Immunopathology of herpetic stromal keratitis: discordance in CD4+ T cell function between euthymic host and reconstituted SCID recipients.
Infection of the mouse cornea with herpes simplex virus (HSV) results in an immunopathologic disease of the eye termed herpetic stromal keratitis (HSK), in which the principal orchestrator is the CD4+ T cell. The mouse genotype largely determines susceptibility or resistance to HSK. BALB/c mice (H2dIgh-1a) are susceptible, while its congenic C.B-17 strain (H2dIgh-1b), which differs only in the Ig heavy chain locus, is resistant to HSK. As the magnitude and duration of viral replication as well as anti-HSV immune responses were similar in both strains, it was determined whether resistance was due to failure of CD4+ T cells to organize the immunopathologic reaction. Adoptive transfer of HSV-primed or naive CD4+ T cells from resistant C.B-17 strain into HSV-infected SCID mice resulted in HSK lesions indistinguishable from those caused by similar transfers of BALB/c CD4+ T cells. Similar results were obtained with transfers of whole T cell populations as well as with unfractionated splenocytes from the resistant mice. These results show that while intact C.B-17 mice exhibit resistance to HSK, they possess potentially pathogenic CD4+ T cells in their repertoire. The data suggest that the HSV-infected SCID mouse provides a proinflammatory microenvironment that overrides regulatory controls and/or cause activation of quiescent cells into aggressive effector T cells that orchestrate HSK.


Renal size and function in patients with neuropathic bladder due to myelomeningocele: the role of growth hormone.
Patients with spina bifida have smaller kidneys than healthy individuals. We evaluated the correlation between small size and decreased renal function, and the possible role of growth hormone deficiency. A total of 54 patients (mean age 11.5 years, median 11, standard deviation +/- 4.52) were healthy except for neuropathic bladder due to spina bifida. Renal function was evaluated with mercaptoacetyltriglycine renal scintigraphy and creatinine clearance. Renal anatomy was evaluated with renal ultrasound and voiding cystourethrography. Serum insulin-like growth factor-1 (IGF-1) levels were measured in all patients with immunoradiometric assay. Renal measurements in our patients were compared using the Sutherland nomogram. A total of 22 patients (41%) had smaller kidneys than normal subjects and 31 appeared to have creatinine clearance values lower than 120 ml per minute per 1.73 m2. The statistical comparison between kidney size and creatinine clearance was significant (p <0.05, r = 0.381). Scintigraphic data showed total effective renal plasma flow less than 568 ml per minute per 1.73 m2 body surface area (normal mean value for age). Comparison between effective renal plasma flow and creatinine clearance was significant (p <0.05, r = 0.31). Serum levels of IGF-1 were normal for age in all patients (mean 332.06 ng/ml, median 303.4, range 39.4 to 732.3). The kidneys are smaller in patients with spina bifida than in healthy subjects when compared using the Sutherland nomogram. There is a significant correlation between smaller renal length and decreased renal function in all patients, even in those who are healthy except for neurogenic bladder secondary to spina bifida. IGF-1 levels were normal for age, and, therefore, these patients had no growth hormone deficiency. These findings call into question the hypothesis that growth hormone deficiency contributes to smaller kidney size. Other hypotheses can be suggested, such as a defect of embryological growth secondary to malformation, or the result of a defect in homocysteine-methionine metabolism.


[Paraneoplastic syndrome in renal cell carcinoma].
Renal cell carcinoma associated paraneoplastic symptoms include constitutional symptoms as well as specific metabolic and biochemical abnormalities. These are present in up to 40% of patients with renal cell carcinoma during the course of the disease. This report provides information on the most common manifestations and their therapy; some rare variants are also mentioned. The importance of paraneoplasia lies partly in the fact that paraneoplastic symptoms may be the precursor of either primary or recurrent disease. The presence of paraneoplastic manifestations does not necessarily imply a poor prognosis or metastatic disease.


Rapid-response and highly sensitive noncross-linking colorimetric nitrite sensor using 4-aminothiophenol modified gold nanorods.
A novel colorimetric nitrite ion sensor was developed utilizing 4-aminothiophenol (4-ATP) modified gold nanorods (GNR). In the presence of nitrite ions, the deamination reaction was induced by heating the 4-ATP modified GNR in ethanol solution, resulting in the reduction of the GNR surface charges, which led to aggregation of GNRs and a colorimetric response that was quantitatively correlated to the concentration of nitrite ions. This simple assay was rapid (<or=10 min) and highly sensitive (<1 ppm of nitrite), and it can be used for rapid monitoring of drinking water quality.


Recording depth and signal competition in heterodyne interferometry.
A common way to measure submicroscopic motion of the organ of Corti is heterodyne interferometry. The depth over which vibration can be accurately measured with heterodyne interferometry is determined by both the optics, which controls to what extent light from nonfocal planes reaches the photodetectors, and demodulation electronics, which determines to what extent signal generated by out-of-focal-plane light influences the measurements. The influence of a second reflecting surface is investigated theoretically and experimentally. By reviewing the theory of FM demodulation and showing tests with a Revox FM demodulator, it is demonstrated that the influence of a secondary signal on a measurement depends on the modulation index. Both high- and low-modulation index signals are encountered in heterodyne interferometry of the cochlea. Using a He-Ne-like diode laser (lambda = 638 nm), the border between low- and high-modulation signals is at a displacement of about 25-100 nm. Confocal interferometry reduces the magnitude of out-of-focus signals, and therefore their effect on vibration measurement. The response of the confocal system to reflected signals from two surfaces separated by distances encountered within the cochlear partition is shown. The results underscore the benefit of steep optical sectioning for intracochlear measurements.


[Pharmaceutical and pharmacological development of antitumor prostaglandins].
Antitumor Prostaglandins such as delta 12PGJ2 and delta 7PGA1 possess a cross-conjugated dienone unit and exhibit unique antitumor effect. Lipid microshere (w/o type emulsion) was selected as pharmaceutical formulation because of physicochemical properties of prostaglandin. 13,14-Dihydro-15-deoxy-delta 7-PGA1 methyl ester (TEI-9826) were selected as a candidate for clinical trial. In a rat and mouse serum in vitro, TEI-9826 rapidly metabolized to 13,14-dihydro-15-deoxy-delta 7-PGA1 (TOK-4528), but TOK-4528 is stable as well as delta 12PGJ2. Lipid microshere containing TEI-9826 at the content of 5 mg/ml exhibited administration route and schedule dependent antitumor effect in vivo using Colon 26 bearing mouse model, which suggested that duration of serum concentration was important for antitumor effect. One of the antitumor mechanism of antitumor PG might be an induction of the cyclin-dependent kinase inhibitor p21. PPAR gamma also might be important. New type homogenizer, high pressure jet flow type homogenizer was developed in the study of antitumor prostaglandin.


Vincristine Chemotherapy Induces Atresia of Growing Ovarian Follicles in Mice.
With great advances in cancer detection and treatment, patient survival rates have improved substantially. Subsequently, significant efforts are now focused on improving the long-term sequelae of anticancer therapies in survivors, which includes fertility. Vincristine is a microtubule destabilizing antimitotic chemotherapeutic agent commonly administered for the treatment of cancers or autoimmune disorders prevalent in girls and women of reproductive age. The potential off-target effects of vincristine on the ovary have not been directly examined. Eight-week and 6-month-old C57BL/6J mice were administered with vincristine (1 mg/kg/bw/day) or saline on day (d)1, d4, and d8, then sacrificed after 24 hours (h), or 14 days (n = 4-6/group). We assessed the impact of vincristine on the ovarian reserve of quiescent primordial follicles, as well as growing follicles, which produce mature ovulatory oocytes. This study clearly demonstrated that multidose vincristine administration caused acute atresia and loss of growing follicles and reduced corpora luteua counts 24 h following final treatment. Treatment also disrupted estrous cycling and reduced serum anti-Müllerian hormone levels. However, primordial follicle numbers were unaffected, and growing follicle populations were restored to control levels 14 days after final treatment. Vincristine exerted similar effects on ovarian follicle populations in both 8-week-old reproductively young mice and reproductively older 6-month-old mice. This study suggests that vincristine, administrated at the current dose, is toxic to growing follicles but does not deplete primordial follicles in mice. Further studies should be performed before extrapolating these data to infer the consequences of vincristine on the ovary in humans.


Observations of Syrian hamster fetuses after exposure to 2450-MHz microwaves.
The teratogenic potential of microwaves was examined in a rodent species, the Syrian hamster. Exposure of hamsters to 2450-MHz CW microwaves at a power density of 20 mW/cm2 (estimated SAR = 6 mW/g) for 100 minutes daily on days 6-14 of gestation caused no significant change in fetal survival, body weight, skeletal maturity, or incidence of terata. Thirty mW/cm2 (estimated SAR = 9 mW/g) caused significantly increased fetal resorptions, decreased fetal body weight, and decreased skeletal maturity. Rectal temperatures of pregnant hamsters after exposure to 20 mW/cm2 were slightly increased (0.4 degrees C) over those of sham-irradiated dams; 30 mW/cm2 caused maternal rectal temperatures to be increased 1.6 degrees C over sham-irradiated dams' temperatures. It appears that the hamster fetus may be more susceptible to microwave radiation than the mouse.


