Remodeling of insulin producing beta-cells during Xenopus laevis metamorphosis.
Insulin-producing beta-cells are present as single cells or in small clusters distributed throughout the pancreas of the Xenopus laevis tadpole. During metamorphic climax when the exocrine pancreas dedifferentiates to progenitor cells, the beta-cells undergo two changes. Insulin mRNA is down regulated at the beginning of metamorphic climax (NF62) and reexpressed again near the end of climax. Secondly, the beta-cells aggregate to form islets. During climax the increase in insulin cluster size is not caused by cell proliferation or by acinar-to-beta-cell transdifferentiation, but rather is due to the aggregation of pre-existing beta-cells. The total number of beta-cells does not change during the 8 days of climax. Thyroid hormone (TH) induction of premetamorphic tadpoles causes an increase in islet size while prolonged treatment of tadpoles with the goitrogen methimazole inhibits this increase. Expression of a dominant negative form of the thyroid hormone receptor (TRDN) driven by the elastase promoter not only protects the exocrine pancreas of a transgenic tadpole from TH-induced dedifferentiation but also prevents aggregation of beta-cells at climax. These transgenic tadpoles do however undergo normal loss and resynthesis of insulin mRNA at the same stage as controls. In contrast transgenic tadpoles with the same TRDN transgene driven by an insulin promoter do not undergo down regulation of insulin mRNA, but do aggregate beta-cells to form islets like controls. These results demonstrate that TH controls the remodeling of beta-cells through cell-cell interaction with dedifferentiating acinar cells and a cell autonomous program that temporarily shuts off the insulin gene.


Ionic mechanisms of action of neurotensin in acutely dissociated neurons from the diagonal band of Broca of the rat.
Whole cell recordings were performed on acutely dissociated neurons from the horizontal limb of the diagonal band of Broca (hDBB) from rats to elucidate the ionic mechanisms of action of neurotensin. Neurotensin caused a decrease in whole cell voltage-activated outward currents and failed to elicit a response when Ca2+ influx was blocked by changing the external solution to the one containing 0 mM Ca2+ and 50 microM Cd2+, suggesting the involvement of Ca2+-dependent conductances. Charybdotoxin, a specific blocker of voltage-sensitive calcium-activated K+ channels (IC), caused a decrease in outward currents comparable with that caused by blocking calcium influx and occluded the neurotensin-induced decrease in outward currents. Similarly, 50 microM tetraethylammonium ions also blocked the neurotensin response. Also neurotensin reduced whole cell barium currents (IBa) and calcium currents (ICa). Amiloride and omega-conotoxin GVIA, but not nimodipine, were able to eliminate the neurotensin-induced decrease in IBa. Thus T- and N- but not L-type calcium channels are subject to modulation by neurotensin, and this may account for its effects on IC. The predicted changes in action potential as a result of the blockade of currents through calcium channels culminating into changes in IC were confirmed in the bridge current-clamp recordings. Specifically, neurotensin application led to depolarization of the resting membrane potential, broadening of spike and a decrease in afterhyperpolarization and accommodation. These alterations in action potential characteristics that resulted in increased firing rate and excitability of the hDBB neurons also were produced by application of charybdotoxin. Neurotensin effects on these properties were occluded by 2 - [(1 - 7 - chloro - 4 - quinolinyl) - 5 - (2, 6 - di - methoxyphenyl) pyrazol-3-yl) carbonylamino] tricyclo (184.108.40.206.)decan-2-carboxylic acid, a nonpeptide high-affinity neurotensin receptor antagonist. Neurotensin blockade of IC, possibly through ICa, is a potential physiological mechanism whereby this peptide may evoke alterations in the cortical arousal, sleep-wake cycle, and theta rhythm.


An extended river buffalo (Bubalus bubalis, 2n = 50) cytogenetic map: assignment of 68 autosomal loci by FISH-mapping and R-banding and comparison with human chromosomes.
We report an extended river buffalo (Bubalus bubalis, 2n = 50; BBU) cytogenetic map including 388 loci, of which 68 have been FISH-mapped on autosomes in the present study. Ovine and caprine BAC clones containing both type I loci (known genes) and type II loci (simple sequence repeats (SRs), microsatellite marker, sequence-tagged sites (STSs)), previously assigned to sheep chromosomes, have been localized on R-banded river buffalo chromosomes (BBU), which expands the cytogenetic map of this important domestic species and increases our knowledge of the physical organization of its genome. The loci mapped in the present study correspond to loci already localized on homoeologous cattle (and sheep) chromosomes and chromosome bands, further confirming the high degree of chromosome homoeologies among bovids. The comparison of the integrated cytogenetic maps of BBU2p/BBU10 and BBU5p/BBU16 with those of human chromosomes (HSA) 6 and 11, respectively, identified, at least, nine conserved chromosome segments in each case and complex rearrangements differentiating river buffalo (and cattle) and human chromosomes.


[Retrospective study of a series of 26 carcinomatous meningitis secondary to lung cancer].
Carcinomatous meningitis occur in approximately 5 to 18% of bronchial carcinoma. We report here the analysis of a retrospective study of 26 cases of carcinomatous meningitis secondary to a bronchial carcinoma. The most frequently involved histological types are adenocarcinoma and small cell lung cancer. The diagnosis is difficult because of the clinical polymorphism and the inconstant presence of neoplasic cells in the cerebrospinal fluid. The prognosis is very poor with a median survival time of 4 weeks. Development of new molecules as well as an earlier diagnosis could contribute to improve the outcome.


Pigmented coalescing papules on the dorsa of the hands: pigmented colloid milium associated with exogenous ochronosis.
Colloid milium is a rare cutaneous deposition disorder that frequently occurs in areas of chronic sun exposure such as the face, neck and backs of the hands and is characterized by multiple small, discrete, usually amber-colored, dome-shaped papules that cluster to form large plaques. A 50-year-old white woman with esophageal squamous cell carcinoma was referred to us with asymptomatic, slowly spreading lesions localized to the dorsa of her hands which had been present for 4 years. The condition was diagnosed histopathologically as pigmented colloid milium associated with exogenous ochronosis (EO). Colloid milium associated with EO is very rarely reported in the published work. We think that a possible interaction between sunlight and exposure to chemical fertilizers may have played a role in the pathogenesis of both of the disorders in our case.


Does carotid intima media thickness indicate coronary atherosclerosis?
Increased carotid intima media thickness (IMT) is relatively simple, inexpensive, and reproducible noninvasive marker of global atherosclerotic disease. It is a frequently used experimental tool in epidemiologic studies to identify and follow cardiovascular disease. There is evidence that early detection of atherosclerotic disease processes and subsequent therapeutic interventions significantly alter the natural course of the disease. Several large prospective studies have evaluated the usefulness of ultrasonographic measurement of IMT and have demonstrated its role in predicting future cardiovascular events. This article will focus on the relation between carotid artery IMT and coronary heart disease, and its utility and limitations in predicting cardiovascular events.


Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model.
Gene expression is modulated by multiple mechanisms, including genetic and/or epigenetic regulation, and associated with the processes of cellular differentiation and morphogenesis. Single nucleotide polymorphisms (SNPs) and DNA methylation play important roles in regulating gene expression. In this study, we focused on revealing the relationship between SNPs, DNA methylation and gene expression in two human populations genome-wide through proposing four regulation patterns and developed maximum likelihood estimate models. Using simulated data with different correlation coefficients between any two traits, the power of our approach showed a favourable performance and relative stability. In all, 6733 SNP-CpG-gene pairs including 957 genes were obtained in Northern European ancestry (CEU) population. As the results showed, SNPs and DNA methylation had approximately the same effect on expression regulation of 49% genes, which was termed cooperative/antagonistic regulation pattern. Less than 30% of genes are controlled only by one of the factors (SNP/DNA methylation). The others showed SNPs that affect methylation have no consequent effects or crosstalk regulation on gene expression. Similar result was shown in Yourba (YRI) population. Specific genes were inferred using the different mechanisms of gene regulation involved in complex diseases by combining literature. This approach provides a method to comprehensively assess regulation patterns of gene expression in the whole genome.


Direct observation of ferrielectricity at ferroelastic domain boundaries in CaTiO3 by electron microscopy.
High-resolution aberration-corrected transmission electron microscopy aided by statistical parameter estimation theory is used to quantify localized displacements at a (110) twin boundary in orthorhombic CaTiO(3). The displacements are 3-6 pm for the Ti atoms and confined to a thin layer. This is the first direct observation of the generation of ferroelectricity by interfaces inside this material which opens the door for domain boundary engineering.


Dispersal in heterogeneous environments drives population dynamics and control of tsetse flies.
Spatio-temporally heterogeneous environments may lead to unexpected population dynamics. Knowledge is needed on local properties favouring population resilience at large scale. For pathogen vectors, such as tsetse flies transmitting human and animal African trypanosomosis, this is crucial to target management strategies. We developed a mechanistic spatio-temporal model of the age-structured population dynamics of tsetse flies, parametrized with field and laboratory data. It accounts for density- and temperature-dependence. The studied environment is heterogeneous, fragmented and dispersal is suitability-driven. We confirmed that temperature and adult mortality have a strong impact on tsetse populations. When homogeneously increasing adult mortality, control was less effective and induced faster population recovery in the coldest and temperature-stable locations, creating refuges. To optimally select locations to control, we assessed the potential impact of treating them and their contribution to the whole population. This heterogeneous control induced a similar population decrease, with more dispersed individuals. Control efficacy was no longer related to temperature. Dispersal was responsible for refuges at the interface between controlled and uncontrolled zones, where resurgence after control was very high. The early identification of refuges, which could jeopardize control efforts, is crucial. We recommend baseline data collection to characterize the ecosystem before implementing any measures.


Direct to Consumer Telemedicine: Is Healthcare From Home Best?
Direct-to-consumer (DTC) telemedicine is increasingly popular and enables patients to obtain medical advice and treatment via electronic media (e.g., computer, telephone, or smartphone) without a prior doctor-patient relationship. Convenience, accessibility, and home delivery make DTC telemedicine attractive to patients. Concerns about DTC telemedicine include: a lack of regulation, transparency, and an established patient-provider relationship (physician and pharmacist). In future, researchers, providers, and insurers need to better understand the concerns and challenges that this new form of healthcare poses.


