The role of melatonin in the cells of the innate immunity: a review.
Melatonin is the major secretory product synthesized and secreted by the pineal gland and shows both a wide distribution within phylogenetically distant organisms from bacteria to humans and a great functional versatility. In recent years, a considerable amount of experimental evidence has accumulated showing a relationship between the nervous, endocrine, and immune systems. The molecular basis of the communication between these systems is the use of a common chemical language. In this framework, currently melatonin is considered one of the members of the neuroendocrine-immunological network. A number of in vivo and in vitro studies have documented that melatonin plays a fundamental role in neuroimmunomodulation. Based on the information published, it is clear that the majority of the present data in the literature relate to lymphocytes; thus, they have been rather thoroughly investigated, and several reviews have been published related to the mechanisms of action and the effects of melatonin on lymphocytes. However, few studies concerning the effects of melatonin on cells belonging to the innate immunity have been reported. Innate immunity provides the early line of defense against microbes and consists of both cellular and biochemical mechanisms. In this review, we have focused on the role of melatonin in the innate immunity. More specifically, we summarize the effects and action mechanisms of melatonin in the different cells that belong to or participate in the innate immunity, such as monocytes-macrophages, dendritic cells, neutrophils, eosinophils, basophils, mast cells, and natural killer cells.


Effect of particle size of hydroxyapatite nanoparticles on its biocompatibility.
Nano-particulate biomaterials have been used in clinical diagnosis and treatment, as drug carrier or in cosmetics because of their excellent performance properties. The toxicity and biocompatibility of nanoparticles (NPs), however, are always a focused concern for a doctor or a scientist. At present, there is almost no systemic evaluation standard or testing methods of safety for nanoparticles. In this study, two kinds of hydroxylapatite, (HAP) NPs with different particle sizes were selected. A number of biocompatibility tests in vivo or in vitro were conducted. They were cytotoxicity (MTT assay), genotoxicity (Ames, Mouse Lymphoma Mutagenesis Assay), and systemic toxicity (Acute and Subacute). The results indicated that, under the concentration of 100 mg/L, both HAP NPs could cause significant inhibition of cell growth. The size of NPs might have close tie with cell response. The mutagenic test in vitro was negative in this study. Histopathological findings showed that both kinds of HAP NPs could induce pseudotubercles in lung. Moreover, smaller size of nanoparticles resulted in a vacuolar degeneration of nephric tubule epithelium at 7 days post-intraveneous injection. The results implied that the size of NPs might play an important role in the biocompatibility of the materials. The kidney might be the main organ of discharge of nanoparticles from body.


Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers.
Loss of heterozygosity at chromosome 8p21-22 is common in human prostate cancer, suggesting the presence of one or more tumor suppressor genes at this locus. A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21. Fine structure in situ mapping showed that NKX3.1 is proximal to MSR32 (macrophage scavenger receptor type II) and LPL (human lipoprotein lipase) and very close to NEFL (human neurofilament light chain) on 8p21. Single-strand conformational polymorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumor-specific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21. NKX3.1 was found to have a polymorphism at nucleotide 154 in codon 52 that resulted in a CGC-->TGC sequence change and an Arg-->Cys amino acid alteration (R52C). This polymorphism was present in 20% of DNA samples. If NKX3.1 is a target of the 8p21 LOH, it is not via disruption of the coding region of the gene.


Methylation of an ETS site in the intron enhancer of the keratin 18 gene participates in tissue-specific repression.
The activities of ETS transcription factors are modulated by posttranscriptional modifications and cooperation with other proteins. Another factor which could alter the regulation of genes by ETS transcription factors is DNA methylation of their cognate binding sites. The optimal activity of the keratin 18 (K18) gene is dependent upon an ETS binding site within an enhancer region located in the first intron. The methylation of the ETS binding site was correlated with the repression of the K18 gene in normal human tissues and in K18 transgenic mouse tissues. Neither recombinant ETS2 nor endogenous spleen ETS binding activities bound the methylated site effectively. Increased expression of the K18 gene in spleens of transgenic mice by use of an alternative, cryptic promoter 700 bp upstream of the enhancer resulted in modestly decreased methylation of the K18 ETS site and increased RNA expression. Expression in transgenic mice of a mutant K18 gene, which was still capable of activation by ETS factors but was no longer a substrate for DNA methylation of the ETS site, was fivefold higher in spleen and heart. However, expression in other organs such as liver and intestine was similar to that of the wild-type gene. This result suggests that DNA methylation of the K18 ETS site may be functionally important in the tissue-specific repression of the K18 gene. Epigenetic modification of the binding sites for some ETS transcription factors may result in a refractory transcriptional response even in the presence of necessary trans-acting activities.


Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 Clinical Trial Study Group.
Previous studies demonstrated that zolmitriptan at doses of 1 to 25 mg was highly effective in treating acute migraine attacks. The 2.5-mg dose had a favorable therapeutic effect with high efficacy and good tolerability. The objective of this study was to further evaluate the efficacy of a single 2.5-mg dose of zolmitriptan (Zomig, formerly known as 311C90) for acute treatment of a single moderate or severe migraine attack. The study was a randomized, double-blind, placebo-controlled clinical trial. Female and male patients, 12 to 65 years old, with migraine (with or without aura) for > or = 1 year, one to six migraines per month, and age at onset < 50 years were included; 327 patients were screened and randomized to receive either zolmitriptan (n = 219) or placebo (n = 108). Patients treated a single moderate or severe migraine headache with 2.5 mg zolmitriptan or placebo and recorded clinical efficacy and adverse events on a diary form. Headache response at 2 hours was 62% for zolmitriptan compared with 36% for placebo (p < 0.001); at 4 hours, headache response was 70% with zolmitriptan and 37% with placebo (p < 0.001). Headache recurrence in patients treated with 2.5 mg zolmitriptan was 22% (versus placebo 30%). The headache response at 4 hours, pain-free rate, and response rate of nonheadache symptoms favored zolmitriptan over placebo. No serious adverse events were associated with zolmitriptan treatment. A 2.5-mg dose of zolmitriptan is clinically effective and well tolerated for the acute treatment of migraine.


[Gastrointestinal findings in HIV infection. Clinical aspects, microbiological findings and endoscopic picture].
Among 200 hospitalized patients treated for HIV infections there were 98 with gastrointestinal symptoms, independent of the stage of the disease. Only 22 had abnormal stool findings. But histological examination and culture of endoscopically obtained biopsies revealed opportunistic infection in 62, of whom 28 had a cytomegalovirus infection. Mycobacterium avium-intracellulare was found in the gastrointestinal mucosa of 25 patients, but its clinical significance is unclear. In 33 of the 98 patients previously classified as positive for HIV or AIDS-related complex, endoscopic demonstration of an opportunistic infection required amendment of their HIV stage. In over 60% endoscopy revealed mucosal changes. A distinction from Crohn's disease or ulcerative colitis could only be made by histology or exclusion of the causative microorganism. Demonstration of the causative microorganism from the biopsy is thus essential in patients with gastrointestinal symptoms, because specific treatment is in principle possible and successful for some opportunistic infections.


Protein synthesis and phosphorylation by elongating 13-15-day-old cattle blastocysts.
Most early embryonic loss in cattle occurs during the period of blastocyst formation and elongation. In this study de novo protein synthesis and phosphorylation by 13-15-day-old cattle blastocysts was determined. Blastocysts were classified by dimension into spherical, ovoid and elongated stages and cultured under oil for 4 h in drops of KSOM medium containing either 35S-methionine or 32P-orthophosphate. Protein content increased with shape from spherical to ovoid to elongated. There were differences (P<0.05) within and among days in the percentage of radiolabel incorporated. Incorporation of 35S-methionine increased with embryo protein content. However, incorporation of 35S-methionine into TCA-insoluble material, expressed per microg of protein, decreased with shape (P<0.001) with more than a 10-fold difference between spherical and elongated 13-day-old blastocysts. Incorporation of 32P-orthophosphate also tended to decrease with shape, with a 3-fold difference between spherical and elongated Day 13 blastocysts. It was concluded that, from Day 13, protein synthesis and phosphorylation, when expressed per unit of protein, decreased from a much higher level, which in the present study was around the time the blastocysts began to elongate.


Plasmid and chromosome partitioning: surprises from phylogeny.
Plasmids encode partitioning genes (par) that are required for faithful plasmid segregation at cell division. Initially, par loci were identified on plasmids, but more recently they were also found on bacterial chromosomes. We present here a phylogenetic analysis of par loci from plasmids and chromosomes from prokaryotic organisms. All known plasmid-encoded par loci specify three components: a cis-acting centromere-like site and two trans-acting proteins that form a nucleoprotein complex at the centromere (i.e. the partition complex). The proteins are encoded by two genes in an operon that is autoregulated by the par-encoded proteins. In all cases, the upstream gene encodes an ATPase that is essential for partitioning. Recent cytological analyses indicate that the ATPases function as adaptors between a host-encoded component and the partition complex and thereby tether plasmids and chromosomal origin regions to specific subcellular sites (i.e. the poles or quarter-cell positions). Two types of partitioning ATPases are known: the Walker-type ATPases encoded by the par/sop gene family (type I partitioning loci) and the actin-like ATPase encoded by the par locus of plasmid R1 (type II partitioning locus). A phylogenetic analysis of the large family of Walker type of partitioning ATPases yielded a surprising pattern: most of the plasmid-encoded ATPases clustered into distinct subgroups. Surprisingly, however, the par loci encoding these distinct subgroups have different genetic organizations and thus divide the type I loci into types Ia and Ib. A second surprise was that almost all chromosome-encoded ATPases, including members from both Gram-negative and Gram-positive Bacteria and Archaea, clustered into one distinct subgroup. The phylogenetic tree is consistent with lateral gene transfer between Bacteria and Archaea. Using database mining with the ParM ATPase of plasmid R1, we identified a new par gene family from enteric bacteria. These type II loci, which encode ATPases of the actin type, have a genetic organization similar to that of type Ib loci.


