High prevalence of postoperative arytenoid dislocation in patients undergoing liver transplantation: A case-control study.
Arytenoid dislocation (AD) is a rare complication of surgery under general anesthesia. The potential factors for AD remain poorly defined, and the identification of risk factors is beneficial for reducing its incidence. We found that patients undergoing liver transplantation appeared to be more susceptible to postoperative AD at our hospital. The present study was designed to clarify this issue. A retrospective hospital-based case-control study was conducted in patients undergoing surgery under general anesthesia between 2017 and 2021. Recorded data for all patients were age, sex, body weight, height, body mass index, position of patients during surgery, duration of surgery, emergency status of surgery, and liver transplantation. Logistic regression analysis was performed to determine risk factors for AD. Thirty thousand one hundred fifty-four patients who underwent general anesthesia between 2017 and 2021 were included. Sixteen (0.05%) patients were diagnosed with AD, including 10 (3.9%) patients among 259 patients who underwent liver transplantation and 6 patients had complications among the 29,895 patients who underwent other operations (P < .0001). Postoperative AD incidence was significantly elevated in patients undergoing liver transplantation. This finding should be clinically relevant and alarming for anesthesiologists and clinicians to help avoid arytenoid dislocation and improve patient outcomes. Further studies that incorporate detailed data are needed to determine risk factors for AD.


The Interplay Between Problematic Online Pornography Use, Psychological Stress, Emotion Dysregulation and Insomnia Symptoms During the COVID-19 Pandemic: A Mediation Analysis.
Although a link between problematic online pornographic use (POPU) and insomnia symptoms has been established, psychological and psychopathological mechanisms underlying this relationship are still not clear. Psychological stress and emotion dysregulation have been pointed out as relevant in the development and maintenance of insomnia. This study aims to explore the associations between POPU, psychological stress, emotion dysregulation and insomnia symptoms and to understand the mediating role of psychological stress and emotion dysregulation in the relationship between POPU and insomnia symptoms. A sample of 776 Italian adults aged 19-48 years (51.4% female; M age = 28.49; SD = 7.33) completed questionnaires regarding demographics, COVID-19-related variables, POPU, psychological stress, emotion dysregulation, and insomnia symptoms. After controlling for demographic covariates and COVID-19-related variables, multiple mediation model showed that higher psychological stress and emotion dysregulation fully mediated the link between POPU and insomnia. The findings underscore the significance of the negative consequences of POPU and underline the importance of working on this and its effects on psychological stress and emotion dysregulation to limit insomnia.


[Gene transfer patterns and transduction efficacy of recombinant adeno-associated virus type 1, 2, and 5 in brain: an experiment with rats].
To investigate the gene transfer patterns and transduction efficacy of different serotypes of recombinant adeno-associated virus (rAAV): rAAV1, 2, and 5 in brain. Fifty-four adult male SD rats were randomly divided into 9 equal groups to be injected with titre and volume-matched rAAV1, rAAV2, and rAAV5 carrying enhanced green fluorescent protein (EGFP) reporter gene into the hippocampus, lateral ventricle, and cortex respectively. Eight weeks later the rats were killed and their brains taken out. Fluorescent microscopy was used to observe the expression of EGFP in the brain. Real-time reverse transcriptase PCR was carried out to quantitate the EGFP expression. In the intra-hippocampal injection groups, the expression of rAAV1-EGFP was significantly stronger than those of rAAV2 and rAAV5 (both P < 0.01). Spread to the whole CA1 and CA2 areas, and the greater part of the CA3 area, the expression of rAAV1 was seen in the most of pyramidal cells and their projections. The expression of rAAV2-EGFP was limited in the multiform cell layer of the hilar region of dentate gyrus; whereas the rAAV5-EGFP expression was sparsely distributed in the structures around the injection sites. In both the intra-ventricular and intra-cortical groups only rAAV1-EGFP was expressed in many structures around the lateral ventricle, such as hippocampus, lateral septal nucleus, and striate body, and around the injection sites in cortex, and diffused to the callus in a small amount; and rAAV2 and rAAV5 were not expressed. More effective in transduction, rAAV1 is a more effective gene-transferring vector to be used in different disorders of the central nervous system.


Primary ovary choriocarcinoma: individual DNA polymorphic analysis as a strategy to confirm diagnosis and treatment.
Primary choriocarcinoma of the ovary is rare. Furthermore, this tumor can arise from gestational tissue or pure germ cells of the ovary, with the latter resulting in non-gestational choriocarcinoma. While the clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to assay for the presence of paternal DNA. Accordingly, in the present case, a patient with primary choriocarcinoma of the ovary with a non-gestational origin was confirmed by DNA analysis. The patient subsequently exhibited an excellent response to chemotherapy, and following surgery, achieved complete remission. A pathological analysis of surgical specimens further confirmed the absence of tumor.


Occupational asthma in a pesticides manufacturing worker.
A 34-year-old chemical manufacturing worker had new onset of work-related asthma after several years of exposure to the fungicide, captafol. On specific bronchial challenge testing, he demonstrated a marked and persistent fall in FEV1. Cessation of exposure resulted in improved symptoms and pulmonary function. The delay in symptoms after several years of workplace exposure and the dual reaction demonstrated on specific bronchial challenge testing suggest sensitization to some component of technical-grade captafol, but an IgE response was not detected.


Analysis of Orthologous SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) Promotor Activity in Herbaceous and Woody Angiosperms.
SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1) is a master regulator of fibre secondary wall deposition in Arabidopsis thaliana (Arabidopsis), with homologs in other angiosperms and gymnosperms. However, it is poorly understood to what extent the fibre-specific regulation of the SND1 promoter, and that of its orthologs, is conserved between diverged herbaceous and woody lineages. We performed a reciprocal reporter gene analysis of orthologous SND1 promoters from Arabidopsis (AthSND1), Eucalyptus grandis (EgrNAC61) and Populus alba × P. grandidentata (PagWND1A) relative to secondary cell wall-specific Cellulose Synthase4 (CesA4) and CesA7 promoters, in both a non-woody (Arabidopsis) and a woody (poplar) system. β-glucuronidase (GUS) reporter analysis in Arabidopsis showed that the SND1 promoter was active in vascular tissues as previously reported and showed interfascicular and xylary fibre-specific expression in inflorescence stems, while reporter constructs of the woody plant-derived promoters were partial to the (pro)cambium-phloem and protoxylem. In transgenic P. tremula × P. alba plants, all three orthologous SND1 promoters expressed the GUS reporter similarly and preferentially in developing secondary xylem, ray parenchyma and cork cambium. Ours is the first study to reciprocally test orthologous SND1 promoter specificity in herbaceous and woody species, revealing diverged regulatory functions in the herbaceous system.


Reference group effects in the measurement of personality and attitudes.
Reference-group effects (discovered in cross-cultural settings) occur when responses to self-report items are based not on respondents' absolute level of a construct but rather on their level relative to a salient comparison group. In this article, we examine the impact of reference-group effects on the assessment of self-reported personality and attitudes. Two studies illustrate that a reference-group effect can be induced by small changes to instruction sets, changes that mirror the instruction sets of commonly used measures of personality. Scales that specified different reference groups showed substantial reductions in criterion-related validities for academic performance, self-reported counterproductive behaviors, and self-reported health outcomes relative to reference-group-free versions of those scales.


Correlation between leukocyte membrane lipid peroxidation and expression of Cu/Zn-superoxide dismutase mRNA in hemodialysis patients.
Previously, we reported an increase in expressions of mRNA of Cu/Zn-superoxide dismutase (SOD) in leukocytes of hemodialysis (HD) patients, and speculated that the increase is associated with oxidative stress on the leukocyte membrane due to the HD process. Expressions of Cu/Zn-SOD mRNA in leukocytes, contents of plasma SOD, and malondialdehyde (MDA) in leukocyte and erythrocyte membranes, respectively, were examined in 25 HD patients and 14 healthy volunteers. These were also determined after using a vitamin E-coated dialyzer (VE dialyzer) for 4 weeks. All values were significantly higher in HD patients. A significant correlation was found between leukocyte Cu/Zn-SOD mRNA expression and membrane MDA. After using the VE dialyzer, all values were significantly lowered, showing a significant correlation between changing rate of leukocyte Cu/Zn-SOD mRNA expression and membrane MDA. In HD patients, oxidative stress is generated on the leukocyte membrane, and the level of Cu/Zn-SOD mRNA in leukocytes can be a useful oxidative stress marker.


Research and Implementation of Children's Speech Signal Processing System.
As people's living standard and the degree of mass culture have been constantly improved, many families are caring more about the healthy growth of early childhood. In this paper, based on the research of domestic and foreign experts and scholars: the guardians (such as parents) take appropriate intervention on children at the early stage can effectively promote children's language and cognitive ability development, and the intervention has obvious effect on the autistic spectrum disorders of children. This paper presents a system for analyzing children's speech signal, calculating the guardian's language words, the number of children's verbal words and the number of guardian and children's dialogue rotation times by voice signal processing and pattern recognition technology. And related personnels use these indicators to analysis the development of children's language and cognitive ability, then adopting appropriate measures for children and providing the basis for decision-making criteria, so as to promote the development of children's language and cognitive status.


Sulfate Uptake and Its Regulation in Lemna paucicostata Hegelm. 6746.
The results of studies of SO(4) (2-) uptake by Lemna paucicostata are most simply interpreted by the hypothesis that at least two components are involved, one saturating and one linear, ;nonsaturating.' The saturating component has a low K(m) and high specificity for SO(4) (2-). Uptake by the nonsaturating component is less affected by pH and temperature than is that of the saturating system. SO(4) (2-) efflux is not quantitatively important in Lemna under standard conditions (20 micromolar SO(4) (2-)) (Datko AH, SH Mudd 1980 Plant Physiol 65: 906-912). 55% of newly taken up (35)SO(4) (2-) enters a slowly turning over compartment (vacuole?); 45% remains in a compartment (cytoplasm?) in which it is rapidly metabolized to organic compounds.Growth in increased concentrations of SO(4) (2-) or cystine, but not methionine, down-regulates the saturating, but not the nonsaturating, system. Growth in limiting SO(4) (2-) up-regulates the saturating system. Overall, a 500-fold change was observed. Reciprocal inhibition experiments demonstrated that molybdate and SO(4) (2-) are taken up by a common mechanism, but growth in molybdate failed to up-regulate SO(4) (2-) uptake. Regulation by growth in SO(4) (2-) or cystine did not markedly affect uptake of phosphate or of several organic compounds.The saturating system contributes 99% of SO(4) (2-) uptake under standard conditions, providing sufficient SO(4) (2-) so it is not limiting. In nature the same system likely contributes at least 65 to 70%.