[Effects of Bushen Jiedu Recipe and Jianpi Jiedu Recipe containing plasma on dendritic cells of chronic hepatitis B virus infection patients under different immune states].
To compare the effects of Bushen Jiedu Recipe (BJR) and Jianpi Jiedu Recipe (JJR) containing plasma on dendritic cells (DCs) of chronic hepatitis B virus (HBV) infection patients under different immune states. Recruited were 36 chronic HBV infection outpatients from First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from April 2010 to January 2011. They were assigned to the immune tolerance group (18 cases) and the immune clearance group (18 cases).Another 10 healthy subjects were recruited as the healthy control group. Their anticoagulated peripheral venous blood was respectively collected. The peripheral blood mononuclear cells (PBMCs) were isolated and further extracted for incubating DCs. The DCs were intervened by BJR and JJR containing plasma. The morphology of DCs was identified. The expressions of CD1alpha, CD80, CD86, and HLA-DR were detected. The level of interferon-alpha (IFN-alpha) in the supernatant was observed by ELISA. The CD80 expression level was lower in the immune clear group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, CD86, and HLA-DR were lower in the immune tolerance group than in the healthy control group before intervention (P < 0.05).The IFN-alpha expression level was lower in the immune tolerance group and the immune clearance group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, HLA-DR, and IFN-alpha were lower in the immune tolerance group than in the immune clearance group before intervention (P < 0.05). Compared with the same group before intervention, the CD80 expression significantly increased in each treatment group (P < 0.05). After intervention the expression levels of CD80 and HLA-DR were higher in the immune tolerance group than in the immune clearance group in the same time phase, and the CD86 expression level was higher in the BJR group than in the immune clearance group in the same time phase, showing statistical difference (P < 0.05). The middle dose BJR and the small dose JJR both could promote the recovery of DCs in chronic HBV infection patients. Besides, BJR showed more prominent effects on the function of DCs in chronic HBV infection patients in the immune tolerance stage.


Work-related risk factors of myocardial infarction.
The aim of the study was to find out which occupational factors account for the risk of the myocardial infarction. A questionnaire survey was performed during the period of one calendar year in all patients (1053 subjects, 692 men and 361 women) hospitalized at the Medical University of Łódź because of the first myocardial infarction. The questionnaire was prepared especially for the purpose of this study and consisted of two parts. The first part comprised: demographic data, health status at admittance, traditional risk factors for the ischaemic heart disease and was filled-in by physicians. Part II was done by occupational hygiene specialists and referred to education, job title and characteristics, employment data, self assessment of work-related and general stress, fatigue, socio-economic status, physical activity, alcohol intake, tobacco smoking, dietary habits. Mean age in the study group was 59.9 ± 10.4 years (26-85 years), 58.7 ± 10.0 (26-84 years) for men and 62.3 ± 10.7 (32-85 years) for women, employment duration was 32.9±8.8 (4-65 years), for men 34.0 ± 8.6 (5-65 years), for women 30.7 ± 8.8 (4-60 years. Most of myocardial infarction cases both in the group of men and women were noted in the age interval 56-60 years, 22.3% vs. 17.4%, respectively. The majority of examined men were farmers, low and middle management and self-employed workers. Among women prevailed clerks, seamstresses and farmers. The most frequent occupational risk factors were: work-related stress, experienced by 54.2% of the examined subjects, occupational noise (45,5%), dust (41,7%) and various chemical factors (33%). A majority of the study group (76.5% women and 54.4% men) linked the cardiac infarction with stress, while 39.1% men vs. 16.5% women correlated it with physical effort. Our studies indicate that, among a wide spectrum of occupational factors, stress, noise and fine particulate dust are major contributors to the increased risk of myocardial infarction.


Astragaloside IV inhibits Angiotensin II-stimulated proliferation of rat vascular smooth muscle cells via the regulation of CDK2 activity.
Astragaloside IV (AS-IV) is the central active component extracted from Radix astragali, an herbal remedy widely used in traditional Chinese medicine for the treatment of cardiovascular diseases. Aberrant proliferation of vascular smooth muscle cells (VSMCs) is closely involved in the initiation and progression of cardiovascular complications, such as atherosclerosis. Here we investigated whether AS-IV inhibited agonist-induced vascular smooth muscle cells (VSMCs) proliferation and the underlying mechanism. Quiescent cultured A10 cells (adult rat VSMCs) were treated with Angiotensin II (AngII) or AngII plus AS-IV for 48 h. The growth rate of A10 cells was analyzed by CCK8 assay. RT-PCR analysis was carried out to examine the expression of α-smooth muscle actin (α-SMA), an important phenotypic modulation marker. In addition, whether the interference of AS-IV on AngII-mediated growth of VSMCs via regulation of cell cycle was evaluated by flow cytometry. In order to explore the role of cell cycle machinery, we measured kinase activity of CDK2 by Kinase assay and the protein level of Cdc25 by western blot, respectively. These data suggested that AS-IV exerted beneficial effects on AngII -induced abnormal growth in rat VSMCs through disturbing cell cycle, especially block G1/S transition by attenuating CDK2 activity, which may hinder the process of pathological vascular remodeling during atherosclerosis.


Miniature inverted-repeat transposable elements: discovery, distribution, and activity.
Eukaryotic organisms have dynamic genomes, with transposable elements (TEs) as a major contributing factor. Although the large autonomous TEs can significantly shape genomic structures during evolution, genomes often harbor more miniature nonautonomous TEs that can infest genomic niches where large TEs are rare. In spite of their cut-and-paste transposition mechanisms that do not inherently favor copy number increase, miniature inverted-repeat transposable elements (MITEs) are abundant in eukaryotic genomes and exist in high copy numbers. Based on the large number of MITE families revealed in previous studies, accurate annotation of MITEs, particularly in newly sequenced genomes, will identify more genomes highly rich in these elements. Novel families identified from these analyses, together with the currently known families, will further deepen our understanding of the origins, transposase sources, and dramatic amplification of these elements.


Vitamin D and topical therapy.
A sequential therapy regimen involving an initial clearing phase of daily applications of calcipotriene 0.005% ointment and halobetasol 0.05% ointment for 2 weeks, followed by halobetasol applied twice daily on weekends and calcipotriene applied twice daily on weekdays, has been shown to be effective in the management of chronic plaque psoriasis. As a clearing regimen, the combined use of halobetasol and calcipotriene for 2 weeks was superior to monotherapy with either agent. Subsequently, the use of halobetasol on weekends and calcipotriene on weekdays allowed 76% of patients to stay in remission for up to 6 months, compared with 40% of patients who applied halobetasol on weekends only and placebo on weekdays. Calcipotriene can be inactivated when mixed with some topical preparations; however, halobetasol propionate 0.05% ointment and cream have been shown to be compatible with calcipotriene for up to 2 weeks. The compatibility of calcipotriene and halobetasol permits the use of these agents together.


Reproductive Stage Drought Tolerance in Wheat: Importance of Stomatal Conductance and Plant Growth Regulators.
Drought stress requires plants to adjust their water balance to maintain tissue water levels. Isohydric plants ('water-savers') typically achieve this through stomatal closure, while anisohydric plants ('water-wasters') use osmotic adjustment and maintain stomatal conductance. Isohydry or anisohydry allows plant species to adapt to different environments. In this paper we show that both mechanisms occur in bread wheat (Triticum aestivum L.). Wheat lines with reproductive drought-tolerance delay stomatal closure and are temporarily anisohydric, before closing stomata and become isohydric at higher threshold levels of drought stress. Drought-sensitive wheat is isohydric from the start of the drought treatment. The capacity of the drought-tolerant line to maintain stomatal conductance correlates with repression of ABA synthesis in spikes and flag leaves. Gene expression profiling revealed major differences in the drought response in spikes and flag leaves of both wheat lines. While the isohydric drought-sensitive line enters a passive growth mode (arrest of photosynthesis, protein translation), the tolerant line mounts a stronger stress defence response (ROS protection, LEA proteins, cuticle synthesis). The drought response of the tolerant line is characterised by a strong response in the spike, displaying enrichment of genes involved in auxin, cytokinin and ethylene metabolism/signalling. While isohydry may offer advantages for longer term drought stress, anisohydry may be more beneficial when drought stress occurs during the critical stages of wheat spike development, ultimately improving grain yield.


Physical interaction between VIVID and white collar complex regulates photoadaptation in Neurospora.
Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular mechanisms are poorly understood. In Neurospora crassa, VIVID (VVD), a small LOV domain containing blue-light photoreceptor protein, affects photoadaptation for most if not all light-responsive genes. We report that there is a physical interaction between VVD and the white collar complex (WCC), the primary blue-light photoreceptor and the transcription factor complex that initiates light-regulated transcriptional responses in Neurospora. Using two previously characterized VVD mutants, we show that the level of interaction is correlated with the level of WCC repression in constant light and that even light-insensitive VVD is sufficient partly to regulate photoadaptation in vivo. We provide evidence that a functional GFP-VVD fusion protein accumulates in the nucleus on light induction but that nuclear localization of VVD does not require light. Constitutively expressed VVD alone is sufficient to change the dynamics of photoadaptation. Thus, our results demonstrate a direct molecular connection between two of the most essential light signaling components in Neurospora, VVD and WCC, illuminating a previously uncharacterized process for light-sensitive eukaryotic cells.


Reactive oxygen species mediate A beta(25-35)-induced activation of BV-2 microglia.
Microglial activation induced by beta-amyloid (A beta) is an important cellular response in the pathogenesis of Alzheimer's disease (AD). In this study, we show that reactive oxygen species (ROS) play a role as signaling molecules for the activation of NF-kappaB and induction of IL-1beta mRNA expression in A beta(25-35)-treated murine microglia BV-2 cells. ROS scavengers such catalase and superoxide dismutase (SOD) mimetics obviously reduced activation of NF-kappaB and the elevated level of IL-1beta transcripts induced by A beta(25-35). In addition, the A beta(25-35)-induced NF-kappaB activation and IL-1beta expression were suppressed by blockers of the ROS generating enzymes such as NADPH oxidase, cyclooxygenase, and lipoxygenase. These data suggest that ROS mediate A beta-induced microglial activation.