Continuous ambulatory peritoneal dialysis. Impact on management of patients with end-stage renal disease.
Continuous ambulatory peritoneal dialysis has been demonstrated to be a successful dialysis therapy for those patients who are emotionally, socially, and intellectually capable of safely performing the self-dialysis technique. Rapid expansion of the procedure, modification of the technique to reduce the incidence of peritonitis, development of experienced personnel and adequate funding by the government can serve to increase the home dialysis population, save tax dollars and free patients from the requirement of machine dialysis.


Arterial hemodynamics in patients after Kawasaki disease.
Histopathological findings in the acute stage of Kawasaki disease (KD) indicate widespread vascular inflammation that involves not only coronary arteries but also systemic arteries. This may cause changes in systemic arterial wall properties after KD, which could have adverse effects on arterial hemodynamics (an important predictor of cardiovascular morbidity and mortality). Systemic arterial hemodynamics were investigated by measuring aortic input impedance during cardiac catheterization in 42 KD patients who had developed coronary artery lesions (CALs) in the acute stage of KD. The KD patients were subdivided into 2 groups according to the angiographic findings (group 1A, 26 patients with persistent CALs; group 1B, 16 patients with regressed CALs), and results were compared with those of 36 referents (group 2). Compared with referents, characteristic impedance was significantly higher for KD patients (137.0+/-5.1, 125.7+/-8.2, and 97.9+/-4.1 dyne x s x cm(-5) x m2 for group 1A, group 1B, and group 2, respectively), and total peripheral arterial compliance indexed to age-specific values was significantly lower for KD patients (group 1A 72.9+/-4.2% of normal; group 1B 70.6+/-5.9% of normal; group 2 97.7+/-4.0% of normal; for both variables, P<0.05 for each KD group versus group 2; P=NS between KD groups), which suggests that both central and peripheral arterial wall stiffness increase after KD regardless of persistence of CALs. Also, indices of arterial wave reflection (reflection coefficient, reflection factor, and augmentation index) were all significantly higher in KD patients than in referents (P<0.05), with the result that the aortic pressure waveforms of the present KD patients resembled those generally observed in the elderly. In addition, levels of circulating markers of endothelial dysfunction (ACE and von Willebrand factor) were associated with increased vascular stiffening in KD patients but not in referents. These results indicating abnormal arterial hemodynamics after KD highlight the importance of regular monitoring of the systemic arterial bed and potentially relevant cardiovascular events in long-term follow-up of KD.


Total synthesis of sulfolipid-1.
Sulfolipid-1, a tetra-acylated sulfotrehalose from Mycobacterium tuberculosis, was isolated over 40 years ago. Being a main component of the mycomembrane of M. tuberculosis, its biosynthesis and function have been studied in depth, but the chemical synthesis of sulfolipid-1 has not been reported. The synthesis presented here is based on iterative catalytic asymmetric conjugate additions of methylmagnesium bromide for the preparation of the phthioceranic and hydroxyphthioceranic acid side chains, a double regioselective reductive ring-opening and a fivefold deprotection in the final step.


Modification of gamma-radiation response in mice by green tea polyphenols.
In this study we evaluated the effect of water extracts of green tea (GT) and mixtures of green tea polyphenols (GTPs), epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells of mice irradiated with gamma-ray. The radioprotective effect of green tea was compared with the effect of diethyldithiocarbamate (DDC). Jejunal crypts were protected by pretreatment of GT and ECG. Administration of GT, GTPs and EC prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of apoptosis in crypt cells was also reduced by pretreatment of GT, GTPs, EGCG, ECG and EGC. In the experiment on the effect of catechins, the effects were partly contradicted in irradiated mice. The rank order of activity was ECG > EGC > EGCG > EC on intestinal crypt survival assay, EC > EGC > ECG > EGCG on the spleen colony formation assay, EGCG > EGC > EC > ECG on inhibiting the death of cells caused by apoptosis. The results indicate that GT and GTPs may have a major radioprotective effect. Each one of the catechins was a much less effective radioprotector, suggesting that total extract or a mixture of GTPs may be more effective than individual catechins.


Methylation of the chicken vitellogenin gene: influence of estradiol administration.
The degree of methylation of the chicken vitellogenin gene has been investigated. Upon induction by administration of estradiol to a rooster, methyl groups at specific sites near the 5'-end of the gene are eliminated. The process of demethylation is slower than the activation of the gene. Demethylation is therefore probably not a prerequisite to gene transcription. At least two other sites in the coding region of the gene are methylated in the liver of estrogenized roosters, but not in the liver of a laying hen, where the gene is naturally active.


Longitudinal association of dietary fat intake with cardiovascular events in a prospective cohort study in Eastern Mediterranean region.
We examined the association of dietary fats intake with the 13-year risk of cardiovascular disease (CVD) among Iranian population. Totally 5432 participants of Isfahan Cohort Study (ICS) aged ≥ 35 years were included in the current study. The frequency of dietary fats including hydrogenated vegetables oil (HVO), non-hydrogenated vegetables oil (nHVO), olive oil, ghee, and animal fats during the preceding year were assessed using a validated food frequency questionnaire. After adjustment for potential confounders, individuals in the top quartile of HVO tended to have 68% greater risk for myocardial infarction compared with those in the first quartile (95% CI: 1.02, 2.78; P = 0.058). No association was found for other dietary fat sources with ischaemic heart disease, stroke, all-cause and CVD mortality after adjustment for all potential confounders. Higher consumption of HVO was associated with increased risk of myocardial infarction.


Incidental pancreatic cysts: do we really know what we are watching?
Most cystic neoplasms of the pancreas (CNPs) are incidentally discovered. Their management continues to be debated and preoperative diagnosis is often inaccurate. Retrospective review of 330 patients with incidentally discovered CNPs. Preoperative and final histological diagnoses were correlated. 41% (136/330) of patients were operated on at diagnosis. 50 patients underwent resection for a presumed branch-duct (Bd) intraductal papillary mucinous neoplasm (IPMN), which was confirmed in only 64% (32/50); of the remaining patients, 20% had main-duct involvement. Mucinous cystic neoplasm was the preoperative diagnosis in 30/136 patients, histologic examination was confirmatory in only 60% (18/30). Most lesions presumed to be main-duct or combined IPMNs or serous cystadenomas were confirmed as such after resection (15/16 and 11/12, respectively). Multifocality was not only associated with Bd-IPMN, and 5% of all cysts were non-neoplastic. Overall, in only 68% of cases did the preoperative and histological diagnoses match. In an experienced, high-volume center, preoperative diagnosis was incorrect in one-third of incidentally discovered CNPs who underwent resection. Of particular concern, 20% of presumed Bd-IPMN had a main-duct component. Conversely, 5% of resected cysts were not even neoplastic. Clearly, better diagnostic methods are needed to aid in formulating appropriate treatment strategies.


Determining reliability of clinical assessment scores in real time.
Assessment score reliability is usually based on a single analysis. However, reliability is an essential component of validity and assessment validation and revision is a never-ending cycle. For ongoing assessments over extended time frames, real-time reliability computations may alert users to possible changes in the learning environment that are revealed by variations in reliability over time. To develop software that calculates the reliability of clinical assessments in real time. Over 2,400 assessment forms were analyzed. We developed software that calculates reliability in real time. Software accuracy was verified by comparing data from our software with a standard method. Factor analysis determined scale dimensionality. Correlation between our software and a standard method was excellent (ICC for kappas = 0.97; Cronbach's alphas differed by < 0.03). Cronbach's alpha ranged from 0.94 to 0.97 and weighted kappa ranged from 0.08 to 0.40. Factor analysis confirmed 3 teaching domains. We describe an accurate method for calculating reliability in real time. The benefit of real time computation is that it provides a mechanism for detecting possible changes (related to curriculum, teachers, and students) in the learning environment indicated by changes in reliability over time. This technique will enable investigators to monitor and detect changes in the reliability of assessment scores and, with future study, isolate aspects of the learning environment that impact on reliability.


Identification of bacteriophage MS2 coat protein from E. coli lysates via ion trap collisional activation of intact protein ions.
Collisional activation of the intact MS2 viral capsid protein with subsequent ion/ion reactions has been used to identify the presence of this virus in E. coli lysates. Tandem ion trap mass spectrometry experiments on the +7, +8, and +9 charge states, followed by ion/ion reactions, provided the necessary sequence tag information (and molecular weight data) needed for protein identification via database searching. The most directly informative structural information is obtained from those charge states that produce a series of product ions arising from fragmentation at adjacent residues. The formation of these product ions via dissociation at adjacent amino acid residues depends greatly on the charge state of the parent ion. Database searching of the charge-state-specific sequence tags was performed by two different search engines: the ProteinInfo program from the Protein information Retrieval On-line World Wide Web Lab or PROWL and the TagIdent program from the ExPASy molecular biology server. These search engines were used in conjunction with the sequence tag information generated via collisional activation of the intact viral coat protein. These programs were used to evaluate the feasibility of generating sequence tags from collisional activation of intact multiply charged protein ions in a quadrupole ion trap.


Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability.
Natural hair colour within European populations is a complex genetic trait. Previous work has established that MC1R variants are the principal genetic cause of red hair colour, but with variable penetrance. Here, we have extensively mapped the genes responsible for hair colour in the white, British ancestry, participants in UK Biobank. MC1R only explains 73% of the SNP heritability for red hair in UK Biobank, and in fact most individuals with two MC1R variants have blonde or light brown hair. We identify other genes contributing to red hair, the combined effect of which accounts for ~90% of the SNP heritability. Blonde hair is associated with over 200 genetic variants and we find a continuum from black through dark and light brown to blonde and account for 73% of the SNP heritability of blonde hair. Many of the associated genes are involved in hair growth or texture, emphasising the cellular connections between keratinocytes and melanocytes in the determination of hair colour.


