Deck the Walls with Anisotropic Colloids in Nematic Liquid Crystals.
Nematic liquid crystals (NLCs) offer remarkable opportunities to direct colloids to form complex structures. The elastic energy field that dictates colloid interactions is determined by the NLC director field, which is sensitive to and can be controlled by boundaries including vessel walls and colloid surfaces. By molding the director field via liquid-crystal alignment on these surfaces, elastic energy landscapes can be defined to drive structure formation. We focus on colloids in otherwise defect-free director fields formed near undulating walls. Colloids can be driven along prescribed paths and directed to well-defined docking sites on such wavy boundaries. Colloids that impose strong alignment generate topologically required companion defects. Configurations for homeotropic colloids include a dipolar structure formed by the colloid and its companion hedgehog defect or a quadrupolar structure formed by the colloid and its companion Saturn ring. Adjacent to wavy walls with wavelengths larger than the colloid diameter, spherical particles are attracted to locations along the wall with distortions in the nematic director field that complement those from the colloid. This is the basis of lock-and-key interactions. Here, we study ellipsoidal colloids with homeotropic anchoring near complex undulating walls. The walls impose distortions that decay with distance from the wall to a uniform director in the far field. Ellipsoids form dipolar defect configurations with the colloid's major axis aligned with the far field director. Two distinct quadrupolar defect structures also form, stabilized by confinement; these include the Saturn I configuration with the ellipsoid's major axis aligned with the far field director and the Saturn II configuration with the major axis perpendicular to the far field director. The ellipsoid orientation varies only weakly in bulk and near undulating walls. All configurations are attracted to walls with long, shallow waves. However, for walls with wavelengths that are small compared to the colloid length, Saturn II is repelled, allowing selective docking of aligned objects. Deep, narrow wells prompt the insertion of a vertical ellipsoid. By introducing an opening at the bottom of such a deep well, we study colloids within pores that connect two domains. Ellipsoids with different aspect ratios find different equilibrium positions. An ellipsoid of the right dimension and aspect ratio can plug the pore, creating a class of 2D selective membranes.


Neurobiology of love.
Romantic love is a "universal... or near universal" human phenomenon. Recently, love, romantic love, also became a theme of interest for scientists. The current research is seeking an explanation to clarify the brain mechanisms that are responsible for love behavior and feelings. Until recently, the study of love has been mainly the field of psychology. The biology of love originates in the primitive parts of brain that eolved long before the cerebral cortex. Discoveries in neuroscience have led to the identification of specific areas, facilities, brain circuits that are involved in the genesis of love. However, love remained a research field mainly for psychologists, despite the massive increase in neuroscientific research. In the last few decades, there has been a significant increase in the number of studies on the neuronal corelates of love, through the use of neuroimaging techniques (fMRI, PET) and in the studies that have investigated the action of the neurotransmitter and neuroendocrine systems.


The terminations and secondary projections of myelinated and non-myelinated fibres of the aortic nerve in the cat.
In anaesthetized cats the projection of myelinated and non-myelinated afferent fibres of the aortic nerve to the brain stem was studied by recording antidromic potentials evoked in the nerve by electrical stimulation of the medulla oblongata. Probable sites of termination of both myelinated and non-myelinated afferent fibres were found to be in the ipsilateral medial lateral subnucleus of the nucleus tractus solitarius, the ipsilateral area postrema, the commissural nucleus and the contralateral nucleus tractus solitarius about the level of the obex. No evidence for a projection of primary afferent fibres in the aortic nerve to the medial reticular formation was found. In a second series of experiments the aortic nerve was electrically stimulated and extracellular recordings were made from neurones in the medulla activated by afferent fibres in this nerve. Neurones activated by myelinated afferent fibres were located in the nucleus tractus solitarius, dorsal vagal motor nucleus, commissural nucleus, area postrema and lateral reticular formation including nucleus ambiguus. Neurones activated by non-myelinated afferent fibres were in or near the medial nucleus tractus solitarius, the area postrema, dorsal motor vagal nucleus and nucleus intercalatus. Few neurones appeared to be activated by both myelinated and non-myelinated afferent fibres and they were located in the medial nucleus tractus solitarius and nucleus ambiguus.


[Analysis of the dynamic changes of cornea after myopic excimer laser in situ keratomileusis using an Orbscan II topography system].
To study the changes and influence factors of an Orbscan II topography system in myopia after excimer laser in situ keratomileusis (LASIK). Two hundred and sixteen myopia patients (230 eyes) were treated by LASIK, their corneal thickness and curve of corneal posterior surface was measured with an Orbscan II topography system before and after surgery. The results of measurement in different time points were compared. The thinnest point of cornea, the mean keratometry of the posterior best fit surface (BFS) and the distance from the apex to the BFS were significant difference before and after operation (P < 0.05). There were significant difference among those groups in different degree of myopia in the same time point (P < 0.05) after surgery, but there were no significant difference in the same group in difference time (P > 0.05). A significant difference in the area of the thinnest cornea before surgery and after surgery was detected among those groups (P < 0.01). The regression equation for preoperative Diff value was established as Y = 0.0941 - 0.000,53X(1) - 0.000,471X(2) - 0.0063X(3) + 0.001,22X(4) (P < 0.01), X(1) = corneal thickness of the thinnest point (microm), X(2) = central corneal thickness (microm), X(3) = corneal diameter (mm), X(4) = length of ocular axis (mm). The regression equation for postoperative decrease Diff value between the third month and the first month was produced as Y = - 0.027 - 0.000,78X(1) + 0.002,01X(2) - 0.0055X(3) (P < 0.01). X(1) = decrease in corneal thickness of the thinnest point (microm), X(2) = intraocular pressure pre-surgery (mmHg), X(3) = decrease in curvature of posterior corneal surface (D). The application of Orbscan II has an important clinical significance before and after LASIK. The Diff value measured before LASIK for myopia is influenced by the corneal thickness, corneal diameter and ocular axis. The postoperative decrease in Diff value between the third and first month is influenced by the postoperative decrease of corneal thinnest point and curvature of posterior corneal surface, and preoperative intraocular pressure.


Thermal formation of homochiral serine clusters and implications for the origin of homochirality.
Spontaneous assembly of amino acids into vapor-phase clusters occurs on heating the solid compounds in air. In comparison to the other amino acids, serine forms clusters to an unusual extent, showing a magic number octamer on sublimation; this octamer can be ionized and characterized by mass spectrometry. Two isomers of the vapor-phase serine octamer are generated, the minor one at 130 degrees C and the major at 220 degrees C. The higher temperature cluster shows a strong homochiral preference, as confirmed by isotopic labeling experiments. This serine cluster, like that generated earlier from solution in electrospray ionization experiments, undergoes gas-phase enantioselective substitution reactions with other amino acids. These reactions transfer the chirality of serine to the other amino acid through enantioselective incorporation into the octamer. Other serine pyrolysis products include alanine, glycine, ethanolamine, and small dipeptides, and many of these, too, are observed to be incorporated into the thermally formed serine octamers. Chiral chromatographic analysis confirmed that L-serine sublimation produced DL-alanine, glycine, and ethanolamine, while in the presence of hydrogen sulfide, L-serine yielded L-cysteine. The data demonstrate that sublimation of serine under relatively mild conditions yields chirally enriched serine octamers and that the chiral preference of the starting serine can be transferred to other compounds through cluster-forming chemical reactions.


The longitudinal influence of home and neighbourhood environments on children's body mass index and physical activity over 5 years: the CLAN study.
To determine the independent contributions of family and neighbourhood environments to changes in youth physical activity and body mass index (BMI) z-score over 5 years. In 2001, 2004 and 2006, 301 children (10-12 years at baseline) had their height and weight measured (BMI was converted to z-scores using Centers for Disease Control and Prevention reference charts; see http://www.cdc.gov/growthcharts) and moderate-to-vigorous physical activity (MVPA) assessed using accelerometers. In 2001, parents reported on the home environment (social support, role modelling, rules and restrictions, physical environment) and perceived neighbourhood environment (local traffic, road safety, sporting venues, public transport), and Geographic Information Systems were used to map features of the neighbourhood environment (destinations, road connectivity, traffic exposure). Generalized estimating equations were used to predict average BMI z-score and MVPA over time from baseline home and perceived and objective neighbourhood environment factors. Among boys, maternal education and heavy traffic were inversely associated, and sibling physical activity, maternal role modelling of MVPA and the presence of dead-end roads were positively associated with MVPA. Having unmarried parents, maternal MVPA role modelling and number of home sedentary items were positively associated with BMI z-score among boys. Among girls, having siblings, paternal MVPA role modelling, physical activity rules and parental physical activity co-participation were positively associated with MVPA. Having unmarried parents and maternal sedentary behaviour role modelling were positively associated, and number of sedentary behaviour rules and physical activity items were inversely associated with BMI z-score among girls. The home environment seems more important than the neighbourhood environment in influencing children's physical activity and BMI z-score over 5 years. Physical activity and weight gain programmes among youth should focus on parental role modelling, rules around sedentary and active pursuits, and parental support for physical activity. Intervention studies to investigate these strategies are warranted.


