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Articles by Tami T. Tamashiro in JoVE

 JoVE Immunology and Infection

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue


JoVE 3814 8/15/2012

1Neuroscience Program, Uniformed Services University, 2Department of Anatomy, Physiology, and Genetics, Uniformed Services University, 3Molecular and Cell Biology, Uniformed Services University

Isolating primary microglia from the cellular heterogeneity of the brain is essential to investigate their role in both physiological and pathological conditions. This protocol describes a mechanical isolation and mixed cell culture technique that provides high yield and high purity, viable primary microglial cells for in vitro study and downstream applications.

Other articles by Tami T. Tamashiro on PubMed

Bypassing Spermiogenesis for Several Generations Does Not Have Detrimental Consequences on the Fertility and Neurobehavior of Offspring: a Study Using the Mouse

This study was conducted to determine whether the omission of spermiogenesis and all prefertilization events for five generations in mice affects the fertility or behavior of offspring.

Distribution and Localization of Cells and Collagens in the Proliferated Intima of Arterially Implanted Autovein Grafts

We examined the microscopic features and distribution of collagens in the hyperplastic intima of arterially implanted autovein bypass grafts under conditions of a reduced blood flow with a poor distal outflow. Vascular anastomosis was made using 7-0 nonabsorbable polypropylene sutures (PP group), or absorbable polydioxanone sutures (PDS group). On the contralateral limb, an autovein bypass graft was performed under normal flow conditions (NF group). The thickness of the intima in the NF group was approximately 50 microm throughout the duration of the study, while in the PP and PDS groups, intimal hyperplasia progressed to 290+/-112 microm and 267+/-123 microm, respectively, at 13 months after grafting. Collagen accumulated significantly in both the PP and PDS groups; types IV and V collagen in particular increased considerably in the deep layer. Regardless of the suture materials, the progression of intimal hyperplasia was considered to be closely related to the poor distal outflow to be and caused by the proliferation of myofibroblasts and active production of collagen. The increase in types IV and V collagen, particularly in the deep layer of the hyperplastic intima, was due to development of numerous vasa vasora in this region.

Amygdala Lesions Produce Analgesia in a Novel, Ethologically Relevant Acute Pain Test

Acute pain tests using mechanical stimuli typically do not involve objects important in the evolutionary history of the subjects, and may fail to evaluate the contribution of biobehavioral defensive reactions to the total pain response. Spines are common structural defenses that protect plants and animals against predation. The present studies examined the reaction to contact with such natural, mechanical pain stimuli in the laboratory rat, utilizing a floor board with protruding pins located in the middle of a novel alley (the "fakir" test). Behavioral responses were characterized in 10-min tests (Experiment 1). Subjects showed voluntary contact with the pins followed by patterns of avoidance and risk assessment (stretch attend and stretch approach). Few subjects crossed the array of pins. The amygdala has been implicated in the perception of pain, particularly in stressful or fearful contexts. In Experiment 2, the fakir test was used to examine, concurrently, the effects of amygdala lesions on analgesiometric (frequency and duration of pin crossings) and anxiometric (risk assessment) measures. Large, bilateral, lesions of the amygdala significantly increased both the number of pin crossings and time spent on the pins without affecting the risk assessment measures. These findings suggest a possible dissociation between anxiety and pain perception with an important (nonaffective) role for the amygdala in the latter.

Excessive Salt or Cholesterol Intake Alters the Balance Among Endothelium-derived Factors Released from Renal Arteries in Spontaneously Hypertensive Rats

We investigated the vasorelaxation in renal arteries isolated from spontaneously hypertensive rats (SHRs) fed a basal, a high-salt, or a high-cholesterol diet for 8 weeks. In renal arterial rings from the control group, acetylcholine (ACh)-induced endothelium-dependent relaxations were markedly increased by indomethacin (IND) and ONO-3708, a prostaglandin H2/thromboxane A2-receptor antagonist, but not affected by OKY-046, a thromboxane A2 synthetase inhibitor. These increased relaxations were partially inhibited by either NG-nitro-L-arginine methyl ester (L-NAME) or charybdotoxin (CTX), and almost completely abolished by the combination of L-NAME plus CTX. The ACh-induced endothelium-dependent relaxations in the absence of IND were significantly attenuated by the high-salt intake but not affected by the high-cholesterol intake. The degrees of relaxations in the presence of IND were approximately equal among the three diet groups. On the other hand, the relaxations in the presence of IND plus L-NAME were significantly augmented by a high-cholesterol intake and abolished by a high-salt intake, and the relaxations in the presence of IND plus CTX were slightly reduced by a high-cholesterol intake and significantly augmented by a high-salt intake. The production of cyclic guanosine monophosphate (cGMP) in response to ACh was significantly decreased by a high-cholesterol intake and tended to be increased by a high-salt intake. These findings indicate that in the renal artery of SHRs, ACh causes production of a sufficient amount of nitric oxide (NO), together with a relaxing factor resembling endothelium-derived hyperpolarizing factors (EDHFs) and also endothelium-derived contracting factors (EDCFs), probably prostaglandin H2. Our results also suggest that excessive salt intake increases the release of EDCF and NO and decreases that of an EDHF-like factor, whereas excessive cholesterol intake increases release of an EDHF-like factor and decreases that of NO.

[Evolution of the Concept of Sustainable Development from "our Common Future" to "a New WHO"]

Postnatal Growth and Behavioral Development of Mice Cloned from Adult Cumulus Cells

Since the first successful cloning of mammals from adult somatic cells, there has been no examination of the learning or behavior of cloned offspring. The possibility of adverse effects on animals produced through adult somatic cell cloning is high because many natural biological processes are bypassed and DNA from adult cells, which presumably contain mutations, are used. In this study, we compared cloned mice produced by microinjection transfer of cumulus cell nuclei into enucleated oocytes, to control mice that were specifically generated to eliminate confounding factors that are unique to our cloning procedure. Postnatal weight gain of clones was significantly greater than that of controls. Preweaning development observations revealed that first appearance or performance of 3 out of 10 measures was delayed in cloned mice; however, results of subsequent tests of learning and memory, activity level, and motor skills were comparable for both groups. Together, these data suggest that nuclear transfer of adult somatic cell nuclei to produce cloned mice may delay the appearance of a few developmental milestones but it does not adversely affect the overall postnatal behavior of mice. In addition, this procedure may cause late onset of significantly increased body weight in cloned offspring, the cause or causes of which are being further examined.

Chernobyl-induced Radiophobia and the Incidence of Tuberculosis

Cloning of Mice to Six Generations

Anti-TNP Monoclonal Antibodies As Reagents for Enzyme Immunoassay (ELISA)

The aim of this study was to produce anti-TNP monoclonal antibodies (MAbs) that could be conjugated and used for the detection of antigen-antibody reactions, in which the antigen specific-antibody had been previously bound to trinitrophenyl (TNP). For hybridoma production, SP2/0-Ag14 cells were fused with spleen cells from mice previously immunized with TNP-ovalbumin (TNP-OVA). After 10 days, enzyme-linked immunoadsorbent assay (ELISA) was used to detect anti-TNP antibodies in the supernatants, and five cultures were found to be strictly positive for TNP. Three of these were subsequently cloned by limiting dilution, and 15 clones were chosen for expansion based on the criterion of high reactivity against TNP. Anti-TNP MAbs produced by those clones were isotyped as IgG1, and purified by Sepharose-protein G affinity cromatography from ascites developed in BALB/c mice. Two purified MAbs (1B2.1B6 and 1B2.1E12) were coupled to horseradish peroxidase (HRPO). The resulting conjugates were evaluated in ELISA tests for interferon-gamma and interleukin-4 detection, in which the secondary anti-cytokine antibodies were coupled either to TNP or biotin. The performance of anti-TNP conjugates in these assays were compared with a biotin-streptavidin/peroxidase system. Both types of conjugates were similarly able to detect cytokines with r2 (linear correlation coefficient) close to unity value. Growth studies of one of those hybridomas (1B2.1B6) yielded a specific growth rate of 0.042 h(-1) and a doubling time of 16.5 h. Data discussed here show that at least two MAbs against TNP raised in this work can be used as a reagent for enzyme immunoassays.

[Some Discussion on Why WHO Definition of Health Has Not Been Revised]

Helix-coil Transition in Homopolypeptides Under Stretching

We consider the effect of an external applied force on the alpha-helix-coil transition of a single-stranded homopolypeptide chain. An annealed scenario is assumed, where the building amino acid monomers may interconvert between random-coiled and ordered alpha-helical configurations. By exact evaluation of the partition function of the freely jointed chain with helix-coil internal degrees of freedom in the thermodynamic limit, we obtain the result that the stress-strain characteristic has an asymmetrical sigmoid shape with a prominent pseudoplateau. Because of the one-dimensional nature of this system, fluctuations dominate over the mean-field approximation, which incorrectly predicts a second-order phase transition.

Risk Factors for Stiffness of the Wall of the Thoracic Aorta in Patients with Mild Atherosis

Previous studies have suggested that aging is associated with progressive arterial stiffness and widening of the pulse pressure, and pulse pressure has been found to be a risk factor of cardiovascular diseases. However, the effects of age, blood pressure (including pulse pressure) or atherogenic factors on thoracic aortic wall stiffness in patients with mild atherosis are unclear, so the present study used transesophageal echocardiography to examine 103 consecutive patients with various cardiovascular diseases. The extent of atherosis was evaluated in terms of intima-medial thickness (IMT), and 2 indices of wall stiffness in the aorta were calculated: elastic modulus and stiffness parameter (beta). In subjects with mild atherosis (IMT <1.0mm), age, body mass index, systolic blood pressure, pulse pressure, triglyceride level, and hypertension were factors significantly associated with high wall stiffness, and multiple logistic stepwise analysis revealed that age, pulse pressure, and triglyceride level were particularly significant.

Significant Association Between the Progression of Coronary Artery Calcification and Dyslipidemia in Patients on Chronic Hemodialysis

Quantification of coronary artery calcification (CAC) determined by electron-beam computed tomography (EBCT), known as the CAC score (CACS), correlates with total plaque amount and coronary risk factors and strongly associates with maximal stenosis in the epicardial arteries. However, data are limited concerning the CACS in chronic dialysis patients, although atherosclerotic vascular disease is the most frequent complication. We examined the relation between coronary risk factors, metabolic factors of calcium and other minerals, and CACS progression in 24 dialysis patients. The mean patient age was 53 +/- 14 (SD) years, and mean duration of dialysis was 64 +/- 69 months. In each patient, the CACS was measured twice, with a mean interscan period of 17 +/- 3 months. The mean CACS progressed from 449 +/- 605 to 669 +/- 894 overall, and the mean change in CACS (DeltaCACS) was 220 +/- 78. Patients were divided into two groups: slow progressors, with DeltaCACS of 7.5 +/- 31 (n = 12), and rapid progressors, with DeltaCACS of 432 +/- 458 (n = 12). Triglyceride concentrations (198 +/- 65 versus 103 +/- 50 mg/dL; P < 0.001) were high, and high-density lipoprotein cholesterol (HDL-C) concentrations (46 +/- 11 versus 60 +/- 18 mg/dL; P < 0.05) were low in rapid progressors. Rapid progression of CAC was associated with high triglyceride and low HDL-C concentrations. The clinical significance of these observations remains to be determined.

Role of Tamm-Horsfall Protein in the Binding and in Vivo Phagocytosis of Type 1 Fimbriated Escherichia Coli by Mouse Peritoneal Macrophages

Tamm-Horsfall glycoprotein (THP) contains manno-oligosaccharides that are recognized by type 1 fimbriae (F1) of Escherichia coli. In the present study, we examined the in vivo phagocytic activity of mouse peritoneal macrophages after treatment of bacteria with THP. At low THP concentrations (12.5 microg/ml and 50 microg/ml) no significant difference was observed in the phagocytosis of E. coli F1+. However, at high THP concentrations (500 microg/ml and 1250 microg/ml) we obtained a reduction of bacterial phagocytosis by mouse peritoneal macrophages.

Ascites Due to Hypothyroidism in a Patient with Alcoholic Cirrhosis

Myxedema is the cause of ascites in less than 1% of new-onset ascites cases, where as only 4% of patients with hypothyroidism present ascites. When ascites is the first manifestation of thyroid insufficiency, there is usually a delay in diagnosis. We report here a case of myxedema ascites occurring in a patient with alcoholic cirrhosis, that was first thought to be the cause of the ascites, and review the features of 48 cases previously reported. Some clinic and analytical findings that have been commonly reported, are the long duration of the ascites before diagnosis, the prompt response (with resolution of ascites) to thyroid replacement treatment, a high total protein concentration in ascites fluid, white moderate white blood cell counts and a lymphocyte predominance. Serum-ascites albumin gradient has been postulated to be high in myxedema ascites, but we believe this has been studied in too few cases thus far, to be conclusive.

Arrhythmogenic Right Ventricular Dysplasia Presenting As Regression of Left Ventricular Dysfunction: a Case Report

Arrhythmogenic right ventricular dysplasia is considered to be a slowly progressive disease in which left ventricular dysfunction and congestive heart failure usually appear at the end stage. The initial clinical presentation of this 56-year-old Japanese woman was left-sided heart failure, and the diagnosis was dilated cardiomyopathy, but her left ventricular size and ejection fraction regressed during 10 years of treatment, whereas her right ventricular parameters showed no change.

Downregulation of Vascular Soluble Guanylate Cyclase Induced by High Salt Intake in Spontaneously Hypertensive Rats

1. Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) - cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR). 2. Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3. In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY. 4. In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake. 5. Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake. 6. These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.

[Health Status and Lifestyle Issues of Homeless People in Sapporo City, 2000]

To clarify the health status and lifestyle issues of homeless people in Sapporo city, voluntary "health consultations and medical examinations" were carried out near an emergency kitchen.

Electron Beam Computed Tomography Evaluation of the Rapid Progression of Coronary Artery Calcification in Chronic Hemodialysis Patients

NK1.1+ Cells and T-cell Activation in Euthymic and Thymectomized C57Bl/6 Mice During Acute Trypanosoma Cruzi Infection

Natural killer (NK) cells may provide the basis for resistance to Trypanosoma cruzi infection, because the depletion of NK1.1 cells causes high levels of parasitemia in young C57Bl/6 mice infected with T. cruzi. Indeed, NK1.1 cells have been implicated in the early production of large amounts of interferon (IFN)-gamma, an important cytokine in host resistance. The NK1.1 marker is also expressed on special subpopulations of T cells. Most NK1.1+ T cells are of thymic origin, and their constant generation may be prevented by thymectomy. This procedure, by itself, decreased parasitemia and increased resistance in young mice. However, the depletion of NK1.1+ cells by the chronic administration of a monoclonal antibody (MoAb) (PK-136) did not increase the parasitemia or mortality in thymectomized C57Bl/6 mice infected with T. cruzi (Tulahuen strain). To study the cross-talk between NK1.1+ cells and conventional T cells in this model, we examined the expression of activation/memory markers (CD45RB) on splenic CD4+ and CD8+ T cells from young euthymic or thymectomized mice with or without depletion of NK1.1+ cells and also in aged mice during acute infection. Resistance to infection correlated with the amount of CD4+ T cells that are already activated at the moment of infection, as judged by the number of splenic CD4+ T cells expressing CD45RB(-). In addition, the specific antibody response to T. cruzi antigens was precocious and an accumulation of immunoglobulin (Ig)M with little isotype switch occurred in euthymic mice depleted of NK1.1+ cells. The data presented here suggest that NK1.1+ cells have important regulatory functions in euthymic, but not in thymectomized mice infected with T. cruzi. These regulatory functions include a helper activity in the generation of effector or activated/memory T cells.

[How Can We Prevent Alveolar Echinococcosis? Ecosystem and Risk Management Viewpoints]

This article focuses on understanding epidemiological features of alveolar echinococcosis and discussing its prevention and control, especially from a viewpoint of the ecosystem and risk management.

Cloned Mice Have an Obese Phenotype Not Transmitted to Their Offspring

Mammalian cloning using somatic cells has been accomplished successfully in several species, and its potential basic, clinical and therapeutic applications are being pursued on many fronts. Determining the long-term effects of cloning on offspring is crucial for consideration of future application of the technique. Although full-term development of animals cloned from adult somatic cells has been reported, problems in the resulting progeny indicate that the cloning procedure may not produce animals that are phenotypically identical to their cell donor. We used a mouse model to take advantage of its short generation time and lifespan. Here we report that the increased body weight of cloned B6C3F1 female mice reflects an increase of body fat in addition to a larger body size, and that these mice share many characteristics consistent with obesity. We also show that the obese phenotype is not transmitted to offspring generated by mating male and female cloned mice.

High-susceptibility of Photosynthesis to Photoinhibition in the Tropical Plant Ficus Microcarpa L. F. Cv. Golden Leaves

The tropical plant Ficus microcarpa L. f. cv. Golden Leaves (GL) is a high-light sensitive tropical fig tree in which sun-leaves are yellow and shade-leaves are green. We compared the response of photosynthetic activities to strong light between GL and its wild-type (WT, Ficus microcarpa L. f.).

Susceptibility of the Mosquitoes Anopheles Minimus, An. Sinensis, and An. Saperoi (Diptera: Culicidae) from the Ryukyu Archipelago, Japan, to the Rodent Malaria Plasmodium Yoelii Nigeriense

The susceptibility of three anopheline mosquitoes, Anopheles minimus Theobald, An. sinensis Wiedemann, and An. saperoi Bohart & Ingram, from the Ryukyu Archipelago to the rodent malaria, Plasmodium yoelii nigeriense was examined to find new vectors other than An. stephensi Liston for rodent malaria studies in the laboratory. The survival rate of the mosquitoes after feeding on mice infected with P. y. nigeriense was also examined. The Beech strain of An. stephensi from India was compared with An. minimus from Ishigaki Island, and An. sinensis and An. saperoi from Okinawa Island. Oocysts were first found on day 3 after feeding on mice infected with P. y. nigeriense in An. stephensi, on day 4 in An. minimus and An. saperoi, and day 6 in An. sinensis. From 8 to 14 d after feeding on malaria-positive mice, oocysts were present in 97.2-100% of An. stephensi, 85.7-100% of An. saperoi, 20-74.1% of An. minimus, and 12.5-13.3% of An. sinensis. The duration of oocyst occurrence in An. saperoi was 55 d, the longest among the anopheline mosquitoes used in this study. On day 8 after feeding, sporozoites were found in the salivary glands and heads of all the mosquitoes tested. From the 10th to 16th d, sporozoites were present in the salivary glands of 14.9% (range, 9.1-28.0%) of An. minimus, 47.3% (40.7-58.1) of An. saperoi, and 96.2% (94.1-97.2) of An. stephensi, but were absent in An. sinensis. Anopheles saperoi could be an excellent vector of P. y. nigeriense because it has comparatively high susceptibility and high longevity even after feeding on infected mice.

[WHO's Framework Convention on Tobacco Control Potential Impact on Tobacco Control in Japan]

The objective of the paper are to introduce the current global tobacco control measures undertaken by WHO and other international organizations, and to describe the impact on domestic tobacco control in Japan.