External Workloads Vary by Position and Game Result in US-based Professional Soccer Players.
Professional soccer is a physically demanding sport that requires players to be highly trained. Advances using GPS allow the tracking of external workloads for individual players in practice and competition, however, there is a lack of evidence on how these measures impact match results. Therefore, we analyzed external workloads by player position and determined if they vary depending on the result of competitive matches. External workloads were analyzed in professional soccer players (n = 25) across 28 competitive games. One-way ANOVA determined if workloads varied by position (striker - ST, wide midfielder - WM, central midfielder - CM, wide defender - WD, central defender - CD) or across games won (n = 8), lost (n = 13) or tied (n = 7). Repeated-measures ANOVA assessed differences in workloads specific to each position in each of the result categories. Statistical significance was set at p < 0.05. Across all games, more high-speed and very-high speed running was done by ST and WD compared to CD (p < 0.001) and CM (p < 0.001 - 0.02). Whole-team data showed no differences in any external workload variable with respect to match result (p > 0.05), however, in games won ST did more very high-speed running than in losing games (p = 0.03) and defending players did more high and very high-speed running in games tied vs. those won or lost (p < 0.05). Whole-team external workloads do not vary depending on the match result; however, high speed running may be a differentiating factor at the positional level. Coaches should consider position-specific analysis when examining player workloads.


Using generic picture cues to promote verbal initiations during play.
Children with autism spectrum disorder often demonstrate difficulty communicating with others, and this may affect the extent to which they can engage in contextually appropriate language during play. This study examined the effects of a social script-training intervention using generic picture cues on the number of contextually appropriate play statements for children with autism spectrum disorder. We also examined the extent to which responding generalized to novel toy sets and analyzed play statement types. A nonconcurrent multiple-baseline-across-participants design with embedded reversal components was used to evaluate the effects of the generic picture-cue intervention on contextually appropriate play statements. Three participants demonstrated a higher number of contextually appropriate play statements in the training condition as compared with the baseline and no-cue conditions. Further, two out of three participants continued to emit a similar number of contextually appropriate play statements when we introduced novel toy sets.


Spatially regularized multifractal analysis for fMRI data.
Scale-free dynamics is nowadays a massively used paradigm to model infraslow macroscopic brain activity. Multifractal analysis is becoming the standard tool to characterize scale-free dynamics. It is commonly used on various modalities of neuroimaging data to evaluate whether arrhythmic fluctuations in ongoing or evoked brain activity are related to pathologies (Alzheimer, epilepsy) or task performance. The success of multifractal analysis in neurosciences remains however so far contrasted: While it lead to relevant findings on M/EEG data, less clear impact was shown when applied to fMRI data. This is mostly due to their poor time resolution and very short duration as well as to the fact that analysis remains performed voxelwise. To take advantage of the large amount of voxels recorded jointly in fMRI, the present contribution proposes the use of a recently introduced Bayesian formalism for multifractal analysis, that regularizes the estimation of the multifractality parameter of a given voxel using information from neighbor voxels. The benefits of this regularized multifractal analysis are illustrated by comparison against classical multifractal analysis on fMRI data collected on one subject, at rest and during a working memory task: Though not yet statistically significant, increased multifractality is observed in task-negative and task-positive networks, respectively.


[Psychosocial Characteristics of Adolescents Treated for Alcohol Intoxication in Emergency Departments].
Psychosocial Characteristics of Adolescents Treated for Alcohol Intoxication in Emergency Departments In Germany, every year a substantial number of adolescents is treated in emergency departments for acute alcohol intoxication. Until now, only few studies have been published investigating psychosocial aspects in this group of adolescents. In the present study 316 adolescents were surveyed in the emergency department regarding their problematic use of alcohol and illicit drugs, their patterns of alcohol consumption, their alcohol-related and mental problems. We reported results for the whole sample. Additionally, the sample was divided in two groups based on the result in an established screening instrument for problematic alcohol use (CRAFFT-d). To compare the two groups we conducted unpaired t tests, chi-square tests and logistic regression analyses. Compared to the other group the adolescents exceeding the cut-off value of the CRAFFT-d reported a statistically significant higher past 30-day binge drinking frequency and number of standard-drinks consumed on a typical drinking occasion, more alcohol-related problems, more frequently a problematic use of illicit drugs and more mental problems (regarding antisocial behavior, anger control problems and self-esteem). Antisocial behavior was the most important factor for the affiliation to one of the two groups. The application of the screening instrument for problematic alcohol use (CRAFFT-d) in the emergency department seems to be a promising approach to identify adolescents with a general higher psychosocial burden.


Probiotics-Containing Mucoadhesive Gel for Targeting the Dysbiosis Associated with Periodontal Diseases.
Periodontitis is a common disorder that leads to the loss of both tooth and personal well-being, contributing to worsen the risk for metabolic and cardiovascular diseases. Recently, probiotics, characterized by rapid oral dispersion, have been topically used. Here, we present data of a mucoadhesive gel containing probiotics, capable of ensuring a slow release of bacteria to prevent and treat periodontitis. An original mucoadhesive gel (AL0005) that is anhydrous and of food grade, loaded with the blend of lactobacilli and plants' dry extracts, has been assayed. The release kinetics of the bacterial mixture in different experimental models in vitro, including simulated saliva or physiological solutions, showed a significant and stable release for 5-8 hours. In one in vivo study of a mouse model of periodontitis, a locally applied mucoadhesive gel enriched with probiotic strains improved significantly the tissue pathology when compared with vehicle-exposed mice. Together, the results suggest that this mucoadhesive gel can be useful in the normalization of the gum bacterial flora and improvement of the tissue pathology of gum disorders.


Juvenile idiopathic arthritis - what the clinician needs to know.
Juvenile idiopathic arthritis (JIA) includes several forms of chronic arthritis in childhood with no apparent cause. JIA is the most common rheumatic disease in children, and may result in pain, joint deformity, and growth im- pairment, with possible persistent active arthritis into adulthood. Prior treatment involved non-specific agents, several with significant adverse effects. The recent use of biologics now provides target-specific therapy, which may be better tolerated. Through continued translational research and clinical trials, one better understands the biology mediating disease, with the hope of offering safer, more effective medicine, and potential cure. This review will outline the clinical features of JIA, as well as provide the latest updates in treatment.


[STRONGYLOIDIASIS]
Human Strongyloidiasis due to nematode strongyloidesstercoralis, represents a diagnostic problem, and its treatment with newdrugs is better than before but no completely successful. Hyperinfectionsyndrome, the most severe clinical form of this helminthiasis, represents a challenge for treatment, and has a very high mortality index.On the other hand, the lack of knowledge about strongyloides immunobiology, and host-parasite relationship, preclude our total understanding of the symptoms and disease evolution.In this paper, we review widely several topics on Human Strongyloidiasis


In-situ confined growth of monodisperse pt nanoparticle@graphene nanobox composites as electrocatalytic nanoreactors.
Monodisperse Pt nanoparticles (NPs) studded in a three-dimensional (3D) graphene nanobox are successfully synthesized through a simple in-situ confined growth route for the first time. The nano-zeolite A was used as a 3D substrate for in-situ growth of tri-layered graphenes on the crystal-surfaces, meanwhile, the inner micropores of which can also be utilized for the confined growth of Pt nanoparticles. The graphene sheets are curved on the edges to form a 3D hollow box morphology, where the monodisperse Pt nanoparticles are homogeneously studded on the inner surfaces. Moreover, the Pt content can be regulated from ∼8 to 50 wt%, and the particle size can be tuned from 2-5 nm by varying the pristine Pt-ion loading amount and CVD temperature. The Pt NP@graphene nanoboxes possess not only large pore volumes to effectively accommodate large amounts of oxygen, but also supply excellent electrical conductivity for the fast transfer of electrons (∼3.96 e(-)), resulting in a high efficiency (175 mA/mg Pt) and long-term stability (above 1000 cycles) for the oxygen reduction reaction.


Hepatocellular injuries observed in patients with an eating disorder prior to nutritional treatment.
Although hepatocellular injuries are occasionally observed in patients with an eating disorder, such as anorexia nervosa (AN), it remains unclear how malnutrition in patients with AN causes hepatocellular damage. In this retrospective study, we aimed to reveal the characteristics of hepatocellular injuries in patients with an eating disorder without any nutritional treatment, to eliminate the possible hepatotoxic effects of nutritional support. Twenty-five patients with an eating disorder who visited St. Luke's International Hospital were enrolled. No nutritional treatment had been performed for these patients. The diagnosis of eating disorder as well as typing (anorexia nervosa or bulimia nervosa) was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-4). We reviewed the charts of these patients and examined the clinical parameters. Elevation of serum alanine aminotransferase (ALT) was found in 13 out of 25 (52%), all of whom were categorized as AN. In 13 AN patients with elevated ALT, the median of serum ALT values was 92 [39-438] IU/L. The body mass index (BMI) was significantly lower (13.5 vs. 17.3, p=0.011), and the duration since the onset of AN was shorter (4.2 years vs. 8.9 years, p=0.037) in patients with elevated ALT. The age was younger in patients with elevated ALT, even though not significant (24.5 vs. 29.8, p=0.139). Logistic regression analysis revealed that only BMI was a significant determinant for the development of hepatocellular injuries (OR=3.46; 95% CI 1.06-11.34, p=0.041). Imaging studies failed to demonstrate any abnormalities, including fatty liver. The current study indicated that lower BMI might significantly contribute to the development of hepatocellular injuries in AN patients prior to any nutritional treatments.