Insights into Pathology and Pathogenesis of Coronavirus Disease 2019 from a Histopathological and Immunological Perspective.
Since the first case of COVID-19 was reported in Wuhan, China, in December 2019, the SARS-CoV-2 epidemic has spread all over the world and has become a significant public health issue. The development of treatments for COVID-19 is currently in progress; however, their effects remain limited, and the development of more effective therapeutics is desired. Thus, sufficient understanding of the pathophysiology of COVID-19 is essential to develop effective therapeutics for this disease. Pathological analyses in particular play an important role to demonstrate the causal link between an infectious disease and the pathogen and elucidate the mechanism of pathogenesis. As per pathological analyses to date, respiratory organs are identified as the major affected organs in most COVID-19 cases; also, various lesions were noted in other organs. Further, there have been increasing reports that show that the immune responses of the host contribute to the deterioration of the pathological condition of COVID-19, and a novel concept of MIS-C/MIS-A is also being established. Thus, in this article, we have provided an overview of the pathology of COVID-19 from a histopathological and immunological perspective focusing on the mechanisms of COVID-19 pathogenesis.


Pulmonary functional assessment: longitudinal study after treatment of pulmonary tuberculosis.
Even when treated adequately, pulmonary tuberculosis can lead to pulmonary sequelae. Patients treated for PTB between 2012 and 2016 answered a standardized questionnaire and underwent chest radiography and spirometry, measurement of absolute pulmonary volume, Diffusing Capacity for Carbon Monoxide (DLCO) and the 6-min walk test (6MWT) on two occasions: within the first year after the end of treatment (follow-up 1), and one and two years after follow-up 1 (follow-up 2). A total of 55 patients they underwent spirometry, 23 (41.82%) had obstructive ventilatory disorder (OVD) and eight (14.5%) had moderate OVD. In total, 29 patients underwent pulmonary function tests (PFTs) and 24 patients underwent the 6MWT on two occasions. The functional changes after PTB treatment appear not to have varied between one and two years of follow-up. There was a correlation between low FEV1 and low DLCO (p<0.001); low DLCO and low 6MWT (p<0.001) and radiographic abnormalities and low FEV1 (p=0.033). The most frequently observed change in spirometry was found in patients with OVD.


Improvements in Modelling Bystander and Resident Exposure to Pesticide Spray Drift: Investigations into New Approaches for Characterizing the 'Collection Efficiency' of the Human Body.
The BREAM (Bystander and Resident Exposure Assessment Model) (Kennedy et al. in BREAM: A probabilistic bystander and resident exposure assessment model of spray drift from an agricultural boom sprayer. Comput Electron Agric 2012;88:63-71) for bystander and resident exposure to spray drift from boom sprayers has recently been incorporated into the European Food Safety Authority (EFSA) guidance for determining non-dietary exposures of humans to plant protection products. The component of BREAM, which relates airborne spray concentrations to bystander and resident dermal exposure, has been reviewed to identify whether it is possible to improve this and its description of variability captured in the model. Two approaches have been explored: a more rigorous statistical analysis of the empirical data and a semi-mechanistic model based on established studies combined with new data obtained in a wind tunnel. A statistical comparison between field data and model outputs was used to determine which approach gave the better prediction of exposures. The semi-mechanistic approach gave the better prediction of experimental data and resulted in a reduction in the proposed regulatory values for the 75th and 95th percentiles of the exposure distribution.


COVID-19 infection among healthcare workers: a cross-sectional study in southwest Iran.
With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated. Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS-CoV-2 PCR tests were obtained from 10th March to 17th May 2020. Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments. HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group.


Nonsurgical management of the neurogenic bladder in children.
The neurogenic bladder can have many serious consequences. However, with proper understanding of the disease spectrum, and with proper awareness of the surveillance and management tools, adverse outcomes can be minimized. The incidence of renal failure is uncommon. With proper medical therapy, one can achieve continence and minimize the risk of symptomatic urinary tract infections. There are a number of nonsurgical strategies described that can help in the management of the neurogenic bladder.


Herpes simplex lymphangitis. Two cases and a review of the literature.
Lymphangitis and lymphedema are rarely reported complications of herpetic hand or genital infection. The natural history of these complications is gradual resolution over 14 to 21 days. Recognition of this presentation of herpes infection avoids unnecessary surgery and antibacterial therapy. Antiviral therapy may have a role in shortening the duration of symptoms and aborting recurrent lymphangitic episodes.


Evaluation of concept mapping in an associate degree nursing program.
The purpose of this project was to evaluate concept mapping as a clinical teaching-learning activity that reflects critical thinking by promoting identification of nonlinear relationships among the components of the nursing process. The sample involved 28 associate degree nursing students from one graduating class. Students completed one map each in the second and fourth semesters and two maps in the fifth semester, for a total of four concept maps. The students' learning activity was to create a concept map on a blank sheet of paper describing the clients' physiological and psychosocial needs and nursing care and the relationships among concepts. As students progressed through the curriculum, there was a steady increase in the mean scores and the average number of cross-links in their concept maps. Cross-links indicated students' ability to use nonlinear thinking to identify relationships among concepts. The results of this study support the use of concept maps as an effective teaching-learning activity and support concept mapping as an evidence-based nursing education strategy.


In vitro testosterone secretion by testicular tissue from young bulls and the effects of chronic and acute exposure to estradiol-17 beta.
The possibility that estradiol-17 beta may directly influence testicular steroidogenesis in bulls was investigated in vitro. Testicular tissues were incubated for 4 h and regression coefficients (b, ng X ml-1 X h-1) based on the increase in testosterone in the medium were used to describe testosterone secretion rates. In the first experiment, testicular tissues from control bulls and bulls chronically implanted with estradiol were incubated in the absence (basal conditions) or presence of 10 mIU/ml human chorionic gonadotropin (hCG). Under basal conditions, testosterone secretion rates were similar for tissues from control (b = 24.1 +/- 6.0) and implanted (b = 34.7 +/- 6.0) bulls. Testosterone secretion rates were increased approximately fourfold during incubation with hCG; tissues from implanted animals secreted testosterone at a higher rate (P less than .05) than control tissues (b = 120.7 +/- 6.0 vs 81.6 +/- 6.0). In a second experiment, testicular tissues were obtained from control bulls and incubated both with and without hCG (10 mIU/ml) and with and without estradiol (concentrations ranging from 3.7 nM to 37 microM). In this experiment, basal secretion rate (b = 12.6 +/- 3.6) was increased threefold during incubation with hCG (b = 37.8 +/- 3.6). Estradiol failed to inhibit hCG-stimulated testosterone secretion when bovine testicular tissue was incubated with 0, 3.7 and 370 nM estradiol. In contrast, 37 microM estradiol suppressed (P less than .05) testosterone secretion, perhaps reflecting a pharmacologic effect. The results suggest that neither chronic nor acute exposure to estradiol directly affects testosterone secretion by the bovine testis.(ABSTRACT TRUNCATED AT 250 WORDS)


HIV transmission in the United States: considerations of viral load, risk behavior, and health disparities.
Ongoing HIV transmission is related to prevalence, risk behavior and viral load among persons with HIV. We assessed the contribution of these factors to HIV transmission with transmission rate models and data reported to National HIV Surveillance and published rates of risk behavior. We also estimated numbers of persons with risk behaviors and unsuppressed viral load among sexual risk groups. The transmission rate is higher considering risk behavior (18.5 infections per 100 people with HIV) than that attributed to unsuppressed viral load (4.6). Since persons without risk behavior or suppressed viral load presumably transmit HIV at very low rates, transmission can be attributed to a combination of these factors (28.9). Service needs are greatest for MSM; their number with unsuppressed viral load engaging in unprotected discordant sex was 8 times the number of male heterosexuals and more than twice the number of female heterosexuals with high-risk transmission potential. While all persons with HIV need optimal care, treatment as prevention is most relevant when risk behavior is present among persons with unsuppressed HIV viral load.


Expression, localisation and functional implications of the transporter protein PEPT2 in the upper respiratory tract.
Infectious diseases of the upper respiratory tract are widespread and may initiate exacerbations of chronic respiratory diseases such as bronchial asthma or chronic obstructive pulmonary disease. Nebulisation of antibiotics as a topic treatment may lead to high local drug concentrations. To provide data on drug transport, the present study analysed a specific drug transport system on the molecular and functional level. Messenger RNA of the proton-coupled transporter PEPT2 that mediates physiological transport of oligopeptides as well as peptidomimetics like beta-lactams and aminolevulinic acid was discovered in rat nasal mucosa by RT-PCR. Real-time PCR studies indicated a lower expression level than control kidney samples. PEPT2 immunoreactivity was identified in nasal mucosa tissue. The protein was expressed in epithelial cells, but goblet cells did not exhibit PEPT2 expression. Functional studies with rat preparations led to uptake of a fluorophore-conjugated substrate into epithelial cells of nasal mucosa. Goblet cells did not exhibit uptake activity. The uptake was competitively inhibited by dipeptides demonstrating similar substrate specificity as reported for PEPT2. Together, these data suggest that PEPT2 is likely to play an important role in mucosal peptide metabolism and may represent a novel target for therapeutic efforts in upper airway diseases.


Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature.
Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors (GISTs). The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here, we report the clinicopathological features of our case, along with a review of the few cases present in the literature.


Pathway engineering for the production of heterologous aromatic chemicals and their derivatives in Saccharomyces cerevisiae: bioconversion from glucose.
Saccharomyces cerevisiae has been extensively engineered for optimising its performance as a microbial cell factory to produce valuable aromatic compounds and their derivatives as bulk and fine chemicals. The production of heterologous aromatic molecules in yeast is achieved via engineering of the aromatic amino acid biosynthetic pathway. This pathway is connected to two pathways of the central carbon metabolism, and is highly regulated at the gene and protein level. These characteristics impose several challenges for tailoring it, and various modifications need to be applied in order to redirect the carbon flux towards the production of the desired compounds. This minireview addresses the metabolic engineering approaches targeting the central carbon metabolism, the shikimate pathway and the tyrosine and phenylalanine biosynthetic pathway of S. cerevisiae for biosynthesis of aromatic chemicals and their derivatives from glucose.


