78 FR 75511 - Special Conditions: Bombardier Inc., Models BD-500-1A10 and BD-500-1A11 Series Airplanes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

... Design Features The C-series airplanes will incorporate the following novel or unusual design features: A.... Conclusion This action affects only certain novel or unusual design features on two model series of airplanes... Inc., Models BD-500-1A10 and BD- 500-1A11 Series Airplanes; Electronic Flight Control System: Control...

Addition of dexmedetomidine to bupivacaine in supraclavicular brachial plexus block.

PubMed

Aksu, Recep; Bicer, Cihangir

2017-06-26

Research is ongoing to determine the lowest dose of local anesthetics in brachial plexus block that provides adequate anesthesia and postoperative analgesia and reduces complications related to local anesthetics. Patients 18-65 years of age who underwent upper limb surgery and who received ultrasound-guided supraclavicular brachial plexus block at the Erciyes University Faculty of Medicine Hospital between February 2014 and January 2015 were included in the study (n=50). Supraclavicular brachial plexus blocks were performed on Group B cases by adding 30 ml 0.33% bupivacaine and on Group BD cases by adding 15 ml 0.33% bupivacaine and 1 µg / kg dexmedetomidine. Block success was evaluated by the onset and block duration of motor and sensory block and the duration of analgesia. The block success of Group B and Group BD was 92.6% and 89.3%, respectively (P = 1.000). Onset time of sensory block, degree of sensory block, duration of sensory block, onset time of motor block, degree of motor block and duration of motor block were similar in both groups in the intergroup comparison (P > 0.05). Duration of analgesia and the operative conditions of groups were similar (P > 0.05). In the implementation of ultrasound-guided supraclavicular brachial plexus block, block success, sensory and motor block and analgesia duration were similar for patients anaesthetized with 30 ml of bupivacaine in comparison with dexmedetomidine+bupivacaine (when the bupivacaine dose was reduced by 50% by the addition of the adjuvant).

The Effect of Human Impact on Batrachochytrium dendrobatidis prevalence in Taricha torosa

NASA Astrophysics Data System (ADS)

Deng, V.; Macario, E.; Tumey, C.

2014-12-01

Batrachochytrium dendrobatidis (Bd) is emerging as a major cause of the amphibian extinction. As amphibians serve an important role as indicator species in their ecosystem and play a vital role in the food chain, Bd will not only affect the amphibian population but also the health of the environment. Bd is an aquatic fungus that blocks the porous skin of amphibians which interrupts electrolyte, gas and water transfer. This imbalances the electrolyte system which causes cells and organs to malfunction, therefore killing the amphibian. While frogs are more common for Bd, it is not often found in newts. However, Dr. Vance Vredenburg recently found an outbreak of Bd in Taricha torosa in Marin Headlands, California. This location was used in the research as the sample site with most human impact and was expected to have the highest prevalence according to the proposed hypothesis that more human impact will correspond with a higher prevalence of Bd. Decreasing the level of human impact, Fairfield Osborn Preserve and Galbreath Preserve were picked as the other sample sites. After the samples went through qPCR, all of them came back negative for Bd. These results did not support the hypothesis, however, it contributed data to explaining the dynamics of Bd when combined with Dr. Vance Vredenburg's data from 2 months earlier. Within the two months, there was a huge difference in the prevalence of Bd as it dropped from 88% to 0%. This shows that Taricha torosa does in fact get Bd. However, it is rarely detected because Bd is fast-acting and has high mortality rates. Therefore, it is least likely for current nonspecific surveys to swab the newts during a short but lethal Bd outbreak.

Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating

PubMed Central

Cottone, Pietro; Wang, Xiaofan; Park, Jin Won; Valenza, Marta; Blasio, Angelo; Kwak, Jina; Iyer, Malliga R; Steardo, Luca; Rice, Kenner C; Hayashi, Teruo; Sabino, Valentina

2012-01-01

Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24 h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1 h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder. PMID:22713906

Dexmedetomidine decreases the required amount of bupivacaine for ultrasound-guided transversus abdominis plane block in pediatrics patients: a randomized study.

PubMed

Raof, Rehab Abdel; El Metainy, Shahira Ahmed; Alia, Doaa Abou; Wahab, Moataza Abdel

2017-02-01

The effect of dexmedetomidine on the potency of bupivacaine for transversus abdominis plane (TAP) block in pediatric patients has not been investigated. The primary objective of this study was to assess the effectiveness of dexmedetomidine to decrease the concentration of bupivacaine needed for analgesia for ultrasound-guided TAP block in a pediatric patient undergoing hernia repair or hydrocelectomy. This is a randomized, double-blind, up-down, dose-finding study. Operating room. Sixty American Society of Anesthesiologists I and II patients aged 1-4 years scheduled for elective unilateral herniorrhaphy or hydrocelectomy. Patients were randomly assigned to 1 of the 2 groups: group B (0.125% bupivacaine, 1mL/kg) TAP block or group BD (0.125% bupivacaine plus 2μg/kg dexmedetomidine, 1mL/kg) TAP block. The response of each child was observed for 60 seconds after skin incision and evaluated as 'unsuccessful' when skin incision caused a change in hemodynamic parameters (heart rate and mean blood pressure) 20% more than the preincision values. If the response was determined to be unsuccessful, the concentration of bupivacaine administrated to the next patient was increased by 0.02%. If it was successful, the concentration of bupivacaine administrated to the next patient was decreased by 0.02%. The minimum local anesthetic concentration of bupivacaine was 0.0839% (0.0137) in the B group and 0.0550% (0.0169) in the BD group. The difference was statistically significant (t=7.165, P=.0001). The total postoperative analgesic dosage of morphine was significantly higher in the B group (0.17±0.04 mg/kg) than the BD group (0.11±0.02 mg/kg, P=.001). The addition of 2μg/kg of dexmedetomidine reduced the minimum local anesthetic concentration of bupivacaine used for a TAP block and improved postoperative analgesia in children undergoing surgery for inguinal hernia repair or hydrocelectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Using theatre to address mental illness stigma: a knowledge translation study in bipolar disorder.

PubMed

Michalak, Erin E; Livingston, James D; Maxwell, Victoria; Hole, Rachelle; Hawke, Lisa D; Parikh, Sagar V

2014-01-01

Reduction of the stigma of mental illness is an international priority; arts- and contact-based approaches represent a promising mode of intervention. This project was designed to explore the impact of a one-woman theatrical performance on attitudes towards bipolar disorder (BD) on people with BD and healthcare providers. A playwright and actress who lives with BD developed a stage performance - 'That's Just Crazy Talk' - targeting stigmatizing attitudes towards BD. Prospective, longitudinal and sequential mixed methods were used to assess the impact of the performance on people with BD (n = 80) and healthcare providers (n = 84). Qualitative interviews were conducted with 33 participants (14 people with BD and 19 healthcare providers). Quantitatively, healthcare providers showed significantly improved attitudes immediately post-performance, but this change was not maintained over time; people with BD showed little quantitative change. Qualitatively, both people with BD and BD healthcare providers showed enduring and broadly positive changes. A theatrical presentation designed to reduce stigma produced immediate impact on healthcare providers quantitatively and significant qualitative impact on people with BD and healthcare providers. Additionally, the utility of using mixed-method approaches in mental health research was demonstrated.

Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician's perspective.

PubMed

Fornaro, Michele; Kardash, Lubna; Novello, Stefano; Fusco, Andrea; Anastasia, Annalisa; De Berardis, Domenico; Perna, Giampaolo; Carta, Mauro Giovanni

2018-03-01

Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings

PubMed Central

Li, Yifu; Xiong, Yunyi; Zhang, Huanxi; Li, Jun; Wang, Dong; Chen, Wenfang; Yuan, Xiaopeng; Su, Qiao; Li, Wenwen; Huang, Huiting; Bi, Zirong; Liu, Longshan; Wang, Changxi

2017-01-01

This study aimed to investigate the protective effects of EGb761, a Ginkgo Biloba extract, against brain death-induced kidney injury. Sixty male Sprague Dawley rats were randomly divided into six groups: sham, brain-death (BD), BD + EGb b48h (48 hours before BD), BD + EGb 2 h (2 hours after BD), BD + EGb 1 h, and BD + EGb 0.5 h. Six hours after BD, serum sample and kidney tissues were collected for analyses. The levels of blood urea nitrogen (BUN) and serum creatinine significantly elevated in the BD group than in sham group. In all the EGb761-treated BD animals except for the BD + Gb 2 h group, the levels of BUN and serum creatinine significantly reduced (all P < 0.01). EGb761 attenuated tubular injury and lowered the histological score. In addition, the longer duration of drug treatment was, the better protective efficacy could be observed. EGb761 significantly reduced IL-1β, IL-6, TNF-α, MCP-1, IP-10 mRNA expression and macrophage infiltration in the kidney. EGb761 treatment at 48 hour before brain death significantly attenuate the levels of p-JNK-MAPK, p-p38-MAPK, and p-STAT3 proteins (all P < 0.05, compared to BD group). In summary, our data showed that EGb761 treatment protected donor kidney from BD-induced damages by blocking SAPK and JAK-STAT signalings. Early administration of EGb761 can provide better protective efficacy. PMID:28332628

Novel synthetic analogues of avian β-defensin-12: the role of charge, hydrophobicity, and disulfide bridges in biological functions.

PubMed

Yang, Ming; Zhang, Chunye; Zhang, Michael Z; Zhang, Shuping

2017-02-23

Avian β-defensins (AvBD) possess broad-spectrum antimicrobial, LPS neutralizing and chemotactic properties. AvBD-12 is a chemoattractant for avian immune cells and mammalian dendritic cells (JAWSII) - a unique feature that is relevant to the applications of AvBDs as chemotherapeutic agents in mammalian hosts. To identify the structural components essential to various biological functions, we have designed and evaluated seven AvBD analogues. In the first group of analogues, the three conserved disulfide bridges were eliminated by replacing cysteines with alanine and serine residues, peptide hydrophobicity and charge were increased by changing negatively charged amino acid residues to hydrophobic (AvBD-12A1) or positively charged residues (AvBD-12A2 and AvBD-12A3). All three analogues in this group showed improved antimicrobial activity, though AvBD-12A3, with a net positive charge of +9, hydrophobicity of 40% and a predicted CCR2 binding domain, was the most potent antimicrobial peptide. AvBD-12A3 also retained more than 50% of wild type chemotactic activity. In the second group of analogues (AvBD-12A4 to AvBD-12A6), one to three disulfide bridges were removed via substitution of cysteines with isosteric amino acids. Their antimicrobial activity was compromised and chemotactic activity abolished. The third type of analogue was a hybrid that had the backbone of AvBD-12 and positively charged amino acid residues AvBD-6. The antimicrobial and chemotactic activities of the hybrid resembled that of AvBD-6 and AvBD-12, respectively. While the net positive charge and charge distribution have a dominating effect on the antimicrobial potency of AvBDs, the three conserved disulfide bridges are essential to the chemotactic property and the maximum antimicrobial activity. Analogue AvBD-12A3 with a high net positive charge, a moderate degree of hydrophobicity and a CCR2-binding domain can serve as a template for the design of novel antimicrobial peptides with chemotactic property and salt resistance.

The user experiences and clinical outcomes of an online personal health record to support self-management of bipolar disorder: A pretest-posttest pilot study.

PubMed

van den Heuvel, Silvio C G H; Meije, Daniëlle; Regeer, Eline J; Sinnema, Henny; Riemersma, Rixt F; Kupka, Ralph W

2018-06-03

Self-management comprises knowledge, behavior, activities and resources providing people with bipolar disorder (BD) control over fluctuating mood and activity-patterns. The 'Self-management and Dialogue in Bipolar Disorder' project entailed the tailoring of an online personal health record (PHR) originally designed for the chronically ill to monitor condition and share information with their clinician to people with BD (PHR-BD). The aim of this study was to evaluate the feasibility, utility and user-experiences of participants with BD, relatives, and healthcare professionals who worked with the PHR-BD. Post-test online closed- and open ended questionnaires were used to collect information on utility, and user-experiences with PHR-BD. A pre-posttest design to evaluate clinical effects on quality of life, empowerment, symptom reduction, changes in mood and activity, and illness burden and severity at baseline and at 12-months follow-up. Sixty-six participants with BD logged in at baseline. At study endpoint thirty-nine participants with BD, eleven professionals and one family caregiver filled out the evaluations. No significant differences in the clinical outcomes from baseline were found. Qualitative evaluations showed a frequent utility of the mood chart modules, improved communication between clinician and participant with BD and, increased insight in influencing factors of mood fluctuations. Small convenience sample, no controls. The option to alternate the interface from a prospective to a retrospective mood chart , and integration with the personal crisis plan was considered to be of added value in self-managing BD. The findings of this study will guide the future implementation of the PHR-BD. Copyright © 2018 Elsevier B.V. All rights reserved.

Finding topological center of a geographic space via road network

NASA Astrophysics Data System (ADS)

Gao, Liang; Miao, Yanan; Qin, Yuhao; Zhao, Xiaomei; Gao, Zi-You

2015-02-01

Previous studies show that the center of a geographic space is of great importance in urban and regional studies, including study of population distribution, urban growth modeling, and scaling properties of urban systems, etc. But how to well define and how to efficiently extract the center of a geographic space are still largely unknown. Recently, Jiang et al. have presented a definition of topological center by their block detection (BD) algorithm. Despite the fact that they first introduced the definition and discovered the 'true center', in human minds, their algorithm left several redundancies in its traversal process. Here, we propose an alternative road-cycle detection (RCD) algorithm to find the topological center, which extracts the outmost road-cycle recursively. To foster the application of the topological center in related research fields, we first reproduce the BD algorithm in Python (pyBD), then implement the RCD algorithm in two ways: the ArcPy implementation (arcRCD) and the Python implementation (pyRCD). After the experiments on twenty-four typical road networks, we find that the results of our RCD algorithm are consistent with those of Jiang's BD algorithm. We also find that the RCD algorithm is at least seven times more efficient than the BD algorithm on all the ten typical road networks.

78 FR 67291 - Special Conditions: Bombardier Inc., Models BD-500-1A10 and BD-500-1A11 Series Airplanes; Design...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... have a novel or unusual design feature associated with an electronic flight control system that... because of a novel or unusual design feature, special conditions are prescribed under the provisions of... same or similar novel or unusual design feature, the special conditions would also apply to the other...

Experimental Analysis and Computational Modeling of Network States and Drug Responses in the PI3K/Akt/mTOR Network

DTIC Science & Technology

2010-09-01

Fixation was in 2% formaldehyde, followed by permeabilization in 100% methanol at -20 C. Blocking and incubation with primary/secondary antibodies ...was performed in Odyssey blocking buffer (LICOR). Primary antibodies were obtained from Cell Signaling, BD Biosciences, and Santa Cruz...Biotechnology, and Alexa fluor 488-, 555-, or 647-conjugated secondary antibodies were obtained from Invitrogen. Data were collected using an Applied Precision

Investigation of relationship between 2,3-butanediol toxicity and production during growth of Paenibacillus polymyxa.