[Pegylated interferon plus ribavirin in chronic hepatitis C. More than half of patients show a lasting response].
In the past ten years, treatment of chronic hepatitis C has made great advances. Only five years ago, not more than 16% of the patients experienced a lasting cure; now the HC virus can be eliminated in 54-56%. This has been made possible by an improvement to interferon-alpha by pegylation, that is, retardation, resulting in appreciably longer and more uniform active levels, together with improved eradication by the combination with ribavirin. At the same time, treatment has become more convenient for the patient, since interferon need now be administrated only once weekly, usually on an outpatient basis. In view of the side effects of interferon, treatment must be closely monitored. In the meantime, concrete treatment recommendations are available for every genetic type of HCV, for patients experiencing relapse, and for primary treatment failures.


[Propafenone in refractory supraventricular arrhythmias].
Twelve patients with ventricular arrhythmias were given 300-900 mg oral of propafenon daily. We have obtained VT's suppression in 6 of 8 cases (75%) and "complex" VEB's suppression or significant reduction in 6 of 10 cases (60%). Total VEB have been strongly reduced (-91,2%) in 7 of 12 patients (58,3%). The effects of Propafenon on electrocardiographic intervals have not been significant at lower doses and only with 900 mg we have noted a significant (p less than 0,05) lengthening of the P-R (+27,1%) and QTc (+10,2%) intervals. Propafenon has never caused important negative inotropic effects. These results have been confirmed during a follow-up period of 5-19 months. In conclusion we believe that Propafenon must be considered a highly efficient drug for the treatment and prevention of refractory ventricular arrhythmias.


Optimizing therapy for vancomycin-resistant enterococcal bacteremia in children.
Uncertainties exist regarding the optimal treatment for vancomycin-resistant enterococcal (VRE) bloodstream infections, particularly in settings in which ampicillin cannot be used. Quinupristin-dalfopristin, linezolid, and daptomycin, all approved between 1999 and 2003, represent the mainstays of therapy for VRE bacteremia, although only linezolid has been specifically approved by the United States Food and Drug Administration for this indication. The main objective of this review is to compare the relative efficacies, dosing strategies, and side-effect profiles of quinupristin-dalfopristin, linezolid, and daptomycin for VRE bacteremia in the pediatric population. A brief description of recently approved broad-spectrum Gram-positive agents that may have a role in the management of VRE bacteremia in upcoming years is also provided. Linezolid, despite its bacteriostatic activity against VRE, may be the most versatile of the available drugs. It has activity against both Enterococcus faecalis and E. faecium, can be administered orally, and resistance appears to be less of a concern with linezolid compared with the other agents. Additionally, the results of two recent meta-analyses demonstrate more favorable outcomes with linezolid compared with daptomycin for the treatment of VRE bacteremia. The clinical pharmacokinetics of linezolid have been well described in children. The most notable concern with linezolid, however, is toxicities associated with prolonged use. Until more prospective data are available, we favor linezolid as first-line therapy for the treatment of VRE bacteremia in children.


A De novo Peptide from a High Throughput Peptide Library Blocks Myosin A -MTIP Complex Formation in Plasmodium falciparum.
Apicomplexan parasites, through their motor machinery, produce the required propulsive force critical for host cell-entry. The conserved components of this so-called glideosome machinery are myosin A and myosin A Tail Interacting Protein (MTIP). MTIP tethers myosin A to the inner membrane complex of the parasite through 20 amino acid-long C-terminal end of myosin A that makes direct contacts with MTIP, allowing the invasion of Plasmodium falciparum in erythrocytes. Here, we discovered through screening a peptide library, a de-novo peptide ZA1 that binds the myosin A tail domain. We demonstrated that ZA1 bound strongly to myosin A tail and was able to disrupt the native myosin A tail MTIP complex both in vitro and in vivo. We then showed that a shortened peptide derived from ZA1, named ZA1S, was able to bind myosin A and block parasite invasion. Overall, our study identified a novel anti-malarial peptide that could be used in combination with other antimalarials for blocking the invasion of Plasmodium falciparum.


The relationship between radiographic parameters and clinical outcome of distal radius fractures in elderly patients.
Treatment of distal radius fractures in elderly patients is controversial. This study explored the relationship between radiographic parameters and clinical outcomes of patients with distal radius fractures following conservative treatment. The study was done using radiographic measurements of distal radius fractures in elderly patients. Ninety-two active, healthy patients with conservatively managed distal radius fractures were included in the study. Functional and radiographic assessments were made 1 year after injury. Fifty patients who underwent corrective osteotomy comprised the control group. Radiographic parameters and clinical outcomes were compared between the two groups. The correlation coefficients of the radiographic parameters were analysed using multiple regression. Radius height (RH), volar tilt (VT) and Mayo wrist and Disabilities of the Arm, Shoulder and Hand (DASH) scores in the experimental group were significantly superior to those of the control group. There was no significant group difference in radial inclination. Multiple regression analysis revealed that the most important factor affecting functional outcome was RH, followed by VT. RH and VT were significantly correlated with the clinical outcomes of conservative treatment of distal radius fractures. RH should be given foremost consideration in elderly patients. Preoperatively, surgeons should evaluate this parameter carefully and be prepared to treat injuries accordingly. Level IV retrospective study.


Comparative study on risk of birth defects in singleton ART birth under high levels of estrogen after fresh embryo transfer and frozen embryo transfer.
To investigate whether high estrogen (E2) levels caused by controlled ovarian hyperstimulation affect the birth defect rate in singleton assisted reproductive technology (ART) birth after conceived by fresh embryo transfer and frozen embryo transfer (FET). This was a retrospective cohort study. A total of 581 women with singletons, as well as those who have become pregnant and have had an unwanted abortion under high E2 levels on trigger day were divided into three groups. Group A received FET and the E2 levels on trigger day were higher than 5000 pg/ml. Group B received fresh embryo transfer and the E2 levels were between 3000 and 5000 pg/ml. Group C received FET and the E2 levels were between 3000 and 5000 pg/ml. There were no significant differences in birth weight, delivery mode, preterm birth rate, and fetal sex between the three groups (p > .05). Birth defect rate in Group B was higher than that in Group A and C, and the rate between Group B and C had significant differences (p < .05). After adjusting for maternal age, BMI, and type of infertility, only a FET cycle is significantly associated with decreased birth defect rate. Fresh embryo transfer under supraphysiological level of estrogen exposure may increase the birth defect rate of ART singletons. Even after prenatal screening and diagnosis, a part of birth defect could not be detected during pregnancy. When the estrogen levels on trigger day were no lower than 3000 pg/ml, FET should be advocated to reduce the occurrence of such risk.


NTA directed protein nanopatterning on DNA Origami nanoconstructs.
Precisely patterning proteins and other molecules at the nanoscale is crucial to future biosensing and optoelectronic applications. One- and two-dimensional DNA nanoconstructs have proven to be useful scaffolds for nanopatterning. This paper demonstrates the application of nitrilotriacetic acid (NTA) forming chelate complexes to localize histidine (His) tagged proteins via Ni(2+) ions onto DNA based structures. Particularly, enhanced green fluorescent protein (EGFP) was directed to specific surface locations on a designed DNA Origami nanoconstruct, and the resulting EGFP nanopattern was visualized using atomic force microscopy (AFM).


Myofasciocutaneous expansion in the tegumentary rehabilitation of the amputation stump.
In post-traumatic amputations, in particular in leg amputations, the presence of an unstable scar or of ulcerous areas that are difficult to heal in the site of the amputation stump constitutes a repair problem that is not easily solved. In this specific field of reconstruction skin expansion has earned significant agreement, and is even considered to be a safe and reliable method for the surgical rehabilitation of the amputation stump, allowing us to obtain high-quality tegumentary covering, with no excessive thickness, that adapts well to the prosthesis and to the underlying skeleton, and that is characterized by good sensitivity of protection. Tegumentary amplification may, in some cases, also become myocutaneous, allowing us to obtain more tissue thickness for protection in patients submitted to chronic loading that lasts longer and in those with thin teguments, in which traditional expansion could determine excessive narrowing of the tegumentary covering, following atrophy caused by compression of the subcutaneous adipose tissue.


Protein phosphatase 2A (PP2A) regulatory subunit B'γ interacts with cytoplasmic ACONITASE 3 and modulates the abundance of AOX1A and AOX1D in Arabidopsis thaliana.
Organellar reactive oxygen species (ROS) signalling is a key mechanism that promotes the onset of defensive measures in stress-exposed plants. The underlying molecular mechanisms and feedback regulation loops, however, still remain poorly understood. Our previous work has shown that a specific regulatory B'γ subunit of protein phosphatase 2A (PP2A) is required to control organellar ROS signalling and associated metabolic adjustments in Arabidopsis thaliana. Here, we addressed the mechanisms through which PP2A-B'γ impacts on organellar metabolic crosstalk and ROS homeostasis in leaves. Genetic, biochemical and pharmacological approaches, together with a combination of data-dependent acquisition (DDA) and selected reaction monitoring (SRM) MS techniques, were utilized to assess PP2A-B'γ-dependent adjustments in Arabidopsis thaliana. We show that PP2A-B'γ physically interacts with the cytoplasmic form of aconitase, a central metabolic enzyme functionally connected with mitochondrial respiration, oxidative stress responses and regulation of cell death in plants. Furthermore, PP2A-B'γ impacts ROS homeostasis by controlling the abundance of specific alternative oxidase isoforms, AOX1A and AOX1D, in leaf mitochondria. We conclude that PP2A-B'γ-dependent regulatory actions modulate the functional status of metabolic enzymes that essentially contribute to intracellular ROS signalling and metabolic homeostasis in plants.


Induction of differentiation in erythroleukemic K562 cells by gamma-irradiation.
Various agents have been shown to induce differentiation in neoplastic cells. The present study aimed at investigating comparable phenomena induced by high doses of gamma-irradiation in the presence of physiological factors. The erythroleukemic K562 cells were gamma-irradiated or treated with cytosine-arabinoside (Ara-C), and examined for cell size, protein content, acetylcholinesterase (AChE)-activity and hemoglobin synthesis in relation to mitotic activity. At doses above 10 Gy, differentiation was induced, as recognized by elevated AChE-activity, accompanied by an increase in cell size and protein content and cessation of cell proliferation. Moreover, irradiation, as well as Ara-C, induced hemoglobin synthesis when cultures were supplemented with hemin prior to treatment. It is suggested that the basic mechanisms of differentiation induction are similar for ionizing radiation and certain chemical agents and are related to continued growth of essential cytoplasmic constituents during inhibition of mitotic activity.


