ERalpha and ERbeta expression and transcriptional activity are differentially regulated by HDAC inhibitors.
The proliferative action of ERalpha largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERbeta displays tumor-suppressor properties, thus supporting the interest to identify compounds that could increase its activity. Here, we show that histone deacetylase inhibitors (HDI) upregulated ERbeta protein levels, whereas it decreased ERalpha expression. Part of this regulation took place at the mRNA level through a mechanism independent of de novo protein synthesis. In addition, we found that, in various cancer cells, the treatment with different HDI enhanced the ligand-dependent activity of ERbeta more strongly than that of ERalpha. On the other hand, in MDA-MB231 and HeLa cells, the expression of ERs modified the transcriptional response to HDI. The use of deletion mutants of both receptors demonstrated that AF1 domain of the receptors was required. Finally, we show that ERbeta expression led to a dramatic increased in the antiproliferative activity of HDI, which correlated with a modification of the transcription of genes involved in cell cycle control by HDI. Altogether, these data demonstrate that the interference of ERbeta and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy.


Nomogram for Predicting In-Hospital Mortality in Patients with Acute ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock after Primary Percutaneous Coronary Intervention.
Mortality after percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients with cardiogenic shock (CS) remains high. However, the real-world risk factors for mortality in these patients are poorly defined. The aim of this study is to establish a clinical prognostic nomogram for predicting in-hospital mortality after primary PCI in STEMI patients with CS. This retrospective, multicenter, observational study included STEMI patients with CS who underwent PCI at 39 hospitals in Hebei Province from January 2018 to December 2019. A multivariate logistic regression model was used to identify the factors associated with in-hospital mortality. These factors were then incorporated into a nomogram and its performance was evaluated by discrimination, calibration, and clinical utility. This study included 274 patients, among whom 179 died in hospital. Sex, random blood glucose on admission, ejection fraction after PCI, no-reflow, and intra-aortic balloon pump (IABP) were independently associated with in-hospital mortality (all P < 0.05). In the training set, the nomogram showed a C-index of 0.819, goodness-of-fit of 0.08, and area under the receiver operating characteristic curve (AUC) of 0.819 (95%CI = 0.759-0.879). In the testing set, the C-index was 0.842, goodness-of-fit was 0.585, and AUC was 0.842 (95%CI = 0.715-0.970). The results indicate that the nomogram had good discrimination and good prediction accuracy and could achieve a good net benefit. We established and validated a nomogram that provided individual prediction of in-hospital mortality for STEMI patients with CS after PCI in a Chinese population.


Oil and natural gas rents and CO2 emissions nexus in MENA: spatial analysis.
Oil rents (OR) and natural gas rents (NGR) have significant contributions to the income of the Middle East and North Africa (MENA) economies and may increase emissions. Moreover, spatial autocorrelation is expected in carbon dioxide (CO2) emissions due to the geographically closed economies in the MENA region. Thus, we examine the impact of OR and NGR on CO2 emissions caring spatial dimensions and analyze the environmental Kuznets curve (EKC). We apply the spatial Durbin model technique on the effects of OR, NGR, and economic growth on CO2 emissions in 17 MENA nations from 2000-2019, i.e., Algeria, Bahrain, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Libya, Morocco, Oman, Qatar, Saudi Arabia, Syria, Tunisia, the United Arab Emirates (UAE), and Yemen. Moreover, diagnostic tests are applied to reach the most appropriate spatial specification and to have the most robust results. The results disclose that CO2 emissions have spillovers and emissions of any country can damage the environment of neighboring countries. The EKC is corroborated with a turning point of 38,698 constant 2015 US dollars. Israel and Qatar are in 2nd phase of the EKC, and 15 MENA economies are in 1st stage. Thus, the economic expansion of most economies has ecological concerns. The effect of natural gas rents is found statistically insignificant. Oil rents have minute negative effects on emissions of local economies with an elasticity coefficient of -0.2117. Nevertheless, these have a positive indirect effect with an elasticity coefficient of 0.5328. Thus, the net effect of oil rents is positive. One percent increase in oil rents could accelerate 0.3211% of emissions. Thus, we suggest the MENA countries reduce reliance on oil rents in their income to avoid the negative environmental effects of the oil sector.


Comparison between R-phycocyanin-labeled and R-phycoerythrin-labeled monoclonal antibody (Mab) probes for the detection of Entamoeba histolytica trophozoites.
A comparison between R-phycocyanin (R-PC)-labeled monoclonal antibody (MAb) probe and R-phycoerythrin (R-PE)-labeled MAb probe for the detection of the three standard reference strains of the cultured-derived Entamoeba histolytica trophozoites, namely HK-9, HM-1:IMSS, and HTH-56:MUTM were evaluated by using direct immunofluorescence antibody (DIFA) assay five times for each strain. Under the blue irradiation of the fluorescent microscope, both R-PC-labeled and R-PE-labeled MAb probes showed consistently greenish-yellow trophozoites and golden-orange trophozoites, respectively. The R-PE-labeled MAb probe stained the trophozoites more brightly and clearly than those stained by the R-PC-labeled MAb probe of the same Eh208C2-2MAb. When observed under the green irradiation, both probes showed the same intensity of brightly red color at the trophozoites of all three strains of E. histolytica. The sensitivity of both tests was 100%. Since this Eh208C2-2MAb could recognize specifically E. histolytica pyruvate:ferredoxin oxidoreductase (PFOR) enzyme, therefore, our two antibody probes would be valuable for use as a rapid, easy and sensitive test for diagnosis of invasive amebiasis. Further applications of these two probes directly onto the fecal sample spots and to more culture-derived strains of E. histolytica/E. dispar of known zymodemes in collaboration with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDRB), Dhaka, Bangladesh, are under investigation.


Method for determining the temporal response of microbial phosphate transport affinity.
Nutrient transport affinities of nutrient-starved microbial populations were measured as initial slopes of plots of limiting-nutrient transport rates versus extracellular limiting-nutrient concentrations. A method was devised for the determination of soluble reactive phosphate (Pi) affinity in Pi-limited continuous culture (aT), which was then used as an indicator of the effects of light/dark cycle (LD) perturbations on the temporal Pi transport abilities of three species of freshwater algae. Cell division was asynchronous for the green alga Selenastrum capricornutum grown in continuous cultures exposed to LD cycles. An apparent rhythm in aT for Pi was greatly affected by the population size parameter. Cell division was phased for the green alga Scenedesmus quadricauda grown in LD continuous culture. A rhythm in aT for Pi was not greatly affected by the biomass parameter. Cell division was also phased in LD continuous culture for the blue-green alga (cyanobacterium) Synechococcus Nägeli, but rhythms in other parameters could not be detected. Synechococcus Nägeli was an extremely efficient Pi transporter at low Pi concentrations in LD continuous culture, and so aT could not be calculated. The results demonstrate that aT is well suited to describing the temporal response of Pi transport in LD-perturbed, Pi-limited continuous culture.


Influence of formulation on photoinactivation of bacteria by lumichrome.
Lumichrome, a photodegradation product of riboflavin, is an endogenous compound in humans. The compound is more photostable and a more efficient photogenerator of singlet oxygen than riboflavin. It absorbs radiation in the UVA and blue-light region, which can be an advantage in antibacterial photodynamic therapy (aPDT) of superficial infections. The aim of this study was to investigate the in vitro aPDT effect of various lumichrome pharmaceutical formulations. Solutions of lumichrome (10(-5) - 10(-3)M) were prepared in plain phosphate buffered saline (PBS) or in PBS solutions containing cyclodextrins, DMSO, PEG 400 or polyoxamers (Pluronic). Supersaturated solutions of lumichrome in PBS were prepared via the cosolvent and solvent evaporation method. Phototoxic effects of selected lumichrome preparations were studied in planktonic Gram-positive (E. faecalis) and Gram-negative (E. coli) bacteria models. The UVA/blue light source emitted mainly in the range 340-440 nm. Lumichrome was up to tenfold more phototoxic against Gram-positive than to Gram-negative bacteria. Bacterial eradication was induced after exposure of lumichrome formulations (PBS, PEG 400 and HPγCD) combined with 24J/cm2 UVA/blue light. Increasing the concentration of lumichrome did not enhance the phototoxic effect, probably due to radiation attenuation in the highly absorbing solution (inner filter effect). Cyclodextrins were efficient enhancers of the lumichrome solubility in aqueous solutions, but inhibited the phototoxic effect. The study demonstrates that assuming the use of an optimized formulation, lumichrome has potential as a UVA/blue light photosensitizer in aPDT.


[Immature solid teratoma of the uterine cervix (author's transl)].
A 27-year-old woman with an inconspicuous anamnesis developed within two years a solid tumor of about 10/5 cm in size, and extending from the left corner of the external os up to the lumen of the vagina and consisting of partly immature ectodermic, mesodermic and endodermic parts. After the radical removal of the tumor by means of abdominal hysterectomy and left-sided adnexectomy no signs of a recurrence could be observed for about ten years. Except a shortly described case of teratoma of the endometrium no further case of a uterine teratoma has been mentioned in the literature so far. A brief discussion of differential diagnosis and etiology is also present.


The international standard for oxytetracycline.
The first attempt to set up an international standard for oxytetracycline, using oxytetracycline hydrochloride, failed because of difficulties in obtaining a preparation whose moisture content was uniform after distribution into ampoules. A preparation of dihydrate of oxytetracycline base was obtained instead, and was compared in an international collaborative assay with a sample of oxytetracycline hydrochloride, which was the current working standard of Chas. Pfizer & Co., Inc., USA. The results of the collaborative assay showed that the potency of the dihydrate was uniform, and that it was a suitable preparation for use as the International Standard.Evidence was obtained, however, that the reference preparation at the time of examination was less potent than had been originally supposed, and that it was hydrated. The potency of the proposed international standard was recalculated after allowance for water in the reference preparation, and the resulting biological potency agreed well with that to be expected on the basis of the physicochemical properties of the preparation. It was agreed, therefore, that the recalculated values should be used, and the preparation of oxytetracycline base dihydrate used in the collaborative assay is established as the International Standard for Oxytetracycline with a potency of 900 International Units per mg.


