP-stimulated phosphorylation of a 49700-Mr Wolfgram protein component in rabbit central nervous system was investigated by using photoaffinity labelling and 2',3'-cyclic nucleotide 3'-phosphodiesterase activity staining after electroblotting on to nitrocellulose paper. Photoaffinity labelling with 8'-azidoadenosine 3',5'-cyclic monophosphate showed a cyclic AMP-binding protein that appeared to be intrinsic to the myelin membrane and appeared to represent the R-subunit of a type I cyclic AMP-dependent protein kinase. This photoaffinity-labelled protein was of larger apparent Mr than the protein showing cyclic AMP-stimulated phosphorylation. Blotting of one-dimensional sodium dodecyl sulphate/polyacrylamide-gel electrophoretograms followed by staining for 2',3'-cyclic nucleotide 3'-phosphodiesterase activity showed two activity bands corresponding to the two components of the Wolfgram protein doublet. Cyclic AMP-stimulated protein phosphorylation corresponded to the upper component of this doublet. Electroblotting of two-dimensional non-equilibrium pH-gradient electrophoretograms also showed co-migration of cyclic AMP-stimulated protein phosphorylation with enzyme activity. It is proposed that central-nervous-system myelin contains an endogenous type I cyclic-AMP dependent protein kinase that phosphorylates the larger subunit of 2',3'-cyclic nucleotide 3'-phosphodiesterase.


[Experimental study on the hemostatic properties of collagen sponge].
To validate the hemostatic properties of collagen sponge made in China. The experimental model of superficial cut of liver was established in 20 Sprague-Dawley adult rats, which were divided into two groups randomly. Collagen sponge or gelatin sponge was used to cover the cut respectively. Hemostatic result was observed. Afterwards, standard liver trauma model by resection left front liver lobe was made, wound was treated with collagen sponge or gelatin sponge respectively. Hemostatic result was observed. Concurrent hemostatic time and bleeding amount were noted. At 7, 14 and 20 days after operation, intra-abdominal adhension, infection and healing state of liver were observed by exploratory laparotomy. The histological changes of regenerate liver tissue were observed by microscopy. Collagen sponge adhered to wound well. Concurrent hemostatic time and bleeding amount in collagen sponge group were superior to those of gelatin sponge (P < 0.05). The histological examination showed that collagen sponge was absorbed and degraded rapidly, regenerative hepatocytes could be induced. Collagen sponge has fine hemostatic properties and can induce regeneration of hepatocytes effectively. It is worth popularizing for its convenience in clinical application and its properties of rapid degradation and absorption.


[Chronic recurrent acalculous cholecystitis--apropos 6 clinical cases].
Over the period 1991 through 1994, a total of 120 patients with chronic cholecystitis are operated on. In six of them (5 per cent) no concrements in the gallbladder and biliary ducts are discovered. In 83.3 per cent the echographic study fails to detect concrements in the gallbladder and biliary ducts. All patients are subjected to cholecystectomy, and in all of them markedly expressed adhesions are found. The early and long-term operative results are estimated as very good. The positive therapeutic effect is durable and persists for many years.


Fabrication of porous calcium polyphosphate implants by solid freeform fabrication: a study of processing parameters and in vitro degradation characteristics.
Solid freeform fabrication (SFF) involves the creation of a solid 3-D object of desired shape by successively adding raw materials in particles or layers. Its use in fabricating surgical implants is being explored. The objective of this study was to determine the feasibility of using SFF to build porous parts of calcium polyphosphate (CPP), a linear condensed phosphate that has been suggested as a material for forming bioresorbable skeletal replacement implants. CPP powders (<25 microm in particle size) were added to an UV curable monomer (SOMOS 6110) at a solids loading of 25 vol %, with the addition of a commercial dispersant to prevent particle agglomeration and settling. Viscosity and cure depth measurements were performed to insure that CPP suspension met the requirements deemed necessary for use in SFF. The CPP suspension was bulk cured and sintered in molds in order to assess binder removal and sintering parameters. Using a three-point bend test, the ultimate bending strength and energy-to-fracture of sintered CPP samples simulating parts to be formed by this strategy were characterized. In vitro degradation studies using 0.1M of tris-buffered solution were performed to assess the effect of aging on mechanical properties of the samples as a function of the processing route and resulting structures. The polymer binder successfully was removed from the cured ceramic suspension by developing a procedure that combined slow heating rates with low temperature dwells. Sintering CPP at 585 degrees C for 1 h produced amorphous material samples with average porosity of 27.7 +/- 2.0%. Sintering CPP at 600 degrees C for 1 h produced a crystalline material with samples having an average porosity of 22.9 +/- 1.3%. Crystalline CPP was found to exhibit superior bend strength and toughness compared with amorphous CPP. Both samples experienced a decline in mechanical properties during in vitro degradation; however, the effects were more pronounced with the amorphous CPP samples. Amorphous CPP was found to degrade four times faster than crystalline CPP, as shown by high levels of phosphate present in the degradation solution and a noticeable increase in the porosity of the samples. Crystalline CPP was more resistant to attack as dissolution was limited to surface features of the sintered particles.