High Salt Intake Impairs Vascular Nitric Oxide/cyclic Guanosine Monophosphate System in Spontaneously Hypertensive Rats

In aortas of spontaneously hypertensive rats (SHRs), excessive dietary salt causes down-regulation of soluble guanylate cyclase (sGC) followed by decreased cyclic GMP production, which leads to impairment of the vascular relaxation response to nitric oxide (NO). The present study aimed to elucidate whether this impaired NO/cyclic GMP system results secondarily from increased blood pressure or from an effect of the salt itself. The antihypertensive drug nifedipine was used on 4-week-old SHRs that received a normal-salt diet or a high-salt diet for 4 weeks. Treatment with nifedipine (30 mg/kg/day, p.o.) reduced the increased blood pressure of SHRs fed the high-salt diet to the level of SHRs fed the normal-salt diet. In aortic rings from SHRs fed the high-salt diet, not only endothelium-dependent relaxations but also endothelium-independent relaxations were significantly impaired. However, these impairments were not alleviated by treatment with nifedipine. Furthermore, nifedipine did not prevent the increase in protein levels of endothelial NO synthase and the decrease in the protein levels of sGC in aortas from SHRs fed the high-salt diet. These alterations by high salt intake were restored after replacement with the normal-salt diet for 4 additional weeks. These results indicate that in SHRs given excessive dietary salt, normalization of salt intake but not blood pressure reduction can ameliorate alterations in the NO/cyclic GMP system. High salt intake may directly affect the vascular smooth muscle and cause impairment of the relaxation response to NO.

Trends of Reproductive Hormones in Male Rats During Psychosocial Stress: Role of Glucocorticoid Metabolism in Behavioral Dominance

Stress in socially subordinate male rats, associated with aggressive attacks by dominant males, was studied in a group-housing context called the visible burrow system (VBS). It has been established that subordinate males have reduced serum testosterone (T) and higher corticosterone (CORT) relative to dominant and singly housed control males. The relationship of the decreased circulating T levels in subordinate males to changes in serum LH concentrations has not been evaluated previously. Since decreases in LH during stress may cause reductions in Leydig cell steroidogenic activity, the present study defined the temporal profiles of serum LH, T, and CORT in dominant and subordinate males on Days 4, 7, and 14 of a 14-day housing period in the VBS. The same parameters were followed in serum samples from single-housed control males. Leydig cells express glucocorticoid receptors and may also be targeted for direct inhibition of steroidogenesis by glucocorticoid. We hypothesize that Leydig cells are protected from inhibition by CORT at basal concentrations through oxidative inactivation of glucocorticoid by 11beta-hydroxysteroid dehydrogenase (11betaHSD). However, Leydig cell steroidogenesis is inhibited when 11betaHSD metabolizing capacity is exceeded. Therefore, 11betaHSD enzyme activity levels were measured in Leydig cells of VBS-housed males at the same time points. Significant increases in LH and T relative to control were observed in the dominant animals on Day 4, which were associated with the overt establishment of behavioral dominance as evidenced by victorious agonistic encounters. Serum LH and T were lower in subordinate males on Day 7, but T alone was lower on Day 14, suggesting that lowered LH secretion in subordinates may gradually be reversed by declines in androgen-negative feedback. Serum CORT levels were higher in subordinate males compared to control at all three time points. In contrast, oxidative 11betaHSD activity in Leydig cells of dominant males was higher relative to control and unchanged in subordinates. These results suggest the following: 1) failure of Leydig cells of subordinate males to compensate for increased glucocorticoid action during stress, by increasing 11betaHSD oxidative activity, potentiates stress-mediated reductions in T secretion; and 2) an inhibition of the reproductive axis in subordinate males at the level of the pituitary.

Involvement of the Parabrachial Nucleus in the Pressor Response to Chemoreflex Activation in Awake Rats

Activation of the chemoreflex with potassium cyanide (KCN, 40 microg/rat, i.v.) in awake rats produces pressor and bradycardic responses as well as a tachypneic response. In the present study, we evaluated the involvement of the periaqueductal gray matter (PAG) and the parabrachial nucleus (PBN) in the neural pathways of the cardiovascular responses to chemoreflex activation. The cardiovascular responses to chemoreflex activation were evaluated before and after bilateral microinjection of 2% lidocaine, a local anesthetic, into the PBN or PAG in order to block in a reversible manner the neuronal activity and axonal conduction of fibers of passage in these areas. The data show that the pressor response to chemoreflex activation 3 min after bilateral microinjection of lidocaine into the dorsolateral aspect of the PBN was significantly reduced in comparison to the control response (32 +/- 5 vs. 48 +/- 4 mm Hg, n = 7), with no significant changes in the bradycardic responses. The effect of lidocaine was reversible since the pressor response was back to control levels 15 min after microinjection of this anesthetic. Bilateral microinjections of lidocaine into the dorsolateral (n = 11) or lateral (n = 8) columns of the PAG in distinct groups of rats produced no significant changes in the pressor or bradycardic responses of the chemoreflex. These data indicate that the PBN is part of the neuronal pathways involved in the sympathoexcitatory component of the chemoreflex while the PAG is not.

Decreases in Neurokinin-3 Tachykinin Receptor-immunoreactive and -mRNA Levels Are Associated with Salt Appetite in the Deoxycorticosterone-treated Rat

Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors. Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis since intracerebroventricular injection of senktide (NK3r agonist) attenuates salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several brain regions thought to be associated with the control of water and electrolyte balance including the bed nucleus of the stria terminalis, central nucleus of the amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius, parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity in all brain regions analyzed except for increases in the amygdala and no changes in the paraventricular nucleus of the hypothalamus. To examine whether DOCA's effects on NK3r synthesis are direct, we used differentiated N1E-115 neuroblastoma cells that express NK3r and treated them with a range of concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance via Northern blotting. The present results suggest that the tachykinin receptors are downregulated after subchronic DOCA treatment and this finding is consistent with the hypothesis that suppressed inhibition of salt appetite as mediated through the tachykininergic system.

[Senior Citizens and Driving--a Note for the Recent Revision of the Road Traffic Law in Japan]

Recovery of Motor Function and Dopaminergic Parameters in a Mouse Model of Parkinson's Disease Induced by Co-administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Diethyldithiocarbamate

Diethyldithiocarbamate (DDC) enhances the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We studied the time course of dopaminergic parameters and motor function of MPTP+DDC-lesioned C57BL/6 mice, a model of Parkinson's disease. MPTP+DDC-lesioned mice showed a decrease in dopamine (DA) and its metabolites contents in their striata 1, 3 and 6 weeks after MPTP+DDC-treatment, compared with those of each control group. The partial and significant recoveries in DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid contents were also observed after 6 weeks, compared with those at 1 week after treatment. In addition, bradykinesia due to DA depletion was observed in mice 1 week after MPTP+DDC-treatment, but it was not significant 3 weeks after the treatment. l-DOPA alone and a co-administration of l-DOPA and a monoamine oxidase-B inhibitor selegiline improved bradykinesia of this model, also suggesting that bradykinesia observed in the model was mediated to dopaminergic deficiency. On the other hand, the serotonin content increased slightly but significantly after 3 or 6 weeks, suggesting compensatory activation of the serotonergic system against DA depletion. Thus, the partial recovery of dopaminergic parameters, the recovery of motor function and the compensatory activation of the serotonergic system were observed in this model 3-6 weeks after MPTP+DDC treatment.

[Possibility of Invasion of Echinococcus into Honshu with Pet Dogs from Hokkaido and Overseas]

The number of pet dogs moving with their owners to Honshu, the main island of Japan, from Hokkaido, and the number of dogs imported from overseas were examined, and the possibility of invasion of Echinococcus multilocularis and E. granulosus with these dogs was discussed.

[Fight Against AIDS--activities by WHO]

Inflammatory Responses Induced in Mice by Lectin from Talisia Esculenta Seeds

A novel lectin from Talisia esculenta seeds (TEL) has recently been purified and characterized. In this study we investigated the proinflammatory activity of TEL in mice using both the air-pouch and peritoneal cavity as well as paw oedema models. TEL (10-40 microg) induced significant neutrophil and mononuclear cell recruitment when injected into either mouse air-pouch or peritoneal cavity. The neutrophil accumulation into the air-pouch was dose- and time-dependent with a maximal response at 16 h, returning to control levels at 72 h whereas maximal mononuclear cell accumulation was observed at 24 h after TEL injection. The same profile of neutrophil accumulation was observed when this lectin was injected into mouse peritoneal cavity, although the maximal mononuclear cell recruitment was observed 48 h after TEL injection. Additionally, TEL (12.5-200 microg/paw) caused a dose-dependent mice paw, as evaluated at 4 h after the lectin injection. D-mannose, better than D-glucose, significantly inhibited TEL-induced neutrophil migration into the peritoneal cavity or air-pouch. D-galactose had no effect on TEL-induced neutrophil migration in either cavity studied. On the other hand, D-mannose slightly inhibited the TEL-induced paw oedema, whereas neither D-glucose nor D-galactose affected this phenomenon. In conclusion, our data show that TEL induces neutrophil and mononuclear cell accumulation by a mechanism related to their specific sugar-binding properties.

Phenotype of Cloned Mice: Development, Behavior, and Physiology

Cloning technology has potential to be a valuable tool in basic research, clinical medicine, and agriculture. However, it is critical to determine the consequences of this technique in resulting offspring before widespread use of the technology. Mammalian cloning using somatic cells was first demonstrated in sheep in 1997 and since then has been extended to a number of other species. We examined development, behavior, physiology, and longevity in B6C3F1 female mice cloned from adult cumulus cells. Control mice were naturally fertilized embryos subjected to the same in vitro manipulation and culture conditions as clone embryos. Clones attained developmental milestones similar to controls. Activity level, motor ability and coordination, and learning and memory skills of cloned mice were comparable with controls. Interestingly, clones gained more body weight than controls during adulthood. Increased body weight was attributable to higher body fat and was associated with hyperleptinemia and hyperinsulinemia indicating that cloned mice are obese. Cloned mice were not hyperphagic as adults and had hypersensitive leptin and melanocortin signaling systems. Longevity of cloned mice was comparable with that reported by the National Institute on Aging and the causes of death were typical for this strain of mouse. These studies represent the first comprehensive set of data to characterize cloned mice and provide critical information about the long-term effects of somatic cell cloning.

Prevention of Alveolar Echinococcosis--ecosystem and Risk Management Perspectives in Japan

We focused on the epidemiology of alveolar echinococcosis especially in Japan and discussed control measures to prevent an epidemic. No effective control measures against alveolar echinococcosis have been identified thus far because it is difficult to fully understand the ecology of the parasite and its hosts, i.e. the precise infection route to humans. In Hokkaido, Japan, infection rates among red foxes have recently risen even in low endemic districts. Infection seems to be spreading not only among wild foxes but also among domestic dogs. Despite only sporadic reports of human cases in Japan, we predict that the incidence of alveolar echinococcosis will increase in the near future if no effective preventive measures are put in place. An Echinococcus multilocularis epidemic would have the potential to affect the economy of Hokkaido, due to its impact on the agricultural and tourist industries. Well-designed epidemiological surveys are, therefore, urgently required prior to large outbreaks, based on understanding of the ecosystem around E. multilocularis.

The L-DOPA-sparing Effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane Hydrochloride [(-)-BPAP] in Reserpine-pretreated Rats

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP], a highly potent enhancer of impulse propagation-mediated release of catecholamines and serotonin in the brain, and significantly increased the locomotor activity of normal rats at the doses of 0.3 and 1 mg/kg s.c. (P < 0.05), while L-DOPA (200 and 400 mg/kg i.p.) had no significant effect. The locomotor activity of rats simultaneously administered L-DOPA and (-)-BPAP was significantly higher than with (-)-BPAP alone (P < 0.05). In rats pretreated with reserpine (1 mg/kg i.v.), the hypolocomotion was significantly reversed by 400 mg/kg i.p. L-DOPA, or 1 or 3 mg/kg s.c. (-)-BPAP (P < 0.05). Furthermore, the combined administration of subthreshold doses of 200 mg/kg i.p. L-DOPA and 0.3 mg/kg s.c. (-)-BPAP highly potentiated the locomotor activity in the reserpine-pretreated rats. However, (-)-BPAP failed to reverse the hypolocomotion in rats pretreated with reserpine + alpha-methyl-DL-p-tyrosine. Thus, (-)-BPAP was demonstrated to possess the L-DOPA-sparing effect in normal and reserpine-pretreated rats.

[Process Leading to the Final Negotiation of the WHO Framework Convention on Tobacco Control and the Future Direction for Its Implementation]

Association Between a Variant of the Glutathione S-transferase P1 Gene (GSTP1) and Hypertension in Pregnancy in Japanese: Interaction with Parity, Age, and Genetic Factors

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene ( GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan. We analyzed the data in the context of other risk factors before pregnancy. The frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly different between the HP (26%) patients and the controls (28%). However, in primiparous patients, the frequency was significantly different in elderly pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P < 0.05). These results suggest that this variant of the GSTP1 may play a role in the manifestation of HP together with other independently and/or synergistically acting factors, particularly in primiparous pregnancy.

Where the Linearized Poisson-Boltzmann Cell Model Fails: the Planar Case As a Prototype Study

The linearized Poisson-Boltzmann (PB) approximation is investigated for the classical problem of two infinite, uniformly charged planes in electrochemical equilibrium with an infinite monovalent salt reservoir. At the nonlinear level, we obtain an explicit expression of the associated electrostatic contribution to the semi-grand-canonical potential. The linearized osmotic-pressure difference between the interplane region and the salt reservoir becomes negative in the low-temperature, large-separation, or high-surface charge limits, in disagreement with the exact (at mean-field level) nonlinear PB solution. We show that these artifacts--although thermodynamically consistent with quadratic expansions of the nonlinear functional--can be traced back to the nonfulfillment of the underlying assumptions of the linearization. Explicit comparison between the analytical expressions of the exact nonlinear solution and the corresponding linearized equations allows us to show that the linearized results are asymptotically exact in the weak-coupling and counterionic ideal-gas limits, but always fail otherwise, predicting negative osmotic-pressure differences. By taking appropriate limits of the full nonlinear PB solution, we provide asymptotic expressions for the semi-grand-canonical potential and the osmotic-pressure difference that involve only elementary functions, which cover the complementary region where the linearized theory breaks down.

Trends and Current Issues in Adult Fecal Incontinence (FI): Towards Enhancing the Quality of Life for FI Patients

Our goals are to review the literature on the definition and epidemiology of fecal incontinence (FI), the risk factors involved, available treatment options, and measurement of the quality of life (QOL) of patients with this condition. Articles included for review were searched following the guidelines set by Cochrane Reviewers' Handbook. FI was defined variously depending upon the duration, type, and amount of leakage. About 17 published papers were reviewed on the prevalence of FI that ranged from 1.4% to 50%. Potential risk factors included perianal injury/surgery, and fair/poor general health. QOL assessment using various grading scales provided an objective method of evaluating patients before and after treatment. Management included medical, physiotherapy, and surgical options. Through the range of various references, a clear definition of FI should be specified, which reflects its epidemiology in the various studies. These differences in definition would significantly affect its prevalence. Many risk factors have been sited but further epidemiological studies are necessary to elucidate FI. Understanding the etiology of the disease is an important initial step to provide adequate treatment of FI. QOL assessment provides objective and subjective method in the analysis of effectiveness of therapy.

Repeated Exposure to Social Stress Has Long-term Effects on Indirect Markers of Dopaminergic Activity in Brain Regions Associated with Motivated Behavior

The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic-pituitary-adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS + NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS + NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.

Metabolic and Endocrine Consequences of Social Stress in a Visible Burrow System

The visible burrow system (VBS) is an ethologically relevant model of social stress, which has been used to study the aggression of male rats in a social context. Previous studies using the VBS have established physiological, endocrine, and neurochemical characteristics associated with chronic social stress in dominant and subordinate animals. A critical criterion in establishing an animal model for research is the replication of findings and the independent validation of the model. Here, we independently confirm previously reported findings and include novel control groups that are important in dissociating the effects of chronic social stress from those resulting from group-housing the male rats in an "enriched environment". Furthermore, we show that whereas the VBS model is useful for males, it is not effective for studies of females because they do not form dominance hierarchies when housed in groups. We also extend the use of the VBS model to examine the etiology of stress-induced anorexia and obesity, finding that weight loss in subordinate rats is attributable to decreased adipose and lean tissue, whereas in dominant rats, it is associated only with adipose tissue loss. Consistent with this, the adiposity hormones leptin and insulin are decreased in subordinates and, to a lesser extent, in dominants, compared with the controls. In summary, the VBS model of chronic social stress is an ethologically relevant animal model and provides a valuable tool for studies of stress-related conditions and pathologies.

Impact of High Coronary Artery Calcification Score (CACS) on Survival in Patients on Chronic Hemodialysis

Electron-beam computed tomography (EBCT) is a noninvasive measure of coronary artery calcification and, therefore, could be a marker of developing cardiovascular disease. Whether the coronary artery calcification score (CACS) is a prognostic marker in chronic dialysis patients is not known.

Indene Bioconversion by a Toluene Inducible Dioxygenase of Rhodococcus Sp. I24

Rhodococcus sp. I24 can oxygenate indene via at least three independent enzyme activities: (i) a naphthalene inducible monooxygenase (ii) a naphthalene inducible dioxygenase, and (iii) a toluene inducible dioxygenase (TID). Pulsed field gel analysis revealed that the I24 strain harbors two megaplasmids of approximately 340 and approximately 50 kb. Rhodococcus sp. KY1, a derivative of the I24 strain, lacks the approximately 340 kb element as well as the TID activity. Southern blotting and sequence analysis of an indigogenic, I24-derived cosmid suggested that an operon encoding a TID resides on the approximately 340 kb element. Expression of the tid operon was induced by toluene but not by naphthalene. In contrast, naphthalene did induce expression of the nid operon, encoding the naphthalene dioxygenase in I24. Cell free protein extracts of Escherichia coli cells expressing tidABCD were used in HPLC-based enzyme assays to characterize the indene bioconversion of TID in vitro. In addition to 1-indenol, indene was transformed to cis-indandiol with an enantiomeric excess of 45.2% of cis-(1S,2R)-indandiol over cis-(1R,2S)-indandiol, as revealed by chiral HPLC analysis. The Km of TID for indene was 380 microM. The enzyme also dioxygenated naphthalene to cis-dihydronaphthalenediol with an activity of 78% compared to the formation of cis-indandiol from indene. The Km of TID for naphthalene was 28 microM. TID converted only trace amounts of toluene to 1,2-dihydro-3-methylcatechol after prolonged incubation time. The results indicate the role of the tid operon in the bioconversion of indene to 1-indenol and cis-(1S,2R)-indandiol by Rhodococcus sp. I24.