[Liver cirrosis and complication risk management].
Liver cirrhosis (LC) takes the main place in the structure of the pathology of the digestive system in terms of the frequency of mortality, as well as in the development of fatal and poorly controlled complications, which requires the search for effective methods for preventing the progression of the disease and the development of complications. The article provides updated information on the role of the intestinal microbiota, as well as endotoxemia and increased intestinal permeability syndromes in the pathophysiology of LC and its complications. The results of recent meta-analyses of the impact of dysbiotic disorders on the prognosis of the LC and the options for their correction are presented. Understanding of the significance of involvement of gut microbiota in the pathogenesis of LC has become one of the levers of management of the risks of complications of LC. In this case, the livergut axis can be considered to be the leading link to the formation of most of the main complications of LC.


Psychiatric caregiver stress: clinical implications of compassion fatigue.
The capacity to work productively is a key component of health and emotional well-being. People who work in health care can be exposed to the fatigue of care. Compassion fatigue has been described as an occupational hazard specific to clinical work related severe emotional distress. In our study, we have evaluated compassion fatigue in a mental health group (47 psychiatric staff) and its relationship with inpatients (237 inpatients) affected by some psychiatric disorders. At baseline, the more significant data indicate a high percentage of Job Burnout and Compassion Fatigue in psychiatric nurses (respectively, 39.28%, 28.57%). Significant Compassion Fatigue percentage is present also in psychologist group (36.36%). Finally, in psychiatrists, the exposure to patients increased vicarious trauma (28.57%), but not job burnout. After a year of participation in Balint Groups, the psychiatric staff presented an overall reduction in total mean score in any administered scale (CBI: p<0.0000045; sCFs: (Vicarious Trauma: p<0.0288; Job Burnout: p<0.000001)). Thus, compassion fatigue causes concern among mental health professionals, and Balint Groups may represent a therapeutic strategy to help health professionals to face difficulties in challenging work environments.


Childhood fevers: developing an evidence-based anticipatory guidance tool for parents.
Misconceptions about childhood fevers heighten parents' concerns leading to frequent use of health care services. Designing, piloting, and evaluating nursing interventions to demystify parents' phobia of fevers are imperative. An evidence-based fever anticipatory guidance tool was designed to assist parents by: dispelling misconceptions, teaching proper care of their febrile child and appropriate use of antipyretics, and providing a list of serious signs that warrant medical attention. Concepts of the Health Belief Model (HBM) are applied to parent behavior to promote a greater understanding of their actions in the face of childhood fever. Informing consumers with accurate and consistent information has direct implications for changing practice in the hospital and community.


Sleep-wake and circadian disturbances in Parkinson disease: a short clinical guide.
Sleep-wake and circadian disturbances are very frequent and often troublesome symptoms in patients suffering from Parkinson disease. Therefore, a concept for the evaluation and therapy of such disturbances must be considered and implemented by all physicians involved in Parkinson care. The present review shall offer a short and condensed guide for the clinician. It summarizes the epidemiology of sleep-wake and circadian disturbances in Parkinson disease, sheds some light into translational studies forwarding knowledge about underlying pathophysiological concepts, and discusses diagnostic approaches and current therapeutic recommendations, albeit the latter being mostly based on insufficient evidence. As most treatments for Parkinson-related sleep-wake disturbances are still off-label, we need more prospective randomized trials for being able to optimize and personalize treatment for every single patient.


Characterization of side population (SP) cells in murine cochlear nucleus.
We characterized side population (SP) cells in the cochlear nucleus (CN). Some genes of stem/progenitor markers in sorted SP cells were identified by microarray analysis and RT-PCR. Furthermore, some cells in the CN also demonstrated self-renewal and clonal expansion activities. These results suggest that tissue stem/ progenitor like cells would be identified and characterized as a slow cycling and immaturity in SP cells of CN. SP cells were sorted and characterized as regards their activity in the CN in order to identify the tissue progenitor/stem cells in the auditory nervous system. Bromodeoxyuridine (BrdU)-injected mice were prepared and the long-term BrdU-retaining cells were detected by flow cytometry. Gene expression of SP and MP cells was analyzed by microarray analysis and RT-PCR. SP cells were cultured in conditioned medium to expand stem/progenitor cells in vitro and to estimate the spheroid-forming activity of stem cells. In all, 1% of cells in the CN were detected as BrdU-positive. SP cells were detected at a frequency of 4.4% and expressed stem/progenitor markers, Abcb1b, Abcg2, Sca1, Notch1, Notch4, Hes1, and Jag1 in microarray analysis. Expression of Abcb1b, Abcg2, Sca1,Oct3/4, and Sox2 as determined by RT-PCR was supported by the microarray data. CN cells also had sphere-forming activity in young mice, but this activity was decreased by aging.


Ethnic differences in the relationship between bioelectrical impedance and body size.
The present study compared the regression equations of bioelectrical impedance on body size among various groups to investigate potential differences due to ethnicity. Data consisted of 30 Japanese and 28 Caucasoid subjects, and other groups of Aborigines, Danes, Melanesians and Polynesians from literature. The relationship between impedance and body weight fot the groups showed the ethnic difference. In the regression equations for Japanese and Caucasoid, a statistically significant difference was observed between both groups. The regression equation for Japanese was lower in the elevation. This seemed to be attributable to differences in the volume of fat-free mass for the same body build, configuration of the body, and fat-free mass density.


Ovarian hormone status and abdominal visceral adipose tissue metabolism.
We examined abdominal sc and visceral adipose tissue metabolism in a sample of 19 regularly cycling premenopausal women (age 46.3 +/- 3.7 yr) and 10 women with natural menopause or pharmacological ovarian suppression (age 51.1 +/- 9.2 yr). Subcutaneous and visceral (omental, epiploic) adipose tissue biopsies were obtained during abdominal hysterectomies. Body composition and adipose tissue distribution were measured before the surgery by dual x-ray absorptiometry and computed tomography, respectively. Ovarian hormone-deficient women tended to be older (P = 0.08) and were characterized by increased visceral adipose tissue area (P < 0.05). Subcutaneous adipocyte size, lipoprotein lipase (LPL) activity, and basal lipolysis were not significantly different between groups. On the other hand, omental fat cell size was significantly higher in ovarian hormone-deficient women, compared with premenopausal women (P < 0.05). The omental/sc LPL activity ratio and omental adipocyte basal lipolysis were also significantly higher in ovarian hormone-deficient women (P < 0.05 for both comparisons). Significant positive correlations were found between visceral adipose tissue area and omental LPL activity (r = 0.54, P < 0.003), omental adipocyte basal lipolysis (r = 0.66, P < 0.0001), and omental fat cell size (r = 0.81, P < 0.0001). In multivariate analyses, ovarian status was no longer a significant predictor of adipose cell metabolism variables after visceral adipose tissue area was entered into the model, with the exception of the omental/sc LPL activity ratio, which remained independently associated with ovarian status. In conclusion, although the size of the visceral adipose tissue compartment was an important determinant of adipocyte metabolism in this depot, the increased omental/sc LPL activity ratio in ovarian hormone-deficient women supports the notion of a predominant visceral fat storage in these women.


Association of Candida sp. with the Degrees of Dysplasia and Oral Cancer: A Study by Calcofluor White under Fluorescent Microscopy.
Candida albicans (C. albicans) play a significant role in oral mucosal carcinogenesis. It can be identified using various techniques in cytological smears. But, very few studies have been conducted on histopathological sections using calcofluor white M2R under fluorescent microscopy. Additionally, detection and quantification of Candida colonies and its correlation with various grades of oral leukoplakia and oral carcinomas have not been explored much. The current retrospective study included 80 samples from archives consisting of 60 samples in the study group (10 cases each of mild, moderate, and severe epithelial dysplasia (totally 30) and 30 cases of oral carcinoma). Sections were stained with calcofluor white (CFW) and 10% KOH for the observation under fluorescent microscopy and correlated with different grades of oral leukoplakia and oral carcinomas. Chi-square test was used in SSPS software to study the presence and absence of Candida sp. in different groups. The study groups of oral carcinoma and dysplasia showed a significant association with Candida sp. (P=0). When carcinoma was compared with each grade of dysplasia, except mild dysplasia (P=4.4E-05), both moderate (P=0.402195) and severe dysplasia (P=0.558746) showed an insignificant P-value. When the groups of mild (13.3%), moderate (30%), and severe (33.3%) dysplasia were considered independently, the incidence of Candida sp. increased as the grade of dysplasia increased. The number of colonies have been counted and the maximum number of colonies have been observed in carcinoma and the least have been observed in mild dysplasia. A significant association of Candida colonies with epithelial dysplasia and oral cancer was established. Further, CFW was found a promising candidate to identify Candida colonies in tissue sections using fluorescent microscopy.


