Reduced tissue inhibitor of metalloproteinase-2 expression is associated with advanced medullary thyroid carcinoma.
Matrix metalloproteinases (MMPs) are enzymes for extracellular matrix remodeling that are involved in tumor growth, progression and metastasis. Among them, MMP-9 has been implicated in tumor angiogenesis. Tissue inhibitor of matrix metalloproteinase (TIMP)-2, a member of the family of MMP inhibitors, induces apoptosis and inhibits various stages of angiogenesis. Previous studies analyzing the expression of MMP-9 and TIMP-2 in medullary thyroid carcinoma (MTC) are scarce. The aims of the current study were to evaluate MMP-9 and TIMP-2 expression in MTC samples and correlate the results with clinical parameters. Paraffin-embedded samples from 77 MTC patients were evaluated for expression by immunohistochemistry. The clinical data in medical records were retrospectively reviewed. In total, 77 patients aged 35.6±17.1 years were enrolled. Of these patients, 36 had hereditary disease (46.8%). Immunohistochemical staining for MMP-9 and TIMP-2 was detected in 89.6 and 93.5% of the samples, respectively. The expression of MMP-9 was not found to correlate with clinical parameters, although, a trend toward a correlation between MMP-9 and distant metastasis was observed (P=0.053). By contrast, TIMP-2 staining was found to correlate with age at diagnosis (P=0.026) and negatively correlate with tumor size and tumoral stage (P=0.002 and P=0.001, respectively). Notably, the highest levels of TIMP-2 expression were observed in patients with intrathyroidal disease. The MMP-9 enzyme involved in extracellular matrix remodeling is overexpressed in MTC lesions and may contribute to tumor vascularization and growth. Reduced levels of TIMP-2 expression may be implicated in tumor progression and spread of disease.


M.BssHII, a multispecific cytosine-C5-DNA-methyltransferase with unusual target recognizing properties.
A new multispecific cytosine-C5-DNA-methyltransferase (C5-MTase), M.BssHII, was identified in Bacillus stearothermophilus H3. The M.BssHII gene was cloned and sequenced. The amino acid sequence deduced shows the characteristic building plan of a C5-MTase. By sequencing bisulfite-treated DNA methylated by M.BssHII and by restriction enzyme analysis, we defined the following methylation targets of M.BssHII: ACGCGT/CCGCGG (MluI/SacII), PuGCGCPy (HaeII), PuCCGGPy (Cfr10I) and GCGCGC (BssHII). The relative location of the specificity determinants in the C5-MTase was derived from the analysis of M.BssHII derivatives carrying deletions within the variable region "V" and chimeric C5-Mtases constructed between M.BssHII and the related monospecific enzyme M.phi3TII. Four of the M.BssHII specificities (MluI, SacII, Cfr10I and BssHII) could be associated with amino acid segments within the variable region "V". The determinant for HaeII activity had to be assigned to sequences defining the enzyme core, the first example of a C5-MTase in which a sequence-specific methylation potential is mediated by structures outside of the variable region. Another intriguing result came from the analysis of one particular chimera made between M.BssHII and M.phi3TII. This construct showed a relaxation of the methylation capacity, both with respect to the target recognized and the targeting of methylation within this sequence.


Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy--a follow-up study in 68 patients.
Although essential thrombocythemia (ET) is usually primarily considered a disorder of middle age, it has been observed in children and young adults. However, the real risk for thrombosis in these patients has not been clearly established. Prospective analysis of consecutive patients younger than 40 at the time of the diagnosis of ET and followed in our department between 1980 and 1998. Sixty-eight patients (28 males and 40 females, median follow-up 99.14 months) affected by ET diagnosed in agreement with the Polycythemia Vera Study Group criteria. Asymptomatic ET patients were not treated. In contrast, patients with associated atherosclerotic risk factors, microvascular disturbances, or a previous major arterial thrombosis were given acetyl salicylic acid (ASA 100 mg/day). Only patients with major thrombotic complications and a platelet count > 1,000 x 10(9)/L received cytoreductive therapy. (1) to evaluate thrombotic complications in young patients with ET, (2) to relate thrombotic risk to the presence of general atherosclerotic risk factors, and (3) to adopt treatment, and (4) to report the outcome of the pregnancies monitored in our population. Fifteen patients had major thrombosis, 11 of which were the presenting features of ET. No rethrombosis has been observed. Only one patient with thrombotic complications was under efficient treatment. Atherosclerotic risk factors are more common in patients with major arterial thrombosis than in asymptomatic subjects. Thirteen normal babies were delivered out of 16 pregnancies, 6 of the pregnant women were on ASA therapy. Most thrombosis in young ET patients occurred at the time of the diagnosis, and venous thrombotic events represent one-third of total thrombosis. Cardiovascular risk factors seem to be concurrent stimuli for arterial thrombosis in ET. The thrombotic complication rate was 2.6/100 patients/year ASA reduces microvascular disturbances, thrombosis, and rethrombosis and possibly reduces obstetric complications in women with ET.


Factors influencing the use of health services by trauma patients according to insurance type and injury severity score in South Korea: Based on Andersen's behavioral model.
This study aims to understand the difference in trauma patients' use of health services in Korea according to insurance type and the Injury Severity Score. Andersen's behavioral model of health service use is employed to identify the factors influencing their use. Claims data from January 1 to December 31, 2016 were extracted from both the Health Insurance Review and Assessment Service and the automobile insurance screening center for all the medical treatments identified with the Korean Triage and Acuity Scale and Injury Severity Score. Using the Health Insurance Review and Assessment Service's remote statistical analysis system, hierarchical regression and negative binomial analyses were conducted to determine the effect of predisposing, enabling, and need factors on health service use. The results demonstrate that the use of Korean health services is relatively equitable since medical expenses for trauma patients are greatly influenced by need factors. However, the length of time trauma patients stay in the hospital appears to differ according to insurance type. This study suggests that healthcare policies need to increase coverage benefits and improve medical billing for patients with severe trauma, as well as develop a more robust screening system for patients with mild to moderate impairments.


Autism Spectrum Disorder and Obesity in Children: A Systematic Review and Meta-Analysis.
Children and adolescents with autism spectrum disorder (ASD) appear to be at greater risk of excess weight gain. The aim of this systematic review and meta-analysis was to examine whether children with ASD have a greater prevalence of obesity and whether the prevalence of ASD is higher in children with obesity. We conducted a systematic search on PubMed, Scopus, and PsychINFO until May 21, 2021. We used the meta package in the R in order to calculate the pooled prevalence and relative risk of obesity in children with ASD. We found 20 eligible studies investigating the prevalence of obesity in children with ASD, with the prevalence ranging from 7.9 to 31.8% and from 1.4 to 23.6% among controls. All but three studies originated from the USA. The proportion of children with obesity in ASD populations was 17% (95% confidence interval [CI]: 13-22). The relative risk of obesity in children with ASD compared with control children was 1.58 (95% CI: 1.34-1.86). There were no controlled studies reporting on the prevalence of ASD in children with obesity. Children and adolescents with ASD have a higher prevalence of obesity than healthy controls. There is a need for further prevalence studies of obesity in children with ASD, especially outside the USA, since the few European studies carried out have failed to show a significant difference between obesity prevalence in children with and without ASD. There is no knowledge at all regarding the prevalence of ASD among children with obesity.


Stercoral perforation associated with parathyroid adenoma.
We describe the case of a patient who presented with stercoral perforation of the sigmoid colon in association with hypercalcaemia caused by a parathyroid adenoma. Colonic resection was followed by successful parathyroidectomy and resulted in a satisfactory outcome. This unusual association is discussed.


Frequency response of cold wires used for atmospheric turbulence measurements in the marine environment.
We have examined the frequency response of cold-wire thermometers using 2.5-micro platinum wires with laboratory-produced salt layers. The salt layers are produced by exposure to a saline aerosol to simulate the marine environment. The frequency response was determined by measuring the response of the coated wires to a white thermal noise air flow produced by a heated wire in an airstream. The wires exhibit a relaxation behavior, with the rolloff frequency varying as the square of the total wire plus salt radius. The results show that the frequency response of the salted wires is controlled by the laminar-air-film boundary layer.


Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing.
Eradication treatment for Helicobacter pylori gastritis is covered by national health insurance since 2013 in Japan. However, eradication failure due to the increase of antimicrobial resistance has become a serious problem. The present study aims to establish a reference panel of Japanese H. pylori strains for antimicrobial susceptibility testing. A total of 28 strains were collected from 4 medical facilities in Japan. Antimicrobial susceptibility tests (ASTs) to clarithromycin (CLR), amoxicillin (AMX), and metronidazole (MNZ), were used to select standard reference strains. Complete genome sequences were also determined. Three H. pylori strains (JSHR3, JSHR6 and JSHR31) were selected as standard reference strains by the Japanese Society for Helicobacter Research (JSHR). The minimum inhibitory concentrations (MICs) of the antibiotics against these 3 strains by agar dilution method with Brucella-based horse-serum-containing agar medium were as follows: JSHR3 (CLR 16 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), JSHR6 (CLR 0.016 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), and JSHR31 (CLR 16 μg/ml, AMX 1 μg/ml and MNZ 64 μg/ml). A reference panel of H. pylori JSHR strains was established. The panel consisted of JSHR6, which was antibiotic-susceptible, JSHR3, which was CLR-resistant, and JSHR31, which was multi-resistant. This reference panel will be essential for standardized ASTs before the optimal drugs are selected for eradication treatment.