Suppression of Nitric Oxide Production in Mouse Macrophages by Soybean Flavonoids Accumulated in Response to Nitroprusside and Fungal Elicitation

The anti-inflammatory properties of some flavonoids have been attributed to their ability to inhibit the production of NO by activated macrophages. Soybean cotyledons accumulate certain flavonoids following elicitation with an extract of the fungal pathogen Diaporthe phaseolorum f. sp. meridionalis (Dpm). Sodium nitroprusside (SNP), a nitric oxide donor, can substitute for Dpm in inducing flavonoid production. In this study, we investigated the effect of flavonoid-containing diffusates obtained from Dpm- and SNP-elicited soybean cotyledons on NO production by lipopolysaccharide (LPS)- and LPS plus interferon-gamma (IFNgamma)-activated murine macrophages.

[A Review of Health Economic Assessment for Liver Transplantation--toward Social Acceptance of Liver Transplantation in Japan]

This paper reviews the literature on health economics assessment (HEA) for liver transplantation (LT) in Europe and USA, and considers prospects in Japan where HEA is currently rarely performed. LT is one of the most expensive health technologies but the health outcome is generally good. It provides the only well-established treatment for end-stage liver disease (ESLD) in the Western world, while in Japan it has yet to be fully implemented because public acceptance is still very low. MEDLINE and Japana Centra Revuo Medicina WEB version Ver. 2 (JCRM2) were systematically used for the literature search. As a result, 6 original papers in Europe and USA that employed accurate methods for HEA were identified through MEDLINE, indicating that LT is cost-effective on long term follow-up. In Japan, however, only one study could be good which tried to estimate it's cost-effectiveness, and the methodology was different from that used in Europe and USA. Through accurate HEA for LT in Japan, we hope that this procedure may become a well-accepted health technology in the future.

Induction of Systemic Tolerance in Normal but Not in Transgenic Mice Through Continuous Feeding of Ovalbumin

The ingestion of most dietary protein can cause systemic tolerance, and such tolerance is easier to induce in younger than in older mice. In this study, we examined whether oral tolerance to ovalbumin (OVA) could be induced in OVA-T-cell receptor (OVA-TCR)-specific transgenic mice. Continuous feeding or gavage with OVA induced tolerance, measured as reduced antibody production, in young and aged BALB/c mice, in a dose-dependent manner, but this effect was not observed in transgenic mice. Once BALB/c mice became tolerant, this state was maintained for over 44 weeks, although the tolerant state could be reversed by adoptive cell transfer. DO11.10 mice did not become tolerant upon continuous feeding with OVA, and the adoptive transfer of naïve cells increased the levels of specific antibodies in their sera after antigenic challenge. The immunization schedule used here leads to a Th2-dependent antibody response in normal BALB/c mice. However, the same schedule induced both Th1- and Th2-antibody responses in transgenic mice. Dendritic cells (DC) from tolerant BALB/c mice were less efficient in the induction of the proliferation of cocultured T cells from both BALB/c and DO11.10 mice, as well as Th1 [interleukin (IL)-2 and interferon (IFN)-gamma] and Th2 (IL-4 and IL-10) cytokine production. The DC from DO11.10 transgenic mice were equally efficient in the induction of T-cell proliferation in both normal and transgenic mice, as well as in the induction of Th1 and Th2 cytokines, whether or not the mice consumed OVA. Transforming growth factor (TGF)-beta secretion was significantly lower in the supernatants of T cells from both normal and transgenic mice cocultured with DC from DO11.10 mice that had consumed OVA, while it was significantly higher in the presence of DC from normal tolerant mice, thus implicating TGF-beta as a regulatory cytokine in oral tolerance in the murine model.

[A Survey on Smoking Behavior in Hokkaido University School of Medicine, 2003]

A survey was carried out to assess smoking among students, and administration and teaching staff in Hokkaido University School of Medicine in 2003.

[WHO Definition of Health: a Historical Perspective]

Flexions of the Popliteal Artery: Dynamic Angiography

Stenting of popliteal artery (PA) with self-expandable stents is a therapeutic option in selected patients with arterial disease. Fractures of these stents may occur, and they are thought to be related to development of hinge points (HPs) secondary to knee flexion. However, it remains obscure how movements of the knee affect the morphology of the PA and where HPs occur.

Self-reported Denture Hygiene of a Sample of Edentulous Attendees at a University Dental Clinic and the Relationship to the Condition of the Oral Tissues

This article aims to evaluate the habits of hygiene and usage of a sample group of Brazilian wearers of complete dentures.

Functional Status and Active Life Expectancy Among Senior Citizens in a Small Town in Japan

The objectives of this study were to understand transition patterns and mechanisms of functional status, and to estimate active life expectancy (ALE) among senior citizens in a small town in Japan. With data drawn from surveys conducted annually from 1998 to 2002 (n=638 at baseline), prevalence and incidence of functional disability in activities of daily living (ADL) and instrumental activities of daily living (IADL) were described and compared between the sexes. Then relationships between potential predictors and functional decline through a 4-year follow-up were examined using logistic regression. Finally, active and disabled life expectancy was estimated by Katz's method. At baseline, 9 and 12% of subjects were dependent in performing ADL and IADL, respectively. Prevalence and incidence rates increased with age. The risk of mortality increased by 2.2-5.0-fold when the subject was functionally dependent at the previous year. Advanced age, difficulty in walking and poor interest were shown to be significant predictors of loss of independence in ADL. Mean durations with disability in ADL and IADL among women were longer than among men by around 1 year. Population-specific preventive care programs considering physical, cognitive and social aspects are needed not only to maximize ALE but also to improve quality of life during survival period with disability especially in old women.

Prolactin Prevents Acute Stress-induced Hypocalcemia and Ulcerogenesis by Acting in the Brain of Rat

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

Sociodemographic Factors Associated with Incidence of Dementia Among Senior Citizens of a Small Town in Japan

Dementia is one of the common causes that lead to dependence of senior citizens in daily living. Clarifying the features of the elderly with dementia is instrumental in planning for their effective care and support in a community, and for attempts at prevention. Our purpose was to investigate the impact of sociodemographic factors among the elderly with the presumptive diagnosis of dementia. We carried out a survey annually from 1998 to 2002 in a dynamic cohort of community-dwelling individuals aged 65 years or older. Of the 945 subjects, 782 were eligible for study because at the first interview they were asymptomatic for dementia and not institutionalized. We found no significant difference in a 5-year average incidence rate between genders. However, the risk of developing dementia increased with age. The study population was categorized into three groups of living arrangement: those living with spouse and others, those living alone, and those living with persons other than the spouse. The incidence rate of dementia among the elderly who lived with spouse and others was significantly lower than for those among the other groups. This was also notable in the subjects without a history of stroke, even after adjustment for age and gender. This result indicates that living with spouse might have an important benefit in reducing the risk of developing dementia, although this effect would vary with the type of dementing disease. We suggest that preventive measures in clinical and community care of the elderly should focus on interactive social conditions such as living environments.

Dynamic Anatomy of the Popliteal Artery: Might Culture Affect the Outcome of Endovascular Therapy?

Gender Differences in the Contributions of Risk Factors to Depressive Symptoms Among the Elderly Persons Dwelling in a Community, Japan

To examine the relative importance of risk factors associated with depressive symptoms and gender differences in exposure to the risk factors among the elderly persons living in the community.

Regarding: "Endovascular Treatment of Popliteal Artery Aneurysms: Results of a Prospective Cohort Study"

Aqueous Suspensions of Charged Spherical Colloids: Dependence of the Surface Charge on Ionic Strength, Acidity, and Colloid Concentration

We theoretically investigate the dependence of the surface charge developed on charged spherical colloids upon several environmental parameters: the ionic strength of the monovalent added electrolyte, acidity (stabilized by a pH buffer solution), and colloid concentration. In the framework of the mean-field Poisson-Boltzmann spherical cell model, we include the charged colloid-microion correlations into the buffer equation, and we allow for the specific binding of ions to the ionizable groups on the colloid surface. Theoretical predictions are compared to the results obtained under the planar-symmetry Gouy-Chapman approximation and analyzed for the experimental conditions of an aqueous dispersion of the phospholipid dimyristoyl phosphatidylglycerol (DMPG). Experimental measurements of the partition ratio of an aqueous soluble cationic spin label on buffered dispersions of polyanionic unilamellar vesicles of DMPG in the presence of added monovalent salt are theoretically interpreted in terms of ion partition due to electrostatic interactions. We show that the specific binding of the probe must be admitted to explain the experimental results.

Assessing Level of Consciousness and Cognitive Changes from Vegetative State to Full Recovery

Although investigations addressing cognitive recovery from the vegetative state have been reported, to date there have been no detailed studies of these patients combining both neuropsychology and functional imaging to monitor and record the recovery of consciousness. This paper describes the recovery of a specific vegetative state (VS) case. The patient (OG) remained in the vegetative state for approximately two months, increasing her level of awareness to a minimally conscious state, where she continued for approximately 70 days. In the course of the ensuing 18 months, she was able to reach an acceptable level of cognitive functioning, with partial levels of independence. Throughout this two year period, she received continuous cognitive evaluation, for which several different tools were applied including coma and low functioning scales, full cognitive batteries, and structural and functional magnetic resonance imaging (MRI). We present here preliminary data on fMRI using a word presentation paradigm before and after recovery; we also discuss the difficulty of how to determine level of consciousness using the tools currently available, and the subsequent improvement in different cognitive domains. We confirm that accurate diagnosis and proper cognitive assessment are critical for the rehabilitation of patients with disorders of consciousness.

Psychological and Psychopathological Reactions in Honduras Following Hurricane Mitch: Implications for Service Planning

Posttraumatic stress disorder (PTSD) and other psychopathological outcomes have not been sufficiently studied in community-based samples in Latin America. This study explored various psychopathological reactions and their respective risk factors two months after Hurricane Mitch struck Honduras in October 1998.

Relationships Between Lifestyle and Dental Health Behaviors in a Rural Population in Japan

The aim of this study was to determine associations of lifestyle with dental health behaviors such as tooth brushing frequency, use of extra cleaning devices, and regular dental visits to a dentist.

Social Stress: from Rodents to Primates

Social stress is associated with development of many psychological and physiological disturbances in humans. Animal models are needed to determine the etiology of these diseases and to develop rational clinical therapies to treat those afflicted. Rodent and non-human primate models of social stress have been developed to address these needs and contribute in complementary ways to the understanding of social stress. In this review, we provide an overview of common rodent and non-human primate models of social stress used in the laboratory with a focus on social hierarchy models. The implications of the current findings on understanding of the development of stress-related disease will also be discussed.

Endovascular Treatment of a Stenosed Anomalous Left Gastric Artery: Unique Open Artery of the Gastrointestinal Tract

Morphological Characterization of a Human Glioma Cell L Ine

A human malignant continuous cell line, named NG97, was recently established in our laboratory. This cell line has been serially subcultured over 100 times in standard culture media presenting no sign of cell senescence. The NG97 cell line has a doubling time of about 24 h. Immunocytochemical analysis of glial markers demonstrated that cells are positive for glial fibrillary acidic protein (GFAP) and S-100 protein, and negative for vimentin. Under phase-contrast microscope, cultures of NG97 showed cells with variable morphological features, such as small rounded cells, fusiform cells (fibroblastic-like cells), and dendritic-like cells. However, at confluence just small rounded and fusiform cells can be observed. At scanning electron microscopy (SEM) small rounded cells showed heterogeneous microextentions, including blebs and filopodia. Dendritic-like cells were flat and presented extensive prolongations, making several contacts with small rounded cells, while fusiform cells presented their surfaces dominated by microvilli.We believe that the knowledge about NG97 cell line may be useful for a deeper understanding of biological and immunological characteristics of gliomas.

Novel Rapid Immunochromatographic Test Based on an Enzyme Immunoassay for Detecting Nucleocapsid Antigen in SARS-associated Coronavirus

A novel severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been discovered. The detection of both antigens and antibodies in SARS-CoV from human specimens with suspected SARS plays an important role in preventing infection. We developed a novel rapid immunochromatographic test (RICT) based on the sandwich format enzyme immunoassay (EIA) with an all-in-one device for detecting the native nucleocapsid antigen (N-Ag) of SARS-CoV using monoclonal antibodies (MoAbs), which we produced by immunizing recombinant N-Ag to mice. RICT is a qualitative assay for respiratory aspirates and serum specimens. With this assay, a positive result can be judged subjectively by the appearance of a blue line on the device 15 min after the sample is applied. RICT with several pairs of MoAbs showed a high sensitivity for the detection of recombinant N-Ag as well as viral N-Ag of SARS-CoV. rSN122 and rSN21-2 were the best MoAbs for immobilized antibody and enzyme labeling, respectively. With regard to analytical sensitivity, RICT detected N-Ag at 31 pg/mL for recombinant N-Ag, and at 1.99 x 10(2) TCID(50)/mL for SARS-CoV. The specificity of RICT was 100% when 150 human sera and 50 nasopharyngeal aspirates (NSPs) were used. RICT based on an EIA using the rSN122/rSN21-2 pair is a sensitive, specific, and reliable rapid assay for detecting N-Ag in SARS-CoV treated with either heat or Triton X-100.

Cloning and Assisted Reproductive Techniques: Influence on Early Development and Adult Phenotype

Over the past 40 years, our increased understanding and development of cell and molecular biology has allowed even greater advances in reproductive biology. This is most evident by the development of various aspects of assisted reproductive techniques (ART), generation of transgenic animals, and most recently generation of mammals through somatic cell cloning. To date, cloning from adult somatic cells has been successful in at least 10 mammalian species. Although generating viable cloned mammals from adult cells is technically feasible and the list of successes will only continue to grow with time, prenatal and perinatal mortality is high and live cloned offspring have not been without health problems. The success of many of the proposed applications of the cloning technique obviously depends upon the health and survival of founder animals generated by nuclear transfer. This article summarizes the health consequences of cloning in mice, and discusses possible mechanisms through which these conditions may arise. In addition, we discuss the effects of ART in animal models and in humans. ART also involves some of the same procedures used in cloning, and there are reports that offspring generated by ART sometimes display aberrant phenotypes as well. It is important to point out that although these techniques do sometimes produce abnormalities, the majority of offspring are born apparently normal and survive to adulthood. Additionally, we must emphasize that the effects of ART and cloning observed in animal models do not necessarily indicate that they will occur in humans. In this article, we review studies examining the phenotype of animals generated by cloning and various ART, and discuss clinical implications of these findings.

The Egogram is a Potent, Independent Risk Factor for Hypertension in Pregnancy

To assess the association between the egogram and hypertension in pregnancy (HP), a case-control study was carried out. Seventy-one HP cases, primiparous aged 20 to 34 years, and 109 controls, were enrolled among pregnant women who visited our hospitals for obstetrical care. Data from a self-administered questionnaire containing a Self Grow-Up Egogram (SGE) were subjected to univariate and multivariate analyses with prepregnancy body mass index (BMI) and angiotensinogen (AGT) genotype. The mean +/- standard error of total scores for the critical parent (CP) scale were 9.7 +/- 0.5 for cases and 8.3 +/- 0.3 for controls, those for the nurturing parent (NP) scale were 13.6 +/- 0.4 for cases and 13.4 +/- 0.3 for controls, those for the adult (A) scale were 11.3 +/- 0.5 for cases and 10.9 +/- 0.3 for controls, those for the free child (FC) scale were 12.3 +/- 0.3 for cases and 13.8 +/- 0.3 for controls, and those for the adapted child (AC) scale were 10.2 +/- 0.4 for cases and 8.5 +/- 0.4 for controls. A low FC scale score (FC < or = 10) and a high AC scale score (AC > 10) were significantly associated with HP ( p < 0.05; p < 0.01, respectively). In the multivariate analysis, FC < or = 10, AC > 10, prepregnancy BMI > or = 24, and homozygosity of the T235 allele genotype of the AGT gene were detected as the potent independent risk factors for HP. The odds ratios were 2.2, 2.8, 4.0, and 2.5, respectively. The present results suggest that a low FC score and a high AC score may be potent, independent risk factors for HP.

Insertion/deletion Polymorphism of the Angiotensin-converting Enzyme Gene and Preeclampsia in Japanese Patients

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.

Prevalence, Risk Factors and Aging Vulnerability for Psychopathology Following a Natural Disaster in a Developing Country

This study explored the psychopathological reactions to a natural disaster and their respective risk factors among the elderly in Honduras and their vulnerability as compared to other adults. STUDY SUBJECTS AND SAMPLE: Eight hundred respondents of both genders aged 15 years and above, of which 103 were 60 and over, were selected from high, middle and low residential status areas in Tegucigalpa that had suffered high and low exposure to the devastating effects of Hurricane Mitch. RESEARCH INSTRUMENTS: CIDI was used to diagnose PTSD and the Impact of Events Scale was administered as a measure of severity of post-traumatic reaction. Depression and alcohol misuse were examined using screening instruments. The SRQ was used as both a measure of emotional distress and dichotomized to screen for probable psychiatric disorder.

Advocacy, Promotion and E-learning: Supercourse for Zoonosis

This paper discusses the history of emerging infectious diseases, risk communication and perception, and the Supercourse lectures as means to strengthen the concepts and definition of risk management and global governance of zoonosis. The paper begins by outlining some of the key themes and issues in infectious diseases, highlighting the way which historical analysis challenges ideas of the 'newness' of some of these developments. It then discusses the role of risk communication to public accountability. The bulk of the paper presents an overview of developments of the Internet-based learning system through the Supercourse lectures that may prove to be a strong arm for the promotion of the latest medical information particularly to developing countries.

Strategic Approach to Information Security and Assurance in Health Research

Information security and assurance are an increasingly critical issue in health research. Whether health research be in genetics, new drugs, disease outbreaks, biochemistry, or effects of radiation, it deals with information that is highly sensitive and which could be targeted by rogue individuals or groups, corporations, national intelligence agencies, or terrorists, looking for financial, social, or political gains. The advents of the Internet and advances in recent information technologies have also dramatically increased opportunities for attackers to exploit sensitive and valuable information.Government agencies have deployed legislative measures to protect the privacy of health information and developed information security guidelines for epidemiological studies. However, risks are grossly underestimated and little effort has been made to strategically and comprehensively protect health research information by institutions, governments and international communities.There is a need to enforce a set of proactive measures to protect health research information locally and globally. Such measures should be deployed at all levels but will be successful only if research communities collaborate actively, governments enforce appropriate legislative measures at national level, and the international community develops quality standards, concluding treaties if necessary, at the global level.Proactive measures for the best information security and assurance would be achieved through rigorous management process with a cycle of "plan, do, check, and act". Each health research entity, such as hospitals, universities, institutions, or laboratories, should implement this cycle and establish an authoritative security and assurance organization, program and plan coordinated by a designatedChief Security Officer who will ensure implementation of the above process, putting appropriate security controls in place, with key focus areas such aspolicies and best practices, enforcement and certification, risk assessment and audit, monitoring and incident response, awareness and training, and modern protection method and architecture. Governments should enforce a comprehensive scheme, and international health research communities should adopt standardized innovative methods and approaches.

BSE Safety Standards: An Evaluation of Public Health Policies of Japan, Europe, and USA

Since the advent of bovine spongiform encephalopathy (BSE) in the United Kingdom in 1986, new BSE cases have recently become rare. However, in Japan and the United States, positive cases have started to be seen recently. The rise in BSE cases paved the way for the human form of this disease, the variant Creutzfeldt-Jakob disease (vCJD). The observed trends in the UK may be attributed to effective implementation of public health policies coupled with increased vigilance through advancement in science and technology, or they may well be a reflection of the natural disease progression. We aim to discuss the BSE chronology of events, and compare examination methods, costs and cost-efficiency, management, and public policies of Japan, Europe, and the USA.