[The effect of the tumor suppressor p53 and its mutant forms on the differentiation and viability of K562 leukemic cells].
Mutations of the p53 tumor suppressor are often observed in various human malignancies including blast crisis of chronic myelogenous leukaemia (CML). The pattern of p53 mutation in CML shows some peculiarities as compared with the majority of other neoplasias. In particular, the substitutions at codon 273, one of the most common p53 alteration in various tumors, are not characteristic of CML. To test whether distinction in the pattern of p53 mutation are associated with certain peculiarities of biological effects of different mutant proteins in myeloid cells, we obtained and analysed a panel of human K562 cell sublines expressing various exogenous p53: human Pro156, His175, His194, Trp248 and His 273, or murine temperature-sensitive (ts) Val135 that has properties of mutant protein at 37 degrees C, but shows activities of wild-type (wt) p53 at 32 degrees C. We have found that expression of wt-p53 enhanced the dependence of cells on growth/survival factors, incubation of sparse (< 10(5) cells per/ml) K562/Val135 cultures at 32 degrees C caused apoptosis. In media conditioned by cells of different origin (K562, colorectal carcinoma LIM 1215, Rat1 fibroblast) the p53-dependent apoptosis was inhibited. In conditions that do not lead to apoptosis, the expression of ts-wt-p53 was accompanied by dramatic increase in the number of cells containing glycophorin A (GlycPhA) and "antigen of erythroblasts"--specific markers of erythroid differentiation. Unlike the wt-p53, the majority of tumor-derived mutant p53 (Pro156, His175, His194, Trp248) increased cells survival in media with low serum content and decreased the number of cell expressing GlycPhA, CD9, CD15 and CD71 differentiation antigens. On the other hand, expression of His273-p53 caused a significant augmentation in the number of CD9-positive cells and enhanced the dependence on growth/survival factors that are present in serum or conditioned media. The data obtained are consistent with the idea that unusual pattern of p53 mutations in CML can reflect the peculiarities of the effects of some mutant proteins on differentiation and/or viability of leukemic cells.


Preferential occurrence of attacks during night sleep and/or upon awakening negatively affects migraine clinical presentation.
It is well known that migraine attacks can preferentially occur during night sleep and/or upon awakening, however the possible implications of this timing on migraine clinical presentation remain unclear. The aim of this study was to assess the possible consequences of sleep-related migraine (defined as ≥ 75% of migraine attacks occurring during night sleep and/or upon awakening) on the migraine clinical picture (i.e. migraine-related disability, attack severity, use of symptomatic drugs), subjective sleep quality, excessive daytime sleepiness and fatigue. Two hundred consecutive migraine without aura patients were enrolled; patients with comorbid disorders or chronic medication use were excluded. 39% of the migraineurs included in the study received a diagnosis of sleep-related migraine. The mean frequency of migraine attacks (days per month) did not significantly differ between the patients with and those without sleep-related migraine, whereas migraine-related disability (p<0.0001), mean attack severity (p<0.0001), and monthly intake of symptomatic drugs (p<0.0001) were significantly higher in patients with migraine preferentially occurring at night-time and/or upon awakening. Subjective sleep quality and excessive daytime sleepiness did not differ significantly between the two groups, whereas fatigue was significantly more present in the patients with sleep-related migraine (p=0.0001). These data seem to support the hypothesis that patients with sleep-related migraine represent a subset of individuals with a more severe and disabling clinical presentation of migraine and greater impairment of daily functioning, as suggested by the higher degree of fatigue. Migraineurs with night-time attacks Preferential occurrence of attacks during night sleep and/or upon awakening negatively affects migraine clinical presentation also showed a greater use of symptomatic drugs, possibly related to delayed use of symptomatic treatment. The identification of subtypes of patients with a higher disability risk profile could have crucial implications for individually tailored management of migraine patients.


Advances in the management of diabetic neuropathy.
The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.


Valence electronic charge density of distorted C60- monomers in polymerized KC60 and RbC60.
We investigate the valence electronic charge density of the C(60) (-) monomers in (C(60) (-))(n) polymer chains in K- and RbC(60) by means of a nonorthogonal tight-binding formalism using experimental data on the positions of the carbon atoms. Various configurations of the C(60) cages are considered. Starting from the ideal icosahedral C(60) structure and moving to the realistic, experimentally determined spatial configuration of the C(60) cages in K- and RbC(60), we observe a systematic increase of the electric quadrupole moments on the C(60) (-) monomers. We also confirm the validity of factorizing the charge density of a C(60) (-) monomer into an angular and a radial part.


RNA-seq reveals regional differences in transcriptome response to heat stress in the marine snail Chlorostoma funebralis.
To investigate the role of gene expression in adaptation of marine ectotherms to different temperatures, we examined the transcriptome-wide thermal stress response in geographically separated populations of the intertidal snail Chlorostoma funebralis. Snails from two southern (heat tolerant) and two northern (heat sensitive) populations were acclimated to a common thermal environment, exposed to an environmentally relevant thermal stress and analysed using RNA-seq. Pooling across all populations revealed 306 genes with differential expression between control and heat-stressed samples, including 163 significantly upregulated and 143 significantly downregulated genes. When considered separately, regional differences in response were widely apparent. Heat shock proteins (Hsps) were upregulated in both regions, but the magnitude of response was significantly greater in northern populations for most Hsp70s, while the southern populations showed greater upregulation for approximately half of the Hsp40s. Of 177 stress-responsive genes in northern populations, 55 responded to heat stress only in northern populations. Several molecular chaperones and antioxidant genes that were not differentially expressed in southern populations showed higher expression under control conditions compared with northern populations. This suggests that evolution of elevated expression of these genes under benign conditions preadapts the southern populations to frequent heat stress and contributes to their higher thermal tolerance. These results indicate that evolution has resulted in different transcriptome responses across populations, including upregulation of genes in response to stress and preadaptation of genes in anticipation of stress (based on evolutionary history of frequent heat exposure). The relative importance of the two mechanisms differs among gene families and among populations.


[Proton spectroscopy findings of meningioma].
To evaluate the characteristics of 1HMRSI and its diagnostic value on meningioma. The findings of conventional MRI and of 1HMRSI from 11 cases of clinically proven meningiomas and from 12 normal volunteers were comparatively analyzed. The imaging sequences included T1-weighted imaging and T2-weighted imaging; additionally T1-weighted imaging with injection of the contrast agent of Gd-DTPA was performed in all meningioma cases. Two-dimensional phase encoding of proton magnetic resonance spectroscopic imaging (2D 1HMRSI) were obtained in all cases. On conventional pre-contrast MRI, the signals in 8 meningioma cases showed medium or faintly low intensities and in 3 cases showed mixed intensities on T1WI. On T2WI, the signals in 7 cases showed medium or faintly high intensities and in 4 cases showed mixed intensities. After injection of Gd-DTPA, the solid portion of tumors exhibited obvious enhancement in all meningioma cases. "Dural trail sign" was revealed in 7 cases. Peri-tumor edema was evident in 11 meningioma cases. Compared with control group, 1HMRSI of all meningiomas revealed different spectral peaks, including absent acetylaspartate (NAA), prominent choline (Cho), and reduced phosphocreatine (Pcr). The ratios of Cho/Pcr obviously increased. The peak of lactate (Lac) was visualized in 2 meningioma cases. Most cases of meningioma can be diagnosed with conventional magnetic resonance imaging (MRI). 1HMRSI can yield more informative findings about meningioma via the observed metabolic materials changes in tumor cells. So conventional MRI is the most important technology for diagnosing meningioma and 1HMRS combined with MRI can improve the diagnostic accuracy. 1HMRSI can be an important supplemental means in the diagnosis of meningiomas.


Supramolecular architectures self-assembled using long chain alkylated spin crossover cobalt(ii) compounds.
Self-assembled hybrid supramolecular architectures formed between amphiphilic anions and long alkylated cationic cobalt(ii) complexes of type [Co(Cn-terpy)2](C12-Glu)2 (n = 15-20) have been synthesized and characterized by TEM, PXRD and magnetic susceptibility measurements. The hybrids display wire or rolled sheet supramolecular arrangements with odd and even alkyl chain dependence, with the cobalt(ii) centres exhibiting gradual spin-crossover behaviours.


Interaction of jack bean (Canavalia ensiformis) urease and a derived peptide with lipid vesicles.
Ureases are metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Jack bean (Canavalia ensiformis) produces three isoforms of urease (Canatoxin, JBU and JBURE-II). Canatoxin and JBU display several biological properties independent of their ureolytic activity, such as neurotoxicity, exocytosis-inducing and pro-inflammatory effects, blood platelets activation, insecticidal and antifungal activities. The Canatoxin entomotoxic activity is mostly due to an internal peptide, named pepcanatox, released upon the hydrolysis of the protein by insect cathepsin-like digestive enzymes. Based on pepcanatox sequence, Jaburetox-2Ec was produced in Escherichia coli. JBU and its peptides were shown to permeabilize membranes through an ion channel-based mechanism. Here we studied the JBU and Jaburetox-2Ec interaction with platelet-like multilamellar liposomes (PML) using Dynamic Light Scattering and Small Angle X-ray Scattering techniques. We also analyzed the interaction of JBU with giant unilamellar vesicles (GUVs) using Fluorescence Microscopy. The interaction of vesicles with JBU led to a slight reduction of hydrodynamic radius, and caused an increase in the lamellar repeat distance of PML, suggesting a membrane disordering effect. In contrast, Jaburetox-2Ec decreased the lamellar repeat distance of PML membranes, while also diminishing their hydrodynamic radius. Fluorescence microscopy showed that the interaction of GUVs with JBU caused membrane perturbation with formation of tethers. In conclusion, JBU can interact with PML, probably by inserting its Jaburetox "domain" into the PML external membrane. Additionally, the interaction of Jaburetox-2Ec affects the vesicle's internal bilayers and hence causes more drastic changes in the PML membrane organization in comparison with JBU.


Relationship between maternal serum C-reactive protein, funisitis and early-onset neonatal sepsis.
The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.