Isolation and Immunochemical Characterization of Plant Glutamine Synthetase in Alfalfa (Medicago sativa L.) Nodules.
Host plant glutamine synthetase (GS) has been purified 100-fold from N(2)-fixing alfalfa (Medicago sativa L.) nodules by a new procedure involving preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a final step. An SDS-polypeptide fraction corresponding to plant GS was identified and consisted of two major polypeptides of 40,000 to 45,000 molecular weight. Antibodies to the SDS-polypeptide fraction were raised in mice by intraperitoneal injection, and antisera were collected as ascitic fluid. Crude extracts of soluble protein from the plant fraction of nodules were resolved by SDS-PAGE and then subjected to electrophoresis in the second dimension into antibody-containing agarose gel. A single immunochemically active protein species was observed using this crossed immunoelectrophoresis method, even though both major GS SDS-polypeptides were apparently resolved in the first (SDS-PAGE) dimension. Plant GS protein in crude nodule extracts was quantitated immunochemically by comparison with immunoprecipitin arcs of similarly treated amounts of pure antigen. Using this technique, it was determined that plant GS was present at 150 micrograms per gram fresh weight or 1.2% of total plant soluble protein in N(2)-fixing alfalfa nodules.Results suggest that alfalfa nodule plant GS consists of two major subunit polypeptides, but only a single immunochemically active native protein was observed. The crossed immunoelectrophoresis procedure described here should be generally applicable for immunochemical detection of lower abundance components of crude plant extracts.


Advances in vitreoretinal surgery: macular hole repair and perfluorocarbon liquids.
1. Idiopathic macular hole was once thought to be an untreatable disorder. During the past several years, surgical techniques have evolved that allow for closure of the macular hole, with restoration of vision in many cases. 2. Perfluorocarbon liquids are an important class of compounds that are under investigation for use in vitreoretinal surgery. The use of these compounds facilitates the performance of intraocular surgical maneuvers in certain difficult-to-manage vitreoretinal disorders. These substances have a high specific gravity and are able to displace water within the eye, facilitating reattachment of the retina in certain types of retinal detachments such as those associated with proliferative vitreoretinopathy and giant retinal tears. PFCLs also aid in the removal of intravitreal lens fragments or foreign bodies and in the repositioning or removal of dislocated intraocular lenses. 3. Ophthalmic nurses and technicians can play an important role in initial screening for these patients. Detection of symptoms may lead to early diagnosis of idiopathic macular hole and subsequent treatment. Patient education emphasizing topics such as the importance of strict postoperative face-down head positioning may be critical for successful surgery.


Holocephalocotyle monstrosae n. gen. n. sp. (Monogenea, Monocotylidae) from the olfactory rosette of the rabbit fish, Chimaera monstrosa (Holocephali, Chimaeridae) in deep waters off Algeria.
Based on a molecular and morphological study, a new monocotylid genus, Holocephalocotyle n. gen. is proposed to accommodate Holocephalocotyle monstrosae n. sp., found on the olfactory rosette of the rabbit fish, Chimaera monstrosa Linnaeus (Chondrichthyes, Chimaeridae), from the Mediterranean Sea off Algeria. Identification of fish hosts was confirmed by molecular barcoding of the COI gene. A partial 28S rDNA sequence (D1-D2 domain) of Holocephalocotyle monstrosae was obtained; it was distinct from all known monocotylid sequences (p-distance: 15.5-23%). A phylogenetic tree constructed from available monocotylid sequences showed that Holocephalocotyle monstrosae was included, and basal, in a robust group including species of Merizocotyle, Mycteronastes and Empruthotrema, confirming that the species is a member of the Merizocotylinae. The new genus is unique among the Merizocotylinae in having a distinctive pattern of haptoral loculi with one central, five peripheral and seven "interperipheral loculi" partially inserted between peripheral loculi and a compartmentalised sclerotised male copulatory organ. The diagnosis of the Merizocotylinae is amended to include this new genus. The new genus represents the second monocotylid genus recorded from holocephalans.


Structure of S. aureus HPPK and the discovery of a new substrate site inhibitor.
The first structural and biophysical data on the folate biosynthesis pathway enzyme and drug target, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), from the pathogen Staphylococcus aureus is presented. HPPK is the second essential enzyme in the pathway catalysing the pyrophosphoryl transfer from cofactor (ATP) to the substrate (6-hydroxymethyl-7,8-dihydropterin, HMDP). In-silico screening identified 8-mercaptoguanine which was shown to bind with an equilibrium dissociation constant, K(d), of ∼13 µM as measured by isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). An IC(50) of ∼41 µM was determined by means of a luminescent kinase assay. In contrast to the biological substrate, the inhibitor has no requirement for magnesium or the ATP cofactor for competitive binding to the substrate site. The 1.65 Å resolution crystal structure of the inhibited complex showed that it binds in the pterin site and shares many of the key intermolecular interactions of the substrate. Chemical shift and (15)N heteronuclear NMR measurements reveal that the fast motion of the pterin-binding loop (L2) is partially dampened in the SaHPPK/HMDP/α,β-methylene adenosine 5'-triphosphate (AMPCPP) ternary complex, but the ATP loop (L3) remains mobile on the µs-ms timescale. In contrast, for the SaHPPK/8-mercaptoguanine/AMPCPP ternary complex, the loop L2 becomes rigid on the fast timescale and the L3 loop also becomes more ordered--an observation that correlates with the large entropic penalty associated with inhibitor binding as revealed by ITC. NMR data, including (15)N-(1)H residual dipolar coupling measurements, indicate that the sulfur atom in the inhibitor is important for stabilizing and restricting important motions of the L2 and L3 catalytic loops in the inhibited ternary complex. This work describes a comprehensive analysis of a new HPPK inhibitor, and may provide a foundation for the development of novel antimicrobials targeting the folate biosynthetic pathway.


[Effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring].
To evaluate the effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring. Twenty children with snoring aged 4-6 years of either gender (ASA grade Ⅰ and Ⅱ) were selected for adenoidectomy.Before, during and 3 days after the operation, salivary melatonin levels of the children were measured at 11 selected time points (T1-T11).The illumination intensity and body temperature of the children were recorded at each time point of measurement.The sleep time of the children in 3 days after the operation was recorded, and postoperative pain scores (FLACC) and Riker and Rehabilitation Quality Rating Scale-15(QoR-15) scores were assessed.Sleep Apnea Life Quality Evaluation Questionnaire (OSA-18) was used to evaluate postoperative recovery of the children at 28 days after the operation.The incidence of major adverse events of the children during hospitalization was recorded. No significant difference was found in baseline salivary melatonin level among the 20 children before the operation.Salivary melatonin level at 7 am after the operation (T8) was significantly lowered as compared with that before the surgery (T4)(P < 0.05) but recovered at 7 am on the second day after the surgery (T11);salivary melatonin levels at T4, T8, and T11 exceeded 3 pg/mL on the third day.No significant difference was found in illumination intensity or body temperature across the time points when melatonin level was measured.The children showed no significant changes in FLACC score, Riker score or QOR- 15 score after the operation, but the OSA-18 score was significantly lowered after the operation (P < 0.05).None of the 20 children had such adverse events as respiratory depression, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea or vomiting during hospitalization. In preschool children with snoring, general anesthesia affects but does not inhibit melatonin secretion on the first night after surgery, and minor surgeries under general anesthesia in the morning do not cause significant changes in melatonin secretion to cause disturbance of the circadian rhythm in these children.


Determination of chlorobiphenyls in seal blubber, marine sediment, and fish: interlaboratory study.
Between 1988 and 1994, the International Council for the Exploration of the Sea, the Intergovernmental Oceanographic Commission, and the Oslo and Paris Commissions organized a stepwise interlaboratory study for determination of chlorobiphenyls (CBs) in marine media. The final parts of this study, in which 53 laboratories from 14 countries participated, focused on long-term precision, cleanup, and extraction. Calibration was controlled continuously by analysis of 10 CBs in an unknown solution. Participants were requested to analyze 3 CBs in a certified reference material fish oil (6 times); 10 CBs in cleaned and uncleaned marine sediment and seal blubber extracts; and 10 CBs in seal blubber oil, dried marine sediment, and wet, lean fish muscle tissue. The long-term precision study showed that, compared with earlier exercises in which only duplicate analyses were required, repeatability increased about 1.5-fold compared with reproducibility. The mean standard error for reproducibility of determination of 10 CBs in standard solutions improved from 1.22 to 1.15. The standard error improved from 1.36 to 1.25 (without CBs 28 and 31) for seal blubber oil and from 1.36 to 1.22 for dried marine sediment. In seal blubber oil and dried marine sediment, the major CBs 118, 138, 153, and 180 can now be determined by the group of participating laboratories with a reproducibility of 1.5 (about 50%). No significant differences were found between results for cleaned-up and uncleaned extracts. No acceptable results could be obtained for determination of CBs in lean fish muscle tissue. Biplots of principal component analyses are extremely helpful in evaluating the data generated by this type of study.


[Expression, purification, and characterization Mycobacterium tuberculosis Rv1168c].
To express and purify the Pro-Pro-Glu (PPE) family protein Rv1168c of Mycobacterium tuberculosis in E. coli. and to study the structure of Rv1168c. The Rv1168c gene was amplified by PCR from Mycobacterium tuberculosis H37Rv strain genomic DNA and cloned into a prokaryotic expression vector pET32a The resulting recombinant expression plasmid pET32a-Rv1168c was then transformed into the E. coli strain DH5alpha and a high-level expression E. coli BL21(DE3) was established after induction with Isopropyl-beta-D-thiogalactopyranoside (IPTG). SDS-PAGE and mass spectrum analysis determined the relative molecular weight of this recombinant Rv1168c protein. It's secondary and 3D structures were determined by circular dichroism and homologous modeling. The Mycobacterium tuberculosis Rv1168c gene (971bp) and high purified recombinant Rv1168c protein was obtained. The relative molecular weight of recombinant Rv1168c protein was determined to be 51.5 kDa (vector included). Secondary structure of Rv1168c had about 34.4% alpha helix, 33.7%, beta tune, 31.9% random coil at 25 delta C. Homologous modeling shows Rv1168c as (beta/alpha)5 protein. This study obtained purified recombinant Rv1168c protein and laid the foundation for exploration of the relationship between the structure and function of Rv1168c in the tuberculosis.