Application of peripheral-blood-derived endothelial progenitor cell for treating ischemia-reperfusion injury and infarction: a preclinical study in rat models.
Our aim was to explore the therapeutic effects of peripheral blood-derived endothelial progenitor cells (PB-EPC) in cardiac ischemia-reperfusion infarction models in rats and in in vitro culture systems. Rat models of ischemia reperfusion and myocardial infarction were developed using male, Sprague-Dawley rats. Cardiomyocyte and endothelial cell cultures were also established. Therapeutic effects of PB-EPCs were examined in vivo and in vitro in both models. Rats underwent either cardiac ischemia-reperfusion (n = 40) or infarction (n = 56) surgeries and were transplanted with genetically modified EPCs. Treatment efficacy in the ischemia-reperfusion group was measured by infarct size, myocardial contraction velocity, and myeloperoxidase activity after transplantation. Cardiomyocyte survival and endothelial cell apoptosis were investigated in vitro. Vascular growth-associated protein expression and cardiac function were evaluated in the myocardial infarction group by western blot and echocardiography, respectively. Infarct size and myeloperoxidase activity were significantly decreased in the ischemia-reperfusion group, whereas myocardial contractility was significantly increased in the EPC and Tβ4 groups compared with that in the control group. In contrast, no differences were found between EPC + shRNA Tβ4 and control groups. Rates of cardiomyocyte survival and endothelial cell apoptosis were significantly higher and lower, respectively, in the EPC and Tβ4 groups than in the control group, whereas no differences were found between the EPC + shRNA Tβ4 and control group. Four weeks after myocardial infarction, cardiac function was significantly better in the EPC group than in the control group. Expressions of PDGF, VEGF, and Flk-1 were significantly higher in EPC group than in control group. Study findings suggest that PB-EPCs are able to protect cardiomyocytes from ischemia-reperfusion or infarction-induced damage via a Tβ4-mediated mechanism. EPCs may also provide protection through increased expression of proteins involved in mediating vascular growth. Autologous peripheral-blood-derived EPCs are readily available for efficient therapeutic use without the concerns of graft rejection.


Can lower limb ultrasonography replace arteriography?
Although duplex ultrasonography offers a number of theoretical and practical advantages over arteriography for the assessment of lower limb arterial disease, it has not yet been widely accepted into clinical practice. This article reviews the current status of lower limb arterial duplex and concludes that arteriography should no longer be regarded as the diagnostic 'gold-standard' and that duplex ultrasonography should now be the first line investigation in patients with lower limb arterial disease.


Treatment with ROS detoxifying gold quantum clusters alleviates the functional decline in a mouse model of Friedreich ataxia.
Friedreich ataxia (FRDA) is caused by the reduced expression of the mitochondrial protein frataxin (FXN) due to an intronic GAA trinucleotide repeat expansion in the FXN gene. Although FRDA has no cure and few treatment options, there is research dedicated to finding an agent that can curb disease progression and address symptoms as neurobehavioral deficits, muscle endurance, and heart contractile dysfunctions. Because oxidative stress and mitochondrial dysfunctions are implicated in FRDA, we demonstrated the systemic delivery of catalysts activity of gold cluster superstructures (Au8-pXs) to improve cell response to mitochondrial reactive oxygen species and thereby alleviate FRDA-related pathology in mesenchymal stem cells from patients with FRDA. We also found that systemic injection of Au8-pXs ameliorated motor function and cardiac contractility of YG8sR mouse model that recapitulates the FRDA phenotype. These effects were associated to long-term improvement of mitochondrial functions and antioxidant cell responses. We related these events to an increased expression of frataxin, which was sustained by reduced autophagy. Overall, these results encourage further optimization of Au8-pXs in experimental clinical strategies for the treatment of FRDA.


[In vitro antibacterial activity of apalcillin on aerobic bacteria and the regression curve].
Minimal inhibitory concentrations (MICs) of apalcillin (APL) were evaluated by agar dilution on 1,201 bacterial strains isolated simultaneously in four university hospitals; agar diffusion tests (disks APL: 75 micrograms) were performed on these strains to establish relationship between MIC and zone diameters. For Enterobacteriaceae naturally non beta-lactamase-producing (E. coli and P. mirabilis), mode MIC was 0.5 microgram/ml; some acquired penicillinase-producing strains were only inhibited by concentrations greater than or equal to 16. Chromosomal penicillinase producing Klebsiella were inhibited by 2 to 8 micrograms/ml but APL was inactive on acquired penicillinase-producing strains. For chromosomal cephalosporinase-producing species (Enterobacter, Citrobacter, Serratia, indole + Proteus and Providencia) two populations of strains were observed: one sensitive and the second resistant to carboxypenicillins: on the first population, mode MIC of APL was 1 to 4 micrograms/ml; on the second MIC were generally greater than or equal to 64 micrograms/ml. P. aeruginosa strains sensitive to carboxypenicillins were inhibited by 1 and 2 micrograms/ml; this activity was diminished on strains resistant to these antibiotics (MIC APL 8-32). MIC of Acinetobacter varied to 0.25 to greater than 128 with a majority of strains inhibited by 4 to 64 micrograms/ml. APL was active against non penicillinase producing Staphylococci; mode MIC was 2 micrograms/ml for Enterococci. Correlation coefficient of regression curve was 0.87. For critical concentrations less than or equal to 8 and greater than 64 micrograms/ml, critical diameters could be greater than or equal to 19 and less than 12 mm.


Large-scale production of recombinant viruses by use of a large culture vessel with active gassing.
Adenovirus and adeno-associated virus (AAV) vectors are increasingly used for gene transduction experiments. However, to produce a sufficient amount of these vectors for in vivo experiments requires large-capacity tissue culture facilities, which may not be practical in limited laboratory space. We describe here a large-scale method to produce adenovirus and AAV vectors with an active gassing system that uses large culture vessels to process labor- and cost-effective infection or transfection in a closed system. Development of this system was based on the infection or transfection of 293 cells on a large scale, using a large culture vessel with a surface area of 6320 cm2. A minipump was connected to the gas inlet of the large vessel, which was placed inside the incubator, so that the incubator atmosphere was circulated through the vessel. When active gassing was employed, the productivity of the adenovirus and AAV vectors significantly increased. This vector production system was achieved by improved CO2 and air exchange and maintenance of pH in the culture medium. Viral production with active gassing is particularly promising, as it can be used with existing incubators and the large culture vessel can readily be converted for use with the active gassing system.


Utility of first trimester obstetric ultrasonography before 13 weeks of gestation: a retrospective study.
First trimester pregnancy is defined as twelve weeks after the last menstrual period. Ultrasonography has revolutionized validation and management of first trimester pregnancies. The aim was to analyze ultrasonographic findings of first trimester pregnancies in University of Uyo teaching hospital (UUTH), Uyo, Nigeria. The departmental ultrasonographic records of pregnant women who were referred to Radiology department of UUTH, Uyo, Nigeria. For ultrasound scans were retrospectively reviewed. The period under consideration was from 8th January 2013 to 8th February, 2016. Demographic data and ultrasonographic parameters of first trimester pregnancies like gestational sacs were recorded. Data were statistically analyzed using SPSS Chicago 13. Exclusion criterion included incomplete data and acyesis despite positive βhCG test. 26.4% (n-645) of the 2438 pregnant women who underwent obstetric ultrasonography had first trimester ultrasonography during the studied period. The peak frequency was seen in the 20-29 age range with 52.2% (n-337) and followed by 30-39 age range with 41.7% (n-269). The commonest first trimester ultrasound findings was viable pregnancy with 42.5% (n-274), followed by incomplete miscarriage with 34.3% (n-221). The least finding was trophoblastic pregnancies 0.3% (n-2). The earliest age at which normal viable pregnancy was diagnosed in this study was 5weeks 5days from the last menstrual period. Only 2.19% (n-6) of the normal viable pregnancies were multiple pregnancies and they were all twins. The highest number of referrals to Radiology Department for first trimester ultrasonography was from accident and emergency unit with 34.42% (n-222) while antenatal clinic referral was only 16.12% (n-104). The commonest first trimester's obstetric ultrasonographic findings in Uyo, Nigeria are viable pregnancies and are predominantly single gestation. The earliest age of ultasonographic pregnancy detection in Uyo is 5week 5days and peak maternal age is second and third decades.


EFFECT OF SMOKING ON MACULAR FUNCTION AND STRUCTURE IN ACTIVE SMOKERS VERSUS PASSIVE SMOKERS.
The aim is to study the effects of cigarette smoking on the structural and functional alterations of the macula in eyes of healthy young smokers. Cross-sectional clinical study included 100 active smokers (Group 1) and 100 age- and sex-matched healthy passive smokers (Group 2). All participants underwent a complete ophthalmologic assessment, axial length measurement, central corneal thickness measurement, spectral domain optical coherence tomography, and multifocal electroretinogram. Urine samples were collected to measure urinary levels of cotinine and creatinine with subsequent calculation of the cotinine creatinine ratio. Central foveal thickness (255.62 ± 17.23 and 264.75 ± 17.35 μm, respectively, with P = 0.0003) and subfoveal choroidal thickness (377.48 ± 30.32 and 385.08 ± 21.10 μm, respectively, with P = 0.04) were significantly lower in active smokers than those of passive smokers. Retinal response density of ring 1 (31.08 ± 2.29 and 33.46 ± 3.83 nV/deg, respectively, with P < 0.001) and Ring 1 (R1) P1 amplitude (0.81 ± 0.07 and 0.95 ± 0.16 μV, respectively, with P < 0.001) were significantly lower, whereas R1 P1 latency (43.02 ± 0.97 and 40.39 ± 2.08 milliseconds, respectively, with P < 0.001) was significantly longer in active smokers than those of passive smokers. The mf-ERG ring ratios were significantly lower in the active smokers than those of passive smokers. In the absence of clinically apparent foveal toxicity, CFT, SFCT together with ring amplitude ratio could be used as good predictors of subclinical nicotine induced foveal changes.