Rayleigh Instability of Charged Aggregates: Role of the Dimensionality, Ionic Strength, and Dielectric Contrast

We extended a previous analysis of the classical Rayleigh instability of spherical charged droplets in the presence of neutralizing monovalent counterions [M. Deserno, Eur. Phys. J. E 6, 163 (2001)], by generalizing the problem for suspensions of aggregates with D-dimensional symmetry, corresponding for D = 2 to infinite (rodlike) cylindrical charged bundles and for D = 3 to spherical charged droplets. In addition, we include the effects of added monovalent salt and of dielectric contrast between the charged aggregate and the surrounding solvent. The electrostatic energy taking the microion screening into account is estimated using uniform profiles within the framework of the cell model. We verify the robustness of these results by also considering Debye-Hückel-type microion profiles that are obtained by the minimization of a linearized Poisson-Boltzmann free-energy functional. In the case when the microions can enter inside the charged aggregates, we confirm the occurrence of a discontinuous phase change between aggregates of finite size and an infinite aggregate, which takes place at a collapse temperature that depends on their volume fraction phi and on the salt content. Decrease of phi shifts the phase-change temperature toward higher values, while salt addition has an opposite effect. We obtain analytical expressions for the phase-separation line in the asymptotic limit of infinite dilution (phi-->0), showing that the collapse temperature depends logarithmically on phi . As an application for D = 3 we discuss the stability of the pearl-necklace structures of flexible polyelectrolytes in poor solvents. The case D = 2 is applied to the problem of finite bundle sizes of stiff polyelectrolytes that attract each other-via, e.g., multivalent counterions-leading to an effective surface tension.

Patient Safety in the Clinical Laboratory: a Longitudinal Analysis of Specimen Identification Errors

Patient safety is an increasingly visible and important mission for clinical laboratories. Attention to improving processes related to patient identification and specimen labeling is being paid by accreditation and regulatory organizations because errors in these areas that jeopardize patient safety are common and avoidable through improvement in the total testing process.

Significance of Coronary Artery Calcification Score (CACS) for the Detection of Coronary Artery Disease (CAD) in Chronic Dialysis Patients

Coronary artery disease (CAD) is a principal cause of death in patients with end-stage renal disease (ESRD). The coronary artery calcification score (CACS), determined by electron-beam computed tomography (EBCT), is useful for the detection of CAD in non-ESRD patients. There are few reports on the usefulness of EBCT for the detection of CAD, however, in ESRD patients. We examined the relation between CACS and CAD in ESRD patients.

Deficient Hippocampal C-fos Expression Results in Reduced Anxiety and Altered Response to Chronic Stress in Female Mice

Stress response is an important neuroendocrine function. Overt or prolonged stress hormone secretion can lead to various disease states. The hippocampus plays an important role in the negative feedback onto the major player in the stress response, the hypothalamo-pituitary-adrenal axis. The transcription factor c-Fos is activated in the hippocampus following a number of stressors, including restraint stress. To determine whether c-fos modulates stress response, we previously generated mutant mice carrying a hippocampal mutation of the c-fos gene. In the current study, we found that female mutant mice display lower anxiety-like behavior than female wild-type mice in the elevated plus maze, whereas male mice are apparently normal. While both male and female mutant mice exhibit normal diurnal glucocorticoid (CORT) production and normal responses to acute restraint stress, female mutant mice habituated faster than female wild-type mice in response to chronic restraint stress. These findings suggest that hippocampal c-fos plays a role in gender-dependent response to stress.

Evaluation of the Efficacy of Supraglottoplasty in Obstructive Sleep Apnea Syndrome Associated with Severe Laryngomalacia

To evaluate the clinical and polysomnographic evolution of patients with severe laryngomalacia who underwent supraglottoplasty.

Retrograde Rotablator in Limb Salvage: a New Technique Using an Open Approach

Conventional vascular surgery and balloon angioplasty have poor results in severe and diffuse atherosclerotic disease of the infrapopliteal arteries. High-speed rotational atherectomy (Auth Rotablator) has not succeeded either, because of poor long-term patency and the non-reflow phenomenon. We report a case of limb salvage with long occlusion of the three infrapopliteal vessels. The anterior tibial artery was treated with retrograde Auth Rotablator atherectomy by an open approach through the pedal artery, resulting in full patency of the anterior tibial artery and healing of the skin lesions. The microparticulate debris from the ablation was drained out through the pedal arteriotomy, avoiding the complications associated with conventional antegrade high-speed rotational atherectomy.

Chronic Social Stress in a Changing Dietary Environment

The human population has slowly transformed from the "hunter-gatherer" period to the current environment of high energy consumption, minimal physical activity and a lifestyle that includes stress and anxiety. Modeling the current environment in the laboratory can help to elucidate mechanisms responsible for the development of obesity, diabetes and, ultimately, the metabolic syndrome. Using the visible burrow system (VBS) model of social stress we have begun to examine the short- and long-term consequences of chronic social stress on energy homeostasis. We demonstrated that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity and have additionally determined that this occurs, in part, through changes in food intake amount and behavior. Changes in body weight and body composition are similar or greater when animals are maintained on a high fat diet. These data suggest that consumption of a high-fat diet during social stress in the VBS, while it does not appear to affect development of a social hierarchy, enhances the effect that chronic stress has on body composition and may be more representative of what happens in humans in modern society where the typical diet has progressively moved toward higher calorie, high-fat foods.

Nonlinear Association of Higher-level Functional Capacity with the Incidence of Falls in Japan

To examine the nonlinear association of higher-level functional capacity with the incidence of falls.

Chronic Social Stress in the Visible Burrow System Modulates Stress-related Gene Expression in the Bed Nucleus of the Stria Terminalis

Prolonged social subjugation produces physiological indices of chronic stress in rats. In the current study, we examined the impact of social stress on glutamic acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in forebrain stress circuitry, using the visible burrow system model of dominance-subordination. Subordinate male rats develop behavioral and neuroendocrine changes consistent with exposure to chronic stress, including marked loss of body weight and elevation of basal plasma corticosterone relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA expression in central stress-regulatory circuits were examined by in situ hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67 expression was decreased in the interfascicular nucleus of the BST in both the subordinate and dominant rats compared to non-burrow control rats. No changes in CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or in the hypothalamic paraventricular nucleus. Collectively, these data suggest that exposure to the visible burrow system attenuates BST GAD expression regardless of social status, whereas the enhanced physiological responses to social stress seen in subordinates may be associated with enhanced CRH expression in the oval nucleus of the BST.

The Impact of Moderate Daily Alcohol Consumption on Aggression and the Formation of Dominance Hierarchies in Rats

Group-housed male rats form social hierarchies, and under these conditions, it has been reported that subordinate (SUB) rats consume more alcohol than dominant (DOM) rats. We tested the hypothesis that a history of drinking alcohol would cause SUB rats to consume even greater amounts of alcohol.

Cost-utility of Living Donor Liver Transplantation in a Single Japanese Center

Living donor liver transplantation is becoming increasingly important in the Western world, but the economic issues remain controversial. We conducted a cost-utility analysis to evaluate whether living donor liver transplantation is cost-effective.

Contribution of Falling and Being Homebound Status to Subsequent Functional Changes Among the Japanese Elderly Living in a Community

Using the data from the community-based longitudinal study of the elderly persons aged 65 or older, this study examined relationships between the occurrence of falls varied by their activity level and subsequent functional decline over time. Of the 705 respondents at baseline, 662 and 632 subjects were assessed at first and second follow-ups. Falling and homebound status at baseline and health function (self-rated general health, activities of daily living (ADLs), instrumental activities of daily living (IADLs), intellectual activity, and social role) at baseline and follow-ups were assessed, and changes in each health function were compared among four groups defined by baseline falling/homebound status. Baseline falling/homebound status was significantly associated with subsequent decline in ADLs over 1 year, and in ADLs, IADLs, intellectual activity, and social role over 2 years. Being homebound might act as a stronger risk factor for ADLs disabilities rather than the occurrence of falls. Moreover, the homebound elderly with no experience of falls was at the greatest risk of the decline of social role. We consider that prevention program and home-based care for homebound elderly should be provided in the community.

Constituents and Antiulcer Effect of Alchornea Glandulosa: Activation of Cell Proliferation in Gastric Mucosa During the Healing Process

Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (85%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.

Use of a Hypodense Sodium Fluorescein Solution for the Endoscopic Repair of Rhinogenic Cerebrospinal Fluid Fistulae

Hypodense fluorescein solution can be used intrathecally to facilitate and accelerate the identification of the fistulous site.

Dynamic Body Weight and Body Composition Changes in Response to Subordination Stress

Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. Although there are strong associations between the incidence of obesity with stress and elevated levels of hormones such as cortisol, there are limited animal models to allow investigation of the etiology of increased adiposity resulting from exposure to stress. Perhaps more importantly, an animal model that mirrors the consequences of stress in humans will provide a vehicle to develop rational clinical therapy to treat or prevent adverse outcomes from exposure to chronic social stress. In the visible burrow system (VBS) model of chronic social stress mixed gender colonies are housed for 2 week periods during which male rats of the colony quickly develop a dominance hierarchy. We found that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity that occurs, in part, through neuroendocrine alterations and changes in food intake amount. Although subordinate rats are hyperphagic following social stress they do not increase their intake of sucrose solution as control and dominants do suggesting that they are anhedonic. Consumption of a high fat diet does not appear to affect development of a social hierarchy and appears to enhance the effect that chronic stress has on body composition. The visible burrow system (VBS) model of social stress may be a potential laboratory model for studying stress-associated metabolic disease, including the metabolic syndrome.

Lentivirus-mediated Downregulation of Hypothalamic Insulin Receptor Expression

Regulation of feeding behavior and energy balance are among the central effects of insulin. For example, intracerebroventricular administration of insulin decreases food intake and body weight, whereas antisense oligodeoxynucleotide downregulation of insulin receptors (IRs) produces hyperphagia. To further examine the role of IRs in the central actions of insulin, we designed an IR antisense lentiviral vector (LV-IRAS) and injected this vector into the third ventricle to selectively decrease IR expression in the rat hypothalamus. Three weeks after LV-IRAS administration, the expression of IRs in the hypothalamus was significantly decreased, whereas no changes were observed in hippocampal IR levels. LV-IRAS administration decreased insulin-stimulated phosphorylation of hypothalamic IRs and translocation of the insulin-sensitive glucose transporter GLUT4 in the hypothalamus; no changes in IR signaling were observed in the hippocampus of LV-IRAS-treated rats. Lentivirus-mediated downregulation of IR expression and signaling produced significant increases in body weight, as well as increases in fat mass that were selective for the subcutaneous compartment. Conversely, lean muscle mass and water mass were not affected in LV-IRAS-treated rats compared to rats treated with control virus. Changes in peripheral adiposity were associated with increases in basal hypothalamic leptin signaling in the absence of changes in leptin receptor expression in LV-IRAS rats. Collectively, these data illustrate the important functional relationships between hypothalamic insulin and leptin signaling in the regulation of body composition and provide insight into the mechanisms through which decreases in IR expression and signaling dysregulates leptin activity, thereby promoting increases in peripheral adiposity.

Curt Richter: Spontaneous Activity and Food Intake

Curt Richter's seminal contributions to the field of psychobiology continue to enlighten us today. His approaches to scientific questions, his ability to design ways of allowing his research subjects (usually rats) to answer his questions and his unique style of data presentation inform current investigations into the biological bases of behavior. One of Richter's earliest interests was identifying the causes of rhythmic spontaneous activity. Richter demonstrated an important relationship between bouts of activity and food intake in the laboratory rat. In his search for a causal link, he invoked contemporary thinking about the relationships between gastric contractions and hunger. Although his idea for a causal role for stomach contractions in eliciting spontaneous activity and food intake was mistaken, this early work identified themes for many of Richter's subsequent contributions and his behavioral observations continue to be relevant for current investigations.

Study of Predominant Bacterial Antigens Triggering Antibody Response in Salmonella Reactive Arthritis: Apropos of a Case

Reactive arthritis (ReA) is a sterile arthritis triggered by distal mucosal infection, which suggests a contribution from bacterial products. The pathogenesis of ReA is unclear. There are no international standards for the serological methods used to confirm ReA. In the present work, we analyzed the predominant bacterial component that triggered an immune response in a 24-year-old woman with acute ReA. The candidate bacterial trigger was investigated by measuring the antibacterial antibodies (all immunoglobulin classes and IgA) to Salmonella enteritidis, Shigella flexneri and Yersinia enterocolitica. ELISA for Salmonella gave a positive result. To identify the bacterial component triggering ReA, antibodies to crude lysate, outer membrane proteins (OMP), cytosolic fraction, supernatant proteins and lipopolysaccharide of S. enteritidis were analyzed in sera and synovial fluid (SF) by ELISA, dot blot, and Western blot. Among the antigen preparations, the antibody response to OMP was dominant in both serum and SF; a strong reaction to seven OMP bands (50-21 kDa) was observed. We concluded that OMP were the main bacterial antigens that trigged ReA in the reported case. Determining the triggering bacterial components in each case can help elucidate the precise causes of ReA and will contribute to the designing of a specific serological diagnostic method for this arthritis.

Aging Reduces the Primary Humoral Response and the in Vitro Cytokine Production in Mice

Aging is accompanied by a decrease in several physiological functions that make older individuals less responsive to environmental challenges. In the present study, we analyzed the immune response of female BALB/c mice (N = 6) of different ages (from 2 to 96 weeks) and identified significant age-related alterations. Immunization with hapten-protein (trinitrophenyl-bovine serum albumin) conjugates resulted in lower antibody levels in the primary and secondary responses of old mice (72 weeks old). Moreover, young mice (2, 16, and 32 weeks old) maintained specific antibodies in their sera for longer periods after primary immunization than did old mice. However, a secondary challenge efficiently induced memory in old mice, as shown by the increased antibody levels in their sera. The number of CD4+ and CD8+ T cells in the spleen increased until 8 weeks of age but there was no change in the CD4+/CD8+ ratio with aging. Splenic T cells from old mice that had or had not been immunized were less responsive to concanavalin-A and showed reduced cytokine production compared to young mice (IL-2: 57-127 vs 367-1104 pg/mL, IFN-gamma: 2344-12,836 vs 752-23,106 pg/mL and IL-10: 393-2172 vs 105-2869 pg/mL in old and young mice, respectively). These data suggest that there are significant changes in the organization of the immune system throughout life. However, the relevance of these alterations for the functioning of the immune system is unknown.

Production of Monoclonal Antibodies for Detection of a Secreted Aspartyl Proteinase from Candida Spp. in Biologic Specimens

Secreted acid proteinases (SAP) constitute an important group of virulence factors in Candida albicans. In the present work, an acid proteinase from C. albicans was sequentially purified from the supernatant of a yeast culture by precipitation with ammonium sulfate, ion exchange chromatography, and molecular exclusion chromatography, yielding a specific enzymatic activity of 204.1 IU/mg on bovine serum albumin (BSA). The molecular mass of the purified proteinase was estimated at 43 kd after exclusion chromatography and at 41 kd by nondenaturating sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified proteinase was able to degrade BSA at pH 2.5, but was not active on collagen, and it was significantly inhibited by pepstatin A. The immunization of BALB/c mice with the purified proteinase and later fusion of their spleen cells with myeloma cells resulted in 19 monoclonal antibody secreting hybridomas (MAbs) capable of detecting SAP in enzyme-linked immunosorbent assay (ELISA) assays. All MAbs obtained are isotype IgG1 kappa (kappa) immunoglobulins and develop a 41 kd protein band by Western blot (WB) in samples of SAP obtained from C. albicans (12-A) and C. dubliniensis (strain 778) crude extracts. The anti-SAP MAbs were used in capture ELISA and two combinations of these antibodies proved suitable for SAP detection, that is, MAP1 (1B1B3) or MAP2 (2D2C10) as coat antibodies, and biotinylated MAP3 (2A6E8) as detect antibody. Capture ELISA using these sets of MAbs detected over 32 ng/mL protein in purified SAP samples as well as in crude C. albicans and C. dubliniensis extracts. The results herein obtained allow for the prediction of how this set of antibodies can be useful for SAP detection in biologic specimens.

Social Stress and Recovery: Implications for Body Weight and Body Composition

Social stress resulting from dominant-subordinate relationships is associated with body weight loss and altered body composition in subordinate (SUB) male rats. Here, we extend these findings to determine whether stress-induced changes in energy homeostasis persist when the social stress is removed, and the animal is allowed to recover. We examined body weight (BW), body composition, and relevant endocrine measures after one or two cycles of 14 days of social stress, each followed by 21 days of recovery in each rat's individual home cage. SUB lost significantly more BW during social housing in a visible burrow system (VBS) compared with dominant (DOM) animals. Weight loss during social stress was attributable to a decrease in adipose tissue in DOM and SUB, with an additional loss of lean tissue in SUB. During both 21-day recovery periods, DOM and SUB regained lost BW, but only SUB were hyperphagic. Following recovery, SUB had a relatively larger increase in adipose tissue and plasma leptin compared with DOM, indicating that body composition changes were dependent on social status. Control animals that were weight matched to SUB or male rats exposed to the VBS environment without females, and that did not form a social hierarchy, did not exhibit changes in body composition like SUB in the VBS. Therefore, chronic social stress causes social status-dependent changes in BW, composition and endocrine measures that persist after repeated stress and recovery cycles and that may ultimately lead to metabolic disorders and obesity.

Revisiting Rabies in Japan: is There Cause for Alarm?

Since 1957 Japan has successfully eradicated human and animal rabies through registration, confinement and compulsory vaccination of family dogs, and elimination of stray dogs. However, in November 2006, two cases of human rabies infections were reported in the country. These patients were bitten by dogs during travel in the Philippines, and did not receive pre- and post-exposure prophylaxes. With the mounting numbers of Japanese travelers every year, the risk of infection increases especially to those who visit regions where the disease is endemic. In this paper, we shall discuss the two recent human deaths from rabies, review the current situation and control measures in Japan and surrounding countries where the disease is prevalent, summarize precautionary measures for travelers, and suggest public health strategies to prevent the re-introduction of rabies in the country.

Association Between Lifestyle Activity and Depressed Mood Among Home-dwelling Older People: a Community-based Study in Japan

In the community-based cross-sectional study, we investigated patterns of lifestyle activities among older people and examined the association between specific types of lifestyle activity and depressed mood status. The participants were 656 men and women aged 65 or older in 2004 who lived in a rural town in Japan, neither institutionalized nor hospitalized and who did not have symptoms of dementia. We found that less interaction with neighbors, society and friends was highly associated with depressed mood for men. Additionally, although they were physically active in gardening/farming, it did not necessarily mean that they were mentally healthy if they did not have close ties with friends, family and children/grandchildren. For women, it seemed important to engage in several types of activities relating to society, leisure and children/grandchildren to be in less depressed mood. Even if they were socially inactive, if they had frequent contact with family and children/grandchildren or going out for pleasure they were less likely to be depressed. Distinguishing gender differences in lifestyle activity patterns and the association of activities with depressed mood will help to guide the development of depression intervention programs.