The role of atypical antipsychotics in glucose/insulin dysregulation and the evolving role of the psychiatrist in a new era of drug treatment options.
This article examines the issue of atypical antipsychotics, glucose/insulin, and other metabolic derangements (ie, metabolic syndrome), including a general introduction to the health concerns of our patients, a review of the literature, possible mechanisms of antipsychotic induced glucose dysregulation, monitoring approaches, and management and prevention of metabolic syndrome. Literature review leads to mechanism hypotheses and risk estimations, leading to guidelines for monitoring and treatment. The patient population suffers from a higher degree of baseline metabolic dysregulation resulting in cardiovascular disease through components of the metabolic syndrome, and this risk increases with administration of atypical antipsychotic medication at different rates, depending on both drug and patient risk factors. The growing knowledge of mechanisms behind drug induced glucose/insulin and other metabolic dysregulation, as well as advances in pharmacogenomics, will help refine drug selection and monitoring for adverse, life-threatening metabolic effects.


Robustness and Radiation Resistance of the Pale Grass Blue Butterfly from Radioactively Contaminated Areas: A Possible Case of Adaptive Evolution.
The pale grass blue butterfly, Zizeeria maha, has been used to evaluate biological impacts of the Fukushima nuclear accident in March 2011. Here, we examined the possibility that butterflies have adapted to be robust in the contaminated environment. Larvae (n = 2432) were obtained from adult butterflies (n = 20) collected from 7 localities with various contamination levels in May 2012, corresponding to the 7th generation after the accident. When the larvae were reared on non-contaminated host plant leaves from Okinawa, the normality rates of natural exposure without artificial irradiation (as an indication of robustness) were high not only in the least contaminated locality but also in the most contaminated localities. The normality rates were similarly obtained when the larvae were reared on non-contaminated leaves with external irradiation or on contaminated leaves from Fukushima to deliver internal irradiation. The normality rate of natural exposure and that of external or internal exposure were correlated, suggesting that radiation resistance (or susceptibility) likely reflects general state of health. The normality rate of external or internal exposure was divided by the relative normality rate of natural exposure, being defined as the resistance value. The resistance value was the highest in the populations of heavily contaminated localities and was inversely correlated with the distance from the Fukushima Dai-ichi nuclear power plant. These results suggest that the butterfly population might have adapted to the contaminated environment within approximately 1 year after the accident. The present study may partly explain the decrease in mortality and abnormality rates later observed in the contaminated areas.


Perspectives on the Designation of Oligonucleotide Starting Materials.
The designation of starting materials (SMs) for pharmaceuticals has been a topic of great interest and debate since the first ICH quality guidance was published. The increase in the number and variety of commercialized oligonucleotides (antisense oligonucleotides-ASOs, small interfering RNAs-siRNAs, etc.) in recent years has reignited dialogue on this topic because of the unique complexity of the monomeric nucleotides and other contributory materials used to manufacture oligonucleotides. The SM working group in the European Pharma Oligonucleotide Consortium (EPOC) was formed to help establish simple, risk-based criteria to guide the justification of oligonucleotide SMs. This article provides a description of the common types of SMs, classes of SM impurities, and control strategies that will be helpful to maintain manufacturing consistency.


New Horizons in Microbiological Food Safety: Ultraefficient Photodynamic Inactivation Based on a Gallic Acid Derivative and UV-A Light and Its Application with Electrospun Cyclodextrin Nanofibers.
An excellent bactericidal effect of octyl gallate (OG)-mediated photodynamic inactivation (PDI) against foodborne pathogens (Escherichia coli and Staphylococcus aureus) was evaluated in relation to the mode of action. UV-A irradiation (wavelength, 365 nm; irradiance, 8.254 ± 0.18 mW/cm2) of the bacterial suspension containing 0.15 mM OG could lead to a >5-log reduction of viable cell counts within 30 min for E. coli and only 5 min for S. aureus. Reactive oxygen species (ROS) formation was considered the main reason for the bactericidal effect of OG + UV-A light treatment because toxic ROS induced by OG-mediated PDI could attack the cellular wall, proteins, and DNA of microbes. Moreover, the bactericidal effect, as well as the yields of ROS, depended on OG concentrations, irradiation time, and laser output power. Furthermore, we prepared an edible photodynamic antimicrobial membrane comprising electrospun cyclodextrin nanofibers (NFs) by embedding OG. The resultant OG/HPβCD NFs (273.6 μg/mL) under UV-A irradiation for 30 min (14.58 J/cm) could cause a great reduction (>5-log) of viable bacterial counts of E. coli. The in situ photodynamic antibacterial activity of OG/HPβCD NF-based packaging was evaluated during the Chinese giant salamander storage. Overall, this research highlights the dual functionalities (antibacterial and photodynamic properties) of OG as both an antibacterial agent and photosensitizer and the effectiveness of electrospun NFs containing OG as an active antibacterial packaging material for food preservation upon UV light illumination.


Exchange of cystine and glutamate across plasma membrane of human fibroblasts.
It is found that both the inward and outward transport of cystine and glutamate through the plasma membrane of cultured human fibroblasts is mediated mostly by a single transport system. Cystine and glutamate at one side of the membrane stimulate the passage of these amino acids present at the other side of the membrane. When the concentration of intracellular glutamate is reduced to near zero, cystine hardly enters the cell, and likewise the release of glutamate from the cell ceases when cystine is absent in the medium. Homocysteate and alpha-aminoadipate share this transport system and, when added, similarly participate in the transport process. Since the intracellular pool of cystine is negligibly small whereas that of glutamate is very large, the physiologic flows via this system are the entry of cystine and the exodus of glutamate coupled together. Measurements of the rate of uptake of cystine into the cells and the rate of release of glutamate from the cells indicate that the entry of cystine and the exodus of glutamate occur at a ratio close to 1:1. Since cystine is known to behave as an anionic form in this transport, it is concluded that the transport system for cystine and glutamate in plasma membrane of human fibroblasts is a kind of an anion-exchanging agency.


Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency.
To define the hormonal criteria via genotypic proof for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency in the adrenals and gonads, we investigated the type II 3beta-HSD genotype in 55 patients with clinical and/or hormonal presentation suggesting compromised adrenal with or without gonadal 3beta-HSD activity. Fourteen patients (11 males and 3 females) had ambiguous genitalia with or without salt wasting and with or without premature pubarche. One female neonate had salt wasting only. Twenty-five children (4 males and 21 females) had premature pubarche only. Fifteen adolescent and adult females had hirsutism with or without menstrual disorder. The type II 3beta-HSD gene, including the promoter region up to -1053 base, all exons I, II, III, IV, and exon and intron boundaries, was sequenced in all subjects. Eight patients had a proven or predictably deleterious mutation in both alleles of the type II 3beta-HSD gene, and 47 patients had no apparent mutation in the gene. ACTH-stimulated (1 h post iv bolus of 250 microg Cortrosyn) serum 17-hydroxypregnenolone (Delta5-17P) levels and basal and ACTH-stimulated ratios of Delta5-17P to cortisol (F) in the genotypic proven patients were unequivocally higher than those of age-matched or pubic hair stage matched genotype-normal patients or control subjects (n = 7-30 for each group). All other baseline and ACTH-stimulated hormone parameters, including dehydroepiandrosterone (DHEA) levels, ratios of Delta5-17P to 17-OHP and DHEA to androstenedione in the genotype-proven patients, overlapped with the genotype-normal patients or control subjects. The hormonal findings in the genotype-proven patients suggest that the following hormonal criteria are compatible with 3beta-HSD deficiency congenital adrenal hyperplasia (numeric and graphic reference standards from infancy to adulthood are provided): ACTH-stimulated Delta5-17P levels in 1) neonatal infants with ambiguous genitalia at or greater than 378 nmol/liter equivalent to or greater than 5.3 SD above the control mean level [95 +/- 53 (SD) nmol/liter]; 2) Tanner I children with ambiguous genitalia at or greater than 165 nmol/liter equivalent to or greater than 35 SD above the control mean level [12 +/- 4.3 (SD) nmol/liter]; 3) children with premature pubarche at or greater than 294 nmol/liter equivalent to or greater than 54 SD above Tanner II pubic hair stage matched control mean level [17 +/- 5 (SD) nmol/liter]; and 4) adults with at or greater than 289 nmol/liter equivalent to or greater than 21 SD above the normal mean level [25 +/- 12 (SD) nmol/liter]. ACTH-stimulated ratio of Delta5-17P to F in 1) neonatal infants at or greater than 434 equivalent to or greater than 6.4 SD above the control mean ratio [88 +/- 54 (SD)]; 2) Tanner I children at or greater than 216 equivalent to or greater than 23 SD above the control mean ratio [12 +/- 9 (SD)]; 3) children with premature pubarche at or greater than 363 equivalent to or greater than 38 SD above the control mean ratio [20 +/- 9 (SD)]; and 4) adults at or greater than 4010 equivalent to or greater than 221 SD above the normal mean ratio [29 +/- 18 (SD)]. Conversely, the hormonal data in the genotype-normal patients suggest the following hormonal criteria are not consistent with 3beta-HSD deficiency congenital adrenal hyperplasia: ACTH-stimulated Delta5-17P levels in children with premature pubarche up to 72 nmol/liter equivalent to up to 11 SD above the control mean level, and in hirsute females up to 150 nmol/liter equivalent to up to 12 SD above the normal female mean level [28 +/- 10 (SD) nmol/liter]; and ACTH-stimulated Delta5-17P to F ratio in children with premature pubarche up to 67 equivalent to up to 5 SD above the control mean ratio, and in hirsute females up to 151 equivalent to up to 10 SD above the normal mean ratio [32 +/- 12 (SD)]. These findings help define newly proposed hormonal criteria to accurately predict inherited 3beta-HSD deficiency.