PubMed

Okonkwo, Christopher Chukwudi; Ujor, Victor; Ezeji, Thaddeus Chukwuemeka

2017-01-25

Understanding the capacity of Paenibacillus polymyxa DSM 365 to tolerate increasing concentrations of 2,3-butanediol (2,3-BD) is critical to engineering a 2,3-BD-overproducing strain. Hence, we investigated the response of P. polymyxa to high 2,3-BD concentrations. In fed-batch cultures (6-L bioreactor) 2,3-BD was accumulated to a maximum concentration of 47g/L despite the presence of residual 13g/L glucose in the medium. Concomitantly, accumulation of acetoin, the precursor of 2,3-BD increased after maximum 2,3-BD concentration was reached, suggesting that 2,3-BD was reconverted to acetoin after the concentration tolerance threshold of 2,3-BD was exceeded. Cultures of P. polymyxa were then challenged with levo-2,3-BD (20, 40 and 60g/L) at 0h in a glucose medium, and a concentration dependent growth inhibition response to levo-2,3-BD was observed. The growth of P. polymyxa was completely inhibited by 60g/L levo-2,3-BD. Furthermore, P. polymyxa was challenged with incremental 2,3-BD concentrations (20, 40 and 60g/L at 12, 24 and 36h, respectively) to mimic 2,3-BD accumulation during fermentation. Interestingly, 2,3-BD was reconverted to acetoin when its concentration reached 60g/L, possibly to alleviate 2,3-BD toxicity. Collectively, our findings indicate that 2,3-BD-mediated toxicity is a major metabolic impediment to 2,3-BD overproduction, thus, making it an important metabolic engineering target towards rational design of a 2,3-BD-overproducing strain. Copyright © 2016 Elsevier B.V. All rights reserved.

Human beta-defensin 3 inhibits cell wall biosynthesis in Staphylococci.

PubMed

Sass, Vera; Schneider, Tanja; Wilmes, Miriam; Körner, Christian; Tossi, Alessandro; Novikova, Natalia; Shamova, Olga; Sahl, Hans-Georg

2010-06-01

Human beta-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against a broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas antimicrobial host defense peptides are assumed to act by permeabilizing cell membranes, the transcriptional response pattern of hBD3-treated staphylococcal cells resembled that of vancomycin-treated cells (V. Sass, U. Pag, A. Tossi, G. Bierbaum, and H. G. Sahl, Int. J. Med. Microbiol. 298:619-633, 2008) and suggested that inhibition of cell wall biosynthesis is a major component of the killing process. hBD3-treated cells, inspected by transmission electron microscopy, showed localized protrusions of cytoplasmic contents, and analysis of the intracellular pool of nucleotide-activated cell wall precursors demonstrated accumulation of the final soluble precursor, UDP-MurNAc-pentapeptide. Accumulation is typically induced by antibiotics that inhibit membrane-bound steps of cell wall biosynthesis and also demonstrates that hBD3 does not impair the biosynthetic capacity of cells and does not cause gross leakage of small cytoplasmic compounds. In in vitro assays of individual membrane-associated cell wall biosynthesis reactions (MraY, MurG, FemX, and penicillin-binding protein 2 [PBP2]), hBD3 inhibited those enzymes which use the bactoprenol-bound cell wall building block lipid II as a substrate; quantitative analysis suggested that hBD3 may stoichiometrically bind to lipid II. We report that binding of hBD3 to defined, lipid II-rich sites of cell wall biosynthesis may lead to perturbation of the biosynthesis machinery, resulting in localized lesions in the cell wall as demonstrated by electron microscopy. The lesions may then allow for osmotic rupture of cells when defensins are tested under low-salt conditions.

Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci▿

PubMed Central

Sass, Vera; Schneider, Tanja; Wilmes, Miriam; Körner, Christian; Tossi, Alessandro; Novikova, Natalia; Shamova, Olga; Sahl, Hans-Georg

2010-01-01

Human β-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against a broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas antimicrobial host defense peptides are assumed to act by permeabilizing cell membranes, the transcriptional response pattern of hBD3-treated staphylococcal cells resembled that of vancomycin-treated cells (V. Sass, U. Pag, A. Tossi, G. Bierbaum, and H. G. Sahl, Int. J. Med. Microbiol. 298:619-633, 2008) and suggested that inhibition of cell wall biosynthesis is a major component of the killing process. hBD3-treated cells, inspected by transmission electron microscopy, showed localized protrusions of cytoplasmic contents, and analysis of the intracellular pool of nucleotide-activated cell wall precursors demonstrated accumulation of the final soluble precursor, UDP-MurNAc-pentapeptide. Accumulation is typically induced by antibiotics that inhibit membrane-bound steps of cell wall biosynthesis and also demonstrates that hBD3 does not impair the biosynthetic capacity of cells and does not cause gross leakage of small cytoplasmic compounds. In in vitro assays of individual membrane-associated cell wall biosynthesis reactions (MraY, MurG, FemX, and penicillin-binding protein 2 [PBP2]), hBD3 inhibited those enzymes which use the bactoprenol-bound cell wall building block lipid II as a substrate; quantitative analysis suggested that hBD3 may stoichiometrically bind to lipid II. We report that binding of hBD3 to defined, lipid II-rich sites of cell wall biosynthesis may lead to perturbation of the biosynthesis machinery, resulting in localized lesions in the cell wall as demonstrated by electron microscopy. The lesions may then allow for osmotic rupture of cells when defensins are tested under low-salt conditions. PMID:20385753

Behçet Disease serum is immunoreactive to neurofilament medium which share common epitopes to bacterial HSP-65, a putative trigger.

PubMed

Lule, S; Colpak, A I; Balci-Peynircioglu, B; Gursoy-Ozdemir, Y; Peker, S; Kalyoncu, U; Can, A; Tekin, N; Demiralp, D; Dalkara, T

2017-11-01

Autoimmune and dysimmune inflammatory mechanisms on a genetically susceptible background are implicated in the etiology of Behçet's Disease (BD). Heat-shock protein-65 (HSP-65) derived from Streptococcus sanguinis was proposed as a triggering factor based on its homology with human HSP-60. However, none of the autoantigens identified so far in sera from BD share common epitopes with bacterial HSP-65 or has a high prevalence. Here, we report that sera from BD patients are immunoreactive against filamentous neuronal processes in the mouse brain, retina and scrotal skin in great majority of patients. By using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and peptide mass fingerprinting, Western blotting and peptide blocking experiments, we have identified neurofilament medium (NF-M) as the probable antigen for the serologic response observed. Clustal Omega analyses detected significant structural homology between the human NF-M and bacterial HSP-65 corresponding to amino acids 111-126, 213-232 and 304-363 of mycobacterial HSP-65, which were previously identified to induce proliferation of lymphocytes obtained from BD patients. We also found that sera immunoreactive against NF-M cross-reacted with bacterial HSP-65. These findings suggest that NF-M may be involved in autoimmunity in BD due to its molecular mimicry with bacterial HSP-65. Copyright © 2017 Elsevier Ltd. All rights reserved.

77 FR 69568 - Special Conditions: Bombardier Aerospace, Model BD-500-1A10 and BD-500-1A11 Airplanes; Sidestick...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... sidestick controller instead of a conventional control column and wheel. This kind of controller is designed... conventional control column and wheel. This kind of controller is designed for one-hand operation. Discussion... controller instead of a conventional wheel or control stick. This kind of controller is designed to be...

78 FR 11089 - Special Conditions: Bombardier Aerospace, Model BD-500-1A10 and BD-500-1A11 Airplanes; Sidestick...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

... controller instead of a conventional control column and wheel. This kind of controller is designed for only... following novel or unusual design feature: A sidestick controller instead of a conventional control column... conventional wheel or control stick. This kind of controller is designed to be operated using only one hand...

Human β-Defensin 3 [corrected] Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid.

PubMed

Semple, Fiona; MacPherson, Heather; Webb, Sheila; Kilanowski, Fiona; Lettice, Laura; McGlasson, Sarah L; Wheeler, Ann P; Chen, Valerie; Millhauser, Glenn L; Melrose, Lauren; Davidson, Donald J; Dorin, Julia R

2015-12-01

Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans.

Human β-D-3 Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid

PubMed Central

Semple, Fiona; MacPherson, Heather; Webb, Sheila; Kilanowski, Fiona; Lettice, Laura; McGlasson, Sarah L.; Wheeler, Ann P.; Chen, Valerie; Millhauser, Glenn L.; Melrose, Lauren; Davidson, Donald J.; Dorin, Julia R.

2015-01-01

Human β-defensin 3 (hBD3) is a cationic host defence peptide and is part of the innate immune response. HBD3 is present on a highly copy number variable block of six β-defensin genes, and increased copy number is associated with the autoimmune disease psoriasis. It is not known how this increase influences disease development, but psoriasis is a T cell-mediated disease and activation of the innate immune system is required for the initial trigger that leads to the amplification stage. We investigated the effect of hBD3 on the response of primary macrophages to various TLR agonists. HBD3 exacerbated the production of type I Interferon-β in response to the viral ligand mimic polyinosinic:polycytidylic acid (polyI:C) in both human and mouse primary cells, although production of the chemokine CXCL10 was suppressed. Compared to polyI:C alone, mice injected with both hBD3 peptide and polyI:C also showed an enhanced increase in Interferon-β. Mice expressing a transgene encoding hBD3 had elevated basal levels of Interferon-β, and challenge with polyI:C further increased this response. HBD3 peptide increased uptake of polyI:C by macrophages, however the cellular response and localisation of polyI:C in cells treated contemporaneously with hBD3 or cationic liposome differed. Immunohistochemistry showed that hBD3 and polyI:C do not co-localise, but in the presence of hBD3 less polyI:C localises to the early endosome. Using bone marrow derived macrophages from knockout mice we demonstrate that hBD3 suppresses the polyI:C-induced TLR3 response mediated by TICAM1 (TRIF), while exacerbating the cytoplasmic response through MDA5 (IFIH1) and MAVS (IPS1/CARDIF). Thus, hBD3, a highly copy number variable gene in human, influences cellular responses to the viral mimic polyI:C implying that copy number may have a significant phenotypic effect on the response to viral infection and development of autoimmunity in humans. PMID:26646717

Between-race differences in the effects of breast density information and information about new imaging technology on breast-health decision-making.

PubMed

Manning, Mark; Purrington, Kristen; Penner, Louis; Duric, Neb; Albrecht, Terrance L

2016-06-01

Some US states have mandated that women be informed when they have dense breasts; however, little is known about how general knowledge about breast density (BD) affects related health decision-making. We examined the effects of BD information and imaging technology information on 138 African-American (AA) and European-American (EA) women's intentions to discuss breast cancer screening with their physicians. Women were randomly assigned to receive BD information and/or imaging technology information via 2 by 2 factorial design, and completed planned behavior measures (e.g., attitudes, intentions) related to BC screening. Attitudes mediated the effects of BD information, and the mediation was stronger for AA women compared to EA women. Effects were more robust for BD information compared to imaging technology information. Results of moderator analyses revealed suppressor effects of injunctive norms that were moderated by imaging technology information. Information about BD favorably influences women's intentions to engage in relevant breast health behaviors. Stronger attitude mediated-effects for AA women suggest greater scrutiny of BD information. Since BD information may influence women's intentions to discuss BC screening, strategies to effectively present BD information to AA women should be investigated given the likelihood of their increased scrutiny of BD information. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of obsessive-compulsive disorder comorbidity on the sociodemographic and clinical features of patients with bipolar disorder.

PubMed

Koyuncu, Ahmet; Tükel, Raşit; Ozyildirim, Ilker; Meteris, Handan; Yazici, Olcay

2010-01-01

In this study, our aim is to determine the prevalence rates of obsessive-compulsive disorder (OCD) comorbidity and to assess the impact of OCD comorbidity on the sociodemographic and clinical features of patients with bipolar disorder (BD). Using the Yale-Brown Obsessive Compulsive Scale Symptom Checklist and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-IV/Clinical Version on bipolar patients, 2 groups, BD with OCD comorbidity (BD-OCD) and BD without OCD comorbidity, were formed. These groups were compared for sociodemographic and clinical variables. Of 214 patients with BD, 21.9% of them had obsession and/or compulsion symptoms and 16.3% had symptoms at the OCD level. Although there was no statistically significant difference between the frequency of comorbid OCD in BD-I (22/185, 11.9%) and BD-II (3/13, 23.1%) patients, but OCD was found to be significantly high in BD not otherwise specified (10/16, %62.5) patients than BD-I (P < .001) and BD-II (P = .03). Six patients (17.1%) of the BD-OCD group had chronic course (the presence of at least 1 mood disorder episode with a duration of longer than 2 years), whereas the BD without OCD group had none, which was statistically significant. There were no statistically significant differences between BD-OCD and BD without OCD groups in terms of age, sex, education, marital status, polarity, age of BD onset, presence of psychotic symptoms, presence of rapid cycling, history of suicide attempts, first episode type, and predominant episode type. Main limitation of our study was the assessment of some variables based on retrospective recall. Our study confirms the high comorbidity rates for OCD in BD patients. Future studies that examine the relationship between OCD and BD using a longitudinal design may be helpful in improving our understanding of the mechanism of this association. 2010 Elsevier Inc. All rights reserved.

Engineering cofactor flexibility enhanced 2,3-butanediol production in Escherichia coli.

PubMed

Liang, Keming; Shen, Claire R

2017-12-01

Enzymatic reduction of acetoin into 2,3-butanediol (2,3-BD) typically requires the reduced nicotinamide adenine dinucleotide (NADH) or its phosphate form (NADPH) as electron donor. Efficiency of 2,3-BD biosynthesis, therefore, is heavily influenced by the enzyme specificity and the cofactor availability which varies dynamically. This work describes the engineering of cofactor flexibility for 2,3-BD production by simultaneous overexpression of an NADH-dependent 2,3-BD dehydrogenase from Klebsiella pneumoniae (KpBudC) and an NADPH-specific 2,3-BD dehydrogenase from Clostridium beijerinckii (CbAdh). Co-expression of KpBudC and CbAdh not only enabled condition versatility for 2,3-BD synthesis via flexible utilization of cofactors, but also improved production stereo-specificity of 2,3-BD without accumulation of acetoin. With optimization of medium and fermentation condition, the co-expression strain produced 92 g/L of 2,3-BD in 56 h with 90% stereo-purity for (R,R)-isoform and 85% of maximum theoretical yield. Incorporating cofactor flexibility into the design principle should benefit production of bio-based chemical involving redox reactions.

78 FR 75287 - Special Conditions: Bombardier Inc., Models BD-500-1A10 and BD-500-1A11 Series Airplanes; Flight...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... appropriate safety standards for the C-series airplanes because of a novel or unusual design feature, special... Features The C-series airplanes will incorporate the following novel or unusual design features: new... Series Airplanes; Flight Envelope Protection: General Limiting Requirements AGENCY: Federal Aviation...

The plastidial 2-C-methyl-D-erythritol 4-phosphate pathway provides the isoprenyl moiety for protein geranylgeranylation in tobacco BY-2 cells.