Androgenic Influences on Behavior, Body Weight, and Body Composition in a Model of Chronic Social Stress

The visible burrow system (VBS) is a model used to study chronic social stress in colony-housed rats. A hierarchy develops among the males resulting in dominant (DOM) and subordinate (SUB) animals. Hierarchy-associated changes in body weight, body composition, behavior, and neuroendocrine measures have been observed. After 14 d of VBS housing, SUB animals have decreased body weight, elevated corticosterone, and decreased testosterone (T), compared with DOM animals and controls, placing SUB animals in an ideal endocrine state to regain lost body weight as adipose tissue. It is hypothesized that maintaining constant androgen concentrations in SUB males during stress will prevent body weight loss by maintaining more lean body mass. To test this, animals were gonadectomized and implanted with SILASTIC implants containing T, 5alpha-dihydrotestosterone (DHT), or cholesterol. Implants maintained constant physiological levels of T. Standard intact, T, and DHT implant colonies formed hierarchies, whereas cholesterol colonies did not. Androgen manipulations significantly altered offensive and defensive behaviors only on the first day of VBS housing. After VBS stress, intact, T, and DHT SUB animals weighed less and lost more adipose and lean tissue than DOM and control males, whereas DOM animals primarily lost adipose tissue. However, on recovery, DHT SUB animals maintained more lean tissue than intact SUB animals. Oral glucose tolerance tests revealed that glucose clears faster in stressed T-implanted males that have increased adipose tissue. Overall, these data suggest that constant androgen concentrations in SUB animals do not prevent weight loss and changes in body composition during stress but do so during recovery.

[Coronary Aneurisms Presumably Secondary to Kawasaki Disease]

Leptin Activates Hypothalamic Acetyl-CoA Carboxylase to Inhibit Food Intake

Hypothalamic fatty acid metabolism has recently been implicated in the controls of food intake and energy homeostasis. We report that intracerebroventricular (ICV) injection of leptin, concomitant with inhibiting AMP-activated kinase (AMPK), activates acetyl-CoA carboxylase (ACC), the key regulatory enzyme in fatty acid biosynthesis, in the arcuate nucleus (Arc) and paraventricular nucleus (PVN) in the hypothalamus. Arc overexpression of constitutively active AMPK prevents the Arc ACC activation in response to ICV leptin, supporting the hypothesis that AMPK lies upstream of ACC in leptin's Arc intracellular signaling pathway. Inhibiting hypothalamic ACC with 5-tetradecyloxy-2-furoic acid, a specific ACC inhibitor, blocks leptin-mediated decreases in food intake, body weight, and mRNA level of the orexigenic neuropeptide NPY. These results show that hypothalamic ACC activation makes an important contribution to leptin's anorectic effects. Furthermore, we find that ICV leptin up-regulates the level of malonyl-CoA (the intermediate of fatty acid biosynthesis) specifically in the Arc and increases the level of palmitoyl-CoA (a major product of fatty acid biosynthesis) specifically in the PVN. The rises of both levels are blocked by 5-tetradecyloxy-2-furoic acid along with the blockade of leptin-mediated hypophagia. These data suggest malonyl-CoA as a downstream mediator of ACC in leptin's signaling pathway in the Arc and imply that palmitoyl-CoA, instead of malonyl-CoA, could be an effector in relaying ACC signaling in the PVN. Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade.

Correlation of the Highest-energy Cosmic Rays with Nearby Extragalactic Objects

Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 x 10(19) electron volts and the positions of active galactic nuclei (AGN) lying within approximately 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Correlation Between Yersinia Enterocolitica and Type I Collagen Reactivity in Patients with Arthropathies

We investigated the association with Yersinia infection in patients with arthropathies in our region. To assess the reactivity to articular antigens, the correlation of anti-Yersinia with anti-type I and type II collagen antibodies was studied. Sera from 124 patients with musculoskeletal symptoms, and 47 synovial fluids (SF) from patients with rheumatoid arthritis (RA), spondyloarthopathies (SpA) or osteoarthritis (OA) were examined. Immunoglobulins against Yersinia enterocolitica, type I and type II collagens were determined by enzyme-linked immunosorbent assay. Immunoglobulin (Ig) A to Yersinia lipopolysaccharide (LPS) was present in 13/124 sera (10%) and 3/47 SF (6%). By Western blot, IgA to Yersinia outer proteins (Yops) was found in 14/124 sera (11%) and 2/47 SF (4%). Yersinia DNA from SF was not amplified by polymerase chain reaction. We found a significant correlation with anti-collagen type I but not type II antibodies. These results suggest different reactivity to articular collagen in patients with Yersinia antibodies.

Developmental, Behavioral, and Physiological Phenotype of Cloned Mice

Cloning from adult somatic cells has been successful in at least ten species. Although generating viable cloned mammals from adult cells is technically feasible, prenatal and perinatal mortality is high and live cloned offspring have had health problems. This chapter summarizes the health consequences of cloning in mice and discusses possible mechanisms through which these conditions may arise. These studies have further significance as other assisted reproductive techniques (ART) also involve some of the same procedures used in cloning, and there are some reports that offspring generated by ART display aberrant phenotypes as well. At the moment, the long-term consequences of mammalian cloning remain poorly characterized. Data available thus far suggest that we should use this technology with great caution until numerous questions are addressed and answered.

Knowledge, Attitudes, and Practices Survey of Rabies in a Community in Sri Lanka

The primary objective of this study was to determine the level of knowledge, attitudes and practices (KAP) of rabies management and control of a sample population. The secondary objective was to compare the KAP with respect to rabies management and control between urban and rural areas and between pet and non-pet owners.

Gender Differences in the Relationships Between Obesity and Lifestyle Risk Factors in a Small Farming Town in Japan

The prevalence of obesity and its relationship to lifestyle habits was studied in Minami Furano Town, a small farming town in Hokkaido, Japan. All residents of Minami Furano Town over 18 years of age were given an anonymous, self-administered questionnaire in March, 2002. Logistic-regression analysis was performed separately for each gender with obesity as the dependent valuable, and lifestyle risk factors as explanatory variables. The prevalence of obesity (BMI > or = 25) was 30.2% in men and 29.2% in women. The risk factors for obesity included "smoking", "having no hobby", "low intake frequency of green vegetables", "high intake frequency of cooking oil" and eating "a large quantity at dinnertime" in men. For women the risk factors included "age", "stress", "drinking alcohol", "eating quickly", "low tooth brushing frequency" and "irregular health checks". Nearly one third of the adults in this town were obese when assessed using the Japanese criteria of BMI > or = 25. Few women were employed full-time and they had limited opportunity for periodic health checks. Improved community-based nutrition activities are needed for women.

Nrf2 Mediates Cancer Protection but Not Prolongevity Induced by Caloric Restriction

Caloric restriction (CR) is the most potent intervention known to both protect against carcinogenesis and extend lifespan in laboratory animals. A variety of anticarcinogens and CR mimetics induce and activate the NF-E2-related factor 2 (Nrf2) pathway. Nrf2, in turn, induces a number of antioxidative and carcinogen-detoxifying enzymes. Thus, Nrf2 offers a promising target for anticarcinogenesis and antiaging interventions. We used Nrf2-disrupted (KO) mice to examine its role on the biological effects of CR. Here, we show that Nrf2 is responsible for most of the anticarcinogenic effects of CR, but is dispensable for increased insulin sensitivity and lifespan extension. Nrf2-deficient mice developed tumors more readily in response to carcinogen exposure than did WT mice, and CR was ineffective in suppressing tumors in the KO mice. However, CR extended lifespan and increased insulin sensitivity similarly in KO and WT mice. These findings identify a molecular pathway that dissociates the prolongevity and anticarcinogenic effects of CR.

[Current Chemoradiation of Uterine Cervical Cancer]

Introduction to the Special Issue. Proceedings from the 2007 Meeting of the Society for the Study of Ingestive Behavior

Upper Limit on the Diffuse Flux of Ultrahigh Energy Tau Neutrinos from the Pierre Auger Observatory

The surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau neutrinos that interact in Earth's crust. Tau leptons from nu(tau) charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 are used to place an upper limit on the diffuse flux of nu(tau) at EeV energies. Assuming an E(nu)(-2) differential energy spectrum the limit set at 90% C.L. is E(nu)(2)dN(nu)(tau)/dE(nu)<1.3 x 10(-7) GeV cm(-2) s(-1) sr(-1) in the energy range 2 x 10(17) eV< E(nu)< 2 x 10(19) eV.

Increasing Access to Places for Physical Activity Through a Joint Use Agreement: a Case Study in Urban Honolulu

To increase levels of physical activity (PA), interventions that create or enhance access to places for PA are recommended. Establishing a joint use agreement is one way to increase access to existing PA and recreational facilities. The purpose of this article is to present a case study of In-Motion, a pilot joint use agreement project at one urban high school in Honolulu, Hawaii.

Reactive Arthritis with Conjunctivitis, Urethritis and Diarrhea in a Child: Immunological Study of Potential Bacterial Trigger

An in Vitro Model of Pseudomonas Aeruginosa Biofilms on Viable Airway Epithelial Cell Monolayers

Chronic rhinosinusitis (CRS) that is refractory to medical or surgical intervention may involve a particularly resistant form of infection known as a bacterial biofilm. Bacterial biofilms are three-dimensional aggregates of bacteria that often are recalcitrant to antibiotics secondary to physical barrier characteristics. To date, all studies investigating biofilms in CRS have been descriptive in either human or animal tissue. To better understand the interactions of bacterial biofilms with respiratory epithelium, we describe an in vitro model of biofilm sinusitis by establishing mature biofilms on airway epithelial air-liquid interface cultures.

[The Large Vestibular Aqueduct Syndrome: a Cause of Neurosensory Dysacusia]

the large vestibular aqueduct syndrome (LVAS) is characterized by the enlargement of the vestibular aqueduct associated with sensorioneural hearing loss. The level of hearing loss varies and may be fluctuant, progressive or sudden. Vestibular symptoms may be present. The diagnosis is reached by imaging methods.

FokI Variant of Vitamin D Receptor Gene and Factors Related to Atherosclerosis Associated with Ossification of the Posterior Longitudinal Ligament of the Spine: a Multi-hospital Case-control Study

A sex- and age-matched case-control study with genotyping of the FokI variant of the vitamin D receptor gene (VDR) was carried out.

Ectopic Expression of Mouse Sry Interferes with Wnt/beta-catenin Signaling in Mouse Embryonal Carcinoma Cell Lines

In mammals, Sry is the master regulator of male sex determination, although how it functions is still unclear. By contrast, female sex determination depends on the action of Rspo1 and Wnt4, the regulators of Wnt/beta-catenin signaling. To seek a possible interaction between male and female sex determination mechanisms, we examined whether Sry affects Wnt/beta-catenin signaling. Using the TOPFLASH reporter system to measure Lef/Tcf-dependent transcriptional activity, we showed that ectopic expression of mouse Sry strongly suppressed Wnt/beta-catenin signaling in mouse embryonal carcinoma and human embryonic kidney cell lines. This inhibition occurred downstream of beta-catenin but upstream of Lef/Tcf, and depended on both the HMG-box and the C-terminal transcriptional activation domain. By contrast, TOPFLASH was not inhibited by human SRY, which apparently lacks a transcriptional activation domain. However, a fusion construct consisting of human SRY attached to the C-terminal domain of mouse Sry was able to inhibit TOPFLASH effectively. Furthermore, Sry constructs carrying point mutations equivalent to those in human sex reversal mutations were less effective in inhibiting Wnt/beta-catenin signaling. Also, we showed that the action of Sry as a transcriptional activator was both necessary and sufficient to inhibit Wnt/beta-catenin signaling, suggesting that the transcriptional targets of Sry are responsible for the inhibition of signaling. Sox9 is a potential transcriptional target of Sry, although quantitative RT-PCR analysis indicates that the expression of Sox9 was not up-regulated by the ectopic expression of mouse Sry in mouse embryonal carcinoma cells. While the present study demonstrates an impact of mouse Sry on Wnt/beta-catenin signaling at an in vitro level, it requires further investigations to assess whether such action also takes place in vivo to regulate male sex determination.

Observation of the Suppression of the Flux of Cosmic Rays Above 4 X 10 (19) EV

The energy spectrum of cosmic rays above 2.5 x 10;{18} eV, derived from 20,000 events recorded at the Pierre Auger Observatory, is described. The spectral index gamma of the particle flux, J proportional, variantE;{-gamma}, at energies between 4 x 10;{18} eV and 4 x 10;{19} eV is 2.69+/-0.02(stat)+/-0.06(syst), steepening to 4.2+/-0.4(stat)+/-0.06(syst) at higher energies. The hypothesis of a single power law is rejected with a significance greater than 6 standard deviations. The data are consistent with the prediction by Greisen and by Zatsepin and Kuz'min.

Uterine Natural Killer Cells Are Immunogenic in Syngeneic Male Mice

Uterine natural killer (uNK) cells expand rapidly during endometrial decidualization and account for 70% of leukocytes in early gestational uteri of humans and rodents. These cells make unique contributions to pregnancy, contributing to the success of embryo implantation and maintenance of decidual tissue that supports placental and fetal development. We postulated that uNK cells express molecules that are not shared by circulating NK (cNK) cells or other leukocytes and, therefore, would be immunogenic for male mice. We isolated viable uNK cells from gestation day 9 pregnant mice and inoculated them into syngeneic males. This induced antibodies reactive with mouse uNK cells but not with cNK cells or other lymphocytes. The antibodies reacted identically with uNK cells in tissue sections from five different mice strains from gestational day 7-12 and in pregnant rat uterus, suggesting that the recognized antigen should be a specific marker of uNK cell. Spleen cells from inoculated males were used subsequently to produce a monoclonal antibody reactive to a uNK cell surface antigen. These experiments confirm that uNK cells are a pregnancy-specific subset of NK cells expressing distinct surface antigen from those found in other tissues.

Increased Rates of White Matter Hyperintensities in Late-onset Bipolar Disorder

Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset >or= 60 years), early-onset BD subjects (EO-BD, illness onset <60 years), and elderly healthy volunteers.

Expanding Research Capacity and Accelerating AIDS Vaccine Development in Asia

According to the Joint UN Program on AIDS (UNAIDS), an estimated 4.9 million adults and children are living with HIV in Asia and the Pacific. Refinement and development of existing and new prevention and treatment technologies--including safe, effective, and accessible AIDS vaccines--are urgent public health priorities. The Asian region faces several challenges for AIDS vaccine development. There are multiple genetic variants of HIV-1 driving the epidemic in the region and too few vaccine candidates in the pipeline targeting those subtypes. Low HIV incidence throughout the region means that trial sites must recruit larger numbers of volunteers and shift their focus to higher-risk populations where incidence is higher. Also, the cultural, economic, and political diversity of the region may render collaboration very complex, but also beneficial at a regional level. Recognizing that collaborating as a region could foster and accelerate AIDS vaccine development, participants at the Sapporo International Consultation recommended that an AIDS Vaccine Asian Network (AVAN) be created to facilitate interactions between donors and funding opportunities, increase regional clinical trial and production capacity, support region-specific advocacy and communication strategies, contribute to the Global HIV Vaccine Enterprise Scientific Plan, prepare a regional approach for future vaccine deployment, and develop a regional platform for clinical trials including harmonized legal, regulatory, and ethical frameworks.

Mainstreaming HIV/AIDS Program into Infrastructure Development and Community Preparedness

Pulmonary Artery Access Embolization in Patients with Massive Hemoptysis in Whom Bronchial And/or Nonbronchial Systemic Artery Embolization is Contraindicated

The objective of this paper is to present an alternative therapeutic approach for the treatment of patients with massive hemoptysis in whom bronchial and/or nonbronchial systemic arterial embolization is not possible. We describe a percutaneous procedure for pulmonary segmental artery embolization. Between May 2000 and July 2006, 27 adult patients with hemoptysis underwent percutaneous treatment at our department; 20 of 27 patients were embolized via bronchial and or nonbronchial systemic arteries and 7 patients were embolized via pulmonary artery. Femoral arterial access for systemic artery catheterization and femoral vein access for pulmonary arterial catheterization were used. Gelfoam particles and coils were used for embolization. In this study, we report on three cases of massive hemoptysis from a systemic arterial source in whom bronchial and/or nonbronchial arteries embolization was not possible. Percutaneous embolization via the pulmonary artery access was successful in all three patients. In conclusion, embolization via pulmonary artery is presented as an alternative approach for the management of hemoptysis in patients in whom bronchial arterial embolization is not possible.

Primary Orbital Mesenchymal Chondrosarcoma: a Case Report and Literature Review

Mesenchymal chondrosarcoma (MC) is a subtype of chondrosarcoma, with an incidence varying from 1 to 8% of all chondrosarcomas. It is an aggressive neoplasm with a high tendency for late recurrence and occasional delayed distant metastasis. Orbital MC is very rare, and only approximately 30 cases have been described in the literature. We describe here one case of primary orbital MC.

Ketoprofen in Topical Formulation Decreases the Matrix Metalloproteinase-2 Expression and Pulmonary Metastatic Incidence in Nude Mice with Osteosarcoma

The aim of this study was to investigate whether ketoprofen (KP) in topical formulation affected the tumor growth and pulmonary metastasis of LM8 cells, which were inoculated subcutaneously into the back space of male nude mice. At 7 days after inoculation, the tumor was treated topically for 3 weeks with either a KP-containing patch (KP group) or a placebo-containing patch (placebo group). The pulmonary metastatic incidence was 100% in the placebo group and 60% in the KP group. The tumor mass of the KP group without pulmonary metastasis, termed the KP/metastasis(-) group, was smaller than that of the placebo group. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) was performed. The tumors of the KP/metastasis(-) group contained fewer PCNA-positive cells and many more TUNEL-positive cells in comparison to the placebo group. In the placebo group, MMP-2 and VEGF were extensively expressed within the tumor, whereas in the KP/metastasis(-) group the expression of these two proteins was very low. In conclusion, the topical treatment of osteosarcoma with KP decreased the expression of MMP-2 and VEGF, thus resulting in the suppression of tumor growth and pulmonary metastasis.

Aggregated P19 Mouse Embryonal Carcinoma Cells As a Simple in Vitro Model to Study the Molecular Regulations of Mesoderm Formation and Axial Elongation Morphogenesis

Because of their capacity to give rise to various types of cells in vitro, embryonic stem and embryonal carcinoma (EC) cells have been used as convenient models to study the mechanisms of cell differentiation in mammalian embryos. In this study, we explored the mouse P19 EC cell line as an effective tool to investigate the factors that may play essential roles in mesoderm formation and axial elongation morphogenesis. We first demonstrated that aggregated P19 cells not only exhibited gene expression patterns characteristic of mesoderm formation but also displayed elongation morphogenesis with a distinct anterior-posterior body axis as in the embryo. We then showed by RNA interference that these processes were controlled by various regulators of Wnt signaling pathways, namely beta-catenin, Wnt3, Wnt3a, and Wnt5a, in a manner similar to normal embryo development. We further showed by inhibitor treatments that the axial elongation morphogenesis was dependent on the activity of Rho-associated kinase. Because of the convenience of these experimental manipulations, we propose that P19 cells can be used as a simple and efficient screening tool to assess the potential functions of specific molecules in mesoderm formation and axial elongation morphogenesis.