Arabidopsis Root-Type Ferredoxin:NADP(H) Oxidoreductase 2 is Involved in Detoxification of Nitrite in Roots.
Ferredoxin:NADP(H) oxidoreductase (FNR) plays a key role in redox metabolism in plastids. Whereas leaf FNR (LFNR) is required for photosynthesis, root FNR (RFNR) is believed to provide electrons to ferredoxin (Fd)-dependent enzymes, including nitrite reductase (NiR) and Fd-glutamine-oxoglutarate aminotransferase (Fd-GOGAT) in non-photosynthetic conditions. In some herbal species, however, most nitrate reductase activity is located in photosynthetic organs, and ammonium in roots is assimilated mainly by Fd-independent NADH-GOGAT. Therefore, RFNR might have a limited impact on N assimilation in roots grown with nitrate or ammonium nitrogen sources. AtRFNR genes are rapidly induced by application of toxic nitrite. Thus, we tested the hypothesis that RFNR could contribute to nitrite reduction in roots by comparing Arabidopsis thaliana seedlings of the wild type with loss-of-function mutants of RFNR2 When these seedlings were grown under nitrate, nitrite or ammonium, only nitrite nutrition caused impaired growth and nitrite accumulation in roots of rfnr2 Supplementation of nitrite with nitrate or ammonium as N sources did not restore the root growth in rfnr2 Also, a scavenger for nitric oxide (NO) could not effectively rescue the growth impairment. Thus, nitrite toxicity, rather than N depletion or nitrite-dependent NO production, probably causes the rfnr2 root growth defect. Our results strongly suggest that RFNR2 has a major role in reduction of toxic nitrite in roots. A specific set of genes related to nitrite reduction and the supply of reducing power responded to nitrite concomitantly, suggesting that the products of these genes act co-operatively with RFNR2 to reduce nitrite in roots.


A multichannel color filter with the functions of optical sensor and switch.
This paper reports a multichannel color filter with the functions of optical sensor and switch. The proposed structure comprises a metal-insulator-metal (MIM) bus waveguide side-couples to six circular cavities with different sizes for filtering ultra-violet and visible lights into individual colors in the wavelength range of 350-700 nm. We used the finite element method to analyze the electromagnetic field distributions and transmittance properties by varying the structural parameters in detail. The designed plasmonic filter takes advantage of filtering out different colors since the light-matter resonance and interference between the surface plasmon polaritons (SPPs) modes within the six cavities. Results show that the designed structure can preferentially select the desired colors and confine the SPPS modes in one of the cavities. This designed structure can filter eleven color channels with a small full width at half maximum (FWHM) ~ 2 nm. Furthermore, the maximum values of sensitivity, figure of merit, quality factor, dipping strength, and extinction ratio can achieve of 700 nm/RIU, 350 1/RIU, 349.0, 65.04%, and 174.50 dB, respectively, revealing the excellent functions of sensor performance and optical switch, and offering a chance for designing a beneficial nanophotonic device.


Excess enthalpies of mixing, effect of temperature and composition on the density, and viscosity and thermodynamic properties of binary systems of {ammonium-based ionic liquid + alkanediol}.
In the present work the excess enthalpies of butyltrimethylammonium bis(trifluoromethyl-sulfonyl)imide, [N1114][NTf2], with 1,2-propanediol, or 1,2-butanediol, or 2,3-butanediol have been measured at T = 298.15 K. Additionally, the density, ρ, and dynamic viscosity, η, for binary solutions containing ionic liquids (ILs) and alkanedioles, {butyltrimethylammonium bis(trifluoromethyl-sulfonyl)imide, [N1114][NTf2], + 1,2-propanediol, 1,2-butanediol, 2,3-butanediol} and {(2-hydroxyethyl)trimethylammonium bis(trifluoro-methylsulfonyl)imide, [N1112OH][NTf2], + 1,2-propanediol, 1,3-propanediol, 1,5-pentanediol}, at wide temperature and composition ranges at ambient pressure have been investigated. From experimental values of the density, ρ, and dynamic viscosity, η, the excess molar volumes, V(E), and dynamic viscosity deviations, Δη, were calculated and correlated using the Redlich-Kister polynomial equation. The temperature dependence of density and viscosity for the tested binary systems was described by an empirical second-order polynomial and by the Vogel-Fucher-Tammann equation, respectively. The variation of density and viscosity as a function of composition has been described by the polynomial correlations. Comparison of the experimental results for the binary mixtures tested in this work allows us to determine the influence of alkanediol carbon chain length, the position of the hydroxyl group in the alcohol, and the influence of the structure of the cation of the ionic liquid on the presented properties.


Three di-O-caffeoylquinic acid derivatives from the heads of Cynara scolymus L.
Three di-O-caffeoylquinic acid derivatives were isolated from the ethanol extracts of the heads of Cynara scolymus L. Their structures were elucidated based on spectra analyses.


Multiple Aspects of Gene Dysregulation in Huntington's Disease.
Huntington's Disease (HD) is a genetic neurodegenerative disease caused by a CAG expansion in the gene encoding Huntingtin (Htt). It is characterized by chorea, cognitive, and psychiatric disorders. The most affected brain region is the striatum, and the clinical symptoms are directly correlated to the rate of striatal degeneration. The wild-type Htt is a ubiquitous protein and its deletion is lethal. Mutated (expanded) Htt produces excitotoxicity, mitochondrial dysfunctions, axonal transport deficit, altered proteasome activity, and gene dysregulation. Transcriptional dysregulation occurs at early neuropathological stages in HD patients. Multiple genes are dysregulated, with overlaps of altered transcripts between mouse models of HD and patient brains. Nuclear localization of Exp-Htt interferes with transcription factors, co-activators, and proteins of the transcriptional machinery. Another key mechanism described so far, is an alteration of cytoplasmic retention of the transcriptional repressor REST, which is normally associated with wild-type Htt. As such, Exp-Htt causes alteration of transcription of multiple genes involved in neuronal survival, plasticity, signaling, and mitochondrial biogenesis and respiration. Besides these transcriptional dysregulations, Exp-Htt affects the chromatin structure through altered post-translational modifications (PTM) of histones and methylation of DNA. Multiple alterations of histone PTM are described, including acetylation, methylation, ubiquitylation, polyamination, and phosphorylation. Exp-Htt also affects the expression and regulation of non-coding microRNAs (miRNAs). First multiple neural miRNAs are controlled by REST, and dysregulated in HD, with concomitant de-repression of downstream mRNA targets. Second, Exp-Htt protein or RNA may also play a major role in the processing of miRNAs and hence pathogenesis. These pleiotropic effects of Exp-Htt on gene expression may represent seminal deleterious effects in the pathogenesis of HD.


Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects.
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype. The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics. ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy. Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.


Idiopathic autonomic neuropathy: comparison of cases seropositive and seronegative for ganglionic acetylcholine receptor antibody.
The clinical characteristics of autoimmune autonomic neuropathy are only partially defined. More than 50% of patients with high levels of ganglionic acetylcholine receptor (AChR) autoantibodies have a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal tract symptoms, and neurogenic bladder. To compare patients with idiopathic autonomic neuropathy who were seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. Retrospective review of autonomic programmatic database. Autonomic Disorders Program Project at Mayo Clinic College of Medicine, Rochester, Minn. We evaluated a cohort of 87 patients with idiopathic autonomic neuropathy who had undergone full autonomic testing and neurological evaluation and who had a complete panel of paraneoplastic and ganglionic AChR antibodies. We compared patients seropositive (n = 19) and seronegative (n = 87) for ganglionic AChR antibodies. The seropositive group had a significant overrepresentation of abnormal pupillary responses (12/18 [67%] vs 12/87 [14%]; P<.001), sicca complex (9/15 [60%] vs 11/47 [23%]; P =.01), and lower gastrointestinal tract dysautonomia (16/19 [84%] vs 48/85 [56%]; P =.02). A subacute mode of onset was more common in the seropositive group (12/19 [63%] vs 23/84 [27%]; P =.004). Results of quantitative autonomic function tests differed significantly in the 2 groups only in the cardiovagal domain. Because subacute onset was overrepresented in the seropositive group, we analyzed the data separately, controlling for temporal profile (ie, the relationship between antibody status and symptoms while controlling for rate of onset). The relationships between antibody status and clinical profile (eg, presence of sicca complex, pupillary abnormalities, and lower gastrointestinal tract symptoms) generally remained significant regardless of onset rate, indicating that the associations are not due to temporal profile. These observations support the concept that ganglionic AChR antibodies are diagnostically and pathophysiologically important. Patients with orthostatic hypotension and prominent cholinergic dysautonomia are most likely to be seropositive for ganglionic AChR antibody.


Role of antibiotics for the prevention of cardiovascular disease.
To evaluate the data regarding the use of antibiotic therapy for the prevention of cardiovascular events. Pertinent literature was identified through a MEDLINE search (1966-September 2001) and through other secondary literature databases and/or bibliographies of pertinent articles. Cardiovascular disease is a common cause of morbidity and mortality among the general population, with well-defined risk factors (e.g., diabetes, hypertension, hyperlipidemia, cigarette smoking, genetic predisposition). Clinical data evaluating the association between the aforementioned risk factors and the development of atherosclerosis and subsequent cardiovascular disease are substantial; however, these risk factors may only partially explain the high prevalence of cardiovascular disease. The presence of Chlamydia pneumoniae within atherosclerotic lesions has been documented and may be an additional risk factor for the development and progression of cardiovascular disease. The results of primary and secondary prevention trials have shown conflicting evidence with regard to the beneficial effects of antibiotic therapy to reduce cardiovascular events. Currently, the lack of certainty in published data does not support the use of antibiotics for the prevention of cardiovascular disease. Clinicians should continue to emphasize interventions proven to reduce adverse cardiovascular events such as smoking cessation, reduction of hyperlipidemia, and control of hypertension.