Daily physical movement and bone mineral density among a mixed racial cohort of women.
The impact of lifestyle physical activity on bone mineral density (BMD) is unclear. We examined the influence of physical activities typical of everyday life on BMD among 151 women (52.0 +/- 0.9 yr). These women were of low socioeconomic status, and 57.6% were Hispanic, 17.2% black, and 24.5% white. BMD was measured at the calcaneus by ultrasound with a Hologic Sahara sonometer. We measured physical activity with two questions from the Yale Physical Activity Survey that assessed h x d(-1) spent in motion typical of the past month and number of flights of stairs climbed up daily. Multivariate ANCOVA adjusted for adiposity and nutrients and medications known to influence BMD determined whether BMD differed between categories of physical activity (<2 vs > or = 2 flights x d(-1) and <7 vs > or = 7 h x d(-1)), menopausal status (pre- vs post-), and ethnic group (white vs nonwhite). Among the premenopausal women (N = 63, 43.2+/-0.9 yr), adjusted mean calcaneal BMD and BMD T-score were similar between categories of stair climbing and accumulated daily movement regardless of ethnic origin (P > 0.05). Among the postmenopausal women (N = 88, 58.1 +/- 1.0 yr), adjusted mean calcaneal BMD (0.561 +/- 0.019 g x cm(-2) vs 0.503 +/- 0.016) (P = 0.022) and BMD T-score (-0.172 +/- 0.166 vs -0.695 +/- 0.143) (P = 0.020) were higher with more flights of stairs climbed daily in the Hispanic and black women only. Similarly, calcaneal BMD (0.579 +/- 0.023 g x cm(-2) vs 0.505 +/- 0.014) (P = 0.010) and BMD T-score (-0.020 +/- 0.209 vs -0.678 +/- 0.129) (P = 0.010) were higher with greater amounts of daily movement in only the older Hispanic and black women. Lifestyle physical activity positively impacted BMD indicators in a mixed racial cohort of postmenopausal women. Older Hispanic and black women should be encouraged to engage in physical activities typical of everyday life to attenuate age-related bone loss.


Vibration-electronic coupling in the quenching of electronically excited alkali atoms by diatomics.
This paper reviews the ionic intermediate curve crossing model and the quenching of electronically excited atoms by simple diatomics and extends previous calculations to include predictions for the partial cross sections of the first electronic state of all the alkali atoms by N(2) and CO. Also included are calculations on the partial cross sections for Na quenching in high vibrational temperature environments, Na quenching by the inert gases, and the relaxation of N(2) vibrational energy in collisions with alkali atoms. An extension of this curve crossing model to ionization processes in the alkali atoms and to reactions involving covalent curve crossing is briefly discussed.


Adrenocortical carcinoma: presentation and outcome of a contemporary patient series.
Adrenocortical carcinoma (ACC) is a rare endocrine carcinoma with poor 5-year survival rates of < 40%. According to the literature, ACC is rarely an incidental imaging finding. However, presentation, treatment and outcome may differ in modern series. We studied all patients (n = 47, four children) from a single centre during years 2002-2018. We re-evaluated radiologic and histopathological findings and assessed treatments and outcome. We searched for possible TP53 gene defects and assessed nationwide incidence of ACC. In adults, incidental radiologic finding led to diagnosis in 79% at median age of 61 years. ENSAT stage I, II, III and IV was 19%, 40%, 19% and 21%, respectively. Nonenhanced CT demonstrated > 20 Hounsfield Units (HU) for all tumours (median 34 (21-45)), median size 92 mm (20-196), Ki67 17% (1-40%), Weiss score 7 (4-9) and Helsinki score 24 (4-48). ACC was more often found in the left than the right adrenal (p < 0.05). One child had Beckwith-Wiedemann and one a TP53 mutation. In adults, the primary tumour was resected in 88 and 79% received adjuvant mitotane therapy. Median hospital stay was significantly shorter in the laparoscopic vs. open surgery group (4 (3-7) vs. 8 (5-38) days, respectively; p < 0.001). In 3/4 patients, prolonged remission of > 5 to > 10 years was achieved after repeated surgery of metastases. Overall 5-year survival was 67%, and 96% vs. 26% for ENSAT stage I-II vs. III-IV (p < 0.0001). ENSAT stage and Ki67 predicted survival, type of surgery did not. Mitotane associated with better survival. Contemporary ACC predominantly presents as an incidental imaging finding, characterised by HU > 20 on nonenhanced CT but variable tumour size (20-196 mm). Malignancy cannot be ruled out by small tumour size only. The 5-year survival of 96% in ENSAT stage I-III compares favourably to previous studies.


Thermotropic phase properties of the hydroxyceramide/cholesterol system.
The interaction of cholesterol with ceramides containing alpha-hydroxy fatty acyl chains (hydroxyceramides) has been studied as a foundation for characterizing the lipid bilayers of the stratum corneum. A relatively large quantity of cerebrosides was obtained from bovine brain and converted to ceramides through removal of the carbohydrate side chain. The ceramides were separated based on the absence or presence of hydroxy fatty acyl chains. The lyophilized hydroxyceramides showed a broad melting region at 92 degrees C. Hydroxyceramides dispersed in water produced a relatively narrow, thermotropic transition at 75 degrees C. The effect of cholesterol on this thermotropic phase transition of hydroxyceramides was determined by differential scanning calorimetry. With respect to the main transition, cholesterol caused a broadening of the phase transition at relatively low levels as well as a decrease in the peak transition temperature. The presence of cholesterol at levels in excess of 7 wt% gave rise to an additional low-temperature transition at 55 degrees C. Upon immediate rescanning, this transition was exothermic, but with increasing incubation time the area under the excess heat capacity curve as a function of temperature became smaller. After two days or more, the transition observed was endothermic. At cholesterol levels between 40 and 50 wt%, multiple peaks were observed. From comparisons with related systems, the cooperative thermal transitions of hydroxyceramides with cholesterol are suggested to result from changes in hydrogen bonding or be due to phase separation. The composition of isolated brain ceramides is being compared with that reported for the stratum corneum.


RNA secondary structure prediction by using discrete mathematics: an interdisciplinary research experience for undergraduate students.
The focus of this Research Experience for Undergraduates (REU) project was on RNA secondary structure prediction by using a lattice walk approach. The lattice walk approach is a combinatorial and computational biology method used to enumerate possible secondary structures and predict RNA secondary structure from RNA sequences. The method uses discrete mathematical techniques and identifies specified base pairs as parameters. The goal of the REU was to introduce upper-level undergraduate students to the principles and challenges of interdisciplinary research in molecular biology and discrete mathematics. At the beginning of the project, students from the biology and mathematics departments of a mid-sized university received instruction on the role of secondary structure in the function of eukaryotic RNAs and RNA viruses, RNA related to combinatorics, and the National Center for Biotechnology Information resources. The student research projects focused on RNA secondary structure prediction on a regulatory region of the yellow fever virus RNA genome and on an untranslated region of an mRNA of a gene associated with the neurological disorder epilepsy. At the end of the project, the REU students gave poster and oral presentations, and they submitted written final project reports to the program director. The outcome of the REU was that the students gained transferable knowledge and skills in bioinformatics and an awareness of the applications of discrete mathematics to biological research problems.


Preparation of Tea Aroma Precursor Glycosides: An Efficient and Sustainable Approach via Chemical Glycosidation.
Tea aroma precursor glycosides are plant-derived natural products with great economic value. However, the preparation of these glycosides remains largely overlooked in the past decades. Herein, we report a mild, efficient, and sustainable chemocatalytic procedure for the production of tea aroma precursor glycosides. During the study of the glycosidation, the catalysts were found to be decisive in the product formation favoring different reaction pathways; in addition, the influence of molecular sieves was elucidated. With regard to these findings, the serious problem of the competing orthoester formation side reaction was successfully overcome with low catalyst loading (1 mol %) and the use of 5 Å molecular sieves, leading to the preparation of a variety of tea aroma precursor β-d-glucopyranosides and β-primeverosides on a gram scale in high yields in an economical way. Taken together, the current approach features catalytic glycosidation with non-toxic and low-cost catalysts, demonstrates highly favorable greenness and sustainability, and promises industrial production of tea aroma precursor glycosides.


[An innovative thoracoscopic surgery for patient ductus arteriosus--a Japanese first case report].
A five-year-old girl with patent ductus arteriosus (PDA) was successfully treated by thoracoscopic surgery, which was the first successful case in Japan. The operation was carried out under general anesthesia with usual endotracheal intubation. Short trocars were inserted through the left intercostal spaces to introduce a flexible video thoracoscope and adequate surgical instruments. After the ductus was carefully dissected and exposed, two titanium clips which were 11 mm in length were applied to interrupt the ductus completely. The continuous heart murmur of PDA was confirmed to disappear by an esophageal stethoscope. Postoperative course was uneventful and the patient was discharged on 6 postoperative day. No residual PDA shunt was revealed by doppler echocardiogram 8 months after surgery. The advantages of thoracoscopic surgery for PDA are: less postoperative pain and discomfort, early recovery and short hospital stay, and cosmetic preservation. Availability of smaller sized surgical instruments should allow this method indicated for smaller children or newborns with PDA.


Alteration of substrate selectivity through mutation of two arginine residues in the binding site of amadoriase II from Aspergillus sp.
Amadoriases I and II are deglycation isoenzymes from Aspergillus sp. of potential relevance for treatment of diabetic complications resulting from excessive protein glycation. Amadoriase II has a preference for anionic substrate with a K(m) of 0.23 and 2.53 mM for fructosylglycine and fructosylpropylamine, respectively. In contrast, the corresponding K(m) values for amadoriase I are 9.75 and 0.023 mM, respectively. Chemical modification of amadoriase II with p-hydroxyphenylglyoxal, a specific arginine-modifying reagent, resulted in an inhibition of enzyme activity toward fructosylglycine, while having less effect on the enzymatic activity toward fructosylpropylamine. Peptide mapping and subsequent mass spectrometry analysis suggest that Arg(112) is one of the sites of p-hydroxyphenylglyoxal modification. Sequence alignment between amadoriase I and amadoriase II revealed that two glutamic acids in amadoriase I align to Arg(112) and Arg(114) in amadoriase II. Site-directed mutation of amadoriase II (R112E, R114E) resulted in reversal of the enzymatic activities toward fructosylglycine and fructosylpropylamine. Our results suggested that Arg(112) and Arg(114) are responsible for the high affinity of amadoriase II toward anionic substrates and determine the substrate selectivity of the enzyme.