Differential effects of intragastric acid and capsaicin on gastric emptying and afferent input to the rat spinal cord and brainstem.
Hydrochloric acid (HCl) is a potential threat to the integrity of the gastric mucosa and is known to contribute to upper abdominal pain. We have previously found that gastric mucosal challenge with excess HCl is signalled to the rat brainstem, but not spinal cord, as visualized by expression of c-fos messenger ribonucleic acid (mRNA), a surrogate marker of neuronal excitation. This study examined whether gastric mucosal exposure to capsaicin, a stimulant of nociceptive afferents that does not damage the gastric mucosa, is signalled to both brainstem and spinal cord and whether differences in the afferent signalling of gastric HCl and capsaicin challenge are related to different effects on gastric emptying. Rats were treated intragastrically with vehicle, HCl or capsaicin, activation of neurons in the brainstem and spinal cord was visualized by in situ hybridization autoradiography for c-fos mRNA, and gastric emptying deduced from the retention of intragastrically administered fluid. Relative to vehicle, HCl (0.5 M) and capsaicin (3.2 mM) increased c-fos transcription in the nucleus tractus solitarii by factors of 7.0 and 2.1, respectively. Capsaicin also caused a 5.2-fold rise of c-fos mRNA expression in lamina I of the caudal thoracic spinal cord, although the number of c-fos mRNA-positive cells in this lamina was very small. Thus, on average only 0.13 and 0.68 c-fos mRNA-positive cells were counted in 0.01 mm sections of the unilateral lamina I following intragastric administration of vehicle and capsaicin, respectively. In contrast, intragastric HCl failed to induce c-fos mRNA in the spinal cord. Measurement of gastric fluid retention revealed that HCl suppressed gastric emptying while capsaicin did not. The findings of this study show that gastric mucosal exposure to HCl and capsaicin is differentially transmitted to the brainstem and spinal cord. Since only HCl blocks gastric emptying, it is hypothesized that the two stimuli are transduced by different afferent pathways. We infer that HCl is exclusively signalled by gastric vagal afferents whereas capsaicin is processed both by gastric vagal and intestinal spinal afferents.


A survey of current in vivo radiotherapy dosimetry practice.
A questionnaire was sent out to 57 radiotherapy physics departments in the United Kingdom to determine the type of dosemeters used for in vivo measurements inside and outside X-ray treatment fields, and whether any correction is made for energy dependence when the dose to critical organs outside the main beam is estimated. 44 responses were received. 11 centres used a semi-conductor for central axis dosimetry compared with only two centres which used thermoluminescent dosimetry (TLD). 37 centres carried out dosimetry measurements outside the main beam; 25 centres used TLD and 12 centres used a semi-conductor detector. Of the 16 centres measuring the dose at both sites. 11 used a semi-conductor for the central axis measurement, but only four of those 11 changed to TLD for critical organ dosimetry despite the latter's lower variation in energy response. None of the centres stated that they made a correction for the variation in detector energy response when making measurements outside the main beam, indicating a need for a more detailed evaluation of the energy response of these detectors and the energy spectra outside the main beam.


Theoretical Method for an Accurate Elucidation of Energy Transfer Pathways in Europium(III) Complexes with Dipyridophenazine (dppz) Ligand: One More Step in the Study of the Molecular Antenna Effect.
A theoretical protocol to study the sensitization and emission mechanism in lanthanide compounds on the basis of multireference CASSCF/PT2 calculations is proposed and applied to [Eu(NO3)3(dppz-CN)] and [Eu(NO3)3(dppz-NO2)] compounds synthesized and characterized herein. The method consists of a fragmentation scheme where both the ligand and the lanthanide fragments were calculated separately but at the same level of theory, using ab initio wave-function-based methods which are adequate for the treatment of quasi-degenerate states. This is based on the fact that the absorption is ligand-localized and the emission is europium-centered. This characteristic allowed us to describe the most probable energy transfer pathways that take place in the complexes, which involved an ISC between the S1 to T1 ligand states, energy transfer to 5D2 in the lanthanide fragment, and further 5D0 → 7FJ emission. For both compounds, the triplet and 5D2 states were determined at the CASPT2 level to be around ∼26000 and ∼22400 cm-1, respectively. This difference is in the optimal range for the energy transfer process. Finally, the emissive state 5D0 was found at ∼18000 cm-1 and the emission bands in the range 550-700 nm, in quite good agreement with the experimental results.


Evaluating subject-treatment interaction when comparing two treatments.
Clinical and other studies that evaluate the effect of a treatment relative to a control often focus on estimating a mean treatment effect; however, the mean treatment effect may be misleading when the effect of the treatment varies widely across subjects. Methods are proposed to evaluate individual treatment heterogeneity (i.e., subject-treatment interaction) and its consequences in clinical experiments. The method of maximum likelihood is used to derive estimators and their properties. A bootstrap procedure that requires fewer assumptions is also presented as a small sample alternative to the maximum likelihood approach. It is shown that estimators for subject-treatment interaction are sensitive to an inestimable correlation parameter. This sensitivity is illustrated using some example data sets and using graphical plots. The practical consequence of subject-treatment interaction is that a proportion of the population may be not be responding to the treatment as indicated by the average treatment effect. Results obtained from the methods reported here can alert the practitioner to the possibility that individual treatment effects vary widely in the population and help to assess the potential consequences of this variation. Applications of the proposed procedures to clinical decision making, pharmacogenetic studies, and other contexts are discussed.


Two approaches to treating unilateral neglect after right hemisphere stroke: a preliminary investigation.
This preliminary study assessed the efficacy of two treatment methods for persistent unilateral or hemispatial neglect following right hemisphere stroke. Two patients received an intervention focusing on the underlying impairment of attention during visual scanning. Two other participants received an intervention that provided repetitive practice during a functional task of oral reading. Standardized tests of attention and neglect were administered before and after treatment. Performance on a functional task assessing generalization of treatment was probed at every session. Results indicate no clear conclusions regarding the efficacy of either approach. Factors contributing to these equivocal findings are addressed.


Function of Nanos1 gene in the development of reproductive organs of Schistosoma japonicum.
Nanos is a necessary factor in the differentiation and migration of primordial germ cells. It is closely associated with the development of genitalia in a wide range of species. We questioned whether Nanos was involved in the reproductive organ development of Schistosoma japonicum. Firstly, by in situ hybridization, S. japonicum Nanos1 (SjNanos1) gene was expressed mainly in reproductive organs of S. japonicum. Then, the paired schistosome of 28 days post-infection (dpi) was transfected with SjNanos1 small interfering RNA three times and cultured in vitro for 10 days. SjNanos1 expression suppression in the mRNA and protein levels were confirmed compared to that of the controls. The morphological changes in reproductive organs and egg production were observed after SjNanos1 gene knockdown. The results observed by confocal laser scanning microscopy showed significant changes in the morphology of reproductive organs of parasites, especially the female ovaries, vitellarium, and the male testes, after RNAi. In addition, SjNanos1 silencing also induced the reduction of eggs, and affected the changes of reproduction-related genes, like Pumilio, CNOT6L, and Fs800. Therefore, our findings demonstrate that the SjNanos1 gene is essential in the development of reproductive organs and the egg production of S. japonicum.


VEGF-A and serum withdrawal induced changes in the transcript profile in human endometrial endothelial cells.
The changes in transcript profile induced by vascular endothelial growth factor (VEGF-A) and serum withdrawal in primary human endometrial endothelial cells (ECs) were investigated using microarrays, gene ontology and pathway analysis. Vascular endothelial growth factor A altered the levels of transcripts involved in angiogenesis, cell survival, and apoptosis, including up-and downregulation of AKT1, BAD, MIF, and IGFBP3 and ANGPT2, respectively. Serum deprivation induced downregulation of cell-cycle-related transcripts such as mitosis regulators CDC20 and SPC25. Of the transcripts regulated by both VEGF-A and partial serum deprivation, remarkably 88 of 89 showed reciprocal regulation (p < 1 x 10(-49)). These are predominantly cell-fate-associated transcripts and this novel observation suggests that endometrial ECs may be particularly dependant on the levels of these transcripts. Our results show that in addition to the known role of VEGF-A as an EC growth and survival promoter, it also regulates apoptosis-related messenger RNAs (mRNAs), many of which were reciprocally regulated following serum withdrawal.


[Neuropharmacological drugs effect on functional activity of rat brain].
The influence of some neuropharmacological drugs was studied as applied to RNA synthesis and animal behaviour. The phosphodiesterase, adenyl cyclase and monoaminoxidase activities in glial cells were investigated as well. The glial cells are stated to possess a high activity of phosphodiesterase, adenyl cyclase and monoaminoxidase A. Neuropharmacological drugs, reserpine and transamine produce a different influence of RNA synthesis in vivo, but have no effect in vitro. Transamine and reserpine accelerate the formation of conditioned defensive reflex but they strongly inhibited the reproduction of this reflex.