Role of Dorsomedial Hypothalamic Neuropeptide Y in Modulating Food Intake and Energy Balance

Previous studies have suggested that neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) serves as an important signaling peptide in the regulation of energy balance. To elucidate such actions, we used the adenoassociated virus (AAV) system to alter Npy gene expression in the DMH and examined the effects of these alterations on food intake and energy balance as well as explored its downstream signaling pathway. We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity. Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. NPY knockdown in the DMH produced a nocturnal and meal size-specific feeding effect. Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation. DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin. Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.

Prenatal Stress or High-fat Diet Increases Susceptibility to Diet-induced Obesity in Rat Offspring

Perturbations to the prenatal environment have been associated with the development of adult chronic disease, findings that gave rise to the "Barker Hypothesis" or the "developmental origins of adult disease" concept. In this study, we used an animal model to determine the metabolic consequences of maternal prenatal stress and high-fat feeding on the developing offspring.

Effects of an LL-37-derived Antimicrobial Peptide in an Animal Model of Biofilm Pseudomonas Sinusitis

LL-37, an innate immunity protein expressed within sinonasal mucosa, has in vitro antibacterial and antifungal properties as well as efficacy against preformed Pseudomonas aeruginosa biofilms. We hypothesize that a 24 amino acid peptide derivative of LL-37 will show efficacy against biofilm-forming P. aeruginosa in an established animal model of sinusitis.

Cigarette Smoke Exposure Impairs Respiratory Epithelial Ciliogenesis

Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation.

Cigarette Smoke Condensate Inhibits Transepithelial Chloride Transport and Ciliary Beat Frequency

Although the pathophysiology leading to rhinosinusitis is complex, evidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature. Normal respiratory epithelial MCC is an important host defense mechanism that is dependent on proper ciliary beating and the biological properties of the airway surface liquid (ASL). The role that tobacco smoke exposure plays as an inhibitor of MCC has yet to be elucidated. The present study investigates the consequences of cigarette smoke exposure on ciliary function and transepithelial chloride (Cl(-)) secretion, a major determinant of ASL.

Similar Metabolic Responses to Calorie Restriction in Lean and Obese Zucker Rats

Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.

Surgical Treatment of Nasal Packing Refractory Epistaxis

Epistaxis is the main otorhinolaryngology emergency and, in severe cases, it can lead to hemodynamic instability and be life threatening.

Brain Structural Variability Due to Aging and Gender in Cognitively Healthy Elders: Results from the Sao Paulo Ageing and Health Study

Several morphometric MR imaging studies have investigated age- and sex-related cerebral volume changes in healthy human brains, most often by using samples spanning several decades of life and linear correlation methods. This study aimed to map the normal pattern of regional age-related volumetric reductions specifically in the elderly population.

A Pilot Study on the Usefulness of Information and Education Campaign Materials in Enhancing the Knowledge, Attitude and Practice on Rabies in Rural Sri Lanka

Rabies remains endemic in Sri Lanka despite a strong government patronized anti-rabies campaign. Personal, cultural or religious beliefs have been thought to influence health practices that could render rabies prevalent in the country.

Knowledge, Attitude and Practice Assessment of Construction Workers for HIV/AIDS in Sri Lanka

Human immunodeficiency virus (HIV) prevalence is relatively lower in Sri Lanka than in other Asian countries; however, the number of HIV-infected persons has rapidly increased in recent years.

4G/5G Variant of Plasminogen Activator Inhibitor-1 Gene and Severe Pregnancy-induced Hypertension: Subgroup Analyses of Variants of Angiotensinogen and Endothelial Nitric Oxide Synthase

Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3).

Serological and Genetic Analysis of Leptospirosis in Patients with Acute Febrile Illness in Kandy, Sri Lanka

Leptospirosis has emerged as an important infectious disease in Sri Lanka and little information is available on circulating leptospiral species and serogroups in this country. Therefore, we studied circulating leptospiral species and serogroups in patients with acute febrile illness using polymerase chain reaction and the microscopic agglutination test, respectively. Anti-leptospiral antibodies were detected in 26 of 107 serum samples studied (24.3%). The predominant reacting serogroups were Sejroe (9/26, 34.6%) and Icterohaemorrhagiae (5/26, 19.2%). Leptospiral DNA was detected in 3 of the 107 serum samples. The deduced leptospiral species were Leptospira interrogans and L. kirschneri (2 and 1 samples, respectively). These results confirm the existence of a wide array of leptospiral species and serogroups in Sri Lanka and would help to thoroughly elucidate the epidemiology of leptospirosis in this country.

In Vivo Effects of Citric Acid/zwitterionic Surfactant Cleansing Solution on Rabbit Sinus Mucosa

Chronic rhinosinusitis that is refractory to medical or surgical intervention may involve a particularly resistant form of infection known as a bacterial biofilm that is recalcitrant to antibiotics secondary to physical barrier characteristics. Recently, a novel sinus cleansing solution, citric acid/zwitterionic surfactant (CAZS) was shown to be extremely effective in disrupting biofilms in vitro. The purpose of this study was to determine the effects of CAZS on sinonasal epithelium In vivo compared with normal saline.

Implications of Bacterial Biofilms in Chronic Rhinosinusitis

The recognition of sessile form of bacteria with particular features, known as biofilm, has given new insights to the understanding of pathogenesis of several chronic diseases, including Chronic Rhinosinusitis (CRS). In this article we review the main characteristics of biofilms, describe the current methods used to demonstrate biofilms in chronic rhinosinusitis and discuss the future directions of research in the field.

Effects of Cigarette Smoking on the Respiratory Epithelium and Its Role in the Pathogenesis of Chronic Rhinosinusitis

The increasing consumption of cigarettes has aroused concerns about the development and worsening of diseases, particularly those related to the respiratory tract. AIM: In this paper we review the evidence suggesting the effects of cigarette smoking on the respiratory epithelium and its role in the pathogenesis in chronic rhinosinusitis. CONCLUSIONS: Although there is evidence supporting a link between smoking and CRS, studies suggest that there might be individual susceptibility to cigarette smoking causing the development and/or maintenance of CRS. Proper patient education to quit smoking as well as reinforcement of antismoking campaigns are extremely important to control this disease of major socio-economic impact.

Measurement of the Depth of Maximum of Extensive Air Showers Above 10{18} EV

We describe the measurement of the depth of maximum, X{max}, of the longitudinal development of air showers induced by cosmic rays. Almost 4000 events above 10;{18} eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106{-21}{+35}) g/cm{2}/decade below 10{18.24+/-0.05} eV, and (24+/-3) g/cm{2}/decade above this energy. The measured shower-to-shower fluctuations decrease from about 55 to 26 g/cm{2}. The interpretation of these results in terms of the cosmic ray mass composition is briefly discussed.

Perinatal Environment and Its Influences on Metabolic Programming of Offspring

The intrauterine environment supports the development and health of offspring. Perturbations to this environment can have detrimental effects on the fetus that have persistent pathological consequences through adolescence and adulthood. The developmental origins of the health and disease concept, also known as the "Barker Hypothesis", has been put forth to describe the increased incidence of chronic disease such as cardiovascular disease and diabetes in humans and animals exposed to a less than ideal intrauterine environment. Maternal infection, poor or excess nutrition, and stressful events can negatively influence the development of different cell types, tissues and organ systems ultimately predisposing the organism to pathological conditions. Although there are a variety of conditions associated to exposure to altered intrauterine environments, the focus of this review will be on the consequences of stress and high fat diet during the pre- and perinatal periods and associated outcomes related to obesity and other metabolic conditions. We further discuss possible neuroendocrine and epigenetic mechanisms responsible for the metabolic programming of offspring. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.

Colonization and Biology of the Frog-feeding Mosquito Uranotaeinia Macfarlanei in the Ryukyu Archipelago

A colony of Uranotaenia macfarlanei, a frog-feeding mosquito, was established in the laboratory. We report the bionomics of the species, as studied in the laboratory colony and in the field on Ryukyu Island, Japan. These include mating activity, feeding and resting habits, manner of oviposition, and egg, larval, and pupal periods.

Glucose Parameters Are Altered in Mouse Offspring Produced by Assisted Reproductive Technologies and Somatic Cell Nuclear Transfer

Fortunately, the majority of children conceived through assisted reproductive technologies (ARTs) appear healthy; however, metabolic abnormalities, including elevated glucose and increased and altered adipose tissue deposition, have been reported in adolescents. To parse out factors that may be responsible, we investigated the effects of two different ARTs--in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI)--as well as somatic cell nuclear transfer (SCNT) on glucose clearance, body weight, and body composition of young adult mice. Female and male mice generated through ART weighed more than control (naturally conceived [STOCK]) mice at birth. No differences in body weight were observed in males up to 8 wk of age. ART females took longer than control mice to clear a glucose bolus, with glucose clearance most impaired in SCNT females. IVF females secreted more insulin and had a higher insulin peak 15 min after glucose injection compared with all other groups. Male mice exhibited no differences in glucose clearance, but IVF males required more insulin to do so. SCNT females weighed more than IVF, ICSI, and STOCK females, and they had higher fat content than ICSI females and higher leptin levels than all other groups. These results show that glucose parameters are altered in young adult mice conceived through techniques associated with ART before onset of obesity and may be responsible for its development later in life. The present study suggests that more investigation regarding the long-term effects of manipulations associated with ART is warranted.

Comparing Different Methods Used to Collect Material for a Microbiological Evaluation of Patients with Chronic Rhinosinusitis

There is still controversy on which is the best method to collect the secretion directly from the middle meatus or maxillary sinus in patients with chronic rhinosinusitis.

Chronic Corticosterone Exposure Increases Expression and Decreases Deoxyribonucleic Acid Methylation of Fkbp5 in Mice

There is evidence for hypercortisolemia playing a role in the generation of psychiatric symptoms and for epigenetic variation within hypothalamic-pituitary-adrenal (HPA) axis genes mediating behavioral changes. We tested the hypothesis that expression changes would be induced in Fkbp5 and other HPA axis genes by chronic exposure to corticosterone and that these changes would occur through the epigenetic mechanism of loss or gain of DNA methylation (DNAm). We administered corticosterone (CORT) to C57BL/6J mice via their drinking water for 4 wk and tested for behavioral and physiological changes and changes in gene expression levels using RNA extracted from hippocampus, hypothalamus, and blood for the following HPA genes: Fkbp5, Nr3c1, Hsp90, Crh, and Crhr1. The CORT mice exhibited anxiety-like behavior in the elevated plus maze test. Chronic exposure to CORT also caused a significant decrease in the hippocampal and blood mRNA levels of Nr3c1 and a decrease in Hsp90 in blood and caused an increase in Fkbp5 for all tissues. Differences were seen in Fkbp5 methylation in hippocampus and hypothalamus. To isolate a single-cell type, we followed up with an HT-22 mouse hippocampal neuronal cell line exposed to CORT. After 7 d, we observed a 2.4-fold increase in Fkbp5 expression and a decrease in DNAm. In the CORT-treated mice, we also observed changes in blood DNAm in Fkbp5. Our results suggest DNAm plays a role in mediating effects of glucocorticoid exposure on Fkbp5 function, with potential consequences for behavior.

AIDS Vaccine for Asia Network (AVAN): Expanding the Regional Role in Developing HIV Vaccines

The HIV/AIDS pandemic continues to spread and an AIDS vaccine is urgently needed. Regional alliances and international collaborations can foster the development and evaluation of the next generation of AIDS vaccine candidates. The importance of coordinating and harmonizing efforts across regional alliances has become abundantly clear. We recently formed the AIDS Vaccine for Asia Network (AVAN) to help facilitate the development of a regional AIDS vaccine strategy that accelerates research and development of an AIDS vaccine through government advocacy, improved coordination, and harmonization of research; develops clinical trial and manufacturing capacity; supports ethical and regulatory frameworks; and ensures community participation.

Maxillary Sinuses Microbiology from Patients with Chronic Rhinosinusitis

There isn't definitive and consistent data concerning the distribution of bacterial species in patients with Chronic Sinusitis (CS). The variability of the results from studies in CS may be due to the different techniques used as collection method, variations in culture methods, previous antibiotic use, and difficulty in distinguishing bacterial flora from pathogenic agents.

Defining the Objectives of the AIDS Vaccine for Asia Network: Report of the WHO-UNAIDS/Global HIV Vaccine Enterprise Regional Consultation on Expanding AIDS Vaccine Research and Development Capacity in Asia

Pleasurable Behaviors Reduce Stress Via Brain Reward Pathways

Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.

Effect of Aging and Oral Tolerance on Dendritic Cell Function

Oral tolerance can be induced in some mouse strains by gavage or spontaneous ingestion of dietary antigens. In the present study, we determined the influence of aging and oral tolerance on the secretion of co-stimulatory molecules by dendritic cells (DC), and on the ability of DC to induce proliferation and cytokine secretion by naive T cells from BALB/c and OVA transgenic (DO11.10) mice. We observed that oral tolerance could be induced in BALB/c mice (N = 5 in each group) of all ages (8, 20, 40, 60, and 80 weeks old), although a decline in specific antibody levels was observed in the sera of both tolerized and immunized mice with advancing age (40 to 80 weeks old). DC obtained from young, adult and middle-aged (8, 20, and 40 weeks old) tolerized mice were less efficient (65, 17 and 20%, respectively) than DC from immunized mice (P < 0.05) in inducing antigen-specific proliferation of naive T cells from both BALB/c and DO11.10 young mice, or in stimulating IFN-g, IL-4 and IL-10 production. However, TGF-beta levels were significantly elevated in co-cultures carried out with DC from tolerant mice (P < 0.05). DC from both immunized and tolerized old and very old (60 and 80 weeks old) mice were equally ineffective in inducing T cell proliferation and cytokine production (P < 0.05). A marked reduction in CD86+ marker expression was observed in DC isolated from both old and tolerized mice (75 and 50%, respectively). The results indicate that the aging process does not interfere with the establishment of oral tolerance in BALB/c mice, but reduces DC functions, probably due to the decline of the expression of the CD86 surface marker.

Antinociceptive Effect of Geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan-17beta-oate Methyl Ester Isolated from Pterodon Pubescens Benth

Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract.

Zinc Increases Ciliary Beat Frequency in a Calcium-dependent Manner

Dynamic regulation of respiratory ciliary beat frequency (CBF) is regulated by fluxes in intracellular calcium (Ca(2+)). P2X receptors (P2XR) are extracellular ATP-gated, Ca(2+)-permeable, nonselective cation channels. Zinc increases intracellular Ca(2+) in a sodium (Na(+))-free environment through activation of P2XR channels. We hypothesize that topical zinc increases CBF in a Ca(2+)-dependent fashion as a result of this mechanism.

Nutrient Specific Feeding and Endocrine Effects of Jejunal Infusions

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. Only intrajejunal infusions of fatty acids decrease food intake beyond the calories infused. To test whether this extra-compensatory decrease in food intake is specific to fatty acids, small volume intrajejunal infusions of glucose (Glu) and casein hydrolysate (Cas), as well as linoleic acid (LA) were administered to male Sprague-Dawley rats. Equal kilocalorie (kcal) loads of these nutrients (11.4) or vehicle were infused into the jejunum over 7 h/day for five consecutive days. Food intake was continuously monitored and body weight was measured daily. After the infusion on the final day, rats were killed and plasma collected. Intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake beyond the caloric load of the infusate with no compensatory increase in food intake after the infusion period. Rats receiving LA and Glu infusions also lost significant body weight across the infusion days. Plasma glucagon-like peptide-1 (GLP-1) was increased in both the LA and Glu rats compared with control animals, with no significant change in the Cas-infused animals. Peptide YY (PYY) levels increased in response to LA and Cas infusions. These results suggest that intrajejunal infusions of LA and Glu may decrease food intake and body weight via alterations in GLP-1 signaling. Thus, particular nutrients are more effective at producing decreases in food intake, body weight, and inducing changes in peptide levels and could lead to a novel therapy for obesity.

Ions at the Water-vapor Interface

We obtain the electrostatic free energy of finite-sized ions near a dielectric interface within the framework of the classical continuum dielectric theory. The ion is modeled as a dielectric sphere with a fixed uniform surface charge density. In order to avoid the generation of additional induced charges on the ionic surface, it is assumed there is no dielectric contrast between the ion core and the external dielectric medium where it is embedded, which allows an exact solution of the electrostatic problem by the image-charge method. It is shown that earlier results reported in the literature, especially when there is partial ionic penetration into the interface, always underestimate the electrostatic free energy associated with nonpolarizable ions. For an ion modeled as a vacuum cavity at the water-vapor interface, it is estimated that the free energy is an order of magnitude larger than prior predictions.

Synphilin-1 Exhibits Trophic and Protective Effects Against Rotenone Toxicity

Synphilin-1 is a cytoplasmic protein with unclear function. Synphilin-1 has been identified as an interaction partner of alpha-synuclein. The interaction between synphilin-1 and alpha-synuclein has implications in Parkinson's disease. In this study, we stably overexpressed human synphilin-1 in mouse N1E-115 neuroblastoma cells. We found that overexpression of synphilin-1 shortened cell growth doubling time and increased neurite outgrowth. Knockdown of endogenous synphilin-1 caused neuronal toxicity and shortened neurite outgrowth. We further found that synphilin-1 increased activation of the extracellular signal-regulated kinases (ERK1/2) and mediated neurite outgrowth. Rotenone, mitochondrial complex I inhibitor, has been shown previously to induce dopaminergic neurodegeneration and Parkinsonism in rats and Drosophila. We found that Rotenone induced apoptotic cell death in N1E-115 cells via caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of synphilin-1 significantly reduced Rotenone-induced cell death, caspase-3 activation and PARP cleavage. The results indicate that synphilin-1 displays trophic and protective effects in vitro, suggesting that synphilin-1 may play a protective role in Parkinson's disease (PD) pathogenesis and may lead to a potential therapeutic target for PD intervention.

Prenatal Interaction of Mutant DISC1 and Immune Activation Produces Adult Psychopathology

Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human disrupted-in-schizophrenia 1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders.

Evaluation of Immobilized Metal-ion Affinity Chromatography (IMAC) As a Technique for IgG(1) Monoclonal Antibodies Purification: the Effect of Chelating Ligand and Support

Monoclonal antibodies (MAbs) have been used for therapies and some analytical procedures as highly purified molecules. Many techniques have been applied and studied, focusing on monoclonal antibodies purification. In this study, an immobilized metal affinity chromatography membrane was developed and evaluated for the purification of anti-TNP IgG(1) mouse MAbs from cell culture supernatant after precipitation with a 50% saturated ammonium sulfate solution. The chelating ligands iminodiacetic acid, carboxymethylated aspartic acid (CM-Asp), nitrilotriacetic acid, and tris (carboxymethyl) ethylenediamine in agarose gels with immobilized Ni(II) and Zn(II) ions were compared for the adsorption and desorption of MAbs. The most promising chelating ligand--CM-Asp--was then coupled to poly(ethylene vinyl alcohol) (PEVA) hollow fiber membranes. According to SDS-PAGE and ELISA analyses, a higher selectivity and a purification factor of 85.9 (fraction eluted at 500 mM Tris) were obtained for IgG(1) using PEVA-CM-Asp-Zn(II). The anti-TNP MAb could be eluted under mild pH conditions causing no loss of antigen binding capacity.