Endoscopic ultrasound in clinical practice.
Endoscopic ultrasonography (EUS) is an accurate technique for the diagnosis and staging of benign and malignant lesions in the gastrointestinal tract and the mediastinum. EUS overcomes the limitations of other imaging diagnostic methods and gives the possibility to obtain tissue for histologic diagnosis (EUS guided FNA). The most useful indications of EUS are differentiation of submucosal tumors, staging for neoplasia, examination of the pancreato-biliary system and therapeutics. EUS can distinguish extrinsic compressions from intramural lesions and defines their nature (solid, cystic or vascular) and origin. EUS is useful for local staging of esophageal, gastric, duodenal, and rectal cancer using the TNM (tumor, node, metastases) system, as well as for diagnosing and staging of pancreatic lesions. The addition of EUS-guided FNA has improved the ability to detect malignant lymph node invasion. EUS is also highly sensitive for the diagnosis of choledocholithiasis, avoiding unnecessary danger of diagnostic ERCP. New therapeutic indications of EUS include drainage of pancreatic pseudocysts and abscesses and celiac plexus block and neurolysis. EUS has become an indispensable diagnostic method in gastroenterological everyday practice and should be part of most endoscopy units.


Whole Genome-Based Characterization of Listeria monocytogenes Isolates Recovered From the Food Chain in South Africa.
Listeria monocytogenes is an important foodborne pathogen which has the ability to adapt and survive in food and food processing facilities where it can persist for years. In this study, a total of 143 L. monocytogenes isolates in South Africa (SA) were characterized for their strain's genetic relatedness, virulence profiles, stress tolerance and resistance genes associated with L. monocytogenes. The Core Genome Multilocus Sequence Typing (cgMLST) analysis revealed that the most frequent serogroups were IVb and IIa; Sequence Types (ST) were ST204, ST2, and ST1; and Clonal Complexes (CC) were CC204, CC1, and CC2. Examination of genes involved in adaptation and survival of L. monocytogenes in SA showed that ST1, ST2, ST121, ST204, and ST321 are well adapted in food processing environments due to the significant over-representation of Benzalkonium chloride (BC) resistance genes (bcrABC cassette, ermC, mdrL and Ide), stress tolerance genes (SSI-1 and SSI-2), Prophage (φ) profiles (LP_101, vB LmoS 188, vB_LmoS_293, and B054 phage), plasmids profiles (N1-011A, J1776, and pLM5578) and biofilm formation associated genes. Furthermore, the L. monocytogenes strains that showed hyper-virulent potential were ST1, ST2 and ST204, and hypo-virulent were ST121 and ST321 because of the presence and absence of major virulence factors such as LIPI-1, LIPI-3, LIPI-4 and the internalin gene family members including inlABCEFJ. The information provided in this study revealed that hyper-virulent strains ST1, ST2, and ST204 could present a major public health risk due to their association with meat products and food processing environments in SA.


Sorption of Cationic Surfactants to Artificial Cell Membranes: Comparing Phospholipid Bilayers with Monolayer Coatings and Molecular Simulations.
This study reports the distribution coefficient between phospholipid bilayer membranes and phosphate buffered saline (PBS) medium (DMW,PBS) for 19 cationic surfactants. The method used a sorbent dilution series with solid supported lipid membranes (SSLMs). The existing SSLM protocol, applying a 96 well plate setup, was adapted to use 1.5 mL glass autosampler vials instead, which facilitated sampling and circumvented several confounding loss processes for some of the cationic surfactants. About 1% of the phospholipids were found to be detached from the SSLM beads, resulting in nonlinear sorption isotherms for compounds with log DMW values above 4. Renewal of the medium resulted in linear sorption isotherms. DMW values determined at pH 5.4 demonstrated that cationic surfactant species account for the observed DMW,PBS. Log DMW,PBS values above 5.5 are only experimentally feasible with lower LC-MS/MS detection limits and/or concentrated extracts of the aqueous samples. Based on the number of carbon atoms, dialkylamines showed a considerably lower sorption affinity than linear alkylamine analogues. These SSLM results closely overlapped with measurements on a chromatographic tool based on immobilized artificial membranes (IAM-HPLC) and with quantum-chemistry based calculations with COSMOmic. The SSLM data suggest that IAM-HPLC underestimates the DMW of ionized primary and secondary alkylamines by 0.8 and 0.5 log units, respectively.


Molecular recognition in the gas phase: benzocaine-phenol as a model of anaesthetic-receptor interaction.
The benzocaine-phenol complex is proposed as a model system of the interaction between the local anaesthetic benzocaine and the tyrosine residue. The complex has been generated by supersonic expansion of benzocaine and phenol in helium and probed by 1- and 2-color mass-resolved laser spectroscopies. The electronic excitation spectrum of the 1 : 1 complex spans some approximately 700 cm(-1) and includes well resolved bands from at least two isomers, as demonstrated using UV-UV hole burning spectroscopy. The combination of ion dip infrared spectroscopy (IDIRS) and ab initio calculations shows that both isomers are stabilized by an OH...N hydrogen bond between the phenol hydroxyl group and the benzocaine amino moiety, differing only in the conformation adopted by the benzocaine monomer (trans and gauche). The application of the fragmentation threshold method to benzocaine-phenol suggests the existence of chemical reactions in the electronic excited state of the complex and/or in the ion. Such hypothesis is also supported by the calculated potential energy curves along the hydrogen bond coordinate.


Item Response Theory Modeling of the International Prostate Symptom Score in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia.
Item response theory (IRT) was used to characterize the time course of lower urinary tract symptoms due to benign prostatic hyperplasia (BPH-LUTS) measured by item-level International Prostate Symptom Scores (IPSS). The Fisher information content of IPSS items was determined and the power to detect a drug effect using the IRT approach was examined. Data from 403 patients with moderate-to-severe BPH-LUTS in a placebo-controlled phase II trial studying the effect of degarelix over 6 months were used for modeling. Three pharmacometric models were developed: a model for total IPSS, a unidimensional IRT model, and a bidimensional IRT model, the latter separating voiding and storage items. The population-level time course of BPH-LUTS in all models was described by initial improvement followed by worsening. In the unidimensional IRT model, the combined information content of IPSS voiding items represented 72% of the total information content, indicating that the voiding subscore may be more sensitive to changes in BPH-LUTS compared with the storage subscore. The pharmacometric models showed considerably higher power to detect a drug effect compared with a cross-sectional and while-on-treatment analysis of covariance, respectively. Compared with the sample size required to detect a drug effect at 80% power with the total IPSS model, a reduction of 5.9% and 11.7% was obtained with the unidimensional and bidimensional IPSS IRT model, respectively. Pharmacometric IRT analysis of the IPSS within BPH-LUTS may increase the precision and efficiency of treatment effect assessment, albeit to a more limited extent compared with applications in other therapeutic areas.


The educational value of peer groups from a general practitioner perspective.
Peer review groups are compulsory for New Zealand (NZ) general practitioners (GPs) but little is known about how they function. This study aimed to understand the educational value of peer group meetings to general practitioners and explore methods of increasing value. A qualitative study was undertaken comprising a single meeting involving 22 NZ GPs with an interest in education and subsequent thematic analysis on the raw data. Respondents indicated a strong belief in the educational value of peer groups. Pastoral care was also perceived as a valuable outcome of peer groups that was somewhat separate from the educational value. It would appear that the majority of peer groups work on the basis of internally driven contemporaneous learning needs based on difficult work experiences. There was limited concern over the wide interpretation of what constitutes acceptable topics for discussion as well as the informal nature of training and structuring the meetings. The interactive nature of peer group learning with subject matter of 'real life' problems would suggest peer groups have the potential to make significant change in the performance of doctors. A broad and differing range of experience in the group is more likely to generate an educationally valuable environment. It would appear that there may be a limited role for assisting peer groups with methods of structuring content and increasing effectiveness.


Electrophysiological and clinical characteristics of catheter ablation for isolated left side atrial tachycardia over a 10-year period.
Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.


A new nanosecond UV laser at 355 nm: early results of corneal flap cutting in a rabbit model.
A new 355 nm UV laser was used for corneal flap cutting in an animal model and tested for clinical and morphologic alterations. Corneal flaps were created (Chinchilla Bastards; n = 25) with an UV nanosecond laser at 355 nm (150 kHz, pulse duration 850 ps, spot-size 1 μm, spot spacing 6 × 6 μm, side cut Δz 1 μm; cutting depth 130 μm) and pulse energies of 2.2 or 2.5 μJ, respectively. Following slit-lamp examination, animals were killed at 6, 12, and 24 hours after treatment. Corneas were prepared for histology (hematoxylin and eosin [HE], TUNEL-assay) and evaluated statistically, followed by ultrastructural investigations. Laser treatment was tolerated well, flap lift was easier at 2.5 μJ compared with 2.2 μJ. Standard HE at 24 hours revealed intact epithelium in the horizontal cut, with similar increase in corneal thickness at both energies. Irrespective of energy levels, TUNEL assay revealed comparable numbers of apoptotic cells in the horizontal and vertical cut at 6, 12, and 24 hours, becoming detectable in the horizontal cut as an acellular stromal band at 24 hours. Ultrastructural analysis revealed regular morphology in the epi- and endothelium, while in the stroma, disorganized collagen lamellae were detectable representing the horizontal cut, again irrespective of energy levels applied. This new UV laser revealed no epi- nor endothelial damage at energies feasible for corneal flap cutting. Observed corneal swelling was lower compared with existing UV laser studies, albeit total energy applied here was much higher. Observed loss of stromal keratinocytes is comparable with available laser systems. Therefore, this new laser is suitable for refractive surgery, awaiting its test in a chronic environment.


An increase in basophils in a case of acute myelomonocytic leukaemia associated with marrow eosinophilia and inversion of chromosome 16.
A patient with acute myelomonocytic leukaemia (M4 subtype) with pericentric inversion of chromosome 16, inv(16)(p13q22), and a marked basophilia is described. Results from transmission electron microscopy suggested that the basophils were immature. Clinically, although leukaemic cells had a tendency to infiltrate a number of tissues and organs, such as skin, gingiva, liver and lung, the patient was successfully treated with chemotherapy. The increase in basophils accompanied by marrow eosinophilia may be the result of abnormal differentiation of leukaemic cells that have the capacity to differentiate into both the eosinophilic and basophilic pathways.