Electron density distribution in tetralithium hypodiphosphate hexahydrate, Li4P2O6·6H2O.
Tetralithium hypodiphosphate hexahydrate, Li4P2O6·6H2O, forms a highly symmetrical crystal structure, where hypodiphosphate anions have \bar 3m (D3d) symmetry. Analysis of the charge distribution (experimental and theoretically calculated) shows that the charges of the P atoms are lower than in phosphates and phosphonates, whereas the O charges are similar. Values of both ρc and ∇(2)ρc suggest that the P-P bond is a weak covalent one, while the P-O one is polarized covalent, with topological parameters similar to those of P-O bonds in phosphates or phosphonates. Theoretical calculations show that the hypodiphosphate anion is relatively insensitive to its coordination environment; this is brought about by the vicinity of cationic P atoms. The localization and delocalization indices have been computed and discussed.


Phase behaviour and the random phase approximation for ultrasoft restricted primitive models.
Phase separation of the ultrasoft restricted primitive model (URPM) with gaussian charges is re-investigated in the random phase approximation (RPA)--the "Level A" approximation discussed by Nikoubashman, Hansen, and Kahl [J. Chem. Phys. 137, 094905 (2012)]. We find that the RPA predicts a region of low temperature vapour-liquid coexistence, with a critical density much lower than that observed in either simulations or more refined approximations (we also remark that the RPA critical point for a related model with Bessel charges can be solved analytically). This observation suggests that the hierarchy of approximations introduced by Nikoubashman et al. should be analogous to those introduced by Fisher and Levin for the restricted primitive model [Phys. Rev. Lett. 71, 3826 (1993)], which makes the inability of these approximations to capture the observed URPM phase behaviour even more worthy of investigation.


Dependence of Grain Size on the Performance of a Polysilicon Channel TFT for 3D NAND Flash Memory.
We investigated the dependence of grain size on the performance of a polycrystalline silicon (poly-Si) channel TFT for application to 3D NAND Flash memory devices. It has been found that the device performance and memory characteristics are strongly affected by the grain size of the poly-Si channel. Higher on-state current, faster program speed, and poor endurance/reliability properties are observed when the poly-Si grain size is large. These are mainly attributed to the different local electric field induced by an oxide valley at the interface between the poly-Si channel and the gate oxide. In addition, the trap density at the gate oxide interface was successfully measured using a charge pumping method by the separation between the gate oxide interface traps and traps at the grain boundaries in the poly-Si channel. The poly-Si channel with larger grain size has lower interface trap density.


Historical perspective.
Development of the first percutaneous catheters for local delivery is described. Understanding of the mechanisms by which circulating materials gain entrance to the artery wall, and the importance of hypertension in accelerating that process were crucial to the conceptual basis of these devices. The double balloon catheter and the porous balloon catheter were systematically studied to quantify the local pressure-wall penetration relationship. Designs for many new catheters that claim advantage over early models require similar systematic demonstration of their performance with normal and diseased arteries. Only in this way can this promising new technique become a clinical advance against human vascular disease.


[Histological and immunohistochemical study and AgNOR analysis of smooth muscle tumors of the digestive tract].
Smooth muscle tumors of the esophagus (n = 29), stomach (n = 30), small intestine (n = 31) and large intestine (n = 12) were examined histologically and immunohistochemically for vimentin (Vim), desmin (Des), S100, fibronectin (FN) and cytokeratin (Cyt) and for nucleolar organizer regions (AgNOR). There were 49 cases of leiomyoma (LM), 51 cases of leiomyosarcoma (LS) and 2 cases of leiomyoblastoma(LB). Histologically, LS was characterized by cellular atypia, more cells in mitosis and invasion to adjacent normal tissue. No mitotic figure was observed in LM. AgNOR was more abundant in number in LS than LM (P < 0.001), but it had no direct relation to tumor size, number of cells in mitosis and patients' survival period. Immunohistochemical studies of Vim, Des, S100, FN and Cyt revealed that none of them was very helpful in the differential diagnosis of LM from LS.


Pathology of tumors in fish associated with retroviruses: a review.
Thirteen proliferative diseases in fish have been associated in the literature with 1 or more retroviruses. Typically, these occur as seasonal epizootics affecting farmed and wild fish, and most lesions resolve spontaneously. Spontaneous resolution and lifelong resistance to reinfection are 2 features of some piscine retrovirus-induced tumors that have stimulated research interest in this field. The purpose of this review is to present the reader with the epidemiological and morphological features of proliferative diseases in fish that have been associated with retroviruses by 1 or more of the following methods: detection of C-type retrovirus-like particles or reverse transcriptase activity in tumor tissues; successful tumor transmission trials using well-characterized, tumor-derived, cell-free inocula; or molecular characterization of the virus from spontaneous and experimentally induced tumors. Two of the diseases included in this review, European smelt spawning papillomatosis and bicolor damselfish neurofibromatosis, at one time were attributed to a retroviral etiology, but both are now believed to involve additional viral agents based on more recent investigations. We include the latter 2 entities to update the reader about these developments.


Carbon burial and storage in tropical salt marshes under the influence of sea level rise.
Coastal vegetated habitats can be important sinks of organic carbon (Corg) and mitigate global warming by sequestering significant quantities of atmospheric CO2 and storing sedimentary Corg for long periods, although their Corg burial and storage capacity may be affected by on-going sea level rise and human intervention. Geochemical data from published 210Pb-dated sediment cores, collected from low-energy microtidal coastal wetlands in El Salvador (Jiquilisco Bay) and in Mexico (Salada Lagoon; Estero de Urias Lagoon; Sian Ka'an Biosphere Reserve) were revisited to assess temporal changes (within the last 100years) of Corg concentrations, storage and burial rates in tropical salt marshes under the influence of sea level rise and contrasting anthropization degree. Grain size distribution was used to identify hydrodynamic changes, and δ13C to distinguish terrigenous sediments from those accumulated under the influence of marine transgression. Although the accretion rate ranges in all sediment records were comparable, Corg concentrations (0.2-30%), stocks (30-465Mgha-1, by extrapolation to 1m depth), and burial rates (3-378gm-2year-1) varied widely within and among the study areas. However, in most sites sea level rise decreased Corg concentrations and stocks in sediments, but increased Corg burial rates. Lower Corg concentrations were attributed to the input of reworked marine particles, which contribute with a lower amount of Corg than terrigenous sediments; whereas higher Corg burial rates were driven by higher mass accumulation rates, influenced by increased flooding and human interventions in the surroundings. Corg accumulation and long-term preservation in tropical salt marshes can be as high as in mangrove or temperate salt marsh areas and, besides the reduction of Corg stocks by ongoing sea level rise, the disturbance of the long-term buried Corg inventories might cause high CO2 releases, for which they must be protected as a part of climate change mitigation efforts.


Central Adiposity Indicators Maintain a Stronger Association With the Risk of Hypertension: A Prospective Cohort Study in Southwest China.
Objectives: Studies have linked obesity to an increased risk of hypertension, but the optimal adiposity indicators to predict hypertension remains controversial. We comprehensively explored the correlation between body mass index, waist circumference (WC), waist-to-height ratio (WHtR), long-term weight and WC change, and hypertension in an adult population in Southwest China. Methods: We studied 9,280 participants from 48 townships of 12 districts with a follow-up of 10 years in the Guizhou Population Health Cohort Study. We used Pearson's correlation coefficients combined with Dunn and Clark's z test and Zou's confidence interval test, receiver operating characteristic (ROC) analyses, and multivariate Cox proportional hazards regressions adjusting for demographic characteristics, lifestyle habits, disease history, and lipid information of participants. Results: Baseline central adiposity indicators (WC and WHtR) had closer associations with hypertension than BMI, and long-term WC change was more predictive of hypertension compared with weight change in the studied population. Conclusion: Central adiposity indicators maintain a stronger association with the risk of hypertension, hinting at the importance of WC management in the precaution of hypertension.


Solitary hypovascular hepatic nodules: comparison and differentiation between peripheral nodular cholangiocarcinoma and atypical liver hemangioma with MRI.
Peripheral nodular cholangiocarcinoma (PCC) and hepatic hemangioma (HG) significantly differ in treatment strategies and prognosis. However, they can present similar imaging characteristics, making them difficult to distinguish. The distinction between PCC and atypical HG using pre-operative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) holds substantial significance. Fifty-four cases of solitary hypovascular hepatic nodules (nodules ≤3 cm in diameter and enhancement not exceeding the hepatic parenchyma) confirmed pathologically were collected, including 25 cases of PCC and 29 cases of HG. The clinical and DCE-MRI features were observed, and the apparent diffusion coefficient (ADC) values were compared. The t-test or Fisher's exact test was used to compare the differences between the two groups. Receiver operating characteristic (ROC) curve analysis was performed on the diagnostic results of the two readings before and after the study by three diagnostic physicians. The signal of PCC was more heterogeneous and could be shown as a ring hyperintensity signal on diffusion weighted imaging (DWI). The T2-weighted imaging (T2WI) signal of HG lesions showed a more homogeneous high-intense signal. The ADC value of PCC patients was lower than that of HG patients. Most of the patients in the two groups presented marginal enhancement in the arterial phase with infrequent abnormal perfusion around. The intratumoral vascular traversal signs in the PCC group showed a diagnostic significance. Among the lesions with marginal enhancement at arterial stage, the enhancement in PCC group was more likely to have annular enhancement with the main manifestation of delay reduction and nebulous or separated/astral center. On the other hand, HG tended to be more likely to have nodular enhancement in the arterial phase with delayed invariance at the margins and with no significant enhancement at the center. The area under the curves (AUC) of the three radiologists before and after the two readings were 0.645 and 0.888, respectively. In the differentiation of PCC and atypical liver hemangioma, the presence of a circular hyper-intense signal in DWI, the ADC values, and the pattern and extent of enhancement of marginal and central lesions were of diagnostic significance.