Arterial thrombosis and the role of thrombophilia.
Thrombophilia is a prominent risk factor for venous thromboembolism. The role of thrombophilia in determining the risk of arterial thrombotic events is less well defined. In this review, we summarize the existing literature on the relationship between thrombophilic defects and the risk of arterial thrombosis, in particular myocardial infarction and stroke. The six defects reviewed are the factor V Leiden mutation, the prothrombin G20210A mutation, protein C deficiency, protein S deficiency, antithrombin deficiency, and the antiphospholipid syndrome. We observed that substantial evidence supports an association between the presence of the antiphospholipid syndrome and the risk of myocardial infarction, particularly among people in whom the atherosclerotic burden is low. The literature contains no solid evidence to support an important relationship between the other thrombophilic defects reviewed and the risk of arterial thrombosis. We conclude that thrombophilia screening in unselected patient populations with myocardial infarction or ischemic stroke is not justified.


Two new species in the fern genus Lomariopsis (Lomariopsidaceae) from East Asia.
Two East Asian Lomariopsis (Lomariopsidaceae, Polypodiales) species, Lomariopsismoorei and Lomariopsislongini, which were previously misidentified as L.spectabilis, are here described as new species based on evidence from morphological characters and a molecular phylogeny. The two species differ from the three other described species in East Asia by their venation, pinna shapes, and perine morphology. A phylogeny based on a combined dataset of three chloroplast regions (rbcL+ rps4-trnS + trnL-L-F) showed that L.moorei and L.longini each formed a well-supported monophyletic group which was distantly related to both L.spectabilis and the other morphologically similar East Asian species, L.boninensis.


Safety Assessment of AAV2-hGDNF Administered Via Intracerebral Injection in Rats for Treatment of Parkinson's Disease.
Glial cell line-derived neurotrophic factor (GDNF) is a potent neuroprotective biologic in Parkinson's disease models. Adeno-associated viral vector serotype 2 (AAV2)-human GDNF safety was assessed in rats treated with a single intracerebral dose of vehicle, 6.8 × 108, 6.8 × 109, or 5.2 × 1010 vector genomes (vg)/dose followed by interim sacrifices on day 7, 31, 90, and 376. There were no treatment-related effects observed on food consumption, body weight, hematology, clinical chemistry, coagulation parameters, neurobehavioral parameters, organ weights, or serum GDNF and anti-GDNF antibody levels. Increased serum anti-AAV2 neutralizing antibody titers were observed in the 5.2 × 1010 vg/dose group. Histopathological lesions were observed at the injection site in the 6.8 × 109 vg/dose (day 7) and 5.2 × 1010 vg/dose groups (days 7 and 31) and consisted of gliosis, mononuclear perivascular cuffing, intranuclear inclusion bodies, and/or apoptosis on day 7 and mononuclear perivascular cuffing on day 31. GDNF immunostaining was observed in the injection site in all dose groups through day 376 indicating no detectable impacts of anti-AAV2 neutralizing antibody. There was no evidence of increased expression of calcitonin gene-related peptide or Swann cell hyperplasia in the cervical and lumbar spinal cord or medulla oblongata at the 5.2 × 1010 vg/dose level indicating lack of hyperplastic effects. In conclusion, no systemic toxicity was observed, and the local toxicity observed at the injection site appeared to be reversible demonstrating a promising safety profile of intracerebral AAV2-GDNF delivery. Furthermore, an intracerebral dose of 6.8 × 108 AAV2-GDNF vg/dose was considered to be a no observed adverse effect level in rats.


Notch signaling is antagonized by SAO-1, a novel GYF-domain protein that interacts with the E3 ubiquitin ligase SEL-10 in Caenorhabditis elegans.
Notch signaling pathways can be regulated through a variety of cellular mechanisms, and genetically compromised systems provide useful platforms from which to search for the responsible modulators. The Caenorhabditis elegans gene aph-1 encodes a component of γ-secretase, which is essential for Notch signaling events throughout development. By looking for suppressors of the incompletely penetrant aph-1(zu147) mutation, we identify a new gene, sao-1 (suppressor of aph-one), that negatively regulates aph-1(zu147) activity in the early embryo. The sao-1 gene encodes a novel protein that contains a GYF protein-protein interaction domain and interacts specifically with SEL-10, an Fbw7 component of SCF E3 ubiquitin ligases. We demonstrate that the embryonic lethality of aph-1(zu147) mutants can be suppressed by removing sao-1 activity or by mutations that disrupt the SAO-1-SEL-10 protein interaction. Decreased sao-1 activity also influences Notch signaling events when they are compromised at different molecular steps of the pathway, such as at the level of the Notch receptor GLP-1 or the downstream transcription factor LAG-1. Combined analysis of the SAO-1-SEL-10 protein interaction and comparisons of sao-1 and sel-10 genetic interactions suggest a possible role for SAO-1 as an accessory protein that participates with SEL-10 in downregulation of Notch signaling. This work provides the first mutant analysis of a GYF-domain protein in either C. elegans or Drosophila and introduces a new type of Fbw7-interacting protein that acts in a subset of Fbw7 functions.


The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model.
The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.


Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US.
To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18-30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55-0.96) for CHD and 0.70 (0.50-0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.