Effects of the histamine H3 receptor antagonist ABT-239 on acute and repeated nicotine locomotor responses in rats.
The addictive potential of nicotine is linked to psychomotor and cognition-enhancing effects. Histamine (H)(3) receptor antagonism has similarly received attention for a role in cognition, however, the role of H(3) receptors are far less studied for affects on nicotine-induced locomotor responses. In the present study we tested whether the H(3) receptor antagonist 4-(2-{2-[(2R)-2 methylpyrrolidinyl] ethyl}-benzofuran-5-yl) benzonitrile (ABT-239) influenced the psychomotor responses to acute and repeated nicotine, including sensitization and conditioned locomotion. ABT-239 (0.3-3 mg/kg) did not alter basal, nicotine-evoked (0.4 mg/kg) locomotor responses, the expression of sensitization, or cue-conditioned locomotion. However, in combination studies rats pretreated with a separate dose of ABT-239 (1 mg/kg) prior to nicotine (0.4 mg/kg) for 5 days and then challenged with nicotine (0.4 mg/kg) after a 5-day withdrawal period, showed significantly higher locomotor hyperactivity in comparison with the effect observed in nicotine-pretreated and challenged rats. Our findings implicate a limited role for H(3) receptors in locomotor responses to nicotine.


Examination of possible toxic and immune mechanisms of clozapine-induced agranulocytosis.
We investigated three patients who developed agranulocytosis and seven patients who demonstrated neutropenia during therapy with clozapine as well as five patients who were asymptomatic while on clozapine. One of the three agranulocytic patients had previously developed severe neutropenia during clozapine therapy. We examined mature neutrophils to determine if these cells demonstrated increased susceptibility to clozapine or clozapine metabolites that had been generated chemically. Increased susceptibility was found in the cells of some patients, but it was not a consistent finding. We also examined the effects of clozapine or its chemically-generated metabolites on the development of haematopoietic precursor cells derived from the peripheral blood. Clozapine metabolites, but not clozapine, directly inhibited colony formation of all lineages in a dose-dependent manner; there was no evidence of a specific sensitivity of the myeloid precursors. Acute sera from one of the three patients who developed agranulocytosis was inhibitory to the growth of all precursor cells at a concentration of 10% but none of the plasma were inhibitory. In six patients with neutropenia or agranulocytosis, attempts were made to isolate antigen-specific T cells, wherein the antigen was a hapten carrier complex of clozapine metabolites covalently bound to leukocyte macromolecules. No clozapine metabolite-specific clones to these antigens were detected.


The Protective Effect of a Dietary Extract of Mulberry (Morus alba L.) Leaves against a High Stocking Density, Copper and Trichlorfon in Crucian Carp (Carassius auratus).
This study was designed to examine the protective effects of the extract of mulberry (Morus alba L.) leaves (EML) on crucian carp (Carassius auratus) against a high stocking density, Cu exposure and trichlorfon exposure, which adversely impact fish growth performance, feed intake and fish locomotion. High stocking densities decreased the activities of amylase, lipase, trypsin, Na+/K+-ATPase and alkaline phosphatase (AKP), and increased the content of malonaldehyde (MDA) in fish digestive organs, indicating an impairment of the digestive function and a disturbance of the antioxidant status. Cu exposure increased the activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in fish digestive organs, suggesting the activation of amino acid metabolism. Furthermore, trichlorfon exposure reduced the activities of lactate dehydrogenase (LDH), glutathione reductase (GR), GOT and GPT, and the capacities of the anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR) in fish muscles, indicating a disruption of the bioenergetic homeostasis and antioxidant status. Our present study indicates that dietary EML supplementation relieved the detrimental effects induced by these stressors.


Data-guide for brain deformation in surgery: comparison of linear and nonlinear models.
Pre-operative imaging devices generate high-resolution images but intra-operative imaging devices generate low-resolution images. To use high-resolution pre-operative images during surgery, they must be deformed to reflect intra-operative geometry of brain. We employ biomechanical models, guided by low resolution intra-operative images, to determine location of normal and abnormal regions of brain after craniotomy. We also employ finite element methods to discretize and solve the related differential equations. In the process, pre- and intra-operative images are utilized and corresponding points are determined and used to optimize parameters of the models. This paper develops a nonlinear model and compares it with linear models while our previous work developed and compared linear models (mechanical and elastic). Nonlinear model is evaluated and compared with linear models using simulated and real data. Partial validation using intra-operative images indicates that the proposed models reduce the localization error caused by brain deformation after craniotomy. The proposed nonlinear model generates more accurate results than the linear models. When guided by limited intra-operative surface data, it predicts deformation of entire brain. Its execution time is however considerably more than those of linear models.


Spatio-temporal frequency separability in area 18 neurons of the cat.
Spatial frequency tuning curves were obtained at a series of temporal frequencies and/or velocities from neurons of Areas 17 and 18 of the cat, in order to assess the interaction between these spatial and temporal parameters. In the great majority of instances, for neurons in both Areas 17 and 18, we found the optimal spatial frequency invariant with the temporal frequency or velocity at which a neuron was tested. Thus in this respect, responses of neurons in Area 18, like those of Area 17, are separable in their dependence on spatial and temporal frequency.


Historical review, epidemiology and natural history of degenerative mitral valve disease.
Chronic mitral valve disease due to myxomatous degeneration (MMVD) is the most common cardiovascular disease in dogs and has been known to cause congestive heart failure for more than 100 years. This article presents an historical perspective of the disease and reviews the most updated data on epidemiology and natural history of MMVD in dogs.


Oxygen loss from Spartina alterniflora and its relationship to salt marsh oxygen balance.
Spartina alterniflora has been reported to lose significant amounts of oxygen to its rhizosphere with potentially important effects on salt-marsh biogeochemical cycling and plant productivity. The potential significance of this oxidative pathway was evaluated using laboratory split-chamber experiments to quantify oxygen loss from intact root systems under a wide variety of pre-treatment and incubation conditions including antibiotics to inhibit microbial respiration. The aerenchyma system of S. alterniflora was found to transport O2, N2, Ar, and CH4 from above-ground sources to its below-ground roots and rhizomes. While non-respiratory gases were observed to move from the lacunae to water bathing the root systems, net O2 loss did not occur; instead oxygen present outside of the roots/rhizomes was consumed. Net oxygen loss was found when resistance to gas transport was reduced in the lacunae-rhizosphere pathway by placing the root systems in a gas phase and when plant respiration was significantly reduced. Root system respiration appeared to be the major variable in the plant oxygen balance. When root and rhizome respiration was inhibited using poisons or lowered by cooling, the oxygen deficit was greatly reduced and oxygen loss was indicated. The effect of seasonal temperature changes on root system "oxygen deficit" presents a possible explanation as to why Spartina produces root systems with respiration rates that cannot be supported by gas transport. Overall, while oxygen loss from individual plant roots is likely, integrating measured root system oxygen loss with geochemical data indicates that the mass amount of oxygen lost from S. alterniflora root systems is small compared to the total oxygen balance of vegetated salt marsh sediments.


Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment.
The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding. In a transgenic mouse model overexpressing the antigen systemically, the ATP switch antibody binds to the antigen in tumors with minimal binding in normal tissues and plasma and inhibits tumor growth. Thus, we demonstrate that elevated extracellular ATP concentration can be exploited to specifically target the TME, giving therapeutic antibodies the ability to overcome on-target off-tumor toxicity.


High-resistance strength training does not affect nerve cross sectional area - An ultrasound study.
The aim was to study the effect of high-resistance strength training on peripheral nerve morphology, by examining properties of peripheral nerves as well as distal and proximal muscle thickness with ultrasound, comparing healthy individuals who perform and do not perform high-resistance strength training. Neuromuscular ultrasound was used to examine cross sectional area (CSA) of the median and musculocutaneous nerves, and muscle thickness of the abductor pollicis brevis muscle, biceps brachii muscle, quadriceps muscle and extensor digitorum brevis muscle, in 44 healthy individuals, of whom 22 performed regular high-resistance strength training. No difference in nerve CSA was found between trained and untrained individuals although trained individuals had thicker biceps brachii muscles. The CSA of the median nerve in the forearm correlated with participants' height and was significantly larger in men than women. In this cohort, CSA of the median and musculocutaneous nerves was not affected by strength training, whereas gender had a prominent effect both on CSA and muscle thickness. This is the first study to examine the effect of high-resistance strength training on peripheral nerves with neuromuscular ultrasound.


New adduct of abietane-type diterpene from Salvia leriifolia Benth.
A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy.


Smoke-free Europe in the year 2000: nongovernmental action (smoking cessation treatment).
Tobacco control has to be performed by following a comprehensive approach. This approach means a variety of strategies including health education and public information, smoking cessation, legislation, price policy, and taxation. It is the responsibility of the health care system to provide treatment for those who are nicotine addicted. There is now sufficient scientific background for cessation to be implemented much more than before. Cessation means offering a wide variety of techniques and methods for different target groups, and providing different organizational structures with different levels of assistance for the smoker. A diversified system of techniques to help the smoker to stop includes the following. Methods to help the already highly motivated, low-dependent smoker (mass media-assisted techniques, simple brochures, self-help techniques) Methods to help motivated, rather highly dependent smokers (e.g., nicotine replacement therapy) Basic for all the other intervention techniques are methods to create and maintain motivation (health education, public information, public education).


MiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma.
MicroRNAs (miRNAs) may function as either oncogenes or tumor suppressors in the malignant progression of different tumor types. MiR-663 was recently reported to be decreased and identified as a tumor suppressor in gastric cancer. We also verified its role in repressing cell proliferation of a gastric cancer cell line. In this study, however, miR-663 was found to be upregulated in nasopharyngeal carcinoma (NPC) cells compared with human immortalized nasopharyngeal epithelium cells, using a miRNA microarray, and this higher expression was confirmed in NPC tissue samples. Indeed, inhibition of miR-663 impaired the proliferation of NPC cells in vitro and the NPC tumor growth of xenografts in nude mice. Mechanistically, miR-663 directly targeted p21(WAF1/CIP1) to promote the cellular G1/S transition, as the inhibitory effects of miR-663 on the G1/S transition could be rescued by p21(WAF1/CIP1) silencing. Our results imply that miR-663 may act as an oncogene in NPC. The newly identified miR-663/p21(WAF1/CIP1) axis clarifies the molecular mechanism of NPC cell proliferation and represents a novel strategy for the diagnosis and treatment of patients with NPC.


Glucose regulates the histone acetylation of gene promoters in decidualizing stromal cells.
Decidualization stimuli activate the insulin signaling pathway and increase the glucose uptake in human endometrial stromal cells (ESCs). The inductions of prolactin (PRL) and IGF-binding protein-1 (IGFBP1), specific markers of decidualization, were inhibited by incubating ESCs under low glucose concentrations. These results suggested that decidualization stimuli activate the insulin signaling pathway, which contributes to decidualization through the increase of glucose uptake. Here, we investigated the mechanisms by which glucose regulates decidualization. ESCs were incubated with cAMP to induce decidualization. We examined whether low glucose affects the expression levels of transcription factors that induce decidualization. Forkhead box O1 (FOXO1) expression was significantly suppressed under low glucose conditions. Knockdown of FOXO1 by siRNA inhibited the expression levels of PRL and IGFBP1 during decidualization. Taken together, our results showed that low glucose inhibits decidualization by decreasing FOXO1 expression. We also examined the levels of histone H3K27 acetylation (H3K27ac), which is related to active transcription, of the promoter regions of FOXO1, PRL and IGFBP1 by ChIP assay. The H3K27ac levels of these promoter regions were increased by decidualization under normal glucose conditions, but not under low glucose conditions. Thus, our results show that glucose is indispensable for decidualization by activating the histone modification status of the promoters of PRL, IGFBP1 and FOXO1.


Using clinical skills exams to evaluate medical student skills in prevention.
In 2006, the Brody School of Medicine Regional Medicine-Public Health Education Center integrated the teaching of prevention into the curriculum for first-, second-, and third-year medical students. The purpose of this article is to report on the use of clinical skills exams (CSEs) in the evaluation of prevention health instruction for the period 2006-2010. Two CSEs were employed to measure preventive skills at the end of the third year of medical school. CSE-1 was a woman aged 56 years with knee pain. The outcome measure is the percentage of students asking three or more prevention history items. CSE-2 was a boy, aged 15 years, undergoing a sports physical/preventive screening. The outcome measure is the number of prevention items queried. For CSE-1, the percentage of students who met the outcome measure increased to 83% in 2010 as compared to 62% in both 2009 and 2007. The improvement between 2007 and 2010 was significant with a p=0.0080 (Fisher's exact test). Of the 64 students taking the third-year medical student objective structured clinical examination-2 in June 2009, the greatest number queried the following preventive items: exercise (98%), alcohol misuse (98%), drug use (98%), school and grades (98%), sexual activity (98%), and tobacco use (97%). By integrating prevention elements into CSE cases, the results are useful for student assessment and may be a powerful influence on curricular design, leading to an increase in prevention content.


[Experimental therapy of Coxsackie B3 virus infection with immunomodulator contained in water-soluble Penthaphylloides fruticosa extract].
The possibility of using water-soluble substance extracted from P. fruticosa in experimental Coxsackie B3 virus infection in newborn mice was studied. The curative action of the extract was studied by its injection to the infected animals for 7 days and its prophylactic action--by introducing it 24 hours and, repeatedly, 1 hour before infection. The study revealed the increase of such characteristics as survival rate, mean survival time, body weight dynamics, as well as decreased level of virus accumulation in the brain, liver and heart tissues of the animalsunder experiment. The immunomodulating properties of the extract were shown.


3D printing in spine care: A review of current applications.
3D printing (3DP) has been brought to medical use since the early part of this century- but it has been widely researched on and publicized only in the last few years. Amongst patients with spinal disorders, 3DP has been utilized in various facets of patient care. These include pre-operative aspects - such as patient education, resident training, pre-operative planning and simulations, intra-operative assistance in the form of customized jigs for pedicle screw insertion, patient specific interbody cages and vertebral body substitutes in complex malignancies and spinal infections. It has also been utilized in deformity surgeries and has opened new avenues in minimally invasive spine care. Guidelines have now been drafted by various organizations including the FDA with a prime focus on quality control measures applicable to this new technology. There has been a recent surge in publications supporting the use of 3DP in spinal disorders, reporting an improvement in various aspects of patient care. As the technology spreads out its wings further, more innovations and applications are expected to unfold in the coming years. Considering the rapid advances that 3DP has made, having a basic understanding of this technology is imperative for all spine surgeons. Despite promising preliminary results, there still exist a few pitfalls of the technology which have hindered the universal application of 3DP. Most importantly, there is a dearth of data related to long term outcomes supporting its clinical use. The prohibitive cost of 3D models, the specialized manpower it necessitates and the need for specific instrumentation are major deterrents to widespread use of this technology, particularly in small-scale healthcare setups. With further advancements in technology, the goal must be to make it more accurate and affordable to hospitals and patients so that the benefits of the technology can reach a wider patient population.


Idiopathic interstitial fibrosis.
The lung has only a limited pattern of response to injury. Idiopathic interstitial fibrosis is a descriptive term, describing the end stage of one pattern of pulmonary fibrosis in which the inflammation lies within the structure of the alveolar walls and around vessels and bronchioli, in the interstitium. The disease is characteristically subpleural in distribution and provides a marked restrictive consequence on pulmonary function which progresses to hypoxic core pulmonale. This is despite the apparent normality of much of the lung at autopsy. Six to fifteen percent develop lung cancer, the proportion depending on the autopsy rate. A nonspecific nature of the changes limits the diagnostic value of transbronchial biopsy, open lung biopsy may be of value in assessing and grading the disease in relationship to therapy.


Measuring knowledge of citizenship rights and responsibilities.
The purpose of this study was to develop and standardize an instrument designed to assess the extent to which people with mental retardation demonstrate knowledge about citizenship rights and responsibilities. The test development phase included: (a) generating 83 items related to six content areas (i.e., human, civil, and legal rights; and moral, civic, and legal responsibilities), and (b) pilot testing these items with 236 members of self-advocacy groups for people with developmental disabilities. The resulting 30-item instrument was standardized with a sample of 391 self-advocates from 13 states. The psychometric properties of the standardized instrument included: a mean performance level of 77% correct; a mean item-total correlation of r-ij = .33; and an internal consistency reliability coefficient of r alpha = .82. The instrument's potential usefulness as a device for screening, diagnosis, and program evaluation was supported by its psychometric properties. Future studies could address the use of the instrument with the secondary school age population that faces the transition from school to community.


A capillary diffusion method for determining hemolytic complement activity in undiluted serum .
A method is presented for measuring the hemolytic activity of undiluted guinea pig serum. Undiluted serum is placed in contact with a column of sensitized sheep red blood cells in an agar matrix in a capillary tube. After incubation, the length of the zone of lysis is measured. Comparison with a standard curve prepared from dilutions of a pool of normal serum allows relative quantitation. Because the serum is not diluted, this method allows detection of reversible inhibitors of the complement system.


A novel slurry sampling analysis of lead in different water samples by electrothermal atomic absorption spectrometry after coprecipitated with cobalt/pyrrolidine dithiocarbamate complex.
A preconcentration/separation technique based on the coprecipitation of lead with cobalt/pyrrolidine dithiocarbamate complex (Co(PDC)(2)) and subsequently its direct slurry sampling determination by electrothermal atomic absorption spectrometry (AAS) was described. For this purpose, at first, lead was coprecipitated with cobalt/pyrrolidine dithiocarbamate complex formed using ammonium pyrrolidine dithiocarbamate (APDC) as a chelating agent and cobalt as a carrier element. The supernatant was then separated and the slurry of the precipitate prepared in Triton X-100 was directly analyzed by electrothermal atomic absorption spectrometry with respect to lead concentration. The effects of experimental conditions on coprecipitation of lead with gathering precipitate as well as homogeneity and stability of the slurry were investigated. After the optimization of experimental parameters, a 100-fold enrichment of the analyte with quantitative recovery (>90%) and high precision (<10% R.S.D.) were obtained. By using the proposed technique, the lead concentrations in heavy matrices of Certified Sea-water and wastewater samples could be practically and rapidly determined in the range of 95% confidence level. The detection limit of the described method for lead using sample-matching blanks was 1.5 ng/L (3 sigma, N=10).


Bisphenol S instead of Bisphenol A: Toxicokinetic investigations in the ovine materno-feto-placental unit.
Bisphenol S (BPS) is widely used as a substitute for Bisphenol A in consumer products. Despite its potential endocrine-disrupting effects and widespread exposure, toxicokinetic data, particularly during the critical period of pregnancy, are not available for BPS. The objectives of our study were to evaluate the mechanisms determining fetal exposure to BPS and to BPS glucuronide (BPSG) and to compare them with those prevailing for BPA. The disposition of BPS and BPSG was evaluated in the materno-fetal unit of the catheterized pregnant ewe model, following intravenous administrations of BPS and BPSG to mothers and their fetuses. In a second experiment, the rate of BPS accumulation in the fetal compartment was determined under steady-state conditions after repeated intravenous BPS administrations to the mother. In the maternal compartment, BPS was mainly metabolized into BPSG and totally eliminated in urine. Only 0.40% of the maternal dose was transferred to the fetus. However, once in the fetal compartment, 26% of the fetal dose was rapidly eliminated through placental transfer, while 46% of BPS was metabolized into BPSG which remained trapped in the fetal compartment. Thus, the elimination of BPSG from the fetal compartment required its back-conversion into bioactive BPS, leading to an 87% enhancement of the fetal BPS exposure. Our findings demonstrate that, despite the low materno-fetal placental transfer of BPS, this substitute for BPA is able to accumulate in the fetal compartment after repeated maternal exposure, leading to chronic fetal exposure to BPS in a range of concentrations similar to those of BPA.