PubMed

Gerber, Esther; Hemmerlin, Andréa; Hartmann, Michael; Heintz, Dimitri; Hartmann, Marie-Andrée; Mutterer, Jérôme; Rodríguez-Concepción, Manuel; Boronat, Albert; Van Dorsselaer, Alain; Rohmer, Michel; Crowell, Dring N; Bach, Thomas J

2009-01-01

Protein farnesylation and geranylgeranylation are important posttranslational modifications in eukaryotic cells. We visualized in transformed Nicotiana tabacum Bright Yellow-2 (BY-2) cells the geranylgeranylation and plasma membrane localization of GFP-BD-CVIL, which consists of green fluorescent protein (GFP) fused to the C-terminal polybasic domain (BD) and CVIL isoprenylation motif from the Oryza sativa calmodulin, CaM61. Treatment with fosmidomycin (Fos) or oxoclomazone (OC), inhibitors of the plastidial 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, caused mislocalization of the protein to the nucleus, whereas treatment with mevinolin, an inhibitor of the cytosolic mevalonate pathway, did not. The nuclear localization of GFP-BD-CVIL in the presence of MEP pathway inhibitors was completely reversed by all-trans-geranylgeraniol (GGol). Furthermore, 1-deoxy-d-xylulose (DX) reversed the effects of OC, but not Fos, consistent with the hypothesis that OC blocks 1-deoxy-d-xylulose 5-phosphate synthesis, whereas Fos inhibits its conversion to 2-C-methyl-d-erythritol 4-phosphate. By contrast, GGol and DX did not rescue the nuclear mislocalization of GFP-BD-CVIL in the presence of a protein geranylgeranyltransferase type 1 inhibitor. Thus, the MEP pathway has an essential role in geranylgeranyl diphosphate (GGPP) biosynthesis and protein geranylgeranylation in BY-2 cells. GFP-BD-CVIL is a versatile tool for identifying pharmaceuticals and herbicides that interfere either with GGPP biosynthesis or with protein geranylgeranylation.

Klotho dysfunction: A pathway linking the aging process to bipolar disorder?

PubMed

Barbosa, Izabela Guimarães; Rocha, Natalia Pessoa; Alpak, Gokay; Vieira, Erica Leandro Marciano; Huguet, Rodrigo Barreto; Rocha, Fabio Lopes; de Oliveira Diniz, Breno Satler; Teixeira, Antonio Lucio

2017-12-01

Although accelerated aging profile has been described in bipolar disorder (BD), the biology linking BD and aging is still largely unknown. Reduced levels and/or activity of a protein named Klotho is associated with decreased life span, premature aging and occurrence of age-related diseases. Therefore, this study was designed to evaluate plasma levels of Klotho in BD patients and controls. Forty patients with type 1 BD and 30 controls were enrolled in this study. After clinical evaluation, peripheral blood samples were drawn and plasma levels of Klotho were measured using enzyme-linked immunosorbent assay. Patients with BD and controls presented similar age and sex distribution. The mean ± SD length of illness was 24.00 ± 12.75 years. BD patients presented increased frequency of clinical comorbidities in comparison with controls, mainly arterial hypertension, diabetes mellitus, and hypothyroidism. Both patients with BD in remission and in mania exhibited increased plasma levels of Klotho in comparison with controls. There was no significant difference between patients in mania and patients in remission regarding the levels of Klotho. Klotho-related pathway is altered in BD. Contrary to our original hypothesis, our sample of patients with BD presented increased plasma levels of Klotho in comparison with controls. Elevated levels of Klotho in long-term BD patients may be associated with the disorder progression. Further studies are needed to better understand the role of Klotho in BD and other mood disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Between-race differences in the effects of breast density information and information about new imaging technology on breast-health decision-making

PubMed Central

Manning, Mark; Purrington, Kristen; Penner, Louis; Duric, Neb; Albrecht, Terrance L.

2016-01-01

Objectives Some US states have mandated that women be informed when they have dense breasts; however, little is known about how general knowledge about breast density (BD) affects related health decision-making. We examined the effects of BD information and imaging technology information on 138 African–American (AA) and European–American (EA) women’s intentions to discuss breast cancer screening with their physicians. Methods Women were randomly assigned to receive BD information and/or imaging technology information via 2 by 2 factorial design, and completed planned behavior measures (e.g., attitudes, intentions) related to BC screening. Results Attitudes mediated the effects of BD information, and the mediation was stronger for AA women compared to EA women. Effects were more robust for BD information compared to imaging technology information. Results of moderator analyses revealed suppressor effects of injunctive norms that were moderated by imaging technology information. Conclusion Information about BD favorably influences women’s intentions to engage in relevant breast health behaviors. Stronger attitude mediated-effects for AA women suggest greater scrutiny of BD information. Practice implications Since BD information may influence women’s intentions to discuss BC screening, strategies to effectively present BD information to AA women should be investigated given the likelihood of their increased scrutiny of BD information. PMID:26847421

New optical architecture for holographic data storage system compatible with Blu-ray Disc™ system

NASA Astrophysics Data System (ADS)

Shimada, Ken-ichi; Ide, Tatsuro; Shimano, Takeshi; Anderson, Ken; Curtis, Kevin

2014-02-01

A new optical architecture for holographic data storage system which is compatible with a Blu-ray Disc™ (BD) system is proposed. In the architecture, both signal and reference beams pass through a single objective lens with numerical aperture (NA) 0.85 for realizing angularly multiplexed recording. The geometry of the architecture brings a high affinity with an optical architecture in the BD system because the objective lens can be placed parallel to a holographic medium. Through the comparison of experimental results with theory, the validity of the optical architecture was verified and demonstrated that the conventional objective lens motion technique in the BD system is available for angularly multiplexed recording. The test-bed composed of a blue laser system and an objective lens of the NA 0.85 was designed. The feasibility of its compatibility with BD is examined through the designed test-bed.

BdCESA7, BdCESA8, and BdPMT utility promoter constructs for targeted expression to secondary cell-wall-forming cells of grasses

DOE PAGES

Petrik, Deborah L.; Cass, Cynthia L.; Padmakshan, Dharshana; ...

2016-02-04

Utility vectors with promoters that confer desired spatial and temporal expression patterns are useful tools for studying gene and cellular function and for industrial applications. To target the expression of DNA sequences of interest to cells forming plant secondary cell walls, which generate most of the vegetative biomass, upstream regulatory sequences of the Brachypodium distachyon lignin biosynthetic gene BdPMT and the cellulose synthase genes BdCESA7 and BdCESA8 were isolated and cloned into binary vectors designed for Agrobacterium-mediated transformation of monocots. Expression patterns were assessed using the β-glucuronidase gene GUSPlus and X-glucuronide staining. All three promoters showed strong expression levels inmore » stem tissue at the base of internodes where cell wall deposition is most active, in both vascular bundle xylem vessels and tracheids, and in interfascicular tissues, with expression less pronounced in developmentally older tissues. In leaves, BdCESA7 and BdCESA8 promoter-driven expression was strongest in leaf veins, leaf margins, and trichomes; relatively weaker and patchy expression was observed in the epidermis. BdPMT promoter-driven expression was similar to the BdCESA promoters expression patterns, including strong expression in trichomes. The intensity and extent of GUS staining varied considerably between transgenic lines, suggesting that positional effects influenced promoter activity. Introducing the BdPMT and BdCESA8 Open Reading Frames into BdPMT and BdCESA8 utility promoter binary vectors, respectively, and transforming those constructs into Brachypodium pmt and cesa8 loss-of-function mutants resulted in rescue of the corresponding mutant phenotypes. This work therefore validates the functionality of these utility promoter binary vectors for use in Brachypodium and likely other grass species. Lastly, the identification, in Bdcesa8-1 T-DNA mutant stems, of an 80% reduction in crystalline cellulose levels confirms that the BdCESA8 gene is a secondary-cell-wall-forming cellulose synthase.« less

Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis Vulgaris

PubMed Central

Tyring, Stephen; Bukhalo, Michael; Alonso-Llamazares, Javier; Olesen, Martin; Lowson, David; Yamauchi, Paul

2016-01-01

Objective: To evaluate the efficacy of fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD). Design: Patients were randomized (100:101:101) to receive Cal/BD foam, Cal foam, or BD foam once daily for four weeks. Setting: Twenty-eight United States centers. Participants: 302 patients (≥18 years) with Psoriasis vulgaris (plaque Psoriasis; ≥mild disease severity by physicians global assessment). Measurements: Treatment success of the body (“clear”/”almost clear” from baseline moderate/severe disease; “clear” from baseline mild disease). Involved scalp treatment success was an additional endpoint. Results: Most patients (76%) had moderate Psoriasis of the body (66% for scalp). At Week 4, 45 percent of Cal/BD foam patients achieved treatment success, significantly more than Cal foam (14.9%; OR 4.34 [95%CI 2.16,8.72] P<0.001) or BD foam (30.7%; 1.81 [1.00,3.26] P=0.047). Fifty-three percent of Cal/BD foam patients achieved treatment success of the scalp, significantly greater than Cal foam (35.6%; 1.91 [1.09,3.35] P=0.021), but not BD foam (47.5%; 1.24 [0.71,2.16] P=0.45). Mean modified Psoriasis area and severity index (population baseline 7.6) improved in all groups, with statistically significant differences in Week 4 Cal/BD foam score (2.37) versus Cal foam (4.39; mean difference -2.03 [-2.63][-1.43] P<0.001) and BD foam (3.37; -1.19 [-1.80][-0.59] P<0.001). Four (Cal/BD), 10 (Cal), and 8 (BD) adverse drug reactions were reported. Conclusion: Cal/BD foam was significantly more effective than Cal foam and BD foam in providing treatment success at Week 4 and effective on involved scalp. Trial registration: NCT01536938. PMID:27313822

BdCESA7, BdCESA8, and BdPMT utility promoter constructs for targeted expression to secondary cell-wall-forming cells of grasses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrik, Deborah L.; Cass, Cynthia L.; Padmakshan, Dharshana

Utility vectors with promoters that confer desired spatial and temporal expression patterns are useful tools for studying gene and cellular function and for industrial applications. To target the expression of DNA sequences of interest to cells forming plant secondary cell walls, which generate most of the vegetative biomass, upstream regulatory sequences of the Brachypodium distachyon lignin biosynthetic gene BdPMT and the cellulose synthase genes BdCESA7 and BdCESA8 were isolated and cloned into binary vectors designed for Agrobacterium-mediated transformation of monocots. Expression patterns were assessed using the β-glucuronidase gene GUSPlus and X-glucuronide staining. All three promoters showed strong expression levels inmore » stem tissue at the base of internodes where cell wall deposition is most active, in both vascular bundle xylem vessels and tracheids, and in interfascicular tissues, with expression less pronounced in developmentally older tissues. In leaves, BdCESA7 and BdCESA8 promoter-driven expression was strongest in leaf veins, leaf margins, and trichomes; relatively weaker and patchy expression was observed in the epidermis. BdPMT promoter-driven expression was similar to the BdCESA promoters expression patterns, including strong expression in trichomes. The intensity and extent of GUS staining varied considerably between transgenic lines, suggesting that positional effects influenced promoter activity. Introducing the BdPMT and BdCESA8 Open Reading Frames into BdPMT and BdCESA8 utility promoter binary vectors, respectively, and transforming those constructs into Brachypodium pmt and cesa8 loss-of-function mutants resulted in rescue of the corresponding mutant phenotypes. This work therefore validates the functionality of these utility promoter binary vectors for use in Brachypodium and likely other grass species. Lastly, the identification, in Bdcesa8-1 T-DNA mutant stems, of an 80% reduction in crystalline cellulose levels confirms that the BdCESA8 gene is a secondary-cell-wall-forming cellulose synthase.« less

Parametric modulation of neural activity by emotion in youth with bipolar disorder, youth with severe mood dysregulation, and healthy volunteers.

PubMed

Thomas, Laura A; Brotman, Melissa A; Muhrer, Eli J; Rosen, Brooke H; Bones, Brian L; Reynolds, Richard C; Deveney, Christen M; Pine, Daniel S; Leibenluft, Ellen

2012-12-01

CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum.

Parametric modulation of neural activity by emotion in youth with bipolar disorder, severe mood dysregulation, and healthy subjects

PubMed Central

Thomas, Laura A.; Brotman, Melissa A.; Muhrer, Eli M.; Rosen, Brooke H.; Bones, Brian L.; Reynolds, Richard C.; Deveney, Christen; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Context Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show amygdala dysfunction during face emotion processing. However, studies have not compared such patients to each other and to comparison subjects in neural responsiveness to subtle changes in face emotion; the ability to process such changes is important for social cognition. We employed a novel parametrically designed faces paradigm. Objective Using a parametrically morphed emotional faces task, we compared activation in the amygdala and across the brain in BD, SMD, and healthy volunteers (HV). Design Case-control study. Setting Government research institute. Participants 57 youths (19 BD, 15 SMD, 23 HV). Main Outcome Measure Blood oxygenated level dependent (BOLD) data. Neutral faces were morphed with angry and happy faces in 25% intervals; static face stimuli appeared for 3000ms. Subjects performed hostility or non-emotional facial feature (i.e., nose width) ratings. Slope of BOLD activity was calculated across neutral-to-angry (N→A) and neutral-to-happy (N→H) face stimuli. Results In HV, but not BD or SMD, there was a positive association between left amygdala activity and anger on the face. In the N→H whole brain analysis, BD and SMD modulated parietal, temporal, and medial-frontal areas differently from each other and from HV; with increasing facial-happiness, SMD increased, while BD decreased, activity in parietal, temporal, and frontal regions. Conclusions Youth with BD or SMD differ from HV in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, BD and SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of face emotion processing in BD and SMD, suggesting these distinct clinical presentations may reflect differing pathologies along a mood disorders spectrum. PMID:23026912

Cognitive flexibility and performance in children and adolescents with threshold and sub-threshold bipolar disorder.

PubMed

Dickstein, Daniel P; Axelson, David; Weissman, Alexandra B; Yen, Shirley; Hunt, Jeffrey I; Goldstein, Benjamin I; Goldstein, Tina R; Liao, Fangzi; Gill, Mary Kay; Hower, Heather; Frazier, Thomas W; Diler, Rasim S; Youngstrom, Eric A; Fristad, Mary A; Arnold, L Eugene; Findling, Robert L; Horwitz, Sarah M; Kowatch, Robert A; Ryan, Neal D; Strober, Michael; Birmaher, Boris; Keller, Martin B

2016-06-01

Greater understanding of cognitive function in children and adolescents with bipolar disorder (BD) is of critical importance to improve our ability to design targeted treatments to help with real-world impairment, including academic performance. We sought to evaluate cognitive performance among children with either BD type I, II, or "not otherwise specified" (NOS) participating in multi-site Course and Outcome of Bipolar Youth study compared to typically developing controls (TDC) without psychopathology. In particular, we sought to test the hypothesis that BD-I and BD-II youths with full threshold episodes of mania or hypomania would have cognitive deficits, including in reversal learning, vs. those BD-NOS participants with sub-threshold episodes and TDCs. N = 175 participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of the simple reversal stage of the CANTAB intra-/extra-dimensional shift task showed that aggregated BD-I/II participants required significantly more trials to complete the task than either BD-NOS participants with sub-syndromal manic/hypomanic symptoms or than TDCs. BD participants across sub-types had impairments in sustained attention and information processing for emotionally valenced words. Our results align with prior findings showing that BD-I/II youths with distinct episodes have specific alterations in reversal learning. More broadly, our study suggests that further work is necessary to see the interaction between neurocognitive performance and longitudinal illness course. Additional work is required to identify the neural underpinnings of these differences as targets for potential novel treatments, such as cognitive remediation.