Fear of Falling and Falls Self-efficacy and Their Relationship to Higher-level Competence Among Community-dwelling Senior Men and Women in Japan

This cross-sectional study examined the relationships of fear of falling and falls self-efficacy with higher-level competence among community-dwelling senior citizens in Japan.

Serological Evidence of Thailand Virus-related Hantavirus Infection Among Suspected Leptospirosis Patients in Kandy, Sri Lanka

A cross-sectional study was undertaken to determine the current prevalence of leptospirosis and hantaviral infections, and the socio-demographic characteristics and risk factors of infected patients, in Kandy, Sri Lanka. This report discusses the serological evidence of hantavirus infections among 105 suspected leptospirosis patients, 8 of whom had hantavirus antibodies. Serotyping ELISA showed that these 8 patients had high optical density values for Thailand virus. Most of the sera showed that the focus reduction neutralization test titer against Thailand virus was higher than that against Seoul virus, thereby suggesting that the hantaviral antibodies found in Sri Lanka are different from Seoul virus but closely related to Thailand virus. These findings imply that the hantaviral infection found in Kandy, Sri Lanka appears to be due to a virus similar to Thailand virus. Epidemiological analysis revealed that the association between hantavirus infection and socio-demographic characteristics was not statistically significant.

Prevalence and Carrier Status of Leptospirosis in Smallholder Dairy Cattle and Peridomestic Rodents in Kandy, Sri Lanka

Leptospirosis is an important bacterial zoonotic disease globally and one of the notifiable diseases in Sri Lanka. Other than human leptospirosis, little information is available on leptospirosis in domestic and feral animals in Sri Lanka. Thus, this study attempted to determine the prevalence and carrier status of leptospirosis in smallholder dairy cattle and peridomestic rodents to understand the impact of the disease on public health in Kandy, Sri Lanka. Cattle and rodent samples were collected from the Yatinuwara and Udunuwara divisional secretaries in Kandy. Serum samples were analyzed for the presence of antileptospiral antibodies using microscopic agglutination test. DNA was extracted from cattle urine and rodent kidney tissue samples, in which polymerase chain reaction was carried out to detect the Leptospira flaB gene. The cattle in 19 (38.8%) of the 49 farms harbored antileptospiral antibodies. Out of 113 cattle serum samples, 23 (20.3%) were positive; 17 (73.9%) and 6 (26.1%) reacted with serogroups Sejroe and Hebdomadis, respectively. Out of the 74 rodent samples, 13 (17.5%) were positive; 8 (61.5%) and 4 (30.8%) had reactions to serogroups Javanica and Icterohaemorrhagiae, respectively. Leptospiral DNA was detected in one cattle urine sample and identified as Leptospira interrogans. This study revealed a high prevalence of leptospirosis in cattle and rodents in Kandy. These animals were infected with a wide array of leptospiral serogroups, which are consistent with the research findings observed in humans in Kandy. Overall, serological data indicate that relative to rodents, cattle may be a more significant reservoir for human transmission and a greater source of potential risk to local agricultural communities.

Prognosis of Acute Invasive Fungal Rhinosinusitis Related to Underlying Disease

Acute invasive fungal rhinosinusitis (AIFRS) is a rare disease with high morbidity and mortality rates. The objective of this study was to correlate the initial clinical features of AIFRS to the prognosis after surgery.

Flexions of the Popliteal Artery: Technical Considerations of Femoropopliteal Stenting

Popliteal artery morphology changes while undergoing knee motion. A main flexion (i.e., the 'hinge point') and other flexions (termed 'accessory flexions') were described as a result of popliteal artery adaptation to knee flexion. Knee dynamics challenge the outcome of popliteal artery endovascular procedures. Complications such us stent fractures were reported despite rapidly improving technology. Understanding popliteal artery dynamics allows us to develop an endovascular technique that facilitates the avoidance of the difficulties of one of the most mobile arteries in the body. Here we report two cases with a novel stent implantation technique in the popliteal artery. The method includes diagnostic angiography, lesion angioplasty, and stenting using both extended and flexed knee in lateral view. The pressure gradients were measured with knee in extension and flexion before and after each step. A successful outcome was achieved in both cases. This method allows us: 1) to identify the flexions of the popliteal artery and its relationship with the lesions; 2) to detect those obstructions not visible with an extended knee; 3) to understand that the hinge point and accessory flexions can develop undesired and unexpected artery obstruction after a stent implantation only observed in knee flexion; and 4) to identify the morphological changes caused in the popliteal artery and its subsequent solution.

Discrimination of Acute Lymphoblastic Leukemia from Systemic-onset Juvenile Idiopathic Arthritis at Disease Onset

To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset.

Bionomics of the Mud Lobster-hole Mosquito Aedes (Geoskusea) Baisasi in the Mangrove Swamps of the Ryukyu Archipelago, Japan

The bionomics of the mud lobster-hole mosquito Aedes (Geoskusea) baisasi in the Ryukyu Archipelago, Japan, was studied in the field and in the laboratory. The studies included the natural habitat, seasonal appearance, flight activity, mating behavior, resistance of eggs to desiccation, and breeding periods of the immature stages of this species. The burrow systems made by the mud lobster Thalassina anomala were excellent as breeding and resting habitats for both the immature and adult stages of the mosquito.

Adaptation of the CHARM DNA Methylation Platform for the Rat Genome Reveals Novel Brain Region-specific Differences

Comprehensive High-throughput Arrays for Relative Methylation (CHARM) was recently developed as an experimental platform and analytic approach to assess DNA methylation (DNAm) at a genome-wide level. Its initial implementation was for human and mouse. We adapted it for rat and sought to examine DNAm differences across tissues and brain regions in this model organism. We extracted DNA from liver, spleen, and three brain regions: cortex, hippocampus, and hypothalamus from adult Sprague Dawley rats. DNA was digested with McrBC, and the resulting methyl-depleted fraction was hybridized to the rat CHARM array along with a mock-treated fraction. Differentially methylated regions (DMRs) between tissue types were detected using normalized methylation log-ratios. In validating 24 of the most significant DMRs by bisulfite pyrosequencing, we detected large mean differences in DNAm, ranging from 33-59%, among the most significant DMRs in the across-tissue comparisons. The comparable figures for the hippocampus vs. hypothalamus DMRs were 14-40%, for the cortex vs. hippocampus DMRs, 12-29%, and for the cortex vs. hypothalamus DMRs, 5-35%, with a correlation of r(2) = 0.92 between the methylation differences in 24 DMRs predicted by CHARM and those validated by bisulfite pyrosequencing. Our adaptation of the CHARM array for the rat genome yielded highly robust results that demonstrate the value of this method in detecting substantial DNAm differences between tissues and across different brain regions. This platform should prove valuable in future studies aimed at examining DNAm differences in particular brain regions of rats exposed to environmental stimuli with potential epigenetic consequences.

2010 Neurobiology of Stress Workshop. Introduction to the Special Issue

A Measure of Glucocorticoid Load Provided by DNA Methylation of Fkbp5 in Mice

Given the contribution of cortisol dysregulation to neuropsychiatric and metabolic disorders, it is important to be able to accurately compute glucocorticoid burden, a measure of allostatic load. One major problem in calculating cortisol burden is that existing measures reflect cortisol exposure over a short duration and have not been proven to reliably quantify cortisol burden over weeks or months.

Maternal Stress and High-fat Diet Effect on Maternal Behavior, Milk Composition, and Pup Ingestive Behavior

Chronic variable prenatal stress or maternal high-fat diet results in offspring that are significantly heavier by the end of the first postnatal week with increased adiposity by weaning. It is unclear, however, what role maternal care and diet play in the ontogenesis of this phenotype and what contributions come from differences already established in the rat pups. In the present studies, we examined maternal behavior and milk composition as well as offspring ingestive behavior. Our aim was to better understand the development of the obese phenotype in offspring from dams subjected to prenatal stress and/or fed a high-fat (HF) diet during gestation and lactation. We found that dams maintained on a HF diet through gestation and lactation spent significantly more time nursing their pups during the first postnatal week. In addition, offspring of prenatal stress dams consumed more milk at postnatal day (PND) 3 and offspring of HF dams consume more milk on PND 7 in an independent ingestion test. Milk from HF dams showed a significant increase in fat content from PND 10-21. Together these results suggest that gestational dietary or stress manipulations can alter the rat offspring's developmental environment, evidence of which is apparent by PND 3. Alterations in maternal care, milk composition, and pup consumption during the early postnatal period may contribute to long-term changes in body weight and adiposity induced by maternal prenatal stress or high-fat diet.

Aging Alters the Production of INOS, Arginase and Cytokines in Murine Macrophages

The limited amount of information on the primary age-related deficiencies in the innate immune system led us to study the production of inducible nitric oxide synthase (iNOS), arginase, and cytokines in macrophages of young (8 weeks old) and old (72 weeks old) female BALB/c mice. We first evaluated iNOS and arginase inducers on peritoneal (PMΦ) and bone marrow-derived (BMMΦ) macrophages of young BALB/c and C57BL/6 mice, and then investigated their effects on macrophages of old mice. Upon stimulation with lipopolysaccharide (LPS), resident and thioglycolate-elicited PMΦ from young mice presented higher iNOS activity than those from old mice (54.4%). However, LPS-stimulated BMMΦ from old mice showed the highest NO levels (50.1%). Identical NO levels were produced by PMΦ and BMMΦ of both young and old mice stimulated with interferon-γ. Arginase activity was higher in resident and elicited PMΦ of young mice stimulated with LPS (48.8 and 32.7%, respectively) and in resident PMΦ stimulated with interleukin (IL)-4 (64%). BMMΦ of old mice, however, showed higher arginase activity after treatment with IL-4 (46.5%). In response to LPS, PMΦ from old mice showed the highest levels of IL-1α (772.3 ± 51.9 pg/mL), whereas, those from young mice produced the highest amounts of tumor necrosis factor (TNF)-α (937.2 ± 132.1 pg/mL). Only TNF-α was expressed in LPS-treated BMMΦ, and cells from old mice showed the highest levels of this cytokine (994.1 ± 49.42 pg/mL). Overall, these results suggest that macrophages from young and old mice respond differently to inflammatory stimuli, depending on the source and maturity of the cell donors.

Risk Factors for Recurrence of Scabies: a Retrospective Study of Scabies Patients in a Long-term Care Hospital

A considerable number of patients suffer recurrence of scabies. To elucidate risk factors for recurrence of scabies, we compared patients who experienced scabies recurrence and those who suffered scabies only once. We conducted a retrospective review of medical records of all scabies patients in a long-term care hospital for the elderly (300 beds; six wards) for a period of 42 months to determine frequency of scabies onsets, underlying diseases, history of treatment, and demographic data such as age and sex. One hundred and forty-eight patients and five hospital staff members suffered scabies during the 42-month study period. All staff members and 98 patients had no recurrence, while 50 patients experienced at least one recurrence of scabies. The cumulative number of scabies diagnoses was 228. The rates of scabies onset and recurrence were considerably different among wards. The dementia unit showed the highest rate of onset and recurrence. In addition to frequent exposure to infectious sources, problematic behavior, such as lying in other patients beds, might cause the high recurrence rate in dementia units. Higher serum total lymphocyte count and topical use of γ-benzene hexachloride were associated with lower risk of scabies recurrence. Recurrence of scabies is not uncommon among elderly patients in institutional settings. Impaired immunity may be a risk factor for recurrence of scabies. Groups with a high onset rate of scabies pose a high likelihood of recurrence. Problematic behavior of demented patients may increase the risk of recurrence. Use of effective topical treatment may effectively prevent recurrence.

First Record of Avian Plasmodium DNA from Mosquitoes Collected in the Yaeyama Archipelago, Southwestern Border of Japan

We studied the prevalence of avian Plasmodium in 509 mosquitoes of 9 species collected from the Ishigaki and Iriomote islands in the Yaeyama Archipelago, located southwest from the mainland of Japan. Two identical avian Plasmodium lineages were detected from Culex (Culiciomyia) nigropunctatus. Detected lineages were phylogenetically classified into different clade to avian Plasmodium lineages from birds and mosquitoes in the mainland of Japan but identical to a lineage detected from a resident bird, White-breasted Waterken (Amaurornis phoenicurus). This is the first detection of avian Plasmodium DNA from mosquitoes in the Yaeyama Archipelago and suggested that resident birds might have been infected with an avian Plasmodium lineage specific to the studied area and C. nigropunctatus could be the candidate vector mosquito species.

New Records of Mosquito Species for Different Islands of the Ryukyu Archipelago, Japan

During an 11-year study period (1999-2010) on the islands of the Ryukyu Archipelago, Japan, 20 mosquito species were identified. The results revealed new records of species hitherto not reported on these islands. This contribution updates the mosquito fauna of the various islands of the Ryukyu Archipelago.

Phase Transitions and Spatially Ordered Counterion Association in Ionic-lipid Membranes: Theory Versus Experiment

Aqueous dispersions of phosphatidylglycerol (PG) lipids may present an anomalous chain-melting transition at low ionic strengths, as seen by different experimental techniques such as calorimetry or light scattering. The anomaly disappears at high ionic strengths or for longer acyl-chain lengths. In this article, we use a statistical model for the bilayer that distinguishes both lipid chain and headgroup states in order to compare model and experimental thermotropic and electrical properties. The effective van der Waals interactions among hydrophobic chains compete with the electrostatic repulsions between polar headgroups, which may be ionized (counterion dissociated) or electrically neutral (associated with counterions). Electric degrees of freedom introduce new thermotropic charge-ordered phases in which headgroup charges may be spatially ordered, depending on the electrolyte ionic strength, introducing a new rationale for experimental data on PGs. The thermal phases presented by the model for different chain lengths, at fixed ionic strength, compare well with an experimental phase diagram constructed on the basis of differential scanning calorimetry profiles. In the case of dispersions of DMPG (dimyristoyl phosphatidylglycerol) with added monovalent salt, the model properties reproduce the main features displayed by data from differential scanning calorimetry as well as the characteristic profile for the degree of ionization of the bilayer surface across the anomalous transition region, obtained from the theoretical interpretation of electrokinetic (conductivity and electrophoretic mobility) measurements.

Chronic Stress, Metabolism, and Metabolic Syndrome

The prevalence of obesity has rapidly escalated and now represents a major public health concern. Although genetic associations with obesity and related metabolic disorders such as diabetes and cardiovascular disease have been identified, together they account for a small proportion of the incidence of disease. Environmental influences such as chronic stress, behavioral and metabolic disturbances, dietary deficiency, and infection have now emerged as contributors to the development of metabolic disease. Although epidemiological data suggest strong associations between chronic stress exposure and metabolic disease, the etiological mechanisms responsible remain unclear. Mechanistic studies of the influence of chronic social stress are now being conducted in both rodent and nonhuman primate models, and phenotypic results are consistent with those in humans. The advantage of these models is that potential neural mechanisms may be examined and interventions to treat or prevent disease may be developed and tested. Further, circadian disruption and metabolic conditions such as diabetes mellitus could increase susceptibility to other stressors or serve as a stressor itself. Here, we review data from leading investigators discussing the interrelationship between chronic stress and development of metabolic disorders.

Metabolic Syndrome: Links to Social Stress and Socioeconomic Status

Socioeconomic stress associated with financial and psychosocial stress is widespread in society. A comprehensive body of research indicates that low socioeconomic status and social stress is associated with a broad spectrum of health risks. This paper reviews epidemiological evidence demonstrating the association between chronic social stress and development of obesity and symptoms leading to metabolic syndrome. The cumulative effects of socioeconomic stress on health and well being are evident throughout the lifespan, affecting children, adolescents, and adults. While the links between stress and metabolic disease are documented, the mechanisms remain less well understood. Animal models are well established and have provided opportunities to systematically investigate contributing mechanisms that may be targeted to develop treatment and prevention strategies against metabolic disorders arising from exposure to chronic social stress.

Dual Roles of Oct4 in the Maintenance of Mouse P19 Embryonal Carcinoma Cells: As Negative Regulator of Wnt/β-catenin Signaling and Competence Provider for Brachyury Induction

Transcription factor Oct4 is expressed in pluripotent cell lineages during mouse development, namely, in inner cell mass (ICM), primitive ectoderm, and primordial germ cells. Functional studies have revealed that Oct4 is essential for the maintenance of pluripotency in inner cell mass and for the survival of primordial germ cells. However, the function of Oct4 in the primitive ectoderm has not been fully explored. In this study, we investigated the role of Oct4 in mouse P19 embryonal carcinoma (EC) cells, which exhibit molecular and developmental properties similar to the primitive ectoderm, as an in vitro model. Knockdown of Oct4 in P19 EC cells upregulated several early mesoderm-specific genes, such as Wnt3, Sp5, and Fgf8, by activating Wnt/β-catenin signaling. Overexpression of Oct4 was sufficient to suppress Wnt/β-catenin signaling through its action as a transcriptional activator. However, Brachyury, a key regulator of early mesoderm development and a known direct target of Wnt/β-catenin signaling, was unable to be upregulated in the absence of Oct4, even with additional activation of Wnt/β-catenin signaling. Microarray analysis revealed that Oct4 positively regulated the expression of Tdgf1, a critical component of Nodal signaling, which was required for the upregulation of Brachyury in response to Wnt/β-catenin signaling in P19 EC cells. We propose a model that Oct4 maintains pluripotency of P19 EC cells through 2 counteracting actions: one is to suppress mesoderm-inducing Wnt/β-catenin signaling, and the other is to provide competence to Brachyury gene to respond to Wnt/β-catenin signaling.

Role of the Mac-1 and VLA-4 Integrins, and Concomitant Th2-cytokine Production, in Nitric Oxide Modulated Eosinophil Migration from Bone Marrow to Lungs in Allergic Mice

Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400 W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24h and 48 h after OVA-challenge. Conversely, adhesion of blood eosinophils from 1400 W-treated mice to VCAM-1 diminished at 24h and was almost completely blocked at 48 h. 1400 W did not induce any change in the adhesion of bone marrow eosinophils to VCAM-1, at 24h, but cells collected 48 h after challenge showed significantly lower adherence. Flow cytometry demonstrated that 1400 W resulted in a significantly increased Mac-1 expression on bone marrow eosinophils at 24h, as compared to control mice. However, at 24h, 1400 W significantly decreased Mac-1 and VLA-4 expressions on blood eosinophils. At 48 h, the expressions of both Mac-1 and VLA-4 returned to previous levels. Results show a temporal effect of iNOS upon Mac-1 expression and function, the chief adhesion molecule involved in the eosinophil efflux from the bone marrow at 24h. In contrast, Mac-1 and VLA-4 were involved in eosinophil mobilization from blood to lungs at 48 h after antigen challenge. Data suggest an important role of the Mac-1 and VLA-4 in the iNOS-modulated migration of eosinophils to the lungs of allergic mice.

