A gene on human chromosome 6 functions in assembly of tissue-specific adenosine deaminase isozymes.
In human tissues, adenosine deaminase (ADA) (adenosine aminohydrolase; EC 188.8.131.52) activity can be separated by gel electrophoresis into several isozymes. A structural gene (ADA) on chromosome 20 codes for the "erythrocyte" isozyme, ADA-1, which is also expressed in some nonerythroid tissues. Nonerythroid cells also differentially express five ADA "tissue isozymes" of a greater molecular weight than ADA-1. Each ADA tissue isozyme has a characteristic electrophoretic mobility and tissue distribution. It has been suggested that these ADA tissue isozymes are composed of ADA-1 and other components. We report that the expression of one of these tissue isozymes, ADA-d, is dependent upon ADA on chromosome 20 and another gene on chromosome 6 which functions in the assembly of the ADA tissue isozymes. In human-mouse hybrids segregating human chromosomes, chromosome 6(+),20(+) hybrids express both ADA-1 and ADA-d; chromosome 6(-),20(+) hybrids express only ADA-1; while 6(+),20(-) hybrids have no human ADA activity. ADA-d formation also occurs in vitro by self-assembly when an extract of human erythrocytes or chromosome 6(-),20(+) hybrids is mixed with a homogenate of chromosome 6(+),20(-) hybrids. The gene on chromosome 6, designated ADCP, codes for an adenosine deaminase complexing protein. The product of ADCP presumably combines with ADA-1 to form the ADA tissue isozymes. The data are consistent with the hypothesis that the distribution of enzymatic activity between ADA-1 and the tissue isozymes depends on the expression of the gene for ADA complexing protein, while the differences in the electrophoretic mobilities of the ADA isozymes, except ADA-1, are generated, as suggested by others, by the degree of glycosylation of the complexing protein.


Expression and Prognostic Significance of CDK8 and β-Catenin in Hepatocellular Carcinoma.
Cyclin-dependent kinase 8 (CDK8) is known to play an important role in the early development and progression of various cancers, and the Wnt/β-catenin pathway is also involved in cancer progression. Nevertheless, relatively little is known about the regulatory mechanisms of the β-catenin pathway in hepatocellular carcinoma (HCC). The complete clinicopathological features of 122 pairs of HCC and adjacent non-tumor tissues were analyzed and immunohistochemistry was used to detect the aberrant expression of CDK8 and β-catenin. Overall survival rates (OSRs) were evaluated using the Kaplan-Meier method and Cox multivariate analysis was used to assess the prognostic values. Aberrant expression of nuclear β-catenin and CDK8 are independent prognostic variables that negatively affect the OSR. The aberrant expression of CDK8 was associated with the dysregulated expression of β-catenin and correlated with a poor prognosis. Inhibition of CDK8 and/or nuclear β-catenin expression pattern could serve as a promising therapeutic strategy for the treatment of HCC.


Prophylaxis of hepatitis B recurrence in post-liver transplantation patients with lamivudine-resistant YMDD mutant.
The most frequently used therapy for post-transplantation recurrence of hepatitis B virus (HBV) infection is lamivudine, but this drug is associated with a high resistance rate due to YMDD mutant. In preliminary reports, adefovir dipivoxil (ADV) has been shown to have activity against lamivudine-resistant strains of HBV. However, clinical experience in treatment of HBV infection after liver transplantation (LT) is still not entirely clear. This study was aimed to evaluate the prophylactic efficacy of ADV plus hepatitis B immunoglobulin (HBIG) in patients with YMDD mutant before LT. From March 2004 to March 2006, 16 patients with chronic hepatitis B had lamivudine-resistant YMDD mutants detected prior to liver transplantation and received treatment with ADV plus additional intramuscular HBIG after LT as prophylaxis against graft reinfection. Tests for liver function, serum HBsAg, anti-HBs (HBIG), HBeAg, anti-HBc, anti-HBe, HBV-DNA, and creatinine were assessed pre- or post-liver transplantation. The median follow-up of these patients post-liver transplantation was 19.4 months. Fifteen patients survived and one patient died of recurrence of hepatocellular carcinoma (HCC). There was significant difference (10.98% vs. 2.26%, P < 0.05) in YMDD mutant rate between the patients with HBV-DNA over 10(6) copies/ml and those with HBV-DNA less than 10(6) copies/ml. Fifteen patients (93.8%) had undetectable HBV-DNA at 4 weeks and 1 (6.3%) at 6 months after LT. No hepatitis B recurrence was detected by persistent testing of HBsAg, HBeAg, and HBV-DNA and no increase of serum creatinine level associated with ADV was observed in any of the patients. ADV combined with intramuscular HBIG can effectively prevent patients with pre-transplantation YMDD mutant from HBV recurrence after LT.


Transcriptional Profiling of Sonic Hedgehog in a Prospective Cohort of Breast Cancer in a Pakistani Population.
Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored. qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed. A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0.0001). A strong positive correlation was seen between SHH and proliferation marker (r=0.635, p=0). SHH expression was significantly high among patients with advanced tumor grade, stage, nodal involvement and metastasis. Furthermore, both luminal-B and triple-negative subtypes of cohort showed increased expression of SHH. Based on these findings, SHH may be used as a potential biomarker for breast carcinogenesis.


Prevalence of SXT/R391-like integrative and conjugative elements carrying blaCMY-2 in Proteus mirabilis.
To characterize the vectors involved in the dissemination of bla(CMY-2) genes in clinical isolates of Proteus mirabilis collected between 1999 and 2007. Plasmid analysis of 19 P. mirabilis carrying ampC genes was performed by PCR-based replicon typing, S1-PFGE and Southern hybridization with ampC and replicon probes. Isolates that could not be characterized were examined for the presence of SXT/R391-like elements. To demonstrate the involvement of these elements in the dissemination of bla(CMY-2), we performed a PCR amplification of the integrase (int) and toxin/antitoxin (TA) genes from SXT/R391-like integrative conjugative elements (ICEs). Later on, I-Ceu-I PFGE gels and hybridization with bla(CMY-2), int and prfC probes were performed. The genetic organization of bla(CMY-2) was also studied. ampC genes were located on large conjugative plasmids in 11 of the 19 (58%) P. mirabilis studied. However, in eight of these isolates a plasmid was not involved in the mobilization of ampC genes. I-Ceu-I PFGE and hybridization analyses revealed that bla(CMY-2) were chromosomally located in these eight P. mirabilis isolates. The genetic organization of bla(CMY-2) and hybridization analyses revealed that bla(CMY-2) was carried by an ICE almost identical to ICEPmiJpan1 in seven out of these eight isolates. The prevalence of ICEs carrying bla(CMY-2) was surprisingly high [37% (7 out of 19)]. This is the first study giving prevalence data on ICEs carrying bla(CMY-2) genes. These results suggest the need to study these mobile genetic elements in the context of dissemination of acquired AmpC β-lactamases and also of other β-lactamases, such as extended-spectrum β-lactamases and carbapenemases.


Induction of Biological Apatite Orientation as a Bone Quality Parameter in Bone Regeneration Using Hydroxyapatite/Poly ɛ-Caprolactone Composite Scaffolds.
Changes in the biological apatite (BAp) c-axis orientation were investigated as a bone quality parameter in bone regeneration using hydroxyapatite/poly ɛ-caprolactone (HA/PCL) composite scaffolds. Three-dimensional (3D) HA/PCL composite scaffolds were fabricated using a layer manufacturing process in three grid sizes (200-, 600-, and 1000 μm) and grafted into the forearm ulna of New Zealand white rabbits. The cross-sectional areas of the bones regenerated from the scaffolds with 600- and 1000-μm grid sizes were significantly larger than those from the scaffold with 200-μm grid sizes, whereas bone mineral density in the regenerated regions did not differ between the three grid sizes. Moreover, the BAp c-axis orientation in the bones regenerated from the scaffolds with grid sizes of 600- and 1000 μm was not significantly different; however, both scaffolds showed enhanced BAp orientation, although the degree of BAp orientation was lower than that in intact bones. In conclusion, HA/PCL composite 3D scaffolds with 600- and 1000-μm grid sizes induced BAp c-axis orientation and showed good bone regeneration behavior in vivo.


The synthesis and structural characterisation of [Ru(eta-Cp)(dppf)SnBr3].
The reaction of [Ru(eta-Cp)(dppf)N(3)] (1) with equimolar amount of SnBr(2) yielded an interesting heterotrimetallic compound [Ru(eta-Cp)(dppf)SnBr(3)] (2) (dppf: 1,1'-bis-diphenylphosphinoferrocene). Compounds 1 and 2 were characterised by IR, NMR (1H, 13C, 31P and 119Sn), and 2, additionally, by 57Fe and 119Sn Mössbauer spectroscopy and X-ray crystallography. The latter results were as follows: monoclinic, C2/c, a = 32.8879(4)A, b = 11.9888(2)A, c = 20.8986(3)A, beta = 92.545(1)degrees, V = 8231.9(2)A(3), Z =8.


Lycopene - antioxidant with radioprotective and anticancer properties. A review.
Ionizing radiation may cause damage to living tissue by producing free radicals like reactive oxygen species (ROS). ROS can randomly react with lipids, proteins and nucleic acids of cell causing oxidative stress and damage in these macromolecules, leading to pathogenesis of chronic diseases and age related and also cancer. The first line of defense from the damaging effects of ROS is antioxidants, which convert the oxidants to less reactive species. Lycopene (LYC) is an acyclic isomer of beta-carotene. It synthesized by plants or autotrophic bacteria but not by animals. Red fruits and vegetables, including tomatoes, watermelons, pink grapefruits, apricots, pink guavas and papaya contain LYC. This carotenoid has very strong antioxidant properties. The many studies confirm that dietary supplementation with LYC reduces risk of cancers of many organs, but also retard the growth of the tumors. LYC has also chemopreventive effects against other diseases such as cardiovascular disease, osteoporosis, male infertility and inhibits the toxic action of other agents. Numerous in vitro and animal studies showed that LYC may provide protection against damages induced by ionizing radiation. It suggests that supplementation of LYC might be useful in diminishing of negative effect of cancer radiotherapy or in mitigating the effects of possible radiation accidents on human health. lycopene, antioxidants, anticarcinogenic agents, radioprotection.