Brachypodium distachyon BdPP2CA6 Interacts with BdPYLs and BdSnRK2 and Positively Regulates Salt Tolerance in Transgenic Arabidopsis

PubMed Central

Zhang, Fan; Wei, Qiuhui; Shi, Jiaochun; Jin, Xia; He, Yuan; Zhang, Yang; Luo, Qingchen; Wang, Yuesheng; Chang, Junli; Yang, Guangxiao; He, Guangyuan

2017-01-01

The phytohormone abscisic acid (ABA) is essential in plant responding to biotic and abiotic stresses. Although ABA signaling model is well established in Arabidopsis, ABA receptor PYL family and clade A PP2C subfamily are not yet characterized in monocot model plant Brachypodium distachyon. In this study, we identified 12 PYLs and 8 clade A PP2Cs from B. distachyon genome and successfully cloned 12 PYLs and 7 clade A PP2Cs. Bioinformatic and expression analyses showed that most of the identified genes respond to several signal molecules and abiotic stresses. Protein–protein interaction analysis revealed that many BdPYLs and BdPP2CAs participate in the classic ABA-PYL-PP2C-SnRK2 signaling pathway. A clade A PP2C, designated BdPP2CA6, interacted with BdPYL11 in the absence of ABA and localized in nucleus. Most clade A PP2C members from Arabidopsis showed negatively regulation in ABA signaling pathway, whereas BdPP2CA6-overexpression transgenic Arabidopsis showed ABA hypersensitive phenotype, resulting in enhanced stomatal closure and salinity tolerance. Our results indicate that BdPP2CA6 positively regulates ABA and stress signal pathway in transgenic Arabidopsis plant seedlings. PMID:28293246

Cognitive Remediation: Potential Novel Brain-Based Treatment for Bipolar Disorder in Children and Adolescents

PubMed Central

Dickstein, Daniel P.; Cushman, Grace K.; Kim, Kerri L.; Weissman, Alexandra B.; Wegbreit, Ezra

2015-01-01

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data shows that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD. PMID:26135596

Vocabulary Is an Appropriate Measure of Premorbid Intelligence in a Sample with Heterogeneous Educational Level in Brazil

PubMed Central

de Oliveira, Maira Okada; Nitrini, Ricardo; Yassuda, Mônica Sanches; Brucki, Sonia Maria Dozzi

2014-01-01

Crystallized intelligence refers to one's knowledge base and can be measured by vocabulary tests. Fluid intelligence is related to nonverbal aspects of intelligence, depends very little on previously acquired knowledge, and can be measured by tests such as Block Design (BD) and Raven Colored Matrices (RCM). Premorbid intelligence quotient (IQ) refers to one's intellectual ability level previous to the onset of disorders like mild cognitive impairment (MCI) and Alzheimer's disease (AD) and it is important to estimate disease severity. The objective was to compare performance in tests that measure crystallized and fluid intelligence in healthy subjects and patients with amnestic MCI (aMCI) and AD. One hundred forty-four participants (aMCI (n = 38), AD (n = 45), and healthy controls (n = 61)) were submitted to neuropsychological tests (WAIS-III vocabulary, BD, and RCM). There were significant among groups, except for vocabulary, indicating a relative stability of crystallized intelligence in the continuum from normal to pathological cognitive decline. Vocabulary seems to be stable during the progression of the disease and useful as a measure of premorbid intelligence, that is, to estimate previous function in relation to the level of education and, as a collateral measure of cognition in people with low education. PMID:24803737

Vocabulary is an appropriate measure of premorbid intelligence in a sample with heterogeneous educational level in Brazil.

PubMed

de Oliveira, Maira Okada; Nitrini, Ricardo; Yassuda, Mônica Sanches; Brucki, Sonia Maria Dozzi

2014-01-01

Crystallized intelligence refers to one's knowledge base and can be measured by vocabulary tests. Fluid intelligence is related to nonverbal aspects of intelligence, depends very little on previously acquired knowledge, and can be measured by tests such as Block Design (BD) and Raven Colored Matrices (RCM). Premorbid intelligence quotient (IQ) refers to one's intellectual ability level previous to the onset of disorders like mild cognitive impairment (MCI) and Alzheimer's disease (AD) and it is important to estimate disease severity. The objective was to compare performance in tests that measure crystallized and fluid intelligence in healthy subjects and patients with amnestic MCI (aMCI) and AD. One hundred forty-four participants (aMCI (n = 38), AD (n = 45), and healthy controls (n = 61)) were submitted to neuropsychological tests (WAIS-III vocabulary, BD, and RCM). There were significant among groups, except for vocabulary, indicating a relative stability of crystallized intelligence in the continuum from normal to pathological cognitive decline. Vocabulary seems to be stable during the progression of the disease and useful as a measure of premorbid intelligence, that is, to estimate previous function in relation to the level of education and, as a collateral measure of cognition in people with low education.

78 FR 67321 - Special Conditions: Bombardier Aerospace Inc., Models BD-500-1A10 and BD-500-1A11 Series...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

..., blended double- bubble design, sized for nominal 5-abreast seating. Each airplane's powerplant consists of... part 25, which are level landing attitudes. For airplanes with traditional braking systems, the current...

Comparison of eigensolvers for symmetric band matrices.

PubMed

Moldaschl, Michael; Gansterer, Wilfried N

2014-09-15

We compare different algorithms for computing eigenvalues and eigenvectors of a symmetric band matrix across a wide range of synthetic test problems. Of particular interest is a comparison of state-of-the-art tridiagonalization-based methods as implemented in Lapack or Plasma on the one hand, and the block divide-and-conquer (BD&C) algorithm as well as the block twisted factorization (BTF) method on the other hand. The BD&C algorithm does not require tridiagonalization of the original band matrix at all, and the current version of the BTF method tridiagonalizes the original band matrix only for computing the eigenvalues. Avoiding the tridiagonalization process sidesteps the cost of backtransformation of the eigenvectors. Beyond that, we discovered another disadvantage of the backtransformation process for band matrices: In several scenarios, a lot of gradual underflow is observed in the (optional) accumulation of the transformation matrix and in the (obligatory) backtransformation step. According to the IEEE 754 standard for floating-point arithmetic, this implies many operations with subnormal (denormalized) numbers, which causes severe slowdowns compared to the other algorithms without backtransformation of the eigenvectors. We illustrate that in these cases the performance of existing methods from Lapack and Plasma reaches a competitive level only if subnormal numbers are disabled (and thus the IEEE standard is violated). Overall, our performance studies illustrate that if the problem size is large enough relative to the bandwidth, BD&C tends to achieve the highest performance of all methods if the spectrum to be computed is clustered. For test problems with well separated eigenvalues, the BTF method tends to become the fastest algorithm with growing problem size.

Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder.

PubMed

MacPherson, Heather A; Ruggieri, Amanda L; Christensen, Rachel E; Schettini, Elana; Kim, Kerri L; Thomas, Sarah A; Dickstein, Daniel P

2018-08-01

Childhood-onset bipolar disorder (BD) is a serious condition that affects the patient and family. While research has documented familial dysfunction in individuals with BD, no studies have compared developmental differences in family functioning in youths with BD vs. adults with prospectively verified childhood-onset BD. The Family Assessment Device (FAD) was used to examine family functioning in participants with childhood-onset BD (n = 116) vs. healthy controls (HCs) (n = 108), ages 7-30 years, using multivariate analysis of covariance and multiple linear regression. Participants with BD had significantly worse family functioning in all domains (problem solving, communication, roles, affective responsiveness, affective involvement, behavior control, general functioning) compared to HCs, regardless of age, IQ, and socioeconomic status. Post-hoc analyses suggested no influence for mood state, global functioning, comorbidity, and most medications, despite youths with BD presenting with greater severity in these areas than adults. Post-hoc tests eliminating participants taking lithium (n = 17) showed a significant diagnosis-by-age interaction: youths with BD had worse family problem solving and communication relative to HCs. Limitations include the cross-sectional design, clinical differences in youths vs. adults with BD, ambiguity in FAD instructions, participant-only report of family functioning, and lack of data on psychosocial treatments. Familial dysfunction is common in childhood-onset BD and endures into adulthood. Early identification and treatment of both individual and family impairments is crucial. Further investigation into multi-level, family-based mechanisms underlying childhood-onset BD may clarify the role family factors play in the disorder, and offer avenues for the development of novel, family-focused therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Projecting the Global Distribution of the Emerging Amphibian Fungal Pathogen, Batrachochytrium dendrobatidis, Based on IPCC Climate Futures.

PubMed

Xie, Gisselle Yang; Olson, Deanna H; Blaustein, Andrew R

2016-01-01

Projected changes in climate conditions are emerging as significant risk factors to numerous species, affecting habitat conditions and community interactions. Projections suggest species range shifts in response to climate change modifying environmental suitability and is supported by observational evidence. Both pathogens and their hosts can shift ranges with climate change. We consider how climate change may influence the distribution of the emerging infectious amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), a pathogen associated with worldwide amphibian population losses. Using an expanded global Bd database and a novel modeling approach, we examined a broad set of climate metrics to model the Bd-climate niche globally and regionally, then project how climate change may influence Bd distributions. Previous research showed that Bd distribution is dependent on climatic variables, in particular temperature. We trained a machine-learning model (random forest) with the most comprehensive global compilation of Bd sampling records (~5,000 site-level records, mid-2014 summary), including 13 climatic variables. We projected future Bd environmental suitability under IPCC scenarios. The learning model was trained with combined worldwide data (non-region specific) and also separately per region (region-specific). One goal of our study was to estimate of how Bd spatial risks may change under climate change based on the best available data. Our models supported differences in Bd-climate relationships among geographic regions. We projected that Bd ranges will shift into higher latitudes and altitudes due to increased environmental suitability in those regions under predicted climate change. Specifically, our model showed a broad expansion of areas environmentally suitable for establishment of Bd on amphibian hosts in the temperate zones of the Northern Hemisphere. Our projections are useful for the development of monitoring designs in these areas, especially for sensitive species and those vulnerable to multiple threats.

Neighboring block based disparity vector derivation for multiview compatible 3D-AVC

NASA Astrophysics Data System (ADS)

Kang, Jewon; Chen, Ying; Zhang, Li; Zhao, Xin; Karczewicz, Marta

2013-09-01

3D-AVC being developed under Joint Collaborative Team on 3D Video Coding (JCT-3V) significantly outperforms the Multiview Video Coding plus Depth (MVC+D) which simultaneously encodes texture views and depth views with the multiview extension of H.264/AVC (MVC). However, when the 3D-AVC is configured to support multiview compatibility in which texture views are decoded without depth information, the coding performance becomes significantly degraded. The reason is that advanced coding tools incorporated into the 3D-AVC do not perform well due to the lack of a disparity vector converted from the depth information. In this paper, we propose a disparity vector derivation method utilizing only the information of texture views. Motion information of neighboring blocks is used to determine a disparity vector for a macroblock, so that the derived disparity vector is efficiently used for the coding tools in 3D-AVC. The proposed method significantly improves a coding gain of the 3D-AVC in the multiview compatible mode about 20% BD-rate saving in the coded views and 26% BD-rate saving in the synthesized views on average.

Association of Lipid Peroxidation and Brain-Derived Neurotrophic Factor with Executive Function in Adolescent Bipolar Disorder.

PubMed

Newton, Dwight F; Naiberg, Melanie R; Andreazza, Ana C; Scola, Gustavo; Dickstein, Daniel P; Goldstein, Benjamin I

2017-02-01

Executive dysfunction is common and impairing in youth bipolar disorder (BD), and oxidative stress (OS) and brain-derived neurotrophic factor (BDNF) have been implicated in executive deficits of adult BD. This study aimed to determine the association between OS and executive dysfunction in BD adolescents and the influence of BDNF on this association. Serum levels of lipid hydroperoxides (LPH) and 4-hydroxy-2-nonenal (4-HNE) and BDNF levels were measured in 29 BD and 25 control adolescents. The intra-extra-dimensional (IED) set-shifting task assessed executive function. Lower IED scores indicated better performance. High and low BDNF subgroups were defined by median split. IED Z-scores were impaired in the BD group compared to controls, whereas biomarker levels were not significantly different between groups. LPH-BDNF correlations were significantly different between BD and controls (Z = 2.046, p = 0.041). In high BDNF BD subjects, LPH was significantly positively correlated with IED completed stage trials (ρ = 0.755, p = 0.001) and pre-extra-dimensional shift errors (ρ = 0.588, p = 0.017). Correlations were opposite in controls. In a linear model, LPH, BDNF, and the LPH-BDNF interaction each significantly explained variance of IED total trials (adjusted) (model r 2  = 0.187, F = 2.811, p = 0.035). There is a negative association between LPH and executive function in BD adolescents, which may be modulated by BDNF. LPH and BDNF may be useful biomarkers of executive function in BD. These findings highlight the importance of examining multiple peripheral biomarkers in relation to cognitive functions in BD adolescents. Future studies should explore these factors in longitudinal designs to determine the directionality of observed associations.

Binge drinking among Brazilian students: a gradient of association with socioeconomic status in five geo-economics regions

PubMed Central

Sanchez, Zila M; Locatelli, Danilo P; Noto, Ana R; Martins, Silvia S

2013-01-01

Aims 1) To describe the characteristics of binge drinking (BD) among high school students in Brazil and 2) the association of BD with students' socioeconomic status (SES) in the five different Brazilian macroregions. Design A national multistage probabilistic sample of high school students. Setting Students were drawn from 789 public and private schools in each of the 27 Brazilian state capitals. Participants 17,297 high school students, aged 14 to 18 years. Measurement Self-report data about BD practices and SES were analyzed via weighted logistic regressions and a funnel plot. Findings Almost 32% of the students engaged in BD in the past-year. Being in the highest SES stratum doubled the risk of BD among students in all five Brazilian macroregions. There was a gradient in the association between past-year BD and socioeconomic status: as SES increased; the chance of having recently engaged in BD also increased. In the Brazilian capitals as a whole, boys versus girls (aOR = 1.40 [95% CI 1.26 to 1.58]), being older (aOR = 1.47 [95% CI 1.40 to 1.55] per each additional year of age) and those attending private schools versus public schools (aOR = 1.39 [95% CI 1.18 to 1.62]), were at greater risk for BD. Conclusions Contrary to what is observed in developed countries, students living in Brazilian capitals may be at an increased risk of BD when they belong to the highest socioeconomic status. Adolescents growing up in other emerging economies might have the same association between high SES and BD. PMID:22771006

Antimicrobial Barrier of an in vitro Oral Epithelial Model

PubMed Central

Kimball, Janet R.; Nittayananta, Wipawee; Klausner, Mitchell; Chung, Whasun O.; Dale, Beverly A.