Frequency of Resistance to Benzimidazoles of Haemonchus contortus Helminths from Dairy Sheep, Goats, Cattle and Buffaloes in Greece.
The study investigated the presence of resistance to benzimidazoles in Haemonchus contortus helminths from ruminant species in Greece through the detection of the Phe/Tyr polymorphism in the amino acid at position 200 of the β-tubulin protein. In total, 288 adult female H. contortus helminths collected from the abomasum of various ruminant animals in Greece were tested. Of these, 96 were collected from sheep, 96 from goats, 48 from cattle, and 48 from buffaloes. The frequencies of the homozygous and heterozygous resistant genotypes at the position 200 of the β-tubulin gene of helminths recovered from sheep were 96.9% and 3.1%, respectively. The frequencies of the homozygous and heterozygous resistant genotypes, respectively, were 100.0% and 0.0% in helminths from goats, 25.0% and 75.0% in helminths from cattle and 8.3% and 91.7% in helminths from buffaloes. In all parasitic populations, no homozygous susceptible genotypes were detected. The present study highlighted, for the first time, the emergence of benzimidazole-resistant H. contortus in goats, cattle, and buffaloes in Greece, using an allele-specific PCR. It is postulated that benzimidazole-resistant alleles were transferred from sheep or goats to cattle and buffaloes at the commonly grazing pastures in Greece.


HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity.
We investigated whether exposure of guinea pig tracheal tissue to hypochlorous acid (HOCl) or hydrogen peroxide (H2O2) by perfusion through the airway lumen affected the responsiveness of airway muscle to ACh, KCl, or substance P in the presence or absence of 1 microM phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Pairs of tracheal segments were immersed in a Krebs solution (pH 7.40 at 37 degrees C) and connected to perfusion circuits so that the lumen of one segment of each pair could be perfused with Krebs solution while the other was perfused for the same time (10 min) with either 0.1 microM HOCl or 10 mM H2O2. Segments after perfusion were cut into rings of similar size and placed in muscle chambers so that airway muscle force generation in vitro could be measured on stimulation by cumulative agonist doses. In addition, cell homogenates were made from other, similarly perfused tracheal segments to assess NEP activity using reverse-phase, high-pressure liquid chromatography (HPLC). We found that smooth muscle of mucosa-intact guinea pig airways perfused with HOCl, but not H2O2, was hyperresponsive to substance P but not to ACh or KCl. HOCl-perfused rings were not different from Krebs solution-exposed rings pretreated with phosphoramidon. There was no increase in substance P responsiveness of HOCl-exposed airways in which the mucosa had been removed before testing in vitro. The substance P hyperresponsiveness of HOCl-exposed, mucosa-intact airways was associated with decreased NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of Recipient Age at Liver Transplantation on Prevalence of Post-Transplant Donor-Specific HLA Antibody.
BACKGROUND Post-transplant donor-specific HLA antibodies (DSA) may have a detrimental effect on long-term outcomes of organ transplantation. The aim of this study was to specifically evaluate the effect of recipient age on the prevalence of DSA over a long-term follow-up after living donor liver transplantation (LDLT). MATERIAL AND METHODS A retrospective analysis of DSA evaluations was performed in 50 pediatric patients with HLA data available. Patients were divided into 2 groups based on their age at the time of LDLT: younger (Y) group, age <3 years; older (O) group, age ≥3 years. DSA evaluation was performed using Luminex single-antigen bead assays, with a mean fluorescence intensity ≥1000 used as a cut-off for positive results. RESULTS There were no between-group differences in terms of sex, ABO incompatibility or acute rejection. Only one of our 50 patients tested positive for class I DSA. Significantly more patients tested positive for HLA-DR DSA in group Y (40.6%) than in group O (11.1%; p=0.02). Recipients <3 years of age at the time of LDLT may be at a higher risk of testing positive for class II DSA. CONCLUSIONS These findings can inform the implementation of cost-effective screening of post-transplant DSA in pediatric LDLT recipients.


Hydrostatic pressure/perfusion culture system designed and validated for engineering tissue.
Tissue engineering to replace or repair damaged tissues using three-dimensional cell constructs is a promising approach to promote tissue regeneration de novo. The production of cell constructs is a critical process for maintaining cell viability and phenotypes in vitro prior to surgical treatment. We have developed a novel hydrostatic pressure (HP)/perfusion culture system for three-dimensional cell constructs with application of mechanical stimuli with HP and continuous medium changes. In this study, we tested and validated the performance of this culture system. This systems' performance was stable at a constant HP up to 5 MPa and at a cyclic HP up to 0-5 MPa at 0.5-0.03 Hz. The performance of medium perfusion in the culture chamber showed laminar flow from an inlet into the chamber parallel to the inner walls. Air bubbles on all inner surfaces of the culture chamber caused unstable HP application because air can be compressed with greater ease than water, consequently impacting fluid compression. Air bubbles in a 3D agarose gel model disappeared due to HP over time and the spaces vacated by the air bubbles were replaced with water. Our validated HP/perfusion culture system allows for a well-regulated constant or cyclic HP application in culture medium and can be applied to other 3D tissue culture for engineering tissue.


Evaluation of the inpatient use of inotuzumab ozogamicin and creation of appropriate use guidelines.
Inpatient use of inotuzumab ozogamicin (IO) at our academic medical center has increased since its FDA approval in 2017. Administration of IO does not require hospitalization and is appropriate for outpatient use. The aim of this report is to assess the appropriateness of use, overall inpatient utilization, and cost of IO. This is a retrospective chart review of patients that received at least one dose of IO while admitted to the hospital. Data points included rationale for inpatient IO administration, hospital admission reason, number of IO doses and number of vials used, length of stay, in-hospital mortality, percentage of admissions that were new-starts, outpatient continuation of IO, use of concomitant regimens, and CD22 positivity. Between September 1, 2017, and June 30, 2022, 55 doses of IO were identified. Of the 29 unique admissions, common rationales for inpatient IO use included high disease burden/tumor lysis syndrome risk (31%) and use of a regimen requiring hospitalization (28%). The rationale for hospitalization was most commonly 'chemotherapy administration' (34%) and 'relapsed/refractory disease' (38%). Median length of stay was 23 days, most were new starts (76%), and 5 patients died during the associated admission. Only 63% of patients continued therapy in the outpatient setting. The inpatient use of IO was associated with a prolonged length-of-stay, a 17% in-hospital mortality, and represents a significant cost burden to the health system. As a result of these findings, guidelines for inpatient use of IO were implemented across the health system.


Protein-protein Interaction Networks of E. coli and S. cerevisiae are similar.
Only recently novel high-throughput binary interaction data in E. coli became available that allowed us to compare experimentally obtained protein-protein interaction networks of prokaryotes and eukaryotes (i.e. E. coli and S. cerevisiae). Utilizing binary-Y2H, co-complex and binary literature curated interaction sets in both organisms we found that characteristics of interaction sets that were determined with the same experimental methods were strikingly similar. While essentiality is frequently considered a question of a protein's increasing number of interactions, we found that binary-Y2H interactions failed to show such a trend in both organisms. Furthermore, essential genes are enriched in protein complexes in both organisms. In turn, binary-Y2H interactions hold more bottleneck interactions than co-complex interactions while both binary-Y2H and co-complex interactions are strongly enriched among co-regulated proteins and transcription factors. We discuss if such similarities are a consequence of the underlying methodology or rather reflect truly different biological patterns.


Effects of pentobarbital and isoflurane on regional cerebral oxygen extraction and consumption with middle cerebral artery occlusion in rats.
When compared with barbiturates, isoflurane may lack protective effects during focal cerebral ischemia. The reason for this difference is not clear. In this study, regional cerebral blood flow (rCBF), arterial and venous O2 saturation, and O2 extraction were compared in the ischemic cortex and in the nonischemic brain regions of rats anesthetized with isoflurane or pentobarbital using a microspectrophotometric technique that directly measures the O2 saturation of blood in the small arteries and veins. Twenty-eight rats were anesthetized with 1.4% isoflurane or 50 mg/kg pentobarbital. One hour after a middle cerebral artery (MCA) occlusion, rCBF was measured in the ischemic cortex and in the nonischemic brain regions using 14C-iodoantipyrine in one-half of each group of animals. Regional arterial and venous O2 saturation were determined using microspectrophotometry in the other one-half of each group. The rCBF of the ischemic cortex (IC) and the non-ischemic contralateral cortex (CC) of the isoflurane group were significantly higher than those of the pentobarbital group. The venous O2 saturation was significantly less, and the O2 extraction was significantly higher, in the IC than in the nonischemic regions in both groups of animals (pentobarbital group, IC 10.5 +/- 1.1 ml O2.100 ml blood-1, CC 6.3 +/- 0.7; isoflurane group, IC 10.8 +/- 0.6, CC 5.9 +/- 0.2). There was no significant difference between the two groups. Because the rCBF was less and the O2 extraction was similar, O2 consumption in the focal ischemic area of the brain during pentobarbital anesthesia must have been less than that during isoflurane anesthesia.