WHO-WHL Hypertension Management Audit Project.
The quality of the control of hypertension has been assessed in 18 European population groups, in a multicentre cooperative project. Five approaches were taken: epidemiological survey, clinical evaluation of samples of patient records, assessment of patient satisfaction, exploration of physicians' attitudes and knowledge, and drug utilisation studies. The participating centres could choose any or all of the above approaches; a total of 31 subprojects was carried out. Undiagnosed hypertension varied in different centres from 17% to 34% of all hypertension, and not more than 29% of all treated hypertensive patients had attained normal BP. Diuretics were the most commonly prescribed drugs, followed by beta-blockers. Although physicians expressed their concern about other cardiovascular risk factors and declared that they considered nonpharmacological treatment important, the findings in the patient survey did not confirm such attitudes. Finally, an analysis of patient satisfaction showed a mixed pattern. In conclusion, the control of hypertension in populations, through detection and treatment, as well as patient education and physician information, was studied.


Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and Adhesion of HeLa Cells.
To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells. Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells. MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells. MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments.


The treatment and management of alternating hemiplegia of childhood.
Alternating hemiplegia of childhood has many factors that make it difficult to manage. These include its rarity of about one case per million, the variability of the manifestations, with seven characteristic features, and the potential for disabilities and acute, often severe, episodes in a disease that is of uncertain cause and for which treatment evidence is sparse. An integrated multidisciplinary team and emergency availability are key medical requirements, as well as an educational setting that understands the variations in performance that occur. The mainstays of treatment have been flunarizine, antiepilepsy drugs for the 50% of patients with epilepsy, attempts to avoid trigger situations, and the rapid encouragement of sleep when attacks begin. The diagnostic and management predicament of child, parent, and paediatrician in complex rare disorders are well illustrated by this condition.


Urocortin 2 acts centrally to delay gastric emptying through sympathetic pathways while CRF and urocortin 1 inhibitory actions are vagal dependent in rats.
We characterized the influence of the selective corticotropin-releasing factor 2 (CRF(2)) receptor agonist human urocortin 2 (Ucn 2), injected intracisternally, on gastric emptying and its mechanism of action compared with intracisternal CRF or urocortin (Ucn 1) in conscious rats. The methylcellulose phenol red solution was gavaged 20 min after peptide injection, and gastric emptying was measured 20 min later. The intracisternal injection of Ucn 2 (0.1 and 1 microg) and Ucn 1 (1 microg) decreased gastric emptying to 37.8 +/- 6.9%, 23.1 +/- 8.6%, and 21.6 +/- 5.9%, respectively, compared with 58.4 +/- 3.8% after intracisternal vehicle. At lower doses, Ucn 2 (0.03 microg) and Ucn 1 (0.1 microg) had no effect. The CRF(2) antagonist astressin(2)-B (3 microg ic) antagonized intracisternal Ucn 2 (0.1 microg) and CRF (0.3 microg)-induced inhibition of gastric emptying. Vagotomy enhanced intracisternal Ucn 2 (0.1 or 1 microg)-induced inhibition of gastric emptying compared with sham-operated group, whereas it blocked intracisternal CRF (1 microg) inhibitory action (45.5 +/- 8.4% vs. 9.7 +/- 9.7%). Sympathetic blockade by bretylium prevented intracisternal and intracerebroventricular Ucn 2-induced delayed gastric emptying, whereas it did not influence intravenous Ucn 2-, intracisternal CRF-, and intracisternal Ucn 1-induced inhibition of gastric emptying. Prazosin abolished the intracisternal Ucn 2 inhibitory effect, whereas yohimbine and propranolol did not. None of the pretreatments modified basal gastric emptying. These data indicate that intracisternal Ucn 2 induced a central CRF(2)-mediated inhibition of gastric emptying involving sympathetic alpha(1)-adrenergic mechanisms independent from the vagus contrasting with the vagal-dependent inhibitory actions of CRF and Ucn 1.


[Laparoscopic tumor nephrectomy].
Initially, laparoscopic surgery in urology was restricted to the treatment of benign diseases, whereas its role in the management of malignant disease was restricted to purely diagnostic procedures. Only recently has laparoscopy been introduced for the treatment of low stage renal cell carcinoma (RCC), and the data on both surgical efficiency and oncologic efficacy are very promising. Therefore, we present our experience with laparoscopic radical nephrectomy and data from literature. The technique of the transperitoneal approach is described in detail. Retroperitoneoscopy is a good alternative, however. Intact removal of the specimen within an organ bag to avoid tumor spillage is an important detail of our technique. Our experience amounts to radical nephrectomy in 121 patients. The indication was clinical stage T1-T2. Mean operative time and blood loss was 2.4 h and 154 ml, respectively. The rate of minor or major complications was 5% and 4%, respectively. There was no conversion to open surgery in any patient. Mean postoperative hospital stay was 6.1 days. Data on tumor control are available for 73 patients with a mean follow-up of 13.3 months. There was no recurrence within this period. Radical nephrectomy for low-stage RCC is associated with low morbidity and great surgical efficiency. The rates for local recurrences and metastases are low, tumor-specific survival is high. However, there is still a lack of long-term data on large series of patients. Despite this fact, laparoscopy is already widely accepted for this indication, and it is quite likely that it will become the standard treatment.


Pubertally born neurons and glia are functionally integrated into limbic and hypothalamic circuits of the male Syrian hamster.
During puberty, the brain goes through extensive remodeling, involving the addition of new neurons and glia to brain regions beyond the canonical neurogenic regions (i.e., dentate gyrus and olfactory bulb), including limbic and hypothalamic cell groups associated with sex-typical behavior. Whether these pubertally born cells become functionally integrated into neural circuits remains unknown. To address this question, we gave male Syrian hamsters daily injections of the cell birthdate marker bromodeoxyuridine throughout puberty (postnatal day 28-49). Half of the animals were housed in enriched environments with access to a running wheel to determine whether enrichment increased the survival of pubertally born cells compared with the control environment. At 4 wk after the last BrdU injection, animals were allowed to interact with a receptive female and were then killed 1 h later. Triple-label immunofluorescence for BrdU, the mature neuron marker neuronal nuclear antigen, and the astrocytic marker glial fibrillary acidic protein revealed that a proportion of pubertally born cells in the medial preoptic area, arcuate nucleus, and medial amygdala differentiate into either mature neurons or astrocytes. Double-label immunofluorescence for BrdU and the protein Fos revealed that a subset of pubertally born cells in these regions is activated during sociosexual behavior, indicative of their functional incorporation into neural circuits. Enrichment affected the survival and activation of pubertally born cells in a brain region-specific manner. These results demonstrate that pubertally born cells located outside of the traditional neurogenic regions differentiate into neurons and glia and become functionally incorporated into neural circuits that subserve sex-typical behaviors.


Antioxidant Properties of Kombucha Made with Tartary Buckwheat Tea and Burdock Tea.
Kombucha is a beverage fermented by SCOBY, which is a symbiotic culture of bacteria and yeast. Recently, kombucha has received significant attention due to its health benefits, which include antioxidant and anti-obesity effects. In this study, we investigated the characteristics of kombucha made with Tartary buckwheat and burdock, both known for their high polyphenols content. First, the total polyphenol content and antioxidant activity were measured by 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays, which revealed a polyphenol content of 180 ug/mL in Tartary buckwheat kombucha and a high radical scavenging ability of over 90% in both kombucha preparations. Analysis of the changes in the organic acid content during fermentation revealed increases in various organic acid contents, such as glucuronic acid, lactic acid, and acetic acid. Glucuronic acid, especially, which has many functional properties in health, was found to be produced at a concentration of 4.03 g/L in Tartary buckwheat kombucha. Pancreatic lipase inhibitory ability analysis revealed inhibitory effects of 40.47% and 57.68% for Tartary buckwheat and burdock kombucha, respectively. The results of this study confirmed the antioxidant and anti-obesity effects of kombucha made from Tartary buckwheat and burdock, indicating the potential value of these ingredients as functional kombucha ingredients.


Ricinus communis agglutinin II-reactive glycoproteins from the ascites of patients with hepatocellular carcinoma and their use in enzyme-linked immunosorbent assay.
Ricinus communis agglutinin II-reactive glycoproteins from the ascites of patients with hepatocellular carcinoma were prepared using lectin affinity chromatography. Normal serum- and cirrhotic ascites-components were removed by columns with immobilized antibodies against them. Ricinus communis agglutinin II-reactive glycoproteins thus obtained were supposed to be hepatocellular carcinoma-associated and less than 0.1% of the protein in the starting material. Polyacrylamide gel electrophoresis of these glycoproteins revealed more than 10 major polypeptides with molecular weights ranging from 20K to 200K daltons. The rabbit antiserum raised against them reacted with at least three components of 45, 52 and 55K daltons. The serum level of this antibody-reactive glycoproteins was assessed by an enzyme-linked immunosorbent assay. It was elevated in 91% of cases of hepatocellular carcinoma, 70% of cases of other gastrointestinal carcinoma, 88% of cases of liver cirrhosis, 55% of cases of chronic hepatitis, and 25% of cases of acute hepatitis. The mean value of hepatocellular carcinoma was significantly greater than those of other groups. These results suggest that some of Ricinus communis agglutinin II-reactive glycoproteins in hepatocellular carcinoma patients may be cancer-associated glycoproteins and that their serum levels are increased in hepatocellular carcinoma patients.