Orofacial cysticercosis: Report of a rare case with review of literature.
Cysticercosis is common in developing countries in which the combination of rural society, crowding, and poor sanitation facilities allows greater contact between humans and pigs and thus more opportunities for fecal contamination of food and water occurs. They are rarely located in oral and perioral tissues, particularly in the muscles of mastication, muscle of the facial expression, suprahyoid muscles, and postcervical musculature and also as in the tongue, buccal mucosa, and lip. Cysticercosis is a potentially fatal parasitic disease that rarely found in the maxillofacial region in humans. This paper reports the case of a young female patient presented with isolated lesion of cysticercosis involving buccinator muscle. In conclusion, we suggest that cysticercosis should be considered in the differential diagnosis of intraoral solitary nodules within the oral and maxillofacial region, especially in endemic areas. High-resolution ultrasonography is an excellent noninvasive and cost-effective modality for the diagnosis and also suggests that localized parasitic infections such as Cysticercus cellulosae can be successfully treated with conservative management using oral antiparasitic (antihelminthic) medication.


Large tunable valley splitting in edge-free graphene quantum dots on boron nitride.
Coherent manipulation of the binary degrees of freedom is at the heart of modern quantum technologies. Graphene offers two binary degrees: the electron spin and the valley. Efficient spin control has been demonstrated in many solid-state systems, whereas exploitation of the valley has only recently been started, albeit without control at the single-electron level. Here, we show that van der Waals stacking of graphene onto hexagonal boron nitride offers a natural platform for valley control. We use a graphene quantum dot induced by the tip of a scanning tunnelling microscope and demonstrate valley splitting that is tunable from -5 to +10 meV (including valley inversion) by sub-10-nm displacements of the quantum dot position. This boosts the range of controlled valley splitting by about one order of magnitude. The tunable inversion of spin and valley states should enable coherent superposition of these degrees of freedom as a first step towards graphene-based qubits.


Atrial fibrillation and anticoagulation in patients with breast cancer.
Objectives. To examine the long-term risk of thromboembolism and bleeding in patients with atrial fibrillation comparing patients with and without recent breast cancer in subgroups with or without anticoagulation therapy, respectively. Design. Using nationwide registries, patients with breast cancer from 1998-2015 and subsequent atrial fibrillation within 3 years were stratified on anticoagulation and matched 1:3 on age, sex and comorbidities with atrial fibrillation patients without breast cancer. Risks of thromboembolism and bleeding were estimated by Aalen-Johansen and multivariable cox regression models. Results. Atrial fibrillation patients with and without anticoagulation were matched, respectively (201 and 525 with breast cancer matched with 603 and 1,575 without breast cancer). In patients with CHA2DS2-VASc-score >1 and anticoagulation the three years risks of thromboembolism were 4.2% (95% confidence interval (CI) 1.1-7.3) and 3.2% (CI 1.5-4.9) in patients with and without breast cancer. The risks of bleeding were 5.3% (CI 1.7-8.9) and 5.1% (CI 3.0-7.1), respectively. Breast cancer was associated with a similar risk of thromboembolism in patients with and without anticoagulation, respectively (Hazard ratio (HR) 1.10, CI 0.63-1.92 and HR 1.11, CI 0.82-1.50) and a similar risk of bleeding in patients with and without anticoagulation, respectively (HR 1.01, CI 0.56-1.84 and HR 0.85, CI 0.57-1.27) compared with the matched controls. Conclusions. Breast cancer was not associated with altered risk of thromboembolism or bleeding in patients with atrial fibrillation irrespective of treatment with anticoagulation. Our analyses suggest that atrial fibrillation diagnosed in patients with breast cancer should be considered as primary atrial fibrillation.


Activation of type B T cells after protein immunization reveals novel pathways of in vivo presentation of peptides.
Type B T cells recognize a peptide-MHC conformer generated in recycling endosomes and eliminated by H2-DM in late endosomes; as a result, they recognize exogenous peptide, but fail to respond to the identical epitope generated from the native protein. To investigate the behavior of these cells in vivo, we generated mice transgenic for a type B TCR recognizing the 48-62 epitope of hen egg white lysozyme (HEL) presented by I-A(k). Type B T cells responded only to peptide ex vivo, but responded in vivo to immunization with either protein or peptide in the presence of Freund's adjuvant or LPS. Presentation of the type B conformer was MyD88-independent, evident within 24 h after HEL immunization, and restricted to the CD11b/c(+) APC subset. Immunization with listeriolysin O, a potent inducer of cell death, also primed type B T cells in vivo, and transfer of HEL-bearing allogeneic dendritic cells activated type B T cells. We conclude that a number of conditions in vivo, some of which induce inflammation and cell death, lead to peptide presentation through mechanisms distinct from the classical pathways involving H-2DM molecules.


A disappearing urban/rural blood pressure difference in Nigerian children: an evaluation of possible determining factors.
Urban Nigerian school children are reported to have a higher systolic blood pressure and diastolic blood pressure than rural community school children until the age of 11-12 years when this difference tends to disappear. We evaluated 874 urban day-school children and 674 rural community school children aged 5-16 (mean 11.9) years in south-eastern Nigeria to confirm this changing pattern, and to assess the contributions of some known factors to the differences as well as the changing pattern. This study confirmed the changing pattern of urban/rural blood pressure of school children. Differences in weight, height and Body Mass Index (BMI), though important, appeared insufficient to explain this pressure difference and the changing pattern. Urban children aged 12-14 years were found to excrete more sodium and (unexpectedly) more potassium in their 24-h urine samples. The observed urban/rural blood pressure difference appears to be sustained by a multiplicity of factors, including differences in weight, BMI, height, electrolytes (especially sodium) consumption, and increased exposure to Western-type education.


Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine.
The first three-dimensional structure of a DNA methyltransferase is presented. The crystal structure of the DNA (cytosine-5)-methyltransferase, M.HhaI (recognition sequence: GCGC), complexed with S-adenosyl-L-methionine has been determined and refined at 2.5 A resolution. The core of the structure is dominated by sequence motifs conserved among all DNA (cytosine-5)-methyltransferases, and these are responsible for cofactor binding and methyltransferase function.


Testing Decision Level (DL) and Minimum Detectable Amount (MDA) for Hanford In Vivo Counting Systems.
Testing the decision level (DL) and minimum detectable amount (MDA) of a radionuclide for a direct bioassay (in vivo) counting system is a requirement for in vivo monitoring programs across the DOE complex. Bottle manikin absorption (BOMAB) and torso phantoms are used in conjunction with point sources to facilitate the testing. This paper describes a method of testing the DL and MDA values of in vivo counting systems with equipment commonly used by in vivo programs. This method is cost effective and minimizes waste since the radiological sources used can have broad ranges for decay activities. The results from the testing indicated that the current DL and MDA values are valid for the equipment and methods used at the Hanford in vivo counting facility.


Nanostructural reorganization of bacterial cellulose by ultrasonic treatment.
In this work, bacterial cellulose was subjected to a high-power ultrasonic treatment for different time intervals. The morphological analysis, scanning electron microscopy, and atomic force microscopy revealed that this treatment changed the width and height of the microfibrillar ribbons and roughness of their surface, originating films with new nanostructures. Differential thermal analysis showed a higher thermal stability for ultrasonicated samples with a pyrolysis onset temperature of 208 degrees C for native bacterial cellulose and 250 and 268 degrees C for the modified samples. The small-angle X-ray scattering experiments demonstrated that the treatment with ultrasound increased the thickness of the ribbons, while wide-angle X-ray scattering experiments demonstrated that the average crystallite dimension and the degree of crystallinity also increased. A model is proposed where the thicker ribbons and crystallites result from the fusion of neighboring ribbons due to cavitation effects.


A dose-ranging study of MF59(®)-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination.
During development of an A/H1N1 pandemic influenza vaccine, this study was performed to identify the antigen and adjuvant content which would provide optimal antibody response and persistence in adults and the elderly. Dose-sparing strategies, such as inclusion of adjuvants, are critical in ensuring the widest possible population coverage in the event of an influenza pandemic, despite a limited global capacity for vaccine manufacture. Healthy subjects aged 18-64 years (n = 1240) and ≥65 years (n = 1352) were vaccinated with 1 of 8 investigational vaccine formulations varying in antigen quantity (3.75 µg to 30 µg of hemagglutinin) and MF59(®) adjuvant (none, half dose, or full dose). All subjects received 2 vaccine doses administered 3 weeks apart. Antibody response was assessed by hemagglutination inhibition assay 1 and 3 weeks after administration of first and second doses. Antibody persistence was assessed after 6 and 12 mo. Vaccine safety was monitored over 12 mo. All 8 investigational A/H1N1 vaccine formulations were well tolerated, and rapidly induced high antibody titers which met all of the Center for Biologics Evaluation and Research (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria 3 weeks after one dose. The highest antibody titers were observed in participants vaccinated with higher quantities of antigen and adjuvant. A single vaccine dose containing 3.75 µg of A/California/7/2009 (H1N1) antigen with MF59 adjuvant was identified as optimal for young to middle-aged (18-64 years) and older (≥65 years) adult populations.