Prevalence and clinical significance of deep vein thrombosis in Hispanic patients with acute pulmonary embolism.
The prevalence of concomitant deep vein thrombosis (DVT) and its impact on 30-day outcomes in Hispanic patients with acute pulmonary embolism (PE) is unknown. We retrospectively studied a cohort of Hispanic patients admitted for acute PE to determine the relationship of concomitant DVT to clot burden on chest computer tomography (CT), right heart strain, and 30-day mortality. We identified 391 patients admitted with acute PE; 168 (42.9%) had concomitant DVTs on admission; 39 patients (9.9%) died during the 30-day follow-up: 12 patients without concomitant DVT and 27 with concomitant DVT, respectively (p < .001). The presence of a proximal DVT independently predicted 30-day mortality even after adjusting for age, gender and admission PE severity index scores (PESI) (hazard ratio [HR] 2.0; 95% confidence interval [CI]: 1.4-3.0, p = .001). Proximal DVTs remained a significant predictor of 30-day mortality in patients with low and intermediate PESI scores (HR 2.5; 95% CI: 1.1-6.0, p = .035). The prevalence of concomitant DVT in Hispanic patients presenting with acute DVT is relatively lower than other ethnic groups. However, a proximal location of a DVT is of significant prognostic relevance. Hispanic patients with acute PE should routinely undergo compression doppler ultrasonography (CDUS) of the lower extremities.


Glycoproteomic analysis reveals the effects of bisecting GlcNAc in intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is the second major subtype of primary liver cancer and has caused more and more attention with increasing incidence and mortality worldwide. Our previous study found that bisecting N-glycans are commonly increased in ICC, while the effects and potential functions of bisecting GlcNAc in ICC are still largely unclear. In this study, we further confirmed that the structures of bisecting GlcNAc were significantly up-regulated in ICC compared with paracancer tissues by glycoproteomic data and lectin histochemistry. The expression of its glycosyltransferase MGAT3 was also up-regulated in ICC tissues at both mRNA and protein levels, and expression of MGAT3 is negatively correlated with overall survival explored by bioinformatic analyses and published datasets from 255 patients. Next, the silencing of MGAT3 could inhibit the growth and invasion of ICC cells, and overexpressing of MGAT3 only promoted ICC cell invasion. Further glycoproteomic analysis showed that the commonly glycoproteins modified by bisecting GlcNAc after MGAT3-overexpression in two ICC cell lines were mainly involved in cell movement-related biological processes, such as cell adhesion, integrin-related and ECM-receptor interaction. This study sheds light on the potential effects of bisecting GlcNAc in ICC cells and suggests that MGAT3 might be used as a potential target in the therapy of ICC.


Pooled analysis of patients with thunderclap headache evaluated by CT and LP: is angiography necessary in patients with negative evaluations?
Severe, abrupt onset headache raises concern for aneurysmal subarachnoid hemorrhage (SAH). The current standard work-up is brain CT scan followed by LP if the CT is non-diagnostic in patients with a normal neurological exam. Some have suggested that angiography is also indicated in this common clinical situation. Is evaluation with brain CT and LP for thunderclap headache to rule out SAH sufficient and is angiography needed? We systematically searched for studies that followed neurologically-intact patients with thunderclap headache and normal CT and LP for at least 1 year. The primary outcome was SAH. We estimated the proportion of patients who developed SAH and the one-sided upper 95% confidence bound. Seven studies including 813 patients were identified. None of the patients developed SAH during follow-up (pooled proportion=0, upper 95% confidence bound=0.004). Although our methods have important limitations, we believe that this analysis will give clinicians better tools to decide whether or not to pursue further work-up with angiography in patients with thunderclap headache and normal neurological exam, CT, and LP.


Suppression of adult cytogenesis in the rat brain leads to sex-differentiated disruption of the HPA axis activity.
The action of stress hormones, mainly glucocorticoids, starts and coordinates the systemic response to stressful events. The HPA axis activity is predicated on information processing and modulation by upstream centres, such as the hippocampus where adult-born neurons (hABN) have been reported to be an important component in the processing and integration of new information. Still, it remains unclear whether and how hABN regulates HPA axis activity and CORT production, particularly when considering sex differences. Using both sexes of a transgenic rat model of cytogenesis ablation (GFAP-Tk rat model), we examined the endocrinological and behavioural effects of disrupting the generation of new astrocytes and neurons within the hippocampal dentate gyrus (DG). Our results show that GFAP-Tk male rats present a heightened acute stress response. In contrast, GFAP-Tk female rats have increased corticosterone secretion at nadir, a heightened, yet delayed, response to an acute stress stimulus, accompanied by neuronal hypertrophy in the basal lateral amygdala and increased expression of the glucocorticoid receptors in the ventral DG. Our results reveal that hABN regulation of the HPA axis response is sex-differentiated.


Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine.
Nerve root irritation induced by factors produced by the intervertebral disc may play a crucial role in the pathophysiology of sciatic pain production. In this study we used immunohistochemistry to investigate the presence of transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc bioptic specimens from 30 patients with disc herniation (protrusion type). Chondrocytes of herniated discs stained positive for TGF-beta1, IGF-1, IL-6 and fibronectin. We demonstrated for the first time the presence of IL-6-R in the chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were used as controls. In these sections no immunoreaction for TGF-beta1, IL-6, or IL-6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities than herniated discs. These results demonstrated the production of factors such as TGF-beta1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc herniation.


The interpretation of retrograde pancreatography in the elderly.
Endoscopic retrograde pancreatography is regarded as the most specific technique in the diagnosis of chronic pancreatitis. In the elderly the relevance of endoscopic retrograde pancreatography changes in establishing the diagnosis is disputed. The pancreatograms of 101 patients aged seventy-five years or more, who had endoscopic retrograde pancreatography for suspected biliary or pancreatic pathology, were reviewed. Only four patients subsequently proved to have unequivocal chronic pancreatitis. There was no significant difference in the size or contour of the main pancreatic duct, or in side branch changes between those patients presenting with common bile duct stones, incidental biliary pathology and pain of probable pancreatic origin. Three definite diagnostic criteria for the diagnosis of chronic pancreatitis emerged--duct obstruction with a stricture, gross irregularity of the main pancreatic duct and the presence of large cavities.


Ephedrine hydrochloride: novel use in the management of resistant non-neurogenic daytime urinary incontinence in children.
To determine whether the adrenoceptor agonist, ephedrine hydrochloride, is an effective treatment for resistant non-neurogenic daytime urinary incontinence in children. From 2000 to 2010, eighteen children with resistant non-neurogenic daytime urinary incontinence were treated with oral ephedrine hydrochloride at our institution. Sixteen were female and two were male. Median age at treatment was 12 years (range 5-15 years). Two children had spina bifida occulta. There were no other co-morbidities. Multiple anticholinergics were prescribed and dose maximized to support a bladder and bowel training programme, without achieving continence in this resistant group of children. Pre-treatment urodynamics were normal in 10, but revealed an open bladder neck in 8 patients. None showed detrusor over-activity. Oral ephedrine hydrochloride was started at 7.5 mg or 15 mg twice daily and titrated up to a maximum of 30 mg four times daily according to response. Median follow-up was 7 years (range 6-8 years). Seventeen children (94%) reported improvement in symptoms and six (33%) achieved complete urinary continence. All patients maintained compliant bladders on post-treatment urodynamics. Seven of the 8 previously open bladder necks were closed. No patients reported any significant side effects. Patients with open bladder necks on pre-treatment urodynamics were more likely to show a full response to ephedrine (odds ratio 15; 95% CI 1.2-185.2). Oral ephedrine hydrochloride is an effective treatment for carefully selected children with resistant non-neurogenic daytime urinary incontinence.


Cyclic AMP formation of isolated human corpora lutea in response to HCG - interference by PGF2 alpha.
Human corpora lutea of defined ages were excised at operation, cut into pieces and incubated in the presence of HCG, PGF2 alpha and PGE2 alone or in combination. Following incubation cAMP formation in tissue and medium was determined. HCG-stimulated tissue cAMP content was most pronounced at a corpus luteum age of 7-10 days after ovulation. This stimulation was antagonized by PGF2 alpha in corpora lutea older than 6 days. PGE2 stimulated cAMP formation per se and this effect was more pronounced when HCG and PGE2 were combined. A possible role for PGF2 alpha as a luteolytic substance in the human is suggested.


Traumatic hyphema in children.
The authors reviewed the medical records of 316 children admitted between January 1977 and March 1985 with a diagnosis of traumatic hyphema. In this group of patients, 1 to 17 years old treated without antifibrinolytics, the incidence of secondary hemorrhage was 7.6% (24 of 316 patients) of whom three required surgical evacuation of the clot. The risk of rebleeding did not correlate with the patient's age, use of topical steroids, or cycloplegics. Of 176 patients followed from 1 month to 7 years post-hospital discharge, 91% achieved 20/30 vision or better, but only 77% of the patients with secondary hemorrhage attained this level of vision. Amblyopia, a potential threat in young children, occurred in only two children both of whom also required cataract extraction. From our captive pediatric population of 228,000 the incidence of traumatic hyphema is 17 per 100,000 children per year.