Transcriptomic Analysis Reveals Important Roles of Lignin and Flavonoid Biosynthetic Pathways in Rice Thermotolerance During Reproductive Stage.
Rice is one of the major staple cereals in the world, but heat stress is increasingly threatening its yield. Analyzing the thermotolerance mechanism from new thermotolerant germplasms is very important for rice improvement. Here, physiological and transcriptome analyses were used to characterize the difference between two germplasms, heat-sensitive MH101 and heat-tolerant SDWG005. Two genotypes exhibited diverse heat responses in pollen viability, pollination characteristics, and antioxidant enzymatic activity in leaves and spikelets. Through cluster analysis, the global transcriptomic changes indicated that the ability of SDWG005 to maintain a steady-state balance of metabolic processes played an important role in thermotolerance. After analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, we found that the thermotolerance mechanism in SDWG00 was associated with reprogramming the cellular activities, such as response to abiotic stress and metabolic reorganization. In contrast, the down-regulated genes in MH101 that appeared to be involved in DNA replication and DNA repair proofreading, could cause serious injury to reproductive development when exposed to high temperature during meiosis. Furthermore, we identified 77 and 11 differentially expressed genes (DEGs) involved in lignin and flavonoids biosynthetic pathways, respectively. Moreover, we found that more lignin deposition and flavonoids accumulation happened in SDWG005 than in MH101 under heat stress. The results indicated that lignin and flavonoid biosynthetic pathways might play important roles in rice heat resistance during meiosis.


GLUT2 immunoreactivity in Gomori-positive astrocytes of the hypothalamus.
A specialized subtype of astrocyte, the Gomori-positive (GP) astrocyte, is unusually abundant and prominent in the arcuate nucleus of the hypothalamus. GP astrocytes possess cytoplasmic granules derived from degenerating mitochondria. GP granules are highly stained by Gomori's chrome alum hematoxylin stain, by the Perl's reaction for iron, or by toluidine blue. The source of the oxidative stress causing mitochondrial damage in GP astrocytes is uncertain, but such damage could arise from the oxidative metabolism of glucose transported into astrocytes by high-capacity GLUT2 glucose transporters. In accord with this hypothesis, the reported anatomical distribution of astrocytes staining positively for GLUT2 glucose transporters closely matches that of GP astrocytes. To examine whether or not these two staining procedures detect the same population of astrocytes, immunocytochemistry was performed on semithin sections to detect GLUT2 protein and sections were then stained with toluidine blue to detect GP granules. It was determined that GP astrocytes are frequently immunoreactive for the GLUT2 transporter protein. These data support the possibility that GP astrocytes may have an important influence upon the reactivity of the hypothalamus to glucose and that a specialized glucose metabolism may in part underlie the development of mitochondrial abnormalities in hypothalamic GP astrocytes.


Climate change and diminishing seasonality in Arctic benthic processes.
The iconic picture of Arctic marine ecosystems shows an intense pulse of biological productivity around the spring bloom that is sustained while fresh organic matter (OM) is available, after which ecosystem activity declines to basal levels in autumn and winter. We investigated seasonality in benthic biogeochemical cycling at three stations in a high Arctic fjord that has recently lost much of its seasonal ice-cover. Unlike observations from other Arctic locations, we find little seasonality in sediment community respiration and bioturbation rates, although different sediment reworking modes varied through the year. Nutrient fluxes did vary, suggesting that, although OM was processed at similar rates, seasonality in its quality led to spring/summer peaks in inorganic nitrogen and silicate fluxes. These patterns correspond to published information on seasonality in vertical flux at the stations. Largely ice-free Kongsfjorden has a considerable detrital pool in soft sediments which sustain benthic communities over the year. Sources of this include macroalgae and terrestrial runoff. Climate change leading to less ice cover, higher light availability and expanded benthic habitat may lead to more detrital carbon in the system, dampening the quantitative importance of seasonal pulses of phytodetritus to seafloor communities in some areas of the Arctic. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.


The structure of glycogen phosphorylase b with an alkyldihydropyridine-dicarboxylic acid compound, a novel and potent inhibitor.
In muscle and liver, glycogen concentrations are regulated by the reciprocal activities of glycogen phosphorylase (GP) and glycogen synthase. An alkyl-dihydropyridine-dicarboxylic acid has been found to be a potent inhibitor of GP, and as such has potential to contribute to the regulation of glycogen metabolism in the non-insulin-dependent diabetes diseased state. The inhibitor has no structural similarity to the natural regulators of GP. We have carried out structural studies in order to elucidate the mechanism of inhibition. Kinetic studies with rabbit muscle glycogen phosphorylase b (GPb) show that the compound (-)(S)-3-isopropyl 4-(2-chlorophenyl)-1,4-dihydro-1-ethyl-2-methyl-pyridine-3,5, 6-tricarboxylate (Bay W1807) has a Ki = 1.6 nM and is a competitive inhibitor with respect to AMP. The structure of the cocrystallised GPb-W1807 complex has been determined at 100K to 2.3 A resolution and refined to an R factor of 0.198 (Rfree = 0.287). W1807 binds at the GPb allosteric effector site, the site which binds AMP, glucose-6-phosphate and a number of other phosphorylated ligands, and induces conformational changes that are characteristic of those observed with the naturally occurring allosteric inhibitor, glucose-6-phosphate. The dihydropyridine-5,6-dicarboxylate groups mimic the phosphate group of ligands that bind to the allosteric site and contact three arginine residues. The high affinity of W1807 for GP appears to arise from the numerous nonpolar interactions made between the ligand and the protein. Its potency as an inhibitor results from the induced conformational changes that lock the enzyme in a conformation known as the T' state. Allosteric enzymes, such as GP, offer a new strategy for structure-based drug design in which the allosteric site can be exploited. The results reported here may have important implications in the design of new therapeutic compounds.


Liraglutide-loaded multivesicular liposome as a sustained-delivery reduces blood glucose in SD rats with diabetes.
Subcutaneous liraglutide-loaded multivesicular liposomes (Lrg-MVLs) were developed as a sustained drug-delivery system for treating diabetes and their properties were characterized. The Lrg-MVLs prepared using a two-step water-in-oil-in-water double emulsification process had a spherical appearance with a mean diameter of 6.69 μm and an encapsulation efficiency of 82.23 ± 4.78% without any initial burst release. Their pharmacodynamics (PD) and pharmacokinetics (PK) were also studied after a single subcutaneous administration to Sprague-Dawley (SD) rats with diabetes. The PD results demonstrated that Lrg-MVLs presented sustained glucose-lowering effects for nearly a week, while the pharmacokinetic parameters showed that the plasma liraglutide concentration of the designed preparation produced Cmax of 81.979 ± 12.140 pg/ml and an MRT0-t of 88.224 ± 3.893 h. Furthermore, retention of Lrg-MVLs at the injection site was studied semiquantitatively by an in vivo imaging system, which can be used to evaluate the drug release from MVLs in vivo. In conclusion, MVLs are a promising carrier for liraglutide and Lrg-MVLs deserve further study for the treatment of diabetes.


Human Papillomavirus awareness, knowledge and vaccine acceptance: a survey among 18-25 year old male and female vocational school students in Berlin, Germany.
Human Papillomavirus (HPV) is a common sexually transmitted infection and is aetiologically linked with a number of health problems. In Germany, HPV vaccination for cervical cancer prevention is recommended for girls aged 12-17 years since 2007; however, a coordinated national immunization programme does not exist. We assessed whether socio-demographic factors and sexual history are associated with awareness of HPV and the HPV vaccine, vaccine uptake and HPV-related knowledge among young women and men. In 2010, a survey was conducted with 18- to 25-year-old students from six vocational schools in Berlin. A total of 259 women and 245 men completed the questionnaire that included socio-demographic and sexual behaviour characteristics, questions about HPV awareness, vaccine status, reasons for not wanting to get vaccinated and HPV-related knowledge. Among women aged 18-20 years (those eligible for reimbursed vaccination), 67% were vaccinated. At trend level, women with low education and those without past sexual intercourse were less likely to be vaccinated. Ninety-five per cent of the women and 80% of the men were aware of the 'vaccine against cervical cancer', but only half of the women and 25% of the men had heard of HPV. Knowledge was poor (M = 2.8; SD = 2.10 for women and M = 1.5; SD = 1.49 for men; possible range 0-11). Fifty-one per cent of the women and 42% of the men thought that only women can be infected with HPV and the majority did not know that HPV is sexually transmitted. Results indicate a need for better education about HPV that should extend beyond its link with cervical cancer.


Gene expression analysis identifies novel genes participating in early murine liver development and adult liver regeneration.
Adult liver tissue regeneration may recapitulate molecular events of liver organogenesis. As gaps in our understanding of the fundamental processes that govern development and regeneration of the liver still exist, we studied gene expression in the developing liver at embryonic day 9.5 post coitum (E d9.5 p.c.). Microarray data from E d9.5 p.c. as well as previously published data from embryonic day 11.5 post coitum (E d11.5 p.c.) and embryonic day 13.5 post coitum (E d13.5 p.c.) were subjected to cluster analysis. This led to the identification of 130 genes which were characterized by continuous expression at all stages of liver development with peak expression of 44 genes at E d9.5 p.c. Five of these genes, previously not known to be associated with early liver development or with adult liver regeneration were selected for further analysis. The expression of the genes was studied by real-time polymerase chain reaction at 0, 2, 4, 6, 12, 24 and 48 hr after partial hepatectomy in the adult liver. Two of the genes, growth arrest protein 43 (GAP43) and paired-like homeodomain transcription factor 2 (Pitx2) were exclusively detected at 24 hr, whereas the genes Twist1, Midkine, and zinc finger protein of cerebellum 1 (Zic1) each showed a specific expression profile in the regenerating liver with peak expressions at 4, 24, and 6 hr, respectively. In summary, we were able to identify novel genes, that may act as regulators during liver formation as well as in the regeneration phase of adult liver. This information may contribute to the development of new targets for the treatment of liver diseases in the future.