Diacylglycerol acyltransferase-1 (DGAT1) inhibition perturbs postprandial gut hormone release.
Diacylglycerol acyltransferase-1 (DGAT1) is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4) inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.


Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos.
The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells.


Has mildness replaced cleanliness next to godliness?
Over the past 30 years we have witnessed a change in our approach to soaps. The turning point was, in fact, the publication of an article by Frosch and Kligman in 1979, in which they described a new method for assessing the irritancy of soaps. They maintained that the chief weakness of the usage tests in the past was that the reactions under normal usage conditions were weak and did not discriminate adequately between different soaps. They proposed a test, called the soap chamber test, which was conducted under extreme conditions, on people known to have a sensitive skin, thereby resulting in strong reactions that emphasized the slight differences between the various soaps. Frosch and Kligman's work opened up a whole new era in the field of assessment of soap quality. Following their initial studies, many other studies were conducted, including the exaggerated use tests, often in conjunction with instrumental methods of evaluation, such as measurement of transepidermal water loss, electrical conductance, skin color and blood flow, and other tests designed to evaluate the irritation potential of various soaps. All those tests had a common purpose: to achieve extreme conditions which would provide greater sensitivity and discriminating power and would accentuate and emphasize the differences between soaps as much as possible: the greater the discrimination and the differences between the products, the more efficient and useful the test. The introduction and publication of tests such as those completely changed out approach to soaps. The sought-after qualities in a soap became safety, mildness, gentleness, less irritation, less drying--in particular, gentleness and mildness were emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)


Schizencephaly in Hereditary Hemorrhagic Telangiectasia.
The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs. A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities. Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs. To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.


Collection and use of peripheral blood stem cells in very small children.
Collections of peripheral blood stem cells (PBSC) from children weighing less than 25 kg have been limited by concern about citrate toxicity. We developed a modified collection technique on the Fenwal CS3000 blood cell separator and used it in three children weighing 8.3, 20 and 24 kg with neuroblastoma involving the marrow. The saline prime was discarded as a mixture of 250 ml red cells, 100 ml fresh frozen plasma, and 100 ml 5% albumin was run into the separator. Heparin (1500 units/h) was used to supplement ACD, which was infused at a low rate (1:25-1:32 vs blood, vs the usual 1:13). No serious difficulties were encountered during or after the collections. A total of 5.7, 4.8 and 6.4 x 10(8) mononuclear cells/kg were collected in six procedures per patient. After cell cryopreservation and patient preparation using high-dose chemotherapy, the cells were thawed in 37 degrees C saline and infused without incident. Hematopoietic recovery was observed, and one of the patients remains in clinical remission after 11 months of follow-up. The addition to previously developed procedures of the use of partial albumin prime, low citrate anticoagulation, and heparin allows convenient and safe collection of PBSC in extremely small children, and these PBSC are effective.


Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types.
Overexpression of the chondroitin sulfate proteoglycan 4 (CSPG4) has been associated with the pathology of multiple types of such as melanoma, breast cancer, squamous cell carcinoma, mesothelioma, neuroblastoma, adult and pediatric sarcomas, and some hematological cancers. CSPG4 has been reported to exhibit a role in the growth and survival as well as in the spreading and metastasis of tumor cells. CSPG4 is overexpressed in several malignant diseases, while it is thought to have restricted and low expression in normal tissues. Thus, CSPG4 has become the target of numerous anticancer treatment approaches, including monoclonal antibody-based therapies. This study reviews key potential anti-CSPG4 antibody and immune-based therapies and examines their direct antiproliferative/metastatic and immune activating mechanisms of action.


[Treatment of postmastectomy edema of the upper extremity using microsurgical technics].
Reconstructive microsurgery carried out in 25 cases of postmastectomy edema of the upper extremity proved to be the most effective and safest in treatment of the said complication. The procedure should be supplemented with phlebolysis of the subclavicular vein (when occlusion of the latter exceeds 50%) or with resection of dermatofascial flap of the brachial area (fibrous stage of lymphostasis). Sequence of stages and the results of the surgical treatment are discussed.


Characterizing the composition of molecular motors on moving axonal cargo using "cargo mapping" analysis.
Understanding the mechanisms by which molecular motors coordinate their activities to transport vesicular cargoes within neurons requires the quantitative analysis of motor/cargo associations at the single vesicle level. The goal of this protocol is to use quantitative fluorescence microscopy to correlate ("map") the position and directionality of movement of live cargo to the composition and relative amounts of motors associated with the same cargo. "Cargo mapping" consists of live imaging of fluorescently labeled cargoes moving in axons cultured on microfluidic devices, followed by chemical fixation during recording of live movement, and subsequent immunofluorescence (IF) staining of the exact same axonal regions with antibodies against motors. Colocalization between cargoes and their associated motors is assessed by assigning sub-pixel position coordinates to motor and cargo channels, by fitting Gaussian functions to the diffraction-limited point spread functions representing individual fluorescent point sources. Fixed cargo and motor images are subsequently superimposed to plots of cargo movement, to "map" them to their tracked trajectories. The strength of this protocol is the combination of live and IF data to record both the transport of vesicular cargoes in live cells and to determine the motors associated to these exact same vesicles. This technique overcomes previous challenges that use biochemical methods to determine the average motor composition of purified heterogeneous bulk vesicle populations, as these methods do not reveal compositions on single moving cargoes. Furthermore, this protocol can be adapted for the analysis of other transport and/or trafficking pathways in other cell types to correlate the movement of individual intracellular structures with their protein composition. Limitations of this protocol are the relatively low throughput due to low transfection efficiencies of cultured primary neurons and a limited field of view available for high-resolution imaging. Future applications could include methods to increase the number of neurons expressing fluorescently labeled cargoes.


NGF-induced cell differentiation and gene activation is mediated by integrative nuclear FGFR1 signaling (INFS).
Nerve growth factor (NGF) is the founding member of the polypeptide neurotrophin family responsible for neuronal differentiation. To determine whether the effects of NGF rely upon novel Integrative Nuclear FGF Receptor-1 (FGFR1) Signaling (INFS) we utilized the PC12 clonal cell line, a long-standing benchmark model of sympathetic neuronal differentiation. We demonstrate that NGF increases expression of the fgfr1 gene and promotes trafficking of FGFR1 protein from cytoplasm to nucleus by inhibiting FGFR1 nuclear export. Nuclear-targeted dominant negative FGFR1 antagonizes NGF-induced neurite outgrowth, doublecortin (dcx) expression and activation of the tyrosine hydroxylase (th) gene promoter, while active constitutive nuclear FGFR1 mimics the effects of NGF. NGF increases the expression of dcx, th, βIII tubulin, nurr1 and nur77, fgfr1and fibroblast growth factor-2 (fgf-2) genes, while enhancing binding of FGFR1and Nur77/Nurr1 to those genes. NGF activates transcription from isolated NurRE and NBRE motifs. Nuclear FGFR1 transduces NGF activation of the Nur dimer and raises basal activity of the Nur monomer. Cooperation of nuclear FGFR1 with Nur77/Nurr1 in NGF signaling expands the integrative functions of INFS to include NGF, the first discovered pluripotent neurotrophic factor.


Metformin is also effective on lactic acidosis-exposed melanoma cells switched to oxidative phosphorylation.
Low extracellular pH promotes in melanoma cells a malignant phenotype characterized by an epithelial-to-mesenchymal transition (EMT) program, endowed with mesenchymal markers, high invasiveness and pro-metastatic property. Here, we demonstrate that melanoma cells exposed to an acidic extracellular microenvironment, 6.7±0.1, shift to an oxidative phosphorylation (Oxphos) metabolism. Metformin, a biguanide commonly used for type 2 diabetes, inhibited the most relevant features of acid-induced phenotype, including EMT and Oxphos. When we tested effects of lactic acidosis, to verify whether sodium lactate might have additional effects on acidic melanoma cells, we found that EMT and Oxphos also characterized lactic acid-treated cells. An increased level of motility was the only gained property of lactic acidic-exposed melanoma cells. Metformin treatment inhibited both EMT markers and Oxphos and, when its concentration raised to 10 mM, it induced a striking inhibition of proliferation and colony formation of acidic melanoma cells, both grown in protons enriched medium or lactic acidosis. Thus, our study provides the first evidence that metformin may target either proton or lactic acidosis-exposed melanoma cells inhibiting EMT and Oxphox metabolism. These findings disclose a new potential rationale of metformin addition to advanced melanoma therapy, e.g. targeting acidic cell subpopulation.


Metabolic diseases: the environment determines the odds, even for genes.
The odds for well-being or illness are determined by the interplay of genetic and environmental impacts. In this review, normal and disturbed body weight regulation are used to demonstrate the role of integrative bioresearch in bridging the gap between identified genotypes and an understanding of the functions of redundant and plastic control systems underlying phenotypes.