Lifestyle interventions after ablation for atrial fibrillation: a systematic review.
Risk factors of atrial fibrillation include diabetes, obesity and physical inactivity. Positive effects such as decreased atrial fibrillation burden have been reported for atrial fibrillation patients who have participated in lifestyle changing interventions after atrial fibrillation ablation treatment. The aim of this study was to assess the evidence on the benefits and harms of lifestyle and risk factor management interventions in patients undergoing atrial fibrillation ablation. Our systematic review searched MEDLINE, EMBASE, CINAHL, Psychinfo, Web of Science and CENTRAL using key terms related to atrial fibrillation and lifestyle, including interventional trials. The primary outcomes were mortality and serious adverse events. Random effects meta-analyses of outcomes were conducted when appropriate. Two randomised controlled trials and two non-randomised interventional trials with a total of 498 patients were included. Six primary events were reported for the intervention groups and five events for the control groups (relative risk of 1.03, 95% confidence interval (CI) 0.3 to 3.1, I2 0%, P = 0.537). Effects in favour of the intervention groups were found for atrial fibrillation frequency (0.82 points, 95% CI -1.60 to -0.03, I2 87.3%, P = 0.005), atrial fibrillation duration (-0.76 points, 95% CI -1.64 to 0.12, I2 89.1%, P = 0.002) and body mass index (-5.40 kg/m2, 95% CI 6.22 to -2.57, I2 83.9%, P = 0.013). Risk of bias in the four studies was judged to be low to moderate. Lifestyle changing interventions seem to have a positive effect on outcomes relevant to patients undergoing atrial fibrillation ablation, but the included studies were small, interventions were inhomogeneous, and the quality of evidence was low to moderate. More studies are warranted.


Crystallographic analysis of phosphoglycerate kinase from the hyperthermophilic bacterium Thermotoga maritima.
Phosphoglycerate kinase from the hyperthermophilic bacterium Thermotoga maritima has been co-crystallized with its substrate 3-phosphoglycerate and the ATP analogue AMP-PNP using the vapour diffusion method. Crystals were obtained from a solution containing polyethylene glycol (MW 3000/8000) as precipitating agent. A complete diffraction data set from orthorhombic crystals was collected up to 2.0 A resolution. The TmPGK crystallizes in the space group P2(1)2(1)2 (cell dimensions: a = 62.0 A, b = 76.9 A, c = 87.5 A) with one molecule in the asymmetric unit. The structure was solved by Patterson search methods using Bacillus stearothermophilus PGK as a search model and was refined to a crystallographic R factor of 22.0%. Compared to the enzyme from B. stearothermophilus, horse, pig and yeast, the Thermotoga enzyme exhibits a drastically reduced interdomain angle, similar to the one reported for PGK from Trypanosoma brucei. Here we present crystallographic data of the first high-resolution structure of a PGK in largely closed conformation, complexed with the two products of the catalyzed reaction, and, at the same time, the first PGK structure from a hyperthermophilic organism.


On the alert for pregnancy-induced hypertension.
Increasing the skills of maternal-child home care nurses can identify early incidences of pregnancy-induced hypertension (PIH) for medical intervention, resulting in the prevention of hospitalization and decrease of potential complications. This article describes one agency's approach to teaching staff these important skills.


News from the Biological Stain Commission No. 14.
In the 14(th) issue of News from the Biological Stain Commission (BSC) the BSC's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 3, In vitro diagnostic products, and from the final plenary meeting of ISO/TC 212, Clinical laboratory testing and in vitro diagnostic test systems, held on 17-19 October 2011 in Las Vegas, NV. Information is also presented from the 26th meeting of CEN/TC 140, In vitro diagnostic medical devices, held on 5 December 2011 in Berlin, Germany.


Effectiveness of the Disinfection of Reusable Make-Up Applicators-Initial Experiences.
Make-up accessories may be subjected to bacterial contamination due to their contact with many surfaces, including the client's skin. Disinfection prevents the spread of infection, but the capacity to eliminate microorganisms varies among disinfection methods. Little is known about disinfection in beauty salons; therefore, we aimed to compare the effectiveness of disinfectants for reusable make-up applicators. We tested reusable make-up applicators (natural brush, synthetic brush, and sponge) with disinfectants (bactericidal soap, 70% ethanol, and Hydro Sept solution). The number of microorganisms present before and after disinfection using the plate method was assessed. In comparison to water, bactericidal soap reduced the number of bacterial colonies. There were 418 versus 83 colonies in natural brush samples, 1,162 versus nine colonies in synthetic brush samples, and 617 versus three colonies in sponge samples. Ethanol eliminated 100% of bacterial growth. Disinfection was more effective on applicators used for dry products (natural brush) than for wet products (sponge, synthetic brush). We conclude that disinfection is a complex process and depends on the type of make-up applicator being disinfected and the type of cosmetics being used. Further research on the selection of appropriate disinfection procedures for individual applicants and for those who prepare makeup is needed.


A Case of Strongyloidiasis: An Immigrant Healthcare Worker Presenting with Fatigue and Weight Loss.
Strongyloides stercoralis is an intestinal nematode parasite classified as a soil-transmitted helminth, endemic in tropical and subtropical regions. Strongyloides stercoralis can remain dormant for decades after the initial infection. We describe a patient who was diagnosed with Strongyloides stercoralis infection three weeks after a left inguinal hernia repair and discuss approaches to prevention, diagnosis, and treatment. Physicians in the United States often miss opportunities to identify patients with chronic strongyloidiasis. Symptoms may be vague and screening tests have limitations. We review current strategies for diagnosis and treatment of chronic intestinal strongyloidiasis in immigrant patients who have significant travel history to tropical regions and discuss the clinical features and management of the infection.


Se-methylselenocysteine inhibits apoptosis induced by clusterin knockdown in neuroblastoma N2a and SH-SY5Y cell lines.
Apoptosis, as a programmed cell death process, is essential for the maintenance of tissue function in organisms. Alteration of this process is linked to many diseases. Over-expression of clusterin (Clu) can antagonize apoptosis in various cells. Selenium (Se) is an essential trace element for human health. Its biological function is also associated with cell apoptosis. To explore the function of Clu and the impact of Se in the process of apoptosis, several short-hairpin RNAs (shRNA) were designed for the construction of two sets of recombinant plasmids: one set for plasmid-transfection of mouse neuroblastoma N2a cells (N2a cells); and the other set for lentiviral infection of human neuroblastoma SH-SY5Y cells (SH-SY5Y cells). These shRNAs specifically and efficiently interfered with the intracellular expression of Clu at both the mRNA and protein levels. The Clu-knockdown cells showed apoptosis-related features, including down-regulation of antioxidative capacity and the Bcl-2/Bax ratio and up-regulation of caspase-8 activity. Se-methylselenocysteine (MSC) at an optimum concentration of 1 μM could reverse the alteration in antioxidative capacity, Bcl2/Bax ratio and caspase-8 activity caused by Clu-knockdown, thus inhibiting apoptosis and maintaining cell viability. The results hereby imply the potentiality of Clu and Se in neuroprotection.


The use of normalized cross-correlation analysis for automatic tendon excursion measurement in dynamic ultrasound imaging.
The work describes an automated method of tracking dynamic ultrasound images using a normalized cross-correlation algorithm, applied to the patellar and gastrocnemius tendon. Displacement was examined during active and passive tendon excursions using B-mode ultrasonography. In the passive test where two regions of interest (2-ROI) were tracked, the automated tracking algorithm showed insignificant deviations from relative zero displacement for the knee (0.01 ± 0.04 mm) and ankle (-0.02 ± 0.04 mm) (P > .05). Similarly, when tracking 1-ROI the passive tests showed no significant differences (P > .05) between automatic and manual methods, 7.50 ± 0.60 vs 7.66 ± 0.63 mm for the patellar and 11.28 ± 1.36 vs 11.17 ± 1.35 mm for the gastrocnemius tests. The active tests gave no significant differences (P > .05) between automatic and manual methods with differences of 0.29 ± 0.04 mm for the patellar and 0.26 ± 0.01 mm for the gastrocnemius. This study showed that automatic tracking of in vivo displacement of tendon during dynamic excursion under load is possible and valid when compared with the standardized method. This approach will save time during analysis and enable discrete areas of the tendon to be examined.


(5-Benzoyl-3,6-dimeth-oxy-naphthalen-2-yl)(phen-yl)methanone.
The asymmetric unit of the title compound, C(26)H(20)O(4), contains two independent conformers. The aromatic rings of the aroyl groups are twisted with respect to the naphthalene ring systems to form dihedral angles of 66.58 (6) and 66.45 (6)° in one conformer, and 75.00 (7) and 81.17 (6)° in the other conformer. The crystal packing is stabilized by weak inter-molecular C-H⋯O hydrogen bonds and by C-H⋯π inter-actions.


High efficiency Brillouin random fiber laser with replica symmetry breaking enabled by random fiber grating.
We report a high efficiency Brillouin random fiber laser (BRFL) enabled by a random fiber grating (RFG) with demonstration of replica symmetry breaking (RSB). The RFG was characterized by optical coherence tomography (OCT) method, which measured the spatially resolved reflectivity of RFG by a tunable delay line. Multiple narrow linewidth peaks appeared in reflection spectrum of RFG, created by frozen scattering centers acting as narrow linewidth filters to select random modes in random fiber lasers based on Brillouin gain. With the scattering from RFG as disordered feedback, a BRFL with slope efficiency of 29.3% and lasing threshold of 10.2 mW was demonstrated with 1 kHz linewidth. Intensity dynamics show that RFG can reduce the noise of BRFL with a symmetric phase portrait, indicating the increased mean path length and coherence time of the Stokes photons. The probability distribution of the Parisi overlap parameter of intensity fluctuation spectra from trace to trace reveal a photonic spin-glass phase with RSB in the RFG enabled BRFL, providing a photonic platform to study the photon glassy behavior of random fiber lasers.


Legionella feeleii: Ubiquitous Pathogen in the Environment and Causative Agent of Pneumonia.
L. feeleii is one of the most frequent Legionella species isolated from natural pools of the central region of Spain. This study aimed to evaluate its ecology and to identify this Legionella species as a respiratory pathogen. A PCR assay for detecting the L. feeleii mip gene was developed to identify it in clinical and environmental samples. Culture and PCR were performed in environmental samples from four drinking water treatment plants (DWTPs). Free L. feeleii was only detected in raw water samples (3.4%), while L. feeleii as an Acanthamoeba endosymbiont was found in 30.7% of raw water, 11.5% of decanter biofilm, and 32% of finished water samples. Therefore, Acanthamoeba spp. plays an essential role in the multiplication, persistence, and spread of Legionella species in the environment. The first case of Legionnaires' disease caused by L. feeleii in Spain is described in this study. The case was diagnosed in an older woman through PCR and sequencing from urine and sputum samples. A respiratory infection could be linked with health care procedures, and the patient presented several risk factors (age, insulin-dependent diabetes, and heart disease). The detection of non-L. pneumophila, such as L. feeleii, is a factor that must be considered when establishing or reviewing measures for the control and prevention of legionellosis.