Selective serotonin reuptake inhibitor treatment and depression are associated with poststroke mortality.
Studies generally do not examine patients' prestroke depression diagnoses and treatments. To examine the association of depression diagnosis and prestroke and/or poststroke selective serotonin reuptake inhibitor (SSRI) treatment with poststroke mortality. We conducted a retrospective study of the medical records of a cohort of veterans with a stroke diagnosis between July 31, 2000, and September 30, 2001. Data regarding demographics, comorbidities, depression diagnosis, and treatment were abstracted from automated databases and electronic medical records for 6 months before and 1 year after the stroke index date. The survival rates of veterans who received an SSRI before and/or after the stroke were estimated using Kaplan-Meier survival analysis. Time-dependent Cox proportional hazards regression model was used to assess the association between risk factors and mortality. Among 870 veterans, 80 died less than 60 days after their stroke. Among the remaining 790, 12% died within 1 year, 26% died by the end of follow-up (May 1, 2007), and more than 62% were alive at the end of follow-up. Veterans were 3 times as likely to die if they had been treated for depression with an SSRI only before their stroke (hazard ratio [HR], 3.12; 95% CI 1.60 to 6.09). In the time-dependent model, SSRI treatment both before and after the stroke was protective compared with no SSRI treatment during the year following the stroke (HR 0.31; 95% CI 0.11 to 0.86). However, the survival curves crossed over and SSRI treatment before and after stroke conferred greater risk at the end of 7 years (HR 1.36; 95% CI 1.00 to 1.87). Depression diagnosis was associated with greater risk of mortality (HR 1.87; 95% CI 1.24 to 2.82). Poststroke SSRI treatment was associated with longer survival even though depression diagnosis was associated with earlier mortality in the unadjusted model. After a stroke, SSRI initiation or resumption of treatment should be considered as part of a medication therapy management service, especially if the patient has a history of depression or was taking an SSRI before the stroke.


Assessment of Aflatoxin M1 and M2 exposure risk through Oaxaca cheese consumption in southeastern Mexico.
The present study evaluated the exposure of Southeast Mexican population to Aflatoxin M1 (AFM1) and M2 (AFM2) through the consumption of Oaxaca cheese. The intake of Oaxaca cheese was assessed via a food 7-day dairy questionnaire (N = 1100, 2014 and 2015). Thirty Oaxaca cheeses were randomly sampled, and the origin of the samples was also investigated. AFM1 and AFM2 were quantified by HPLC-FD. The exposure was assessed through the combination of the Probabilistic Density Functions (probabilistic approach). The percentage of the population at risk was calculated through the population exceeding the toxicological reference values (TDI). The risk assessment revealed that the population at higher risk to AFM1 and AFM2 was the children, followed by the adolescents and adult women. To our knowledge, the present study is the first to assess the exposure risk of different age groups of a population to AFM1 and AFM2 through the consumption of cheese.


Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.
Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.


Using Health Impact Assessment as an Interdisciplinary Teaching Tool.
Health Impact Assessment (HIA) courses are teaching public health and urban planning students how to assess the likely health effects of proposed policies, plans, and projects. We suggest that public health and urban planning have complimentary frameworks for training practitioners to address the living conditions that affect health. Planning perspectives emphasize practical skills for impacting community change, while public health stresses professional purpose and ethics. Frameworks from both disciplines can enhance the HIA learning experience by helping students tackle questions related to community impact, engagement, social justice, and ethics. We also propose that HIA community engagement processes can be enriched through an empathetic practice that focuses on greater personal introspection.


Genotoxicity of poorly soluble particles.
Poorly soluble particles such as TiO2, carbon black, and diesel exhaust particles have been evaluated for their genotoxicity using both in vitro and in vivo assays, since inhalation of these compounds by rats at high concentrations has been found to lead to tumor formation. Two principle modes of genotoxic action can be considered for particles, referred to as primary and secondary genotoxicity. Primary genotoxicity is defined as genetic damage elicited by particles in the absence of pulmonary inflammation, whereas secondary genotoxicity implies a pathway of genetic damage resulting from the oxidative DNA attack by reactive oxygen/nitrogen species (ROS/RNS), generated during particle-elicited inflammation. Conceptually, primary genotoxicity might operate via various mechanisms, such as the actions of ROS (e.g., as generated from reactive particle surfaces), or DNA-adduct formation by reactive metabolites of particle-associated organic compounds (e.g., polycyclic aromatic hydrocarbons). Currently available literature data, however, merely indicate that the tumorigenesis of poorly soluble particles involves a mechanism of secondary genotoxicity. However, further research is urgently required, since (1) causality between pulmonary inflammation and genotoxicity has not yet been established, and (2) effects of inflammation on fundamental DNA damage responses that orchestrate mutagenesis and carcinogenic outcome,that is, cell cycle arrest, DNA repair, proliferation, and apoptosis, are currently poorly understood.


Direct resin composite approach to orthodontic relapse. Case report.
The treatment of malaligned teeth represents a challenge, especially in the presence of root resorption. Options to improve aesthetics are limited and often involve high costs. Direct composite restorations offer an alternative for the realignment of orthodontic-relapsed teeth where orthodontic retreatment is not indicated. Their reasonable cost, conservativeness and excellent aesthetics have allowed resin composites to gain popularity in recent years. This report describes a direct composite approach to the realignment of teeth with anterior root resorption. Furthermore, the article describes the use of a "silicon lingual matrix" to facilitate the polychromatic layering of composite and the manipulation of illusions to improve perception of tooth alignment.


Empirical Analysis for Stock Price Prediction Using NARX Model with Exogenous Technical Indicators.
Stock price prediction is one of the major challenges for investors who participate in the stock markets. Therefore, different methods have been explored by practitioners and academicians to predict stock price movement. Artificial intelligence models are one of the methods that attracted many researchers in the field of financial prediction in the stock market. This study investigates the prediction of the daily stock prices for Commerce International Merchant Bankers (CIMB) using technical indicators in a NARX neural network model. The methodology employs comprehensive parameter trails for different combinations of input variables and different neural network designs. The study seeks to investigate the optimal artificial neural networks (ANN) parameters and settings that enhance the performance of the NARX model. Therefore, extensive parameter trails were studied for various combinations of input variables and NARX neural network configurations. The proposed model is further enhanced by preprocessing and optimising the NARX model's input and output parameers. The prediction performance is assessed based on the mean squared error (MSE), R-squared, and hit rate. The performance of the proposed model is compared with other models, and it is shown that the utilisation of technical indicators with the NARX neural network improves the accuracy of one-step-ahead prediction for CIMB stock in Malaysia. The performance of the proposed model is further improved by optimising the input data and neural network parameters. The improved prediction of stock prices could help investors increase their returns from investment in stock markets.


Reconstruction of the Wide Scalp Defects Using Free Latissimus Dorsi Flap Assisted With Arteriovenous Loop.
Reconstructions of the wide scalp defects are still a challenging task because of the accompanied recipient vessel issues. Arteriovenous loop (AVL) grafts are a suitable vascular conduit that can be used to support free tissue transfer, when adjacent blood supply is inadequate. We report 2 patients of successful wide scalp reconstruction, using a free latissimus dorsi (LD) flap assisted with AVL. Both flaps and AVL grafts fully survived postoperatively. No complications related to the recipient and donor areas developed. The flaps obtained a durable barrier and an acceptable aesthetic appearance. We believe that AVL can be a useful adjunct for increasing the success rate of wide scalp reconstructions with inadequate adjacent arterial inflow or venous outflow. The free LD flap is a good option with its wide surface, rich vascularity and relatively low donor morbidity in such reconstructions.


[Study of the secondary structure of a single-stranded DNA fragment using self-modification reaction].
Electrophoretic analysis of the products of chemical destruction at modified base residues was used to determine the site-directedness of self-alkylation of the 26-mer DNA fragment pTTGCCTTGAATGGGAAGAGGGTCATT (T26). This fragment possesses a 4-[N-methyl-N-(2-chloroethyl)amino]benzylamido group (CIR-), covalently attached to the 5'-terminal phosphate group both in the presence and in the absence of the oligonucleotide effector (Phn-L)pTGACCCTCp(L-Phn), where Phn is an N-(2-hydroxyethyl)phenazinium residue and L is an ethylenediamine linker. Molecular modeling with the method of molecular mechanics/dynamics (MM/D) was used to investigate the secondary structure of the CIR-T26 conjugate and to interpret the change of the alkylation site upon treatment with CIR-T26 in the presence of an effector.


Faceting of nanocrystals during chemical transformation: from solid silver spheres to hollow gold octahedra.
We demonstrate that performing a replacement reaction on single crystalline Ag nanospheres of approximately 10 nm in diameter in an organic solvent produces hollow Au nanocrystals with an octahedral shape. Different from those Au shells made by starting with Ag particles about 1 order of magnitude larger, which largely reproduce that of the sacrificial Ag counterparts, the hollow nanocrystals obtained in this work show significant changes in the external morphology from the spherical Ag precursors. This evolution of a faceted external morphology during chemical transformation is made possible by the enhanced role of surface effects in our smaller nanocrystals. The competition between the Au atom deposition and Ag atom dissolution on various nanocrystal surfaces is believed to determine the final octahedral shape of the hollow Au nanocrystals. Simultaneous achievement of surface-mediated shape control and a hollow morphology in a one-pot, single-step synthetic procedure in this study promises an avenue to finer tuning of particle morphology, and thus physical properties such as surface plasmon resonance.


Organosolv Processes.
Biofuels and chemicals can be produced from lignocellulosic feedstocks using biotechnological processes. The effective utilization of carbohydrates from biomass for the production of biofuels necessitates the development of pretreatment technologies to enhance their enzymatic digestibility. Among all the various pretreatment methods currently studied and developed, the organosolv processes, in which organic solvents or aqueous organic solvent mixtures are used as the pretreatment medium, appear to be specially promising in the context of the biorefinery because (1) they produce cellulosic pulp with a good enzymatic digestibility for monomeric glucose production and (2) they allow a clean fractionation of the major biomass components (cellulose, lignin, and hemicelluloses) into three process streams. In this chapter we give an updated overview of organosolv methods using conventional solvents and ionic liquids which have recently gained considerable interest as solvents for lignocellulosic biomass and pretreatment.