Endoscopic management of esophagogastric varices in Japan.
Esophagogastric varices are the most common complication in patients with portal hypertension, and endoscopy plays an important role in their diagnosis and in the prevention of acute bleeding from these structures. Recently, new modalities such as endoscopic ultrasonography (EUS) and narrow-band imaging have been introduced for the diagnosis of esophagogastric varices. In Japan, endoscopic therapy has become the first choice for the treatment of acutely bleeding esophageal or gastric varices. The two principal methods used to treat esophageal varices are endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL). Recently, combinations of EIS plus EVL and EVL plus argon plasma coagulation were reported to be more effective than EVL or EIS alone. Additionally, endoscopic cyanoacrylate injection is superior to EIS and EVL for the treatment of acutely bleeding gastric varices.


New trends in treatment of muscle fatigue throughout rehabilitation of elderlies with motor neuron diseases.
Muscle fatigue is a problem in rehabilitation, particularly in elderlies and patients with motor neuron diseases. There are high contradictions in the effectiveness of the used methods to decrease muscle fatigue during rehabilitation. They mainly concentrate on increasing rest periods, decreasing training load, or using an ascending intensity of manner of exercise. The training should focus on the newly discovered sensory system of muscle fatigue because of the important role of the sensory system in driving the motor system. Thus, this editorial provides insight on using proprioceptive training to enhance the sensory system of muscle fatigue.


Association Between Thyroid Radiation Dose and Hypothyroidism in Breast Cancer Patients Undergoing Volumetric Modulated Arc Therapy for Regional Nodal Irradiation.
To investigate the association between the thyroid dysfunction and thyroid radiation dose in regional nodal irradiation (RNI) using volumetric modulated arc therapy (VMAT) for breast cancer. We reviewed medical data of 67 patients with breast cancer who underwent curative surgery followed by adjuvant radiotherapy, including RNI using VMAT, between 2018 and 2021. All patients had normal thyroid functional test results, including thyroid stimulating hormone (TSH), T3, and free-T4. We defined subclinical hypothyroidism as increased TSH with or without decreased levels of free-T4 and T3 after the completion of VMAT. We calculated dose-volume histogram parameters (DVHPs), including the mean dose and relative thyroid volume receiving at least 10, 20, 30, and 40 Gy. The median follow-up time was 23.2 months. The 3-year locoregional failure-free survival, progression-free survival, and overall survival rates were 96.3%, 94.7%, and 96.2%, respectively. The mean thyroid dose was 21.4 Gy (range=11.5-29.4 Gy). Subclinical hypothyroidism was noted in 14 patients (20.9%) and the median time to the event was 4.1 months. Among the DVHPs, the relative volume receiving ≥20 Gy (V20Gy) was associated with subclinical hypothyroidism. The 2-year rates of subclinical hypothyroidism were 24.8% and 59.1% in patients with V20Gy ≤46.3% and >46.3%, respectively. A significant proportion of patients with breast cancer developed subclinical hypothyroidism after undergoing VMAT for RNI. Our findings highlight the importance of considering the thyroid as an organ at risk for VMAT planning, and suggest that V20Gy could be a useful dose-volume constraint.


Human growth plate development in the fetal and neonatal period.
The development of the normal human upper tibial growth plate was studied at autopsy in 46 stillborns and 79 newborns of 20-41 weeks gestational age. During this time period, the histology of this plate evolves from a highly cellular structure with relatively poor columnar organization and matrix development to the well known structure seen later in postnatal life. The thickness of the growth plate, assessed in the area surrounding the longitudinal tibial axis, decreases continuously from 1.15 mm on the 20th week to 0.6 mm on the 38th week. This decrease results from losses of both matrix and cellular components, mostly of the latter. However, the relative fraction of area occupied by the matrix significantly increased (12%) and matrix area per cell increased 1.5 times over the last half of gestation, indicating a maturation process of the plate towards a more matrix-oriented structure with age. In this maturation process the number of cells per unit area does not change and the average size of the cells appears to decrease. Plate thickness does not decrease further in the final 3 weeks of pregnancy and increases in early neonatal life; this has no apparent influence on the tibial growth rate. In the period under study the relative anatomical participation of the upper tibial growth plate decreases from approximately 4% of the radiographic length of the tibia on the 20th week to less than 1% at term. Present data will provide fetal and neonatal growth plate standards needed to obtain a better understanding of this structure during both normal and abnormal conditions.


C-kit expression identifies cardiac precursor cells in neonatal mice.
Through directed differentiation of embryonic stem cells, it has been demonstrated that mesodermal lineages in the mammalian heart (smooth muscle, endothelial, and cardiac) develop from a common, multipotent cardiovascular precursor (Dev Biol 265:262-275, 2004; Cell 127:1137-1150, 2006; Dev Cell 11:723-732, 2006). Identification of cardiovascular precursor cells at various stages of lineage commitment has been determined by expression of multiple markers, including the stem cell factor receptor c-kit. Utilizing a bacterial artificial chromosome (BAC) transgenic mouse model in which EGFP expression is placed under control of the c-kit promoter (c-kit(BAC)-EGFP), work from our laboratory indicates that c-kit expression identifies a multipotent cardiovascular precursor cell population within the early postnatal heart that can be isolated, expanded, and differentiated in vitro into all three cell lineages that specify the heart (Proc Natl Acad Sci U S A 106:1808-1813, 2009).


Identification of causative pathogens in mouse eyes with bacterial keratitis by sequence analysis of 16S rDNA libraries.
The clone library method using PCR amplification of the 16S ribosomal RNA (rRNA) gene was used to identify pathogens from corneal scrapings of C57BL/6-corneal opacity (B6-Co) mice with bacterial keratitis. All 10 samples from the eyes with bacterial keratitis showed positive PCR results. All 10 samples from the normal cornea showed negative PCR results. In all 10 PCR-positive samples, the predominant and second most predominant species accounted for 20.9 to 40.6% and 14.7 to 26.1%, respectively, of each clone library. The predominant species were Staphylococcus lentus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The microbiota analysis detected a diverse group of microbiota in the eyes of B6-Co mice with bacterial keratitis and showed that the causative pathogens could be determined based on percentages of bacterial species in the clone libraries. The bacterial species detected in this study were mostly in accordance with results of studies on clinical bacterial keratitis in human eyes. Based on the results of our previous studies and this study, the B6-Co mouse should be considered a favorable model for studying bacterial keratitis.


Schizophrenics know more than they can tell: probabilistic classification learning in schizophrenia.
Previous studies have demonstrated impaired explicit and preserved implicit memory functions in schizophrenia. However, it is less clear whether schizophrenics can learn complex information (e.g. probabilistic stimulus response associations) with or without access for conscious recollection. In this study we applied a classification learning task to assess explicit and implicit processes concurrently. Two test procedures were administered to 40 schizophrenic subjects and 20 healthy volunteers: a probabilistic classification learning (PCL) task to evaluate implicit memory functions; and a category cue recognition test to investigate the explicit memory system. The PCL task included feedback guided category learning of geometrical shapes. These shapes were called category cues, predicting class membership with certain probabilities. The gradual increase of categorization performance during the feedback learning was a potentially implicit process, whereas the subsequent recognition of category cues required explicit memory functions. The schizophrenic patients improved their categorization performance to a similar extent to the controls, but they failed to recognize the category cues. Memory performances were independent of the positive and negative symptoms. Patients with schizophrenia were able to establish representations of complex categories, but these remained unconscious. This is consistent with earlier reports, suggesting damaged explicit and spared implicit memory in schizophrenia.


Regression model of partial pressures of PCBs, PAHs, and organochlorine pesticides in the Great Lakes' atmosphere.
The gas-phase concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and organochlorine pesticides have been measured at six sites around the Great Lakes every 12 days since the early 1990s as part of the Integrated Atmospheric Deposition Network. After converting the concentrations into partial pressures, data from all of the sites were combined and fitted using a multiple linear regression equation that included time (indicating the effect of a chemical's regulation), atmospheric temperature (indicating seasonality of use or release), the human population within a 25 km radius of the site (indicating the effect of urbanization) and wind speed and wind direction (indicating the source of the chemical). The atmospheric levels of lindane (gamma-HCH), DDTs, endosulfans, and chlordanes were largely related to seasonality, with much higher levels in the warm summer months. The levels of SigmaPCBs, SigmaPAHs, SigmaDDTs, and chlordanes were related to urbanization (this was a secondary factor for the latter two), a result that was unexpected for the two pesticides. The levels of only two compounds, alpha- and gamma-HCH, decreased rapidly as a function of time; conversely, most other compounds are declining at much slower rates. Wind speed and wind direction were statistically significant but unimportant variables for most of the compounds.


Neutralization of IL-10 exacerbates cycloheximide-induced hepatocellular apoptosis and necrosis.
Cycloheximide (CHX)-induced liver injury in rats has been characterized by hepatocellular apoptosis and necrosis. We previously reported that Kupffer cell inactivation causes a reduction of IL-10 production, resulting in the exacerbation of CHX-induced liver injury. In this study, we directly evaluate the role of IL-10 in liver injury by a pretreatment with anti-IL-10 neutralizing antibody (IL-10Ab). Rats were given goat IgG or IL-10Ab before being treated with CHX (CHX group or IL-10Ab/CHX group). In the CHX group, the CHX treatment markedly induced hepatic mRNA and serum protein levels of IL-10. The up-regulation of IL-10 was significantly suppressed in the IL-10Ab/CHX group. Blocking IL-10 in the IL-10Ab/CHX group led to greater increases in hepatic mRNA and serum levels of proinflammatory cytokines, such as TNF-alpha and IL-6. The IL-10Ab/CHX group developed more severe hepatocellular apoptosis, neutrophil transmigration, and necrotic change of hepatocytes compared with the CHX group. The caspase activities and mRNA levels of Cc120, LOX-1, and E-selectin in the livers were significantly higher in the IL-10Ab/CHX group than the CHX group. These results demonstrate that IL-10 plays an important role in counteracting the effect of proinflammatory cytokines, such as a TNF signaling cascade, and in attenuating the CHX-induced liver injury.