Financial Strain, Major Family Life Events, and Parental Academic Involvement During Adolescence.
Parental academic involvement-whether through school participation and communication, or supervision and assistance at home-often has been cited as a way to enhance academic achievement. Yet, little is known about how the financial and life pressures faced by families can compromise parents' ability to become involved in their adolescents' education. In the current study, these dynamics were examined among Mexican-origin families, who often may face challenging financial and familial circumstances, and whose students may have more difficulty in secondary school. Parents of Mexican-origin ninth and tenth grade students from two high schools in Los Angeles (N = 428; 50 % female) completed quantitative interviews. The results revealed that financial strain predicted less involvement at school, and major family life events predicted less involvement at home, even after controlling for potentially confounding factors. Moreover, both of the associations between parental stress and parental academic involvement were mediated by lower levels of relationship quality between parents and adolescents, but not by conflict within the parent-adolescent dyad or parental depressive and somatic symptoms. The findings suggest that stress may limit parents' ability to become involved their adolescents' education, and highlight the importance of understanding family dynamics when examining parental academic involvement among Mexican-origin families.


Olfaction, "olfiction," and the schizophrenia-spectrum: an updated meta-analysis on identification and acuity.
Olfaction deficits in individuals with schizophrenia are well documented. A meta-analysis conducted nearly a dozen years ago on the topic revealed a deficit of a full standard deviation in magnitude compared to nonpatient controls. Recent efforts have been attempted to determine whether deficits in olfactory identification and acuity reflect a vulnerability marker of schizophrenia-spectrum pathology. To address this issue, the present study conducted a meta-analysis of 16 studies of individuals with schizotypy, defined in terms of a) "ultra-high risk" status, b) having an affected biological family member, or c) having extreme scores on a schizotypy questionnaire. We also conducted an updated meta-analysis of 40 studies of olfactory functioning in schizophrenia. Consistent with the prior meta-analysis, patients with schizophrenia showed impairments in olfaction identification on a full standard deviation in magnitude (d = -.99). Individuals with schizotypy showed much more subtle (d = -.24) differences in olfaction, though the effect sizes were higher for studies examining individuals at "ultra-high risk" (d = -.67) versus studies examining individuals with psychometrically-defined (d = -.14) schizotypy. Differences in olfactory acuity, relative to their respective control groups, were small for both the schizophrenia (d = -.45) and schizotypy (d = -.38) studies but were similar in magnitude. The present findings argue against the notion that deficits in olfaction identification are a vulnerability marker of schizophrenia. Suggestions for future research are recommended.


Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics.
A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.


GPFrontend and GPGraphics: graphical analysis tools for genetic association studies.
Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.


Cytotoxic T cells reactive to an immunodominant leukemia-associated antigen can be specifically primed and expanded by combining a specific priming step with nonspecific large-scale expansion.
Identification of dominant leukemia-associated neoantigens and favoring specific priming and subsequent expansion of T cells reactive to these antigens might harbor therapeutic potential. Here, a new strategy combines a specific T-cell activation step using tumor lysate-pulsed bone marrow-derived dendritic cells with a nonspecific large-scale expansion method. The leukemia cell line C1498 transduced with a potentially immunodominant antigen (ovalbumin) was used to track expansion and functionality of antigen-specific cytotoxic T cell (CTL), both in vitro and in vivo. Three times more leukemia-specific CTL could be generated when compared with the respective controls. CTL generated after increasing the antigen-specific T-cell precursor frequency in vitro cured up to 80% of mice bearing leukemia with the respective antigen (P < 0.005, as compared with controls). Alternatively, the yield of CTL reactive to a immunodominant neoantigen increased by factor 2 to 6 when T-cell donors were immunized with dendritic cell presenting the respective antigen. However, increasing the leukemia-reactive precursor frequency to a clinically exploitable level will be the key for the design of successful T-cell therapy trials.


The 8 : 1 : 1 ternary hybrid framework in the system [EDT-TTF +][1,4-bis(iodoethynyl)benzene][Re6Se8(CN)6]4-: dual noncovalent expression of the octahedral halogen-bond hexa-acceptor nanonode.
Complementary shapes of the neutral symmetrical halogen-bond bis-donor core and octahedral inorganic cluster core prevent halogen-bonded polymers developing in more than one direction, favouring further templating by conducting radical cation slabs and yielding an 8 : 1 : 1 phase formulation instead of n : 2 : 1, with a 2D net, or m : 3 : 1, with a pseudo-cubic architecture, which may in principle also be targeted.


Identification of a characteristic 31P NMR signal in acute experimental pancreatitis with the aid of 1H-31P correlated 2D measurements of intact pancreas.
Two-dimensional 1H-31P correlation spectroscopy and relaxation time measurements of intact diseased pancreas were performed in order to identify an unknown peak appearing at -0.18 +/- 0.04 ppm in a 31P NMR spectrum of taurocholate-induced experimental acute pancreatitis in rats. The signal was identified as a solubilized lecithin taurocholate complex.


Synovitis and radiographic progression in non-erosive and erosive hand osteoarthritis: is erosive hand osteoarthritis a separate inflammatory phenotype?
To compare the prevalence of synovitis, pain and radiographic progression in non-erosive and erosive hand osteoarthritis (HOA), and to explore whether the different rate of disease progression is explained by different levels of synovitis and structural damage. We included 31 and 34 participants with non-erosive and erosive HOA at baseline, respectively. Using Generalized Estimating Equations, we explored whether participants with erosive HOA had more synovitis (by MRI, ultrasound and clinical examination) independent of the degree of structural damage. Similarly, we explored whether pain at baseline and radiographic progression after 5 years were higher in erosive HOA, independent of the levels of synovitis and structural damage. All analyses were adjusted for age and sex. Power Doppler activity was found mainly in erosive HOA. Participants with erosive HOA demonstrated more moderate-to-severe synovitis, assessed by MRI (OR = 1.73, 95% CI 1.11-2.70), grey-scale ultrasound (OR = 2.02, 95% CI 1.25-3.26) and clinical examination (OR = 1.80, 95% CI 1.44-2.25). The associations became non-significant when adjusting for more structural damage. The higher frequency of joint tenderness in erosive HOA was at least partly explained more structural damage and inflammation. Radiographic progression (OR = 2.53, 95% CI 1.73-3.69) was more common in erosive HOA independent of radiographic HOA severity and synovitis (here: adjusted for grey-scale synovitis by ultrasound). Erosive HOA is characterized by higher frequency and more severe synovitis, pain and radiographic progression compared to non-erosive HOA. The higher rate of disease progression was independent of baseline synovitis and structural damage.


Expression analysis of MMP14: Key enzyme action in modulating visceral adipose tissue plasticity in patients with obesity.
Compromised adipose tissue plasticity is a hallmark finding of obesity orchestrated by the intricate interplay between various extracellular matrix components. Collagen6 (COL6) is well characterized in obese visceral adipose tissue (VAT), not much is known about MMP14 which is hypothesized to be the key player in matrix reorganization. Subjects with obesity (BMI ≥40; n = 50) aged 18-60 years undergoing bariatric surgery and their age-matched controls (BMI < 25; n = 30) were included. MMP14, Col6A3 and Tissue inhibitor of metalloproteinase 2 (TIMP2) mRNA expression was assessed in VAT and their serum levels along with endotrophin were estimated in both groups preoperatively and post-operatively in the obese group. The results were analysed statistically and correlated with anthropometric and glycaemic parameters, namely fasting glucose and insulin, HbA1c, HOMA-IR, HOMA-β and QUICKI. Circulating levels as well as mRNA expression profiling revealed significant differences between the individuals with and without obesity (p < .05), more so in individuals with diabetes and obesity (p < .05). Follow-up serum analysis revealed significantly raised MMP14 (p < .001), with decreased Col6A3, endotrophin and TIMP2 levels (p < .01, p < .001 and p < .01, respectively). A rise in serum MMP14 protein, simultaneous with post-surgical weight loss and decreased serum levels of associated extracellular matrix (ECM) remodellers, suggests its crucial role in modulating obesity-associated ECM fibrosis and pliability of VAT.


Structures of asparagine linked oligosaccharides of immunoglobulins (IgY) isolated from egg-yolk of Japanese quail.
Structures of the Asn linked oligosaccharides of quail egg-yolk immunoglobulin (IgY) were determined in this study. Asn linked oligosaccharides were cleaved from IgY by hydrazinolysis and labelled with p-aminobenzoic acid ethyl ester (ABEE) after N-acetylation. The ABEE labelled oligosaccharides were then fractionated by a combination of Concanavalin A-agarose column chromatography and anion exchange, normal phase and reversed phase HPLC before their structures were determined by sequential exoglycosidase digestion, methylation analysis, HPLC, and 500 MHz 1H-NMR spectroscopy. Quail IgY contained only neutral oligosaccharides of the following categories: the glucosylated oligomannose type (0.6% Glc alpha 1-3Glc alpha 1-3Man9GlcNAc2; 35.6%, Glc alpha 1-3Man7-9GlcNAc2). oligomannose type (15.0%, with the structure Man5-9GlcNAc2) and biantennary complex type with core structures of -Man alpha 1-3(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc (9.9%), -Man alpha 1-3 (GlcNAc beta 1-4)(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc (25.1%) and -Man alpha 1-3(GlcNAc beta 1-4)(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc (11.4%). Although never found in mammalian proteins, glucosylated oligosaccharides (Glc1Man7-9GlcNAc2) have been located previously in hen IgY.