Genomic Characterization of Low- and High-Grade Pancreatic Mucinous Cystic Neoplasms Reveals Recurrent KRAS Alterations in "High-Risk" Lesions.
Pancreatic ductal adenocarcinoma arises from the following 3 distinct precursor lesions: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm (MCN). Genetic abnormalities in the first 2 precursor lesions have been well characterized, but there are limited data on progression pathways in MCNs. This study aimed to characterize genomic differences between MCNs with low-grade (LG) and high-grade (HG) dysplasia or carcinoma. Neoplastic epithelium from surgical resections of 25 MCNs, 16 with LG dysplasia and 9 with HG dysplasia or invasive carcinoma, was analyzed by targeted massively parallel sequencing. KRAS mutations were most frequent, present in 9 HG (100%) and 3 LG (19%) tumors, 2 of the latter also having discrete areas of HG tumor with the same mutation. TP53 mutations and CDKN2A loss were identified in 5 HG tumors (56%) each but not in LG tumors. The low frequency of KRAS alterations in cysts without a HG component suggests that a subset of MCNs may have a low risk for malignant progression. Novel single-nucleotide variants that occur at a lower rate may help identify this group and provide a substrate for new diagnostic, prognostic, and therapeutic targets.


« Moi d'abord ! » ou l'égocentrisme ordinaire : Une revue critique de l'effet de priorité au Soi.
The self is a crucial component of the psychic life and plays a central role for the adaptation to the environment. In daily life, this adaptative function is ensured, inter alia, by numerous biases filtering information and favoring those which are self-related. After succinctly reviewing the most documented among them which are affective and mnesic biases, the current paper provides a critical review of literature about a bias which is supposed to be perceptive, the self-prioritization effect (SPE). That has been revealed by Sui et al. (2012, Journal of Experimental Psychology: Human Perception and Performance, 38(5), 1105) with an astute matching task and consists in the fact that arbitrarily tagging shapes to a word referring to the participant (e.g., you-square) leads to faster and more accurate responses as compared to shapes tagged to a word referring to another identity (e.g., strange-circle). The methodological variations of this task and the SPE's both extension and putative origins will be presented, as well as the restrictions which border it, related to the individuals, to the experimental situation and to some more general properties of the self. Finally, some avenues for future research will be proposed, drawing some promising paths: beyond being a robust and intriguing phenomenon, SPE can indeed be considered as a convenient tool to assess some mechanisms underlying social cognition, in various fields using an experimental approach such as developmental psychology and social psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Efficient N-heterocyclic carbene-catalyzed O- to C-acyl transfer.
[reaction: see text] An N-heterocyclic carbene promotes the rearrangement of alpha-amino acid derived O-acyl carbonates to their corresponding C-acylated isomers, generating a C-C bond and a quaternary stereocenter with high efficiency, under mild reaction conditions and with low catalyst loadings.


Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.
In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.


[Clinical and epidemiological characteristics of chronic open angle glaucoma at a Yaoundé Hospital].
This retrospective study examined the files of patients who consulted at the Women's and Children's Hospital of Yaoundé in Cameroon from March 2003 through December 2006. The main objective was to determine the epidemiological and clinical characteristics of patients diagnosed with chronic open-angle glaucoma (COAG). Of 8,123 files reviewed, 184 patients (54.3% women) were diagnosed with COAG, all but one binocular. Their mean age was 62.2+/-13.01 years. According to the WHO definition of blindness, the rate of bilateral blindness was 34.2%, that of unilateral blindness 21% and low vision 17.4%. Significant statistic correlations were observed between the cup depth of the optic disc and visual acuity on one hand, and between the level of intraocular pressure and cup depth on the other, p=0.0001. Approximately 90.67% of the eyes with glaucoma had high pressure and 9.23% normal pressure. COAG is a major cause of visual disability in Cameroon. Intraocular pressure is an important risk factor, but its positive predictive value for the impairment of optic disc fibres is low (R=0.29); other factors (apoptosis and ischemia of the optic disc) are associated with it. Advanced strategies for early diagnosis of COAG are essential, for this disease is an important cause of blindness. Such programmes would significantly delay the onset of visual disabilities.


Growth pulsations in symmetric dendritic crystallization in thin polymer blend films.
The crystallization of polymeric and metallic materials normally occurs under conditions far from equilibrium, leading to patterns that grow as propagating waves into the surrounding unstable fluid medium. The Mullins-Sekerka instability causes these wave fronts to break up into dendritic arms, and we anticipate that the normal modes of the dendrite tips have a significant influence on pattern growth. To check this possibility, we focus on the dendritic growth of polyethylene oxide in a thin-film geometry. This crystalline polymer is mixed with an amorphous polymer (polymethyl-methacrylate) to "tune" the morphology and clay was added to nucleate the crystallization. The tips of the main dendrite trunks pulsate during growth and the sidebranches, which grow orthogonally to the trunk, pulsate out of phase so that the tip dynamics is governed by a limit cycle. The pulsation period P increases sharply with decreasing film thickness L and then vanishes below a critical value L(c) approximately 80 nm. A change of dendrite morphology accompanies this transition.


Optimization of a rapid and sensitive identification system for Salmonella enteritidis by capillary electrophoresis with laser-induced fluorescence.
A system coupling capillary electrophoresis (CE) with a laser-induced fluorescence (LIF) system for the identification of Salmonella enteritidis was developed. Addition of an appropriate amount of sodium alginate and NaCl to the running buffer made it possible to obtain a reproducible sharp peak. Two fluorescent staining methods using a cell-permeable nucleic acid stain and a salmonellae-specific polyclonal antibody were adapted to the system. The CE-LIF successfully detected as few as three cells per injection from a pure culture of S. enteritidis. The CE-LIF system can be conveniently used for rapid and highly sensitive identification of S. enteritidis.


Scatter correction of transmission near-infrared spectra by photon migration data: quantitative analysis of solids.
The scope of this work is a new methodology to correct conventional near-infrared (NIR) data for scattering effects. The technique aims at measuring the absorption coefficient of the samples rather than the total attenuation measured in conventional NIR spectroscopy. The main advantage of this is that the absorption coefficient is independent of the path length of the light inside the sample and therefore independent of the scattering effects. The method is based on time-resolved spectroscopy and modeling of light transport by diffusion theory. This provides an independent measure of the scattering properties of the samples and therefore of the path length of light. This yields a clear advantage over other preprocessing techniques, where scattering effects are estimated and corrected for by using the shape of the measured spectrum only. Partial least squares (PLS) calibration models show that, by using the proposed evaluation scheme, the predictive ability is improved by 50% as compared to a model based on conventional NIR data alone. The method also makes it possible to predict the concentration of active substance in samples with other physical properties than the samples included in the calibration model.


Observation and understanding of anisotropic strain relaxation in selectively grown SiGe fin structures.
The performance of heterogeneous 3D transistor structures critically depends on the composition and strain state of the buffer, channel and source/drain regions. In this paper we used an in-line high resolution x-ray diffraction (HRXRD) tool to study in detail the composition and strain in selectively grown SiGe/Ge fin structures with widths down to 20 nm. For this purpose we arranged fins of identical dimensions into larger arrays which were then analyzed using an x-ray beam several tens of micrometers in size. Asymmetric reciprocal space maps measured both parallel and perpendicular to the fins allowed us to extract the lattice parameters in all three spatial directions. Our results demonstrate an anisotropic in-plane strain state of the selectively grown SiGe buffer in case of narrower fins with significantly reduced relaxation in the direction along the fin. This observation was verified using nano-beam electron diffraction, and is explained based on the reduced probability for dislocation half-loops to evolve in trenches narrower than a few times the critical radius. Moreover, we introduce and discuss in detail a methodology for the determination of the composition in case of an anisotropic in-plane strain state which differs from the procedure commonly used for blanket layers. Our findings verify the importance of in-line HRXRD measurements for process development and monitoring as well as the fundamental study of relaxation and defect formation in confined volumes.


Energization of the sugar transport mechanism in the plasmalemma of isolated mesophyll protoplasts.
The mechanism of 3-O-methyl-d-glucose transport through the plasmalemma has been investigated in protoplasts isolated from the mesophyll of Pisum sativum L. var. Dan.Analysis of the fluxes after 50 minutes of uptake showed that the gradual decrease in slope of the net uptake curve with time was not due to any decline in uptake capacity; it represented the approach to flux equilibrium of a small compartment of the protoplast, probably the cytoplasm.The energy of activation for initial flux into this compartment was 20 kilocalories per mole between 17 and 27 C. Very high discrimination was shown with regard to sugar isomers. Light strongly promoted flux (by a factor of 2.5 in the case of methyl glucose). Initial flux showed sharply contrasting inhibitor sensitivity in the light and the dark. Light uptake was sensitive to the proton conductor carbonyl cyanide m-chlorophenylhydrazone (CCCP), but stable for at least the first 10 minutes to the ATPase inhibitors quercetin, rutin, and diethylstilbestrol, as well as to arsenate. Dark uptake, on the other hand, was stable to CCCP but was immediately depressed by quercetin, rutin, diethylstilbestrol, and arsenate.Protoplasts which received a light pretreatment before incubation in the dark took up methyl glucose at the accelerated light rate for the first 7 minutes. Moreover, the light pretreatment sensitized subsequent initial dark uptake to CCCP, and conferred on it the stability to ATPase inhibitors and arsenate characteristic of light uptake. After about 7 minutes the characteristic inhibitor responses of dark uptake were resumed.It is proposed that more than one mode of energy-coupling for sugar transport may operate in these protoplasts.