Experimental infection of Phlebotomus papatasi with sand fly fever Sicilian virus.
Experimental studies were conducted to evaluate humans as hosts infecting the sand fly Phlebotomus papatasi with sand fly fever Sicilian (SFS) virus. Viral antigen and infectious virus circulated in the blood of infected volunteers on days 4 and 5 after intravenous inoculation with SFS virus. Viremia levels during the latter period were high enough to infect feeding sand flies, but only 13% (9/69) of the flies became infected. One out of every 3 infected sand flies that survived to feed a second time transmitted SFS to a hamster. These results confirm a vertebrate-sand fly-vertebrate transmission cycle for SFS virus, and demonstrate that horizontal transmission may contribute to the maintenance of this virus in nature.


Characteristics of dissolved ozone flotation for the enhanced treatment of bio-treated drilling wastewater from a gas field.
Working fluid preparation using treated drilling wastewater is of great potential for drilling wastewater reuse, especially in water-deficient and ecologically fragile areas, which require low levels of organic matter and suspended solids (SS). This study established the dissolved ozone flotation (DOF) process as the advanced treatment process to replace the original electrocatalytic system (ECS) which exhibited low organic and suspended solids removal efficiency. Higher and more stable organic matter, suspended solids and turbidity removal efficiency were obtained for the DOF process. Consequently, the lower fouling potential and higher water production rate of treated water from DOF process was observed for the following reverse osmosis (RO) system. In addition, brine drilling fluids can be successfully prepared using DOF effluent directly, which exhibited promising practical implications in the advanced drilling wastewater treatment. Based on organic matter fractionation and redundancy analysis (RDA), the hydrophobic acid (HOA), hydrophobic neutral (HON) and hydrophilic fraction (HI) contents significantly impacted brine drilling fluid preparation. Based on X-ray photoelectron spectroscopy (XPS) analysis, the aromatic carbon species in the HOA, HON and HI fractions were found to be the critical factors deteriorating the brine drilling fluid preparation. However, oxygen-containing groups played a positive role. The favorable brine drilling fluid preparation performance using DOF effluent directly can be ascribed to the removal of HOA, HON and HI fractions and enhanced generation of oxygen-containing groups in ozone flotation zone.


Trichomonas vaginalis infection in pre-pubertal girls.
This short paper discusses the implications of Trichomonas vaginalis infection of the genital tract in children with respect to suspected child abuse. Two case reports are described to illustrate the problems that can arise in the investigation of such cases T. vaginalis is usually transmitted sexually but the potential for non-sexual transmission does exist.


Short Communication: Differences in Levels of Free Amino Acids and Total Protein in Human Foremilk and Hindmilk.
Free amino acids (FAAs) in human milk are indicated to have specific functional roles in infant development. Studies have shown differences between human milk that is expressed at the beginning of a feed (i.e., foremilk) and the remainder of the milk expressed (i.e., hindmilk). For example, it is well established that human hindmilk is richer in fat and energy than foremilk. Hence, exclusively feeding hindmilk is used to enhance weight gain of preterm, low birthweight infants. Whether FAAs occur differently between foremilk and hindmilk has never been reported, but given their bioactive capacities, this is relevant to consider especially in situations where hindmilk is fed exclusively. Therefore, this study analyzed and compared the FAA and total protein content in human foremilk and hindmilk samples donated by 30 healthy lactating women. The total protein content was found to be significantly higher in hindmilk (p < 0.001), whereas foremilk contained a significantly higher total content of FAAs (p = 0.015). With regards to individual FAAs, foremilk contained significantly higher levels of phenylalanine (p = 0.009), threonine (p = 0.003), valine (p = 0.018), alanine (p = 0.004), glutamine (p < 0.001), and serine (p = 0.012) than hindmilk. Although statistical significance was reached, effect size analysis of the milk fraction on FAA levels in milk revealed that the observed differences were only small. To what extent these differences are of physiological importance for infant development remains to be examined in future research.


"Managing the unmanageable" the U.S. Department of Health and Human Services, 1989-1993.
The author served as the 17th U.S. Secretary of Health and Human Services, from March 1, 1989 until January 20, 1993. The department had 250 programs and 38 percent of the expenditures of the federal government ($600.0 billion), the fourth largest budget in the world. The history of the department included the fact that the tenure of previous Secretaries had ranged from only eight months up to 37 months, and had averaged 27.5 months, resulting in the view that the department was unmanageable. The author's tenure as Secretary was 47 months, and, in the author's view, the department was indeed manageable. The United States Department of Health, Education and Welfare (DHEW) was created as a cabinet agency in 1953, during the administration of President Dwight D. Eisenhower. The Department was formed by bringing together the Social Security Administration (founded in 1935), the United States Commissioner of Education, and the United States Public Health Service (founded in 1798) to serve the United States Merchant Marines). This new cabinet department contained the nation's major domestic programs concerned with income security, public health and education. Oveta Culp Hobby of Texas was the first Secretary of the Department. By 1989, the department's programs had increased to more than 250, including Medicare, Medicaid, Headstart, Welfare, and others. During the administration of President Jimmy Carter, the Education programs were separated into a new cabinet agency, the U.S. Department of Education, and the name of the U.S. Department of Health, Education and Welfare became the U.S. Department of Health and Human Services (DHHS).


Peripheral nerve lesion-induced uptake and transport of choleragenoid by capsaicin-sensitive c-fibre spinal ganglion neurons.
In the present experiments the effect of systemic capsaicin treatment on the retrograde labelling of sensory ganglion cells was studied following the injection of choleratoxin B subunit-horseradish peroxidase conjugate (CTX-HRP) into intact and chronically transected peripheral nerves. In the control rats CTX-HRP injected into intact sciatic nerves labelled medium and large neurons with a mean cross-sectional area of 1,041 +/- 39 gm2. However, after injection of the conjugate into chronically transected sciatic nerves of the control rats, many small cells were also labelled, shifting the mean cross-sectional area of the labelled cells to 632 +/- 118 microm2. Capsaicin pretreatment per se induced a moderate but significant decrease in the mean cross-sectional area of the labelled neurons (879 +/- 79 microm2). More importantly, systemic pretreatment with capsaicin prevented the peripheral nerve lesion-induced labelling of small cells. Thus, the mean cross-sectional areas of labelled neurons relating to the intact and transected sciatic nerves, respectively, did not differ significantly. These findings provide direct evidence for a phenotypic switch of capsaicin-sensitive nociceptive neurons after peripheral nerve injury, and suggest that lesion-induced morphological changes in the spinal cord may be related to specific alterations in the chemistry of C-fibre afferent neurons rather than to a sprouting response of A-fibre afferents.


Toxigenic Pasteurella multocida in rabbits with naturally occurring atrophic rhinitis.
In a commercial rabbitry nasal swabs were taken from 36 animals with enzootic upper respiratory disease resembling porcine atrophic rhinitis. 35 Pasteurella multocida strains were isolated from 17 rabbits. Among 30 strains tested for dermonecrotic toxin production 3, derived from 3 animals, were positive in the guinea pig skin test. 15 Bordetella bronchiseptica strains were recovered from 14 rabbits. No toxigenic strains were found among 6 isolates tested using the same method.


Microperimetry and optical coherence tomography in a case of traumatic macular hole and associated macular detachment with spontaneous resolution.
The association of macular detachment with posttraumatic macular hole is a known but rare occurrence. Spontaneously occurring resolution of the detachment and closure of the macular hole has been reported only once in the literature. We describe a similar rare event in a young male, the documentation of which was done serially by microperimetry (MP) and optical coherence tomography (OCT). A 17-year-old male presented with a decrease in vision following a closed globe injury to the left eye. A coexisting macular hole and macular detachment were detected in the affected eye. Serial follow-up with OCT and MP documented complete resolution of the macular hole and the macular detachment within 1 week of presentation. The case highlights that spontaneous resolution of traumatic macular hole and related macular detachment may occur and a waiting period is advisable before undertaking any corrective surgical procedure. The pathophysiologic mechanisms of causation and the resolution of posttraumatic macular hole-related retinal detachment are discussed.


How do Crocodylian embryos process yolk? Morphological evidence from the American alligator, Alligator mississippiensis.
Recent studies have demonstrated a mechanism of embryonic yolk processing in lizards, snakes and turtles that differs markedly from that of birds. In the avian pattern, cells that line the inside of the yolk sac take up products of yolk digestion and deliver nutrients into the vitelline circulation. In contrast, in squamates and turtles, proliferating endodermal cells invade and fill the yolk sac cavity, forming elongated strands of yolk-filled cells that surround small blood vessels. This arrangement provides a means by which yolk material becomes cellularized, digested, and transported for embryonic use. Ultrastructural observations on late-stage Alligator mississippiensis eggs reveal elongated, vascular strands of endodermal cells within the yolk sac cavity. The strands of cells are intermixed with free yolk spheres and clumps of yolk-filled endodermal cells, features that reflect early phases in the yolk-processing pattern. These observations indicate that yolk processing in Alligator is more like the pattern of other reptiles than that of birds.