Loss of XBP1 Leads to Early-Onset Retinal Neurodegeneration in a Mouse Model of Type I Diabetes.
Retinal neuronal injury and degeneration is one of the primary manifestations of diabetic retinopathy, a leading cause of vision loss in working age adults. In pathological conditions, including diabetes and some physiological conditions such as aging, protein homeostasis can become disrupted, leading to endoplasmic reticulum (ER) stress. Severe or unmitigated ER stress can lead to cell death, which in retinal neurons results in irreversible loss of visual function. X-box binding protein 1 (XBP1) is a major transcription factor responsible for the adaptive unfolded protein response (UPR) to maintain protein homeostasis in cells undergoing ER stress. The purpose of this study is to determine the role of XBP1-mediated UPR in retinal neuronal survival and function in a mouse model of type 1 diabetes. Using a conditional retina-specific XBP1 knockout mouse line, we demonstrate that depletion of XBP1 in retinal neurons results in early onset retinal function decline, loss of retinal ganglion cells and photoreceptors, disrupted photoreceptor ribbon synapses, and Müller cell activation after induction of diabetes. Our findings suggest an important role of XBP1-mediated adaptive UPR in retinal neuronal survival and function in diabetes.


Development of a convenient detection method for Trichomonas vaginalis based on loop-mediated isothermal amplification targeting adhesion protein 65.
Trichomoniasis resulting from Trichomonas vaginalis (T. vaginalis) has been considered as a commonly seen disease with the transmission way of sex. At present, the detection methods of T. vaginalis mainly include wet mount microscopy, culture, PCR, immunofluorescence and ELISA. However, all of these detection methods exist shortcomings. In this study, a loop-mediated isothermal amplification (LAMP) assay that targeted the species-specific sequence of adhesion protein 65 (AP65) gene had been conducted to detect T. vaginalis. The optimum reaction system and conditions were optimized in this rapid detection method. The results of sensitivity analysis showed that the LAMP assay targeting the AP65 gene was 1000 times more sensitive than the nested PCR targeting the actin gene commonly used for detection of T. vaginalis, and the detecting limitation of the former was 10 trichomonad. Moreover, the amplification of the target gene AP65 by LAMP assay exhibited high specificity and the product was exclusively from T. vaginalis. The detection technique of LAMP did not exhibit cross-reactivity with the common pathogens of Trichinella spiralis, Toxoplasma gondii, Escherichia coli, Candida albicans, Staphylococcus aureus, Haemophilus. According to the present study, the LAMP assay with the target of AP65 gene, was suitable for the early diagnosis of T. vaginalis infections. Consequently, the LAMP assay was proposed by the current study as a point-of-care examination and an alternative molecular tool which exhibited the potential value in the treatment, control and prevention of trichomoniasis transmission and relevant complication.


[High mechanical stretch stress promotes degeneration of the human nucleus pulposus cells through NF-κb signaling pathway].
Objective: To investigate the effect of high mechanical stretch stress(HMS)on human nucleus pulposus cells and its regulatory mechanism. Methods: The non-degenerated nucleus pulposus tissue (Pfirrmann<grade Ⅲ) removed from the patient's surgery was harvested and the human nucleus pulposus cells were isolated and cultured. In the presence or absence of pretreatment with the NF-κB specific blocker Bay11-7082, the cultured human nucleus pulposus cells were loaded cyclic mechanical stretch stress(CMS) with different parameters using the Flexercell system.The cell culture medium was collected and the secretion of inflammatory cytokines was detected by Elisa. The nucleus pulposus cells loaded with cyclic mechanical stretch stress(CMS) was collected, the changes of NF-κB/P65 signal pathway were detected, The mRNA and protein levels' expression changes were detected by RT-PCR and WB; after human nucleus pulposus cells were exposed to IL-1β, with or without Bay11-7082, the changes of P65 were detected by immunofluorescence. Results: Those mechanical stretch stress of high amplitude (9%, 19%), low frequency (0.01 Hz) and long duration (72 h) led to degeneration of human nucleus pulposus cells, while the mechanical stretch stress of low amplitude (3%), low frequency and long duration could not promote the degeneration process; the mechanical stretch stress of high amplitude(19%), low-frequency(0.01 Hz) could promote the release of inflammatory cytokines of human nucleus pulposus cells after 24 h duration; high-amplitude, low-frequency mechanical stretch stress could activate the NF-κB signaling pathway in human nucleus pulposus cells, Bay11-7082 could block the process; immunofluorescence showed that IL-1β could promote the phosphorylation of P65 in the cytoplasm of human nucleus pulposus cells and promote the entry of P65 into the cell nucleus process, Bay11-7082 could block those processes; Bay11-7082, the specific blocking agent of NF-κB signaling pathway, could block the degeneration process of human nucleus pulposus cells induced by high cyclic mechanical stretch stress(CMS) in a dose-dependent. Conclusions: High cyclic mechanical stretch stress promotes human nucleus pulposus cells degeneration through NF-κB signaling pathway.


The national trauma triage protocol: how EMS perspective can inform the guideline revision.
The Field Triage Guidelines (FTG) support emergency medical service (EMS) decisions regarding the most appropriate transport destination for injured patients. While the components of the algorithm are largely evidenced-based, the stepwise approach was developed with limited input from EMS providers. FTG are only useful if they can easily be applied by the field practitioner. We sought to gather end-user input on the current guidelines from a broad group of EMS stakeholders to inform the next revision of the FTG. An expert panel composed an end-user feedback tool. Data collected included: demographics, EMS agency type, geographic area of respondents, use of the current FTG, perceived utility, and importance of each step in the algorithm (1: physiologic, 2: anatomic, 3 mechanistic, 4: special populations). The American College of Surgeons Committee on Trauma (ACS COT), in partnership with several key organizations, distributed the tool to reach as many providers as possible. 3958 responses were received (82% paramedics/emergency medical technicians, 9% physicians, 9% other). 94% responded directly to scene emergency calls and 4% were aeromedical providers. Steps 2 and 3 were used in 95% of local protocols, steps 1 and 4 in 90%. Step 3 was used equally in protocols across all demographics; however, step 1 was used significantly more in the air medical services than ground EMS (96% vs 88%, p<0.05). Geographic variation was demonstrated in FTG use based on the distance to a trauma center, but step 3 (not step 1) drove the majority of the decisions. This point was reinforced in the qualitative data with the comment, "I see the wreck before I see the patient." The FTG are widely used by EMS in the USA. The stepwise approach is useful; however, mechanism (not physiological criteria) drives most of the decisions and is evaluated first. Revision of the FTG should consider the experience of the end-users. V.


Effectiveness of CoQ10 Oral Supplements as an Adjunct to Scaling and Root Planing in Improving Periodontal Health.
Deficiency of CoQ 10 was found in human inflamed gingiva and has been found to be responsible for periodontal destruction. To evaluate the effectiveness of CoQ 10 supplementation as an adjunct to scaling and rootplaning in reducing gingival inflammation and periodontal pocket depth. The study was a randomized, double-blind, controlled, parallel group design clinical trial. Thirty subjects with plaque induced gingival inflammation and having atleast three nonadjacent interproximal sites with a probing pocket depth ≥ 5mm were included in the study. The subjects were randomly divided into two groups. The test group (n=15) in which patients were given oral CoQ10 supplements after scaling and root planing and the control group (n=15) in which patients were given an oral placebo after scaling and rootplaning. The plaque index, gingival index and probing depth were recorded at baseline, 1 month and 3 months. Statistical analysis done by using Student's paired t-test for intragroup comparison and unpaired t-test for inter-group comparison. Both the groups showed marked reduction of afore mentioned periodontal parameters at one month and three months when compared to baseline. Though there was no significant difference in plaque index and probing pocket depth between the two groups at any given time period, test group showed significant difference in gingival inflammation at one month and three months when compared to control group. In the present study use of Coenzyme Q10 oral supplements as an adjunct to scaling and root planing showed significant reduction in gingival inflammation when compared to scaling and rootplaning alone.


[Dental museums: the Museo del Circulo Odontologico de Rosario].
Dr. J. Emilio Fernández, important figure of Rosarine Odontology, has been one of the pioneers in the growing of its societary movement and principal promotor in the foundation of the Odontologic Circle Rosario Museum. In this article the origins of the Museum in his charge are described from its foundation up to of present, depicting the principal pieces of its rich collection.


Self-initiated behavioral change and disease resurgence on activity-driven networks.
We consider a population that experienced a first wave of infections, interrupted by strong, top-down, governmental restrictions and did not develop a significant immunity to prevent a second wave (i.e., resurgence). As restrictions are lifted, individuals adapt their social behavior to minimize the risk of infection. We explore two scenarios. In the first, individuals reduce their overall social activity towards the rest of the population. In the second scenario, they maintain normal social activity within a small community of peers (i.e., social bubble) while reducing social interactions with the rest of the population. In both cases, we investigate possible correlations between social activity and behavior change, reflecting, for example, the social dimension of certain occupations. We model these scenarios considering a susceptible-infected-recovered epidemic model unfolding on activity-driven networks. Extensive analytical and numerical results show that (i) a minority of very active individuals not changing behavior may nullify the efforts of the large majority of the population and (ii) imperfect social bubbles of normal social activity may be less effective than an overall reduction of social interactions.