Registering Particle Data Sets Using a Rotation and Translation Invariant Nearest-Neighbor Algorithm.
It can be useful to register (or align) two sets of particle data measured from the same physical sample. However, if the two data sets were collected at different translational or rotational offsets, finding the optimal registration can be a challenge. We will present an algorithm that efficiently determines the rotation and translational offset that best registers (in a least-squares sense) the corresponding particles in two or more data sets measured from the same sample. This algorithm can be used to merge two data sets that have been collected on overlapping but otherwise distinct regions on the sample. Alternatively, it can be used to overlay data sets that have been collected on the same sample area to compare replicate data for quality control and measurement efficiency purposes.


Growth performance, carcass traits, meat chemical composition and blood serum metabolites of broiler chicken fed on diets containing flaxseed oil.
1. This study evaluated the effects of diets with partial and total substitution of soya bean oil (SO) with flaxseed (linseed) oil (FO) on broiler chicken performance, carcass traits, meat chemical composition and blood serum metabolites. 2. A total of 448 one-d-old Cobb 500 broiler chicken were used. They were allotted among 4 treatments with 8 replications, using a completely randomised design, for 35 d. Four diets were compared: T1 = 100% SO (3%, 1-7 d; 4%, 8-21 d; and 5%, 22-35 d); T2 = 50% SO + 50% FO; T3 = 25% SO + 75% FO and T4 = 100% FO. 3. No significant differences were observed in body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and blood serum metabolites (total triglycerides, TRI; total cholesterol, CHO; high-density lipoprotein, HDL; low-density lipoprotein, LDL; glucose, GLU; albumin, ALB; globulin, GLO; and total proteins, TPs). Significant effects were observed for TRI, CHO, HDL, GLU, HDL, LDL, ALB and GLO with regard to the day of collection. 4. Carcass traits did not show significant differences for the treatments. No significant differences were observed for breast and drumstick chemical compositions, with the exception of drumstick fat concentration (quadratic effect). 5. In conclusion, the partial or total substitution of SO with FO did not affect growth performance, carcass traits, meat chemical composition or blood serum profile in broiler chicken. Therefore, FO can be an alternative to SO in the diet formulation for broiler chicken.


Supraspinal and spinal potency of selective opioid agonists in the mouse writhing test.
Three agonists with the highest degree of selectivity available for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO), delta ([ D-Pen2,D-Pen5]enkephalin, DPDPE) and kappa (U-50,488H, U50) opioid receptors were compared for their activity in inhibiting acetic acid-induced writhing in mice. Additionally, three reference agonists for mu (morphine), delta ([ D-Ala2,D-Leu5]enkephalin, DADLE) and kappa (ketocyclazocine, KC) receptors were also studied in this test. The agonists were given directly into the lateral cerebral ventricle (i.c.v.) or into the lumbar spinal subarachnoid space (intrathecal), and the potency of each compound was compared across injection sites and with data previously obtained in a thermal analgesic test (mouse hot-plate test). The rank order of potency for inhibition of writhing after i.c.v. administration was DAGO greater than DADLE greater than morphine greater than DPDPE; KC and U50 showed no significant activity by this route. After intrathecal administration, the compounds inhibited writhing with a rank potency order of DAGO greater than KC greater than morphine = DADLE greater than DPDPE greater than U50. All compounds were more potent in inhibiting writhing at spinal sites than at supraspinal sites; DPDPE and DAGO were 15 and 24 times more potent after intrathecal than after i.c.v. administration, respectively. The proposed delta agonists DPDPE and DADLE inhibited writhing at both spinal and supraspinal sites. Further, although the proposed kappa-acting compounds KC and U50 were effective at relatively low doses at spinal levels, these compounds lacked activity at supraspinal sites at doses not causing sedation.(ABSTRACT TRUNCATED AT 250 WORDS)


A Case Report of Rubinstein-Taybi Syndrome Presenting with Extensive Keloid Formation and Review of Literature.
Rubinstein-Taybi syndrome (RSTS) is an extremely rare genetic disorder affecting multi-organ systems. A tendency to form keloid is one of the common dermatologic manifestations. We describe a 23-year-old female presented with extensive keloids which developed spontaneously. She had typical facial features, broad thumbs, and dental defects, which were suspicious features of genetic syndrome. Direct sequencing for cyclic-AMP-regulated enhancer binding protein revealed a novel mutation. So far, 23 cases of RSTS have been reported in Korean literature. To the best of our knowledge, this is the first report in Korea to describe confirmed case of RSTS with extensive keloids as a chief manifestation.


Update on epidermal growth factor receptor mutations in non-small cell lung cancer.
In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non-small cell lung cancer. Since then, multiple groups have examined the biological properties that such mutations confer as well as the clinical relevance of these mutations in patients with non-small cell lung cancer. Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions.


Enhanced decomposition of 1,4-dioxane in water by ozonation under alkaline condition.
1,4-Dioxane is a probable human carcinogenic and refractory substance that is widely detected in aquatic environments. Traditional wastewater treatment processes, including activated sludge, cannot remove 1,4-dioxane. Removing 1,4-dioxane with a reaction kinetic constant of 0.32 L/(mol·s) by using ozone, a strong oxidant, is difficult. However, under alkaline environment, ozone generates a hydroxyl radical (•OH) that exhibits strong oxidative potential. Thus, the ozonation of 1,4-dioxane in water under different pH conditions was investigated in this study. In neutral solution, with an inlet ozone feed rate of 0.19 mmol/(L·min), the removal efficiency of 1,4-dioxane was 7.6% at 0.5 h, whereas that in alkaline solution was higher (16.3-94.5%) within a pH range of 9-12. However, the removal efficiency of dissolved organic carbon was considerably lower than that of 1,4-dioxane. This result indicates that several persistent intermediates were generated during 1,4-dioxane ozonation. The pseudo first-order reaction further depicted the reaction of 1,4-dioxane. The obvious kinetic constants (kobs) at pH 9, 10, 11 and 12 were 0.94, 2.41, 24.88 and 2610 L/(mol·s), respectively. Scavenger experiments on radical species indicated that •OH played a key role in removing 1,4-dioxane during ozonation under alkaline condition.


Electric-Field Modulation of Interface Magnetic Anisotropy and Spin Reorientation Transition in (Co/Pt)3/PMN-PT Heterostructure.
We report electric-field control of magnetism of (Co/Pt)3 multilayers involving perpendicular magnetic anisotropy with different Co-layer thicknesses grown on Pb(Mg,Nb)O3-PbTiO3 (PMN-PT) FE substrates. For the first time, electric-field control of the interface magnetic anisotropy, which results in the spin reorientation transition, was demonstrated. The electric-field-induced changes of the bulk and interface magnetic anisotropies can be understood by considering the strain-induced change of magnetoelastic energy and weakening of Pt 5d-Co 3d hybridization, respectively. We also demonstrate the role of competition between the applied magnetic field and the electric field in determining the magnetization of the sample with the coexistence phase. Our results demonstrate electric-field control of magnetism by harnessing the strain-mediated coupling in multiferroic heterostructures with perpendicular magnetic anisotropy and are helpful for electric-field modulations of Dzyaloshinskii-Moriya interaction and Rashba effect at interfaces to engineer new functionalities.


Network structure of resource use and niche overlap within the endophytic microbiome.
Endophytes often have dramatic effects on their host plants. Characterizing the relationships among members of these communities has focused on identifying the effects of single microbes on their host, but has generally overlooked interactions among the myriad microbes in natural communities as well as potential higher-order interactions. Network analyses offer a powerful means for characterizing patterns of interaction among microbial members of the phytobiome that may be crucial to mediating its assembly and function. We sampled twelve endophytic communities, comparing patterns of niche overlap between coexisting bacteria and fungi to evaluate the effect of nutrient supplementation on local and global competitive network structure. We found that, despite differences in the degree distribution, there were few significant differences in the global network structure of niche-overlap networks following persistent nutrient amendment. Likewise, we found idiosyncratic and weak evidence for higher-order interactions regardless of nutrient treatment. This work provides a first-time characterization of niche-overlap network structure in endophytic communities and serves as a framework for higher-resolution analyses of microbial interaction networks as a consequence and a cause of ecological variation in microbiome function.


Electric fields caused by blood flow modulate vascular endothelial electrophysiology and nitric oxide production.
Endothelial cells are exposed to a ubiquitous, yet unexamined electrical force caused by blood flow: the electrokinetic vascular streaming potential (EVSP). In this study, the hypothesis that extremely low frequency (ELF) electric fields parameterized by the EVSP have significant biological effects on endothelial cell properties was studied by measuring membrane potential and nitric oxide production under ELF stimulation between 0 and 2 Hz and 0-6.67 V/m. Using membrane potential and nitric oxide sensitive fluorescent dyes, bovine aortic endothelial cells (BAECs) in culture were studied in the presence and absence of EVSP-modeled electric fields. The transmembrane potential of BAECs was shown to depolarize between 1 and 7 mV with a strong dependency on both the magnitude and frequency of the isolated ELF field. The findings also support a field interaction with a frequency-dependent tuning curve. The ELF field complexly modulates the nitric oxide response to adenosine triphosphate stimulation with potentiation seen with up to a sevenfold increase. This potentiation was also frequency and magnitude dependent. An early logarithmic phase of NO production is enhanced in a field strength-dependent manner, but the ELF field does not modify a later exponential phase. This study shows that using electric fields on the order of those generated by blood flow influences the essential biology of endothelial cells. The inclusion of ELF electric fields in the paradigm of vascular biology may create novel opportunities for advancing both the understanding and therapies for treatment of vascular diseases.


The surgical treatment of herpetic keratitis.
At present, corneal transplantation is the only definitive means of controlling or terminating recurrent or chronic herpetic keratitis. Of 48 keratoplastic operations for various forms of corneal herpes, 16 in quiescent cases and 32 in cases of active keratitis, all but three brought about improvement. Recurrence of keratitis in the graft is particularly likely if the visible lesion is not excised completely and a portion of the graft border lies in contact with diseased tissue. The mode of action of corneal transplantation in improving herpetic keratitis is not clear but several possibilities have been suggested. At least in chronic stromal herpes the removal of diseased and necrotic tissue appears to be a very important factor.