Synthesis and characterization of dual stimuli responsive macromers based on poly(N-isopropylacrylamide) and poly(vinylphosphonic acid).
Stimulus responsive materials hold great promise in biological applications as they can react to changes in physiological stimuli to produce a desired effect. Stimulus responsive macromers designed to respond to temperature changes at or around 37 degrees C and the presence of divalent cations were synthesized from N-isopropylacrylamide, pentaerythritol diacrylate monostearate, 2-hydroxyethyl acrylate, and vinylphosphonic acid by free radical polymerization. Monomers were incorporated into the macromers in ratios approximating the molar feed ratios, and macromers underwent thermogelation around normal body temperature (36.2-40.5 degrees C) as determined by rheology and differential scanning calorimetry. Macromers containing vinylphosphonic acid interacted with calcium ions in solution, displaying decreased sol-gel transition temperatures (27.6-34.4 degrees C in 100 mM CaCl(2)), with decreases of greater magnitude observed for macromers with higher relative vinylphosphonic acid content. Critical micellar concentrations also decreased in a dose-dependent manner with increased vinylphosphonic acid incorporation in solutions with CaCl(2) but not in solutions with NaCl. These dually responsive macromers allow examination of the effect of increasing vinylphosphonic acid content in a macromer, which holds promise in biological applications such as drug and cell delivery or tissue engineering due to the macromer responsiveness at physiological temperatures and concentrations of calcium.


[Imaging of tumors of the pituitary gland].
Macrotumors of the sella region usually involve the suprasellar and less commonly the parasellar space. The suprasellar extension of pituitary adenoma, meningeoma, craniopharyngioma, and hypothalamic or chiasmatic glioma count for the most frequent neoplastic entities. In macroadenomas of the pituitary gland invasion of parasellar spaces may occur in 6-10%. Imaging techniques are directed to increase the likelihood of surgical cure and to detect aggressive tumour invasion into surrounding tissues. A dedicated classification basing on indirect MRI signs of tumour extension has been established. With high-resolution high-field (3T) MRI the sella region may be displayed to provide better information compared to lower field strengths.


Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application.
Choroidal neovascularization (CNV) secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of "from bench to bedside", initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia.


Differences in Lipid Composition between Undifferentiated and Mature Maize Chloroplasts.
Lipid compositions of undifferentiated maize (Zea mays) chloroplasts, capable of fixing CO(2), were compared with the lipid compositions of mature chloroplasts, which do not fix CO(2), located in both the mesophyll and bundle sheath cells. The major lipids found in all three chloroplast types were the glycolipids, monogalactosyl diglyceride and digalactosyl diglyceride, followed by decreasing amounts of sulfolipid, phosphatidyl glycerol, phosphatidyl choline, phosphatidyl inositol, and diphosphatidyl glycerol. Quantitative differences in lipid components were observed among the chloroplast types. The mesophyll and bundle sheath maize chloroplasts differed in their chlorophyll a/chlorophyll b ratios (2.27 and 4.13 respectively) and their content of glycolipid relative to chlorophyll (51.8% glycolipid to 20.9% chlorophyll and 84.5% glycolipid to 10.1% chlorophyll respectively). A comparison between the lipid compositions of maize mesophyll chloroplasts and mesophyll chloroplasts obtained from spinach, sugar beet, and tobacco showed many similarities.


Effects of temperature on reproductive neuroendocrine function in Aplysia californica.
Egg laying in the gastropod mollusk Aplysia californica is a temperature-dependent behavior, facilitated by warm temperature and attenuated by cold. The purpose of this work was to determine which components of the reproductive axis controlling egg laying are affected by temperature. There were three neural/reproductive tissues investigated: (1) the head ganglia that transmit neural signals to the neuroendocrine bag cells, (2) the bag cells that synthesize and secrete egg-laying hormone (ELH), and (3) the ovotestis that extrudes eggs into the hermaphroditic duct in response to ELH. There was no significant effect of temperature on the ability of ELH to stimulate egg laying, suggesting that temperature does not alter responsiveness of the ovotestis to hormonal stimulation. There was evidence that the bag cells play a secondary role in mediating the effects of temperature on egg-laying behavior, that is, using both bioassays and radioimmunoassay for detection or measurement of ELH, hormone secretion was shown to be inhibited by cooler temperatures in some preparations. However, the inconsistency of this response suggested that the primary effect of temperature is upstream from the bag cells. Results from an experiment in which the head ganglia were chemically stimulated to activate bag cell electrical activity suggested that the primary site of temperature regulation lies within the head ganglia.


Surface charge reversal for inorganic anion determination in capillary electrophoresis with an ion-selective microelectrode as detector.
The effect of surface charge reversal of a fused-silica capillary was investigated for the conditions used in the determination of inorganic anions with potentiometric detection. A 25-micron-i.d. capillary was coated with permanently bonded polyacrylamide incorporating a quaternary amine, and a sodium sulfate solution was employed as electrolyte. As expected, it was found that the analysis time is reduced in comparison with an uncoated column of the same length. However, the effect is much less pronounced than that for the common chromate buffer. Since the reduction in analysis time also causes a loss of resolution, the effect is very close to that obtained simply by using a shorter capillary; therefore, coating was not found to be of benefit here. This is in contrast to results reported for the conditions usually employed for the indirect photometric detection of anions.


Access to 4-alkylaminopyridazine derivatives via nitrogen-assisted regioselective Pd-catalyzed reactions.
3-Substituted, 6-substituted, and unsymmetrical 3,6-disubstituted 4-alkylaminopyridazines were prepared from a sequence of three chemo- and regioselective reactions combining amination and palladium-catalyzed cross-coupling reactions, such as reductive dehalogenation and Suzuki-Miyaura reactions. Extension of the methodology to Sonogashira reaction yielded a novel class of 3-substituted pyrrolopyridazines.


Comparison of the quantity and quality of the microbiological content of sludge in countries with low and high content of pathogens.
The parasites present in the residual sludge generate by the diverse treatment processes of residual water vary, depending on the socioeconomic and epidemiological conditions of different communities. And although data exist at the global level regarding the microbiological quality of sludge, these data are practically nonexistent in developing countries. Therefore, this project compares the content of the four principal groups of parasites in residual sludge from the United States and Mexico. The marked differences between the orders of magnitude found in the two countries (coliphages 10(3)-10(6) and 1.3 x 10(5) PFU/gTS, fecal coliforms 10(7)-10(10) and 10(7), Salmonella typhi 10(6)-10(8) and 10(3) MPN/gTS, Giardia lamblia 10(2)-10(4) and 10(2) cysts/gTS and helminth ova from 73-177 and <1 to 10 viable HO/gTS, respectively) will permit proposing real, effective and economical stabilization processes (undoubtedly different from those of industrialized countries), and will thus take advantage of the benefits represented by the reuse and disposal of sludge, in addition to developing regulations in agreement with the conditions of each region.


The sympathetic nervous system and the kidney: its importance in renal diseases.
There is a two-way relation between the sympathetic nerve system and the kidney. On the one hand the sympathetic nerve system affects renal function, i.e. renal hemodynamics, renin secretion and tubular sodium transport. On the other hand the kidney is the source of activating afferent signals, presumably via stimulation of chemoreceptors and baroreceptors. This concept is supported by clinical observations in endstage and pre-endstage renal disease, where sympathetic overactivity is present. It has been shown to depend on the presence of the diseased kidney and is abolished by bilateral nephrectomy. Experimentally, interruption of afferent nerve traffic by dorsal rhizotomy partially prevents hypertension in renal damage models. Imidazoline-preferring binding sites are found in the kidney. In the rat, natriuresis is elicited by injection of moxonidine into the renal artery. In humans, there is no definite evidence for a natriuretic effect, but some observations point in this direction. In renal disease, the issue arises whether sympathetic overactivity contributes to progression of renal failure. Indirect evidence in this direction could be the marked acceleration of progression by smoking, a state of known sympathetic overactivity. In experimental models of renal damage, treatment with moxonidine in antihypertensive doses markedly attenuated development of glomerulosclerosis. Preliminary observations show that even non-antihypertensive doses of moxonidine interfere with the development of glomerulosclerosis. Sympathicolytic agents are obviously rational in the antihypertensive therapy of the renal patient, because uraemia is a state of sympathetic overactivity and because blood pressure-independent effects of sympathetic activation on progression are likely.


Co-ordinating innate and adaptive immunity to viral infection: mobility is the key.
The host counters a viral infection through a complex response made up of components belonging to both the innate and the adaptive immune system. In this report, we review the mechanisms underlying this response, how it is induced and how it is co-ordinated. As cell-cell communication represents the very essence of immune system physiology, a key to a rapid, efficient and optimally regulated immune response is the ability of the involved cells to rapidly shift between a stationary and a mobile state, combined with stringent regulation of cell migration during the mobile state. Through the co-ordinated recruitment of different cell types intended to work in concert, cellular co-operation is optimized particularly under conditions that may involve rare cells. Consequently, a major focus is placed on presenting an overview of the co-operative events and the associated cell migration, which is essential in mounting an efficient host response and co-ordinating innate and adaptive immunity during a primary viral infection.


A new animal model of postsurgical bowel inflammation and fibrosis: the effect of commensal microflora.
Ileocaecal resection (ICR) is common in Crohn's disease. Inflammation and fibrosis frequently recur at the site of anastomosis or in the small intestine (SI). No animal models of postsurgical inflammation and fibrosis exist. A model of ICR was developed in interleukin 10 (IL10) null and wild-type (WT) mice to test the hypothesis that ICR promotes postsurgical inflammation and fibrosis in the SI or anastomosis of genetically susceptible IL10 null, but not WT or germ-free (GF)-IL10 null mice. GF-IL10 null mice were conventionalised (CONV) and 3 weeks later randomised to ICR, transection (T) or no treatment (NoTx). Age-matched conventionally raised (CONV) WT and GF-IL10 null mice received ICR, T or NoTx. Animals were killed 28 days later. Histological scoring, real-time PCR for tumour necrosis factor alpha and collagen, and immunostaining for CD3(+) T cells assessed inflammation and fibrosis. After ICR, CONV-IL10 null, but not CONV-WT mice, developed significant inflammation and fibrosis in the SI and inflammation in anastomosis compared with NoTx or T controls. Fibrosis occurred in the anastomosis of both CONV-IL10 null and CONV-WT mice following ICR. GF-IL10 null mice developed little or no inflammation or fibrosis in the SI or anastomosis after ICR. ICR in CONV-IL10 null mice provides a new animal model of postsurgical inflammation and fibrosis in the SI and anastomosis. Absence of inflammation and fibrosis in the SI of CONV-WT and GF-IL10 null mice following ICR indicates that postsurgical small bowel disease occurs only in genetically susceptible IL10 null mice and is bacteria dependent.