2008-01-01

Objective Oral epithelia function as a microbial barrier and are actively involved in recognizing and responding to bacteria. Our goal was to examine a tissue engineered model of buccal epithelium for its response to oral bacteria and proinflammatory cytokines and compare the tissue responses with those of a submerged monolayer cell culture. Design The tissue model was characterized for keratin and β-defensin expression. Altered expression of β-defensins was evaluated by RT-PCR after exposure of the apical surface to oral bacteria and after exposure to TNF-α in the medium. These were compared to the response in traditional submerged oral epithelial cell culture. Results The buccal model showed expression of differentiation specific keratin 13, hBD1 and hBD3 in the upper half of the tissue; hBD2 was not detected. hBD1 mRNA was constitutively expressed, while hBD2 mRNA increased 2-fold after exposure of the apical surface to three oral bacteria tested and hBD3 mRNA increased in response to the non-pathogenic bacteria tested. In contrast, hBD2 mRNA increased 3–600 fold in response to bacteria in submerged cell culture. HBD2 mRNA increased over 100 fold in response to TNF-α in the tissue model and 50 fold in submerged cell culture. Thus, the tissue model is capable of upregulating hBD2, however, the minimal response to bacteria suggests that the tissue has an effective antimicrobial barrier due to its morphology, differentiation, and defensin expression. Conclusions The oral mucosal model is differentiated, expresses hBD1 and hBD3, and has an intact surface with a functional antimicrobial barrier. PMID:16815238

Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus.

PubMed

Crack, L R; Jones, L; Malavige, G N; Patel, V; Ogg, G S

2012-07-01

There is mounting evidence that antimicrobial peptides have an important role in cutaneous defence, but the expression of these antimicrobial peptides in atopic eczema (AE) is still unclear. There are several families of antimicrobial peptides, including cathelicidins and human β-defensins. Patients with AE are more susceptible to severe cutaneous viral infections, including varicella zoster virus (VZV). To characterize the functional activity of the antimicrobial peptides LL-37 (human cathelicidin) and human β-defensin (hBD)-2 keratinocytes were infected with VZV, in a skin-infection model. Flow-cytometry analysis was used to investigate LL-37 expression in normal human keratinocytes, and quantitative PCR was used to determine viral loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL-37 and hBD-2. LL-37 expression was present in keratinocytes, and both exogenous LL-37 and hBD-2 significantly reduced VZV load in infected keratinocytes and B cells. Specific antibodies blocked the antiviral action exhibited by these antimicrobial peptides. Pre-incubation of VZV with LL-37, but not hBD-2, further reduced VZV load. Both LL-37 and hBD-2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE. © The Author(s). CED © 2012 British Association of Dermatologists.

Hypovirulence of the Phytopathogenic Fungus Botryosphaeria dothidea: Association with a Coinfecting Chrysovirus and a Partitivirus

PubMed Central

Wang, LiPing; Jiang, JingJing; Wang, YanFen; Hong, Ni; Zhang, Fangpeng

2014-01-01

ABSTRACT Botryosphaeria dothidea is an important pathogenic fungus causing fruit rot, leaf and stem ring spots and dieback, stem canker, stem death or stool mortality, and decline of pear trees. Seven double-stranded RNAs (dsRNAs; dsRNAs 1 to 7 with sizes of 3,654, 2,773, 2,597, 2,574, 1,823, 1,623, and 511 bp, respectively) were identified in an isolate of B. dothidea exhibiting attenuated growth and virulence and a sectoring phenotype. Characterization of the dsRNAs revealed that they belong to two dsRNA mycoviruses. The four largest dsRNAs (dsRNAs 1 to 4) are the genomic components of a novel member of the family Chrysoviridae (tentatively designated Botryosphaeria dothidea chrysovirus 1 [BdCV1]), a view supported by the morphology of the virions and phylogenetic analysis of the putative RNA-dependent RNA polymerases (RdRps). Two other dsRNAs (dsRNAs 5 and 6) are the genomic components of a novel member of the family Partitiviridae (tentatively designated Botryosphaeria dothidea partitivirus 1 [BdPV1]), which is placed in a clade distinct from other established partitivirus genera on the basis of the phylogenetic analysis of its RdRp. The smallest dsRNA, dsRNA7, seems to be a noncoding satellite RNA of BdPV1 on the basis of the conservation of its terminal sequences in BdPV1 genomic segments and its cosegregation with BdPV1 after horizontal transmission. This is the first report of a chrysovirus and a partitivirus infecting B. dothidea and of a chrysovirus associated with the hypovirulence of a phytopathogenic fungus. IMPORTANCE Our studies identified and characterized two novel mycoviruses, Botryosphaeria dothidea chrysovirus 1 (BdCV1) and Botryosphaeria dothidea partitivirus 1 (BdPV1), associated with the hypovirulence of an important fungus pathogenic to fruit trees. This is the first report of a chrysovirus and a partitivirus infecting B. dothidea and of a chrysovirus associated with the hypovirulence of a phytopathogenic fungus. BdCV1 appears to be a good candidate for the biological control of the serious disease induced by B. dothidea. Additionally, BdPV1 is placed in a clade distinct from the established genera. The BdCV1 capsid has two major structural proteins, and the capsid is distinct from that made up by a single polypeptide of the typical chrysoviruses. BdPV1 is the second partitivirus in which the putative capsid protein shares no significant identity with any mycovirus protein. A small accompanying dsRNA that is presumed to be a noncoding satellite RNA of BdPV1 is the first of its kind reported for a partitivirus. PMID:24760881

The role of ZA channel water-mediated interactions in the design of bromodomain-selective BET inhibitors.

PubMed

Bharatham, Nagakumar; Slavish, Peter J; Shadrick, William R; Young, Brandon M; Shelat, Anang A

2018-05-01

The Bromodomain and Extra-Terminal domain (BET) family of proteins are involved in the regulation of gene transcription, and their dysregulation is implicated in several diseases including cancer. BET proteins contain two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine residues and appear to have distinct biological roles. We compared several published co-crystal structures and found five positions near the substrate binding pocket that vary between BET bromodomains. One position located in the ZA loop has unique properties. In BRD2-4, this residue is glutamine in BD1 and lysine in BD2; in BRDT, this residue is arginine in BD1 and asparagine in BD2. Using molecular modeling, we identified differences in the water-mediated network at this position between bromodomains. Molecular dynamics simulations helped rationalize the observed bromodomain selectivity for exemplar BET inhibitors and a congeneric series of tetrahydroquinolines (THQ) that differed by a single heteroatom near the ZA channel. The 2-furan SJ830599, the most BD2-selective THQ analog, did not disrupt the water-mediated networks in either domain, but was electrostatically-repulsed by the specific arrangement of the W5 water dipole in BD1. Our work underscores the value of exploring water-mediated interactions to study ligand binding, and highlights the difficulty of optimizing polar interactions due to high desolvation penalties. Finally, we suggest further modifications to THQ-based BET inhibitors that would increase BD2-selectivity in BRD2-4, while minimizing affinity for one or both bromodomains of BRDT. Copyright © 2018 Elsevier Inc. All rights reserved.

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

PubMed Central

Zhao, Jing; Ha, Yonju; Liou, Gregory I.; Gonsalvez, Graydon B.; Smith, Sylvia B.; Bollinger, Kathryn E.

2014-01-01

Purpose. To evaluate the effects of the σ 1 receptor (σR1) agonist, (+)-pentazocine, on lipopolysaccharide (LPS)–induced inflammatory changes in retinal microglia cells. Methods. Retinal microglia cells were isolated from Sprague-Dawley rat pups. Cells were treated with LPS with or without (+)-pentazocine and with or without the σR1 antagonist BD1063. Morphologic changes were assayed. Cell viability was assessed by using MTT assay. Supernatant levels of tumor necrosis factor α (TNF-α), interleukin 10, (IL-10), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO) were determined. Reactive oxygen species (ROS) formation was assayed, and levels of mitogen-activated protein kinases (MAPKs) were analyzed by using Western blot. Results. The σR1 protein was expressed in retinal microglia. Incubation with LPS and/or (+)-pentazocine did not alter cell viability or σR1 protein levels. Incubation with LPS for 24 hours induced a marked change in microglial morphology and a significant increase in secreted levels of TNF-α, IL-10, MCP-1, and NO. Pretreatment with (+)-pentazocine inhibited the LPS-induced morphologic changes. Release of TNF-α, IL-10, MCP-1, and NO was reduced with (+)-pentazocine. Intracellular ROS formation was suppressed with (+)-pentazocine. Phosphorylation of extracellular signal–regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was reduced in the presence of (+)-pentazocine. The σR1 antagonist BD1063 blocked the (+)-pentazocine–mediated inhibition of LPS-induced morphologic changes. In addition, BD1063 treatment blocked (+)-pentazocine–mediated suppression of LPS-induced TNF-α, IL-10, MCP-1, NO, and intracellular ROS release. Conclusions. Treatment with (+)-pentazocine suppressed inflammatory responses of retinal microglia and inhibited LPS-induced activation of ERK/JNK MAPK. In neurodegenerative disease, (+)-pentazocine may exert neuroprotective effects through manipulation of microglia. PMID:24812552

78 FR 65233 - Special Conditions: Bombardier Inc., Models BD-500-1A10 and BD-500-1A11 Series Airplanes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... a novel or unusual design feature associated with aluminum-lithium fuselage construction that may... of the Bombardier C-series airplanes will be fabricated using aluminum-lithium construction. Structure fabricated from aluminum-lithium may provide different levels of protection from post-crash fuel...

Projecting the Global Distribution of the Emerging Amphibian Fungal Pathogen, Batrachochytrium dendrobatidis, Based on IPCC Climate Futures

PubMed Central

Olson, Deanna H.; Blaustein, Andrew R.

2016-01-01

Projected changes in climate conditions are emerging as significant risk factors to numerous species, affecting habitat conditions and community interactions. Projections suggest species range shifts in response to climate change modifying environmental suitability and is supported by observational evidence. Both pathogens and their hosts can shift ranges with climate change. We consider how climate change may influence the distribution of the emerging infectious amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), a pathogen associated with worldwide amphibian population losses. Using an expanded global Bd database and a novel modeling approach, we examined a broad set of climate metrics to model the Bd-climate niche globally and regionally, then project how climate change may influence Bd distributions. Previous research showed that Bd distribution is dependent on climatic variables, in particular temperature. We trained a machine-learning model (random forest) with the most comprehensive global compilation of Bd sampling records (~5,000 site-level records, mid-2014 summary), including 13 climatic variables. We projected future Bd environmental suitability under IPCC scenarios. The learning model was trained with combined worldwide data (non-region specific) and also separately per region (region-specific). One goal of our study was to estimate of how Bd spatial risks may change under climate change based on the best available data. Our models supported differences in Bd-climate relationships among geographic regions. We projected that Bd ranges will shift into higher latitudes and altitudes due to increased environmental suitability in those regions under predicted climate change. Specifically, our model showed a broad expansion of areas environmentally suitable for establishment of Bd on amphibian hosts in the temperate zones of the Northern Hemisphere. Our projections are useful for the development of monitoring designs in these areas, especially for sensitive species and those vulnerable to multiple threats. PMID:27513565

Federal Logistics Information System (FLIS) Procedures Manual. Volume 13. Change 1.

DTIC Science & Technology

1997-01-01

BD 06 TA 67 BD BD TU BD TU BD FBDA DF BD 06 TA 96 BD BD TU BD TU BD FBDD DF BD 06 TD 96 BD BD TU BD TU BD FBDE DF BD 06 SE 96 BD BD TU BD TU BD FBDG...XN TD FAZD DF AZ 06 TD 96 AZ AZ TU AZ TU TD FAZ7 DF AZ 22 TD 97 AZ AZ TU AZ TU TD FBDD DF BD 06 TD 96 BD BD TU BD TU TD FBD7 DF BD 22 TD 97 BD BD TU...48 TU TU FBDA DF BD 06 TA 96 BD BD TU BD TU TU FBDD DF BD 06 TD 96 BD BD TU BD TU TU FBDE DF BD 06 SE 96 BD BD TU BD TU TU FBDG DF BD 06 TG 96 BD BD TU

Retinal photography: A window into the cardiovascular-brain link in adolescent bipolar disorder.

PubMed

Naiberg, Melanie R; Hatch, Jessica K; Selkirk, Beth; Fiksenbaum, Lisa; Yang, Victor; Black, Sandra; Kertes, Peter J; Goldstein, Benjamin I

2017-08-15

The burden of cardiovascular disease in bipolar disorder (BD) exceeds what can be explained by traditional cardiovascular risk factors (CVRFs), lifestyle, and/or medications. Moreover, neurocognitive deficits are a core feature of BD, and are also related to CVRFs. We examined retinal vascular photography, a proxy for cerebral microvasculature, in relation to CVRFs, peripheral microvascular function, and neurocognition among BD adolescents. Subjects were 30 adolescents with BD and 32 healthy controls (HC). Retinal photography was conducted using a Topcon TRC 50 DX, Type IA camera, following pupil dilation. Retinal arteriolar and venular caliber was measured, from which the arterio-venular ratio (AVR) was computed. All measures were conducted masked to participant diagnosis. Peripheral arterial tonometry measured endothelial function. Neurocognition was assessed using the Cambridge Neuropsychological Tests Automated Battery. AVR was not significantly different between groups (Cohen's d=0.18, p=0.103). Higher diastolic blood pressure (BP) was associated with lower (worse) AVR in BD (r=-0.441, p=0.015) but not HC (r=-0.192, p=0.293). Similarly, in the BD group only, higher (better) endothelial function was associated with higher AVR (r=0.375, p=0.041). Hierarchical regression models confirmed that, independent of covariates, retinal vascular caliber was significantly associated with diastolic BP and endothelial function in BD. Within the BD group, mood scores were significantly negatively correlated with AVR (β=-0.451, p=0.044). This study's limitations include a small sample size, a cross-sectional study design, and a heterogeneous sample. Retinal photography may offer unique insights regarding the cardiovascular and neurocognitive burden of BD. Larger longitudinal studies are warranted. Copyright © 2017. Published by Elsevier B.V.

78 FR 76734 - Special Conditions: Bombardier Inc., Models BD-500-1A10 and BD-500-1A11 Series Airplanes; Seats...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... Series Airplanes; Seats With Non-Traditional, Large, Non- Metallic Panels AGENCY: Federal Aviation... airplanes will have a novel or unusual design feature associated with seats that include non-traditional, large, non-metallic panels that would affect survivability during a post-crash fire event. The...

Endoscopic ultrasound-guided biliary drainage using a newly designed metal stent with a thin delivery system: a preclinical study in phantom and porcine models.

PubMed

Minaga, Kosuke; Kitano, Masayuki; Itonaga, Masahiro; Imai, Hajime; Miyata, Takeshi; Yamao, Kentaro; Tamura, Takashi; Nuta, Junya; Warigaya, Kenji; Kudo, Masatoshi

2017-12-08

This study was designed to evaluate the feasibility and safety of a newly designed self-expandable metal stent for endoscopic ultrasound-guided biliary drainage (EUS-BD) when it was delivered via three different stent delivery systems: a 7.5Fr delivery catheter with a bullet-shaped tip (7.5Fr-bullet), a 7Fr catheter with a bullet-shaped tip (7Fr-bullet), or a 7Fr catheter with a tee-shaped tip (7Fr-tee). This experimental study utilized a porcine model of biliary dilatation involving ten pigs. In the animal study, technical feasibility and clinical outcomes of the stent when placed with each of the delivery systems were examined. In addition, a phantom model was used to measure the resistance of these delivery systems to advancement. Phantom experiments showed that, compared with 7Fr-bullet, 7Fr-tee had less resistance force to the advancement of the stent delivery system. EUS-BD was technically successful in all ten pigs. Fistulous tract dilation was necessary in 100% (2/2), 75% (3/4), and 0% (0/4) of the pigs that underwent EUS-BD using 7.5Fr-bullet, 7Fr-bullet, and 7Fr-tee, respectively. There were no procedure-related complications. Our newly designed metal stent may be feasible and safe for EUS-BD, particularly when delivered by 7Fr-tee, because it eliminates the need for fistulous tract dilation.