Manipulation of beat length and wavelength dependence of a polarization beam splitter using a subwavelength grating.
A polarization beam splitter assisted by a subwavelength grating (SWG) is proposed. The SWG enables nearly 20-fold beat length reduction for TE, which makes the high extinction ratio (ER) possible. On the other hand, the embedded SWG preferably affects the refractive index of the even mode in the coupling region and broadens the bandwidth of the splitter. As a result, the ER of 28.7 dB (24.8 dB) for TE (TM) is obtained, while the insertion loss is only 0.10 dB (0.11 dB) at the wavelength of 1550 nm. The ER is more than 10 dB in the wavelength range of 1450-1625 nm for TE and 1495-1610 nm for TM.


[The need for strict control of cardiovascular risk factors in type 2 diabetic patients].
HIGH CARDIOVASCULAR RISK: The clinical and metabolic anomalies observed in patients with type 2 diabetes are associated with high risk of cardiovascular disease (particularly coronary heart disease), which is responsible for 75% of all deaths in diabetic patients. CLASSICAL RISK FACTORS: Several large-scale surveys have demonstrated the role of classic risk factors such as hypercholesterolemia, smoking and hypertension in the development of ischemic heart disease compared with the general population. OTHER RISK FACTORS: Other risk factors in the diabetic patient include risk associated with the metabolic anomalies (blood glucose levels, insulin resistance) as well as to left ventricular hypertrophy and microalbuminuria, which are often found together in hypertensive diabetics. INTERNATIONAL GUIDELINES: The importance of these risks has led several organizations to issue guidelines, particularly regarding the need for stricter blood pressure control. Regular screening for microalbuminuria and renal dysfunction (creatinine clearance) is also recommended, as well as more rigorous objectives for lipid levels.


[Surgical treatment strategy for cT4bM0 colon cancer].
Colon cancer may invade the adjacent organ in the absence of distant metastasis, which is called stage T4bM0 colon cancer according to the 7th edition of TNM staging system. It is not rare in clinical setting, and usually recognized intraoperatively. How to deal with this situation is a big challenge for the surgeons. It is difficult to distinguish between dense adhesion and cancerous invasion. Intraoperative biopsy should be avoided because of the risk of tumor cell dissemination and frozen often gives false-negative results. After evaluating the resectability of the tumor sufficiently, the surgeon should make every effort to do an en bloc multivisceral resection and to achieve a margin-free (R0) resection if there is no absolute contraindication. This effort will bring long-term prognosis benefit for the patients with stage cT4bM0 colon cancer.


Eating under observation: a systematic review and meta-analysis of the effect that heightened awareness of observation has on laboratory measured energy intake.
Laboratory paradigms are commonly used to study human energy intake. However, the extent to which participants believe their eating behavior is being measured may affect energy intake and is a methodologic factor that has received little consideration. Our main objective was to examine available evidence for the effect that heightened awareness of observation has on energy intake in a laboratory setting. We systematically reviewed laboratory studies that allowed for experimental examination of the effect that heightened awareness of observation has on energy intake. From these experimental studies we combined effect estimates using inverse variance meta-analysis, calculating the standardized mean difference (SMD) in energy intake between heightened-awareness and control conditions and qualitatively synthesized potential moderators of this effect. Nine studies, providing 22 comparisons, were eligible for inclusion. These studies largely sampled young women and examined the energy intake of energy-dense snack foods. Evidence indicated that heightened awareness of observation was associated with reduced energy intake when compared with the control condition (random-effects SMD: 0.45; 95% CI: 0.25, 0.66; P < 0.0001). We found little evidence that the type of experimental manipulation used to heighten awareness moderated the overall effect. The available evidence to date suggests that heightened awareness of observation reduces energy intake in a laboratory setting. These findings suggest that laboratory studies should attempt to minimize the degree to which participants are aware that their eating behavior is being measured.


[The evaluation of ketoprofen pharmaceutical availability in the presence of a dry extract from goldenrod (Solidago virgaurea L.) of synthetic polymer vehicles].
The aim of this study was to produce hydrogels for topical use and having strengthened anti-inflammatory, analgesic and antirheumatic activity. To obtain the above effect dry standardized plant extract was added to enrich a formulation containing therapeutic agent (ketoprofen) from the group of nonsteroidal anti-inflammatory drugs. Dry standardized extract from Solidago virgaurea L. of confirmed anti-inflammatory activity was selected for this purpose. The derivatives of acrylic acid polymers (Carbopol Ultrez and Carbopol 980) were used as the formulation vehicles. These vehicles were selected owing to their high applicative properties--transparency, resistance to changes of temperature, perfect tactile and esthetic qualities, no sensitizing agents, no toxicity and lack of influence on therapeutic properties of the therapeutic agent and compatibility in the pharmaceutical phase. The produced formulations were exposed to basic physicochemical tests--pH, viscosity parameters (structural viscosity, yield stress and thixotropy), pharmaceutical availability and durability after six months of storage. The effect of component plant extracts on the process of ketoprofen diffusion to acceptor fluid through a semipermeable membrane was also compared. The obtained results indicate that dry standardized extract from Solidago virgaurea L. does not affect significantly the process of ketoprofen release from the tested preparations. After six months of storage the preparations with ketoprofen demonstrate rheological stability and high pharmaceutical availability.


Detection of Black Plastics in the Middle Infrared Spectrum (MIR) Using Photon Up-Conversion Technique for Polymer Recycling Purposes.
The identification of black polymers which contain about 0.5 to 3 mass percent soot or black master batch is still an essential problem in recycling sorting processes. Near infrared spectroscopy (NIRS) of non-black polymers offers a reliable and fast identification, and is therefore suitable for industrial application. NIRS is consequently widely used in polymer sorting plants. However, this method cannot be used for black polymers because small amounts of carbon black or soot absorb all light in the NIR spectral region. Spectroscopy in the mid infrared spectral region (MIR) offers a possibility to identify black polymers. MIR spectral measurements carried out with Fourier-transform infrared spectrometers (FTIR) are not fast enough to meet economic requirements in sorting plants. By contrast, spectrometer systems based on the photon up-conversion technique are fast and sensitive enough and can be applied to sort black polymer parts. Such a system is able to measure several thousand spectra per second hence is suitable for industrial applications. The results of spectral measurements of black polymers are presented.


Malignancy as a possible complication of complex regional pain syndrome: a case report.
A synovial sarcoma presented in the knee of a young woman 20 years after the onset of pain which was attributed to complex regional pain syndrome (CRPS). Was this a chance occurrence, or could there be any link between the two conditions? Did the pain itself and the persistent inflammatory and immunological response to pain contribute to the development of malignancy, or could the malignancy have been present subclinically for many years and have contributed to the ongoing pain syndrome? This case report looks into the diagnosis of synovial sarcoma and CRPS and the relationship between the neurogenic inflammation seen in CRPS and that seen in malignancies. The diagnosis of CRPS is a diagnosis of exclusion. Constant vigilance of patients with this unpleasant condition is necessary.


Individualising Anticoagulant Therapy in Atrial Fibrillation Patients.
Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations.


Cervical radiculopathy following botulinum toxin therapy for cervical dystonia.
The development of transient right-sided lower cervical root impairment is reported in a 49-year-old woman affected by cervical dystonia, who had previously received botulinum toxin injections into the left sternocleidomastoid and the right trapezius. The possibility of a causal relationship was discussed with consideration of: 1) the absence of intercurrent illness or trauma; 2) the positive correlation between sensory-motor disturbances and the botulinum toxin-induced remission of cervical dystonia; 3) the reversibility of cervical radiculopathy (there was no recurrence in the two years following the interruption of the treatment). Magnetic resonance imaging investigation disclosed an abnormal cervical spine geometry together with moderate spondylosis. We feel that mechanical postural changes following the successful botulinum toxin treatment for cervical dystonia might have played some role in the development of cervical radiculopathy. Thus, skeletal abnormalities should be checked when attempting to correct muscle overactivity by botulinum toxin.


Rational protection of subjects in research and quality improvement activities.
This Open Forum illuminates shortcomings with the basis for determining degree of oversight of health services research and quality improvement activities. Using a federally regulated definition of research rather than a direct appraisal of risk to patients can misallocate effort from activities with higher risk for patients to those with lower risk. The case of the Johns Hopkins multicenter study of central line safety checklists in intensive care units is cited. Definitions of research promulgated by the Office of Human Research Protection are reviewed, and an alternative model based on patient risk is proposed. Suggestions for how quality improvement work fits into the larger paradigm of research are made.


[A case of hard metal lung disease presenting a type of chronic hypersensitivity pneumonitis].
A 35-year-old man was admitted to our hospital because of abnormal shadows on the chest radiograph and dry cough and exertional dyspnea. He was given a diagnosis of hard metal lung disease 15 years previously and was treated with corticosteroid. Laboratory examination revealed hypoxemia and reduced pulmonary vital capacity. Chest radiograph and high-resolution computed tomography (HRCT) on admission showed ground-glass opacities with volume loss and small cystic spaces. Bronchoalveolar lavage fluid (BALF) demonstrated bizarre multinucleated giant cells and transbronchial lung biopsy (TBLB) specimens showed interstitial pneumonia with multinucleated giant cells. He has worked as a metal grinder, and tungsten was detected in his BALF metal analysis. His illness was diagnosed as hard metal lung disease with giant cell interstitial pneumonia (GIP). We considered this case as a type of chronic hypersensitivity pneumonitis due to his high sensitivity and his disease worsened gradually for four years. Since hard metal lung disease may recur in individuals with high sensitivity, we should always be aware of the possibility of recurrence of this disease.