Human kidney aldose and aldehyde reductases.
Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D-xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain substrates of perceived spatial separation between speech sources under simulated reverberant listening conditions in schizophrenia.
People with schizophrenia recognize speech poorly under multiple-people-talking (informational masking) conditions. In reverberant environments, direct-wave signals from a speech source are perceptually integrated with the source reflections (the precedence effect), forming perceived spatial separation (PSS) between different sources and consequently improving target-speech recognition against informational masking. However, the brain substrates underlying the schizophrenia-related vulnerability to informational masking and whether schizophrenia affects the unmasking effect of PSS are largely unknown. Using psychoacoustic testing and functional magnetic resonance imaging, respectively, the speech recognition under either the PSS or perceived spatial co-location (PSC) condition and the underlying brain substrates were examined in 20 patients with schizophrenia and 16 healthy controls. Speech recognition was worse in patients than controls. Under the PSS (but not PSC) condition, speech recognition was correlated with activation of the superior parietal lobule (SPL), and target speech-induced activation of the SPL, precuneus, middle cingulate cortex and caudate significantly declined in patients. Moreover, the separation (PSS)-against-co-location (PSC) contrast revealed (1) activation of the SPL, precuneus and anterior cingulate cortex in controls, (2) suppression of the SPL and precuneus in patients, (3) activation of the pars triangularis of the inferior frontal gyrus and middle frontal gyrus in both controls and patients, (4) activation of the medial superior frontal gyrus in patients, and (5) impaired functional connectivity of the SPL in patients. Introducing the PSS listening condition efficiently reveals both the brain substrates underlying schizophrenia-related speech-recognition deficits against informational masking and the schizophrenia-related neural compensatory strategy for impaired SPL functions.


Association between the ACE I/D polymorphism and muscle injuries in Italian and Japanese elite football players.
ACE I/D polymorphism has been recently associated with the susceptibility to inflammation and muscle damage after exercise. The aim of this study was to understand the association between the ACE I/D polymorphism and muscle injuries in a large cohort of elite football players from two different countries. Seven hundred and ten male elite football players from Italy (n = 341) and Japan (n = 369) were recruited for the study. Genomic DNA was extracted from either the buccal epithelium or saliva using a standard protocol. Structural-mechanical injuries and functional muscle disorders were recorded from 2009 to 2018. A meta-analysis was performed using Review Manager 5.3.5. In the Japanese cohort, the ACE I/D polymorphism was significantly associated with muscle injury using the D-dominant model (OR: 0.48, 95% CI: 0.24-0.97, P = 0.040). The meta-analysis showed that in the pooled model (Italian and Japanese populations), the frequencies of the DD+ID genotypes were significantly lower in the injured groups than in non-injured groups (OR: 0.61, 95% CI: 0.38-0.98, P = 0.04) with a low degree of heterogeneity (I2 = 0%). Our findings suggest that the ACE I/D polymorphism could influence the susceptibility to developing muscle injuries among football players.


The Efficacy of Psychological Therapies in Reducing Weight and Binge Eating in People with Bulimia Nervosa and Binge Eating Disorder Who Are Overweight or Obese-A Critical Synthesis and Meta-Analyses.
Recurrent binge eating episodes, the core feature of Bulimia Nervosa (BN) and Binge Eating Disorder (BED), are frequently comorbid with obesity. Psychological interventions, notably Cognitive Behavioural Therapy (CBT), are effective for binge eating reduction in BED or BN but less so for weight loss. Behavioural Weight Loss Therapy (BWLT) shows effectiveness for binge eating reduction and weight loss but the latter appears poorly sustained over time. Our aim was to review evidence for efficacy of psychological therapies for BN/BED associated with overweight or obesity in reducing binge frequency and weight. A systematic search for randomized controlled trials with adult samples who had BN or BED was conducted considering articles in English, French, Spanish and Portuguese with no restrictions for the timeline publication ending in March 2016. A quality appraisal of the trials and meta-analyses comparing BWLT to CBT were done. This review identified 2248 articles for screening and 19 published articles were selected. No trials of BN were identified. This review found CBT was favoured compared to BWLT with regard to short-term binge eating reduction. However, insufficient evidence was found for superiority for BWLT efficacy compared to CBT considering binge eating remission, reduction of binge eating frequency and weight loss. More research is needed to test the efficacy of psychological treatments for BED or BN with co-morbid overweight or obesity, including trials evaluating binge eating remission and weight loss in the long-term.


VanB phenotype-vanA genotype Enterococcus faecium with heterogeneous expression of teicoplanin resistance.
Six VanB phenotype-vanA genotype isolates of Enterococcus faecium with heterogeneous expression of teicoplanin resistance which gave rise to an outbreak at a Korean tertiary care teaching hospital have IS1216V in the coding region of vanS. This could be the underlying cause of the VanB phenotype-vanA genotype with heterogeneous expression of teicoplanin resistance.


A Crystalline π-Stack Containing Five Stereoisomers: Insights into Conformational Isomorphism, Chirality Inversion, and Disorder.
An unprecedented crystal-packing arrangement of a tetramethoxy-bay-substituted perylene bisimide (PBI) consists of three crystallographically independent molecules, that is, an achiral (AC) PBI of saddle-shaped geometry along with two pairs of propeller-like twisted (P)- and (M)-enantiomeric PBI frameworks. All these five conformations are observed within a single π-stack revealing an intriguing packing sequence with an inversion of chirality from P to M via AC. Nudged elastic band calculations for the isolated molecule show that AC is a local minimum of the P to M interconversion path. In addition, two minor conformations were observed in the crystal, one of which resembles a transition-state molecule. Theoretical studies of dimeric and trimeric stacks reveal that the coexistence of all these structures in the crystal lattice is aided by the strong dispersion interactions between PBI cores and perfectly interdigitated dodecyl chains which stabilize energetically higher conformations.


A pre-in vitro maturation medium containing cumulus oocyte complex ligand-receptor signaling molecules maintains meiotic arrest, supports the cumulus oocyte complex and improves oocyte developmental competence.
Can a pre-in vitro maturation (pre-IVM) medium containing signaling molecules rather than chemical/pharmaceutical agents, sustain meiotic arrest and improve developmental competence of in vitro matured oocytes in CF1 outbred mice? A short 2 h period of pre-IVM prevents spontaneous meiotic resumption, improves mitochondria activity in subsequently matured oocytes, and increases developmental competence, pregnancy rate and implantation of resulting embryos. Spontaneous resumption of meiosis in vitro is detrimental for oocyte developmental competence. Pre-IVM systems that prevent spontaneous meiotic resumption with chemical/pharmaceutical agents are a promising approach to improving IVM oocyte competence; however, the success of these methods has proven to be inconsistent. This study consisted of a series of experiments using cumulus oocyte complexes (COC) derived from outbred mice following ovarian stimulation. The study was designed to examine if a novel, ligand/receptor-based pre-IVM treatment could sustain meiotic arrest in vitro and improve oocyte developmental competence, compared to control IVM. Two pre-IVM durations (2 h and 24 h) were evaluated, and the effect of the mitochondrial stimulator PQQ during 24 h pre-IVM was studied. Murine (outbred CF1) immature COC were cultured in vitro in the presence of C-type natriuretic peptide (CNP) (30 nM), estradiol (100 nM), FSH (1 × 10-4 IU/ml) and bone morphogenic protein 15 (BMP15) (100 ng/ml) for 2 h or 24 h prior to IVM. Meiotic status during pre-IVM and IVM was analyzed using orcein staining, and functionality of gap junction communication was confirmed using the functional gap junction inhibitor carbenoxolone (CBX). Oocytes exposed to pre-IVM treatment were compared to control oocytes collected on the same day from the same females and undergoing standard IVM. Developmental competence and embryo viability was assessed by oocyte mitochondrial activity and ATP concentration, in vitro embryo development following IVF and in vitro culture, blastocyst cell number and allocation, embryo morphokinetics, and embryo transfer. Differences were determined to be significant when P < 0.05. Both a short (2 h) and long (24 h) pre-IVM period successfully prevented spontaneous resumption of meiosis. Moreover, gap junctions remained open during the pre-IVM period, as shown by the resumption of meiosis (95.9 ± 2.1%) in the presence of CBX during pre-IVM. A 2 h pre-IVM treatment improved blastocyst development after 96 h of culture per cleaved embryo compared to control (71.9 ± 7.4% versus 53.3 ± 6.2%, respectively), whereas a longer 24 h pre-IVM had no effect on development. A short 2 h period of pre-IVM increased mitochondrial activity in mature oocytes. On the contrary, mitochondrial activity was reduced in mature oocytes following 24 h of arrest and IVM. Treatment of arrested COC with pyrroloquinoline quinone (PQQ) during the 24 h pre-IVM period successfully maintained mitochondrial activity equal to control. However, PQQ was not able to improve blastocyst development compared to pre-IVM 24 h without PQQ. Moreover, ATP concentration in mature oocytes following pre-IVM and/or IVM, did not differ between treatments. A 2 h pre-IVM period prior to IVM improved pregnancy rate following transfer to recipient females. Implantation was also improved after transfer of embryos derived from oocytes arrested for either 2 h or 24 h prior to IVM, compared to control IVM derived embryos (41.9 ± 9%, 37.2 ± 9.5% and 17.2 ± 8.3%, respectively), although fetal development did not differ. Slower meiotic resumption and enhanced mitochondrial activity likely contribute to improved developmental competence of oocytes exposed to pre-IVM for 2 h, but further experiments are required to identify specific mechanisms. Maintaining oocytes in meiotic arrest for 24 h with this approach could be a potential window to improve oocyte quality. However, an initial attempt to utilize this period of arrest to manipulate quality with PQQ, a mitochondrial stimulator, did not improve oocyte competence. IVM could be an attractive clinical alternative to conventional IVF, with reduced time, cost and reliance on high doses of exogenous hormones to stimulate follicle growth, thus eliminating ovarian hyperstimulation syndrome (OHSS). Currently IVM is not widely used as it results in reduced embryo development and lower pregnancy outcomes compared to embryos produced from in vivo matured oocytes. Our approach to IVM, incorporating a ligand/receptor pre-IVM period, could improve human oocyte quality following IVM leading to routine adoption of this patient friendly technology. In addition, our methodology of pre-IVM containing signaling molecules rather than chemical/pharmaceutical agents may prove to be more consistent at improving oocyte quality than those focusing only on cAMP modulation with pharmacological agents. Finally, a reliable method of maintaining oocytes in meiotic arrest in vitro provides a novel window of opportunity in which the oocyte may be manipulated to address specific physiological deficiencies prior to meiotic resumption. N/A. This study was supported by the Colorado Center for Reproductive Medicine (CCRM, Lone Tree, Colorado USA). We declare no conflict of interest.


Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery.
We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.


Characterization of Vertical Accelerations Experienced by Older People Attending an Aerobics Class Designed to Produce High Impacts.
The purpose of this study was to establish the feasibility of using an aerobics class to produce potentially bone protective vertical impacts of ≥ 4g in older adults and to determine whether impacts can be predicted by physical function. Participants recruited from older adult exercise classes completed an SF-12 questionnaire, short physical performance battery, and an aerobics class with seven different components, performed at low and high intensity. Maximum g and jerk values were identified for each activity. Forty-one participants (mean 69 years) were included. Mean maximal values approached or exceeded the 4g threshold for four of the seven exercises. In multivariate analyses, age (-0.53; -0.77, -0.28) (standardized beta coefficient; 95% CI) and 4-m walk time (-0.39; -0.63, -0.16) were inversely related to maximum g. Aerobics classes can be used to produce relatively high vertical accelerations in older individuals, although the outcome is strongly dependent on age and physical function.


Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting.
Liposomes may be engineered to target inflamed endothelium by mimicking ligand-receptor interactions between leukocytes and cytokine-activated endothelial cells (ECs). The upregulation and assembly of vascular cell adhesion molecule-1 (VCAM1) and E-selectin on the cell membrane upon exposure to cytokines have shown potential for drug delivery vehicles to target sites of chronic endothelial inflammation, such as atherosclerosis and cancer. Herein, we characterized EC surfaces by measuring the E-selectin and VCAM1 surface densities and adhesion forces of aVCAM1 and aE-selectin to ECs. We quantified the antibody density, ratio, and diffusivity of liposomes to achieve significant binding and internalization. At 1 h, the 1:1 ratio of VCAM1:E-selectin antibodies was significantly higher than 1:0 and 0:1. Significant binding and uptake was achieved at aE-selectin densities as low as 400 molecules/μm(2). The highest levels of binding and uptake were achieved when using a 1:1 ratio of VCAM1:E-selectin antibodies at a density of 1000 molecules/μm(2); this density is 85% lower than previous reports. The binding and uptake of functionalized liposomes were reduced to levels comparable to IgG functionalized liposomes upon a 10-fold reduction in liposome membrane diffusivity. We conclude with a liposomal design that discriminates between healthy and inflamed endothelium while reducing antibody surface presentation.


Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway.
Convergence of somatic and visceral inputs occurs at the levels of nervous system ranging from spinal cord to cerebral cortex. This anatomical organization gave explanation to a referred pain phenomenon. However, it also presents a problem: How does the brain know what information is coming for processing-somatic or visceral - if both are transferred by the same spinal cord fibers by means of the standard neuronal spikes? Recent studies provided evidence for cortical processing of interoceptive information largely occurring in sleep, when somatosensation is suppressed, and for the corresponding functional brain networks rearrangement. We suggest that convergent units of the spinal cord would be able to collectively provide mainly somatosensory information in wakefulness and mainly visceral in sleep, solving the puzzle of somatovisceral convergence. We recorded spiking activity from the spinal cord lemniscus pathway during multiple sleep-wake cycles in freely behaving rabbits. In wakefulness high increased spiking corresponded to movements. When animals stopped moving this activity ceased, the fibers remained silent during passive wakefulness. However, upon transition to sleep fibers began firing again. Analysis of spiking patterns of individual fibers revealed that in the majority of them spiking rates recovered in slow wave sleep. Thus, despite cessation of motion and a corresponding decrease of somatic component of the convergent signal, considerable ascending signaling occurs during sleep, that is likely to be visceral. We also recorded evoked responses of the lemniscus pathway to innocuous electrostimulation of the abdominal viscera, and uncovered the existence of two groups of responses depending upon the state of vigilance. Response from an individual fiber could be detected either during wakefulness or in sleep, but not in both states. Wakefulness-responsive group had lower spiking rates in wakefulness and almost stopped spiking in sleep. Sleep-responsive retained substantial spiking during sleep. These groups also differed in spike amplitudes, indicative of fiber diameter differences; however, both had somatic responses during wakefulness. We suggest a mechanism that utilizes differences in somatic and visceral activities to extract both types of information by varying transmission thresholds, and discuss the implications of this mechanism on functional networks under normal and pathological conditions.


A phylogenetically based secondary structure for the yeast telomerase RNA.
Telomerase is a ribonucleoprotein complex whose RNA moiety dictates the addition of specific simple sequences onto chromosomes ends. While relevant for certain human genetic diseases, the contribution of the essential telomerase RNA to RNP assembly still remains unclear. Phylogenetic analyses of vertebrate and ciliate telomerase RNAs revealed conserved elements that potentially organize protein subunits for RNP function. In contrast, the yeast telomerase RNA could not be fitted to any known structural model, and the limited number of known sequences from Saccharomyces species did not permit the prediction of a yeast specific conserved structure. We cloned and analyzed the complete telomerase RNA loci (TLC1) from all known Saccharomyces species belonging to the "sensu stricto" group. Complementation analyses in S. cerevisiae and end mappings of mature RNAs ensured the relevance of the cloned sequences. By using phylogenetic comparative analysis coupled with in vitro enzymatic probing, we derived a secondary structure prediction of the Saccharomyces cerevisiae TLC1 RNA. This conserved secondary structure prediction includes a central domain that is likely to orchestrate DNA synthesis and at least two accessory domains important for RNA stability and telomerase recruitment. The structure also reveals a potential tertiary interaction between two loops in the central core. The predicted secondary structure of the TLC1 RNA of S. cerevisiae reveals a distinct folding pattern featuring well-separated but conserved functional elements. The predicted structure now allows for a detailed and rationally designed study to the structure-function relationships within the telomerase RNP-complex in a genetically tractable system.


Clustering of mutations blocking synthesis of xanthan gum by Xanthomonas campestris.
Mutations that block the synthesis of xanthan gum by Xanthomonas campestris B1459S-4L-II were isolated as nonmucoid colonies after treatment with ethyl methanesulfonate. Complete libraries of DNA fragments from wild-type X. campestris were cloned into Escherichia coli by using a broad-host-range cosmid vector and then transferred into each mutant strain by conjugal mating. Cloned fragments that restored xanthan gum synthesis (Xgs+; mucoidy) were compared according to restriction pattern, DNA sequence homology, and complementation of a subset of Xgs- mutations. Groups of clones that contained overlapping homologous DNA were found to complement specific Xgs- mutations. The results suggest clustering of the genetic loci involved in xanthan synthesis. The clustering occurred within three unlinked regions. Two forms of complementation were observed. In most instances, independently isolated cosmid clones that complemented a single mutation were found to be partially homologous. Less frequent was the second form of complementation, in which two cosmid clones that lacked any homologous sequences restored the mucoid phenotype to a single mutant. Finally, xanthan production was measured for wild-type X. campestris carrying multiple plasmid copies of the cloned xanthan genes.


The RNA helicases Dbp2 and Mtr4 regulate the expression of Xrn1-sensitive long non-coding RNAs in yeast.
The expression of yeast long non-coding (lnc)RNAs is restricted by RNA surveillance machineries, including the cytoplasmic 5'-3' exonuclease Xrn1 which targets a conserved family of lncRNAs defined as XUTs, and that are mainly antisense to protein-coding genes. However, the co-factors involved in the degradation of these transcripts and the underlying molecular mechanisms remain largely unknown. Here, we show that two RNA helicases, Dbp2 and Mtr4, act as global regulators of XUTs expression. Using RNA-Seq, we found that most of them accumulate upon Dbp2 inactivation or Mtr4 depletion. Mutants of the cytoplasmic RNA helicases Ecm32, Ski2, Slh1, Dbp1, and Dhh1 did not recapitulate this global stabilization of XUTs, suggesting that XUTs decay is specifically controlled by Dbp2 and Mtr4. Notably, Dbp2 and Mtr4 affect XUTs independently of their configuration relative to their paired-sense mRNAs. Finally, we show that the effect of Dbp2 on XUTs depends on a cytoplasmic localization. Overall, our data indicate that Dbp2 and Mtr4 are global regulators of lncRNAs expression and contribute to shape the non-coding transcriptome together with RNA decay machineries.


[Radiosurgical treatment of cervical intraepithelial neoplasia].
In the present study we present our experience and data with loop electrosurgical excision procedures for the treatment of human papilloma virus (HPV)-associated lesions and intraepithelial neoplasia of the cervix. 58 patients underwent loop excision because of colposcopically suspect cervical lesions. In 78 cases cone biopsy (large loop excision of the transformation zone, LLETZ + partial resection of the cervical canal) was performed. In 80% of the loop excisions the lesions were removed with clear resection margins. Patients undergoing LLETZ conization were compared to patients who had a cold knife conization previously. The two groups were matched with regard to age, parity and histology. The cone specimen of patients with LLETZ conization revealed lesion-free margins in 93% compared to 87% in the group with cold knife conization. Operation time and duration of hospital stay were significantly shorter in the group of LLETZ conization. Loop electrosurgical excision procedures therefore represent an adequate method for the treatment of HPV-associated lesions and intraepithelial neoplasia of the cervix.