Current Knowledge of Beta-Blockers in Chronic Hemodialysis Patients.
Beta-blockers include a large spectrum of drugs with various specific characteristics, and a well-known cardioprotective efficacy. They are recommended in heart failure, hypertension and arrhythmia. Their use in chronic hemodialysis patients is still controversial, mainly because of the lack of specific randomized clinical trials. Large observational studies and two important clinical trials have reported almost unanimously their efficacy in chronic hemodialysis patients, which seems to be related to their levels of dialyzability and cardioselectivity. A recent meta-analysis suggested that high dialyzable beta-blockers are correlated to a reduced risk of all-cause mortality and cardiovascular complications compared with low dialyzable beta-blockers. Despite their benefits, beta-blockers may have adverse effects, such as intradialytic hypotension with low dialyzability beta-blockers or the risk of sub-therapeutic plasma concentration of high dialyzable ones during dialysis sessions. Both cases are linked to adverse cardiovascular events. A solution for both high and low dialyzable drugs could be their administration after dialysis sessions. Futhermore, the bulk of existing literature seems to favor cardioselective beta-blockers with moderate-to-high dialyzability as the ideal agents in dialysis patients, but further, larger studies are needed. This review aims to analyze beta-blockers' characteristics, indications and evidence-based role in chronic hemodialysis patients.


Traumatic clival subdural hematoma in an adult.
Retroclival hematomas are a rare entity. They are usually associated with significant trauma, and patients frequently have focal neurological deficits, especially cranial nerve palsies. Previous case reports of epidural clival hematomas have been described almost exclusively in the pediatric population. The authors report a unique case of traumatic clival subdural hematoma, which has never been described in an adult except in the context of hemophilia. An 18-year-old man presented with continuing nausea and headaches following a seemingly trivial head injury. He was found to have a posterior fossa retroclival hematoma extending into the spinal subdural space but without any neurological deficits. He was treated conservatively, with a good outcome. The authors discuss the possible mechanisms of injury, management, and complications related to this rare condition, and they review the pertinent literature.


Anticoagulation for acute coronary syndromes: from heparin to direct thrombin inhibitors.
The anticoagulant properties of heparin were discovered in 1916, and by the 1930s researchers were evaluating its therapeutic use in clinical trials. Treatment of unstable angina with unfractionated heparin (UFH), in addition to aspirin, was introduced into clinical practice in the early 1980s. UFH was combined with aspirin to suppress thrombin propagation and fibrin formation in patients presenting with acute coronary syndromes (ACS) or patients undergoing percutaneous coronary intervention (PCI). However, UFH stimulates platelets, leading to both activation and aggregation, which may further promote clot formation. Clinical trials have demonstrated that newer agents, such as the low-molecular-weight heparins (LMWHs), are superior to UFH for medical management of unstable angina or non-ST-segment elevation myocardial infarction. Increasingly, the LMWHs have been used as the anticoagulant of choice for patients presenting with ACS. For patients undergoing PCI, LMWH provides no sub-stantial benefit over UFH for anticoagulation; however, direct thrombin inhibitors (DTIs) have demonstrated safety and efficacy in this setting. UFH is likely to be replaced by more effective and safer antithrombin agents, such as DTIs. DTIs have antiplatelet effects, anticoagulant action, and most do not bind to plasma proteins, thereby providing a more consistent dose-response effect than UFH. The FDA has approved 4 parenteral DTIs for various indications: lepirudin, argatroban, bivalirudin, and desirudin. The antiplatelet, anticoagulant, and pharmacokinetic properties of bivalirudin support its use as the anticoagulant of choice for both lower- and higher-risk patients, including those undergoing PCI.


Ascorbic acid synthesis and transportation capacity in old laying hens and the effects of dietary supplementation with ascorbic acid.
Laying hens over 75 weeks of age commonly show great declines in immunity and production performance. It is unclear whether these declines can be relieved by supplementing with ascorbic acid (AA) in feed. Two trials were conducted to investigate the synthesis and metabolism of AA in layers of different ages and the effects of dietary supplemental AA on the performance and the immune and antioxidant statuses of 78 weeks old hens. In Exp. 1, equal numbers (24 hens) of 35 weeks old (Young) and 75 weeks old (Old) layers were fed the same diet without AA supplementation for 4 weeks. In Exp. 2, 360 healthy 78 weeks old laying hens were randomly assigned to 4 treatments (basal diet supplemented with 0, 0.25, 0.5, or 1 g AA/kg diet) in an 8-week feeding trial. The old hens tended to have decreased L-gulonolactone oxidase (GLO) synthase activity in the kidney and liver than that of the young hens (P = 0.07 and P = 0.05, respectively). Compared with the young hens, the old hens had lower hepatic antioxidant capacity allowing for the lower thioredoxin (TXN), thioredoxin reductase (TXNR) and cytochrome b5 reductase (CYB5R) gene expression (P < 0.05), whereas increased sodium-dependent vitamin C transporter (SVCT) 1 expression levels in the ileum and kidney and enhanced splenic and hepatic AA concentrations (P < 0.05). Dietary supplementation with AA significantly decreased GLO enzyme activity but increased splenic AA concentration and anti-bovine serum albumin IgG levels (P < 0.05) and tended to increase CD4+ T lymphocyte numbers (P = 0.06) in serum. Supplementation of 0.25 g AA/kg diet significantly increased hepatic total antioxidant capacity (T-AOC, P < 0.05) relative to the control group. Laying hens could synthesize AA in both the kidney and the liver, though the GLO enzyme activities were 100 times greater in kidneys than in livers. The old laying hens had greater absorption and reabsorption capacity and higher AA retention in some tissues that did the young hens. Dietary supplementation of AA can improve the health of old layers by enhancing immunity and antioxidant capacity.


Circadian rhythms, the molecular clock, and skeletal muscle.
Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle.


Cibotium barometz polysaccharides stimulate chondrocyte proliferation in vitro by promoting G1/S cell cycle transition.
Cibotium barometz polysaccharides (CBPS) are one of the most important bioactive components extracted from the Cibotium barometz plant, which belongs to the Dicksoniaceae family. It has been widely used for the treatment of orthopedic diseases in traditional Chinese medicine. However, the molecular mechanisms behind the therapeutic effects of CBPS remain to be clarified. In the present study, the concentration of CBPS was detected by phenol-vitriol colorimetry. Furthermore, the effects stimulated by CBPS on the viability and G1/S cell cycle transition in primary chondrocytes from Sprague-Dawley rats were investigated. A cell viability assay demonstrated that chondrocyte proliferation may be enhanced by CBPS in a dose‑ and time‑dependent manner. The mechanism underlying the promotion of chondrocyte cell cycle was suggested to involve the stimulation of G1 to S phase transition. To further confirm the results, reverse transcription‑quantitative polymerase chain reaction and western blot analyses were used to detect the expression of mRNA and protein levels of cyclin D1, cyclin‑dependent kinase 4 and retinoblastoma protein. The results suggested that CBPS may stimulate chondrocyte proliferation via promoting G1/S cell cycle transition. Since osteoarthritis is characterized by deficient proliferation in chondrocytes, the present study indicates that CBPS may potentially serve as a novel method for the treatment of osteoarthritis.


Myeloperoxidase Antineutrophil Cytoplasmic Antibody (MPO-ANCA) Associated Crescentic and Necrotizing Glomerulonephritis (GN) with Membranoproliferative GN Features.
A 77-year-old man presented with a fever, non-productive cough, and edema formation. A laboratory analysis showed an elevated creatinine level (2.5 mg/dL), a high titer of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (99 U/mL), positive reaction for antinuclear antibody (×320), hematuria, and massive proteinuria (3.33 g/day). A renal biopsy revealed crescentic and necrotizing glomerulonephritis (GN) with membranoproliferative GN features [double contour appearance of the glomerular basement membrane, granular deposition of immunoglobulin (Ig) G, IgM, and C3 along the capillary wall, subendothelial and subepithelial deposits with mesangial interposition]. A potential relationship between MPO-ANCA associated GN and membranoproliferative GN is discussed.


Clot-blood contrast in fast gradient-echo magnetic resonance imaging.
Contrast between clot and blood in magnetic resonance imaging (MRI) at 1.5T using fast gradient-echo pulse sequences (fast GRE), with 8 ms < TR < 20 mseconds was studied both in vitro and in clinical human deep venous thrombosis (DVT) to assess whether good contrast could be obtained at such short repetition times and at clinically relevant flow rates. In vitro studies used an apparatus that contained flowing MnCl2[aq] (water adjusted with manganese chloride to have T1, T2 similar to blood) and an immobilized clot (T1, T2 similar to those in DVT) for flow velocities between 0 and 16.5 cm/sec. Seven patients with DVT were imaged with the fast GRE sequences to observe the clot-blood contrast in vivo. Peak contrast-to-noise ratio (CNR) was achieved using flip angles between 20 degrees and 40 degrees (increasing with flow velocity) with or without radiofrequency "spoiling," consistent with a natural spoiling effect of flow. The CNR between MnCI2[aq] and clot decreased less than 10% as TR was reduced 56% from 18 mseconds to 8 mseconds (30 degrees flip angle). In four patients with nonocclusive DVT, fast GRE imaging provided good contrast while in occlusive cases (three patients) the contrast was not as good as conventional GRE sequences with longer TR values (TR = 33 mseconds). A fast GRE sequence with TR = 8 mseconds, TE = 3 mseconds, and a flip angle = 40 degrees is a promising approach to speeding up the detection of nonocclusive clinical DVT.