Opening the file drawer: Unexpected insights from a chytrid infection experiment.

PubMed

Byrne, Allison Q; Poorten, Thomas J; Voyles, Jamie; Willis, Craig K R; Rosenblum, Erica Bree

2018-01-01

Infection experiments are critical for understanding wildlife disease dynamics. Although infection experiments are typically designed to reduce complexity, disease outcomes still result from complex interactions between host, pathogen, and environmental factors. Cryptic variation across factors can lead to decreased repeatability of infection experiments within and between research groups and hinder research progress. Furthermore, studies with unexpected results are often relegated to the "file drawer" and potential insights gained from these experimental outcomes are lost. Here, we report unexpected results from an infection experiment studying the response of two differentially-susceptible but related frogs (American Bullfrog Rana catesbeiana and the Mountain yellow-legged frog Rana muscosa) to the amphibian-killing chytrid fungus (Batrachochytrium dendrobatidis, Bd). Despite well-documented differences in susceptibility between species, we found no evidence for antibody-mediated immune response and no Bd-related mortality in either species. Additionally, during the study, the sham-inoculated R. catesbeiana control group became unexpectedly Bd-positive. We used a custom genotyping assay to demonstrate that the aberrantly-infected R. catesbeiana carried a Bd genotype distinct from the inoculation genotype. Thus R. catesbeiana individuals were acquired with low-intensity infections that could not be detected with qPCR. In the Bd-inoculated R. catesbeiana treatment group, the inoculated genotype appeared to out-compete the cryptic infection. Thus, our results provide insight into Bd coinfection dynamics, a phenomenon that is increasingly relevant as different pathogen strains are moved around the globe. Our experiment highlights how unexpected experimental outcomes can serve as both cautionary tales and opportunities to explore unanswered research questions. We use our results as a case study to highlight common sources of anomalous results for infection experiments. We argue that understanding these factors will aid researchers in the design, execution, and interpretation of experiments to understand wildlife disease processes.

The implementation of high fermentative 2,3-butanediol production from xylose by simultaneous additions of yeast extract, Na2EDTA, and acetic acid.

PubMed

Wang, Xiao-Xiong; Hu, Hong-Ying; Liu, De-Hua; Song, Yuan-Quan

2016-01-25

The effective use of xylose may significantly enhance the feasibility of using lignocellulosic hydrolysate to produce 2,3-butanediol (2,3-BD). Previous difficulties in 2,3-BD production include that the high-concentration xylose cannot be converted completely and the fermentation rate is slow. This study investigated the effects of yeast extract, ethylenediaminetetraacetic acid disodium salt (Na2EDTA), and acetic acid on 2,3-BD production from xylose. The central composite design approach was used to optimize the concentrations of these components. It was found that simultaneous addition of yeast extract, Na2EDTA, and acetic acid could significantly improve 2,3-BD production. The optimal concentrations of yeast extract, Na2EDTA, and acetic acid were 35.2, 1.2, and 4.5 g/L, respectively. The 2,3-BD concentration in the optimized medium reached 39.7 g/L after 48 hours of shake flask fermentation, the highest value ever reported in such a short period. The xylose utilization ratio and the 2,3-BD concentration increased to 99.0% and 42.7 g/L, respectively, after 48 hours of stirred batch fermentation. Furthermore, the 2,3-BD yield was 0.475 g/g, 95.0% of the theoretical maximum value. As the major components of lignocellulosic hydrolysate are glucose, xylose, and acetic acid, the results of this study indicate the possibility of directly using the hydrolysate to effectively produce 2,3-BD. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison among methods of effective energy evaluation of corn silage for beef cattle.

PubMed

Wei, Ming; Chen, Zhiqiang; Wei, Shengjuan; Geng, Guangduo; Yan, Peishi

2018-06-01

This study was conducted to compare different methods on effective energy evaluation of corn silage for beef cattle. Twenty Wandong bulls (Chinese indigenous yellow cattle) with initial body weight of 281±15.6 kg, were assigned to 1 of 5 dietary treatments with 4 animals per treatment in a randomized complete block design. Five dietary treatments included group 1 with corn silage only diet, group 2 with corn silage-concentrate basal diet (BD) and 3 groups with 3 test diets, which were the BD partly substituted by corn silage at 10%, 30%, and 60%. The total collection digestion trial was conducted for 5 d for each block after a 10-d adaptation period, and then an open-circuit respiratory cage was used to measure the gas exchange of each animal in a consecutive 4-d period. The direct method-derived metabolizable energy and net energy of corn silage were 8.86 and 5.15 MJ/kg dry matter (DM), expressed as net energy requirement for maintenance and gain were 5.28 and 2.90 MJ/kg DM, respectively; the corresponding regression method-derived estimates were 8.96, 5.34, 5.37, and 2.98 MJ/kg DM, respectively. The direct method-derived estimates were not different (p>0.05) from those obtained using the regression method. Using substitution method, the nutrient apparent digestibility and effective energy values of corn silage varied with the increased corn silage substitution ratio (p<0.05). In addition, the corn silage estimates at the substitution ratio of 30% were similar to those estimated by direct and regression methods. In determining the energy value of corn silage using substitution method, there was a discrepancy between different substitution ratios, and the substitution ratio of 30% was more appropriate than 10% or 60% in the current study. The regression method based on multiple point substitution was more appropriate than single point substitution on energy evaluation of feedstuffs for beef cattle.

Biological monitoring to determine worker dose in a butadiene processing plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtold, W.E.; Hayes, R.B.

1995-12-01

Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to bettermore » assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.« less

Study of Interpolated Timing Recovery Phase-Locked Loop with Linearly Constrained Adaptive Prefilter for Higher-Density Optical Disc

NASA Astrophysics Data System (ADS)

Kajiwara, Yoshiyuki; Shiraishi, Junya; Kobayashi, Shoei; Yamagami, Tamotsu

2009-03-01

A digital phase-locked loop (PLL) with a linearly constrained adaptive filter (LCAF) has been studied for higher-linear-density optical discs. LCAF has been implemented before an interpolated timing recovery (ITR) PLL unit in order to improve the quality of phase error calculation by using an adaptively equalized partial response (PR) signal. Coefficient update of an asynchronous sampled adaptive FIR filter with a least-mean-square (LMS) algorithm has been constrained by a projection matrix in order to suppress the phase shift of the tap coefficients of the adaptive filter. We have developed projection matrices that are suitable for Blu-ray disc (BD) drive systems by numerical simulation. Results have shown the properties of the projection matrices. Then, we have designed the read channel system of the ITR PLL with an LCAF model on the FPGA board for experiments. Results have shown that the LCAF improves the tilt margins of 30 gigabytes (GB) recordable BD (BD-R) and 33 GB BD read-only memory (BD-ROM) with a sufficient LMS adaptation stability.

Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing R,R-2,3-Butanediol by Paenibacillus polymyxa ZJ-9.

PubMed

Cao, Can; Zhang, Li; Gao, Jian; Xu, Hong; Xue, Feng; Huang, Weiwei; Li, Yan

2017-06-01

R,R-2,3-butanediol (R,R-2,3-BD) was produced by Paenibacillus polymyxa ZJ-9, which was capable of utilizing inulin without previous hydrolysis. The Jerusalem artichoke pomace (JAP) derived from the conversion of Jerusalem artichoke powder into inulin extract, which was usually used for biorefinery by submerged fermentation (SMF), was utilized in solid state fermentation (SSF) to produce R,R-2,3-BD. In this study, the fermentation parameters of SSF were optimized and determined in flasks. A novel bioreactor was designed and assembled for the laboratory scale-up of SSF, with a maximum yield of R,R-2,3-BD (67.90 g/kg (JAP)). This result is a 36.3% improvement compared with the flasks. Based on the same bath of Jerusalem artichoke powder, the total output of R,R-2,3-BD increased by 38.8% for the SSF of JAP combined with the SMF of inulin extraction. Overall, the utilization of JAP for R,R-2,3-BD production was beneficial to the comprehensive utilization of Jerusalem artichoke tuber.

Configural and Featural Face Processing Influences on Emotion Recognition in Schizophrenia and Bipolar Disorder.

PubMed

Van Rheenen, Tamsyn E; Joshua, Nicole; Castle, David J; Rossell, Susan L

2017-03-01

Emotion recognition impairments have been demonstrated in schizophrenia (Sz), but are less consistent and lesser in magnitude in bipolar disorder (BD). This may be related to the extent to which different face processing strategies are engaged during emotion recognition in each of these disorders. We recently showed that Sz patients had impairments in the use of both featural and configural face processing strategies, whereas BD patients were impaired only in the use of the latter. Here we examine the influence that these impairments have on facial emotion recognition in these cohorts. Twenty-eight individuals with Sz, 28 individuals with BD, and 28 healthy controls completed a facial emotion labeling task with two conditions designed to separate the use of featural and configural face processing strategies; part-based and whole-face emotion recognition. Sz patients performed worse than controls on both conditions, and worse than BD patients on the whole-face condition. BD patients performed worse than controls on the whole-face condition only. Configural processing deficits appear to influence the recognition of facial emotions in BD, whereas both configural and featural processing abnormalities impair emotion recognition in Sz. This may explain discrepancies in the profiles of emotion recognition between the disorders. (JINS, 2017, 23, 287-291).

Identifying and describing patients' learning experiences towards self-management of bipolar disorders: a phenomenological study.

PubMed

Van den Heuvel, S C G H; Goossens, P J J; Terlouw, C; Van Achterberg, T; Schoonhoven, L

2015-12-01

Existing evidence suggest that patient education in promoting self-management strategies of bipolar disorder (BD) is effective. However, results across the full range of service users with BD vary. Learning experiences of service users look to be a crucial factor to take into account when designing, delivering, and evaluating effective interventions that promote self-management in chronic illness. What learning activities service users actually undertake themselves when self-managing BD that might explain varying success rates, and guide future self-management educational programmes has not been examined. Unlike previous studies that suggest that outcomes in self-management depend on individual learning activities, the current study found that learning to self-manage BD takes place in a social network that functions as a learning environment in which it is saved for service users to make mistakes and to learn from these mistakes. Especially, coping with the dormant fear of a recurrent episode and acknowledging the limitations of an individual approach are important factors that facilitate this learning process. Practitioners who provide patient education in order to promote self-management of BD should tailor future interventions that facilitate learning by reflecting on the own experiences of service users. Community psychiatric nurses should keep an open discussion with service users and caregivers, facilitate the use of a network, and re-label problems into learning situations where both play an active role in building mutual trust, thereby enhancing self-management of BD. Existing evidence suggest that self-management education of bipolar disorder (BD) is effective. However, why outcomes differ across the full range of service users has not been examined. This study describes learning experiences of service users in self-managing BD that provide a possible explanation for this varying effectiveness. We have conducted a phenomenological study via face-to-face, in-depth interviews, guided by a topic list, along service users with BD I or II (n = 16) in three specialised community care clinics across the Netherlands. Interviews were digitally recorded and transcribed verbatim prior to analysis in Atlas.ti 7. Unlike existing studies, which suggest that individual abilities of service users determine outcomes in self-management of BD, the current study found that self-management of BD is a learning process that takes place in a collaborative network. We identified five categories: acknowledgment of having BD, processing the information load, illness management, reflecting on living with BD, and self-management of BD. The success of self-management depends on the acknowledgment of individual limitations in learning to cope with BD and willingness to use a social network as a back-up instead. Especially, the dormant fear of a recurrent episode is a hampering factor in this learning process. © 2015 John Wiley & Sons Ltd.

A joint precoding scheme for indoor downlink multi-user MIMO VLC systems

NASA Astrophysics Data System (ADS)

Zhao, Qiong; Fan, Yangyu; Kang, Bochao

2017-11-01

In this study, we aim to improve the system performance and reduce the implementation complexity of precoding scheme for visible light communication (VLC) systems. By incorporating the power-method algorithm and the block diagonalization (BD) algorithm, we propose a joint precoding scheme for indoor downlink multi-user multi-input-multi-output (MU-MIMO) VLC systems. In this scheme, we apply the BD algorithm to eliminate the co-channel interference (CCI) among users firstly. Secondly, the power-method algorithm is used to search the precoding weight for each user based on the optimal criterion of signal to interference plus noise ratio (SINR) maximization. Finally, the optical power restrictions of VLC systems are taken into account to constrain the precoding weight matrix. Comprehensive computer simulations in two scenarios indicate that the proposed scheme always has better bit error rate (BER) performance and lower computation complexity than that of the traditional scheme.

Thyroid autoimmunity in bipolar disorder: A systematic review.

PubMed

Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella

2017-10-15

Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation safety analysis of the ISS bone densitometer

NASA Astrophysics Data System (ADS)

Todd, Paul; Vellinger, John C.; Barton, Kenneth; Faget, Paul

A Bone Densitometer (BD) has been developed for installation on the International Space Station (ISS) with delivery by the Space-X Dragon spacecraft planned for mid 2014. After initial tests on orbit the BD will be used in longitudinal measurements of bone mineral density in experimental mice as a means of evaluating countermeasures to bone loss. The BD determines bone mineral density (and other radiographic parameters) by dual energy x-ray absorptiometry (DEXA). In a single mouse DEXA “scan” its 80 kV x-ray tube is operated for 15 seconds at 35 kV and 3 seconds at 80 kV in four repetitions, giving the subject a total dose of 2.5 mSv. The BD is a modification of a commercial mouse DEXA product known as PIXImus(TM). Before qualifying the BD for utilization on ISS it was necessary to evaluate its radiation safety features and any level of risk to ISS crew members. The BD design reorients the PIXImus so that it fits in an EXPRESS locker on ISS with the x-ray beam directed into the crew aisle. ISS regulation SSP 51700 considers the production of ionizing radiation to be a catastrophic-level hazard. Accidental exposure is prevented by three independent levels of on-off control as required for a catastrophic hazard. The ALARA (As Low as Reasonably Achievable) principle was applied to the BD hazard just as would be done on the ground, so deliberate exposure is limited by lead shielding according to ALARA. Hot spots around the BD were identified by environmental dosimetry using a Ludlum 9DP pressurized ionization chamber survey meter. Various thicknesses of lead were applied to the BD housing in areas where highest dose-per-scan readings were made. It was concluded that 0.4 mm of lead shielding at strategic locations, adding only a few kg of mass to the payload, would accomplish ALARA. With shielding in place the BD now exposes a crew member floating 40 cm away to less than 0.08 microSv per mouse scan. There is an upper limit of 20 scans per day, or 1.6 microSv per day, which may occur a few times per year. This dose may be compared with the 400 microSv per day received by crew members in low earth orbit. The designed shielding level also protects adjacent payloads by maintaining less than 2 mrad/day at 5 cm - a requirement for the protection of electronic instrumentation. It is concluded that the ISS Bone Densitometer minimizes ionizing radiation risks associated with its operation. Research supported by NASA Contract NNJ13GA01C and the Center for the Advancement of Science in Space (CASIS).

Reward anticipation revisited- evidence from an fMRI study in euthymic bipolar I patients and healthy first-degree relatives.