Role of endogenous prostacyclin in myocardial blood flow regulation distal to a severe coronary stenosis.
To test the hypothesis that endogenous prostacyclin is required to maintain reduced arteriolar tone distal to a severe coronary arterial stenosis under basal conditions and during challenge with a vasoconstrictor eicosanoid such as thromboxane A2 10 closed chest, domestic swine were prepared with an artificial stenosis, which reduced the luminal diameter of the left anterior descending coronary artery by 80%. Haemodynamic variables, regional myocardial blood flow (microsphere method), and lactate metabolism were measured at control (1); after infusion of U46619 (thromboxane A2 mimetic) distal to the stenosis at 1 microgram.min-1 for 10 min and 5 micrograms.min-1 for 10 min; at control (2); after indomethacin infusion distal to the stenosis; and after repeat infusion of U46619. At the end of the study the animal hearts were removed and their coronary vessels harvested for in vitro determination of prostacyclin (PGI2) production. Regional myocardial blood flow in all layers of the heart distal to the stenosis did not change compared with control during the initial 1 microgram.min-1 dose of U46619 but was reduced significantly after the 5 micrograms.min-1 dose (approximately 20% vs control). Distal zone flow (all layers) returned to baseline at control (2) and remained unchanged after indomethacin infusion. Although distal zone flows were reduced significantly in response to the second 5 micrograms.min-1 dose, the reduction in each layer after indomethacin was comparable to that observed with the 5 micrograms.min-1 dose before indomethacin infusion. Finally, the in vitro production of PGI2 by coronary vessels was considerably impaired by indomethacin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


[Syndrome of mild encephalopathy with a reversible splenial corpus callosum lesion].
Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome that has been associated with a variety of underlying etiologies including viral and bacterial infections, epilepsy and antiepileptic drug cessation, hypoglycemia and electrolyte imbalance. We report a case of a 24-year-old woman who had an isolated splenial lesion in the corpus callosum on neuroimaging associated with MERS.


Maternal Thinness and Obesity and Customized Fetal Weight Charts.
The aim of the study was to determine if customized fetal growth charts developed excluding obese and underweight mothers (CC(18.5-25)) are better than customized curves (CC) at identifying pregnancies at risk of perinatal morbidity. Data from 20,331 infants were used to construct CC and from 11,604 for CC(18.5-25), after excluding the cases with abnormal maternal BMI. The 2 models were applied to 27,507 newborns and the perinatal outcomes were compared between large for gestational age (LGA) or small for gestational age (SGA) according to each model. Logistic regression was used to calculate the OR of outcomes by the group, with gestational age (GA) as covariable. The confidence intervals of pH were calculated by analysis of covariance. The rate of cesarean and cephalopelvic disproportion (CPD) were higher in LGAonly by CC(18.5-25) than in LGAonly by CC. In SGAonly by CC(18.5-25), neonatal intensive care unit (NICU) and perinatal mortality rates were higher than in SGAonly by CC. Adverse outcomes rate was higher in LGAonly by CC(18.5-25) than in LGAonly by CC (21.6%; OR = 1.61, [1.34-193]) vs. (13.5%; OR = 0.84, [0.66-1.07]), and in SGA only by CC(18.5-25) than in SGAonly by CC (9.6%; OR = 1.62, [1.25-2.10] vs. 6.3%; OR = 1.18, [0.85-1.66]). The use of CC(18.5-25) allows a more accurate identification of LGA and SGA infants at risk of perinatal morbidity than conventional CC. This benefit increase and decrease, respectively, with GA.


What is atopy? Sidestepping semantics.
Atopy may be viewed as the manifestation of a still-undefined defect. It is characterized by certain clinical findings and frequently by derangements of the immune and autonomic nervous systems. The atopic diseases are a group of seemingly unrelated conditions--eczema, asthma, rhinitis, and perhaps hypertrophic sinusitis, vernal conjunctivitis, and migraine--which cluster in individuals and families. In the respiratory tract and eye, eosinophils in tissues and secretions are characteristic and are not dependent on the presence of immediate hypersensitivity. Symptoms suggestive of mast-cell mediator release are common to all the atopic diseases, and there is some evidence that nonimmunologic mediator release is enhanced in atopic patients. In the most clearly defined atopic diseases, eczema and asthma, approximately 80% of patients have increased IgE responses to normal environmental allergens. Accompanying and perhaps underlying the enhanced IgE responses are deficiencies of T cell numbers and function, particularly in suppressor T lymphocytes. Evidence exists that decreased beta 2-adrenergic function and increased cholinergic and alpha-adrenergic responsiveness accompany and perhaps underlie the atopic diseases, whether allergic or nonallergic.


Informal speech processes can be categorical in nature, even if they affect many different words.
This paper investigates the nature of reduction phenomena in informal speech. It addresses the question whether reduction processes that affect many word types, but only if they occur in connected informal speech, may be categorical in nature. The focus is on reduction of schwa in the prefixes and on word-final /t/ in Dutch past participles. More than 2000 tokens of past participles from the Ernestus Corpus of Spontaneous Dutch and the Spoken Dutch Corpus (both from the interview and read speech component) were transcribed automatically. The results demonstrate that the presence and duration of /t/ are affected by approximately the same phonetic variables, indicating that the absence of /t/ is the extreme result of shortening, and thus results from a gradient reduction process. Also for schwa, the data show that mainly phonetic variables influence its reduction but its presence is affected by different and more variables than its duration, which suggests that the absence of schwa may result from gradient as well as categorical processes. These conclusions are supported by the distributions of the segments' durations. These findings provide evidence that reduction phenomena which affect many words in informal conversations may also result from categorical reduction processes.


trk immunoreactivity at neuronal dendrite and cell body.
Neurotrophins homologous to the nerve growth factor (NGF) bind the neurotrophic receptors of the trk gene family. Since the target tissues release these neurotrophic factors to the neuron, it has been believed that their trophic effects are mediated by the retrograde axonal transport. However it remains an open question whether the neurotrophins act through the autocrine or the paracrine mechanisms, since the protein-level expression of trk has not been studied so far. We have made polyclonal antibodies against the recombinant proteins of chicken trkC and rat trkB. These antibodies showed immunoreactivity at the dendrite and the cell body of neuron. This subcellular localization strongly suggests the autocrine or the paracrine mechanism of the neurotrophic factors. At the same time, our data provide basic knowledge to decide where to deliver these neurotrophic factors in the therapy of neurodegenerative diseases.


Effects of pharmacologically manipulated amplitude and starting point on edinger-westphal-stimulated accommodative dynamics in rhesus monkeys.
The aim of this study was to determine whether pharmacologically manipulated resting refraction, amplitude, and starting point affect accommodative and disaccommodative dynamics in anesthetized adolescent rhesus monkeys. Pilocarpine and atropine were applied topically to manipulate resting refraction, accommodative amplitude, starting point, and end point in two monkeys with permanent electrodes in the Edinger-Westphal nucleus. Accommodation was centrally stimulated with submaximal and maximal current amplitudes. Dynamic accommodative responses were measured with infrared photorefraction before and during the course of action of the drugs. Accommodative and disaccommodative dynamics were analyzed in terms of peak velocity as a function of amplitude, starting point, and end point. Pilocarpine caused a myopic shift in resting refraction of 11.62 +/- 1.17 D. Centrally stimulated accommodative amplitude was 10.08 +/- 1.15 D before pilocarpine and 0.68 +/- 0.29 D after pilocarpine. Changes were found in accommodative dynamics as a function of starting point and in disaccommodative dynamics as a function of amplitude and end point. Accommodative amplitude was 11.25 +/- 0.18 D before atropine administration and 0.52 +/- 0.11 D after atropine administration. Accommodative dynamics as a function of amplitude were not substantially altered during the course of pilocarpine-induced accommodation or atropine-induced cycloplegia. Accommodative response amplitude is reduced with pilocarpine by shifting the eye to a more myopic state and with atropine by cycloplegia. Pharmacologic manipulations showed that accommodative and disaccommodative dynamics in anesthetized monkeys depend on amplitude, starting point, and end point of the response and on the contributions of neural and receptor activity.


Work values and communication styles among Generation X, Y, and Z nurses: A cross-sectional study.
To compare and contrast nurses' work values and communication styles across Generation X, Y, and Z. Intergenerational differences in the work values of nurses are well known, but the commonalities remain largely uninvestigated. It is also unclear if there are intergenerational differences and commonalities in the rhetorical communication style of nurses. This study used a cross-sectional research design. Participants were 243 nurses of Generation X (n = 78), Y (n = 86), and Z (n = 79) working at a general hospital in Korea. Structured questionnaires were used to collect the data from September to October 2019. The differences in work values and communication types were measured and analyzed using the χ2 test. The work values of Generation X differed from those of Generation Y and Z, who preferred extrinsic work values. There was no significant intergenerational difference in communication types, although Generation X and Y were similar to each other in communication types and different from Generation Z. Although the work values of the three generations are different, their communication styles are similar so that they may reduce the generational gap through communication. In particular, Generation Y nurses prefer extrinsic work values and share some work values with Generation Z; however, the dominant communication type of Generation Y is similar to Generation X, not Z. Therefore, Generation Y could play a key role in connecting Generation X with Z during communication. Nursing organizations should delegate the authority to Generation Y so that Y may have a voice in the nursing group as the mediator between X and Z.