Population structure attributable to reproductive time: isolation by time and adaptation by time.
Many populations are composed of a mixture of individuals that reproduce at different times, and these times are often heritable. Under these conditions, gene flow should be limited between early and late reproducers, even within populations having a unimodal temporal distribution of reproductive activity. This temporal restriction on gene flow might be called "isolation by time" (IBT) to acknowledge its analogy with isolation by distance (IBD). IBD and IBT are not exactly equivalent, however, owing to differences between dispersal in space and dispersal in time. We review empirical studies of natural populations that provide evidence for IBT based on heritabilities of reproductive time and on molecular genetic differences associated with reproductive time. When IBT is present, variation in selection through the reproductive season may lead to adaptive temporal variation in phenotypic traits [adaptation by time (ABT)]. We introduce a novel theoretical model that shows how ABT increases as (i) selection on the trait increases; (ii) environmental influences on reproductive time decrease; (iii) the heritability of reproductive time increases; and (iv) the temporal distribution of reproductive activity becomes increasingly uniform. We then review empirical studies of natural populations that provide evidence for ABT by documenting adaptive temporal clines in phenotypic traits. The best evidence for IBT and ABT currently comes from salmonid fishes and flowering plants, but we expect that future work will show these processes are more widespread.


Hypocotyl Elongation Inhibition of Melatonin Is Involved in Repressing Brassinosteroid Biosynthesis in Arabidopsis.
Melatonin functions as a plant hormone/regulator in the regulation of growth and development. However, the underlying mechanisms are still unclear. In this study, we found that a high dose of melatonin inhibited hypocotyl elongation in a dose-dependent manner in Arabidopsis. An expression profile analysis showed that hypocotyl growth inhibition by melatonin was involved in reprograming the expression of cell elongation genes and brassinosteroid (BRs) biosynthetic genes. Furthermore, similar to BR biosynthetic inhibitor brassinazole (BRZ), a high concentration of melatonin upregulated BR-biosynthetic genes and downregulated BR-induced genes involved in cell elongation, while melatonin was inefficient in brassinazole-resistant mutants like the bzr1-1D and bes1-D in hypocotyl inhibition. The comparative expression profile analysis showed an opposite expression mode in the co-regulated genes between melatonin and BZR1 or melatonin and brassinolide (BL). Additionally, exogenous BL rescued the repressive phenotype of BR biosynthesis-deficient mutant like det2-1 even in the presence of high-dose melatonin, but not BR receptor mutant bri1-5 or signal transduction mutant bin2-1. A biochemical analysis further confirmed that melatonin reduced endogenous BR levels in a dose-dependent manner in Arabidopsis. Taken together, these results indicate that melatonin inhibits BR biosynthesis but does not block BR signaling in the inhibition of hypocotyl elongation and extends insights on the role of melatonin in cross-talking with plant hormone signaling.


Measuring death anxiety: conceptual, psychometric, and factor-analytic aspects.
This study was undertaken to construct a brief, reliable, and valid questionnaire for measuring attitudes toward death and dying. In Stage 1, four groups of individuals ranging in age from 30 to 82 years completed the Death Anxiety Questionnaire (DAQ), a brief anxiety scale (MAS), and a depression scale (DP). During Stage 2, results on these scales were cross-validated on a new sample of subjects, and the Templer and Dickstein measures of death anxiety were also completed. Internal consistency of the DAQ as determined by coefficient alpha was .83 (n = 230) and test-retest reliability was .87 (n = 30). No significant sex or age differences were found for any of the groups tested. Results provided evidence for both construct and concurrent validity of the DAQ and for discriminant validity of the items. A principal-components factor analysis suggested four independent dimensions of death anxiety: Fear of the Unknown; Fear of Suffering; Fear of Loneliness; and Fear of Personal Extinction. Recommendations for future research include an investigation of the degree to which scores on these four dimensions might differentiate among different sex, age, personality, affective, and diagnostic groupings.


High frequency of the expression of the MAGE gene family in human esophageal carcinoma.
The human gene MAGE encodes tumor specific peptide antigens and consists of at least 12 families. Some antigens coded by the MAGE genes may be potentially useful for cancer specific immunotherapy. There is, however, so far little information on the expression of these gene families in human esophageal carcinomas. We investigated the expression of MAGE-1, -2, -3, -4, -6, -8, -9, -10, -11, and -12 genes in 24 human esophageal carcinoma cell lines, and in 50 pairs of tumor and corresponding normal tissue specimens from the human esophagus by means of reverse transcription polymerase chain reaction. The expression rate varied from 13% of MAGE-6 and 8 to 79% of MAGE-4 in the esophageal carcinoma cell lines, and from 6% of MAGE-6 to 62% of MAGE-4 in clinical tumor samples. The most frequently and the least expressed gene were the MAGE-4 and MAGE-6 genes, respectively, in both the cell lines and the clinical samples. Forty-seven of the 50 clinical tumors expressed at least one MAGE gene. No significant clinicopathologic difference between the tumor cases was observed, regardless of the presence or absence of MAGE gene expression. The findings of this study thus demonstrated that the MAGE gene family is frequently expressed in clinical samples as well as in the cell lines of human esophageal carcinomas. Therefore, to identify the MAGE gene family may be useful, not only for esophageal tumor specific immunotherapy but for molecular diagnostic usage as well.


Scalable Bayesian Nonparametric Clustering and Classification.
We develop a scalable multi-step Monte Carlo algorithm for inference under a large class of nonparametric Bayesian models for clustering and classification. Each step is "embarrassingly parallel" and can be implemented using the same Markov chain Monte Carlo sampler. The simplicity and generality of our approach makes inference for a wide range of Bayesian nonparametric mixture models applicable to large datasets. Specifically, we apply the approach to inference under a product partition model with regression on covariates. We show results for inference with two motivating data sets: a large set of electronic health records (EHR) and a bank telemarketing dataset. We find interesting clusters and competitive classification performance relative to other widely used competing classifiers. Supplementary materials for this article are available online.


Comparison of Artemisia annua Bioactivities between Traditional Medicine and Chemical Extracts.
The present work investigates the efficacy of using Artemisia annua in traditional medicine in comparison with chemical extracts of its bioactive molecules. In addition, the effects of location (Egypt and Jericho) on the bioactivities of the plant were investigated. The results showed that water extracts of Artemisia annua from Jericho have stronger antibacterial activities than organic solvent extracts. In contrast, water and organic solvent extracts of the Artemisia annua from Egypt do not have anti-bacterial activity. Furthermore, while the methanol extract of EA displayed high anticancer affects, the water extract of Egypt and the extracts of Jericho did not show significant anticancer activity. Finally, the results showed that the methanol and water extracts of Jericho had the highest antioxidant activity, while the extracts of Egypt had none. The current results validate the scientific bases for the use of Artemisia annua in traditional medicine. In addition, our results suggest that the collection location of the Artemisia annua has an effect on its chemical composition and bioactivities.


Reversible accumulation of PEGylated single-walled carbon nanotubes in the mammalian nucleus.
Carbon nanotubes (CNTs) have been shown to cross cell membranes and can mediate the internalization of macromolecules. These characteristics have constituted CNTs as an exciting new tool for drug delivery and biological sensing. While CNTs exhibit great potential in biomedical and pharmaceutical applications, neither the cell penetration mechanism of CNTs nor the intracellular fate of the internalized CNTs are fully understood. In this study, time-lapse fluorescence microscopy was used to investigate the intracellular distribution of FITC labeled PEGylated single-walled CNTs (FITC-PEG-SWCNTs) in living cells and shown that PEGylated SWCNTs entered the nucleus of several mammalian cell lines in an energy-dependent process. The presence of FITC-PEG-SWCNTs in the cell nucleus did not cause discernible changes in the nuclear organization and had no effect on the growth kinetics and cell cycle distribution for up to 5 days. Remarkably, upon removal of the FITC-PEG-SWCNTs from the culture medium, the internalized FITC-PEG-SWCNTs rapidly moved out of the nucleus and were released from the cells. Thus, the intracellular PEGylated SWCNTs were highly dynamic and the cell penetration of PEGylated SWCNTs appeared as bidirectional. These observations suggest SWCNTs may be used as an ideal nanovector in biomedical and pharmaceutical applications.


Reconstruction of volume data with quadratic super splines.
We propose a new approach to reconstruct nondiscrete models from gridded volume samples. As a model, we use quadratic trivariate super splines on a uniform tetrahedral partition. We discuss the smoothness and approximation properties of our model and compare to alternative piecewise polynomial constructions. We observe, as a nonstandard phenomenon, that the derivatives of our splines yield optimal approximation order for smooth data, while the theoretical error of the values is nearly optimal due to the averaging rules. Our approach enables efficient reconstruction and visualization of the data. As the piecewise polynomials are of the lowest possible total degree two, we can efficiently determine exact ray intersections with an isosurface for ray-casting. Moreover, the optimal approximation properties of the derivatives allow us to simply sample the necessary gradients directly from the polynomial pieces of the splines. Our results confirm the efficiency of the quasi-interpolating method and demonstrate high visual quality for rendered isosurfaces.


Transcutaneous bilirubinometry in Chinese, Malay and Indian infants.
The objective of this study was to investigate the correlation of transcutaneous bilirubinometry (TcB) and plasma bilirubin concentrations in full-term Chinese, Malay and Indian infants. TcB was performed with the Minolta Airshields bilirubinometer on Chinese, Malay and Indian fullterm infants. The readings were taken on the chest (sternum) and forehead (glabella) when capillary blood was sampled for bilirubin determination. Five hundred and forty TcB indices in 253 Chinese infants, 282 in 169 Malay infants, and 182 in 120 Indian infants were obtained over the sternum and forehead. A good correlation between the TcB indices and the bilirubin concentrations was observed in Chinese, Malay and Indian infants: r = 0.78 (chest), r = 0.73 (forehead); r = 0.86 (chest), r = 0.84 (forehead); and r = 0.84 (chest), r = 0.82 (forehead). The correlation was just as good when the combined values were evaluated together: r = 0.80 (chest) r = 0.75 (forehead). In Chinese infants, correlation at values below 250 mumol l-1 was significantly better than that at values over 250 mumol l-1 r = 0.80 versus r = -0.20, p < 0.00001 (chest), and r = 0.74 versus r = 0.07, p < 0.00001 (forehead). However, a safer cut-off point clinically would be 200 mumol l-1, since only relatively few higher bilirubin values were encountered when TcB indices were below 200 mumol l-1. The same pattern was noticed with the other two groups, and the combined group. Thus, TcB provides a non-invasive, cost-effective screening method for significant neonatal jaundice, sparing infants and parents physical and emotional stress, and medical and nursing personnel extra work and inconvenience.