Analytic expressions for the constitutive parameters of magnetoelectric metamaterials.
Electromagnetic metamaterials are artificially structured media typically composed of arrays of resonant electromagnetic circuits, the dimension and spacing of which are considerably smaller than the free-space wavelengths of operation. The constitutive parameters for metamaterials, which can be obtained using full-wave simulations in conjunction with numerical retrieval algorithms, exhibit artifacts related to the finite size of the metamaterial cell relative to the wavelength. Liu [R. Liu, T. J. Cui, D. Huang, B. Zhao, and D. R. Smith, Phys. Rev. E 76, 026606 (2007)] showed that the complicated, frequency-dependent forms of the constitutive parameters can be described by a set of relatively simple analytical expressions. These expressions provide useful insight and can serve as the basis for more intelligent interpolation or optimization schemes. Here, we show that the same analytical expressions can be obtained using a transfer-matrix formalism applied to a one-dimensional periodic array of thin, resonant, dielectric, or magnetic sheets. The transfer-matrix formalism breaks down, however, when both electric and magnetic responses are present in the same unit cell, as it neglects the magnetoelectric coupling between unit cells [C. R. Simovski, Metamaterials 1, 62 (2007)]. We show that an alternative analytical approach based on the same physical model must be applied for such structures. Furthermore, in addition to the intercell coupling, electric and magnetic resonators within a unit cell may also exhibit magnetoelectric coupling. For such cells, we find an analytical expression for the effective index, which displays markedly characteristic dispersion features that depend on the strength of the coupling coefficient. We illustrate the applicability of the derived expressions by comparing to full-wave simulations on magnetoelectric unit cells. We conclude that the design of metamaterials with tailored simultaneous electric and magnetic response-such as negative index materials-will generally be complicated by potentially unwanted magnetoelectric coupling.


Chickenpox monoarthritis: demonstration of varicella-zoster virus in joint fluid by polymerase chain reaction.
A case of chickenpox monoarthritis is described. The presence of varicella zoster virus (VZV) within the joint was demonstrated by the detection of viral DNA in synovial fluid at a time when peripheral blood cells were negative. This strongly suggests a direct role of VZV in causing monoarthritis complicating chickenpox. The use of the polymerase chain reaction allows more rapid (2 days) confirmation of the diagnosis. Early enough diagnosis would raise the question of using acyclovir to shorten the duration of arthritis.


The attenuation effect of chlorpromazine on electro-acupuncture analgesia: involvement of dopamine system.
The effect of chlorpromazine (CPZ) (0.1 or 0.5 mg/kg, iv) on electroacupuncture analgesia (EAA) was examined by using potassium dolorimetry in rabbits. CPZ itself induced hyperanalgesia, whereas it attenuated EAA in terms of maximal increase of pain threshold as well as EAA after effect. Therefore, CPZ is not a good candidate for enhancing EAA in clinics. Monoamines and their metabolites in cerebrospinal fluid (CSF) of the rabbits were detected by high pressure liquid chromatography coupled to electrochemical detector (HPLC-ECD) method. It was revealed that CPZ enhanced DOPAC and HVA contents in CSF in both the presence and absence of electroacupuncture. CPZ attenuated EAA with elevations of DOPAC and HVA concentration in CSF. There was a positive correlation between the increases of DOPAC and HVA contents in CSF and attenuation effect of CPZ on EAA. These results suggested that activation of dopamine system be unfavorable for EAA.


Facial pain with localized and widespread manifestations: separate pathways of vulnerability.
Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P=0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P=0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P=1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P=0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P=1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background.


Effects of heparin and N-acetyl heparin on ischemia/reperfusion-induced alterations in myocardial function in the rabbit isolated heart.
Evidence is presented that heparin pretreatment produces protective effects on myocardial tissue distinct from its anticoagulant activity. The present study examines the ability of heparin sulfate and N-acetyl heparin (a derivative of heparin devoid of anticoagulant effects) to protect the heart from injury associated with global ischemia and reperfusion. Male New Zealand White rabbits were administered either heparin sulfate (n = 7, 300 U/kg i.v.), N-acetyl heparin (n = 6, 1.73 mg/kg i.v.), or vehicle (n = 6). Two hours after treatment, the hearts were removed, perfused on a Langendorff apparatus, and subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. During reperfusion, creatine kinase concentrations in the coronary sinus effluent were greater in hearts from vehicle-treated rabbits compared with hearts from N-acetyl heparin-treated and heparin-treated rabbits. Left ventricular end-diastolic pressure after 45 minutes of reperfusion in the vehicle-treated group was 64 +/- 15 mm Hg compared with 17 +/- 4 and 10 +/- 3 mm Hg in the heparin-pretreated and N-acetyl heparin-pretreated groups, respectively. Heparin, but not N-acetyl heparin, increased the activated partial thromboplastin time, consistent with its known anticoagulant action. Heparin and N-acetyl heparin inhibited complement-mediated erythrocyte lysis in a concentration-dependent manner. The glycosaminoglycans, in contrast to r-hirudin, reduced complement activation-induced injury in the rabbit isolated heart. The results demonstrate that heparin or N-acetyl heparin, administered to the intact rabbit, protects the isolated heart from subsequent myocardial dysfunction secondary to ischemia/reperfusion. The cardioprotective effects of heparin and N-acetyl heparin are independent of an antithrombin mechanism.


Long noncoding RNA ANRIL regulates endothelial cell activities associated with coronary artery disease by up-regulating CLIP1, EZR, and LYVE1 genes.
Coronary artery disease (CAD) is the leading cause of death worldwide. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts of > 200 nucleotides and are increasingly recognized as playing functional roles in physiology and disease. ANRIL is an lncRNA gene mapped to the chromosome 9p21 genetic locus for CAD identified by the first series of genome-wide association studies (GWAS). However, ANRIL's role in CAD and the underlying molecular mechanism are unknown. Here, we show that the major ANRIL transcript in endothelial cells (ECs) is DQ485454 with a much higher expression level in ECs than in THP-1 monocytes. Of note, DQ485454 expression was down-regulated in CAD coronary arteries compared with non-CAD arteries. DQ485454 overexpression significantly reduced monocyte adhesion to ECs, transendothelial monocyte migration (TEM), and EC migration, which are critical cellular processes involved in CAD initiation, whereas siRNA-mediated ANRIL knockdown (KD) had the opposite effect. Microarray and follow-up quantitative RT-PCR analyses revealed that the ANRIL KD down-regulated expression of AHNAK2, CLIP1, CXCL11, ENC1, EZR, LYVE1, WASL, and TNFSF10 genes and up-regulated TMEM100 and TMEM106B genes. Mechanistic studies disclosed that overexpression of CLIP1, EZR, and LYVE1 reversed the effects of ANRIL KD on monocyte adhesion to ECs, TEM, and EC migration. These findings indicate that ANRIL regulates EC functions directly related to CAD, supporting the hypothesis that ANRIL is involved in CAD pathogenesis at the 9p21 genetic locus and identifying a molecular mechanism underlying lncRNA-mediated regulation of EC function and CAD development.


Biomechanical Comparison of Perpendicular Versus Oblique In Situ Screw Fixation of Slipped Capital Femoral Epiphysis.
Percutaneous in situ single screw fixation is the preferred treatment for stable and unstable slipped capital femoral epiphysis (SCFE). The recommended screw placement is in the center of the epiphysis and perpendicular to the physis, which necessitates an anterior starting point for most SCFEs. A recent clinical study has shown good clinical results with a laterally based screw for SCFE, which is oblique to the physis. We sought to biomechanically compare these 2 techniques for load to failure and hypothesized that the laterally based oblique screw is equivalent or superior to an anteriorly based perpendicular screw. Twenty-two paired immature porcine femurs were used to compare the techniques. A SCFE model was created in all femurs using a previously published technique by performing a 30-degree posterior closing wedge osteotomy through the proximal physis. In the control group, a screw was placed perpendicular to the slip with an anterior starting point. In the experimental group, the screw was started as close to the mid-lateral cortex of the proximal femur as possible while maintaining the screw anterior to the posterior cortex of the femoral neck and ending at the apex of the epiphysis ignoring the resultant angle to the physis for the experimental group. The specimens were then potted and loaded in a physiologically relevant posteroinferior direction (30 degrees posterior from vertical) to determine load to failure (N) and stiffness (N/mm). No statistical difference was found between the 2 groups in maximum load to failure or stiffness (P>0.05). A laterally based screw oblique to the physis for in situ fixation in mild SCFE is not significantly different than an anteriorly based screw perpendicular to the physis in load to failure and stiffness in our study model. In light of no difference in load to failure of these 2 constructs, surgeons may be more comfortable with the traditional lateral entry point while still aiming for screw placement in the center of head.


It's easy to like or dislike Tony Blair: accessibility experiences and the favourability of attitude judgments.
The present study investigated the circumstances under which accessibility experiences would impact the favourability of political attitudes. Participants who were either interested or uninterested in British politics generated either two (or five) positive (or negative) attributes about Tony Blair before indicating their attitude toward him. The results revealed that politically uninterested participants rated Blair more favourably when they had accessed either a small number of positive attributes or a large number of negative attributes. The favourability ratings of politically interested participants were unaffected by the number and type of accessed attributes. Implications of the findings on the nature of accessibility experiences and attitudes are discussed.