PubMed

Kollmann, Bianca; Scholz, Vanessa; Linke, Julia; Kirsch, Peter; Wessa, Michèle

2017-09-01

Symptomatic phases in bipolar disorder (BD) are hypothesized to result from a hypersensitive behavioral activation system (BAS) being sensitive to potential rewards. However, studies on the neuronal underpinnings of reward anticipation in BD are scarce with contradictory findings and possibly confounded by effects of dopaminergic medication, necessitating further research on dysfunctional motivation in BD. Moreover, its role as vulnerability marker for BD is unclear. Functional imaging was conducted in 16 euthymic BD-I patients free from dopaminergic medication and 19 healthy first-degree relatives using a monetary incentive delay task and compared to parallelized control groups. Further, reward proneness, using the BIS/BAS questionnaire, and its relationship to neural reward anticipation was investigated. BD-I patients displayed greater anterior cingulate cortex (ACC) activity during reward anticipation and higher BIS total scores compared to controls, with a positive relationship between the two measures. There were no neural or self-report group differences between relatives and controls. Due to the experimental design, the role of the ACC during receipt of reward remains unknown, sample sizes were rather small, and patients were not naïve to dopaminergic drugs, making an exclusion of medication effects on findings impossible. Our findings give new insights on reward anticipation in BD. BD-I patients rated themselves as more risk avoidant and showed larger recruitment of the ACC rather than ventral striatum compared to controls during reward anticipation, possibly to down-regulate hyperactive limbic reward regions. This activation seems to be a consequence of rather than a vulnerability marker for the disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Variability among Research Diagnostic Interview Instruments in the Application of "DSM-IV-TR" Criteria for Pediatric Bipolar Disorder

ERIC Educational Resources Information Center

Galanter, Cathryn A.; Hundt, Stephanie R.; Goyal, Parag; Le, Jenna; Fisher, Prudence W.

2012-01-01

Objective: The "DSM-IV-TR "criteria for a manic episode and bipolar disorder (BD) were developed for adults but are used for children. The manner in which clinicians and researchers interpret these criteria may have contributed to the increase in BD diagnoses given to youth. Research interviews are designed to improve diagnostic reliability and…

Structure-function analysis of Avian β-defensin-6 and β-defensin-12: role of charge and disulfide bridges.

PubMed

Yang, Ming; Zhang, Chunye; Zhang, Xuehan; Zhang, Michael Z; Rottinghaus, George E; Zhang, Shuping

2016-09-09

Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as alternatives to antibiotics has been the subject of interest. However, the mechanisms of action remain to be fully understood. The present study characterized the structure-function relationship of AvBD-6 and AvBD-12, two peptides with different net positive charges, similar hydrophobicity and distinct tissue expression profiles. AvBD-6 was more potent than AvBD-12 against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended spectrum beta lactamase (ESBL)-positive E. coli and K. pneumoniae. AvBD-6 was more effective than AvBD-12 in neutralizing LPS and interacting with bacterial genomic DNA. Increasing bacterial concentration from 10(5) CFU/ml to 10(9) CFU/ml abolished AvBDs' antimicrobial activity. Increasing NaCl concentration significantly inhibited AvBDs' antimicrobial activity, but not the LPS-neutralizing function. Both AvBDs were mildly chemotactic for chicken macrophages and strongly chemotactic for CHO-K1 cells expressing chicken chemokine receptor 2 (CCR2). AvBD-12 at higher concentrations also induced chemotactic migration of murine immature dendritic cells (DCs). Disruption of disulfide bridges abolished AvBDs' chemotactic activity. Neither AvBDs was toxic to CHO-K1, macrophages, or DCs. AvBDs are potent antimicrobial peptides under low-salt conditions, effective LPS-neutralizing agents, and broad-spectrum chemoattractant peptides. Their antimicrobial activity is positively correlated with the peptides' net positive charges, inversely correlated with NaCl concentration and bacterial concentration, and minimally dependent on intramolecular disulfide bridges. In contrast, their chemotactic property requires the presence of intramolecular disulfide bridges. Data from the present study provide a theoretical basis for the design of AvBD-based therapeutic and immunomodulatory agents.

Effects of amphibian phylogeny, climate and human impact on the occurrence of the amphibian-killing chytrid fungus.

PubMed

Bacigalupe, Leonardo D; Soto-Azat, Claudio; García-Vera, Cristobal; Barría-Oyarzo, Ismael; Rezende, Enrico L

2017-09-01

Chytridiomycosis, due to the fungus Batrachochytrium dendrobatidis (Bd), has been associated with the alarming decline and extinction crisis of amphibians worldwide. Because conservation programs are implemented locally, it is essential to understand how the complex interactions among host species, climate and human activities contribute to Bd occurrence at regional scales. Using weighted phylogenetic regressions and model selection, we investigated geographic patterns of Bd occurrence along a latitudinal gradient of 1500 km within a biodiversity hot spot in Chile (1845 individuals sampled from 253 sites and representing 24 species), and its association with climatic, socio-demographic and economic variables. Analyses show that Bd prevalence decreases with latitude although it has increased by almost 10% between 2008 and 2013, possibly reflecting an ongoing spread of Bd following the introduction of Xenopus laevis. Occurrence of Bd was higher in regions with high gross domestic product (particularly near developed centers) and with a high variability in rainfall regimes, whereas models including other bioclimatic or geographic variables, including temperature, exhibited substantially lower fit and virtually no support based on Akaike weights. In addition, Bd prevalence exhibited a strong phylogenetic signal, with five species having high numbers of infected individuals and higher prevalence than the average of 13.3% across all species. Taken together, our results highlight that Bd in Chile might still be spreading south, facilitated by a subset of species that seem to play an important epidemiological role maintaining this pathogen in the communities, in combination with climatic and human factors affecting the availability and quality of amphibian breeding sites. This information may be employed to design conservation strategies and mitigate the impacts of Bd in the biodiversity hot spot of southern Chile, and similar studies may prove useful to disentangle the role of different factors contributing to the emergence and spread of this catastrophic disease. © 2017 John Wiley & Sons Ltd.

Bipolar disorder in pregnancy and childbirth: a systematic review of outcomes.

PubMed

Rusner, Marie; Berg, Marie; Begley, Cecily

2016-10-28

Bipolar Disorder (BD) is a mental disorder usually diagnosed between 18 and 30 years of age; this coincides with the period when many women experience pregnancy and childbirth. As specific problems have been reported in pregnancy and childbirth when the mother has BD, a systematic review was carried out to summarise the outcomes of pregnancy and childbirth, in mother and child, when the mother has BD diagnosed before pregnancy. An a priori protocol was designed and a systematic search conducted in PubMed, CINAHL, Scopus, PsycINFO and Cochrane databases in March 2015. Studies of all designs were included if they involved women with a diagnosis of bipolar disorder prior to pregnancy, who were pregnant and/or followed up to one year postpartum. All stages of inclusion, quality assessment and data extraction were done by two people. All maternal or infant outcomes were examined, and narrative synthesis was used for most outcomes. Meta-analysis was used to achieve a combined prevalence for some outcomes and, where possible, case and control groups were combined and compared. The search identified 2809 papers. After screening and quality assessement (using the EPHPP and AMSTAR tools), nine papers were included. Adverse pregnancy outcomes such as gestational hypertension and antepartum haemorrhage occur more frequently in women with BD. They also have increased rates of induction of labour and caesarean section, and have an increased risk of mood disorders in the postnatal period. Women with BD are more likely to have babies that are severely small for gestational age (<2nd-3rd percentile), and it appears that those women not being treated with mood stabilisers in pregnancy might not have an increased risk of having a baby with congenital abnormalities. Due to heterogeneity of data, particularly the use of differing definitions of bipolar disorder, narrative synthesis was used for most outcomes, rather than a meta-analysis. It is evident that adverse outcomes are more common in women with BD and their babies. Large cohort studies examining fetal abnormality outcomes for women with BD who are not on mood stabilisers in pregnancy are required, as are studies on maternal-infant interaction.

[Russian treadmill BD-1 as a backup of the NASA TVIS].

PubMed

Iarmanova, E N; Kozlovskaia, I B; Bogomolov, V V; Rumiantseva, O N; Sukhachev, V I; Mel'nik, K A

2006-01-01

Already during the early ISS increments malfunctioning of NASA TVIS (treadmill with vibration isolation system) posed major problems for regular crew training and particularly scamper, one of the key exercises on the Russian physical training program. During ISS increment-3, TVIS unscheduled repairs took virtually all the training time. In search for TVIS backup, Russian and NASA engineers considered jointly Russian treadmill BD-1, originally designed for Russian "shuttle" Buran and accepted it as a suitable backup in case of complete TVIS failure. To enter into the "dialogue" with BD-1, i.e., to record and downlink training data, the treadmill speed indicator, a part of the treadmill stand, was replaced by PC.

Gray matter brain volumes in childhood-maltreated patients with bipolar disorder type I: A voxel-based morphometric study.

PubMed

Duarte, Dante G G; Neves, Maila de Castro Lourenço; Albuquerque, Maicon R; de Souza-Duran, Fábio L; Busatto, Geraldo; Corrêa, Humberto

2016-06-01

Childhood maltreatment (CM) may be related to clinical expression and outcome of bipolar disorder (BD). Several neuroimaging studies have detected brain morphological changes in specific neural networks of adults who suffered maltreatment in their childhood. We investigated alterations in gray matter volume (GMV) to determine a possible neuroanatomical basis of vulnerability in patients with CM having type I BD (BD-I). We assessed 39 euthymic DSM-IV BD-I patients with (n=20) and without (n=19) a history of CM and 20 healthy controls without maltreatment as defined by the Childhood Trauma Questionnaire (CTQ). Voxel-based morphometry (VBM) was used to compare GMV differences between patients and controls and perform linear correlations in overall BD group between GMV and CTQ scores. BD-I patients had significant negative correlations between CTQ total score and GMV in the right dorsolateral prefrontal cortex (PFC) and the right thalamus; between physical abuse and GMV in the right dorsolateral PFC; between physical neglect and GMV in the thalamus bilaterally; and between emotional neglect and GMV in the right thalamus. Pharmacological treatment could have altered GMV findings. Results emerged only when using SVC approach. CTQ, a retrospective self-report, has the risk of potential recall bias. The cross-sectional design limits longitudinal and neurodevelopmental inferences. The severity of self-reported CM in BD-I patients is associated with morphological changes in GMV of specific neural networks relevant to responses to stress and to modulate emotional behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Negative symptoms in bipolar disorder and schizophrenia: A psychometric evaluation of the brief negative symptom scale across diagnostic categories.

PubMed

Strauss, Gregory P; Vertinski, Mary; Vogel, Sally J; Ringdahl, Erik N; Allen, Daniel N

2016-02-01

Past studies have demonstrated that the Brief Negative Symptom Scale (BNSS) has excellent psychometric properties in patients with schizophrenia. In the current study, we extended this literature by examining psychometric properties of the BNSS in outpatients diagnosed with bipolar disorder (n=46), outpatients with schizophrenia (n=50), and healthy controls (n=27). Participants completed neuropsychological testing and a clinical interview designed to assess negative, positive, disorganized, mood, and general psychiatric symptoms. Results indicated differences among the 3 groups in the severity of all BNSS items, with SZ and BD scoring higher than CN; however, SZ and BD only differed on blunted affect and alogia items, not anhedonia, avolition, or asociality. BD patients with a history of psychosis did not differ from those without a history of psychosis on negative symptom severity. The BNSS had excellent internal consistency in SZ, BD, and CN groups. Good convergent and discriminant validity was apparent in SZ and BD groups, as indicated by relationships between the BNSS and other clinical rating scales. These findings support the validity of the BNSS in broadly defined serious mental illness populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Predicting the potential distribution of the amphibian pathogen Batrachochytrium dendrobatidis in East and Southeast Asia.

PubMed

Moriguchi, Sachiko; Tominaga, Atsushi; Irwin, Kelly J; Freake, Michael J; Suzuki, Kazutaka; Goka, Koichi

2015-04-08

Batrachochytrium dendrobatidis (Bd) is the pathogen responsible for chytridiomycosis, a disease that is associated with a worldwide amphibian population decline. In this study, we predicted the potential distribution of Bd in East and Southeast Asia based on limited occurrence data. Our goal was to design an effective survey area where efforts to detect the pathogen can be focused. We generated ecological niche models using the maximum-entropy approach, with alleviation of multicollinearity and spatial autocorrelation. We applied eigenvector-based spatial filters as independent variables, in addition to environmental variables, to resolve spatial autocorrelation, and compared the model's accuracy and the degree of spatial autocorrelation with those of a model estimated using only environmental variables. We were able to identify areas of high suitability for Bd with accuracy. Among the environmental variables, factors related to temperature and precipitation were more effective in predicting the potential distribution of Bd than factors related to land use and cover type. Our study successfully predicted the potential distribution of Bd in East and Southeast Asia. This information should now be used to prioritize survey areas and generate a surveillance program to detect the pathogen.

Mechanism and influencing factors on critical pulse width of oil-immersed polymer insulators under short pulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Liang, E-mail: zhaoliang@ninit.ac.cn; Li, Rui; Zheng, Lei

2015-04-15

The critical pulse width (τ{sub c}) is a pulse width at which the surface flashover threshold (E{sub f}) is equal to the bulk breakdown threshold (E{sub BD}) for liquid-polymer composite insulation systems, which is discovered by Zhao et al. [Annual Report Conference on Electrical Insulation and Dielectric Phenomena (IEEE Dielectrics and Electrical Insulation Society, Shenzhen, China, 2013), Vol. 2, pp. 854–857]. In this paper, the mechanism of τ{sub c} is interpreted in perspective of the threshold and the time delay (t{sub d}) of surface flashover and bulk breakdown, respectively. It is found that two changes appear as the pulse widthmore » decreases which are responsible for the existence of τ{sub c}: (1) E{sub BD} is lower than E{sub f}; (2) t{sub d} of bulk breakdown is shorter than t{sub d} of surface flashover. In addition, factors which have influences on τ{sub c} are investigated, such as the dielectric type, the insulation length, the dielectric thickness, the dielectrics configuration, the pulse number, and the liquid purity. These influences of factors are generalized as three types if τ{sub c} is expected to increase: (1) factors causing E{sub BD} to decrease, such as increasing the pulse number or employing a dielectric of lower E{sub BD}; (2) factors causing E{sub f} to increase, such as complicating the insulator's configuration or increasing the liquid purity; (3) factors causing E{sub BD} and E{sub f} to increase together, but E{sub f} increases faster than E{sub BD}, such as decreasing the dielectric thickness or the insulation length. With the data in references, all the three cases are verified experimentally. In the end, a general method based on τ{sub c} for solid insulation design is presented and the significance of τ{sub c} on solid insulation design and on solid demolition are discussed.« less

Parental communication style and family relationships in children of bipolar parents.

PubMed

Vance, Yvonne H; Huntley Jones, Steven; Espie, Jonathan; Bentall, Richard; Tai, Sara

2008-09-01

To examine relationships between parental communication styles and family environment in parents with bipolar disorder (BD) and their children (CBP). On measures of parental communication styles and family environment, 20 BD parents and their 23 children (CBP) were compared to controls. Children completed a current mood measure. BD parents endorsed more negative communication styles and were less expressive than controls. CBP presented with more current or lifetime mood disorder diagnoses than control children (CC). Current depressive mood was associated with different perceptions of family environment for both CBP and CC. This familial high risk design indicated differences in family environment, parenting style, and in children of bipolar parents' perception of their family environment as it relates to their current mood.