Effect of acute regional ischemia on pressure in the subepicardium and subendocardium.
The effects of acute ischemia on regional intramyocardial pressure were studied in eight open-chest dogs. Aortic, left ventricular, subepicardial, and subendocardial pressures were measured with catheter-tip micromanometers. During the control period subendocardial pressure during systole (180 +/- 13 mmHg; mean +/- SE) was higher than left ventricular intracavitary pressure (137 +/- 9 mmHg; P less than 0.001). Subepicardial pressure during systole was lower (95 +/- 6 mmHg; P less than 0.001). Acute ischemia caused a reduction of subendocardial pressure during systole to levels below left ventricular systolic pressure (92 +/- 7 mmHg vs. 116 +/- 6 mmHg; P less than 0.01). Ischemia also caused a reduction of systolic subepicardial pressure to 67 +/- 2 mmHg (P less than 0.001). After reperfusion all pressures returned nearly to control values. During diastole subendocardial pressure during the control period (13 +/- 1 mmHg) was high than left ventricular end-diastolic pressure (6 +/- 1 mmHg; P less than 0.001). Subepicardial pressure during diastole (29 +/- 2 mmHg) was higher than subendocardial pressure and left ventricular end-diastolic pressure (P less than 0.001). Acute ischemia had little or no effect on subendocardial pressure during diastole, whereas it caused a reduction of subepicardial diastolic pressure to 16 +/- 1 mmHg (P less than 0.001). Reperfusion of the ischemic region caused a return of all diastolic pressures nearly to control values. These observations indicate that coronary extravascular resistance is affected by ischemia and that the most prominent effects are in the subendocardium during systole and in the subepicardium during diastole.


A randomized double-blind study comparing 25 and 50 mg TC-1734 (AZD3480) with placebo, in older subjects with age-associated memory impairment.
Cognitive decline is a feature of ageing and can be defined as normal (age-associated memory impairment) or pathological (mild cognitive impairment/Alzheimer's disease). Stimulation of selective brain-specific neuronal nicotinic acetylcholine receptors might offer symptomatic treatment for normal ageing. The objective of this study was to assess the safety, tolerability and efficacy of TC-1734 (AZD3480), a selective α4β2 nicotinic agonist, in the treatment of age-associated memory impairment. A randomized placebo-controlled trial was conducted in 16 community-based centers within the USA. Subjects who met objective criteria for age-associated memory impairment were recruited between November 2004 and December 2005. Subjects were randomly assigned to receive orally 25 mg (n = 59), 50 mg (n = 68) TC-1734 (AZD3480) or placebo (n = 66) in a double-blind fashion for 16 weeks. Main outcome measures included routine clinical safety measures, tolerability, cognitive assessment via the Cognitive Drug Research computerized test battery and a Subject Global Impression Scale of Cognition (SCI-Cog). Two outcomes from the computerized test battery - a factor assessing attention and one assessing episodic memory, along with the SGI-Cog were defined as co-primary outcome variables. Baseline to Week 16 differences from placebo for 50 mg TC-1734 (AZD3480) were considered of primary importance. For 50 mg TC-1734 (AZD3480) attention factor the mean drug-placebo difference was 22.9 (95% confidence interval 4.8 to 41.4) p = 0.01 for episodic memory factor the difference was -7.6 (95% confidence interval -14.4 to -0.8), p = 0.029, and for the SGI-Cog the difference was 0.99 (95% confidence interval 0.2 to 1.8), p = 0.015. As all three co-primary outcomes were positive it can be concluded the compound likely had a beneficial effect on cognition. TC-1734 (AZD3480) appeared safe and well tolerated in this study.


Physical activity, physical fitness, and general health perception among individuals with rheumatoid arthritis.
To describe self-reported physical activity and physical fitness and to identify correlates of physical activity and general health perception. Data on self-reported physical activity, physical fitness, activity performance, and disease activity were collected from a sample of 298 patients with rheumatoid arthritis (RA). Forty-seven percent of our sample reported physical activity behaviors that did not comply with public health recommendations. A majority of the patients had decreased lower-limb muscle function (72%), grip force (94%), joint motion (94%), and functional balance (68%). Correlations between self-reported physical activity and other variables were r(s) = 0.25 or less. Variation in general health perception was explained (total adjusted R(2) = 0.65) by pain and activity performance. Our findings indicate that there is a case for recommendations on and support for healthy physical activity behaviors among people with RA.


Genetics moving to neuronal networks.
Neuronal circuits are essential components of the nervous system and determine various body functions. To understand how neuronal circuits operate it is necessary to identify the participating neuronal subpopulations and to dissect the function of the neurons at the molecular level. The locomotor central pattern generator that coordinates body movements is well suited for elucidating the assembly and identity of the participating neurons. Remarkable advances in the field of genetics are making studies in neuroscience more efficient and precise so that now, using nematode worms, fruit flies, zebrafish and mice as model organisms, a genetic approach can be used to identify molecules and neurons crucial for locomotor network functionality.


The diatom genus Pseudo-nitzschia (Bacillariophyceae) in New South Wales, Australia: morphotaxonomy, molecular phylogeny, toxicity, and distribution.
Species belonging to the potentially harmful diatom genus Pseudo-nitzschia, isolated from 16 localities (31 sampling events) in the coastal waters of south-eastern Australia, were examined. Clonal isolates were characterized by (i) light and transmission electron microscopy; (ii) phylogenies, based on sequencing of nuclear-encoded ribosomal deoxyribonucleic acid (rDNA) regions and, (iii) domoic acid (DA) production as measured by liquid chromatography-mass spectrometry (LC-MS/MS). Ten taxa were unequivocally confirmed as Pseudo-nitzschia americana, P. arenysensis, P. calliantha, P. cuspidata, P. fraudulenta, P. hasleana, P. micropora, P. multiseries, P. multistriata, and P. pungens. An updated taxonomic key for south-eastern Australian Pseudo-nitzschia is presented. The occurrence of two toxigenic species, P. multistriata (maximum concentration 11 pg DA per cell) and P. cuspidata (25.4 pg DA per cell), was documented for the first time in Australia. The Australian strains of P. multiseries, a consistent producer of DA in strains throughout the world, were nontoxic. Data from 5,888 water samples, collected from 31 oyster-growing estuaries (2,000 km coastline) from 2005 to 2009, revealed 310 regulatory exceedances for "Total Pseudo-nitzschia," resulting in six toxic episodes. Further examination of high-risk estuaries revealed that the "P. seriata group" had highest cell densities in the austral summer, autumn, or spring (species dependent), and lowest cell densities in the austral winter, while the "P. delicatissima group" had highest in winter and spring.


An update on AIDS-related cholangiopathy.
Both hepatic parenchymal and biliary tract diseases are common in patients with human immunodeficiency virus (HIV). In this paper, the authors focus mainly on clinical aspects of acquired immunodeficiency syndrome (AIDS)-related cholangiopathy. Although the etiology is unclear, several opportunistic infections (cytomegalovirus, Cryptosporidium and others) are suspected to cause it. Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic gold standard and it offers a therapeutic means to provide symptomatic relief in case of papillary stenosis. The most common ERCP pattern is diffuse sclerosing cholangitis in combination with papillary stenosis. Clinically, the presentation may be variable, although right upper quadrant pain and fever accompanied by an elevated serum alkaline phosphatase (ALP) level are the most common manifestations. Jaundice is unusual suggesting that complete ductal obstruction is rare. While ERCP results and the need of sphincterotomy do not influence the prognosis, antiretroviral therapy is a protective factor and, on the contrary, high ALP level is related to a less favorable outcome. Regarding the possible pathogenic mechanisms through which HIV infection could be involved in AIDS-related cholangiopathy, in vitro experiments have shown that concurrent active HIV replication and Cryptosporidium parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies.


Contribution of small conductance K+ channels to sinoatrial node pacemaker activity: insights from atrial-specific Na+ /Ca2+ exchange knockout mice.
Repolarizing currents through K+ channels are essential for proper sinoatrial node (SAN) pacemaking, but the influence of intracellular Ca2+ on repolarization in the SAN is uncertain. We identified all three isoforms of Ca2+ -activated small conductance K+ (SK) channels in the murine SAN. SK channel blockade slows repolarization and subsequent depolarization of SAN cells. In the atrial-specific Na+ /Ca2+ exchanger (NCX) knockout mouse, cellular Ca2+ accumulation during spontaneous SAN pacemaker activity produces intermittent hyperactivation of SK channels, leading to arrhythmic pauses alternating with bursts of pacing. These findings suggest that Ca2+ -sensitive SK channels can translate changes in cellular Ca2+ into a repolarizing current capable of modulating pacemaking. SK channels are a potential pharmacological target for modulating SAN rate or treating SAN dysfunction, particularly under conditions characterized by abnormal increases in diastolic Ca2+ . Small conductance K+ (SK) channels have been implicated as modulators of spontaneous depolarization and electrical conduction that may be involved in cardiac arrhythmia. However, neither their presence nor their contribution to sinoatrial node (SAN) pacemaker activity has been investigated. Using quantitative PCR (q-PCR), immunostaining and patch clamp recordings of membrane current and voltage, we identified all three SK isoforms (SK1, SK2 and SK3) in mouse SAN. Inhibition of SK channels with the specific blocker apamin prolonged action potentials (APs) in isolated SAN cells. Apamin also slowed diastolic depolarization and reduced pacemaker rate in isolated SAN cells and intact tissue. We investigated whether the Ca2+ -sensitive nature of SK channels could explain arrhythmic SAN pacemaker activity in the atrial-specific Na+ /Ca2+ exchange (NCX) knockout (KO) mouse, a model of cellular Ca2+ overload. SAN cells isolated from the NCX KO exhibited higher SK current than wildtype (WT) and apamin prolonged their APs. SK blockade partially suppressed the arrhythmic burst pacing pattern of intact NCX KO SAN tissue. We conclude that SK channels have demonstrable effects on SAN pacemaking in the mouse. Their Ca2+ -dependent activation translates changes in cellular Ca2+ into a repolarizing current capable of modulating regular pacemaking. This Ca2+ dependence also promotes abnormal automaticity when these channels are hyperactivated by elevated Ca2+ . We propose SK channels as a potential target for modulating SAN rate, and for treating patients affected by SAN dysfunction, particularly in the setting of Ca2+ overload.