Fluid balance in food-deprived lactating goats drinking saline.
Fluid balance was studied in four lactating goats during two 3 week periods, which included 30 h periods of food deprivation. In one period the goats were given 0.9% NaCl to drink, and in the other they were given water. Prior to food deprivation, fluid intake and urinary flow were similar in the two groups, but urinary Na+ excretion was higher in the saline-drinking goats. The plasma renin activity was depressed in saline-drinking goats, while the plasma aldosterone concentration was the same both in saline-drinking and water-drinking animals. Food deprivation depressed fluid intake and urine flow in all goats, but the reduction was more pronounced in goats drinking saline. The urinary Na+ and K+ excretion also decreased, in both groups, as did plasma Na+ concentration and osmolality. The plasma protein concentration increased in both groups, indicating that hypovolaemia had developed. The renin-angiotensin-aldosterone system (r.a.a.s.) became activated in goats drinking water, but not in the group drinking saline. It is suggested that sodium retention may have attenuated the activation of the r.a.a.s. in the latter group. The results of this study show that hyponatraemic hypovolaemia develops during starvation in lactating goats, regardless of the sodium state of the animals. The possibility that the hyponatraemic hypovolaemia is secondary to an impeded Na+ and fluid absorption from the rumen reticulum is discussed.


Magnetic resonance colonography with fecal tagging: an innovative approach without bowel cleansing.
To date, virtual colonography mandates bowel cleansing in a manner similar to colonoscopy. Because more than half of patients undergoing bowel preparation complain about negative side effects, patient acceptance is negatively impacted. To assure high patient acceptance of MR colonography, bowel cleansing needs to be eliminated. This can be accomplished by fecal tagging, a concept based on altering the signal intensity of stool by adding contrast-modifying substances to regular meals. This article describes different fecal tagging approaches and points out both advantages and limitations of these strategies.


Potential of Persimmon Dietary Fiber Obtained from Byproducts as Antioxidant, Prebiotic and Modulating Agent of the Intestinal Epithelial Barrier Function.
Appropriate nutrition targets decrease the risk of incidence of preventable diseases in addition to providing physiological benefits. Dietary fiber, despite being available and necessary in balanced nutrition, are consumed at below daily requirements. Food byproducts high in dietary fiber and free and bonded bioactive compounds are often discarded. Herein, persimmon byproducts are presented as an interesting source of fiber and bioactive compounds. The solvent extraction effects of dietary fiber from persimmon byproducts on its techno- and physio-functional properties, and on the Caco-2 cell model after being subjected to in vitro gastrointestinal digestion and probiotic bacterial fermentation, were evaluated. The total, soluble, and insoluble dietary fiber, total phenolic, carotenoid, flavonoid contents, and antioxidant activity were determined. After in vitro digestion, low quantities of bonded phenolic compounds were detected in all fiber fractions. Moreover, total phenolic and carotenoid contents, as well as antioxidant activity, decreased depending on the extraction solvent, whereas short chain fatty acids production increased. Covalently bonded compounds in persimmon fiber mainly consisted of hydroxycinnamic acids and flavanols. After probiotic bacterial fermentation, few phenolic compounds were determined in all fiber fractions. Results suggest that persimmon's dietary fiber functional properties are dependent on the extraction process used, which may promote a strong probiotic response and modulate the epithelial barrier function.


Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria.
Research. The goal of this study was to investigate whether Propionibacteria acnes infection of the intervertebral disc can be detected noninvasively by nuclear magnetic resonance (NMR) spectroscopy. Microbiological studies of surgical samples suggest that a significant subpopulation of back pain patients may have occult disc infection with P. acnes bacteria. This hypothesis is further supported by a double-blind clinical trial showing that back pain patients with Modic type 1 changes may respond to antibiotic treatment. Because significant side effects are associated with antibiotic treatment, there is a need for a noninvasive method to detect whether specific discs in back pain patients are infected with P acnes bacteria. P. acnes bacteria were obtained from human patients. NMR detection of a propionic acid (PA) in the bacteria extracts was conducted on 500 MHz high-resolution spectrometer, whereas in vivo NMR spectroscopy of an isolated bovine disk tissue infected with P. acnes was conducted on 7 T magnetic resonance imaging scanner. NMR spectra of P. acnes metabolites revealed a distinct NMR signal with identical chemical shits (1.05 and 2.18 ppm) as PA (a primary P. acne metabolite). The 1.05 ppm signal does not overlap with other bacteria metabolites, and its intensity increases linearly with P. acnes concentration. Bovine disks injected with P. acnes bacteria revealed a very distinct NMR signal at 1.05 ppm, which linearly increased with P. acnes concentration. The 1.05 ppm NMR signal from PA can be used as a marker of P. acnes infection of discs. This signal does not overlap with other disc metabolites and linearly depends on P. acnes concentration. Consequently, NMR spectroscopy may provide a noninvasive method to detect disc infection in the clinical setting. N/A.


Exudative Retinal Detachment Following Chimeric Antigen Receptor T-Cell Therapy in Relapsed B-Cell Acute Lymphoblastic Leukemia.
Chimeric antigen receptor (CAR) T-cell therapy has become a novel approach in the treatment of many hematologic malignancies. However, ocular adverse effects have not been well described. This report presents a case of a pediatric patient with relapsed B-cell acute lymphoblastic leukemia with ocular involvement treated with CAR T-cell therapy who developed an exudative retinal detachment likely secondary to an inflammatory response to CAR T-cell therapy. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:113-115.].


CE: Original Research: Examining the Links Between Lifestyle Factors and Metabolic Syndrome.
: Background: As it is in many other developed countries, obesity is a growing health concern in Taiwan, affecting nearly 20% of the adult population. Obesity can increase the risk of developing metabolic syndrome, diabetes, and cardiovascular disease. Recent data indicate that the prevalence of metabolic syndrome in Taiwan is 25.5%. Yet some overweight and obese individuals have normal metabolic profiles. It's not clear why some overweight or obese people remain metabolically healthy while others do not. The purpose of this study was to examine lifestyle risk factors for metabolic syndrome in people who are overweight or obese. We were particularly interested in distinguishing those lifestyle factors associated with metabolic health in this population. Data collected from community-based physical examinations in northern Taiwan were used for this cross-sectional study. A survey was conducted from 2013 to 2014. We collected data on demographic variables, clinically pertinent measures (weight; height; waist circumference; blood pressure; and levels of fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol), and lifestyle factors (smoking, drinking, exercise, and dietary habits). To analyze the data, we used percentage, mean, standard deviation, χ test, independent t test, the Fisher exact test, phi correlation, and logistic regression. The overall prevalence of metabolic syndrome among all 734 participants was 36.4%. For the normal weight, overweight, and obese groups, the prevalence of metabolic syndrome was 12.4%, 36.4%, and 61.6%, respectively. The results of logistic regression showed, however, that obese individuals who exercised regularly and ate sufficient amounts of fruit were less likely to have metabolic syndrome, and that overweight individuals who were nonsmokers and ate sufficient amounts of vegetables were also less likely to have metabolic syndrome. Lifestyle factors may significantly affect the development of metabolic syndrome in people who are overweight or obese. Our findings indicate that practicing healthy lifestyle behaviors may be the best way to prevent metabolic syndrome. Public health interventions promoting smoking cessation, regular exercise, and good dietary habits can be created and conducted at relatively low cost. At the community level, all nurses can prioritize such interventions for their overweight and obese patients.


Optimized rapid and reliable identification of Tuber spp. by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
Intentional substitution of food ingredients and misleading or false declarations of food products can lead to large economic damage in the food sector. An example is the truffle, an edible mushroom, with different species having a similar morphology. This makes it difficult to distinguish, for example, the high-quality black Périgord truffle from Europe and the lower quality black truffle from China. To detect and prevent potential food fraud and to be able to carry out quality assurance measures, the demand for suitable, fast and cost-effective examination methods for individual foodstuffs is increasing. In this article we present a method based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which can differentiate and identify commercial truffles. For this purpose, highly specific mass spectrometric fingerprints of 73 truffle tubers from eight different species were generated. These were checked and compared under the criteria of a score evaluation, their protein spectra, and cluster formation. Standard laboratory equipment was used for this purpose, so that apart from the MALDI-TOF no expensive equipment or reagents were required. The study shows that the MALDI-TOF MS method can distinguish and identify Tuber spp. reliably, quickly and efficiently and can therefore be used for quality assurance and fraud control in the truffle market.


Differential visual and auditory effects in a crossmodal induced Roelofs illusion.
For vision and audition to accurately inform judgments about an object's location, the brain must reconcile the variable anatomical correspondence of the eyes and ears, and the different frames of reference in which stimuli are initially encoded. To do so, it has been suggested that multisensory cues are eventually represented within a common frame of reference. If this is the case, then they should be similarly susceptible to distortion of this reference frame. Following this reasoning, we asked participants to locate visual and auditory probes in a crossmodal variant of the induced Roelofs effect, a visual illusion in which a large, off-center visual frame biases the observer's perceived straight-ahead. Auditory probes were mislocalized in the same direction and with a similar magnitude as visual probes due to the off-center visual frame. However, an off-center auditory frame did not elicit a significant mislocalization of visual probes, indicating that auditory context does not elicit an induced Roelofs effect. These results suggest that the locations of auditory and visual stimuli are represented within a common frame of reference, but that the brain does not rely on stationary auditory context, as it does visual, to maintain this reference frame. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The Syrian refugee crisis: how local governments and NGOs manage their image via social media.
This study, based on situational crisis communication theory and set in the context of the Syrian refugee crisis, seeks first to conduct a comparative analysis of the management of online citizen engagement by local governments and non-governmental organisations (NGOs). Second, it aims to examine the relationship between certain factors pertaining to the types of responses submitted by citizens via the social media of the aforementioned actors. The sample is composed of several Spanish local governments and NGOs belonging to Red de Municipios de Acogida de Refugiados (Local Government Network for Refugee Allocation). The main findings are that NGOs' online engagement with citizens is more than that of local governments. Notably, NGOs are much more active on their Facebook pages than are local governments. The two actors converge, though, in terms of disseminating instructive information and paying less attention to 'basic crisis response options'. Moreover, the factors 'content type', 'reputation', and 'woman' affect the type of response messages sent by citizens.