The association between maternal intra-abdominal pressure and hypertension in pregnancy.
Pregnancy leads to a state of chronically increased intra-abdominal pressure (IAP) caused by a growing fetus, fluid, and tissue. Increased intra-abdominal pressure is leading to state of Intra-Abdominal Hypertension (IAH) and Abdominal Compartment Syndrome. Clinical features and risk factors of preeclampsia is comparable to abdominal compartment syndrome. IAP may be associated with the hypertension in pregnancy (HIP). The study aimed to determine the antepartum and postpartum IAP levels in women undergoing caesarean delivery (CD) and association between hypertension in pregnancy, and antepartum and postpartum IAP levels in women undergoing CD. Seventy pregnant women (55 normotensive, 15 HIP) undergoing antepartum, non-emergency CD, had their intravesical pressure measured before and after the CD, the intravesical pressure measurements obtained with the patient in the supine position were considered to correspond to the IAP. Multivariable linear regression models were used to study associations between intraabdominal pressure and baseline characteristics in normotensive pregnancies and hypertensive pregnancies. In normotensive pregnancies at mean gestation age of 38.2 weeks (95%CI 37.9 to 38.6), mean antepartum IAP was 12.7 mmHg(95%CI 11.6 to 13.8) and the mean postpartum IAP was 7.3 mmHg (95% CI 11.6 to 13.8). Multivariable linear regression models showed HIP group antepartum IAP positively associated with coefficient value of 1.617 (p = 0.268) comparing with normotensive pregnancy group. Postpartum IAP in HIP group positively associated with coefficient value of 2.519 (p = 0.018) comparing with normotensive pregnancy group. IAP difference is negatively associated with HIP (coefficient -1.013, p = 0.179). In normotensive pregnancies at term, the IAP was in the IAH range of the non-pregnant population. Higher Antepartum IAP and Postpartum IAP are associated with HIP. Reduction of IAP from antepartum period to postpartum period was less with HIP.


Neonatal exposure to a wild-derived microbiome protects mice against diet-induced obesity.
Obesity and its consequences are among the greatest challenges in healthcare. The gut microbiome is recognized as a key factor in the pathogenesis of obesity. Using a mouse model, we show here that a wild-derived microbiome protects against excessive weight gain, severe fatty liver disease and metabolic syndrome during a 10-week course of high-fat diet. This phenotype is transferable only during the first weeks of life. In adult mice, neither transfer nor severe disturbance of the wild-type microbiome modifies the metabolic response to a high-fat diet. The protective phenotype is associated with increased secretion of metabolic hormones and increased energy expenditure through activation of brown adipose tissue. Thus, we identify a microbiome that protects against weight gain and its negative consequences through metabolic programming in early life. Translation of these results to humans may identify early-life therapeutics that protect against obesity.


Job level risk assessment using task level ACGIH hand activity level TLV scores: a pilot study.
Existing upper extremity musculoskeletal disorder analytical tools are primarily intended for single or mono-task jobs. However, many jobs contain more than 1 task and some include job rotation. This case/control study investigates methods of modifying an existing tool, the American Conference of Governmental Industrial Hygienists (ACGIH) Hand Activity Level (HAL) Threshold Limit Value (TLV), to assess the upper extremity risk of multi-task jobs. Various methods of combining the task differences and ratios into a job level assessment were explored. Two methods returned significant odds ratios, (p < .05) of 18.0 (95% CI 1.8-172) and 12.0 (95% CI 1.2-120). These results indicate that a modified ACGIH HAL TLV may provide insight into the work-related risk of multi-task jobs. Further research is needed to optimize this process.


Comparison of pneumatic, ultrasonic and combination lithotripters in percutaneous nephrolithotripsy.
We aimed to compare the outcomes of pneumatic (PL), ultrasonic (UL) and combined (PL/UL) lithotripsy performed in percutaneous lithotripsy (PNL) according to success rates and stone clearence. The medical records of 512 patients treated with PNL between April 2010 and April 2013 were evaluated. Postoperative stone analysis revealed as calcium oxalate in 408 of these patients. The operation notes of 355 patients recorded in detail with complete parameters were reviewed. According to stone disintegration method, patients were divided into three groups: PL only in Group I, UL only in Group II, and UL/PL combination in Group III. Number of patients was 155, 110 and 90, respectively. Fluoroscopy screening time was significantly shorter in group II, and III compared to group I (p<0.001). The failure rates were 13.5% (21 patients) for group I, 3.6% (4 patients) for group II, and 3.3% (3 patients) for group III. There was a significant statistical difference in favor of group II and III by means of success (p=0.023). Group II and III had larger FSA, and this was statistically significant (p=0.032). Stone disintegration time (SDT) was 64.0 ± 41.92 minutes for group I, 49.5 ± 34.63 for group II, and 37.7 ± 16.89 for group III. Group III has a statistically significant shorter SDT (p=0.011). We concluded that, in cases with high stone burden, where faster and efficient lithotripsy is needed, combined ultrasonic / pneumatic lithotripter may be the ideal choice and in suitable cases ultrasonic lithotripter usage provides important advantages to the surgeon.


Ventriculosubgaleal shunts at Columbus Children's Hospital: Neurosurgical implant placement in the neonatal intensive care unit.
The authors review all cases in which ventriculosubgaleal (VSG) shunts were placed at Columbus Children's Hospital for the treatment of posthemorrhagic hydrocephalus in order to assess the surgical procedure, effectiveness of surgery, and complications of cerebrospinal fluid diversion to the subgaleal space. The purpose of the review is to make a comparison between cases in which shunts were placed in the operating room (OR) and those in which they were placed in the neonatal intensive care unit (NICU). Considerations and complications specific to patient transport to the OR or surgical implantation in the NICU are discussed. Seventeen infants with posthemorrhagic hydrocephalus were treated with VSG shunt placement over a period of 4 years. A retrospective analysis of these cases was performed to evaluate multiple aspects of the procedure. Specifically, the surgical procedure, duration of shunt function prior to shunt conversion, neuroimaging changes, operative complications, and risk of infection are discussed. The authors also performed a comparative analysis of shunt placement in the NICU and the OR. The length of the procedure was similar in the two locations. No differences in perioperative or intraoperative risks and no increased risk of infection were seen in either location in this pilot study. Interestingly, the mean lifespan of primary implants placed in the NICU (73 days) was longer than that of those placed in the OR (43 days). Ventriculosubgaleal shunt placement offers a safe and effective temporary means of treating post-hemorrhagic hydrocephalus and can be reliably and safely performed at the bedside.


Microsatellite (STRAf) genotyping cannot differentiate between invasive and colonizing Aspergillus fumigatus isolates.
We studied whether short tandem repeats of Aspergillus fumigatus (STRAf) can differentiate between invasive and colonizing genotypes of A. fumigatus. Of the 395 genotypes detected (n = 1,373 isolates), 50 were clusters and 24 (6% of all genotypes) involved the patients with invasive aspergillosis and those colonized with A. fumigatus, indicating that genotyping cannot discriminate between invasive and colonizing isolates.


Perceptions, attitudes and beliefs towards soya among healthy Asian women participating in a soya randomised controlled trial.
The soya-breast cancer risk relationship remains controversial in Asia due to limited and inconsistent research findings and is exacerbated by difficulties in recruiting and retaining participants in intervention trials. Understanding public perceptions towards soya is important for designing effective intervention trials. Here, we administered a close-ended, quantitative survey to healthy, peri- and post-menopausal Asian women in the Malaysian Soy and Mammographic Density (MiSo) Study to assess perception towards soya and explore motivators and barriers that affect study adherence using the Capability, Opportunity, Motivation and Belief (COM-B) Model and Theoretical Domains Framework (TDF). Of 118 participants, the majority reported the belief that soya promotes good health (Supplement = 85⋅7 %, Diet = 90⋅0 %, Control = 87⋅9 %). Most participants reported obtaining information about soya from the internet (Supplement = 61⋅0 %, Diet = 55⋅3 %, Control = 35⋅9 %), while health professionals were least reported (Supplement = 9⋅8 %, Diet = 7⋅9 %, Control = 5⋅1 %). Stratified analyses by study completion and adherence status yielded comparable findings. By the end of the study, dietary arm participants reported a strong belief that soya has no impact on their health (Supplement = 7⋅1 % v. Diet = 20⋅0 % v. Control = 0⋅0 %, P = 0⋅012). Motivation and opportunity strongly facilitated soya consumption, while psychological capability was the most common barrier to consumption though less evident among dietary arm participants. While most Asian women have a positive perception towards soya, theory-based intervention trials are warranted to understand the perception-study adherence relationship and to accurately inform the public of the health effects of soya.


Radiologic morphology of the calcaneus: a study of radiologic angles in a pediatric population.
The Fowler-Philip, calcaneal pitch, and total calcaneal angles define the radiologic morphology of the rearfoot. We studied these angles in healthy adolescents. We studied 141 feet. Patients with inflammatory or traumatic injuries were excluded. The mean participant age was 11.5 years. The Fowler-Philip, calcaneal pitch, and total calcaneal angles were measured on lateral weightbearing radiographs. The statistics included descriptive, sample size (α=0.05 and β=0.20), the Student t test, and analysis of variance; P < .05 was considered significant. The samples were 141 and 35 radiographs for the Fowler-Philip and calcaneal pitch angles, respectively. Ninety percent, 25.1%, and 97.4% of the adolescents had normal Fowler-Philip, calcaneal pitch, and total calcaneal angles, respectively. In addition, 9.9%, 74.9%, and 2.6% of the values were outside the reference ranges, respectively. The Fowler-Philip angle decreased and the calcaneal pitch angle increased significantly with age (P = .0005). The total calcaneal angle did not change with age (P = .65). The mean angle values in a pediatric population did not differ from those in adults. We found a high percentage of calcaneal pitch angles outside the reference range. Age influenced the Fowler-Philip and calcaneal pitch angles but not the total calcaneal angle.