Administrative behaviors in allied health.
The purpose of this study was to explore the applicability of current industrially oriented management techniques to allied health personnel in both academic and patient care settings. Medical technology, nursing, occupational therapy, and physical therapy faculty and practitioners at five universities, two community colleges, and five hospitals were surveyed to determine both their preferred and actual administrative behaviors perceived over ten administrative functions. The results revealed a significant difference between the preferred administrative behaviors and those perceived, as well as discrepancies between preferences and current management techniques and concepts.


Adrenomedullin, transcriptionally regulated by vitamin D receptors, alleviates atherosclerosis in mice through suppressing AMPK-mediated endothelial ferroptosis.
Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs. Endothelial dysfunction cell model was constructed by oxidized low-density lipoprotein (ox-LDL). An animal model of atherosclerosis was established in male homozygous Apoe-/- mice (6 weeks) on a high fat diet for 6 weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins. Overexpression of VDR in HUVECs inhibits ox-LDL-induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox-LDL-induced endothelial dysfunction and ferroptosis. ADM regulates ox-LDL-induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice inhibited lipid deposition and plaque area in atherosclerotic mice. VDR inhibits ox-LDL-induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice.


Design of a MEMS discretized hyperbolic paraboloid geometry ultrasonic sensor microarray.
Design of a discretized hyperbolic paraboloid geometry beamforming array of capacitive micromachined ultrasonic transducers (CMUT) has been presented. The array can intrinsically provide a broadband constant beamwidth beamforming capability without any microelectronic signal processing. A mathematical model has been developed and verified to characterize the array response. A design methodology has been presented that enables determination of the array's physical dimensions and CMUT modeling in a straightforward manner. Developed methodology has been used to design two discretized hyperbolic paraboloid geometry beamforming CMUT arrays: one in the 2.3 MHz to 5.2 MHz frequency range and another in the 113 kHz to 167 kHz frequency range. CMUTs have been designed using a cross-verification method that involves lumped element modeling, 3-D electromechanical finite element analysis (FEA), and microfabrication simulation. The developed array has the potential to be used in real-time automotive collision-avoidance applications, medical diagnostic imaging and therapeutic applications, and industrial sensing.


The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study.
To reduce the risk of brain damage children with acute lymphoblastic leukaemia (ALL) are nowadays mainly treated with intrathecal chemotherapy (ITC) instead of central nervous system (CNS) radiation therapy (CRT) to prevent CNS relapse. However, chemotherapy may also lead to cognitive deficits. As growth hormone deficiency (GHD) or impaired growth hormone secretion are frequently found in ALL patients treated with cranial radiation therapy and/or chemotherapy, we hypothesized that GH therapy may reduce cognitive deficits in these patients. Twenty young adult survivors of childhood ALL with reduced bone mineral density (<-1 SD) and/or low IGF-I SD-scores (<-1 SD) were included in the study. A final group of 13 patients (9 males and 4 females), mean age 23.7 +/- 2.9 years (range 20 - 29.7) completed a 2-year treatment with GH.IQ and neuropsychological performance were assessed at pre-treatment (T1) and after one (T2) and two (T3) years. ANOVA was performed with assessment at T1, T2 and T3 as repeated measurements factor. Relations between test score changes and changes of IGF-I levels were determined by calculating the Pearson correlation coefficient. Scores on the cognitive tests were in the normal range. Verbal short- and long-term memory performance decreased between T1 and T2, and increased between T2 and T3. Performance at T3 was not significantly different from that at T1. Performance for sustained attention improved from T1 to T2 and from T1 to T3. Visual-spatial memory was improved after one year of GH treatment. A significant positive correlation was found for Delta IGF-I (T2-T1) with difference scores of visual-spatial memory (T2-T1 and T3-T1), indicating that IGF-I increase after one year of GH treatment is associated with increase in cognitive-perceptual performance at month 12 and 24. Since the level of intellectual functioning of our patient cohort was in the normal range the present finding that GH treatment has negative effects on verbal memory and positive on attention and visual-spatial memory warrants similar studies in other groups of ALL survivors. Also, a lower dose of GH should be determined inducing as much IGF as needed to improve verbal as well as visual cognitive functions. The present findings indicate that more knowledge is needed before GH treatment may be recommended to enhance cognitive functions in ALL survivors.


Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness.
Tight junctions between adjacent epithelial cells are essential for the maintenance of compositionally distinct fluid compartments in various organs, such as the liver, lungs, kidneys, and intestine. These epithelial organs are commonly affected in the condition known as multiple organ dysfunction syndrome, which can complicate the clinical course of patients with sepsis or other conditions associated with poorly controlled systemic inflammation. The gut serves as a useful model for this problem, and studies using reductionist in vitro models and experiments carried out using laboratory animals are starting to clarify the cellular and biochemical mechanisms that are responsible for intestinal epithelial hyperpermeability secondary to critical illness. One key factor that has been identified is excessive production of nitric oxide and related species, although other factors, such as increased expression of the cytokine interleukin 6, appear to be important as well. A newly described, cytokine-like molecule, high-mobility group B1, increases permeability of cultured epithelial monolayers in vitro and murine ileal mucosa in vivo. Epithelial dysfunction may be a common final pathway contributing to organ dysfunction in sepsis and other forms of critical illness.


Differential regulation of bcl-2 and bcl-x by CD3, CD28, and the IL-2 receptor in cloned CD4+ helper T cells. A model for the long-term survival of memory cells.
In this study, we examined the molecular signals that control apoptosis in cloned CD4+ helper T cells. Resting T cells were highly resistant to spontaneous death in the absence of exogenous stress, and they expressed low levels of bcl-x protein and no detectable bcl-2. Upon exposure to gamma radiation, resting cells rapidly underwent apoptotic death. Incubation with IL-2 prevented this cell death and led to a large increase in bcl-2 protein expression and only a modest up-regulation in bcl-x. The combination of anti-CD3 and anti-CD28 mAbs was also effective in protecting the cells against radiation-induced apoptosis; however, this protection was associated predominantly with bcl-x up-regulation, and only a small induction of bcl-2 protein was observed. Finally, cyclosporin A blocked both IL-2 secretion and bcl-2 induction in response to CD3 plus CD28 stimulation, suggesting a role for endogenous lymphokine production in the induction of bcl-2. These data support a model in which memory T cells remain resistant to apoptosis because intermittent contact with Ag-bearing APC and IL-2R occupancy result in the expression of the life-proteins bcl-2 and bcl-x.


[Defecation disorders in children: treatment with colonic irrigation through an appendicostomy].
In 3 patients with serious constipation or faecal incontinence the appendix was sewn open-ended into the abdominal wall (Malone-stoma) allowing antegrade bowel washouts. The patients were a 4-year-old boy with Hirschsprung's disease, a 15-year-old boy with chronic functional constipation and encopresis, and a 5.5-year-old boy with incontinence associated with a meningomyelocele. Following the procedure they were free from bowel problems. Faecal incontinence has a major detrimental effect on the psychosocial development of children. Severe constipation and faecal incontinence which do not optimally respond to conventional therapy can be treated by this procedure. Treatment is effective in around three-quarters of these children. Complications occur in an equal number of children, stenosis being the most frequently seen.


Growth hormone enhances thymic function in HIV-1-infected adults.
Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4(+) T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4(+) T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.


Ionizing radiation exposure effects across multiple generations: evidence and lessons from non-human biota.
A Task Group (TG121) of the International Commission on Radiological Protection (ICRP) Committee 1 was launched in 2021 to study the effects of ionizing radiation in offspring and next generations. In this report, we summarize the evidence of multi- and trans-generational effects in non-human biota species that was discussed at the ICRP workshop entitled "Effects of Ionizing Radiation Exposure in Offspring and Next Generations" in June 2022. Epigenetic changes, including changes in DNA methylation, have been observed in trans- and multi-generational irradiation studies in both plants and animals. There were also reports of changes in offspring survival and reproduction. The reported evidence for altered reproduction is an area of potential concern, due to possible effects at the population or ecosystem level. Different considerations are also discussed regarding non-human biota data, such as transferability of data between different species or extending knowledge to humans, differences in species radiosensitivity, the presence of adaptive responses, and dose reconstruction for exposures that occur across multiple generations. Overall, there is a diverse range of available data of the effects in non-human biota, and it will require careful consideration when incorporating this evidence into the system of radiological protection of humans and of the environment.


False-positive Aspergillus real-time PCR assay due to a nutritional supplement in a bone marrow transplant recipient with GVH disease.
PCR screening for circulating DNA, especially when combined with antigen testing, has shown promise for the definitive diagnosis of invasive aspergillosis. False positives for Aspergillus real-time PCR assays have been described in several reports, but no sources of fungal DNA contamination could be clearly identified. We report a false-positive case for both galactomannan (GM) antigenemia and Aspergillus PCR due to nutritional supplement intake in a bone marrow transplant recipient with digestive graft-versus-host disease. Our case report also suggests that fungal DNA can pass into the serum from the intestinal tract in the same way as fungal GM. Clinicians should be aware of this possibility, so that the administration of costly, unnecessary antifungal treatments with potential adverse side-effects can be avoided.