Immunostaining with EGFR mutation-specific antibodies: a reliable screening method for lung adenocarcinomas harboring EGFR mutation in biopsy and resection samples.
Mutation analysis of epidermal growth factor receptor (EGFR) is essential in determining the therapeutic strategy for lung adenocarcinoma. Immunohistochemical (IHC) staining with EGFR mutation-specific antibodies of del E746-A750 in exon 19 and L858R in exon 21 has been evaluated in resection specimens in a few studies but rarely in biopsy samples. A total of 169 cases (78 biopsies and 91 resected specimens) of lung adenocarcinoma with EGFR mutation status predefined by direct DNA sequencing were histologically examined, and IHC was performed using EGFR mutation-specific antibodies of del E746-A750 and L858R. The cases with positive results by IHC but negative results by direct DNA sequencing were examined by amplified refractory mutation system. Our results showed that the frequency of EGFR mutations for both E746-A750 deletion and L858R mutation was 38.5% (65/169) by DNA sequencing or amplified refractory mutation system and 34.3% (58/169) by IHC in lung adenocarcinomas. Based on molecular test results, the overall sensitivity, specificity, positive predictive value, and negative predictive value of IHC using these 2 antibodies in all (biopsy/resection) cases were 87.7% (80%/94.3%), 99.0% (97.9%/100%), 98.3% (96%/100%), and 92.8% (88.7%/96.6%), respectively. Lung adenocarcinomas with a predominant acinar, papillary, lepidic, or solid growth pattern more often harbor EGFR mutation of del E746-A750 or L858R. In conclusion, the immunostaining with EGFR del E746-A750 and L858R mutation antibodies is a reliable screening method with high specificity and sensitivity for identifying the EGFR mutation in both resected and biopsied lung adenocarcinomas.


Linking environmental risk factors with epigenetic mechanisms in Parkinson's disease.
Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disease, with a complex risk structure thought to be influenced by interactions between genetic variants and environmental exposures, although the full aetiology is unknown. Environmental factors, including pesticides, have been reported to increase the risk of developing the disease. Growing evidence suggests epigenetic changes are key mechanisms by which these environmental factors act upon gene regulation, in disease-relevant cell types. We present a systematic review critically appraising and summarising the current body of evidence of the relationship between epigenetic mechanisms and environmental risk factors in PD to inform future research in this area. Epigenetic studies of relevant environmental risk factors in animal and cell models have yielded promising results, however, research in humans is just emerging. While published studies in humans are currently relatively limited, the importance of the field for the elucidation of molecular mechanisms of pathogenesis opens clear and promising avenues for the future of PD research. Carefully designed epidemiological studies carried out in PD patients hold great potential to uncover disease-relevant gene regulatory mechanisms. Therefore, to advance this burgeoning field, we recommend broadening the scope of investigations to include more environmental exposures, increasing sample sizes, focusing on disease-relevant cell types, and recruiting more diverse cohorts.


Infective endocarditis: clinical features in young and elderly patients.
The elderly constitute an increasing percentage of patients with infective endocarditis. The disease manifestations and outcomes in 53 episodes of endocarditis in patients over the age of 60 were reviewed and compared with 55 episodes of endocarditis in patients less than 40 years of age and 46 episodes of endocarditis in patients aged 40 to 60. The percentage of cases caused by staphylococci and streptococci were roughly equal in all groups. Enterococci, Streptococcus bovis, and coagulase-negative staphylococci were more common in the elderly. In the elderly, invasive vascular procedures were the most common source of infection. Endocarditis acquired nosocomially accounted for 23 percent of all episodes in older patients. The elderly reported fewer symptoms and showed a diminished febrile response. Errors in diagnosis were noted in 68 percent of elderly patients, and a delay in initiating appropriate therapy was more common in this age group. The mortality rate was significantly higher in the elderly (45.3 percent) than in the middle-aged (32.6 percent) and young (9.1 percent). Endocarditis in elderly patients is often nosocomially acquired, is difficult to diagnose, and is associated with a higher mortality than noted in younger patients.


Chronic hepatitis. An emerging syndrome in dogs.
Chronic active hepatitis has been recognized in humans since the 1950s but has been recognized only recently as a disease syndrome in dogs. The author describes this diverse group of chronic inflammatory liver diseases and discusses the factors related to its etiology, pathogenesis, diagnosis, and therapy.


Hurling-related hand injuries.
Hurling is a contact sport, associated with significant morbidity. We have identified specific hand injuries sustained by participants and quantified the functional and financial implications of these injuries. Over a 3-month period, all hand injuries seen in the fracture clinic of our regional trauma unit were studied prospectively. Of the 123 consecutive injuries, 41 (33%) were sustained during hurling matches. Metacarpal (47%) and proximal phalangeal (37%) fractures were the most frequent. Eight hurlers (20%) required surgical intervention. Only four (10%) of the injured players were wearing hand protection. The mean cost of injury to the player was pound 615. We suggest the introduction of the mandatory use of hand protection for hurling.


A new pathway for phosphatidylserine synthesis in rat liver microsomes.
It has been shown that the phosphate moiety of glycerophosphate is incorporated into phosphatidylserine of rat liver microsomes, but not of mitochondria. The reaction is dependent on CMP. This observation suggests that the new pathway of acyl-specific synthesis of phosphatidylserine proposed by J.P. Infante [(1984) FEBS Lett. 170, 1-14] can proceed in rat liver microsomes.


Simultaneous multislice imaging of the heart using multiband balanced SSFP with blipped-CAIPI.
In this work, we explore the use of multiband (MB) balanced steady-state free precession (bSSFP) with blipped-controlled aliasing in parallel imaging (CAIPI), which avoids the issues of altered frequency response associated with RF phase cycling, and show its application to accelerating cardiac cine imaging. Blipped and RF-cycled CAIPI were implemented into a retrospective-gated segmented cine multiband bSSFP sequence. The 2 methods were compared at 3T using MB2 to demonstrate the effect on frequency response. Further data (4 subjects) were acquired at both 1.5T and 3T collecting 12-slice short axis stacks using blipped-CAIPI with MB acceleration factors of 1-4. The impact on SNR and contrast was evaluated along with g-factors at different accelerations. Data acquired with blipped-CAIPI multiband bSSFP up to factor 4 yielded functional cine data with good SNR and contrast, while reliably keeping dark-band artefacts clear of the heart at 1.5T. SAR limits the maximum MB acceleration, particularly at 3T, where minimum TR increase is problematic and leakage artefacts are more prevalent. Mean g-factors across the heart were measured at 1.00, 1.06, and 1.12 for MB2-MB4, whereas blood-pool SNR measures (end-diastole) decreased by 11.8, 21.5, and 36.9%; ultimately LV-myocardium CNR remained sufficient at 1.5T with values ranging: 15.6, 13.4, 11.9, and 9.6 (MB1-MB4). Blipped-CAIPI multiband bSSFP can be used in cardiovascular applications without affecting the frequency response because of controlled aliasing and can be readily incorporated into segmented cine acquisitions without adding any additional constraints because of phase cycling requirements. The method was used to collect full ventricular coverage within a single breath-hold.


Transcriptional activity of PIF and Pong-like Class II transposable elements in Triticeae.
Transposable elements are major contributors to genome size and variability, accounting for approximately 70-80% of the maize, barley, and wheat genomes. PIF and Pong-like elements belong to two closely-related element families within the PIF/Harbinger superfamily of Class II (DNA) transposons. Both elements contain two open reading frames; one encodes a transposase (ORF2) that catalyzes transposition of the functional elements and their related non-autonomous elements, while the function of the second is still debated. In this work, we surveyed for PIF- and Pong-related transcriptional activity in 13 diploid Triticeae species, all of which have been previously shown to harbor extensive within-genome diversity of both groups of elements. The results revealed that PIF elements have considerable transcriptional activity in Triticeae, suggesting that they can escape the initial levels of plant cell control and are regulated at the post-transcriptional level. Phylogenetic analysis of 156 PIF cDNA transposase fragments along with 240 genomic partial transposase sequences showed that most, if not all, PIF clades are transcriptionally competent, and that multiple transposases coexisting within a single genome have the potential to act simultaneously. In contrast, we did not detect any transcriptional activity of Pong elements in any sample. The lack of Pong element transcription shows that even closely related transposon families can exhibit wide variation in their transposase transcriptional activity within the same genome.


Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration.
There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK (glycogen synthase kinase)-3α and -3β and down-regulation of E-cadherin (CDH1). Morpholino-mediated knockdown of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10 The non-redundant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying prion protein (PrP)-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programmes, such as EMT.


Changing patterns of mental health care.
The evaluation of intra- and extramural psychiatric care nowadays calls for new models and methods of services research as the transition from custodial to community mental health care results in patterns of utilization of high complexity. Not only the capacity and the components of the care system has changed considerably but also the composition of the cared patient groups. In Mannheim 3/4 of the schizophrenic patients requiring institutioned care for one year or more are admitted to sheltered homes and apartments due to the establishment of complementary services in the last 15 years. Data of a representation cohort of 148 schizophrenics observed over a period of 18 months show that corresponding to the multiple needs of the patients multiple utilization prevails. The effectiveness of extramural care can be demonstrated by a reduced probability of readmission to inpatient treatment. The economic efficiency of the provision of complementary care was evaluated by analyzing costs of service use by the cohort. The direct costs per case of all the services utilized over one year averaged 43% compared with an uninterrupted stay in a mental state hospital. Also in community mental health care almost 80% of the total costs accrue from hospital readmission due to relapses.


Reported disease and psychological well-being in Swiss adults.
In Switzerland, and in many other countries as well, the distribution of morbidity and perceived health in the general population and their determining factors have not been systematically studied so far. This article reports on exploratory study of prevalence of two complex health indicators, long-standing disease (Disease) and psychological well-being (Well-being) and of their environmental, person-specific and behavioural determinants. Data from a health survey conducted in five cantons and three language regions as part of the Swiss Intercantonal Health Indicators Project were used. Whereas distributions of prevalence of Disease according to gender, age, level of education and place of living confirm results of other studies, unexpected prevalence patterns were found for Well-being, especially with regard to gender differences. Multivariate analyses by general linear models (independent sub-samples of the study population were used to develop and validate models) showed different sets of environmental, person-specific and behavioural factors to explain inter-individual differences of Disease and Well-being, both in the total validation sample and in sub-samples of women and men. The results are discussed with regard to implications for socioepidemiological health research.