Multiple metastases in a novel LNCaP model of human prostate cancer.
Metastasis is a frequent and lethal consequence of prostate cancer. Current treatments for metastasis are palliative only. Thus, experimental animal models of metastatic prostate cancer are required for investigations of its pathogenesis and for the development of treatment strategies; however, few models exist at present. In the present study, the LNCaP prostate cancer cell line was co-transfected with a PGK-luciferase-GFP lentivirual vector (LNCaP-luc). Repeated subcutaneous injections of LNCaP-luc cells with Matrigel in nude mice followed by isolation of the cells from tumors resulted in the generation of the LNCaP1-luc cell line. We used CCK-8 and Transwell migration assays, western blot analysis and polymerase chain reaction to detect differences in the characteristics between the LNCaP-luc and LNCaP1-luc cells, and used LNCaP cells to generate a mouse model of metastatic prostate cancer by intracardiac injection. Metastasis was evaluated by bioluminescence imaging, and histological and immunohistochemical staining. the characteristics of the LNCaP1-luc cells differed from those of LNCaP cells, and LNCaP1-luc cells showed increased cell proliferation, cell invasion, tumorigenicity and metastasis potential, and underwent epithelial-mesenchymal transition. In addition, the LNCaP1-luc cells induced multiple metastases in mice when injected into the left cardiac muscle.


Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects.
Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker. Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment. Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention. Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.


585-nm pulsed dye laser treatment of glottal dysplasia.
Management of glottal dysplasia can be difficult and often results in a suboptimal treatment outcome. The surgeon and patient must cooperatively balance decisions regarding the effects of possible malignancy, vocal dysfunction, and recurrences leading to multiple use of general anesthetics. A pilot study was done in 57 cases (36 patients and 97 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 450-micros pulse width, 19 to 76-J/cm2 fluence, 1- to 2-mm spot size) in the treatment of vocal fold keratosis. Forty of the 57 cases had bilateral treatment. Phonomicrosurgical resection was done in 35 of the 57 cases after PDL treatment. Of this group, 10 cases were found to have hyperplasia, 21 dysplasia, 4 carcinoma in situ, and 1 carcinoma. One patient had phonomicrosurgical resection before PDL treatment. In 21 of the 57 cases, the disease was irradiated without resection (4 unilateral lesions and 17 bilateral lesions). Approximately 80% of the patients in this series had a greater than 70% reduction in the size of the lesion with the use of the PDL irrespective of whether they underwent resection. Clinical observation revealed no new anterior commissure web formation despite bilateral anterior commissure treatment in 28 of the 57 cases. The PDL enhanced the epithelial excision by improving hemostasis and by creating an optimal dissection plane between the basement membrane and the underlying superficial lamina propria. In this initial trial, the PDL provided relatively safe and effective treatment for glottal dysplasia. Analysis of patterns of recurrence will require longer follow-up.


Strain-stiffening seal.
An elastomeric seal needs to be soft to accommodate installation but stiff to block fluid flow. Here we show that the two requirements are better fulfilled by a strain-stiffening elastomer than a neo-Hookean elastomer. We represent the strain-stiffening elastomer using the Gent model, and calculate the deformation in the elastomeric seal using an approach analogous to the lubrication theory of a viscous fluid between rigid walls. We determine the sealing pressure on the basis of two modes of leak. The seal leaks by elastic deformation when the fluid pressure exceeds the contact pressure between the seal and the rigid wall. The seal leaks by rupture when the energy release rate of a crack exceeds the toughness of the elastomer. For both modes of leak, a strain-stiffening elastomer enhances the sealing pressure compared to a neo-Hookean elastomer. We construct diagrams in which the two modes of leak are demarcated. It is hoped that this study will aid in the development of materials and geometries of seals.


Fragile (X) X-linked mental retardation. II. Frequency and replication pattern of fragile (X)(q28) in heterozygotes.
The frequency of cytologic expression and the replication pattern of the fragile (X) [fra(X)] were investigated in 28 fra(X) heterozygotes, of which 25 agreed to psychological assessment. One-third of the heterozygotes in this study are mentally retarded. The intellectually impaired carriers had a higher frequency of fra(X) and a higher proportion of early-replicating fra(X) than the normally intelligent carriers. The early-replicating fra(X) accounted for 39% of the variability in IQ and the late-replicating fra(X) for 12%. Age had a minimal inverse effect on fra(X) expression and replication pattern. Thus, it appears that mental retardation in females heterozygous for the fra(X) may largely be a function of the proportion of cells with an early-replicating, active X chromosome possessing the fragile site.


New citrinin derivatives from the deep-sea-derived fungus Cladosporium sp. SCSIO z015.
During the course of our search for novel bioactive compounds from marine fungi, four new citrinin derivatives, cladosporins A-D (1-4) were isolated from a culture broth of the deep-sea-derived fungus Cladosporium sp. SCSIO z015. Their complete structural assignments were elucidated by the extensive spectroscopic investigation. The absolute configurations of 1-3 were established by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 1-4 showed weak toxicity towards brine shrine naupalii with LC50 values of 72.0, 81.7, 49.9 and 81.4 μM, respectively. And 4 also showed significant antioxidant activity against ɑ,α-diphenyl-picrylhydrazyl (DPPH) radicals with an IC50 value of 16.4 μM.


[Organization and results of surgical care for ulcerative gastroduodenal bleeding in the hospitals of Central Federal District].
To present treatment of 52 149 patients with ulcerative gastroduodenal bleeding (UGDB) who were treated in different regions of Central Federal District (CFD) for the period 2011-2014. It is noted that UGDB incidence per 100 thousands is increased proportionally from 32.9 to 77.8 according to population less than 20 and over 100 thousands, respectively. In hospitals of small and medium settlements the number of UGDB patients without surgery reaches 81.6 and 81.1%, the number of operated patients - 18.4 and 18.9% respectively. In hospitals of large settlements this ratio is 90.1 and 90.6%, the number of operated patients - 9.9 and 9.4%, respectively. In areas of Central Federal District the mortality rate in patients without surgery is 3.9-8.2%, in operated patients - 17.4-36.9%. Structured analysis of the organization of surgical care in Central Federal District revealed the relationship between outcomes and efficient use of endoscopic diagnostics and haemostasis. In municipal hospitals of Central District endoscopic technologies are insufficiently used for final elimination of ulcerative bleeding.


A principal component analysis (PCA) based assessment of the gait performance.
The gait assessment is instrumental for evaluating the efficiency of rehabilitation of persons with a motor impairment of the lower extremities. The protocol for quantifying the gait performance needs to be simple and easy to implement; therefore, a wearable system and user-friendly computer program are preferable. We used the Gait Master (instrumented insoles) with the industrial quality ground reaction forces (GRF) sensors and 6D inertial measurement units (IMU). WiFi transmitted 10 signals from the GRF sensors and 12 signals from the accelerometers and gyroscopes to the host computer. The clinician was following in real-time the acquired data to be assured that the WiFi operated correctly. We developed a method that uses principal component analysis (PCA) to provide a clinician with easy to interpret cyclograms showing the difference between the recorded and healthy-like gait performance. The cyclograms formed by the first two principal components in the PCA space show the step-to-step reproducibility. We suggest that a cyclogram and its orientation to the coordinate system PC1 vs. PC2 allow a simple assessment of the gait. We show results for six healthy persons and five patients with hemiplegia.


[Cryptosporidium parvum Gastroenteritis in a Patient with Renal Transplantation].
In this study, a case who starting abundant watery diarrhea on the 14th day of renal transplantation is presented. Stool sample was analyzed for Cryptosporidium spp. by carbol fuchsin staining method, copro-ELISA and nested polimeraze chain reaction (PCR). From sample found positive by Carbol-fuchsin staining method and Copro-ELISA, DNA sequence analysis was performed, gel-purified from amplicon obtained by nested PCR. As a result of DNA sequence analysis was determined to be Cryptosporidium parvum. Although C. parvum is a rare causative agent of gastroenteritis it can be cause serious clinical diarrhea solid organ transplantation patient. As a result, also C.parvum must be considered as a causative agent of diarrhea occurring after organ transplantation.


[Advances on gene-based association analysis].
Genome-wide association studies (GWAS) have been widely used for hunting the susceptibility genes for common diseases in the past years; however, the abundant information for the disease mechanism based on the GWAS data has not been fully mined. Recently, some researchers focused on the biological network and pathway analysis for the GWAS data to explore the potential disease mechanism. Since genes are the basic units for the biological network and pathway, the genetic effects from all or part of single nucleotide polymorphisms (SNPs) in the genes should be integrated into genetic scores, which are so-called "gene-based association analysis". Gene-based association analysis takes into account some important factors such as genetic effects of the SNPs, the number of the SNPs in the genes and the linkage disequilibrium structure of the SNPs. In this review, we will focus on the progress, principle and application of gene-based association analysis.


Protein synthesis in rabbit reticulocytes: characteristics of CO-eIF-2 protein complex.
A high molecular weight reticulocyte protein factor, named Co-eIF-2, contains Co-eIF-2A, Co-eIF-2B, and Co-eIF-2C activities and stimulates Met-tRNAf binding to eIF-2 both in the presence and absence of Mg2+. Some characteristics of this stimulation in the absence of Mg2+ are: (1) Stimulation is most pronounced at low eIF-2 levels. (2) Stimulation is partially resistant to heat and NEM treatment, and thus appears to be due to the combined action of both heat and NEM-insensitive Co-eIF-2A, and heat and NEM-sensitive Co-eIF-2C activities. (3) [3H]GDP bound in eIF-2 . [3H]GDP complex is rapidly displaced by unlabelled GTP during ternary complex formation Co-eIF-2 stimulates Met-tRNAf binding to eIF-2 even when added after the [3H]GDP from eIF-2 . [3H]GDP has been completely displaced. This indicates that Co-eIF-2-stimulation is not due to GDP displacement from eIF-2 . GDP. We propose that eIF-2 molecules become inactive in the presence of Mg2+ and at high dilution, and Co-eIF-2 restores the inactive eIF-2 molecules into an active form.