The Mediterranean Diet Score Is More Strongly Associated with Favorable Cardiometabolic Risk Factors over 2 Years Than Other Diet Quality Indexes in Puerto Rican Adults.
Background: Multiple diet quality scores have been used to evaluate adherence to specific dietary recommendations or to consumption of healthful foods and nutrients. It remains unknown which score can more strongly predict longitudinal changes in cardiometabolic risk factors.Objective: We aimed to determine associations of 5 diet quality scores [AHA diet score (AHA-DS), Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI)-2005, Mediterranean diet score (MeDS), and Alternative Healthy Eating Index (AHEI)] with 2-y changes in cardiometabolic risk factors in adults 45-75 y old.Methods: Data from the Boston Puerto Rican Health Study were analyzed (n = 1194). Diet quality scores were calculated from a baseline-validated food-frequency questionnaire. Multivariable-adjusted, repeated-subjects, mixed-effects models, adjusted for baseline measures, estimated associations between each z score and 14 individual cardiometabolic factors measured at 2 y.Results: MeDS was significantly associated with lower 2-y waist circumference (β coefficient ± SE: -0.52 ± 0.26, P = 0.048); body mass index (BMI; -0.23 ± 0.08, P = 0.005); log-insulin (-0.06 ± 0.02, P = 0.005); log-homeostasis model assessment of insulin resistance (HOMA-IR; -0.05 ± 0.02, P = 0.030), and log-C-reactive protein (-0.13 ± 0.03, P = 0.0002). Similar but weaker associations were observed for the AHEI with BMI, insulin, and HOMA-IR. The AHA-DS was inversely associated with BMI (-0.17 ± 0.08, P = 0.033). Neither the HEI-2005 nor DASH was significantly associated with any variable. Traditional Puerto Rican foods consumed by individuals with high MeDSs included vegetables and meats in homemade soups, orange juice, oatmeal, beans and legumes, fish, whole milk, corn oil, and beer.Conclusions: The MeDS comprises food components and scores associated with a favorable cardiometabolic profile over 2 y in Puerto Rican adults. An overall healthy diet may be particularly beneficial for maintaining a lower BMI. These results can help identify suitable measures of diet quality in epidemiologic studies and craft meaningful nutritional messages and dietary recommendations for the intended population. This study was registered at clinicaltrials.gov as NCT01231958.


Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.
A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.


Synergism of amphotericin B and 2-deoxyglucose against Histoplasma capsulatum yeasts in vitro.
The glucose analogue, 2-deoxyglucose (2DG), enhances both the fungistatic and the fungicidal action of amphotericin B in Fungizone (Squibb) against Histoplasma capsulatum yeasts in vitro. This synergistic effect is more pronounced when the test substances are incorporated in double-diffusion agar plates than in liquid medium. Minimum inhibitory concentrations for 2DG and amphotericin B in Fungizone have been established. The effects of components of Fungizone other than amphotericin B as clinically administered were also studied. Neither sodium desoxycholate nor phosphate buffer had any effect on the test organisms when used in recommended clinical concentrations. The 5% glucose infusion solution greatly enhanced the growth of the pathogen and markedly decreased the effectiveness of amphotericin B. H. capsulatum yeasts quickly became resistant to stepwise increases of Fungizone but not of 2DG. Susceptibility to amphotericin B and to 2DG increased with time within certain limits of exposure. The A (albino) phenotype of H. capsulatum is considerably more resistant to amphotericin B than the B (brown) phenotype, but there are no differences in susceptibilities to 2DG. The potential clinical applications of these studies are discussed, since experimental animals and man are reported to tolerate large amounts of 2DG. The incorporation of 2DG in the polyene antibiotic preparation would render it more effective at lower doses and would decrease clinical toxicity.


Effect of LDL apheresis on oxygen tension in skeletal muscle in patients with cardiac allograft vasculopathy and severe lipid disorder.
In this study, the extent to which intramuscular pO2 is influenced by a single HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) was investigated in 10 patients with cardiac allograft vasculopathy (CAV) and severe lipid disorder. For this purpose, a sterile flexible pO2 microcatheter was inserted into the anterior tibial muscle and pO2 monitoring was begun 10 minutes before starting apheresis treatment. The intramuscular pO2 values were recorded continuously until the end of apheresis treatment and a subsequent 30-minute further observation phase. The patients with CAV and severe lipid disorder presented with 11.6+/-3.8 mmHg significantly and pathologically reduced intramuscular pO2 (p<0.001). LDL apheresis resulted in a significant increase in pO2 in the anterior tibial muscle. Thirty minutes after the end of HELP-apheresis, intramuscular partial oxygen pressure had increased by 162% and showed values at this point, 30.3+/-9.8 mmHg, similar to those found in healthy subjects.


Effect of maternal pyridoxine X HCl supplementation on the vitamin B-6 status of mother and infant and on pregnancy outcome.
The effect of maternal pyridoxine X HCl (PN-HCl) supplementation on the vitamin B-6 status of pregnant women and their infants at birth and on pregnancy outcome was investigated. Volunteer subjects were randomly assigned a daily vitamin B-6 supplement containing 0, 2.6, 5, 7.5, 10, 15 or 20 mg of PN-HCl in a double-blind study. The mean dietary vitamin B-6 intake of the group was 1.43 +/- 1.28 mg/day as estimated from 24-hour dietary recalls. Maternal plasma pyridoxal 5'-phosphate (PLP) levels were positively correlated with vitamin B-6 supplementation at 30 weeks gestation (r = 0.55, P less than 0.0005) and at delivery (r = 0.54, P less than 0.01). Cord plasma PLP levels reached a maximum when maternal PN-HCl supplementation was 7.5 mg and greater. Supplemental PN-HCl at the 7.5-mg level was required to prevent a decrease in maternal plasma PLP at delivery. Apgar scores at 1 minute after birth were higher (P less than 0.05) for infants whose mothers took 7.5 mg or more supplemental PN-HCl than for infants of mothers who took 5 mg or less. These findings indicate that a vitamin B-6 intake between 5.5 and 7.6 mg/day (diet plus supplement as pyridoxine equivalents) was required to maintain maternal plasma PLP levels at term at a level comparable to initial values.


Growth of anaerobic methane-oxidizing archaea and sulfate-reducing bacteria in a high-pressure membrane capsule bioreactor.
Communities of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB) grow slowly, which limits the ability to perform physiological studies. High methane partial pressure was previously successfully applied to stimulate growth, but it is not clear how different ANME subtypes and associated SRB are affected by it. Here, we report on the growth of ANME-SRB in a membrane capsule bioreactor inoculated with Eckernförde Bay sediment that combines high-pressure incubation (10.1 MPa methane) and thorough mixing (100 rpm) with complete cell retention by a 0.2-m-pore-size membrane. The results were compared to previously obtained data from an ambient-pressure (0.101 MPa methane) bioreactor inoculated with the same sediment. The rates of oxidation of labeled methane were not higher at 10.1 MPa, likely because measurements were done at ambient pressure. The subtype ANME-2a/b was abundant in both reactors, but subtype ANME-2c was enriched only at 10.1 MPa. SRB at 10.1 MPa mainly belonged to the SEEP-SRB2 and Eel-1 groups and the Desulfuromonadales and not to the typically found SEEP-SRB1 group. The increase of ANME-2a/b occurred in parallel with the increase of SEEP-SRB2, which was previously found to be associated only with ANME-2c. Our results imply that the syntrophic association is flexible and that methane pressure and sulfide concentration influence the growth of different ANME-SRB consortia. We also studied the effect of elevated methane pressure on methane production and oxidation by a mixture of methanogenic and sulfate-reducing sludge. Here, methane oxidation rates decreased and were not coupled to sulfide production, indicating trace methane oxidation during net methanogenesis and not anaerobic methane oxidation, even at a high methane partial pressure.


Rational synthesis of hierarchical magnetic mesoporous silica microspheres with tunable mesochannels for enhanced enzyme immobilization.
Hierarchical magnetic mesoporous silica microspheres (MMSMs) with a core-shell structure have been fabricated through an improved water/oil biphase synthesis strategy. We firstly reported that the mesopore size can be readily tuned from 6.1 to 11.4 nm by the synergistic effect of surfactant concentration and an amphiphilic agent, thus holding a bright future in many possible applications.


Isolation and Biological Evaluation of Prenylated Flavonoids from Maclura pomifera.
Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds (I-IV) along with eleven known compounds (V-XV). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and μ opioid receptors (-49.7 and -53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and μ opioid receptors (-88.4 and -27.2% displacement, resp.) and showed moderate activity (60.5% displacement) towards CB1 receptor. Compound II exhibited moderate activity towards cannabinoid receptors CB1 and CB2 (47.9 and 42.3% displacement, resp.). The known compounds (V-VIII) exhibited prominent activity towards cannabinoid receptors: pomiferin (V) (IC50 of 2.110 and 1.318 μM for CB1 and CB2, resp.), auriculasin (VI) (IC50 of 8.923 μM for CB1), warangalone (VII) (IC50 of 1.670 and 4.438 μM for CB1 and CB2, resp.), and osajin (VIII) (IC50 of 3.859 and 7.646 μM for CB1 and CB2, resp.). The isolated compounds were also tested for inhibition of human monoamine oxidase-A and monoamine oxidase-B enzymes activities, where all the tested compounds showed fewer inhibitory effects on MAO-A compared to MAO-B activities: auriculasin (VI) (IC50 of 1.91 and 45.98 μM for MAO-B and MAO-A, resp.).