Optically active benzo[c]phenanthrene diol epoxides bind extensively to adenine in DNA.
Reactions of diol epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons with DNA are thought to initiate the carcinogenic process. Although formation of a benzo[a]pyrene (BaP) diol epoxide-deoxyguanosine adduct has been held responsible for biological activity, the more potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) binds extensively to deoxyadenosine residues in DNA, suggesting that hydrocarbon carcinogen-deoxyadenosine adducts may be instrumental in tumour initiation. Because the bay region diol epoxides of benzo[c]phenanthrene (BcPh) are very active tumour initiators, and the relative activities of the four configurationally isomeric 3,4-diol 1,2-epoxides (Fig. 1) are known, we examined their reactions with DNA. Each BcPh diol epoxide isomer exhibits a remarkable preference for covalent binding to DNA over hydrolysis, each yields a unique distribution of products with the nucleosides of DNA and each reacts extensively with deoxyadenosine residues in DNA. The relative tumour initiating activities of these stereoisomers is best reflected by the relative yields of one of the deoxyadenosine adducts formed.


Fibronectin is not a serum spreading factor for HeLa cells.
The spreading of HeLa cells on plastic substratum is mediated by fibronectin-depleted foetal calf serum but not by fibronectin isolated by gelatin-Sepharose affinity chromatography. The same is true for freshly explanted chick embryonic chondrocytes. In contrast, BHK cell spreading exceeds 67% after 120 min at 37 degrees C in fibronectin-supplemented (10 micrograms ml-1) serum-free medium. Long-term cultivation of HeLa cells in Eagle's MEM supplemented with fibronectin-free serum is associated with the accumulation of cells in mitosis or before cytokinesis; many cells die and the remaining living cells, characterized by marked changes in morphology, multiply very slowly. It can be concluded therefore that fibronectin does not produce spreading in HeLa cells but forces them into mitosis.


Anterior vs. Retzius-sparing robotic assisted radical prostatectomy: can the approach really make a difference?
Retzius-sparing Robotic Assisted Radical Prostatectomy (RS-RARP) is a novel surgical approach to radical prostatectomy. Its pioneers have suggested an improved recovery of urinary continence, while maintaining adequate cancer control. The aim of this systematic review was to explore available data on RS-RALP and compare functional, oncologic, and perioperative results of RS-RARP compared to anterior RARP. A search following PRISMA guidelines was performed including the combination of the following words: "Retzius" AND "sparing" AND "radical" AND "prostatectomy." Ninety-three articles were identified and 13 were included in the systematic review, including 3 randomized controlled trials (RCT), 4 prospective studies and 6 retrospective studies. All available randomized trials confirmed an improved immediate continence for RS-RARP, with rates ranging 51-71%, compared to 21-48% for anterior RARP. However, this advantage was progressively lost with no significant difference found after 6 months. Moreover, a prospective study found no discrepancy in terms of quality of life across the two techniques. Erectile function was difficult to compare, as patients had different baseline erectile function across studies and rate of neurovascular preservation was not comparable. Surgical approach remains controversial regarding positive margin rate, although related to the surgeon's experience and clinical stage. Biochemical recurrence-free survival appears similar between the two approaches. RS-RARP improves early urinary continence recovery compared to anterior RARP, with this advantage being lost after 3 to 6 months. Erectile function and quality of life were however comparable between the two techniques. The results concerning the rate of positive margins remained controversial. Future studies with longer follow-up are needed to better assess oncologic outcomes.


The Identification and Management of Small Intestinal Bacterial Overgrowth: A Functional Medicine Approach.
Small intestinal bacterial overgrowth (SIBO) can exist in common conditions such as irritable bowel syndrome, obesity, cirrhosis, and Parkinson. Using the functional medicine matrix broadens the lens of how to evaluate SIBO. Assessing the predisposing factors, triggers, and contributors of SIBO enables the provider to better understand possible management strategies. Applying the functional medicine 5R program, remove, replenish, repair, reinoculate, and rebalance includes conventional treatment of SIBO and expands the provider's toolbox on different modalities to restore gut function.


Natural polymorphisms of HIV-1 subtype-C integrase coding region in a large group of ARV-naïve infected individuals.
Integrase (IN) is an enzyme produced by human immunodeficiency virus (HIV)-1 that enables its genetic material to be integrated into the DNA of the infected cell. Still now, few data are available with detailed analysis of the natural IN polymorphisms of HIV-1 subtype-C in datasets retrieved from antiretroviral-naïve patients; this study focuses on these polymorphisms. The analysis included 335 HIV-1 subtype-C IN sequences (one per patient). Multi-alignment of IN sequences was performed, and for the definition of a polymorphism, only amino acid changes with prevalence ≥3 % among treatment-naïve patients were considered. Seventy IN amino acid positions were fully conserved. Differently, forty-six IN amino acid polymorphic positions were observed, 12 within the N-terminal domain and 13 within the C-terminal domain. In the DDE-catalytic motif, only one mutation per site (D64G/D116G/E152K) was found, while a low variability (<1 %) was observed for IN positions interacting with LEDGF/p75. A major drug resistance mutation for raltegravir (RAL) and elvitegravir (EVG), Q148H, was retrieved from one patient and another RAL primary resistance mutation, Y143H, was also retrieved from another patient. The results from the IN sequences analyzed underlined that some unexpected baseline substitutions affecting the susceptibility to RAL/EVG could be detected in drug-naïve individuals, and, therefore, it should be genotyped before the consideration of HIV-1 IN inhibitors (INIs). The impact of these mutations on the baseline drug susceptibility of HIV-1 subtype-C to INIs may need to be addressed prior to the introduction of these drugs in some Asiatic and African countries.


The Role of 18F-FDG PET/CT in Suspected Intraocular Sarcoidosis and Tuberculosis.
Purpose: To determine the utility of fluorine-18 fluorodeoxyglucose Positron Emission Tomography Computed Tomography (FDG PET/CT) in patients with suspected ocular sarcoidosis (OS) or intraocular tuberculosis (IOTB) in a resource-constrained, TB endemic area.Methods: Independent review of the FDG PET/CTs, Computed Tomography (CT) scans and chest radiographs (CXRs) of patients with suspected OS or IOTB and inconclusive conventional workup.Results: Twenty-nine PET/CTs and CXRs were reviewed, with 38% of PET/CTs and CTs demonstrating evidence of TB or sarcoidosis, compared to 21% of CXRs. The sensitivity, specificity, positive and negative predictive values for PET/CT and CT were similar - 85.7%, 95.5%, 85.7% and 95.5% for OS, and 33.3%, 100%, 100% and 68% for IOTB respectively and for CXR, 57.1%, 100%, 100% and 88% for OS, and 16.7%, 100%, 100% and 63% for IOTB.Conclusion: PET/CT added no significant additional benefit over Chest CT in patients with suspected OS or IOTB.


Updates on Human Neural Stem Cells: From Generation, Maintenance, and Differentiation to Applications in Spinal Cord Injury Research.
Human neural stem cells (hNSCs) and human induced pluripotent stem cells (hiPSCs) have been the primary focuses in basic science and translational research as well as in investigative clinical applications. Therefore, the capability to perform reliable derivation, effective expansion, and long-term maintenance of uncommitted hNSCs and hiPSCs and their targeted phenotypic differentiations through applying chemically and biologically defined medium in vitro is essential for expanding and enriching the fundamental and technological capacities of stem cell biology and regenerative medicine. In this chapter, we systematically summarized a set of protocols and unique procedures that have been developed in the laboratories of Prof. Teng and his collaborators. These regimens have been, over the years, reproducibly and productively used to derive, propagate, maintain, and differentiate hNSCs, including those derived from hiPSCs. We emphasize the multimodal methodologies that were pioneered and established in our laboratories for characterizing functional multipotency of stem cells and its value in basic science as well as translational biomedical studies.


Lethal chondrodysplasia punctata.
The radiological findings in five infants, with chondrodysplasia punctata, who died during the neonatal period are presented to illustrate the role of radiology in diagnosis and prognosis in this syndrome. Rhizomelic shortening of the limbs almost inevitably indicates an early demise. In the non-rhizomelic group, features such as excessive stippling and tracheal calcification are unreliable prognostic factors of early morbidity and mortality.


Race is a Risk Factor for the Deferral of Resection and Radiation for Early-Stage Lung Cancer.
There remain profound race-related disparities in the treatment of non-small cell lung cancer (NSCLC). Deferral of operative management for early-stage disease is recognized as driver of this disparity. Black race has been associated with higher rates of surgical deferral. It remains unclear how race impacts likelihood of receiving radiation therapy after declining surgical management of NSCLC. A retrospective cohort analysis was completed using data from the National Cancer Database (NCBD) for patients 18 and over with stage I NSCLC offered surgical resection from 2004 to 2015 (N = 89,462). Multivariable logistic regression identified predictors of surgical deferral and predictors for deferral of radiation after deferral of surgery. Kaplan-Meier survival analysis with log-rank tests and multivariable Cox proportional hazards regressions were performed. 87,293 (97.6%) patients underwent surgery, 2169 (2.4%) deferred. Patients who deferred had 2.1 times higher hazard ratio for mortality, (HR = 2.08, [1.97, 2.29], P < .001). Of those that deferred, 1250 (57.6%) received postdeferral radiation. Compared to White patients, Black patients had OR of 1.82 for deferring both surgery and radiation (aOR: 1.82, [1.31, 2.53], P < .001) and Asian and Pacific Island (API) patients had an OR of 2.67 (aOR: 2.67, [1.27, 4.64], P = .008). Other predictors of deferral of therapy included: Medicare or lack of insurance, and treatment at nonacademic medical centers. Insurance status and Black race, and API race are associated with deferring surgical therapy and radiation therapy for NSCLC. These findings are consistent with the large body of work showing worse outcomes for treatment of NSCLC in minority patients.