Cyclization of arylacetoacetates to indene and dihydronaphthalene derivatives in strong acids. Evidence for involvement of further protonation of O,O-diprotonated beta-ketoester, leading to enhancement of cyclization.
The chemical features, such as substrate stability, product distribution, and substrate generality, and the reaction mechanism of Brønsted superacid-catalyzed cyclization reactions of aromatic ring-containing acetoacetates (beta-ketoesters) were examined in detail. While two types of carbonyl cyclization are possible, i.e., keto cyclization and ester cyclization, the former was found to take place exclusively. The reaction constitutes an efficient method to synthesize indene and 3,4-dihydronapthalene derivatives. Acid-base titration monitored with (13)C NMR spectroscopy showed that the acetoacetates are fully O(1),O(3)-diprotonated at H(0) = -11. While the five-membered ring cyclization of the arylacetoacetates proceeded slowly at H(0) = -11, a linear increase in the rate of the cyclization was found with increasing acidity in the high acidity region of H(0) = -11.8 to -13.3. Therefore, the O(1),O(3)-diprotonated acetoacetates exhibited some cyclizing reactivity, but they are not the reactive intermediates responsible for the acceleration of the cyclization in the high acidity region. The reactive cationic species might be formed by further protonation (or protosolvation) of the O(1),O(3)-diprotonated acetoacetates; i.e., they may be tricationic species. Thermochemical data on the acid-catalyzed cyclization of the arylacetoacetates showed that the activation energy is decreased significantly as compared with that of the related acid-catalyzed cyclization reaction of a compound bearing a single functional group, such as a ketone. These findings indicate that intervention of the trication contributes to the activation of the cyclization of arylacetoacetates in strong acid, and the electron-withdrawing nature of the O-protonated ester functionality significantly increases the electrophilicity of the ketone moiety.


Targeting cancer cell metabolism in pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided.


Antisense inhibition of engrailed genes in mouse embryos reveals roles for these genes in craniofacial and neural tube development.
The roles of engrailed-1 (En-1) and engrailed-2 (En-2) have been investigated during gastrulation and neurulation in mouse embryos. Using antisense oligonucleotides and murine whole embryo culture, early somite embryos were injected with antisense phosphorothioated oligonucleotides directed against En-1 or En-2 transcripts and then grown in vitro for 48 hr. Inhibition of En-1 by antisense targeting during this period resulted in embryos with craniofacial abnormalities, specifically loss of mid- and hindbrain tissue and hypoplasia in associated neural crest derived areas such as the face and first and second pharyngeal arches. In addition, En-1 appeared to be essential in early patterning of the neural tube. Embryos removed from culture as early as 8 hr following injection exhibited undulations in the presumptive spinal cord. Histological analysis of the affected neural tubes at 48 hr showed disrupted cytoarchitecture and in some cases, apparent dorsal-ventral duplication of the neural tube and underlying notochord. Using S100 beta as a notochord marker, embryos removed from culture at 8 or 12 hr following injection exhibited loss of S100 beta expression in the notochord region subjacent to affected neural tube segments, suggesting that S100 beta, or other notochordal genes, may be downstream components of the En-1 regulatory cascade. Furthermore, antisense inhibition of En-1 induced caudal dysgenesis, suggesting disruption in primitive streak function. Antisense targeting of En-2 expression of early somite stages produced few alterations in development, although approximately one third of the embryos exhibited a series of lateral folds in the spinal cord at the level of the forelimb-bud.(ABSTRACT TRUNCATED AT 250 WORDS)


Participation of functionally different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic injury.
Macrophages are crucial in hepatic fibrogenesis. In acute hepatic necrosis induced in rats by a single injection of 300 mg/kg body weight (BW) of thioacetamide (TAA), macrophage properties were investigated using single or double immunohistochemistry. Macrophages reacting with anti-CD68, anti-CD163, or major histocompatibility complex (anti-MHC) class II antibody appeared in injured centrilobular areas on days 1-5 after injection. Increased expression of CD68 and CD163 reflect phagocytosis and production of pro-inflammatory factors, respectively. There were also macrophages double-positive to CD68/CD163, CD68/MHC class II, or CD163/MHC class II; of these, macrophages double-positive to CD68/MHC class II were most frequent, indicating that macrophages with enhanced phagocytic activity came to express MHC class II. The appearance of these macrophages corresponded to increased expression of mRNAs of monocyte chemoattractant protein-1 (MCP-1), a chemokine, on day 1, and TGF-beta1, a fibrogenic factor, on day 3. Some hepatic stellate cells (HSCs) in injured areas reacted with anti-MCP-1 antibody. To investigate the effects of MCP-1, we added MCP-1 to HS-P, a rat macrophage line. Addition of MCP-1 increased immunoexpression for CD68 and CD163 and up-regulated TGF-beta1 mRNA expression. Collectively, macrophages in acute hepatic necrosis may express different properties such as phagocytosis, MHC class II expression, and TGF-beta1 production; such expression may be influenced by MCP-1 produced by HSCs.


Artificial Neural Network for Predicting Iodine Deficiency in the First Trimester of Pregnancy in Healthy Women.
Iodine deficiency in Spain is a persisting public health problem and the prescription of potassium iodide is recommended during pregnancy. The purpose of this study was to develop an Artificial Neural Network (ANN) to predict the risk factors of iodine deficiency during pregnancy, and compare the results obtained with a logistic regression model. Two hundred forty-four healthy pregnant women were included in a descriptive and prospective study in their first trimester of pregnancy. The women enrolled were asked specifically about their use of supplements containing potassium iodide, iron, folic acid and/or multivitamins during pregnancy. The consumption of iodine-rich foods was assessed through a food frequency questionnaire. A median UIC of 57.4 μg/L (IQR 32.8-99.3) was obtained, with 89.3% < 150 μg/L, the minimum recommended ioduria level by the WHO. There was no correlation between urinary iodine concentrations and maternal age, BMI or gestation week at recruitment. The urinary iodine concentrations were significantly higher in women who reported taking iodized supplements and/or iodized salt than those who did not. Number of gestations, age, body mass index, and intake of iodized supplements and iodized salt were the most important predictors of iodine deficiency. Based on Receiver Operating Characteristic analysis, the diagnostic performance of the ANN model was superior to the logistic regression model. The ANN model, with variables on pregnancy and the intake of iodine rich foods, iodized supplement and iodized salt may be useful for predicting iodine deficiency in the early pregnancy.


Soy Phytoestrogens Do Not Fully Reverse Changes in Rat Pituitary Castration Cells: Unbiased Stereological Study.
The aim of the study was to examine the potential of the principal soy isoflavones, genistein and daidzein, or isoflavone rich soy extract to recover pituitary castration cells in orchidectomized adult male rats in comparison with the effects of estradiol. Two weeks post orchidectomy (Orx), animals received estradiol-dipropionate, genistein, daidzein or soy extract subcutaneously for 3 weeks. Control sham-operated (So) and Orx rats received just the vehicle. Changes in the volumes of pars distalis, of individual follicle-stimulating hormone (FSH) and luteinizing hormone (LH) containing cells, their volume, numerical density and number were determined by unbiased design-based stereology. The intracellular content of βFSH and βLH was estimated by relative intensity of fluorescence (RIF). Orchidectomy increased all examined stereological parameters and RIF. Compared to Orx, estradiol increased the volume of pars distalis, but reversed RIF and all morphometric parameters of gonadotropes to the level of So rats, except their number. Treatments with purified isoflavones and soy extract decreased RIF to the control So level, expressing an estradiol-like effect. However, the histological appearance and morphometrical features of gonadotropes did not follow this pattern. Genistein increased the volume of pars distalis, decreased the volume density of LH-labeled cells and raised the number of gonadotropes. Daidzein decreased the cell volume of gonadotropic cells but increased their number and numerical density. Soy extract induced an increase in number and numerical density of FSH-containing cells. Therefore, it can be concluded that soy phytoestrogens do not fully reverse the Orx-induced changes in pituitary castration cells. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.


Self-Bonded Hydrogel Inverse Opal Particles as Sprayed Flexible Patch for Wound Healing.
Wound healing is an important issue for regenerative medicine. Attempts in this area tend to develop functional wound patches to promote the healing. Here, we present self-bonded hydrogel inverse opal particles as sprayed flexible patch for wound healing. Such particles were fabricated by infusing drugs-loaded gelatin (GT) and carrageenan (CG) pregel into inverse opal scaffolds, which were composed of biocompatible hyaluronic acid methacryloyl (HAMA) and gelatin methacryloyl (GelMA) with graphene oxide quantum dots (GO QDs) doping. Due to the photothermal conversion capability of GO QDs and temperature reversible phase-changing performance of GT/CG, the hybrid particles could undergo GT/CG liquid transformation under the near-infrared (NIR) irradiation, which made them adhere to each other and finally form a flexible patch. Following by the phase-change of GT/CG hydrogel, the encapsulated drugs were also controllably released from the inverse opal scaffold. As the inverse opal scaffolds of the hybrid particles were maintained, their drug release induced refractive index changes could be detected as visual structural color shifting, which could be utilized to monitor their delivery processes. Based on these features, we have demonstrated that the self-bonded particles, administered in the form of spray, could be applied for wound tissue healing and drug delivery monitoring. These results indicate that the self-bonded hydrogel particles have potential value as a multifunctional patch for clinical applications.