Morbidity and mortality after hip fracture: the impact of operative delay.
The relationship between the timing of surgery after hip fracture and the subsequent survival of the patient has been studied extensively, yet still remains a controversy. This study aims to assess the impact of operative delay on the 1-year survival of patients and on the rate of complications during the postoperative hospital stay. Medical and demographic data were extracted from the hospital records of 651 consecutive hip fracture patients over 60 years old. Information on mortality was obtained by cross-linkage with the Department of Interior population files. The multivariate survival analysis model was utilized to assess the association between the time from fracture incident to surgery and the outcome (1-year survival and postoperative complications). The hazard ratio (HR) of 1-year mortality for postponing surgery beyond 48 h was 1.63 (95%CI 1.11-2.40), as derived by the Cox proportional hazards model. Other variables found to be independently associated with decreased survival are: male gender (HR=1.54), mental deterioration (HR=2.94), postoperative mobility (HR=2.45), and severity of pre-existing diseases (HR=1.96). Occurrence of general complications during the postoperative hospital stay was a significant predictor of decreased 1-year survival (HR=1.83). These findings suggest that early (within 48 h) surgical treatment of hip fractures is associated with improved 1-year survival.


[Role of the SYNTAX score in assessing the outcomes of percutaneous interventions in patients with ST segment elevation myocardial infarction].
Based on the findings of a single-centre study of 327 patients presenting with ST segment elevation myocardial infarction (STEMI) subjected to primary percutaneous coronary intervention (PCI) we examined the prognostic role of severity of atherosclerotic multivascular lesion (ML) of the coronary bed. The patients were subdivided into three groups depending on the quantitative index assessing severity of coronary atherosclerosis in points with the help of the SYNTAX scale. Group One was composed of 207 patients with the SYNTAX score≤22 points (moderate lesion), Group Two comprised 89 patients with severe coronary atherosclerosis and the SYNTAX equalling 23-32 points, whereas 31 patients were included into Group Three with extremely severe lesion and the SYNTAX score>32 points. During 30 days and 12 months of follow up we assessed the effect of severity of coronary atherosclerosis on the outcomes of myocardial revascularization. The end points of the study were such unfavourable cardiovascular events as death, recurrent myocardial infarction (MI), secondary unplanned revascularization (SUR) of coronary arteries and in-stent thrombosis (IST). We obtained the findings suggesting that severity of the lesion of the coronary bed according to the SYNTAX scale>23 is associated with a decrease in the global myocardial contractility, increased incidence of postinfarction cardiosclerosis (PICS) and more pronounced manifestation of acute left ventricular insufficiency as compared to patients with moderately pronounced coronary atherosclerosis (SYNTAX<23 points). Characteristic features of patients with severe and utterly severe atherosclerotic lesions of the coronary bed were three-vessel lesions and a trend towards a decrease in the incidence rate of success of the primary PCI as compared with patients having moderate severity of coronary atherosclerosis. The prognostic significance of the SYNTAX score was evidenced both at the stage of the 30-day and 12-month period of follow up, which manifested itself in a considerable increase of frequency of fatal outcomes, in-stent thrombosis and the composite end point amongst patients with severity of the coronary bed lesion by the SYNTAX score>23 points. Thus, the SYNTAX scale developed and adapted for optimal choice of the method of revascularization in patients with stable coronary artery disease (CAD) may successfully be used for stratification of the risk and search for optimal strategies of treatment also amongst patients with STEMI in multivascular lesions of the coronary bed, subjected to urgent revascularization with the help of primary PCI.


Clinical relationship between cervical spinal canal stenosis and traumatic cervical spinal cord injury without major fracture or dislocation.
The purpose of the study was to evaluate the clinical relationship between cervical spinal canal stenosis (CSCS) and incidence of traumatic cervical spinal cord injury (CSCI) without major fracture or dislocation, and to discuss the clinical management of traumatic CSCI. Forty-seven patients with traumatic CSCI without major fracture or dislocation (30 out of 47 subjects; 63.83 %, had an injury at the C3-4 segment) and 607 healthy volunteers were measured the sagittal cerebrospinal fluid (CSF) column diameter at five pedicle and five intervertebral disc levels using T2-weighted midsagittal magnetic resonance imaging. We defined the sagittal CSF column diameter of less than 8 mm as CSCS based on the previous paper. We evaluated the relative and absolute risks for the incidence of traumatic CSCI related with CSCS. Using data from the Spinal Injury Network of Fukuoka, Japan, the relative risk for the incidence of traumatic CSCI at the C3-4 segment with CSCS was calculated as 124.5:1. Moreover, the absolute risk for the incidence of traumatic CSCI at the C3-4 segment with CSCS was calculated as 0.00017. In our results, the relative risk for the incidence of traumatic CSCI with CSCS was 124.5 times higher than that for the incidence without CSCS. However, only 0.017 % of subjects with CSCS may be able to avoid developing traumatic CSCI if they undergo decompression surgery before trauma. Our results suggest that prophylactic surgical management for CSCS might not significantly affect the incidence of traumatic CSCI.


Multiple forms of selection shape reproductive isolation in a primate hybrid zone.
Speciation occurs when populations diverge and become reproductively isolated from each other. Natural selection is commonly accepted to play a large role in this process, and it has been widely assumed that reproductive isolation often results as a by-product of divergence driven by adaptation in allopatry. When such populations come into secondary contact, reinforcement can act to strengthen reproductive isolation, but the frequency and importance of this process are still unknown. Here, we explored genomic signatures of selection in allopatry and sympatry for loci associated with reproductive isolation using a natural primate hybrid zone. By analysing reduced-representation sequencing data, we quantified admixture and population structure across a howler monkey hybrid zone and examined the relationship between locus-specific differentiation and introgression. We detected extensive admixture that was mostly limited to the narrow contact zone. Loci with reduced introgression into the heterospecific genomic background (the pattern expected for loci associated with reproductive isolation due to selection against hybrids) were significantly more differentiated between allopatric parental populations than loci with neutral and increased introgression, supporting the hypothesis that reproductive isolation is a by-product of divergence in allopatry. Further, loci with reduced introgression showed greater differentiation in sympatry than in allopatry, suggesting a role for reinforcement. Thus, our results reflect multiple forms of selection that have shaped reproductive isolation in this system. We conclude that reproductive isolation may have initially been driven by divergence in allopatry, but later reinforced by divergent selection in sympatry.


Spiritual needs experienced by the patient's family caregiver under Oncology palliative care.
To understand the spiritual needs of the patients' family caregiver under Oncology palliative care. A descriptive, qualitative study with 20 family caregivers of patients hospitalized in an Oncology palliative unit. The data were collected through a phenomenological interview, and analyzed by the method of Amadeo Giorgi supported in the Merleau-Ponty's Phenomenology of Perception. The categories were unveiled: "Spirituality as a foundation for life"; "Spiritual needs sublimated by the family caregiver"; and "Care expected by the nurse". Family caregivers appropriate spirituality as a coping strategy and meeting the purpose and meaning of the moment experienced. It is profitable for the nurse to contemplate the spiritual needs of the caregiver in order to provide a guided assistance in the humanization of care and comprehensive care. Therefore, there is a need for new studies that address this dimension to the family caregiver in the field of Oncology, since this care is incipient by the nurse.


Carboxyl-terminal repressor domain of MBP-1 is sufficient for regression of prostate tumor growth in nude mice.
Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of male cancer death in the United States. Early detection and improved procedures for surgical intervention and radiation therapy have reduced the fatalities; however, there is no effective cure for men with advanced disease and additional therapy is urgently needed. We have previously shown that MBP-1 acts as a general transcriptional repressor and exerts an antiproliferative effect on several human cancer cells. MBP-1 possesses two repressor domains, located at the amino and carboxyl termini. In this study, we have examined the potential of the repressor domains of MBP-1 as a gene therapeutic candidate in regression of prostate tumor growth. Our results suggested that replication-deficient adenovirus-mediated delivery of amino-terminal (MBP-AR) or carboxyl-terminal (MBP-CR) repressor domain of MBP-1 exerted an antiproliferative effect, like the full-length MBP-1, and induced caspase-independent apoptosis in prostate cancer cells. Next, we investigated the therapeutic effectiveness of MBP-1 repressor domain on prostate tumors. When tested in human tumor xenografts in nude mice, MBP-CR suppressed prostate tumor growth more effectively than full-length MBP-1, whereas MBP-AR delayed prostate tumor growth. Together, these results suggested that MBP-CR expression has an antiproliferative effect in human prostate cancer cells, being more effective than the full-length MBP-1 in preventing tumor growth.


Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti-angiogenic therapy: a report from the Children's Oncology Group Phase I Consortium.
Pre-clinical studies suggest that anti-angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti-angiogenic therapy. Targeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti-cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti-angiogenic effects (n = 35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n = 13), or angiopoietin (n = 5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow-up radiographs were obtained after odd-numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3. Baseline and follow-up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n = 1] or pazopanib [n = 4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible. Growth plate abnormalities occur in a small, but relevant number of patients undergoing anti-angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti-angiogenic therapy, and for improved methods to assess toxicity of anti-angiogenic agents to the developing skeleton.


Pneumothorax with liposuction, awareness of rare complication: a case report.
Liposuction is the most commonly performed procedure in aesthetic plastic surgery worldwide, the complications and morbidity are under evaluated. Pneumothorax is thought to be a rare complication after liposuction but the exact rate still unknown. We presented to you a 45-year-old Arabian female with history of hypertension underwent lipoabdominoplasty, back liposuction and gluteal lipofilling. On the first postoperative day, the patient was complaining of chest pain accompanied with tachypnea and tachycardia, oxygen saturation was maintained on room air. Upon chest auscultation, diminished air entry was markedly noted on her left side, immediate chest x-ray and electrocardiogram (ECG) was done, which showed unremarkable x-ray and ECG shows sinus tachycardia. Computed tomography (CT) carried out and showed left side pneumothorax. An urgent thoracic surgery consultation was done and chest tube was inserted. The patient reported immediate improvement of her symptoms and the vital signs retain to normal range. On day 3, air leak stopped, chest tube was clipped by thoracic surgery, and the chest tube was removed 24 h later. The patient had a relatively smooth recovery with no other complications. Pneumothorax have possibility to happen with liposuction, awareness of possible risk factors should detect by plastic surgeon, to manage earlier as soon as possible.