Artificial sphincter with colonic reservoir for severe anal incontinence because of imperforate anus and short-bowel syndrome: report of a case.
Anal sphincter replacement is a treatment option for severe anal incontinence that is not amenable to direct repair. We describe the unusual case of a 25-year-old male who has been successfully treated by implantable artificial sphincter for severe anal incontinence caused by imperforate anus and concomitant short-bowel syndrome. In early life, the patient underwent several surgical procedures, including a perineal colostomy for a high imperforate anus associated with a rectourethral fistula. At aged 21 years, he underwent a subtotal small-bowel resection and a restorative jejunotransverse anastomosis for acute intestinal necrosis related to intestinal malrotation with volvulus. The length of remnant jejunum was 90 cm. Consequently. the patient became permanently incontinent and required nutritional therapy. An artificial sphincter, after the creation of colonic reservoir, was implanted around the pulled-through colon. At two-year follow-up after implantation, despite short remnant bowel, the patient was fully continent without medication. Normal nutritional status was maintained under 100 percent oral nutrition. The patient's quality of life improved dramatically. He has returned to work and had no major restriction in his level of social functioning. Our case illustrates for the first time the original concept of artificial anal artificial sphincter implantation around a pulled-through colon, which constitutes a different situation from disease with rectum in place.


Sera from patients with halothane hepatitis contain antibodies to halothane-induced liver antigens which are not detectable by immunoblotting.
In previous studies, immune responses to novel, halothane-induced hepatic antigens have been implicated in the mechanism of halothane hepatitis. Experiments performed using the technique of immunoblotting have indicated that the halothane-induced antigens comprise a group of halothane metabolite-modified microsomal proteins (trifluoroacetylated proteins). In the present report, we describe detection of an additional and quite distinct group of halothane-induced antigens. The novel halothane-induced antigens were expressed in microsomal fractions from livers of halothane-treated rats and could be detected by enzyme-linked immunosorbent assay (ELISA), but not by immunoblotting. In contrast to the major trifluoroacetyl-protein antigens detectable by immunoblotting, which were soluble in buffer containing 0.1% sodium deoxycholate, the novel antigens detectable by ELISA were not soluble in 0.1% sodium deoxycholate but were soluble in 2% sodium deoxycholate. Expression of the novel antigens was reduced markedly when rats were treated with deuterated halothane, in place of halothane. This suggests that their expression requires metabolism of halothane via the same oxidative, cytochrome P450-mediated pathway known to be responsible for generation of the antigens detectable by immunoblotting. Both the antigens detectable by ELISA and the antigens detected by immunoblotting were expressed slowly in livers of halothane-treated rats and were long-lived. Overall, these results indicate that the technique of immunoblotting is of limited value for detection and characterization of antigens involved in immune-mediated adverse drug reactions.


Behavioral differentiation of the stimulus properties of a dopaminergic D1 agonist from a D2 agonist.
This study examined the hypothesis that the stimulus properties of a dopaminergic D1 agonist should be functionally discriminable from those of a D2 agonist. Rats were trained in a two-lever food-reinforced drug discrimination paradigm to discriminate either the D1 agonist SKF 38393 from apomorphine (SKF/APO), SKF from saline (SKF/SAL) or apomorphine from saline (APO/SAL), at an APO dose previously established to have D2-mediated stimulus properties. Results showed the SKF/APO discrimination to be readily acquired. The SKF cue showed similar stimulus properties under both the SKF/APO and SKF/SAL training conditions which were mediated by the D1 receptor: the SKF response was blocked by the D1 antagonist SCH 23390, but not by the D2 antagonist haloperidol. Run length data suggested a graded rather than quantal effect of SKF dose on responding during SKF generalization tests. In APO/SAL-trained animals, the APO cue was D2 mediated; responding was blocked by haloperidol, but not by SCH 23390 and APO responding generalized to the selective D2 agonist LY 171555 (quinpirole), but not to SKF. In the SKF/APO condition, APO responding did not decrease with APO dose, nor were antagonists effective in blocking responding, reflecting the lack of an alternative no-drug response option. Higher doses of APO appear to have D1 properties; doses above the training dose engendered SKF responding in both the SKF/SAL and SKF/APO groups, a response which could be blocked by the D1 antagonist SCH 23390, but not by the D2 antagonist, haloperidol. In all three training conditions, generalization test outcomes could be influenced by the conditions of the previous test session.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterizations of long-term oxycodone/acetaminophen prescriptions in veteran patients.
Long-term management of chronic pain with opioids may be stable over time or may be complicated by problematic dose increases, drug dependencies, and toxic effects. To determine clinical contexts in which stability or problems may occur, we examined the pharmacologic and clinical correlates of long-term prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting opioid formulation. We analyzed linked, archival outpatient pharmacy and clinical databases from the New England Veterans Integrated Service Network between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids, benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined. In aggregate, 2195 patients (31% with cancer diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification) received oxycodone/acetaminophen for more than 9 months at a mean prescribed daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal changes in daily prescribed mean dose over time. Patients with cancer were more likely than other patients to receive concurrent long-acting opioids. For patients without cancer, a higher mean daily dose was associated with duration, older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions were associated with anticonvulsant prescriptions and with psychogenic pain and alcohol abuse and/or dependence diagnoses. In veteran patients who received long-term oxycodone/acetaminophen prescriptions, mean daily doses were typically modest and stable, likely reflecting a selection of patients with successful, long-term management. Among patients without cancer, however, associations of higher oxycodone/acetaminophen doses with benzodiazepine prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid prescription management problems.


Recurrent seizure and sustained encephalopathy associated with dimethylsulfoxide-preserved stem cell infusion.
We report the case of a patient who received two infusions of dimethylsulfoxide (DMSO) cryopreserved autologous peripheral blood progenitor cells (PBPCs) after myeloablative chemotherapy for a relapsing lymphoma. A 49-year-old man presented an episode of tonic-clonic seizure over a few minutes after the start of each infusion and developed a profound and sustained but reversible encephalopathy with coma after the second infusion. The patient's neurological condition correlated well with the electrophysiological findings (electroencephalogram and multimodality evoked potentials) and, to a lesser extent, with the radiological abnormalities (magnetic resonance imaging). Severe but reversible neurological complications may occur with the infusion of PBPCs cryopreserved with DMSO.


[FEMALE PARAURETHRAL LEIOMYOSARCOMA: A CASE REPORT].
A 54-year-old woman visited another hospital with complaining of a palpable mass in vagina and dysuria. The mass had gradually enlarged since the past 2 years. Ultrasonography and CT revealed the tumor located between the urethra and vaginal mucosa. Histopathological examination was well-differentiated leiomyosarcoma from transvaginal needle biopsy. She was referred to our hospital. On MRI, the 4-cm tumor showed no infiltration into the vaginal mucosa or urethra. PET/CT showed a high uptake of FDG. No metastatic disease was evident. We performed excision of the tumor transvaginally. The tumor cells demonstrated immunoreactivity for estrogen receptors and partially progesterone receptors in histopathological examination. We speculated that the developmental mechanism of female paraurethral leiomyosarcoma was associated with female leiomyosarcoma in other surrounding pelvic organs.


Academic self-disclosure in adolescence.
Adolescents' dialogues with friends and classmates about their academic performance constitute a central arena of self-disclosure for developing teenagers. Yet researchers have generally limited the range of their study of academic self-disclosure to gifted students. This study brings together the literature on self-disclosure, academic achievement, and adolescent development to elucidate the overlapping elements at play in adolescents' everyday decisions to talk about their academic performance. With an ethnically diverse sample of San Francisco Bay Area ("Silicon Valley") 10th and 12th graders, the authors developed a 12-scenario instrument specifying both interpersonal context (attraction/friendship) and relative-intelligence relationship (more, less, or equally smart), querying degrees of academic self-disclosure associated with these contexts. The results indicated that self-disclosure was highly (positively) influenced by the achievement level of both the discloser and listener, modestly influenced by friendship versus romantic interest, and influenced in anticipated directions by gender and age.


Postural motor learning in Parkinson's disease: The effect of practice on continuous compensatory postural regulation.
Although balance training is considered the most effective treatment for balance impairments in Parkinson's disease (PD), few studies have examined if learning for balance control remains intact with PD. This study aimed to determine if learning for automatic postural responses is preserved in people with PD. Eleven participants with moderate PD (68±6.4years; H&Y: 2-3) on their usual medication maintained balance on a platform that oscillated forward and backward with variable amplitude and constant frequency. Participants completed 42 trials during one training session, and retention and transfer tests following a 24-h delay. Performance was measured by comparing spatial and temporal measures of whole-body centre of mass (COM) with platform displacements. Learning was compared between participants with PD and previously reported, age-matched older adults (Van Ooteghem et al., 2010). Although postural responses in participants with PD were impaired compared to control participants, a majority of PD participants improved their postural responses with practice as revealed by reduced COM displacements and improved phase relationships between COM and platform motion. Rates of improvement were comparable between groups demonstrating preserved adaptive capacity for participants with PD. Similar to control participants, the PD group moved toward anticipatory COM control as a strategy for improving stability, exhibited short-term retention of performance improvements, and demonstrated generalizability of the learned responses. Rate of improvement with practice, but not retention, was related to severity of motor impairments. Patients with moderate PD on medication demonstrate retention of improvements in automatic postural responses with practice suggesting that intrinsic postural motor learning is preserved in this group.