Challenges and Strategies for Diabetes Management in Community-Living Older Adults.
The prevalence of diabetes is increasing, especially in older people, mainly because of an increase in life expectancy. The number of comorbidities also increases with increasing age, leading to a unique diabetes phenotype in old age that includes vascular disease, physical and neuropathic complications, and mental dysfunction. These three categories of complications appear to have a synergistic effect that can lead to a vicious cycle of deterioration into disability. Early assessment and appropriate, timely interventions may delay adverse outcomes. However, this complex phenotype constitutes a great challenge for health care professionals. This article reviews the complex diabetes phenotype in old age and explores management strategies that are predominantly based on the overall functional status of patients within this heterogeneous age-group.


Delivery of antibiotics to the eye using a positively charged polysaccharide as vehicle.
The positively charged polysaccharide chitosan is able to increase precorneal residence time of ophthalmic formulations containing active compounds when compared with simple aqueous solutions. The purpose of the study was to evaluate tear concentration of tobramycin and ofloxacin after topical application of chitosan-based formulations containing 0.3% wt/vol of antibiotic and to compare them with 2 commercial solutions: Tobrex and Floxal, respectively. The influence of the molecular weight, deacetylation degree, and concentration of 4 different samples of chitosan on pharmacokinetic parameters (area under the curve values [AUC(eff)] and time of efficacy [t(eff)]) of tobramycin and ofloxacin in tears was investigated over time. It was demonstrated that the 2 chitosan products of high molecular weight (1350 and 1930 kd) and low deacetylation degree (50%) significantly increased antibiotic availability when compared to the controls, with AUC(eff) showing a 2- to 3-fold improvement. The time of efficacy of ofloxacin was significantly increased from about 25 minutes to 46 minutes by the chitosan of higher Mw (1930 kd) at a concentration of 0.5% wt/vol, whereas a similar performance was achieved by a chitosan of low Mw (580 kd) at a concentration of 1.5% wt/vol in the case of tobramycin.


[Mammography in Lodz--doses and conditions of diagnostic devices].
Mammography is a radiodiagnostic technique that has been long recognized and highly praised, nevertheless it should be remembered that it is beneficial only if the X-ray picture quality ensures correct diagnosis and the dose received by patients is reasonably low. The authors present the results of dose measurements in patients. The study covered 12 mammographs used in the Łódź radiological laboratories. Thermoluminescent dosimeters placed directly on the patient's breast during the examination in cranio-caudal projection were used for dose measurements. Although the measurements were taken only in patients with the compressed breast thickness close to 5 cm--a standard adopted for accreditation phantom--a sixfold difference between extreme dose values was observed (ranging from 4 to 24 mGy). Nine mammographs were also tested for quality control according to the protocol consistent with the recommendations of the European Commission, and elaborated by the Department of Radiological Protection of the Nofer Institute of Occupational Medicine in Łódź. An improper functioning of the automatic exposure control, especially with respect to the selection of the amount of emitted radiation in relation to the thickness of the object examined, was found to be the most frequent defect (in 7 of the 9 mammographs). Regarding that so called automatic option of the apparatus is used in a large majority of examinations, this may denote poor picture quality or too high dose received by patients, and even wrong diagnosis. In addition, the unsatisfactory quality of accredited phantom picture was found in three mammographs, which was equal to rather poor quality of clinical picture, and consequently a very limited legibility of anatomic details. The results of the measurements show that a certain part of mammographic examinations is performed in a way far from being perfect. But an actual improvement of the present situation depends on ensuring permanent quality control and, even more important, on providing funds necessary to cover all costs involved in remedial interventions.


Differential contributions of basal ganglia and thalamus to song initiation, tempo, and structure.
Basal ganglia-thalamocortical circuits are multistage loops critical to motor behavior, but the contributions of individual components to overall circuit function remain unclear. We addressed these issues in a songbird basal ganglia-thalamocortical circuit (the anterior forebrain pathway, AFP) specialized for singing and critical for vocal plasticity. The major known afferent to the AFP is the premotor cortical nucleus, HVC. Surprisingly, previous studies found that lesions of HVC alter song but do not eliminate the ability of the AFP to drive song production. We therefore used this AFP-driven song to investigate the role of basal ganglia and thalamus in vocal structure, tempo, and initiation. We found that lesions of the striatopallidal component (Area X) slowed song and simplified its acoustic structure. Elimination of the thalamic component (DLM) further simplified the acoustic structure of song and regularized its rhythm but also dramatically reduced song production. The acoustic structure changes imply that sequential stages of the AFP each add complexity to song, but the effects of DLM lesions on song initiation suggest that thalamus is a locus of additional inputs important to initiation. Together, our results highlight the cumulative contribution of stages of a basal ganglia-thalamocortical circuit to motor output along with distinct involvement of thalamus in song initiation or "gating."


Effects of pulmonary artery banding in doxorubicin-induced left ventricular cardiomyopathy.
Central pulmonary banding has been proposed as a novel alternative for the treatment of left ventricular dilated cardiomyopathy in children. We sought to investigate the effects of central pulmonary banding in an experimental model of doxorubicin-induced left ventricular dilated cardiomyopathy. Four-month-old sheep (n = 28) were treated with intermittent intracoronary injections of doxorubicin (0.75 mg/kg/dose) into the left main coronary artery. A total dose of up to 2.15 mg/kg of doxorubicin was administered until signs of left ventricular dilation with functional impairment occurred by transthoracic echocardiography evaluation. Animals that survived were treated with surgical central pulmonary banding through a left anterior thoracotomy or sham surgery. Transthoracic echocardiography and pressure-volume loop measurements were used to compare left ventricular function preoperatively and 3 months later. Macroscopic and microscopic histologic examinations followed after hearts were harvested. Nine animals from the central pulmonary banding group and 8 animals from the sham group survived and were included in the final analysis. Both groups showed similar inflammation and fibrosis upon histologic examination consistent with the toxic myocardial effects of doxorubicin. There were no differences in the echocardiographic measurements before central pulmonary banding or sham operation. Baseline measurements before the central pulmonary banding/sham operation were considered as 100%. The central pulmonary banding group had better left ventricular ejection fraction (102.5% ± 21.6% vs 76.7% ± 11.7%, P = .01), with a tendency for smaller left ventricular end-diastolic (101.2% ± 7.4% vs 120.4% ± 10.8%, P = .18) and significantly smaller end-systolic (100.3% ± 12.9% vs 116.5 ± 9.6%, P = .02) diameter of the left ventricle in comparison with the sham animals at 3 months. The end-systolic volume (101.4% ± 31.6% vs 143.4% ± 28.6%, P = .02) was significantly lower in the central pulmonary banding group 3 months postoperatively. Fractional shortening in the long axis (118.5% ± 21.5% vs 85.2% ± 22.8%, P = .016) and short axis (122.5% ± 18% vs 80.9% ± 13.6%, P = .0005) revealed significantly higher values in the central pulmonary banding group. In the conductance catheter measurements, no significant differences were seen between the groups for the parameters of systolic and diastolic function. Central pulmonary artery banding in the setting of experimental toxic left ventricular dilated cardiomyopathy improved left ventricular echocardiographic function and dimensions.


Comparison of the effect of DDE on the Ca metabolism of the eggshell gland and its subcellular fractions of the duck and the domestic fowl.
In a strain of ducks sensitive to the eggshell-thinning effect of p-p'-DDE, administration of 40 mg kg of the compound in the food for 45 days reduced the eggshell index (EI) by 13% and the content of calcium in the fluid of the shell gland forming an eggshell by 36%, and raised the calcium content of the shell gland mucosa by 19%, compared with the control values. DDE inhibited the translocation (secretion) of calcium between the gland mucosa and the uterine cavity. The ATP-dependent binding of Ca2+ to the subcellular fractions of the gland mucosa was reduced in DDE-treated ducks. The Ca2+ binding to a microsomal subfraction (FI) rich in fragments of the plasma membrane was reduced by 16%, whereas that to a subfraction FIII which bound Ca2+ at a very high rate was reduced by 36%. The latter may contain calcium-secreting granules of the gland. In the mitochondrial fraction the Ca2+ binding was reduced by 35%. In the domestic fowl DDE did not lower EI or interfered with the translocation of calcium between the shell gland mucosa and uterine cavity. DDE administration increased the Ca2+ binding to FI by 26%; the binding to other subfractions was not changed significantly. DDE may interfere with the stimulus-secretion mechanism of the eggshell gland in ducks through its effect on Ca2+ binding.


Seven-membered vibsane-type diterpenes with a 5,10-cis relationship from Viburnum awabuki.
New five seven-membered vibsane-type diterpenes named 5-epi-vibsanin C, 5-epi-vibsanin H, 5-epi-vibsanin K, 18-O-methyl-5-epi-vibsanin K and 5-epi-vibsanin E have been isolated from the leaves of Viburnum awabuki (Caplifoliaceae). Their structures have been elucidated by analyses of spectroscopic data and comparison of their spectral data with those of the previously known seven-membered vibsane-type diterpenes. The occurrence of these seven-membered vibsane-type diterpenes with a cis relationship on the C-5 and C-10 positions in nature have been predicted by conformational analysis of vibsanin B, an eleven-membered vibsane-type diterpene. Vibsanin C, 5-epi-vibsanin C and 5-epi-vibsanin H exhibited moderate cytotoxic activities on KB cells.


Effect of transglutaminase on the mechanical and barrier properties of whey protein/pectin films prepared at complexation pH.
The behavior of pectin and thermally denatured whey proteins at both different protein/polysaccharide ratios and different pH values was investigated. Our findings suggest the formation at pH 5.1 (complexation pH) of transglutaminase-catalyzed cross-links among soluble ionic whey protein/pectin complexes, which could be responsible for the observed increase of both tensile strength (2-fold) and elongation to break (10-fold) of films obtained in the presence of enzyme. Conversely, a significant reduction of elasticity, probably due to the formation of covalent bonds among single whey protein molecules, was observed when the films were prepared in the presence of the enzyme at pH 6.0. In addition, the presence of the enzyme at complexation pH significantly reduced film permeability. Atomic force and scanning electron microscopy revealed significant changes in the microstructure of the films prepared in the presence of TGase as well as in the morphology of their surface.