Human naive T cells activated by cytokines differentiate into a split phenotype with functional features intermediate between naive and memory T cells.
We have recently shown that CD45RA+CD4+ naive T cells can be activated to proliferate by a combination of IL-2, TNF-alpha and IL-6, but, at variance with TCR-mediated activation, they do not acquire the CD45RO molecule. This prompted us to investigate the phenotype of these cells and the functional features they display upon TCR stimulation. Naive T cells expanded by cytokines, though remaining CD45RA+, express a variety of activation and adhesion molecules which are peculiar to effector or memory T cells. Naive cells primed by cytokines, when activated with anti-CD3 mAb, produce a broad spectrum of cytokines, express CD40 ligand, but are unable to help B cells for Ig synthesis. A subset of CD4+CD45RA+RO-T cells with a phenotype (HLA-DR-, VLA-2+ or IL-2R+) similar to that of cells activated by cytokines in vitro can be found in vivo. These results demonstrate that activation signals delivered by cytokines, in the absence of TCR stimulation, can activate naive T cells to proliferate and differentiate into a 'split phenotype' with elements common to both naive and memory T cells. This novel antigen-independent activation may help to maintain the naive T cell repertoire and facilitate the antigen-responsiveness of naive T cells.


Reduction of zolpidem sensitivity in a freeze lesion model of neocortical dysgenesis.
Early postnatal freeze lesions in rat neocortex produce anatomic abnormalities resembling those observed in human patients with seizure disorders. Although in vitro brain slices containing the lesion are hyperexcitable, the mechanisms of this alteration have yet to be elucidated. To test the hypothesis that changes in postsynaptic inhibitory receptors may underlie this hyperexcitability, we examined properties of gamma-aminobutyric acid type A receptor (GABAAR)-mediated miniature inhibitory postsynaptic currents (mIPSCs). Recordings were obtained in layer II/III pyramidal cells located 1-2 mm lateral to the lesion. mIPSC peak amplitude and rate of rise were increased relative to nonlesioned animals, whereas decay time constant and interevent interval were unaltered. Bath application of zolpidem at a concentration (20 nM) specific for activation of the type 1 benzodiazepine receptor had no significant effect on decay time constant in six of nine cells. Exposure to higher concentrations (100 nM) enhanced the decay time constant of all cells tested (n = 7). Because mIPSCs from unlesioned animals were sensitive to both concentrations of zolpidem, these results suggest that freeze lesions may decrease the affinity of pyramidal cell GABAARs for zolpidem. This could be mediated via a change in alpha-subunit composition of the GABAAR, which eliminates the type 1 benzodiazepine receptor.


Sensitivity of indirect immunofluorescence test in the diagnosis of pemphigus.
Indirect immunofluorescence testing of sera from patients with pemphigus produces a positive intercellular staining on a variety of epithelial substrates with different sensitivity. We aimed to determine the sensitivity of indirect immunofluorescence (IIF) test in detecting pemphigus antibodies, using two different substrates: guinea pig lip and human skin. IIF detected antibodies in 66 out of 109 patients with different types of pemphigus. Sensitivity of IIF performed with guinea pig lip was 40%, while with human skin it increased to 69%. However, we found that neither human skin nor guinea pig lip was sensitive enough to make an IIF test reliable for the diagnosis of pemphigus.


Carbon assimilation through a vertical light gradient in the canopy of invasive herbs grown under different temperature regimes is determined by leaf and whole-plant architecture.
This study examined the acclimation to temperature of two globally invasive species Iris pseudacorus and Lythrum salicaria, which share the same habitat type but differ in morphology. Iris pseudacorus has long vertical leaves, allowing light penetration through the canopy, while L. salicaria has stems with small horizontal leaves, creating significant self-shading. We aimed to build a physiological understanding of how these two species respond to different growth temperatures with regard to growth and gas exchange-related traits over the canopy. Growth and gas exchange-related traits in response to low (15 °C) and high (25 °C) growth temperature regimes were compared. Plants were grown in growth chambers, and light response curves were measured with infrared gas analysers after 23-33 days at three leaf positions on each plant, following the vertical light gradient through the canopy. After 37 days of growth, above-ground biomass, photosynthetic pigments and leaf N concentration were determined. The maximum photosynthesis rate was lower in lower leaf positions but did not differ significantly between temperatures. Iris pseudacorus photosynthesis decreased with decreasing leaf position, more so than L. salicaria. This was explained by decreasing N and chlorophyll concentrations towards the leaf base in I. pseudacorus, while pigment concentrations increased towards the lower canopy in L. salicaria. Biomass, shoot height and specific leaf area increased with temperature, more so in I. pseudacorus than in L. salicaria. Light response curves revealed that L. salicaria had a higher degree of shade acclimation than I. pseudacorus, probably due to self-shading in L. salicaria. High temperature decreased C assimilation at the bottom of the canopy in L. salicaria, while C assimilation in I. pseudacorus was less affected by temperature. As vegetative growth and flowering was stimulated by temperature, the invasive potential of these species is predicted to increase under global warming.


Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity.
In earlier studies, we had determined that class II (Ia) major histocompatibility complex (MHC) antigen expression in the normal rat lung was limited to dendritic cells and type II alveolar cells. In order to characterize the Ia+ pulmonary dendritic cells of the lung parenchyma, Lewis rat lungs were dissected free of their major airways, enzymatically digested, and serially subjected to density centrifugation on bovine serum albumin, overnight adherence, and immunopanning with a murine anti-rat monoclonal antibody (anti-OX-6) that reacts specifically with class II (Ia) MHC antigens. The purified Ia+ pulmonary cells displayed the morphologic and functional features of dendritic accessory cells, including extended cell processes, absence of nonspecific esterase staining, minimal phagocytosis of latex beads, rapid clustering with T lymphocytes, and co-stimulation of T-cell mitogen responses. Detailed immunophenotyping by cytofluorimetry and immunohistology showed that the purified dendritic cells were Ia (OX-6)+, CD45R (OX-1)+, CD45Rb (OX-22)-, ICAM-1+, and OX-43-. As many as 50% of the cells bound heat-aggregated IgG, while a smaller percentage expressed the CD43 sialophorin antigens (W3/13) expressed by a variety of blood-derived cells, and/or the OX-41 and RMA macrophage antigens. We conclude that Ia+ dendritic cells of lung are heterogeneous with respect to their expression of surface membrane differentiation antigens and may prove to be functionally distinct with respect to their accessory activities.


Sodium Butyrate Attenuated Diabetes-Induced Intestinal Inflammation by Modulating Gut Microbiota.
Diabetes mellitus (DM) continues to be one of the world's most costly and complex metabolic disorders. Accumulating evidence has shown that intestinal dysbiosis and associated inflammation can facilitate the onset and progression of DM. In this work, our goal was to investigate how sodium butyrate (SB) controls the gut microbiota to reduce the intestinal inflammation brought on by diabetes. Male KK-Ay mice were randomized into two groups: the DM model group (intragastric administration of 0.9% normal saline) and the SB treatment group (intragastric administration of 1,000 mg/kg/d SB). The C57BL/6J mice were used as the control group (intragastric administration of 0.9% normal saline). These mice were administered via gavage for 8 weeks. The results revealed that SB-treated mice significantly reduced fasting blood glucose (FBG), body weight, 24 h food and water intake, and improved islet histopathology in DM model mice. SB reduced TNF-α, IL-1β, and iNOS, whereas it enhanced the expression of the anti-inflammatory Arg-1 marker on intestinal macrophages and the secretion of anti-inflammatory IL-10. Specifically, SB was linked to a marked drop in the expression of the Th17 marker RORγt and a substantial increase in the expression of the Treg marker Foxp3. SB treatment was associated with significant reductions in the levels of Th17-derived cytokines such as IL-17 and IL-6, whereas anti-inflammatory Treg-derived cytokines such as TGF-β were increased. Additionally, the analysis results from 16S rDNA sequencing suggested that SB significantly reversed the variations in intestinal flora distribution and decreased the relative abundance of Weissella confusa and Anaerotruncus colihominis DSM 17241 at the species level as well as Leuconostocaceae, Streptococcaceae, and Christensenellaceae at the family, genus, and species levels. These distinct florae may serve as a diagnostic biomarker for DM-induced intestinal inflammation. In addition, the heat map of phylum and OTU level revealed a close relationship between DM-induced intestinal inflammation and intestinal microbiota. The present study suggested that SB may reduce DM-induced intestinal inflammation by regulating the gut microbiota.


Resting-state connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in clinical anxiety
The central nucleus of the amygdala and bed nucleus of the stria terminalis are involved primarily in phasic and sustained aversive states. Although both structures have been implicated in pathological anxiety, few studies with a clinical population have specifically focused on them, partly because of their small size. Previous work in our group used high-resolution imaging to map the restingstate functional connectivity of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in healthy subjects at 7 T, confirming and extending structural findings in humans and animals, while providing additional insight into cortical connectivity that is potentially unique to humans. In the current follow-up study, we contrasted resting-state functional connectivity in the bed nucleus of the stria terminalis and central nucleus of the amygdala at 7 T between healthy volunteers (n = 30) and patients with generalized and/or social anxiety disorder (n = 30). Results revealed significant voxel-level group differences. Compared with healthy volunteers, patients showed stronger resting-state functional connectivity between the central nucleus of the amygdala and the lateral orbitofrontal cortex and superior temporal sulcus. They also showed weaker resting-state functional connectivity between the bed nucleus of the stria terminalis and the dorsolateral prefrontal cortex and occipital cortex. These findings depart from a previous report of resting-state functional connectivity in the central nucleus of the amygdala and bed nucleus of the stria terminalis under sustained threat of shock in healthy volunteers. This study provides functional MRI proxies of the functional dissociation of the bed nucleus of the stria terminalis and central nucleus of the amygdala, and suggests that resting-state functional connectivity of key structures in the processing of defensive responses do not recapitulate changes related to induced state anxiety. Future work needs to replicate and further probe the clinical significance of these findings.