Prevalence of Helicobacter pylori infection in children from urban and rural West Virginia.
Our objective was to evaluate the prevalence rate of Helicobacter pylori (HP) in children from urban and rural areas of West Virginia. In all, 1164 blood samples were collected from children who attended a local health fair, pediatric clinics, and emergency departments of four different hospitals located in urban and rural counties. Socioeconomic status was determined in 303 children. Serum HP antibody (IgG) was measured by enzyme immunoassay (EIA). A total of 468 (40%) samples were HP positive. HP acquisition correlated with increasing age, family crowding, and community location (urban/rural) but not with gender, water source used (city/well), or socioeconomic status. The prevalence rate of HP in the children of West Virginia is higher than any data previously reported from the United States. The results correlated with only few socioeconomic criteria, suggesting that other factors may contribute to the increased prevalence of HP infection in the children of West Virginia.


An in vitro model of radiation-induced craniofacial bone growth inhibition.
Radiation-induced craniofacial bone growth inhibition is a consequence of therapeutic radiation in the survivors of pediatric head and neck cancer. Previously, the infant rabbit orbitozygomatic complex (OZC) was established as a reliable animal model. The purpose of this study was to develop a cell culture model from the rabbit OZC to study the effects of radiation in the craniofacial skeleton. Infant (7-week-old) New Zealand white rabbits were used in this study. Periostea from both OZC were harvested in sterile conditions, introduced into cell culture by way of sequential digestion, and subcultured at confluence. Cultures were analyzed for cellular proliferation (methylthiazoletetrazolium assay), alkaline phosphatase activity, collagen type I expression, and mineralization. Electron microscopy was performed to reveal the in vitro ultrastructure. Subsequently, rabbits were irradiated with sham or 15 Gy radiation, and cell cultures were developed and analyzed for cell numbers. Cell cultures, grown from OZC periostea, expressed osteoblast-like phenotype, with high alkaline phosphatase activity, collagen type 1 expression, and mineralization in an osteogenic environment. Electron microscopy confirmed the characteristic ultrastructural features of osteogenesis in vitro. Finally, significantly (P < 0.01) fewer cells were obtained from animals treated with 15 Gy radiation compared with those from control animals.A primary cell culture with osteoblast-like cellular phenotype was developed from infant rabbit OZC periosteum. This cell culture system responded to in vivo administered radiation by a significant decrease in cell numbers. This in vitro model will be subsequently used to study the cellular mechanisms of radiation and radioprotection in craniofacial osteoblast-like cells.


Distinct lines of chickens express different splenic cytokine profiles in response to Salmonella Enteritidis challenge.
Chicken meat and eggs contaminated with Salmonella result in economic losses in the poultry industry and potential human infection. Intestinal parasites have been shown to lead to a reduction in the utilization of nutrients and performance in poultry. This study provides insight into the immune responses used by hens of 3 genetically distinct chicken lines (broiler, Leghorn, and Fayoumi) in the presence and absence of Salmonella Enteritidis infection. Understanding the range of immune responses used by different lines in response to Salmonella Enteritidis may help the poultry industry genetically select birds that are more pathogen resistant. The splenic mRNA levels of several immune-related genes [IL-6, IL-8, IL-10, IL-18, macrophage inflammatory protein 1β, interferon (IFN)-γ, transforming growth factor β1, and regulated upon activation, normal T cell expressed, and secreted (RANTES)] were analyzed by quantitative PCR. Line, challenge, and their interaction were considered fixed effects. Line had a significant effect on the mRNA expression of RANTES (P < 0.02) and IFN-γ (P < 0.03). Broilers expressed significantly more splenic RANTES mRNA than Fayoumis, and significantly more splenic IFN-γ mRNA than Leghorns (P < 0.05). There was a significant interaction of genetic line and challenge on IL-18 (P < 0.02) and IL-6 (P < 0.01) mRNA expression. Although there was a significant interaction of genetic line and challenge for IL-18, Tukey's test analysis only showed differences at a suggestive level (P < 0.1). Bacterial challenge had a significant effect on IL-6 mRNA expression only within the Fayoumi line. Challenged Fayoumis expressed significantly less IL-6 mRNA than nonchallenged Fayoumis (P < 0.05). The observed differences in mRNA expression of selected cytokines support the concept that these distinct genetic lines utilize different immune responses at homeostasis and in response to Salmonella Enteritidis infection.


Statistics for Radiology Research.
Biostatistics is an essential component in most original research studies in imaging. In this article we discuss five key statistical concepts for study design and analyses in modern imaging research: statistical hypothesis testing, particularly focusing on noninferiority studies; imaging outcomes especially when there is no reference standard; dealing with the multiplicity problem without spending all your study power; relevance of confidence intervals in reporting and interpreting study results; and finally tools for assessing quantitative imaging biomarkers. These concepts are presented first as examples of conversations between investigator and biostatistician, and then more detailed discussions of the statistical concepts follow. Three skeletal radiology examples are used to illustrate the concepts.


Changes in Vasodilator-Stimulated Phosphoprotein Phosphorylation, Profilin-1, and Cofilin-1 in Accreta and Protection by DHA.
Accreta and gestational trophoblastic disease (ie, choriocarcinoma) are placental pathologies characterized by hyperproliferative and invasive trophoblasts. Cellular proliferation, migration, and invasion are heavily controlled by actin-binding protein (ABP)-mediated actin dynamics. The ABP vasodilator-stimulated phosphoprotein (VASP) carries key regulatory role. Profilin-1, cofilin-1, and VASP phosphorylated at Ser157 (pVASP-S157) and Ser239 (pVASP-S239) are ABPs that regulate actin polymerization and stabilization and facilitate cell metastases. Docosahexaenoic acid (DHA) inhibits cancer cell migration and proliferation. We hypothesized that analogous to malignant cells, ABPs regulate these processes in extravillous trophoblasts (EVTs), which exhibit aberrant expression in placenta accreta. Placental-myometrial junction biopsies of histologically confirmed placenta accreta had significantly increased immunostaining levels of cofilin-1, VASP, pVASP-S239, and F-actin. Treatment of choriocarcinoma-derived trophoblast (BeWo) cells with DHA (30 µM) for 24 hours significantly suppressed proliferation, migration, and pVASP-S239 levels and altered protein profiles consistent with increased apoptosis. We concluded that in accreta changes in the ABP expression profile were a response to restore homeostasis by counteracting the hyperproliferative and invasive phenotype of the EVT. The observed association between VASP phosphorylation, apoptosis, and trophoblast proliferation and migration suggest that DHA may offer a therapeutic solution for conditions where EVT is hyperinvasive.


[Methodologic aspects of detecting microadenomas of the pituitary in autopsy material].
Macro- and microscopic examinations of 64 randomly selected hypophyses were carried out to evaluate the dependence of the frequency of findings of hypophysis microadenomas in the section material upon the method of morphological examination and to solve the problems of differential diagnosis of microadenomas and other focal accumulations of adenocytes. Of the 7 microadenomas found 6 were detected only by microscopy. The frequency of finding of microadenomas was determined by the number of sections (blocks) examined from each hypophysis: 2 +/- 2% with 1-2 blocks per hypophysis, and 38 +/- 12% with 3-4 blocks. In addition to the previously described diagnostic criteria for microadenomas, two cytologic signs are described: cytoplasmic degranulation and a high nucleus-cytoplasm ratio in tumor cells.


Comparative study of the fluidity of plasma and disc membranes of bovine rod outer segments by electron-spin resonance.
The fluidity of isolated plasma and disc membranes from bovine rod outer segments has been compared by electron-spin resonance spectroscopy using the stearic acid spin labels 5-SASL and 16-SASL. This comparison is of interest, given the fact that the disc membranes arise by invagination from the plasma membrane. Analysis of the order parameter in the hydrophilic part of the membrane, and of rotational correlation time in the hydrophobic part, showed a difference of fluidity between these two types of membranes, with a higher fluidity in the disc membranes in both their hydrophilic and hydrophobic regions. For example, at a temperature of 37 degrees C, plasma and disc membranes exhibited values of 0.64 and 0.61 for the order parameter (S), and 9.1 and 14.5 s-1 for the rotational correlation frequency (v), respectively. These findings are discussed in relation to previously described differences in the biochemical compositions of the membranes.


[A sulfadiazine-tetroxoprim combination (co-tetroxazine) in the treatment of the acute exacerbation of chronic bronchitis].
After considering the bacterial flora which is most common in relapses in patients with bronchitis, 40 patients with chronic bronchitis have been treated with tetroxoprim a recently synthetized benzyl pyrimidine associated with sulfadiazine. One 350 mg tablet was administered every 12 hours for different periods, from 7 to 14 days. This study has shown how tetroxoprim has a wide antibacterial range, how it is well tolerated and extremely powerful in treating relapses of chronic infections in bronchi.