Analysis of osteonecrosis following Pemberton acetabuloplasty in developmental dysplasia of the hip: long-term results.
The favorable results of Pemberton acetabuloplasty in children with developmental dysplasia of the hip have been well reported. We reviewed our long-term results related to osteonecrosis of the femoral head after this surgery, especially with regard to the effect of excessive inferior displacement of the femoral head. From 1993 to 1997, we performed 167 Pemberton acetabuloplasties in patients with developmental dysplasia of the hip who were eighteen months of age or older. Patients who had had prior treatment or developmental dysplasia of the hip due to neuromuscular disease were excluded. We selected patients who had unilateral developmental dysplasia of the hip, had undergone simultaneous open reduction and Pemberton acetabuloplasty between the ages of eighteen and thirty-six months, and had been followed for a minimum of ten years. Forty-nine patients met these criteria. The patients were divided into osteonecrosis-absent and osteonecrosis-present groups according to the criteria described by Kalamchi and MacEwen. Preoperative, interim follow-up and final radiographs were available for evaluation, as were the results of clinical examination. We used the femoral head inferior displacement percentage, measured on the radiographs, to quantify the amount of excessive correction postoperatively. Outcomes were measured with use of the McKay criteria and the Severin criteria. The mean age at the time of surgery was 20.8 months, and the mean duration of follow-up was 134.6 months. Twenty-four patients (49%) were classified as not having osteonecrosis (the osteonecrosis-absent group) and twenty-five patients (51%), as having osteonecrosis (the osteonecrosis-present group). There were no significant differences between the two groups in terms of sex, age, laterality, Tönnis grade, or preoperative acetabular index. Seven of the cases of osteonecrosis were type I, thirteen were type II, one was type III, and four were type IV. The inferior displacement percentage revealed significant differences between the two groups (p < 0.0001). In the osteonecrosis-absent group, 96% of the patients had a radiographically satisfactory result (Severin class I or II); however, only 76% of the patients in the osteonecrosis-present group had a radiographically satisfactory result (p < 0.0001). According to the McKay criteria, there were significant clinical differences between the groups (p < 0.0001). Our results showed significant correlation between excessive reduction of the femoral head and the development of osteonecrosis. In light of the high prevalence of type-II osteonecrosis, we postulated that the lateral epiphyseal branch of the medial circumflex artery was vulnerable to compression with increased inferior displacement of the femoral head. The latest radiographic and functional results corresponded to the severity of the osteonecrosis.


Intravascular bronchiolo-alveolar tumor (IVBAT): A low-grade sclerosing epithelioid angiosarcoma of lung.
Intravascular bronchiolo-alveolar tumor (IVBAT) is a rare and highly distinctive pulmonary tumor of disputed cellular nature. Both epithelial and endothelial differentiation of this neoplasm have been suggested. We have studied multiple nodules of IVBATs from three patients by light and electron microscopy and by immunohistochemical methods for Factor VIII-related antigen (FVIII RAG). Our light and ultrastructural studies are in essential agreement with the previous suggestion of the endothelial nature of the neoplasm and our demonstration of the presence of FVIII RAG in many of the tumor cells offers new evidence strongly supportive of their endothelial differentiation. We believe that IVBAT and a group of extrapulmonary tumors described as epithelioid hemangioendothelioma and endovascular papillary angioendothelioma are similar biologically indolent neoplasms of epithelioid and dendritic endothelial cells characterized by stromal sclerosis, intravascular spread, a low incidence of metastases and slow clinical evolution. Thus, we regard IVBAT as a low-grade sclerosing angiosarcoma of the lung.


Effects of obesity treatment on female reproduction: results do not match expectations.
The adverse effects of obesity of female reproduction have been extensively documented. However, there are few prospective studies that have examined preconception weight loss interventions. There is a need to develop successful interventions with significant weight loss and compliance and most importantly document the effects of preconception interventions on important perinatal outcomes such as live birth and the health of the infant and mother. The existing data from randomized trials that come closest to meeting these criteria have failed to document improved live-birth rates after the intervention compared with control groups. There is a tendency to equate favorable weight change both before and during pregnancy with a direct qualitative improvement in all perinatal outcomes, yet the results from the most successful treatment of morbid obesity, that is, bariatric surgery, with on average 40% weight loss, suggest a mixed risk-benefit ratio on perinatal outcomes. Although interventions to control gestational weight gain have been more completely studied than preconception ones, and have documented successful interventions to achieve appropriate weight gain, there is no clear evidence that controlling gestational weight gain actually improves any important perinatal outcome. Future studies must develop more successful and effective interventions, capture perinatal outcomes instead of weight change as the primary outcomes, use, at least preconception, new antiobesity drugs (in combination with other therapies), and study bariatric surgery in prospective trials to improve our understanding of the effectiveness of obesity treatment before pregnancy.


Secondary Metabolites from the Leaves of the Medicinal Plant Goldenseal (Hydrastis canadensis).
The study presented herein constitutes an extensive investigation of constituents in Hydrastis canadensis L. (Ranunculaceae) leaves. It describes the isolation and identification of two previously unknown compounds, 3,4-dimethoxy-2-(methoxycarbonyl)benzoic acid (1) and 3,5,3'-trihydroxy-7,4'-dimethoxy-6,8-C-dimethyl-flavone (2), along with the known compounds (±)-chilenine (3), (2R)-5,4'-dihydroxy-6-C-methyl-7-methoxy-flavanone (4), 5,4'-dihydroxy-6,8-di-C-methyl-7-methoxy-flavanone (5), noroxyhydrastinine (6), oxyhydrastinine (7) and 4',5'-dimethoxy-4-methyl-3'-oxo-(1,2,5,6-tetrahydro-4H-1,3-dioxolo-[4',5':4,5]-benzo[1,2-e]-1,2-oxazocin)-2-spiro-1'-phtalan (8). Compounds 3-8 have been reported from other sources, but this is the first report of their presence in H. canadensis extracts. A mass spectrometry based assay was employed to demonstrate bacterial efflux pump inhibitory activity against Staphylococcus aureus for 2, with an IC50 value of 180 ± 6 μM. This activity in addition to that of other bioactive compounds such as flavonoids and alkaloids, may explain the purported efficacy of H. canadensis for treatment of bacterial infections. Finally, this report includes high mass accuracy fragmentation spectra for all compounds investigated herein which were uploaded into the Global Natural Products Social molecular networking library and can be used to facilitate their future identification in H. canadensis or other botanicals.


Effects of omega-3 polyunsaturated Fatty acids on heart function and oxidative stress biomarkers in pediatric patients with dilated cardiomyopathy.
Dilated cardiomyopathy is the most prevalent type of cardiomyopathy in children, which results in congestive heart failure and causes significant morbidity and mortality. This study, aims to investigate the effect of supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) on heart function and oxidative stress biomarkers in these patients. The present research was a case-control study on pediatric patients with dilated cardiomyopathy, who received n-3 PUFA and anti-failure therapy for 6 months (group 1, n = 6), or anti-failure therapy alone for 6 months (group 2, n = 6), as well as age matched normal individuals (group 3, n = 6), and evaluated the cardiac function and biomarkers of oxidative stress. Echocardiographic parameters, such as left ventricular ejection fraction, shortening fraction, tissue Doppler Ea and Aa waves of lateral annulus of tricuspid valve, and Ea and S wave of septum, were significantly improved in group 1 after n-3 PUFA compared to pre- treatment status, while they were not changed after treatment in group 2. Antioxidant enzymes, including catalase and glutathione peroxidase activities in erythrocytes were slightly decreased, while plasma 8-iso-prostaglandin F2α concentrations were somewhat increased in group 1 compared to groups 2 and 3, however these changes were not statistically significant. Total antioxidant capacity of plasma was similar in all 3 groups. The results indicate that some echocardiographic parameters were significantly improved in patients receiving omega-3 fish oil. However, omega-3 had no significant effect on oxidative stress biomarkers.


Atheroprotective Vaccination with MHC-II Restricted Peptides from ApoB-100.
Subsets of CD4(+) T-cells have been proposed to serve differential roles in the development of atherosclerosis. Some T-cell types are atherogenic (T-helper type 1), while others are thought to be protective (regulatory T-cells). Lineage commitment toward one type of helper T-cell versus another is strongly influenced by the inflammatory context in which antigens are recognized. Immunization of atherosclerosis-prone mice with low-density lipoprotein (LDL) or its oxidized derivative (ox-LDL) is known to be atheroprotective. However, the antigen specificity of the T-cells induced by vaccination and the mechanism of protection are not known. Identification of two peptide fragments (ApoB3501-3516 and ApoB978-993) from murine ApoB-100 was facilitated using I-Ab prediction models, and their binding to I-Ab determined. Utilizing a vaccination scheme based on complete and incomplete Freund's adjuvant (CFA and IFA) [1 × CFA + 4 × IFA], we immunized Apoe(-/-)mice with ApoB3501-3516 or ApoB978-993 emulsified in CFA once and subsequently boosted in IFA four times over 15 weeks. Spleens, lymph nodes, and aortas were harvested and evaluated by flow cytometry and real time RT-PCR. Total atherosclerotic plaque burden was determined by aortic pinning and by aortic root histology. Mice immunized with ApoB3501-3516 or ApoB978-993 demonstrated 40% reduction in overall plaque burden when compared to adjuvant-only control mice. Aortic root frozen sections from ApoB3501-3516 immunized mice showed a >60% reduction in aortic sinus plaque development. Aortas from both ApoB3501-3516 and ApoB978-993 immunized mice contained significantly more mRNA for IL-10. Both antigen-specific IgG1 and IgG2c titers were elevated in ApoB3501-3516 or ApoB978-993 immunized mice, suggesting helper T-cell immune activity after immunization. Our data show that MHC Class II restricted ApoB-100 peptides can be atheroprotective, potentially through a mechanism involving elevated IL-10.