Chromatin Remodeling, Cell Proliferation and Cell Death in Valproic Acid-treated HeLa Cells

Valproic acid (VPA) is a potent anticonvulsant that inhibits histone deacetylases. Because of this inhibitory action, we investigated whether VPA would affect chromatin supraorganization, mitotic indices and the frequency of chromosome abnormalities and cell death in HeLa cells.

Phase Transitions and Spatially Ordered Counterion Association in Ionic-lipid Membranes: a Statistical Model

We propose a statistical model to account for the gel-fluid anomalous phase transitions in charged bilayer- or lamellae-forming ionic lipids. The model Hamiltonian comprises effective attractive interactions to describe neutral-lipid membranes as well as the effect of electrostatic repulsions of the discrete ionic charges on the lipid headgroups. The latter can be counterion dissociated (charged) or counterion associated (neutral), while the lipid acyl chains may be in gel (low-temperature or high-lateral-pressure) or fluid (high-temperature or low-lateral-pressure) states. The system is modeled as a lattice gas with two distinct particle types--each one associated, respectively, with the polar-headgroup and the acyl-chain states--which can be mapped onto an Ashkin-Teller model with the inclusion of cubic terms. The model displays a rich thermodynamic behavior in terms of the chemical potential of counterions (related to added salt concentration) and lateral pressure. In particular, we show the existence of semidissociated thermodynamic phases related to the onset of charge order in the system. This type of order stems from spatially ordered counterion association to the lipid headgroups, in which charged and neutral lipids alternate in a checkerboard-like order. Within the mean-field approximation, we predict that the acyl-chain order-disorder transition is discontinuous, with the first-order line ending at a critical point, as in the neutral case. Moreover, the charge order gives rise to continuous transitions, with the associated second-order lines joining the aforementioned first-order line at critical end points. We explore the thermodynamic behavior of some physical quantities, like the specific heat at constant lateral pressure and the degree of ionization, associated with the fraction of charged lipid headgroups.

A Novel Obesity Model: Synphilin-1-induced Hyperphagia and Obesity in Mice

AIMS:The pathogenesis of obesity remains incompletely understood and the exploration of the role of novel proteins in obesity may provide important insights into its causes and treatments. Here, we report a previously unidentified role for synphilin-1 in the control of food intake and body weight. Synphilin-1, a cytoplasmic protein, was initially identified as an interaction partner of alpha-synuclein, and has implications in Parkinson's disease pathogenesis related to protein aggregation.SUBJECTS AND METHODS:To study the in vivo role of synphilin-1, we characterized a human synphilin-1 transgenic mouse (SP1) by assessing synphilin-1 expression, plasma parameters, food intake and spontaneous activity to determine the major behavioral changes and their consequences in the development of the obesity phenotype.RESULTS:Expression of human synphilin-1 in brain neurons in SP1 mice resulted in increased food intake, body weight and body fat. SP1 mice also displayed hyperinsulinemia, hyperleptinemia and impaired glucose tolerance. Pair-feeding SP1 mice to amounts consumed by non-transgenic mice prevented the increased body weight, adiposity, hyperinsulinemia and hyperleptinemia demonstrating that these were all the consequences of increased food intake. Transgenic expression of synphilin-1 was enriched in hypothalamic nuclei involved in feeding control, and fasting-induced elevated endogenous synphilin-1 levels at these sites, suggesting that synphilin-1 is an important player in the hypothalamic energy balance regulatory system.CONCLUSION:These studies identify a novel function of synphilin-1 in controlling food intake and body weight, and may provide a unique obesity model for future studies of obesity pathogenesis and therapeutics.International Journal of Obesity advance online publication, 13 December 2011; doi:10.1038/ijo.2011.235.

Accelerating the Development of an AIDS Vaccine: the AIDS Vaccine for Asia Network (Avan)

HIV/AIDS is a major public health problem worldwide, especially in developing countries. The development of a safe and effective HIV vaccine is central to stopping the epidemic and would be a great public health tool. The AIDS Vaccine for Asia Network (AVAN) is a group of concerned investigators committed to assisting regional and global HIV vaccine efforts. AVAN's focus on improving the coordination and harmonization of research, ethical reviews, clinical trial capacity, regulatory frameworks, vaccine manufacturing, community participation, and government advocacy could help accelerate HIV vaccine efforts in the region. At a meeting in November 2010, researchers from various countries in Asia presented their progress in HIV vaccine research and development. Six working groups discussed the current status, gaps and methods to strengthen capacity and infrastructure in various areas related to AIDS vaccine research and development. These discussions led to the development of prioritized action plans for the next 5 years. This report describes the gaps and challenges HIV vaccine research faces in the region and recommends improvement and standardization of facilities, and coordination and harmonization of all activities related to AIDS vaccine research and development, including possible technology transfer when a vaccine becomes available.

Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8(+) and CD4(+) T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103(+) cells in CD4(+) T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β(+) T-cell subset in IELs of TGN. The frequency of Foxp3(+) cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25(+) subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

TRAF6 Activation in Multiple Myeloma: a Potential Therapeutic Target

Multiple myeloma (MM) is an incurable B-lymphocyte malignancy. New therapeutic options have become available during the past several years; however nearly all patients acquire resistance to currently available therapeutic agents. Mechanisms contributing to the pathogenesis and chemoresistance of MM include genetic abnormalities, chromosomal translocations, gene mutations, the interaction between MM cells and the bone marrow microenvironment, and defects in the apoptotic signaling pathways. Survival signaling pathways associated with the pathogenesis of MM and bone marrow stromal cells play crucial roles in promoting growth, survival, adhesion, immortalization, angiogenesis, and drug resistance. The receptor activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B ligand/tumor necrosis factor receptor-associated factor (RANK/RANKL-TRAF6) signal pathway mediates osteolytic bone lesions through the activation of the NF-κB and Janus kinase/signal transducer and activator of transcription (JNK) pathways in osteoclast precursor cells and thus contributes to the main clinical manifestations of bone disease. TRAF6 has also been identified as a ligase for Akt ubiquitination and membrane recruitment and its phosphorylation on growth factor stimulation. The inhibition of TRAF6 by silencing RNA or by decoy peptides decreases MM tumor cell proliferation and increases apoptosis as well as bone resorption. Some proteasome inhibitors and benzoxadiazole derivatives showed inhibitory effects on the activity and function of TRAF6. Overall, we propose that TRAF6 may be considered as a potential therapeutic target for the treatment of MM.

Glucocorticoid-induced Loss of DNA Methylation in Non-neuronal Cells and Potential Involvement of DNMT1 in Epigenetic Regulation of Fkbp5

Glucocorticoids may play a significant role in the etiology of neuropsychiatric illnesses. Abnormalities in plasma cortisol levels, glucocorticoid sensitivity, and HPA-axis function often accompany clinical symptoms of stress-related illnesses such as PTSD and depression. Of particular interest are genetic association studies that link single nucleotide polymorphisms of HPA-axis genes with illnesses only in the context of an early-life trauma exposure such as child abuse. These studies suggest that dysregulation of HPA-axis function can have lasting repercussions in shaping mood and anxiety, long after termination of the traumatic experience. As persistent glucocorticoid-induced loss of DNA methylation in FK506 binding protein 5 (Fkbp5) was previously observed in the hippocampus and blood and in the neuronal cell line HT-22, we asked whether these epigenetic alterations occur in non-neuronal, HPA-axis relevant cells. We used the pituitary adenoma cell line AtT-20 to demonstrate that the intronic enhancer region of Fkbp5 undergoes loss of DNA methylation in response to dexamethasone treatment in a dose-dependent manner. We also focused on the mouse hippocampal dentate gyrus to test whether these changes would be enriched in a region implicated in the HPA-axis stress response, neurogenesis, and synaptic plasticity. We observed an increase in enrichment of DNA methylation loss in the dentate gyrus, as compared to whole hippocampal tissues that were similarly treated with glucocorticoids. We then asked whether DNA methyltransferase 1 (Dnmt1), a methyltransferase enzyme involved in maintaining DNA methylation following cell division, is involved in the observed epigenetic alterations. We found a dose-dependent decrease of Dnmt1 expression in the AtT-20 cells following dexamethasone treatment, and a similar decrease in corticosterone-treated mouse hippocampus. Taken together, we provide evidence that these glucocorticoid-induced epigenetic alterations have a broader validity in non-neuronal cells and that they may involve the DNA methylation machinery.

Analysis of Hospital-based Sentinel Surveillance Data on Leptospirosis in Sri Lanka, 2005-2008

In Sri Lanka, leptospirosis is a notifiable disease. In addition to having a routine disease reporting system, Sri Lanka has implemented a hospital-based sentinel surveillance system since 2004. This report discusses the findings of a descriptive analysis of the sentinel surveillance data collected from 2005 to 2008. Of the 4,000 suspected leptospirosis cases, 46.9% and 26.8% were recorded from the Western and Sabaragamuwa provinces, respectively. Most of the individuals were male (83.5%), and approximately 45.6% were aged 30-49 years. Farmers accounted for 16.5%, and laborers for 16.1%; however, the occupation of nearly half (44.8%) of the study population was unknown. More than half (53.9%) of the individuals worked in paddy fields. Almost all had acute fever (98.8%), myalgia (92.9%), and headache (92.7%), but fewer had other related symptoms. Out of the 4,000 individuals, 2,496 (62.4%) underwent a laboratory test; however, the laboratory test results of only 1,445 (57.9%) and the microscopic agglutination results of 41 (2.8%) were available at the sentinel sites. Less than 2% of the reported individuals underwent prophylactic treatment. These findings will help enhance the ongoing efforts for controlling and preventing leptospirosis in Sri Lanka. Sentinel surveillance is a useful tool, but the data quality needs to be improved by supplementing the findings with adequate laboratory diagnosis data.

Effect of Peripheral Administration of Cholecystokinin on Food Intake in Apolipoprotein AIV Knockout Mice

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

Nkx1-2 is a Transcriptional Repressor and is Essential for the Activation of Brachyury in P19 Mouse Embryonal Carcinoma Cell

Activation of Wnt/β-catenin signaling is crucial for the differentiation of pluripotent stem cells, namely the epiblast, embryonic stem, and embryonal carcinoma cells, into mesendoderm. However, downstream events of Wnt/β-catenin signaling that control the formation of mesendoderm are still unclear. In the present study, we used mouse P19 embryonal carcinoma cells as a model, and identified a homeodomain protein Nkx1-2 as a key regulator of mesendoderm formation. In the mouse embryo, Nkx1-2 was expressed in the primitive streak, in which the nascent mesendoderm emerges. In P19 cells, the expression of Nkx1-2 was activated by Wnt/β-catenin signaling independently of Brachyury, an evolutionary conserved early mesendoderm gene. In contrast, the expression of Nkx1-2 was both necessary and sufficient for the activation of Brachyury. Nkx1-2 acted as a transcriptional repressor to mediate the action of Wnt/β-catenin signaling to activate the Brachyury expression. We found Tcf3 as a potential target of gene repression by Nkx1-2, and the down-regulation of Tcf3 was partly required for effective activation of Brachyury by Wnt/β-catenin signaling. These results suggest that Nkx1-2 is a critical component of the gene regulatory network that operates downstream of Wnt/β-catenin signaling to regulate the formation of mesendoderm.

Gender Gaps in Life Expectancy: Generalized Trends and Negative Associations with Development Indices in OECD Countries

BACKGROUND: Life expectancy (LE) is a major marker of individual survival. It also serves as a guide to highlight both the progress and the gaps in total social and societal health. Comparative LE in concert with measures of gender-specific experience, indices of empowerment and societal happiness and development offer a comparative tool to examine trends and similarities of societal progress as seen through the lens of cross-national experience. METHODS: To determine the gender gaps in LE (GGLE) trends, we performed a longitudinal analysis, covering a period of 49 years (1960-2008). To examine the association of GGLE with development indices, we used the 2007 GGLE data, the newest happiness data mostly drawn from 2006; the 2006 Human Development Index (HDI) data and the 2006 Gender Empowerment Measure (GEM) data. RESULTS: It revealed that most of the Organization for Economic Co-operation and Development (OECD) countries had a GGLE trend that occurred in an inverted U-curve fashion. We divided them into three subgroups based on the peak years of respective GGLE. The earlier the peak year, the happier the countries, the higher the HDI and the smaller the current GGLE are. Association analysis indicates that Happiness, HDI and GEM are all negatively associated with GGLE. CONCLUSION: This pattern suggests that GGLE undergoes three phases of growth, peak and stability and decline. Japan will soon be seeing its GGLE gradually shrinking in the foreseeable future. The continuing increases in Happiness, HDI and GEM are associated with a decrease in GGLE, which should be carefully taken into consideration.

Early Motor Predictors of Recovery in Patients with Severe Traumatic Brain Injury

Retrospective observational study.

Endovascular Treatment of an Aortoiliac Tuberculous Pseudoaneurysm

We report a rare case of a tuberculous mycotic aortoiliac pseudoaneurysm treated with an endovascular procedure and follow-up of 36 months. The patient was a white 72-year-old man with pulmonary tuberculosis and a former smoker with hypertension, chronic renal failure, and dyslipidemia. A computed tomographic scan of the abdomen and pelvis revealed a left paravertebral cavity with fluid content and involvement of vertebrae L2-L4. After a surgical repair attempt, the patient was treated with the implant of a bifurcated endoprosthesis. Because it is unlikely that any center has extensive experience in the management of this rare manifestation of the disease, we reviewed the literature for similar cases.

Maternal High-Fat Diet During Gestation or Suckling Differentially Affects Offspring Leptin Sensitivity and Obesity

Maternal high-fat (HF) diet throughout gestation and suckling has long-term consequences on the offspring's metabolic phenotype. Here we determine the relative contribution of pre- or postnatal maternal HF diet on offspring's metabolic phenotype. Pregnant Sprague-Dawley rats were maintained on normal chow or HF diet throughout gestation and suckling. All litters were cross-fostered to chow or HF dams on postnatal day (PND)1, resulting in four groups. Body weight, body composition, and glucose tolerance were measured at weaning and in adulthood. Leptin sensitivity was assessed by signal transducer and activator of transcription (STAT)3 activation on PND10 and PND21. Pups cross-fostered to HF dams gained more body weight than chow pups by PND7 and persisted until weaning. Postnatal HF pups had greater adiposity, higher plasma leptin concentration, impaired glucose tolerance, and reduced phosphorylated STAT3 in response to leptin in the arcuate nucleus at weaning. After weaning, male offspring cross-fostered to HF dams were hyperphagic and maintained greater body weight than postnatal chow pups. Postnatal HF diet during suckling continued to impair glucose tolerance in male and female offspring in adulthood. Maternal HF diet during suckling has a greater influence in determining offspring's metabolic phenotype than prenatal HF diet exposure and could provide insight regarding optimal perinatal nutrition for mothers and children.

Environmental Influences That Alter the Stress Circuitry

Evaluation of the National Kidney Foundation of Hawai'i's Kidney Early Detection Screening Program

Discussion of the formative program evaluation results of the National Kidney Foundation of Hawai'i (NKFH) Kidney Early Detection Screening (KEDS) program for Chronic Kidney Disease (CKD). The formative program evaluation had 921 participants who enrolled in the NKFH KEDS screening program between 2006-2009. The evaluation included 14 KEDS sites in Honolulu, Maui, and Hawai'i counties.

High Rates of Detection of Respiratory Viruses in Tonsillar Tissues from Children with Chronic Adenotonsillar Disease

Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

Neuroprotective Role of Sirt1 in Mammalian Models of Huntington's Disease Through Activation of Multiple Sirt1 Targets

Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report that overexpression of sirtuin 1 (Sirt1), a mediator of the beneficial metabolic effects of calorie restriction, protects neurons against mutant HTT toxicity, whereas reduction of Sirt1 exacerbates mutant HTT toxicity. Overexpression of Sirt1 improves motor function, reduces brain atrophy and attenuates mutant-HTT-mediated metabolic abnormalities in Huntington's disease mice. Further mechanistic studies suggested that Sirt1 prevents the mutant-HTT-induced decline in brain-derived neurotrophic factor (BDNF) concentrations and the signaling of its receptor, TrkB, and restores dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) concentrations in the striatum. Sirt1 deacetylase activity is required for Sirt1-mediated neuroprotection in Huntington's disease cell models. Notably, we show that mutant HTT interacts with Sirt1 and inhibits Sirt1 deacetylase activity, which results in hyperacetylation of Sirt1 substrates such as forkhead box O3A (Foxo3a), thereby inhibiting its pro-survival function. Overexpression of Sirt1 counteracts the mutant-HTT-induced deacetylase deficit, enhances the deacetylation of Foxo3a and facilitates cell survival. These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease.

Critical Roles of Asp270 and Trp273 in the α-repeat of the Carbohydrate-binding Module of Endo-1,3-β-glucanase for Laminarin-binding Avidity

A carbohydrate-binding module from family 13 (CBM13), appended to the catalytic domain of endo-1,3-β-glucanase from Cellulosimicrobium cellulans, was overexpressed in E. coli, and its interactions with β-glucans, laminarin and laminarioligosaccharides, were analyzed using surface plasmon resonance biosensor and isothermal titration calorimetry. The association constants for laminarin and laminarioligosaccharides were determined to be approximately 10(6) M(-1) and 10(4) M(-1), respectively, indicating that 2 or 3 binding sites in the α-, β-, and γ-repeats of CBM13 are involved in laminarin binding in a cooperative manner. The binding avidity is approximately 2-orders higher than the monovalent binding affinity. Mutational analysis of the conserved Asp residues in the respective repeats showed that the α-repeat primarily contributes to β-glucan binding. A Trp residue is predicted to be exposed to the solvent only in the α-repeat and would contribute to β-glucan binding. The α-repeat bound β-glucan with an affinity of approximately 10(4) M(-1), and the other repeats additionally bound laminarin, resulting in the increased binding avidity. This binding is unique compared to the recognition mode of another CBM13 from Streptomyces lividans xylanase.

Byrsonima Intermedia A. Juss.: Gastric and Duodenal Anti-ulcer, Antimicrobial and Antidiarrheal Effects in Experimental Rodent Models

An ethnopharmacological survey indicated that the leaves of Byrsonima intermedia A. Juss. (Malpighiaceae), a medicinal species commonly found in the Brazilian Cerrado, can be used against gastroduodenal disorders, such as gastric ulcers and diarrhea.

Which Categories of Social and Lifestyle Activities Moderate the Association Between Negative Life Events and Depressive Symptoms Among Community-dwelling Older Adults in Japan?

Social and lifestyle activities may serve as potential moderators of the association between negative life events (NLEs) and depressive symptoms among older adults. In this study, we examined whether social and lifestyle activities moderate the association between NLEs and depressive symptoms among older adults, and which activities are significant moderators.

Biofilm Accumulation on Endotracheal Tubes Following Prolonged Intubation

To demonstrate that patients who have been intubated for prolonged periods of time will have an increased likelihood of developing bacterial biofilm on their endotracheal tubes.

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