Satellite-Based Estimates of Daily NO2 Exposure in China Using Hybrid Random Forest and Spatiotemporal Kriging Model.
A novel model named random-forest-spatiotemporal-kriging (RF-STK) was developed to estimate the daily ambient NO2 concentrations across China during 2013-2016 based on the satellite retrievals and geographic covariates. The RF-STK model showed good prediction performance, with cross-validation R2 = 0.62 (RMSE = 13.3 μg/m3) for daily and R2 = 0.73 (RMSE = 6.5 μg/m3) for spatial predictions. The nationwide population-weighted multiyear average of NO2 was predicted to be 30.9 ± 11.7 μg/m3 (mean ± standard deviation), with a slowly but significantly decreasing trend at a rate of -0.88 ± 0.38 μg/m3/year. Among the main economic zones of China, the Pearl River Delta showed the fastest decreasing rate of -1.37 μg/m3/year, while the Beijing-Tianjin Metro did not show a temporal trend ( P = 0.32). The population-weighted NO2 was predicted to be the highest in North China (40.3 ± 10.3 μg/m3) and lowest in Southwest China (24.9 ± 9.4 μg/m3). Approximately 25% of the population lived in nonattainment areas with annual-average NO2 > 40 μg/m3. A piecewise linear function with an abrupt point around 100 people/km2 characterized the relationship between the population density and the NO2, indicating a threshold of aggravated NO2 pollution due to urbanization. Leveraging the ground-level NO2 observations, this study fills the gap of statistically modeling nationwide NO2 in China, and provides essential data for epidemiological research and air quality management.


Analysis of apoptosis-associated molecules Erythroid differentiation regulator 1, bcl-2 and p53 in actinic keratosis after treatment with ingenol mebutate.
Actinic keratosis (AK) is the most common cutaneous premalignant neoplasm precursor of malignant skin tumors. The aberrant apoptotic pathway is thought to be associated with pathogenesis of AK. Ingenol mebutate has been shown to be effective and safe for treatment of AK. However, the effect of ingenol mebutate on apoptosis-related molecules using human skin samples has not been studied well. Erythroid differentiation regulator 1 (Erdr1) was recently reported to play a crucial role in malignant skin cancers like malignant melanoma. The role of Erdr1 in premalignant actinic keratosis (AK) has not been explored. The purpose of this study was to investigate whether the expression of apoptosis-associated molecules such as Erdr1, p53 and bcl-2 was affected by the treatment of ingenol mebutate in AK. Nine patients with AK underwent skin biopsy at baseline and 8 weeks after treatment with ingenol mebutate for immunohistochemical evaluation with Erdr1, p53 and bcl-2. In addition, skin samples from five control subjects were retrieved. Upregulation of Erdr1 and a significant decrease in expression of p53 and bcl-2 were observed after treatment with ingenol mebutate. Ingenol mebutate treatment for AK resulted in the modulation of apoptosis-associated molecules with an increase in the expression of Erdr1 and a decrease in the expression of p53 and bcl-2.


Marine mammals and Emperor penguins: a few applications of the Krogh principle.
The diving physiology of aquatic animals at sea began 50 years ago with studies of the Weddell seal. Even today with the advancements in marine recording and tracking technology, only a few species are suitable for investigation. The first experiments were in McMurdo Sound, Antarctica. In this paper are examples of what was learned in Antarctica and elsewhere. Some methods employed relied on willingness of Weddell seals and emperor penguins to dive under sea ice. Diving depth and duration were obtained with a time depth recorder. Some dives were longer than an hour and as deep as 600 m. From arterial blood samples, lactate and nitrogen concentrations were obtained. These results showed how Weddell seals manage their oxygen stores, that they become reliant on a positive contribution of anaerobic metabolism during a dive duration of more than 20 min, and that nitrogen blood gases remain so low that lung collapse must occur at about 25 to 50 m. This nitrogen level was similar to that determined in elephant seals during forcible submersion with compression to depths greater than 100 m. These results led to further questions about diving mammal's terminal airway structure in the lungs. Much of the strengthening of the airways is not for avoiding the "bends," by enhancing lung collapse at depth, but for reducing the resistance to high flow rates during expiration. The most exceptional examples are the small whales that maintain high expiratory flow rates throughout the entire vital capacity, which represents about 90% of their total lung capacity.


Lens subluxation as a complication of cyclocryotherapy.
There are many well known complications of cyclocryotherapy. This case represents what we believe to be the first report of cyclocryotherapy leading to lens subluxation. The patient was a 14-year-old boy with a history of ocular trauma that had resulted in intractable glaucoma. Six locations were treated inferiorly using the freeze-thaw-freeze technique. Postoperatively the patient's zonular attachment was disrupted inferiorly and the lens subluxated superiorly. While remote trauma may have been partly responsible, we suspect that the cyclocryotherapy precipitated the lens subluxation.


HLA public determinants are target antigens of cell-mediated cytotoxicity.
HLA public antigens X and Y have been shown to be common determinants on the heavy chains of molecules belonging to the HLA-B7 and HLA-B5 cross-reactive groups (CREG), respectively. The ability of these antigens to act as targets for cytotoxic lymphocytes was investigated. After stimulating B7-CREG cells in an in vitro primary and secondary culture with mitomycin-treated B27-positive cells, the effector cells generated lysed cells bearing B7, Bw22, B27, or B40, all of which bear X. No lysis was seen with cells not bearing X. Parallel results were obtained in the B5-CREG, where the effector cells lysed target cells bearing B5, B15, B18, or Bw35, all of which bear Y. No lysis was seen with cells not bearing Y. That these public antigens were the determinants actually recognized by the cytotoxic effector cells was demonstrated by the ability of appropriate antibody to inhibit cytolysis. These results suggest possible immunopathogenic mechanisms that may explain the apparent association of X with spondyloarthropathy and of Y with Behçet's disease.


Liver-Targeted Delivery of Oligonucleotides with N-Acetylgalactosamine Conjugation.
The potential therapeutic application of oligonucleotides (ONs) that selectively suppress target genes through antisense and RNA interference mechanisms has attracted great attention. The clinical applications of ONs have overcome multiple obstacles and become one of the most active areas for the development of novel therapeutics. To achieve efficient and specific cellular internalization, conjugation of a variety of functional groups to ONs has been the subject of intensive investigations over the past decade. Among them, a promising liver-targeted N-acetylgalactosamine (GalNAc) ligand has been evaluated in multiple preclinical and clinical trials for improving the cellular uptake and tissue specific delivery of ONs. GalNAc-based delivery relies on the fact that liver hepatocytes abundantly and specifically express the asialoglycoprotein receptor that binds and uptakes circulating glycoproteins via receptor-mediated endocytosis. In recent years, encouraging progress has been made in the field of GalNAc conjugates. This review aims to provide an overview of GalNAc-mediated liver-targeted delivery of small interfering RNA and antisense oligonucleotides, and the immense effort as well as recent advances in the development of GalNAc-conjugated agents are described.


[Vegetations associated with infective endocarditis in children].
The purpose of this study were clinical analysis of vegetations associated with infective endocarditis. Between 1990-1999 years 7 children (aged 2-17 years) with infective endocarditis were study in the Cardiology Department Children's Memorial Health Institute. Analysed clinical features of vegetations associated with endocarditis. The most of them vegetations were localized on the mitral valve and in children without congenital heart disease (CHD). Remaining patients were: girl with bicuspidal aortic valve-vegetation on the aortic valve, boy with simple ventricle, pulmonary stenosis and atrial septal defect-vegetation on the pulmonary valve, boy with double outlet right ventricle, pulmonary stenosis and atrial septal defect-vegetation on the tricuspid valve, boy with patent ductus arteriosus-vegetation on the pulmonary valve. In all patients were regurgitations of this valves (> II degree). 71% patients had fever, 57% another murmur in the heart, 43% hepatosplenomegalia. Positive result of the blood sowing was in 72% patients. After medical treatment of vegetations good result was in 4 children. Chirurgical treatment were performance in 3 children. 1. Vegetations in the echocardiographic examination were in 21.8% children associated with infective endocarditis. 2. The most of them vegetations were localized on the mitral valve and in children without CHD. 3. Good result after medical treatment of vegetations was in 57% patients.


Tension Enhances the Binding Affinity of β1 Integrin by Clamping Talin Tightly: An Insight from Steered Molecular Dynamics Simulations.
Integrin activation is a predominant step for cell-cell and cell-ECM interactions. Talin and Kindlin are mechanosensitive adaptor proteins that bind to the integrin cytoplasmic tail and mediate integrin activation, cytoskeleton rearrangement, and focal adhesion assembly. However, knowledge about how Talin and Kindlin synergistically assist integrin activation remains unclear. Here, we performed so-called "ramp-clamp" SMD simulations, which modeled the mechanosignaling from Kindlin, to investigate the effect of tension on the interaction of the β1 integrin cytoplasmic tail with the Talin-F3 domain. The present results showed that mild but not excessive stretching enhanced the binding of integrin with Talin. This mechanical regulation on integrin affinity to Talin referred to an event cascade, in which under stretching, the integrin cytoplasmic tail adopted allostery in response to the mechanical stimulus, remodeling of integrin in favor of Talin-association ensued, and finally, a stable, close-knit complex was formed. In the cascade, the torsion angle transition of integrin was the cue for the stable interaction of the complex under tensile force. The present work suggested a model for Talin and Kindlin to synergistically activate integrin. It should help understand integrin activation and its mechanochemical regulation mechanism, integrin-related innate cellular immune responses, cell adhesion, cell-cell interaction, and integrin-related drug development.


Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials.
The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761(®) in dementia. Seven of 15 randomized, placebo-controlled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22-26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (-0.52; 95% confidence interval [CI] -0.98, -0.05; P=0.03), activities of daily living (-0.44; 95% CI -0.68, -0.19; P<0.001), and global rating (-0.52; 95% CI -0.92, -0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia.


Utility of a brief index to measure diet quality of Australian preschoolers in the Feeding Healthy Food to Kids Randomised Controlled Trial.
The aim was to evaluate the utility of a brief dietary intake assessment tool in measuring nutritional adequacy of preschoolers and differences in food and nutrient intake between quartiles stratified by overall diet quality. Dietary intakes of preschoolers (n = 146) from the Feeding Healthy Food to Kids trial were reported by parents/caregivers using a 120-item food frequency questionnaire (FFQ). Diet quality was assessed using the Australian Recommended Food Score for Preschoolers. Analyses were performed using Kruskal-Wallis one-way analysis of variance, adjusted for Type 1 error. Participants were grouped into quartiles by total food score for comparison of subscale scores, food groups and nutrient intakes from the FFQ. Participants who scored less than the median total food score of 36 were more likely to have suboptimal micronutrient intakes. Median fruit (9 vs 5, P < 0.0001) and vegetable (14 vs 7, P < 0.0001) subscale scores for preschoolers in the highest quartile were significantly higher than the lowest quartile, indicating much greater fruit and vegetable variety. Statistically significant differences in diet quality score by quartiles (P < 0.05) were found for total energy and percentage energy from core foods, protein, fibre and 11 micronutrients. The Australian Recommended Food Score for Preschoolers is a practical brief diet quality assessment tool to measure food variety and nutritional adequacy in Australian preschoolers. Stratifying children by baseline diet quality in future nutrition interventions is recommended in order to identify those who are likely to benefit or require more targeted approaches to address specific nutritional needs in order to optimise food and nutrient intakes.


Review on computerized prediction of nutrients in thermally processed canned food.
Basic principles are briefly discussed for mathematical evaluation of nutrient concentration in thermally processed food. This evaluation is based on the use of equations for predicting the temperature of food subjected to a thermal process and for evaluating the rates of thermal degradation of a nutrient at different temperatures. Several computer programs were prepared by various researchers to minimize manual calculations required for estimating nutrient retention in thermally processed food. The computational characteristics of these programs are critically examined.


Mutagenesis induced by site specifically placed 4'-hydroxymethyl-4,5',8-trimethylpsoralen adducts.
Closed circular double stranded M13mp19 DNA containing a site-specifically placed HMT (4'-hydroxymethyl-4-5'-8-trimethylpsoralen) monoadduct or crosslink was synthesized in vitro. The damaged DNA were scored for loss of infectivity by transfection into repair proficient or deficient E. coli and into SOS induced E. coli. Mutant phages were detected by the loss of alpha-complementation between the viral and the host Lac Z genes or by the acquisition of resistance to kpn I digestion. Our results indicate that HMT mutagenesis is targeted and that deletion or transversion of the modified thymidine is the predominant sequence change elicited by a monoadduct or a crosslink. Transfection of the monoadducted DNA into a Uvr A deficient strain did not change the mutation pattern but did increase the respective mutation frequencies. Transfection of the crosslinked DNA into a SOS induced host resulted in the appearence of other types of mutations attributable to an increase in both targeted and untargeted mutations.


The lateral septum and anterior hypothalamus act in tandem to regulate burying in the shock-probe test but not open-arm avoidance in the elevated plus-maze.
Both the lateral septum (LS) and anterior hypothalamus (AHA) regulate behavioural defense. We tested whether those two interconnected structures act in serial in that regard. Infusions of the GABAA agonist muscimol into one side of the LS and the contralateral (but not ipsilateral) AHA suppressed rats' burying in the shock-probe test whereas none of our muscimol infusion approaches altered their open-arm avoidance in the elevated plus-maze. These results suggest that the LS-AHA circuit serves a specialized role in defensive responses towards discrete, localizable threat stimuli but not towards potential threats.


Endocrine pancreatic development: impact of obesity and diet.
During embryonic development, multipotent endodermal cells differentiate to form the pancreas. Islet cell clusters arising from the pancreatic bud form the acini tissue and exocrine ducts whilst pancreatic islets form around the edges of the clusters. The successive steps of islet differentiation are controlled by a complex network of transcription factors and signals that influence cell differentiation, growth and lineage. A Westernized lifestyle has led to an increased consumption of a high saturated fat diet, and an increase in maternal obesity. The developing fetus is highly sensitive to the intrauterine environment, therefore any alteration in maternal nutrition during gestation and lactation which affects the in-utero environment during the key developmental phases of the pancreas may change the factors controlling β-cell development and β-cell mass. Whilst the molecular mechanisms behind the adaptive programming of β-cells are still poorly understood it is established that changes arising from maternal obesity and/or over-nutrition may affect the ability to maintain fetal β-cell mass resulting in an increased risk of type 2 diabetes in adulthood.


Lycopene attenuates diabetes-associated cognitive decline in rats.
Diabetes-induced learning and memory impairment, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involve direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of lycopene, a potent anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. Cognitive functions were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 1.8 fold in the cerebral cortex of diabetic rats. There was about 2 fold and 2.2 fold rise in thiobarbituric acid-reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Non-protein thiol levels and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Total nitric oxide levels in cerebral cortex and hippocampus was increased by 2.4 fold and 2 fold respectively. Serum tumor necrosis factor-alpha, an inflammatory marker, was found to increase by 8 fold in diabetic rats. Chronic treatment with lycopene (1, 2 and 4 mg/kg; p.o.) significantly and dose dependently attenuated cognitive deficit, increased acetylcholinesterase activity, oxidative-nitrosative stress and inflammation in diabetic rats. The results emphasize the involvement of oxidative-nitrosative stress and peripheral inflammation in the development of cognitive impairment in diabetic animals and point towards the therapeutic potential of lycopene in diabetes-induced learning and memory impairment.


Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus.
The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact. We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies. The assay had a specificity of 100% (95% CI 98·9-100; 339 of 339 controls tested negative) and sensitivity of 95·9% (89·8-98·9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47·6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12·0% (95% CI 6·1-20·4; 11 of 92) with symptoms at the time other household members had EVD, and 2·6% (1·2-4·7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level. This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions. Wellcome Trust ERAES Programme, Save the Children.


Non-prefabricated nanocrystal mesoporous TiO2-based photoanodes tuned by a layer-by-layer and rapid thermal process.
We describe a flexible and competent solution for fabrication of non-prefabricated nanocrystal mesoporous TiO2-based photoanodes whose thicknesses are tunable from several hundreds of nanometers up to 12.4 microm. The combination of rapid thermal process and layer-by-layer spin-coating is successfully used to manipulate the structure and morphology of non-prefabricated nanocrystal mesoporous TiO2 films. The photovoltaic performances of mesoporous TiO2-based dye-sensitized solar cells depended on the thickness and the annealing temperature of mesoporous photoanodes. We systematically investigated and noted that the non-prefabricated nanocrystal mesoporous TiO2 films approximately 6.3 microm thick annealed at 500 degrees C displayed better features in the short-circuit current density and overall conversion efficiency of mesoporous TiO2-based dye-sensitized solar cells.


Acanthocephala of marine fishes off Fiji Islands, with descriptions of Filisoma longcementglandatus n. sp., Neorhadinorhynchus macrospinosus n. sp. (Cavisomidae), and gravid females of Rhadinorhynchus johnstoni (Rhadinorhynchidae); and keys to species of the genera Filisoma and Neorhadinorhynchus.
A parasitological collection from marine fishes off the Fiji Islands yielded 5 species of acanthocephalans from 4 species of fish as follows: Filisoma longcementglandatus n. sp. from scat Scatophagus argus; Neorhadinorhynchus macrospinosus n. sp. from vermiculated rabbit fish Siganus vermicularis; Neorhadinorhynchus nudum (Harada, 1938) Yamaguti, 1939 (Cavisomidae) from mackerel tuna Euthynnus affinis; Rhadinorhynchus johnstoni Golvan, 1969 (Rhadinorhynchidae) from E. affinis; and Neoechinorhynchus agilis (Rudolphi, 1819) Van Cleave, 1916 (Neoechinorhynchidae) from striped mullet Mugil cephalus. All are new locality records and, except for N. agilis, new host records. Filisoma longcementglandatus is distinguished from all other species of the genus by its very long cement glands and size and armature of its proboscis. Neorhadinorhynchus macrospinosus has distinctly larger proboscis hooks than all other members of the genus. Keys to species of the genera Filisoma and Neorhadinorhynchus are included. Gravid females of the inadequately described R. johnstoni are described for the first time. Taxonomic notes on the other acanthocephalan species are also included.