Are we giving too much iron? Low-dose iron therapy is effective in octogenarians.
Elderly patients are vulnerable to the dose-dependent adverse effects of iron replacement therapy. Our study examines whether low-dose iron therapy can efficiently resolve iron-deficiency anemia in patients over the age of 80 years and reduce adverse effects. Ninety hospitalized patients with iron-deficiency anemia were randomized to receive elemental iron in daily doses of 15 mg or 50 mg as liquid ferrous gluconate or 150 mg of ferrous calcium citrate tablets for 60 days. Thirty control patients without anemia were given 15 mg of iron for 60 days. A 2-hour iron absorption test was performed after the initial dose. Hemoglobin and ferritin levels were measured on day 1, 30, and 60 after initiating therapy. Each patient completed a weekly questionnaire regarding drug-induced adverse effects. Serum iron rose significantly in the anemic patients beginning 15 minutes after the first dose but not in nonanemic patients. Two months of iron treatment significantly increased hemoglobin and ferritin concentrations similarly in all 3 groups of iron-deficiency anemia patients (for example, hemoglobin levels rose from 10.0 g/dL to 11.3 g/dL with 15 mg/d of iron therapy and from 10.2 g/dL to 11.6 g/dL with 150 mg/d). Abdominal discomfort, nausea, vomiting, changes in bowel movements, and black stools were significantly more common at higher iron doses. Low-dose iron treatment is effective in elderly patients with iron-deficiency anemia. It can replace the commonly used higher doses and can significantly reduce adverse effects.


Genetic variation of Haemonchus contortus (Trichostrongylidae) in sheep and goats from Malaysia and Yemen.
The large stomach worm, Haemonchus contortus, commonly known as "the barber's pole worm", is a blood-sucking nematode found in the abomasa of sheep and goats. This work is the first documentation on the ND4 sequences of H. contortus from sheep and goats in Malaysia and Yemen and the results provide a preliminary insight on the genetic differences of H. contortus found in the two countries. In general, this study showed a high degree of diversity and low population structure of this species within the same country in comparison with higher genetic structuring at a wider geographical scale. The results also showed that the majority of genetic variance was within H. contortus populations. The Malaysian sheep and goat populations investigated appeared to share the same isolate of H. contortus while different isolates may be found in Yemen which must be taken into account in the design of an effective control strategy. Analysis of the internal transcribed spacer-2 (ITS-2) confirmed that all samples investigated in this study belonged to H. contortus. However presence of other Haemonchus species parasitizing these two hosts can only be confirmed by further detailed studies.


Early Protection against Pertussis Induced by Live Attenuated Bordetella pertussis BPZE1 Depends on TLR4.
Pertussis is a severe respiratory disease mainly caused by Bordetella pertussis Despite wide global vaccination coverage with efficacious pertussis vaccines, it remains one of the least well-controlled vaccine-preventable diseases, illustrating the shortcomings of the current vaccines. We have developed the live attenuated nasal pertussis vaccine BPZE1, currently undergoing clinical evaluation in human phase 2 trials. We have previously shown that in mice, BPZE1 provides strong and long-lasting protection against B. pertussis challenge by inducing potent Ab and T cell responses as well as secretory IgA and IL-17-producing resident memory T lymphocytes in the nasal cavity. In this study, we show that BPZE1 induces protection in mice against B. pertussis within days after vaccination, at a time when Ab and T cell responses were not detectable. Early protection was independent of T and B cell responses, as demonstrated by the use of SCID mice. Instead, it was due to TLR4-dependent signaling through the MyD88-dependent pathway of the innate immune response, as demonstrated in experiments with TLR4-deficient and MyD88-knockout mice. TLR2-dependent signaling did not play a major role in early protection. In addition, this study also shows that even at high doses, BPZE1 is safe in the severely immunocompromised MyD88-deficient mice, whereas virulent B. pertussis caused a severe pathological condition and death in these mice, even at a low dose. Finally, coadministration of virulent B. pertussis with BPZE1 did not cause exacerbated outgrowth of the virulent strain, thereby adding to the safety profile of this live vaccine candidate.


Enhancement of interleukin-3-dependent mast cell proliferation by suppression of c-jun expression.
We have previously shown that protein kinase C (PKC) depletion is associated with an increase in the proliferation of interleukin 3 (IL-3)-induced mast cells. Here we show that the AP-1 components c-Jun and c-Fos are induced by IL-3. While c-Jun's induction by IL-3 is totally dependent on PKC, c-Fos induction by IL-3 is only attenuated by PKC depletion. AP-1 binding activity was also induced by IL-3 but this induction was PKC independent. These results indicated a possible involvement of c-Jun in the inhibition of IL-3-induced growth regulation. A support for this assumption came from experiments in which an increase in thymidine incorporation into mast cells was noted when c-jun antisense oligomers were administered to IL-3-treated cells. Since the only known effect of direct inhibition of c-Jun on proliferation rates in several cellular systems was a reduction of proliferation, we verified that our c-jun antisense oligomer could also inhibit proliferation rates in fibroblasts where such a repression was previously reported. Thus c-Jun has an inhibitory effect on IL-3 induction of mast cells proliferation that is distinct from its role in several other cellular environments. These observations reveal the involvement of AP-1 and its components in IL-3-induced signal transduction and the importance of the mast cell environment in determining their specific cellular function.


Effect of hypoglycemic sulfonylureas on Ca2+ fluxes across lipid bilayers.
Black lipid membranes and liposomes loaded with Ca2+ or 5,6-carboxyfluorescein were used for exploring the mechanism of action of insulin-releasing sulfonylureas. Unlike the Ca2+/H+ exchanging ionophore A-23187, tolbutamide did not stimulate the net efflux of Ca2+ from the liposomes. Glibenclamide caused a sustained release of Ca2+, but this effect could be attributed to labilization of the liposomal membrane as indicated by a quantitatively similar loss of the stability marker 5,6-carboxyfluorescein. Unlike the neutral ionophore nonactin or the channel forming quasi-ionophore gramicidin A, the sulfonylureas did not alter the conductance of black lipid membranes in medium containing Na+, K+, Ca2+, Mg2+, and Cl-. It is concluded that the sulfonylureas tested lack ionophore properties but that glibenclamide can labilize membranes.


Metabolic changes and retinal remodeling in Heterozygous CRX mutant cats (CRXRDY/+).
CRX is a transcription factor essential for normal photoreceptor development and survival. The CRXRdy cat has a naturally occurring truncating mutation in CRX and is a large animal model for dominant Leber congenital amaurosis. This study investigated retinal remodeling that occurs as photoreceptors degenerate. CRXRdy/+ cats from 6 weeks to 10 years of age were investigated. In vivo structural changes of retinas were analyzed by fundus examination, confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography. Histologic analyses included immunohistochemistry for computational molecular phenotyping with macromolecules and small molecules. Affected cats had a cone-led photoreceptor degeneration starting in the area centralis. Initially there was preservation of inner retinal cells such as bipolar, amacrine and horizontal cells but with time migration of the deafferented neurons occurred. Early in the process of degeneration glial activation occurs ultimately resulting in formation of a glial seal. With progression the macula-equivalent area centralis developed severe atrophy including loss of retinal pigmentary epithelium. Microneuroma formation occured in advanced stages as more marked retinal remodeling occurred. This study indicates that retinal degeneration in the CrxRdy/+ cat retina follows the progressive, phased revision of retina that have been previously described for retinal remodeling. These findings suggest that therapy dependent on targeting inner retinal cells may be useful in young adults with preserved inner retinas prior to advanced stages of retinal remodeling and neuronal cell loss.


E-cadherin and plakoglobin recruit plakophilin3 to the cell border to initiate desmosome assembly.
A decrease in the levels of the desmosomal plaque protein, plakophilin3 (PKP3), leads to a decrease in desmosome size and cell-cell adhesion. To test the hypothesis that PKP3 is required for desmosome formation, the recruitment of desmosomal components to the cell surface was studied in the PKP3 knockdown clones. The PKP3 knockdown clones showed decreased cell border staining for multiple desmosomal proteins, when compared to vector controls, and did not form desmosomes in a calcium switch assay. Further analysis demonstrated that PKP3, plakoglobin (PG) and E-cadherin are present at the cell border at low concentrations of calcium. Loss of either PG or E-cadherin led to a decrease in the levels of PKP3 and other desmosomal proteins at the cell border. The results reported here are consistent with the model that PG and E-cadherin recruit PKP3 to the cell border to initiate desmosome formation.


Global impact of COVID-19 on childhood tuberculosis: an analysis of notification data.
There is concern that the COVID-19 pandemic has damaged global childhood tuberculosis management. Quantifying changes in childhood tuberculosis notifications could support more targeted interventions to restore childhood tuberculosis services. We aimed to use time-series modelling to evaluate the impact of COVID-19 on child tuberculosis notifications. Annual tuberculosis case notification data reported to WHO by 215 countries were used to calculate annual notification counts for the years 2014-20, stratified by age groups (0-4, 5-14, and ≥15 years) and sex. We used time-series modelling to predict notification counts for 2020, and calculated differences between these predictions and observed notifications in 2020 for each of the six WHO regions and at the country level for 30 countries with high tuberculosis burden. We assessed associations between these differences and the COVID-19 stringency index, a measure of COVID-19 social impact. From 2014 to 2019, annual tuberculosis notification counts increased across all age groups and WHO regions. More males than females in the 0-4 years age group and ≥15 years age group had notifications in all years from 2014 to 2020 and in all WHO regions. In the 5-14 years age group, more females than males were notified globally in all years, although some WHO regions had higher notifications from males than females. In 2020, global notifications were 35·4% lower than predicted (95% prediction interval -30·3 to -39·9; 142 525 observed vs 220 794 predicted notifications [95% prediction interval 204 509 to 237 078]) for children aged 0-4 years, 27·7% lower (-23·4 to -31·5; 256 398 vs 354 578 [334 724 to 374 431]) in children aged 5-14 years, and 18·8% lower (-15·4 to -21·9; 5 391 753 vs 6 639 547 [6 375 086 to 6 904 007]) for people aged 15 years or older. Among those aged 5-14 years, the reduction in observed relative to predicted notifications for 2020 was greater in males (-30·9% [-24·8 to -36·1]) than females (-24·5% [-18·1 to -29·9]). Among 28 countries with high tuberculosis burden, no association was observed between the stringency of COVID-19 restrictions and the relative difference in observed versus predicted notifications. Our findings suggest that COVID-19 has substantially affected childhood tuberculosis services, with the youngest children most affected. Although children have mostly had fewer severe health consequences from COVID-19 than have adults, they have been disproportionately affected by the effects of the pandemic on tuberculosis care. Observed sex differences suggest that targeted interventions might be required. As countries rebuild health systems following the COVID-19 pandemic, it is crucial that childhood tuberculosis services are placed centrally within national strategic plans. Medical Research Council.