Expressions of vascular endothelial growth factor and nitric oxide synthase III in the thyroid gland of ovariectomized rats are upregulated by estrogen and selective estrogen receptor modulators.
Estrogen promotes the growth of thyroid cells. Therefore, we analyzed the influence of estrogen and selective estrogen receptor modulators (SERMs) on the expression of vascular endothelial growth factor (VEGF) and nitric oxide synthase III (NOS III) in the thyroid gland of ovariectomized (Ovx) rats. Wistar rats were divided into five groups, and bilateral ovariectomies were performed, except on the Sham-operated controls (Sham). Rats were grouped as follows: Sham; Ovx; and Ovx rats treated with daily subcutaneous injections of estradiol benzoate 3.5 microg/kg, tamoxifen 2.5 mg/kg, or raloxifene 2.5 mg/kg for 50 consecutive days. Control animals received vehicle (propyleneglycol), and at the end of the treatment, rats were sacrificed. The thyroid glands were excised, weighed, and processed for analysis of the expression of VEGF or NOS III by immunohistochemistry. The mean vascular areas were evaluated by immunodetection of alpha-smooth muscle actin. Thyroid weight and mean vascular area were lower in Ovx as compared with Sham, Ovx + estradiol benzoate, Ovx + Tam, or Ovx + Ral (p < 0.01). VEGF (p < 0.01) and NOS III expressions (p < 0.05) were significantly lower in the Ovx group, as compared with Sham, Ovx + estradiol benzoate, Ovx + Tam, and Ovx + Ral. Immunoreactivity for both VEGF and NOS III was mainly detected in the cytoplasm of the follicular epithelial cells. Our data suggest that estrogen and SERMs regulate the thyroid gland vascularization and that tamoxifen and raloxifene behave like estrogen does. Estrogen and SERMs upregulate VEGF and NOS III in such a way as to reverse the effects detected on the thyroid microvasculature of the Ovx rats.


Gas chromatographic/mass spectrometric assay for profiling the enantiomers of 3,4-methylenedioxymethamphetamine and its chiral metabolites using positive chemical ionization ion trap mass spectrometry.
A qualitative GC/MS profile was obtained and its mass spectrometric features characterized for the analysis of the enantiomers of (RS)-3,4-methylenedioxymethamphetamine (MDMA) and its metabolites (RS)-3,4-methylenedioxyamphetamine (MDA), (RS)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (RS)-4-hydroxy-3-methoxyamphetamine (HMA). A chiral derivatization method was selected to obtain the diastereomers required for the separation of the respective enantiomers with a non-chiral GC stationary phase. The selected derivatization consisted of a reaction with N-heptafluorobutyryl-(S)-prolyl chloride combined with a consecutive reaction with N-methyl-N-trimethylsilyltrifluoroacetamide, resulting in N-[heptafluorobutyryl-(S)-prolyl]-O-trimethylsilyl derivatives. Detection was carried out with electron ionization and positive chemical ionization (PCI) ion trap mass spectrometry. Mass spectra of the derivatives of reference standards of the compounds of interest obtained with PCI demonstrated that this method simultaneously induces proton and charge-transfer reactions in the ion trap. The advantage is that high mass information is provided while some fragmentation remains to elucidate structural details. Subsequently, in three urine samples obtained from different and unrelated MDMA intoxications, the enantiomers of MDMA and MDA were identified. In some urine samples also HMMA and/or HMA were found. In addition to these compounds, an unexpected compound and/or additional chiral metabolite, N-hydroxy-(RS)-3,4-methylenedioxyamphetamine, was identified in two out of three urine samples. Preliminary results also indicated an enantioselective metabolism in the N-demethylation pathway for MDMA in humans.


Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats.
As a model for the analysis of the fibrosuppressive role of estradiol, hepatic fibrosis was induced in male and female rats by the administration of a single dose of dimethylnitrosamine (DMN). The fibrotic response of the male liver after DMN treatment was significantly stronger than that of the female liver. In the male DMN model, estradiol reduced hepatic mRNA for type I and III procollagens and the tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as deposition of type I and III collagen protein total hepatic collagen and malondialdehyde (MDA), a product of lipid peroxidation. Concomitant administration of a neutralizing antibody against rat estradiol enhanced fibrogenesis, as judged by the same parameters. Ovariectomy in the female model had a fibrogenic effect, inducing the hepatic expression of both types of procollagen and TIMP-1; in addition, the number of alpha-smooth muscle actin (alpha-SMA)-positive cells in the liver increased; estradiol replacement was fibrosuppressive in the castrated-female model. In rat hepatic stellate cells incubated in primary culture with estradiol, cell number, type I collagen production, and alpha-SMA expression were all reduced. These findings suggest that estradiol suppressed the induction of hepatic fibrosis, and may in part underlie the more rapid progression in males of hepatic fibrosis and its complications.


Perfluoroalkyl compounds in dust from Asian, Australian, European, and North American homes and UK cars, classrooms, and offices.
Perfluoroalkyl compounds (PFCs) were measured in dust from Australian, Canadian, French, German, Kazahkstani, Thai, UK, and US homes, and UK cars, classrooms, and offices. Most PFCs were significantly lower in Kazahkstan and Thailand than elsewhere; 2-(N-methylperfluoro-1-octanesulfonamido)-ethanol (MeFOSE) and 2-(N-ethylperfluoro-1-octanesulfonamido)-ethanol (EtFOSE) were significantly lower in Canada than in the UK and the US; perfluoro-1-hexanesulfonate (PFHxS) was significantly lower in Canada than in the UK, and N-ethylperfluoro-1-octanesulfonamide (EtFOSA) was significantly higher in Australia than in the UK. High EtFOSA concentrations in some samples may be consistent with its use as an insecticide. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), PFHxS, and MeFOSE were significantly higher in classrooms than in cars, homes, and offices; N-methylperfluoro-1-octanesulfonamide (MeFOSA) was significantly lower in classrooms than in homes and offices, and perfluoro-1-octanesulfonamide (FOSA) was significantly lower in classrooms than in cars, homes, and offices. While homes are usually the most important vector of dust exposure (typically > 60%), offices and classrooms make important contributions. While diet is usually the main exposure pathway for UK adults and children (~1-6 years) for PFOS, PFOA, and PFHxS; dust ingestion can be significant under high dust ingestion scenarios. Even under high-end exposure scenarios for dust and diet, PFOS and PFOA exposures are well within the European Food Safety Authority tolerable daily intakes.


Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model.
Ionic calcium can help in the prevention of the process of osseous decalcification. This study aimed to evaluate the physicochemical properties and toxic effects of ionic calcium-fiber supplement (ICa+) and its impact on bone health preservation in mice C57/BL6 fed a calcium-deficient diet. Physicochemical properties include FTIR, apparent calcium solubility estimated by the calcium ratio obtained by ionization chromatography and atomic absorption. In vitro genotoxicity and cytotoxicity of the ICa+ were assessed. Twenty-five 7-week-old C57/BL6 mice were fed calcium-free diet (CFD) or CFD plus CaCO3 (1.33 mg Ca) or CFD plus ICa+ (1.33-6.66 mg Ca) for six weeks. After that, bone mass and microstructure parameters were assessed. Histological staining was performed to determine calcium deposits. ICa+ (100%) exhibited an apparent calcium solubility higher than CaCO3 (12.3%). ICa+ showed no cytotoxic and genotoxic in vitro activities. Histomorphometry analysis showed that the ICa+ treated group displayed a higher trabecular number than the trabecular space. Also, the ratio BV/TV was increased compared with all treatments. Ionic calcium-fiber supplementation prevents bone deterioration compared to mice fed a calcium-deficient diet.


Development and characterization of a Mantle Cell Lymphoma Cell Bank in the American Type Culture Collection.
Mantle cell lymphoma (MCL) is a rare B-cell malignancy that carries a relatively poor prognosis compared to other forms of non-Hodgkin lymphoma. Standardized preclinical tools are desperately required to hasten the discovery and translation of promising new treatments for MCL. Via an initiative organized through the Mantle Cell Lymphoma Consortium and the Lymphoma Research Foundation, we gathered MCL cell lines from laboratories around the world to create a characterized MCL Cell Bank at the American Type Culture Collection (ATCC). Initiated in 2006, this collection now contains eight cell lines, all of which have been rigorously characterized and are now stored and available for distribution to the general scientific community. We believe the awareness and use of these standardized cell lines will decrease variability between investigators, harmonize international research efforts, improve our understanding of the pathogenesis of the disease and hasten the development of novel treatment strategies.


Immobilized liposome chromatography for analysis of interactions between lipid bilayers and peptides.
Liposomes were sterically immobilized in gel beads to be used for isocratic chromatographic analysis of interactions between lipid bilayers, amino acids, and water-soluble peptides. Tryptophan was more retarded on the immobilized liposomes than were other amino acids, and peptides with C-terminal cysteine were much more retarded than were peptides with serine or aminobutyric acid instead of the cysteine. Peptide sequences could affect the peptide-liposome interactions. For peptides corresponding to polypeptide segments of a membrane protein, the human red cell glucose transporter (Glut1), the retention volumes increased with decreasing water-to-oil transfer free energy of the peptides and were related to the transfer free energy distribution within the peptides as shown by hydropathy plots and to the presence of cysteine. Among these peptides, the partially hydrophobic peptides 125GRFIIGVYCG134 and 201CIVLPFCPES210 and the hydrophilic peptide 421CFQYVEQLC429 were most strongly retarded on immobilized phosphatidylcholine liposomes. The results indicated that the peptide-liposome interactions were mainly of hydrophobic nature and that the structure of the interfacial head-group region of the lipid bilayers was important.


The use of imatinib mesylate as a lifesaving treatment of chronic myeloid leukemia relapse after bone marrow transplantation.
We describe the response of imatinib as lifesaving treatment of chronic myeloid leukemia (CML) relapse in seven patients who underwent allogeneic bone marrow transplantation (alloBMT) at our institution over a period of 4 years. Retrospective analysis of their medical records revealed that a mean age at transplant was 45.2 years. The median time to diagnosis was 7.4 years after transplant. At relapse, four, two, and one patients were classified as having hematologic, major molecular, and cytogenetic relapse, respectively. At imatinib initiation, five had CML in a chronic phase, while one patient was diagnosed as having accelerated phase and blast crisis. All these patients could be evaluated for the therapeutic efficacy. At a mean of follow-up of 1.9 years of therapy, all evaluable patients achieved major molecular response without compromising safety. Consistent with available data, our results indicate that imatinib is safe and effective treatment option for patients with relapse after BMT.