Effect of feeding rumen-protected rice bran on mineral status of non-lactating dairy heifers.
Adapting Ca homeostasis of dairy cows before calving can prevent milk fever. Rice bran, treated with formaldehyde to prevent ruminal degradation of phytic acid, was fed to heifers to study its effect on Ca homeostasis. For 3 weeks 18 heifers were supplemented 3 kg of two feeds: placebo (PF) and rice bran (RBF), defining three treatments: control (CRT), low dose (LD) and high dose (HD). In weeks 1 and 3, all animals received 3 kg of PF and in week 2: CRT received 3 kg of PF, LD received 1.5 kg of PF and 1.5 kg of RBF and HD received 3 kg of RBF. Treatments did not affect dry matter intake (DMI). Feed intakes and growth rates indicated that all heifers had nutritional requirements that exceeded their Ca intakes. Serum Ca, urinary Ca, calcitriol or hydroxyproline remained unaffected. Urinary Ca was consistently low indicating high renal Ca reabsorption, which is indicative of insufficient Ca supply. Rice bran feed influenced P, Mg and Zn intakes and serum and urine presence of these minerals. Most heifers already presented an upregulated Ca metabolism, being inadequate to study adaptive changes in Ca homeostasis of multiparous dry cows. This metabolic difference can be explanatory to the very low susceptibility of heifers to milk fever, further supporting the induction of homeostatic adaptation before calving to prevent milk fever. Rice bran feed did not reduce DMI, and was not detrimental to P, Mg or Zn status.


Overall Survival of Nonmetastasized NSCLC Patients Treated With Add-On Viscum album L: A Multicenter Real-World Study.
Recent data suggest a beneficial effect of add-on treatment with Viscum album L (VA) on the survival in cancer patients. The objective of this study was to compare the impact of standard oncological therapy plus add-on VA treatment (S+VA) versus standard oncological therapy alone (S) on the overall survival (OS) of patients with nonmetastasized non-small cell lung carcinoma (NSCLC). The multicenter real-world data study was conducted using data from the Network Oncology Clinical Registry. The primary end point was OS. OS and impact on hazard in both treatment groups were compared. A total of 275 patients with stages I to IIIA NSCLC were enrolled (mean age = 67.6 years, 57.2% male patients). No significant difference of OS was observed between both groups. Even though not significant, for a subgroup of unresected patients with stage I NSCLC, adenocarcinoma or squamous cell carcinoma, a medium effect size OS improvement was observed for S+VA compared to S. Our findings support the importance of surgery as the most effective intervention in nonmetastasized NSCLC patients. Add-on VA therapy shows here no additional effect in resected patients. However, a small subgroup analysis suggests a possible role of add-on VA for nonresected subgroups. Our results complement existing knowledge on the clinical impact of add-on VA therapy in NSCLC patients and may serve as hypothesis-generating data for further examinations in this cohort. Further research could be directed towards the role of combined therapy for nonresected early-stage NSCLC.


[Myocardial metabolism during dynamic exercise].
The development of Webster catheterization has enabled us to make clinical measurement of coronary sinus blood flow and to estimate the kinetics in myocardial substrate uptake. In this study, exercise tolerance test using supine multistage bicycle ergometer test was performed and exercise-induced hemodynamic alteration was evaluated in 18 patients with ischemic heart disease (16 males and 2 females, average age 56.3 years). The change in substrate kinetics in myocardial metabolism was also examined in terms of two indexes; myocardial uptake rate and myocardial uptake. The following results were obtained. 1) The myocardial uptake rates of glutamate and free fatty acid were significantly decreased by exercise, while those of glucose and lactate showed no significant change. 2) The myocardial uptakes of glutamate, glucose and lactate were significantly increased by exercise, but that of free fatty acid did not change significantly. 3) A significant negative correlation (r = -0.52, p < 0.05) was observed between the change in myocardial glutamate uptake and the change in pulmonary artery wedge pressure induced by exercise, suggesting that patients with ischemic heart disease might fail in glutamate uptake induced by exercise. The difference in the kinetics of myocardial uptake rate and myocardial uptake for glutamate, alanine, glucose, free fatty acid and lactate is observed. This difference occurs from the decrease in uptake rate due to the increase in coronary sinus blood flow. Myocardial uptake, which directly reflects myocardial energy metabolism is regarded as a more useful index of myocardial metabolism than myocardial uptake rate.


From leader to leadership: clinician managers and where to next?
Individual clinician leadership is at the forefront of health reforms in Australia as well as overseas with many programs run by health departments (and hospitals) generally focus on the development of individual leaders. This paper argues, along with others, that leadership in the clinician management context cannot be understood from an individualistic approach alone. Clinician managers, especially in the ranks of doctors, are usually described as 'hybrid-professional managers' as well as reluctant leaders for whom most leadership theories do not easily apply. Their experiences of leadership development programs run by health departments both in Australia and internationally are likely to be based on an individual leader-focussed approach that is driving health care reforms. These approaches work from three key assumptions: (1) study and fix the person; (2) give them a position or title; and (3) make them responsible for results. Some would argue that the combination of these three approaches equates to heroic and transformational leadership. Several alternative approaches to leadership development are presented to illustrate how reforms in healthcare, and notably in hospitals, must incorporate alternative approaches, such as those based on collective and relational forms of leadership. This does not mean eschewing individual approaches to leadership but rather, thinking of them differently and making them more relevant to the daily experiences of clinician managers. We conclude by highlighting several significant challenges facing leadership development for clinician managers that arise from these considerations.


Patterns of antimicrobial, multidrug and methicillin resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory in Tennessee, USA: a descriptive study.
Multidrug- and methicillin-resistant staphylococci are both veterinary and public health concerns due to their zoonotic potential. Therefore, the objective of this study was to investigate patterns of antimicrobial, multidrug, and methicillin resistance among four Staphylococcus spp. commonly isolated from canine clinical specimens submitted to the Clinical Bacteriology Laboratory at the University of Tennessee College of Veterinary Medicine (UTCVM). Results of antimicrobial susceptibility testing and mecA polymerase chain reaction (PCR) for isolates of four common Staphylococcus spp. isolates were obtained from the Bacteriology Laboratory at the UTCVM between 01/01/2006 and 12/31/2017. Cochran-Armitage trend test was used to assess temporal trends of antimicrobial resistance (AMR), multidrug resistance (MDR), and methicillin resistance. Kappa test of agreement was used to assess agreement between the results of PCR and disk diffusion tests. Most of the 7805 isolates were S. pseudintermedius (6453 isolates), followed by S. coagulans (860), S. aureus (330), and S. schleiferi (162). Among S. pseudintermedius isolates, 45.5% were MDR, and 30.8% were methicillin-resistant (MRSP). There was a significant temporal increase in MRSP (p = 0.017). Chloramphenicol resistance increased among both MRSP and methicillin-susceptible (MSSP) isolates (p < 0.0001). Among S. aureus isolates, 40.9% were MDR, 37.4% were methicillin-resistant (MRSA), and the proportion of MRSA isolates increased significantly (p = 0.0480) over time. There was an increasing temporal trend in the proportion of MDR isolates among MSSP (p = 0.0022), but a decrease among MRSP (p < 0.0001) and MRSA (p = 0.0298). S. schleiferi had the highest percentage (56.9%) of methicillin-resistant isolates. Oxacillin disk diffusion was superior to cefoxitin for the detection of mecA-mediated resistance and had almost perfect agreement with mecA PCR assay for S. pseudintermedius (95.4% agreement, kappa (κ) = 0.904; p < 0.0001), S. coagulans (95.6%, κ = 0.913; p < 0.0001) and S. schleiferi (97.7%, κ = 0.945; p < 0.0001). However, cefoxitin disk diffusion was superior to oxacillin disk diffusion and had almost perfect agreement with mecA PCR assay for S. aureus (95.3%, κ = 0.834; p < 0.0001). The levels of resistance and increasing temporal trends are concerning. These findings have implications for treatment decisions and public health due to the zoonotic potential of staphylococci. Continued surveillance and use of antibiograms to guide clinical decisions will be critical.


Convulsive seizures and some behavioral comorbidities are uncoupled in the Scn1aA1783V Dravet syndrome mouse model.
Dravet syndrome (Dravet) is a severe childhood epileptic encephalopathy. The disease begins with a febrile stage, characterized by febrile seizures with otherwise normal development. Progression to the worsening stage features recurrent intractable seizures and the presentation of additional nonepileptic comorbidities, including global developmental delay, hyperactivity, and motor deficits. Later in life, at the stabilization stage, seizure burden decreases, whereas Dravet-associated comorbidities persist. To date, it remains debated whether the nonepileptic comorbidities result from severe epilepsy or represent an independent phenotypic feature. Dravet mice (DS) faithfully recapitulate many clinical aspects of Dravet. Using wild-type (WT) and DS at different ages, we monitored multiple behavioral features as well as background electroencephalogram (EEG) activity during the different stages of Dravet epilepsy. Behavioral tests of WT and DS demonstrated that some deficits manifest already at the pre-epileptic stage, prior to the onset of convulsive seizures. These include motor impairment and hyperactivity in the open field. Deficits in cognitive functions were detected at the onset of severe spontaneous seizures. Power spectral analysis of background EEG activity, measured through development, showed that DS exhibit normal background oscillations at the pre-epileptic stage, a marked reduction in total power during the onset of severe epilepsy, and a subsequent smaller reduction later in life. Importantly, low EEG power at the stage of severe frequent convulsive seizures correlated with increased risk for premature death. Our data provide a comprehensive developmental trajectory of Dravet epilepsy and Dravet-associated comorbidities in mice, under controlled settings, demonstrating that the convulsive seizures and some nonepileptic comorbidities may be uncoupled. Moreover, we report the existence of an inverse correlation, on average, between the power of background EEG and the severity of epileptic phenotypes, suggesting that such measurements may potentially serve as a biomarker for Dravet severity.