Effects of aging and irradiation time on the properties of a highly translucent resin-based composite.
This study investigated the effects of aging and irradiation time on the macro- and micro-mechanical properties of a highly translucent nanohybrid composite (IPS Empress Direct, Trans Opal shade, Ivoclar Vivadent). Flexural strength, flexural modulus, indentation modulus, Vickers hardness, and creep were measured after being irradiated with different durations (5, 10, 20, and 40 s) and aged under different conditions (24 h at 37°C in water; 5,000 times of thermocycling between 5°C and 55°C followed by 4-week storage in artificial saliva or alcohol). Rate of cure was also measured for these four irradiation times at composite specimen surface and at 2 mm depth. Effects of aging and irradiation time were statistically analyzed using one-way ANOVA with Tukey's HSD post hoc test (α=0.05), partial eta-squared statistic, and Weibull analysis. Alcohol aging significantly reduced the mechanical properties. Aging in saliva produced a positive effect on micro-mechanical properties. Irradiation time should be at least 20 s to yield favorable mechanical properties.


One-Pot Approach to Organo-Phosphorus-Chalcogen Macrocycles Incorporating Double OP(S)SCn or OP(Se)SeCn Scaffolds: A Synthetic and Structural Study.
The development of new methodology for the preparation of functional macrocycles with practical applications is an important research area in macromolecular science. In this study, we report a new one-pot route for the synthesis of a series of macro-heterocycles by incorporating two phosphorus atoms and two chalcogen atoms and two oxygen atoms (double OP(S)SCn or OP(Se)SeCn scaffolds). The three-component condensation reactions of 2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide (FcLR, a ferrocene analogue of Lawesson's reagent) or 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (LR, Lawesson's reagent), or 2,4-diphenyl-1,3,2,4-diselenadiphosphetane 2,4-diselenide (WR, Woollins' reagent), disodium alkenyl-diols, and dihalogenated alkanes are performed, giving rise to soluble and air or moisture-stable macrocycles in good-to-excellent yields (up to 92 %). This is the first systemically preparative and readily scalable example of one-pot ring opening/ring extending reaction of three-components to prepare phosphorus-chalcogen containing macrocycles. We also provide a systematic crystallographic study.


Characterization and carcinogen sensitivity of an established endothelial-like cell line derived from adult rat liver tissue.
To define the in vitro response of nonparenchymal liver cells to chemical carcinogens, an endothelial-like cell line (RLC-1) derived from adult rat hepatic tissue was established in long-term culture. The RLC-1 line exhibited morphologic, ultrastructural and cytoskeletal characteristics consistent with derivation from mesenchymal vascular elements within the liver. Using various criteria to monitor changes in growth properties, RLC-1 cells were determined to be resistant to transformation by diethylnitrosamine, partially transformed by benzo[a]pyrene, and completely transformed by methylazoxymethanol acetate and N-methyl-N'-nitro-N-nitrosoguanidine. The RLC-1 cell system provides a means to assess potential effects of procarcinogens, as well as intrinsically reactive compounds, on an isolated nonparenchymal liver cell population.


Intravenous self-administration of an enkephalin analog, EK-399, by rats.
The novel enkephalin analog Tyr-D-Met (O)-Gly-EtPhe-NHNHCOCH3 . AcOH (EK-399) was examined for psychic dependence potential by a self-administration test in rats. Five groups of experimentally naive rats were given an intravenous dose of EK-399 (0.032, 0.064 or 0.125 mg/kg), morphine HCl (0.5 mg/kg) or cocaine HCl (0.5 mg/kg) via a cannula implanted in the jugular vein when they pressed a lever. No animals initiated self-administration of EK-399 in the first 3 or 4 weeks of the experimental period. In contrast, almost all of the animals receiving morphine or cocaine initiated a high rate of self-administration within 1 or 2 weeks. However, when the doses of EK-399 were subsequently decreased, 4 of the 10 animals increased their rate of self-administration slightly. Furthermore, an increase in the rate of EK-399 self-administration was observed in 1 of 4 rats made physically dependent on EK-399. These results suggest that EK-399 has a very weak reinforcing effect on drug-taking behavior, which is slightly enhanced by the development of physical dependence on the compound, and it may possess a low psychic dependence potential.


Immature Colon Carcinoma Transcript 1 Is Essential for Prostate Cancer Cell Viability and Proliferation.
Prostate cancer is the second leading cause of cancer-related death among men in the United States. More recently, immature colon carcinoma transcript 1 (ICT1) has been reported to be overexpressed in various kinds of cancer cells. However, the role of ICT1 in human prostate cancer has not yet been determined. The authors selected two ICT1-specific short hairpin RNA (shRNA) sequences to block its endogenous expression in human androgen-independent prostate cancer cell lines DU145 and PC-3. Decreased ICT1 expression by either specific shRNA significantly inhibited cell viability and proliferation. Moreover, compared to controls, ICT1-silenced cells were more inclined to redistribute in the G2/M phase, leading to cell cycle arrest. Flow cytometry and Annexin V-APC/7-AAD double staining confirmed that knockdown of ICT1 increased late apoptotic cells. Furthermore, they found that ICT1 knockdown restricting G2-M transition may be partly through suppression of CDK1 and Cyclin B1. Knockdown of ICT1 induced apoptosis through activation of poly ADP-ribose polymerase and caspase 3, upregulation of Bax expression, and downregulation of Bcl-2 expression in DU145 cells. In conclusion, this study highlights the crucial role of ICT1 in promoting prostate cancer cell proliferation in vitro. The depletion of ICT1 by lentivirus-mediated shRNA or small molecular inhibitor may provide a novel therapeutic approach for the treatment of prostate cancer.


Use of synthetic oligonucleotide DNA probes for identification and direct detection of Bacteroides forsythus in plaque samples.
Oligonucleotide DNA probes complementary to the hypervariable region of the 16S rRNA of Bacteroides forsythus were tested for their specificity and sensitivity against reference and clinical isolates of 73 different species of bacteria. The probes were used to detect the organism directly from nucleic acid extracts of subgingival plaque samples, and the results were compared with results of detection by culture methods. The data demonstrate that the probes are very specific (100%) and sensitive (100% when they are compared with those obtained by the culture method) and could reliably detect the organism in plaque samples. When a probe to a conserved region of the 16S rRNA (UP9A) was used to estimate the quantity of bacteria present in plaque samples, it gave results comparable to those of culture methods. The data suggest that total microbial load may be a parameter in periodontal disease.


Modeling and predicting stress-induced immunosuppression in mice using blood parameters.
Previous studies have shown that the area under the corticosterone concentration vs. time curve (AUC) can be used to model and predict the effects of restraint stress and chemical stressors on a variety of immunological parameters in the mouse spleen and thymus. In order to complete a risk assessment parallelogram, similar data are needed with blood as the source of immune system cells, because this is the only tissue routinely available from human subjects. Therefore, studies were conducted using treatments for which the corticosterone AUC values are already known: exogenous corticosterone, restraint, propanil, atrazine, and ethanol. Immunological parameters were measured using peripheral blood from mice treated with a series of dosages of each of these agents. Flow cytometry was used to quantify MHC II, B220, CD4, and CD8 cells. Leukocyte and differential counts were done. Spleen cell number and NK cell activity were evaluated to confirm similarity to previous studies. Immune parameter data from mouse blood indicate that MHC II expression has consistent quantitative relationships to corticosterone AUC values, similar to but less consistent than those observed in the spleen. Other immune parameters tended to have greater variability in the blood than in the spleen. The pattern observed in the spleen in which the chemical stressors generally produced very similar effects as noted for restraint stress (at the same corticosterone AUC values) was not observed for blood leukocytes. Nevertheless, MHC class II expression seems to provide a reasonably consistent indication of stress exposure in blood and spleen.


[Arrhythmias with normal heart rate].
Arrhythmias with ventricular rate between 60-100/min are discussed. Premature ventricular complex is considered to be a risk factor for sudden cardiac death and sustained ventricular tachycardia under some particular conditions, especially after myocardial infarction. To improve the prognosis of patients with ventricular arrhythmias, many trial were performed. Ventricular arrhythmia hypothesis was based on the thought that the patients' prognosis would be improved by suppression of ventricular arrhythmias with antiarrhythmic agents. However, CAST study showed unexpected results. Recently, some investigators suggest that antiectopic action and antifibrillatory action are different and empiric therapy with amiodarone is reported. Other arrhythmias with normal heart rate are considered to have little risk for survival. Then antiarrhythmic therapy should be based on quality of life.


Simulation of cardiac electrophysiology on next-generation high-performance computers.
Models of cardiac electrophysiology consist of a system of partial differential equations (PDEs) coupled with a system of ordinary differential equations representing cell membrane dynamics. Current software to solve such models does not provide the required computational speed for practical applications. One reason for this is that little use is made of recent developments in adaptive numerical algorithms for solving systems of PDEs. Studies have suggested that a speedup of up to two orders of magnitude is possible by using adaptive methods. The challenge lies in the efficient implementation of adaptive algorithms on massively parallel computers. The finite-element (FE) method is often used in heart simulators as it can encapsulate the complex geometry and small-scale details of the human heart. An alternative is the spectral element (SE) method, a high-order technique that provides the flexibility and accuracy of FE, but with a reduced number of degrees of freedom. The feasibility of implementing a parallel SE algorithm based on fully unstructured all-hexahedra meshes is discussed. A major computational task is solution of the large algebraic system resulting from FE or SE discretization. Choice of linear solver and preconditioner has a substantial effect on efficiency. A fully parallel implementation based on dynamic partitioning that accounts for load balance, communication and data movement costs is required. Each of these methods must be implemented on next-generation supercomputers in order to realize the necessary speedup. The problems that this may cause, and some of the techniques that are beginning to be developed to overcome these issues, are described.


[Difficulties in becoming a woman and staying a woman. On the problems of female identity in menopause].
With a very few exceptions, the sparse psychoanalytic literature on menopause has regarded it almost exclusively as a kind of ailment, a process of decay and loss. By contrast, recent feminist discourse has demonstratively set itself apart from Freud's theory of femininity and emphasized the opportunities that the menopause brings, albeit at the expense of female sexual desire. Hettlage-Varjas and Kurz suggest that critical review of Freud's theories and more recent concepts of femininity can be integrated into psychoanalytical theory on the psychology of conflict and instinctual drives. They thus avoid the equally dangerous temptations either of classifying the female climateric as pathological or else denying the anxieties and sense of loss that involves and declaring it a conflict-free zone.