Is compliance with hospital accreditation associated with length of stay and acute readmission? A Danish nationwide population-based study.
To examine the association between compliance with hospital accreditation and length of stay (LOS) and acute readmission (AR). A nationwide population-based follow-up study from November 2009 to December 2012. Public, non-psychiatric Danish hospitals. In-patients admitted with one of 80 diagnoses. Accreditation by the first version of The Danish Healthcare Quality Programme. Using an on-site survey, surveyors assessed the level of compliance with the standards. The hospital was awarded either fully (n = 11) or partially accredited (n = 20). LOS including transfers between hospitals and all-cause AR within 30 days after discharge. The Cox Proportional Hazard regression was used to compute hazard ratios (HRs) adjusted for potential confounding factors and cluster effect at hospital level. For analyses of LOS, 275 589 in-patients were included of whom 266 532 were discharged alive and included in the AR analyses. The mean LOS was 4.51 days (95% confidence interval (CI): 4.46-4.57) at fully and 4.54 days (95% CI: 4.50-4.57) at partially accredited hospitals, respectively. After adjusting for confounding factors, the adjusted HR for time to discharge was 1.07 (95% CI: 1.01-1.14). AR within 30 days after discharge was 13.70% (95% CI: 13.45-13.95) at fully and 12.72% (95% CI: 12.57-12.86) at partially accredited hospitals, respectively, corresponding to an adjusted HR of 1.01 (95% CI: 0.92-1.10). Admissions at fully accredited hospitals were associated with a shorter LOS compared with admissions at partially accredited hospitals, although the difference was modest. No difference was observed in AR within 30 days after discharge.


Ligand Based Pharmacophore Modeling and Virtual Screening Studies to Design Novel HDAC2 Inhibitors.
Histone deacetylases 2 (HDAC2), Class I histone deacetylase (HDAC) family, emerged as an important therapeutic target for the treatment of various cancers. A total of 48 inhibitors of two different chemotypes were used to generate pharmacophore model using 3D QSAR pharmacophore generation (HypoGen algorithm) module in Discovery Studio. The best HypoGen model consists of four pharmacophore features namely, one hydrogen bond acceptor (HBA), and one hydrogen donor (HBD), one hydrophobic (HYP) and one aromatic centres, (RA). This model was validated against 20 test set compounds and this model was utilized as a 3D query for virtual screening to validate against NCI and Maybridge database and the hits further screened by Lipinski's rule of 5, and a total of 382 hit compounds from NCI and 243 hit compounds from Maybridge were found and were subjected to molecular docking in the active site of HDAC2 (PDB: 3MAX). Finally eight hit compounds, NSC108392, NSC127064, NSC110782, and NSC748337 from NCI database and MFCD01935795, MFCD00830779, MFCD00661790, and MFCD00124221 from Maybridge database, were considered as novel potential HDAC2 inhibitors.


cDNA cloning, expression, and mutagenesis of scytalone dehydratase needed for pathogenicity of the rice blast fungus, Pyricularia oryzae.
We purified scytalone dehydratase from the rice blast fungus, Pyricularia oryzae, and cloned its cDNA on the basis of its amino acid sequence. The deduced amino acid sequence was 62% identical to the scytalone dehydratase from Colletotrichum lagenarium. The expression of this gene was induced transcriptionally in the stationary phase when melanin synthesis occurs. We constructed a heterologous expression system for the enzyme in Escherichia coli, did deletion analysis with this system, and found that a C-terminal region is essential for the enzyme function.


Abnormal development of the suprachiasmatic nuclei of the hypothalamus in a strain of genetically anophthalmic mice.
In the anophthalmic mutant of the mouse the optic primordia are "genetically enucleated" well before the usual emergence of retinal ganglion cell axons (Silver and Hughes, '74). In eyeless animals, a portion of the mediobasal hypothalamus and one of its constituent nuclear pairs, nucleus suprachiasmaticus (SCN), were markedly abnormal in the embryo and adult. It has been reported that the ventral portion of the SCN receives a substantial, direct retinal innervation (Moore and Lenn, '72) and that these nuclei may mediate several light-induced hormonal and behavioral circadian rhythms (Stetson and Whitmyre, '76). During day 13 of mutant embryogenesis, just prior to the time of optic chiasm formation in normal animals, a large portion of ependyma and adjacent brain tissue herniated into the lumen of the would-be suprachiasmatic region of the third ventricle. In 70% of the animals examined histologically during the latter phase of development and as adults, regulation occurred and the brains were largely comparable with those of controls. However, in the remaining mutant mice, the overall size of either, or sometimse both, SCN was much reduced. The basal (but not the apical) dendrites of SCN neurons failed to develop fully. Some basal dendrites normally invade the optic chiasm below. In several mutant animals one or the other SCN had greatly increased numbers of cells, while the contralateral one had diminished numbers. These observations suggest that regular formation of the suprachiasmatic region of the hypothalamus and especially the suprachiasmatic nuclei, may depend during development upon the presence of the eye or the subjacent optic axons.


Childhood acne: evaluation and management.
Acne is a disease that can be seen in the first year of life, early childhood, prepubertal age, and puberty. The purpose of this article is to review the clinical presentation and pathogenesis of the various forms of prepubertal acne and to propose guidelines regarding its evaluation and treatment. The early clinical recognition of the disease and prompt initiation of therapy in these age groups will help prevent the sequelae of emotional distress and severe scarring in both the child and parents.


Vaccinations for international travellers travelling from Greece.
The aim of this prospective, questionnaire-based study is to assess pre-travel vaccinations for international travellers who receive pre-travel advice in Greece. A total of 2494 travellers were studied from January 1, 2009 through December 31, 2010. Travellers sought pre-travel advice at a median of 16 days (range: 0-349 days) before departure. Sub-Saharan Africa was the most common destination (34.7%). Most travellers (60.8%) travelled for <1 month, for recreation purposes (58.9%), stayed in hotels (65.3%), and in urban areas (53.6%). Yellow fever, tetravalent meningococcal, typhoid fever, cholera, and rabies vaccines were administered to 1629 (65.3%), 666 (26.7%), 615 (24.7%), 28 (1.1%), and/or 12 (0.5%) travellers, respectively. Of those who received Yellow fever vaccine, 737 (45.2%) travelled to sub-Saharan Africa, 332 (20.4%) travelled to South America, 949 (58.3%) stayed for short term, and 762 (46.8%) stayed in urban areas. Of the 1629 travellers vaccinated against Yellow fever, 150 (9.2%) and 226 (13.8%) travelled to areas of sub-Saharan Africa and South America respectively, where the vaccine is not or generally not recommended. Of those travellers who received meningococcal vaccine, 327 (49.1%) travelled to the Middle East for the Hajj, 251 (29%) travelled to sub-Saharan Africa, 410 (61.6%) for short term, and 540 (64.4%) stayed in urban areas. Of those travellers who received typhoid vaccine, 241 (39.2%) travelled to sub-Saharan Africa, 78 (12.7%) to the Indian subcontinent, 234 (38%) for short term, and 419 (68.1%) stayed in urban areas. Regarding routine vaccines, tetanus-diphtheria, poliomyelitis, and measles-mumps-rubella vaccines were administered to 707 (28.3%), 639 (25.6%) and/or 149 (6%) travellers, respectively. Of those to whom poliomyelitis vaccine was recommended, 295 (46.2%) and 137 (21.4%) travelled to sub-Saharan Africa and the Middle East, respectively, and 362 (56.7%) travelled for short term. In conclusion, this study revealed that there is a need for more selective vaccine recommendations for travellers to developing countries, taking under consideration travellers and travel characteristics as well. Strategies to target travel health consultants should be developed in order to increase awareness in travel health issues.


Gendered impact of solid fuel use on acute respiratory infections in children in China.
Indoor Air Pollution (IPA) is a serious environmental problem that can have detrimental effects on child health. In China, the major sources of indoor pollution are biomass fuel or solid cooking fuels and familial smoking. Previous studies posit that the effects of IAP on health outcomes may be worse for female children, but the empirical evidence has been mixed. In this paper we use the China Health and Nutrition Survey to examine the association of solid fuel use and paternal smoking on acute respiratory infections (ARIs) in children focusing on child gender differences. We used conditional logistic regression to examine gender differences in incidents of ARIs in the 4 weeks prior to the survey collection. We modeled gender difference by including an interaction between child gender and solid fuel use and child gender and paternal smoking. We also conducted stratified analyses by child gender. When examining both genders together, female children exposed to solid fuel had an elevated risk of a ARIs, but the coefficient was not statistically significant. When using a stratified models by gender, female children had a higher risk of having ARIs in the past 4 weeks when exposed to solid fuels (OR=3.28; 95% CI 1.34-8.03) and paternal smoking (OR=2.27; 95% CI 1.08-4.77). Whereas neither exposure to solid fuel nor parental smoking had any significant influence on ARIs for male children. While many have hypothesized that female children may be more vulnerable to IAP, the empirical evidence has been limited. In our study we found empirical support for gender difference in the effects of solid cooking fuel use on ARIs. Gender differences in ARIs suggest that realized exposures, as opposed to ambient exposures, are likely higher for female children and are important to consider.


Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma.
In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific differences in the response to drug treatment may contribute to differences in disease outcomes. Genetic variants at the beta(2)-adrenergic receptor (beta(2)AR) may modify asthma severity and albuterol responsiveness. We tested the association of beta(2)AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma. We used both family-based and cross-sectional tests of association with 8 beta(2)AR single nucleotide polymorphisms in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity, and bronchodilator drug responsiveness. Among Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV(1) with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in those with FEV(1) > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma. Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.


Was there significant tax evasion after the 1999 50 cent per pack cigarette tax increase in California?
Several states, including California, have implemented large cigarette excise tax increases, which may encourage smokers to purchase their cigarettes in other lower taxed states, or from other lower or non-taxed sources. Such tax evasion thwarts tobacco control objectives and may cost the state substantial tax revenues. Thus, this study investigates the extent of tax evasion in the 6-12 months after the implementation of California's 0.50 dollars/pack excise tax increase. Retrospective data analysis from the 1999 California Tobacco Surveys (CTS), a random digit dialled telephone survey of California households. Sources of cigarettes, average daily cigarette consumption, and reported price paid. Very few (5.1 (0.7)% (+/-95% confidence limits)) of California smokers avoided the excise tax by usually purchasing cigarettes from non- or lower taxed sources, such as out-of-state outlets, military commissaries, or the internet. The vast majority of smokers purchased their cigarettes from the most convenient and expensive sources: convenience stores/gas (petrol) stations (45.0 (1.9)%), liquor/drug stores (16.4 (1.6)%), and supermarkets (8.8 (1.2)%). Despite the potential savings, tax evasion by individual smokers does not appear to pose a serious threat to California's excise tax revenues or its tobacco control objectives.