Assessing the Effect of Diesel Fuel on the Seed Viability and Germination of Medicago sativa Using the Event-Time Model.
The remediation of contaminated sites using plant-based techniques has gained increasing attention in recent decades. However, information on the effects of contaminant imbibition on seed viability and germination rates are often lacking in the literature. To this end, our research investigated, by means of an event-time model, the effect of diesel fuel imbibition on the seed viability and germination rate of Medicago sativa, a plant species with great potential for remediation of organic contaminants. The event-time model provided an accurate and biologically relevant method for analysing germination data. Our results reveal that the direct imbibition of diesel fuel by M. sativa seeds for ≤48 h, or their exposure to soil diesel fuel concentrations of 0-10 g/kg diesel fuel, affects their germination rates, as shown by increasing t50 values from 90.6 (±2.78) to 114.2 (±2.67) hours, without significantly affecting seed viability. On the other hand, diesel fuel imbibition of longer duration, or the exposure of M. sativa seeds to ≥20 g/kg diesel fuel-contaminated soils, leads to no further effect on time to seed emergence. Instead, these conditions compromise seed viability, resulting in a decrease in the proportion of germinated seeds from 0.91 (±0.03) in 10 g/kg diesel fuel contaminated soil to 0.84 (±0.04) and 0.70 (±0.05) in 20 and 30 g/kg diesel fuel-contaminated soils, respectively. The fact that low concentrations of diesel fuel and 0-48 h of direct imbibition delayed seed emergence without adversely affecting the percentage of viable seeds suggests that this inhibitory effect on germination at low diesel fuel exposure could be attributed more to physical constraints rather than biological damage on the seeds. The models used in this study provide an accurate and biologically relevant method for the analyses of germination data. This is vital since expensive germination experiments, be it in the field of toxicology or agriculture, deserve to be accurately analysed.


Synthesizing the effects of mental simulation on behavior change: Systematic review and multilevel meta-analysis.
Mental simulation of future scenarios is hypothesized to affect future behavior, but a large and inconsistent literature means it is unclear whether, and under what conditions, mental simulation can change people's behavior. A meta-analysis was conducted to synthesize the effects of mental simulation on behavior and examine under what conditions mental simulation works best. An inclusive systematic database search identified 123 (N = 5,685) effect sizes comparing mental simulation to a control group. After applying a multilevel random effects model, a statistically-reliable positive effect of Hedges' g = 0.49, 95% CI [0.37; 0.62] was found, which was significantly different than zero. Using a taxonomy to identify different subtypes of mental simulation (along two dimensions, class [process, performance, outcome] and purpose [whether an inferior, standard, superior version of that behavior is simulated]), it was found that superior simulations garnered more reliable beneficial effects than inferior simulations. These findings have implications for integrating theories of how mental simulations change behavior, how mental simulations are classified, and may help guide professionals seeking evidence-based and cost-effective methods of changing behavior.


New electrophysiological assessments for the early diagnosis of encephalopathy and peripheral neuropathy in chronic uraemia.
The clinical manifestations of neuropathy in chronic uraemia are late in occurring. However, at an early stage it is possible to detect damage to either the central or peripheral nervous system by means of modern electrophysiological investigation methods. We examined 29 patients with CRF (plasma creatinine 7.0 +/- 4.0 mg%) on conservative diet. The following electrophysiological tests were carried out at least once: Electroencephalogram (EEG), Electromyogram (EMG), Motor Nerve Conduction Velocity (MNCV), Sensory Nerve Conduction Velocity (SNCV), Visual Evoked Potentials (VEPs) using the pattern reversal transient stimulation method. At the same time the following blood tests were performed: BUN, creatinine, uric acid, glucose, cholesterol, triglycerides, lipid electrophoresis, total protein (electrophoretic method), Na, K, Ca, P, red cells blood count and PTH. MNCV, SNCV and VEPs appeared to slow down early, sometimes even where there were no clinical symptoms. In addition, there is a direct correlation with decreasing renal function. MNCV and SNCV were correlated directly, reciprocally although the compromise of SNCV appeared an earlier phenomenon. The significant direct correlation between MNCV, SNCV and serum PTH suggests that the latter has an important peripheral neurotoxic role. VEP recording permits detection of early abnormalities in the central nervous system with residual renal function values around 40%.


Regulation of luteal activity in adult female rats treated neonatally with testosterone propionate.
The present study was concerned with the control of luteal activity in female rats which had been treated neonatally with 1.25 mg testosterone propionate (TP). Treatment of such rats in adulthood with 15 i.u. human chorionic gonadotrophin induced ovulation followed by a period of luteal activity. The two daily surges of prolactin secretion, typical for a period of luteal activity in the normal female rat, were not observed in TP-treated females. Instead, higher basal levels of prolactin were observed in TP-treated females than in normal female rats. Furthermore, uterine traumatization at 5 days after ovulation did not result in the formation of decidual tissue. In intact TP-treated females luteal activity, induced and temporarily sustained by an ectopic pituitary transplant, persisted after removal of the pituitary graft. In contrast, in TP-treated females which had been ovariectomized on day 25 of age and had received an ovarian transplant before induction of the luteal phase, luteal activity ended within a week after removal of the ectopic pituitary gland. Females treated with TP which had been ovariectomized on day 25 of life had lower plasma levels of prolactin and higher levels of dopamine in hypophysial stalk plasma than intact TP-treated females when measured at 4 months of age. Treatment of ovariectomized rats with oestradiol-17 beta increased levels of prolactin in plasma and lowered levels of dopamine in hypophysial stalk plasma. It is concluded that the control of luteal activity in TP-treated females shows 'male' characteristics. However, the presence of the ovaries in such rats leads to decreased hypothalamic release of dopamine and increased plasma levels of prolactin, probably due to increased oestrogen levels. These increased levels of prolactin are sufficient to maintain luteal activity.


Cholinergic-mediated bronchoconstriction induced by prostaglandin D2, its initial metabolite 9 alpha,11 beta-PGF2, and PGF2 alpha in asthma.
In this study, we have investigated the contribution of cholinergic-mediated bronchoconstriction in the airway response provoked by inhaled prostaglandin (PG)D2, its metabolite 9 alpha, 11 beta-PGF2, and PGF2 alpha, which are generated during mast cell activation in vivo and are potent bronchoconstrictor agonists in humans. The effect of prior inhalation of 1 mg ipratropium bromide (IB) on the bronchoconstrictor response to inhaled methacholine (MCh), PGD2, 9 alpha, 11 beta-PGF2, and PGF2 alpha was determined in 7 allergic asthmatic subjects by measuring changes in SGaw, FEV1, and Vmax30. Methacholine, PGD2, and 9 alpha, 11 beta-PGF2 caused concentration-related bronchoconstriction with PGD2 and 9 alpha, 11 beta-PGF2 being between 45 and 112 times more potent than MCh (p less than 0.05), depending on the method used to measure airway caliber. Preinhalation of IB displaced the concentration response curves to MCh between 69- and 196-fold to the right, and this was significantly greater than that observed with PGD2 (12- to 23-fold, p less than 0.02) and 9 alpha, 11 beta-PGF2 (12- to 22-fold, p less than 0.02). Ipratropium bromide inhibited the bronchoconstriction achieved with the highest concentration of agonist by 73 to 91% with MCh, 46 to 79% with PGD2, and 32 to 38% with 9 alpha, 11 beta-PGF2. Ipratropium bromide did not affect the bronchoconstriction pattern to inhaled PGF2 alpha, irrespective of the nature of the response. We conclude that although PGD2 and 9 alpha, 11 beta-PGF2 are potent contractile agonists of human smooth muscle in vitro, bronchoconstriction observed with these mediators in vivo results from a combination of both direct and cholinergic-mediated mechanisms.


Comparison of nerve cell and nerve cell plus Schwann cell cultures, with particular emphasis on basal lamina and collagen formation.
The availability of cultures of normal cells (NCs) and Schwann cells (SCs) with and without fibroblasts has allowed us to investigate the sources of endoneurial and perineurial constituents of peripheral nerve. NCs cultured alone, devoid of ensheathment but healthy in appearance, lack basal lamina and extracellular fibrils. In contrast, when SCs accompany NCs, basal lamina and extracellular fibrils are consistently visible around SCs in outgrowth areas formed de novo in culture. These fibrils average 18 nm in diameter, exhibit a repeating banding pattern, and are trypsin-resistant and collagenase-sensitive. Collagen synthesis is also indicated by the incorporation of [14C]proline into peptide-bound hydroxy-proline in NC + SC or SC cultures. That the [14C]hydroxyproline polypeptides formed in NC + SC cultures are collagenous was determined in part by pepsin digestion-ammonium sulfate precipitation-polyacrylamide gel electrophoresis techniques; the 14C-polypeptides migrate to the positions of alpha 1 (I), alpha 2, alpha 1 (III), and alpha B chains of type I, type III, and A-B collagens. Also formed are thin, ruthenium red-preserved strands interconnecting basal laminae. SC ensheathment of axons is similar to that found in the animal; one SC is related to a number of unmyelinated axons or a single myelinated axon. This proclivity to ensheathe and myelinate axons indicates that SC function is not lost during the preparative procedures or after lengthy isolation in culture and provides the most reliable means for SC identification. Perineurial ensheathment and macrophages are lacking in NC + SC culture preparations divested of fibroblasts. We conclude that SCs do not form perineurium or the larger diameter collagen fibrils typical of endoneurium but that in combination with neurons they generate biochemically detectable collagens and morphologically visible basal lamina and thin collagenous fibrils.