Combined effects of chemical dispersant and suspended minerals on the dispersion process of spilled oil.
The dispersion process of spilled oil is an important concern for the effective disposal of oil spills. The dispersed oil concentration and oil droplets size distribution were studied through a wave tank test under the application of chemical dispersant and suspended minerals. The results indicated that dispersant and minerals increased the dispersed oil concentration and the effect of dispersant was more significant, and they had a synergistic effect on oil dispersion. When dispersant and minerals were applied together, the volume mean diameter of oil droplets decreased in the first 30 min, then increased and reached a maximum value at 90-120 min, and decreased again. Moreover, suspended minerals could inhibit the coalescence of oil droplets. This study can afford data support for oil spill emergency response that occurs in inshore or estuaries.


Cytotoxicity of denture adhesives.
Ten commercially available denture adhesives, nine soluble formulations (six creams, three powders) and one insoluble product (pad), were analyzed regarding the cytotoxicity profile in direct and indirect assays using L929 fibroblast cells. In the direct assay, fibroblasts were seeded over the surface of a thick adhesive gel (5%, creams; 2.5%, powders and pad). In the indirect assay, cells were cultured in the presence of adhesive extracts prepared in static and dynamic conditions (0.5-2%, creams; 0.25-1%, powders and pad). Cell toxicity was assessed for cell viability/proliferation (MTT assay) and cell morphology (observation of the F-actin cytoskeleton organization by confocal laser scanning microscopy). Direct contact of the L929 fibroblasts with the thick adhesive gels caused no, or only a slight, decrease in cell viability/proliferation. The adhesive extracts (especially those prepared in dynamic conditions) caused significantly higher growth inhibition of fibroblasts and, in addition, caused dose- and time-dependent effects, throughout the 6-72 h exposure time. Also, dose-dependent effects on cell morphology, with evident disruption of the F-actin cytoskeleton organization, were seen in the presence of most adhesives. In conclusion, the adhesives possessed different degrees of cytotoxicity, but similar dose- and time-dependent biological profiles.


Aging affects L-arginine and its metabolites in memory-associated brain structures at the tissue and synaptoneurosome levels.
L-arginine, one of the most metabolically versatile amino acids, can be metabolized to form a number of bioactive molecules. The present study systematically investigated age-related changes in L-arginine and its metabolites in the hippocampus, parahippocampal region, and prefrontal cortex at the tissue (crude homogenates) and synaptoneurosome (a subcellular preparation enriched for synaptic material) levels. As aging leads to reduced water content in the brain, age-related changes in neurochemical levels in tissue homogenates normalized by wet tissue weight and protein level were compared. There were significant differences in L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, and glutamate, but not GABA, in the CA1, CA2/3, and dentate gyrus sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, and postrhinal cortices in 24 (aged) and 4 (young) months old rats in a region-specific manner. The overall pattern of age-related changes in amino acids (L-arginine, L-citrulline, L-ornithine, glutamate, and GABA) was largely similar between homogenates and synaptoneurosomes, whereas the pattern for the amines (agmatine, putrescine, spermidine, and spermine) was quite different. Furthermore, the pattern of age-related changes in neurochemical levels in tissue homogenates normalized by wet tissue weight and protein level was very similar for all 9 neurochemicals measured. These findings suggest that there are differential effects of aging on L-arginine metabolism at the tissue and synaptoneurosome levels and that the way of data normalization (tissue weight vs. protein level) has no or very minor effects on 9 neurochemicals measured.


Depression and smoking: a 5-year prospective study of patients with major depressive disorder.
Major depressive disorder (MDD) and smoking are major public health problems and epidemiologically strongly associated. However, the relationship between smoking and depression and whether this is influenced by common confounding factors remain unclear, in part due to limited longitudinal data on covariation. In the Vantaa Depression Study, psychiatric out- and inpatients with DSM-IV MDD and aged 20-59 years at were followed from baseline to 6 months, 18 months, and 5 years. We investigated course of depression, smoking, and comorbid alcohol-use disorders among the 214 patients (79.6% of 269) participating at least three time points; differences between smoking versus nonsmoking patients, and covariation of MDD, smoking, and alcohol-use disorders. Overall, 31.3% of the patients smoked regularly, 41.1% intermittently, and 27.6% never. Smokers were younger, had more alcohol-use disorders and Cluster B and C personality disorder symptoms, a higher frequency of lifetime suicide attempts, higher neuroticism, smaller social networks, and lower perceived social support than never smokers. Smoking and depression had limited longitudinal covariation. Depression, smoking, and alcohol-use disorders all exhibited strong autoregressive tendencies. Among adult psychiatric MDD patients, smoking is strongly associated with substance-use and personality disorders, which may confound research on the impact of smoking. Rather than depression or smoking covarying or predicting each other, depression, smoking, and alcohol-use disorders each have strong autoregressive tendencies. These findings are more consistent with common factors causing their association than either of the conditions strongly predisposing to the other.


Alexithymia according to Bucci's multiple code theory: A preliminary investigation with healthy and hypertensive individuals.
To evaluate the relation between alexithymia and Referential Activity (RA), a linguistic measure of the process by which non-verbal emotional experience is connected to language. The 20-Item Toronto Alexithymia Scale (TAS-20) and the Toronto Structured Interview for Alexithymia (TSIA) were administered to 20 postgraduate students and 15 outpatients with hypertension. The Weighted Referential Activity Dictionary (WRAD) and other linguistic measures (Reflection, Disfluency, and Somatic Sense) were applied to texts derived from the TSIA using the Discourse Attributes Analysis Program (DAAP). Multiple linear regressions performed in the whole sample showed a relation between TSIA scores and Somatic Sense. Comparing the two groups, hypertensive subjects yielded higher scores on the TSIA than the young adult sample; no differences in DAAP measures emerged. A significant negative correlation was found between the TAS-20 Difficulty Describing Feelings score and the DAAP measure of references to body activations (Somatic Sense) both in the young adult sample and in hypertensives. In the young adult sample, negative relations emerged between different TSIA factors, WRAD score, and Somatic Sense; a positive relation with fragmented speech (Disfluency) and use of rationalization (Reflection) was also found. In hypertensive subjects, using the TSIA, a negative correlation between alexithymia and Somatic Sense and a positive correlation between alexithymia and the Mean High WRAD (a measure of intensity of engagement during the speech) were found. The TSIA seems to be a more adequate instrument than the TAS-20 to explore relations between alexithymia and RA. Results appear to suggest a complex, nonlinear relation between alexithymia and RA, presumably influenced by subject-specific characteristics. A relation between alexithymia and RA has been proposed on theoretical grounds, but there has been minimal empirical investigation. This was the first study to employ both a self-report measure and a structured interview for measuring alexithymia in relation to RA. The results of this study suggest a complex, nonlinear relation between alexithymia and RA; this finding is essentially obtained with the structured interview measure of alexithymia. This relation is presumably influenced by subject-specific characteristics.


Neospora caninum: in vivo and in vitro treatment with artemisone.
Neosporosis caused by Neospora caninum has global economic, clinical, and epidemiological impacts, mainly in the cattle industry. Currently, there is no useful drug for treatment of neosporosis. This publication is the first to describe the significant benefits that artemisone has on Neospora infections both in vitro and in vivo. Artemisone is a new semi-synthetic 10-alkylamino artemisinin that is superior to other artemisinin derivatives in terms of its significantly higher antimalarial activity, its tolerance in vivo, lack of detectable neurotoxic potential, improved in vivo pharmacokinetics and metabolic stability. Low micromolar concentrations of artemisone inhibited in vitro Neospora development. Prophylactic and post-infection treatment profoundly reduced the number of infected cells and parasites per cell. In the in vivo gerbil model, a non-toxic dose prevented typical cerebral symptoms, in most animals. There were no signs of clinical symptoms and brain PCR was negative. Most treated gerbils produced high specific antibody titer and were protected against a challenge. Overall, artemisone could be considered as a future drug for neosporosis.


Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus.
Somatostatin is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings point to a role for somatostatin in the central processing of nociception. We studied the effects of somatostatin receptor modulation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Somatostatin (10 microg/microl) and the somatostatin antagonist cyclo-somatostatin (50 microg/microl) were microinjected into the PH and the effects on responses of neurons in the trigeminal subnucleus caudalis studied. Injection of somatostatin (n=11) did not affect A- and C-fibre responses to dural electrical stimulation, nor was spontaneous activity altered (P>0.05). Injection of cyclo-somatostatin (n=10) into the PH reduced A-(-35.5+/-5.8%) and C-fibre (-43.1+/-7.5%) responses to dural stimulation and resulted in decreased spontaneous activity (-38.1+/-7.3%, P<0.05). Responses to facial thermal stimulation were decreased by 51.2+/-5.8% (n=5). Control injections had no significant effect (n=9). Blockade of somatostatin receptors in the PH has an anti-nociceptive effect on dural and facial input, probably mediated via GABAergic mechanisms. As somatostatin is also involved in hypothalamic regulation of metabolic, neuroendocrine and autonomic functions, somatostatin receptor mechanisms in the PH may play a role in the pathophysiology of primary headache disorders, such as migraine or cluster headache.