Laparoscopic management of a degenerating cystic leiomyoma imitating an ovarian cyst: A case report.
Leiomyomas are usually easily identifiable on routine imaging. However, there is increasing difficulty with diagnosing leiomyomas following degeneration. Subserosal leiomyomas that undergo cystic degeneration can imitate ovarian pathology. We present the case of a 39-year-old nulligravid woman who underwent surgery for a large pelvic mass originally suspected to be of ovarian origin. Intraoperatively, the mass was found to originate from the uterus and determined to be a large pedunculated, fluid-filled cyst arising from a fibroid which had undergone cystic degeneration. The mass was successfully removed laparoscopically through a single, two-centimeter port. Gynecologists and radiologists should take into account this presentation when encountering suspected enlarged ovarian cysts without clearly identifying an origin. Laparoscopic intervention should be considered as the first line of management.


Effect of Magnesium Sulfate and Clonidine in Attenuating Hemodynamic Response to Pneumoperitoneum in Laparoscopic Cholecystectomy.
Pneumoperitoneum in laparoscopic procedures is associated with hemodynamic response, due to the release of catecholamines and vasopressin. Magnesium and clonidine have been used to attenuate such hemodynamic responses by inhibiting release of these mediators. We conducted this randomized, double-blinded study to assess which of the two attenuates hemodynamic response better. Ninety American Society of Anesthesiologists health status Classes I and II patients posted for elective laparoscopic cholecystectomy were randomized into three groups of thirty patients each. Group C received injection clonidine 1 μg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group M received injection magnesium sulfate 50 mg/kg diluted in 10 mL normal saline over 10 min, prior to pneumoperitoneum. Group NS received 10 mL normal saline intravenously over 10 min, prior to pneumoperitoneum. Hemodynamic parameters were recorded before induction (baseline values), at the end of magnesium sulfate/clonidine/saline administration and before pneumoperitoneum (P0), 5 min (P5), 10 min (P10), 20 min (P20), 30 min (P30), and 40 min (P40) after pneumoperitoneum. Systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were all significantly higher in the normal saline group compared to magnesium and clonidine. On comparing patients in Group M and Group C, DBP, MAP, and HR were significantly lower in the magnesium group. Mean extubation time and time to response to verbal commands were significantly longer in the magnesium group. Both magnesium and clonidine attenuated the hemodynamic response to pneumoperitoneum. However, magnesium 50 mg/kg, attenuated hemodynamic response better than clonidine 1 μg/kg.


The Vienna nomogram: validation of a novel biopsy strategy defining the optimal number of cores based on patient age and total prostate volume.
We conducted a trial in patients with prostate specific antigen (PSA) levels from 2 to 10 ng/ml to validate a newly developed nomogram that defines the optimal number of biopsy cores required for prostate cancer (PCa) detection based on patient age and total prostate volume (Vienna nomogram). A total of 502 patients underwent transrectal ultrasound guided prostate biopsy using the Vienna nomogram. These results were compared with those of a previous group of 1,051 patients who had standard octant biopsies followed by systematic repeat biopsies after 6 to 8 weeks if the initial biopsy result was negative for PCa. The overall PCa detection rate using the Vienna nomogram was 36.7% compared with 22% on first and 10% on repeat biopsy in the control group. The PCa detection rate using the Vienna nomogram was superior (p=0.002) to the octant biopsy technique, and comparable to a combination of first and repeat biopsy in the control group. Multivariate analysis of the Vienna nomogram showed that only PSA and the number of cores were independent predictors of PCa detection (chi-square = 49, p <0.001). Total prostate volume, transition zone volume and age were not independent predictors of PCa detection. The Vienna nomogram offers an easy tool to select the optimal number of prostate biopsy cores based on patient age and total prostate volume in PSA range 2 to 10 ng/ml. Cancer detection is significantly improved (66.4%) compared to the control group. The bias factor of larger prostate volume is eliminated by using the Vienna nomogram. Moreover, the Vienna nomogram is advantageous not only in terms of the improved PCa detection rate but also economically makes systematic repeat biopsies unnecessary.


Metabolism and excretion of polycyclic aromatic hydrocarbons in rat and in human.
Polycyclic aromatic hydrocarbons have shown to be an important class of environmental and occupational carcinogens. By balancing the carcinogenic potential PAH were found to predominantly contribute to the biological activity of environmental matter such as vehicle exhaust, used motor oil, and hard-coal combustion effluents. Due to the individual ratio of toxifying and detoxifying processes PAH-exposure measurements are not appropriate to be used for risk assessment without any further information on their metabolic fate. Accordingly, metabolite profiles of phenanthrene, pyrene, chrysene, benz(a)anthracene and fluoranthene have been recorded in both tar-pitch exposed Wistar rats and coke plant workers. The results show that metabolite profiles are invariant individual parameters which, however, vary from one individual to another. Significant differences with regard to the ratio of k-region and non-k-region hydroxylation of phenanthrene have been observed in a greater number of coke plant workers. This ratio might be helpful for risk assessment studies since it reflects the various cytochrome P450-dependent monooxygenase isoforms participating in the metabolism of PAH. Studies of this kind can only be carried out with substrates possessing several nonequivalent double bonds (phenanthrene, chrysene) whereas pyrene--commonly used for biomonitoring--does not satisfy this condition. The excretion rate (excretion versus exposure) seems to be an individual parameter.


Malnutrition among children younger than 5 years-old in conflict zones of Chiapas, Mexico.
We performed a cross-sectional, community-based survey, supplemented by interviews with community leaders in Chiapas, Mexico, to examine the prevalence and predictors of child malnutrition in regions affected by the Zapatista conflict. The prevalence rates of stunting, wasting, and underweight were 54.1%, 2.9%, and 20.3%, respectively, in 2666 children aged younger than 5 years. Stunting was associated with indigenous ethnicity, poverty, region of residence, and intracommunity division. The results indicate that malnutrition is a serious public health problem in the studied regions.


Chitosan nanoparticles for siRNA delivery: optimizing formulation to increase stability and efficiency.
This study aims at developing chitosan-based nanoparticles suitable for an intravenous administration of small interfering RNA (siRNA) able to achieve (i) high gene silencing without cytotoxicity and (ii) stability in biological media including blood. Therefore, the influence of chitosan/tripolyphosphate ratio, chitosan physicochemical properties, PEGylation of chitosan as well as the addition of an endosomal disrupting agent and a negatively charged polymer was assessed. The gene silencing activity and cytotoxicity were evaluated on B16 melanoma cells expressing luciferase. We monitored the integrity and the size behavior of siRNA nanoparticles in human plasma using fluorescence fluctuation spectroscopy and single particle tracking respectively. The presence of PEGylated chitosan and poly(ethylene imine) was essential for high levels of gene silencing in vitro. Chitosan nanoparticles immediately released siRNA in plasma while the inclusion of hyaluronic acid and high amount of poly(ethylene glycol) in the formulation improved the stability of the particles. The developed formulations of PEGylated chitosan-based nanoparticles that achieve high gene silencing in vitro, low cytotoxicity and high stability in plasma could be promising for intravenous delivery of siRNA.


Alterations of surface charges of plasma lipoproteins in ischemic heart disease.
For a charged and an uncharged long chain spin probe the partition between the aqueous phase and the lipoproteins LDL, HDL2 and HDL3 was measured by use of ESR spectroscopy. The partition coefficients were compared for lipoproteins from normal donors and lipoproteins from patients with ischemic heart disease. The partition coefficients of the uncharged spin probe are not different. However, the charged spin probe has a significantly different partition for LDL and HDL3. This difference results from changes in the surface charge. Patients with ischemic heart disease have LDL which is more electropositively charged and HDL3 is more electronegatively charged compared to the corresponding lipoproteins of normal subjects. The surface charge of HDL2 is not changed. The results are discussed in the light of current concepts of the pathogenesis of atherosclerosis.


Variability in contrast agent uptake by different but similar stem cell types.
The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies.


Increase of experimental hypertension following inhibition of prostaglandin biosynthesis.
To demonstrate the role of endogenous renal prostaglandins as modulators of the renin-angiotensin-system in renal hypertension, rats with acute and chronic renal hypertension were pretreated with different inhibitors of the prostaglandin biosynthesis (indomethacin, mefenamic acid, acetylsalicylic acid. Development and course of acute and chronic renal hypertension after treatment were highly significantly different from untreated animals concerning elevation, duration and intensity of renal hypertension. Moreover, indomethacin enhanced renal vasoconstrictor effect of angiotensin II in the dog; accordingly, inhibition of prostaglandin biosynthesis increases acute and chronic renal hypertension. It seems that prostaglandins play an important part in blood pressure regulation.


Progress and Prospects of Natural Glycoside Sweetener Biosynthesis: A Review.
To achieve an adequate sense of sweetness with a healthy low-sugar diet, it is necessary to explore and produce sugar alternatives. Recently, glycoside sweeteners and their biosynthetic approaches have attracted the attention of researchers. In this review, we first outlined the synthetic pathways of glycoside sweeteners, including the key enzymes and rate-limiting steps. Next, we reviewed the progress in engineered microorganisms producing glycoside sweeteners, including de novo synthesis, whole-cell catalysis synthesis, and in vitro synthesis. The applications of metabolic engineering strategies, such as cofactor engineering and enzyme modification, in the optimization of glycoside sweetener biosynthesis were summarized. Finally, the prospects of combining enzyme engineering and machine learning strategies to enhance the production of glycoside sweeteners were discussed. This review provides a perspective on synthesizing glycoside sweeteners in microbial cells, theoretically guiding the bioproduction of glycoside sweeteners.