Evidence-based practice in Behçet’s disease: identifying areas of unmet need for 2014

PubMed Central

2014-01-01

Background Behçet’s Disease (BD) is characterized by a relapsing-remitting course, with symptoms of varying severity across almost all organ systems. There is a diverse array of therapeutic options with no universally accepted treatment regime, and it is thus important that clinical practice is evidence-based. We reviewed all currently available literature describing management of BD, and investigated whether evidence-based practice is possible for all disease manifestations, and assessed the range of therapeutic options tested. Methods We conducted an internet search of all literature describing management of BD up to August 2013, including pharmacological and non-pharmacological interventions. We recorded treatment options investigated and disease manifestations reported as primary and secondary study outcomes. Quality of data was assessed according to the Scottish Intercollegiate Guideline Network (SIGN) hierarchy of evidence. Results Whilst there is much literature describing treatment of ocular and mucocutaneous disease, there is little to guide management of rheumatoid, cardiovascular and neurological disease. This broadly reflects the prevalence of disease manifestations of BD, but not the severity. Biologic therapies are the most commonly investigated intervention. The proportion of SIGN-1 graded studies is declining, and there are no SIGN-1 graded studies investigating neurological or gastrointestinal manifestations of BD. Conclusions This is the first study to investigate trends in published literature for management of BD over time. It identifies neurological, cardiovascular and gastro-intestinal disease as particular areas of unmet need and suggests that overall quality of evidence is declining. Future research should be designed to address these areas of insufficiency to facilitate evidence-based practice in BD. PMID:24475935

Hyper- and hypocortisolism in bipolar disorder - A beneficial influence of lithium on the HPA-axis?

PubMed

Maripuu, Martin; Wikgren, Mikael; Karling, Pontus; Adolfsson, Rolf; Norrback, Karl-Fredrik

2017-04-15

A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naïve to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Cross sectional study design. There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis. Copyright © 2017 Elsevier B.V. All rights reserved.

Early interventions for youths at high risk for bipolar disorder: a developmental approach.

PubMed

Benarous, Xavier; Consoli, Angèle; Milhiet, Vanessa; Cohen, David

2016-03-01

In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

PubMed

Li, Linling; Ji, Erni; Tang, Fei; Qiu, Yunhai; Han, Xue; Zhang, Shengli; Zhang, Zhiguo; Yang, Haichen

2018-06-16

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

A Systematic Review and Critical Appraisal of Economic Evaluations of Pharmacological Interventions for People with Bipolar Disorder.

PubMed

Mavranezouli, Ifigeneia; Lokkerbol, Joran

2017-03-01

Bipolar disorder (BD) is a chronic mood disorder that causes substantial psychological and financial burden. Various pharmacological treatments are effective in the management and prevention of acute episodes of BD. In an era of tighter healthcare budgets and a need for more efficient use of resources, several economic evaluations have evaluated the cost effectiveness of treatments for BD. The aim of this study was to systematically review and appraise published economic evaluations of pharmacological interventions for BD. A systematic search combining search terms specific to BD with a health economics search filter was conducted on six bibliographic databases (EMBASE, MEDLINE, PsycINFO, HTA, NHS EED, CENTRAL) in order to identify trial- or model-based full economic evaluations of pharmacological treatments of any phase of the disorder that were published between 1 January 1990 and 18 December 2015. Studies that met the inclusion criteria were critically appraised using the Quality of Health Economic Studies (QHES) checklist, and synthesised in a narrative way. The review included 19 economic studies, which varied with regard to the type and number of interventions assessed, the study design, the phase of treatment (acute or maintenance), the source of efficacy data and the method for evidence synthesis, the outcome measures, the time horizon and the countries/settings in which the studies were conducted. The study quality was variable but the majority of studies were of high or fair quality. Pharmacological interventions are cost effective, compared with no treatment, in the management of BD, both in the acute and maintenance phases. However, it is difficult to draw safe conclusions on the relative cost effectiveness between drugs due to differences across studies and limitations characterising many of them. Future economic evaluations need to consider the whole range of treatment options available for the management of BD and adopt appropriate methods for evidence synthesis and economic modelling, to explore more robustly the relative cost effectiveness of pharmacological interventions for people with BD.

Perception of Physical Fitness and Exercise Self-Efficacy and Its Contribution to the Relationship between Body Dissatisfaction and Physical Fitness in Female Minority Children.

PubMed

Flanagan, Emily W; Perry, Arlette C

2018-06-06

Body Dissatisfaction (BD) and low physical self-concept and exercise efficacy have been linked to poor physical fitness levels and adverse health outcomes in children. The purpose of this study was to examine the relationship between BD, physical fitness, exercise self-efficacy, and self-Perception of Physical Fitness (PFP) in Latina and Black female children. Twenty-eight Latina and Black children enrolled in an elementary afterschool program, aged 8⁻12, completed surveys evaluating body dissatisfaction, exercise efficacy, PFP, and measures of physical fitness. Subjects exhibited moderate but significant inverse relationships between BD and PFP in strength ( r = −0.459), agility ( r = −0.382), aerobic fitness ( r = −0.354), and flexibility ( r = −0.461) ( p < 0.05 for all). There was a significant negative correlation between exercise efficacy and BD ( r = −4.2; p < 0.05). Power ( r = 0.51) and flexibility ( r = 0.42) were the only physical fitness measures significantly and positively related to children’s PFP ( p < 0.05). A significant medium inverse relationship was also found between BD and aerobic fitness scores ( r = −0.381; p < 0.05). However, after controlling for exercise efficacy or perception of physical fitness, the relationship between BD and aerobic fitness was not significant ( p > 0.05). Findings suggest that positive PFP and positive performance in several physical fitness measures are associated with lower levels of BD in minority female children. Furthermore, evidence suggests exercise efficacy and PFP can mediate the relationship body image and aerobic fitness. These findings suggest that PFP, more so than measured physical fitness, was associated with lower levels of BD in minority female children. These results have important implications for programs designed to improve physical fitness and mental health in minority children.

Novel ex vivo model for hands-on teaching of and training in EUS-guided biliary drainage: creation of "Mumbai EUS" stereolithography/3D printing bile duct prototype (with videos).

PubMed

Dhir, Vinay; Itoi, Takao; Fockens, Paul; Perez-Miranda, Manuel; Khashab, Mouen A; Seo, Dong Wan; Yang, Ai Ming; Lawrence, Khek Yu; Maydeo, Amit

2015-02-01

EUS-guided biliary drainage (EUS-BD) has emerged as an alternative rescue method in patients with failed ERCP. Opportunities for teaching and training are limited because of a low case volume at most centers. To evaluate a stereolithography/3-dimensional (3D) printing bile duct prototype for teaching and training in EUS-BD. Prospective observational feasibility study. Tertiary referral center. Twenty endosonographers attending an interventional EUS workshop. A prototype of a dilated biliary system was prepared by computer-aided design and 3D printing. The study participants performed guidewire manipulation and EUS-BD procedures (antegrade procedure and/or choledochoduodenostomy) on the prototype. Participants were scored with the device on a scale of 1 to 5 via a questionnaire. Participants' success rate for various steps of the EUS-BD procedure was noted. Subjective and objective evaluation of the prototype regarding its overall applicability, quality of radiographic and EUS images, and 4 steps of EUS-BD procedure (needle puncture, guidewire manipulation, tract dilation, stent placement). Fifteen participants returned the questionnaire, and 10 completed all 4 steps of EUS-BD. The median score for overall utility was 4, whereas that for EUS and US views was 5. Participants with experience in performing more than 20 EUS-BD procedures scored the prototype significantly lower for stent placement (P = .013) and equivalent for needle puncture, tract dilation, and wire manipulation. The success rate of various steps was 100% for needle puncture and tract dilation, 82.35% for wire manipulation, and 80% for stent placement. The mean overall procedure time was 18 minutes. Small number of participants. The 3D printing bile duct prototype appears suitable for teaching of and training in the various steps of EUS-BD. Further studies are required to elucidate its role. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Quality of life in bipolar disorder: A review of the literature

PubMed Central

Michalak, Erin E; Yatham, Lakshmi N; Lam, Raymond W

2005-01-01

A sizable body of research has now examined the complex relationship between quality of life (QoL) and depressive disorder. Uptake of QoL research in relation to bipolar disorder (BD) has been comparatively slow, although increasing numbers of QoL studies are now being conducted in bipolar populations. We aimed to perform a review of studies addressing the assessment of generic and health-related QoL in patients with bipolar disorder. A literature search was conducted in a comprehensive selection of databases including MEDLINE up to November 2004. Key words included: bipolar disorder or manic-depression, mania, bipolar depression, bipolar spectrum and variants AND quality of life, health-related QoL, functional status, well-being and variants. Articles were included if they were published in English and reported on an assessment of generic or health-related QoL in patients with BD. Articles were not included if they had assessed fewer than 10 patients with BD, were only published in abstract form or only assessed single dimensions of functioning. The literature search initially yielded 790 articles or abstracts. Of these, 762 did not meet our inclusion criteria, leaving a final total of 28 articles. These were sub-divided into four categories (assessment of QoL in patients with BD at different stages of the disorder, comparisons of QoL in Patients with BD with that of other patient populations, QoL instrument evaluation in patients with BD and treatment studies using QoL instruments to assess outcome in Patients with BD) and described in detail. The review indicated that there is growing interest in QoL research in bipolar populations. Although the scientific quality of the research identified was variable, increasing numbers of studies of good design are being conducted. The majority of the studies we identified indicated that QoL is markedly impaired in patients with BD, even when they are considered to be clinically euthymic. We identified several important avenues for future research, including a need for more assessment of QoL in hypo/manic patients, more longitudinal research and the development of a disease-specific measure of QoL for patients with BD. PMID:16288650

A Pilot Study Investigating TNF-α as a Potential Intervening Variable of Atypical Antipsychotic Associated Metabolic Syndrome in Bipolar Disorder

PubMed Central

Prossin, A. R.; Zalcman, S. S.; Evans, S. J.; McInnis, M. G.; Ellingrod, V. L.

2013-01-01

Background Strong associations exist between tumor necrosis factor-α (TNF-α) and metabolic syndrome (MetS). While TNF-α is associated with Bipolar depression, its role in atypical antipsychotic (AAP) associated MetS in Bipolar Disorder (BD) is unclear. Here we investigate the potential intervening role TNF-α in the indirect relationship between AAP treatment and MetS in BD. Materials and Methods Using a cross-sectional design, 99 euthymic BD volunteers were stratified by presence/absence of MetS (NCEP-ATP-III). Serum TNF-α concentration, determined via chemiluminescent immunometric assays, was compared between groups (i.e. MetS or no MetS). We investigated the intervening effect of TNF-α on the relation between AAP treatment and MetS in BD using regression techniques. Results Treatment with antipsychotics believed associated with a higher risk for MetS (i.e. AAPs; olanzapine, quetiapine, risperidone, paliperidone, clozapine), was found to be associated with significantly greater TNF-α (F1,88=11.2, p=0.001, mean difference of 1.7 +/− 0.51) and a higher likelihood of MetS (F1,88=4.5, p=0.036) than in those not receiving treatment with an AAP. Additionally, TNF-α was greater (trending towards significance; T52=2.0, p=0.05) in BD volunteers with MetS and was found to have a statistically significant effect on the indirect relationship between AAP treatment and elevated waist circumference in these BD volunteers. Discussion These results identify TNF-α as a potential intervening variable of AAP associated MetS in BD, not previously identified in this population. Future prospective studies could assess the predictive potential of TNF-α in determining risk of AAP associated MetS in BD. Given previous evidence relating TNF-α and mood state in BD, this study increases the importance in understanding the role of TNF-α in “mind-body” interactions and renews discussions of the utility of research into the clinical efficacy of TNF-α antagonist treatment in mood disorders. PMID:23503445

Development of the International Classification of Functioning, Disability and Health core sets for bipolar disorders: results of an international consensus process.

PubMed

Ayuso-Mateos, José L; Avila, Carolina C; Anaya, Celia; Cieza, Alarcos; Vieta, Eduard

2013-01-01

The International Classification of Functioning, Disability and Health (ICF) is a tool of the World Health Organization (WHO) designed to be a guide to identify and classify relevant domains of human experience affected by health conditions. The purpose of this article is to describe the process for the development of two Core Sets for bipolar disorder (BD) in the framework of the ICF. The Comprehensive ICF Core Set for BD intends to be a guide for multidisciplinary assessment of patients diagnosed with this condition, while the Brief ICF Core Set for BD will be useful when rating aspects of patient's experience for clinical practice or epidemiological studies. An international consensus conference involving a sample of experts with different professional backgrounds was performed using the nominal group technique. Various preparatory studies identified a set of 743 potential ICF categories to be included in the Core Sets. A total of 38 ICF categories were selected to be included in the Comprehensive Core Set for BD. A total of 19 ICF categories from the Comprehensive Core Set were chosen as the most significant to constitute the Brief Core Set for BD. The formal consensus process integrating evidence and expert opinion on the ICF led to the formal adoption of the ICF Core Sets for BD. The most important categories included are representative of the characteristics usually associated with BD. The next phase of this ICF project is to conduct a formal validation process to establish its applicability in clinical settings. Implications for Rehabilitation Bipolar disorder (BD) is a prevalent condition that has a great impact on people who suffer it, not only in health but also in daily functioning and quality of life. No standard has been defined so far regarding the problems in functioning of persons with BDs. The process described in this article defines the set of areas of functioning to be addressed in clinical assessments of persons with BD and establish the starting point for the development of condition-specific outcome measures.

Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions.

PubMed

Veronese, Nicola; Solmi, Marco; Luchini, Claudio; Lu, Ru-Band; Stubbs, Brendon; Zaninotto, Leonardo; Correll, Christoph U

2016-06-01

Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD. Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis. Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning. Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results. Copyright © 2016 Elsevier B.V. All rights reserved.

The addition of STEPPS in the treatment of patients with bipolar disorder and comorbid borderline personality features: a protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar disorder (BD) and borderline personality disorder (BPD) both are severe and chronic psychiatric disorders. Both disorders have overlapping symptoms, and current research shows that the presence of a BPD has an adverse effect on the course of BD. The limited research available shows an unfavorable illness course, a worse prognosis and response to medication, longer treatment duration, more frequent psychiatric admissions, higher drop-out, increased risk of substance abuse, increased risk of suicide, and more impairment of social and occupational functioning. However, there is no research available on the effect of specific psychotherapeutic treatment for this patients. Methods/Design This paper presents the protocol of a RCT to investigate the presence of borderline personality features in patients treated for BD (study part 1) and the effectiveness of STEPPS (Systems Training for Emotional Predictability and Problem Solving) added to treatment as usual (TAU) for BD compared to TAU in patients with BD and comorbid borderline personality features (study part 2). STEPPS is a validated and effective intervention for BPD. The study population consists of patients treated for BD at specialized outpatient clinics for BD in the Netherlands. At first the prevalence of comorbid borderline personality features in outpatients with BD is investigated. Inclusion criteria for study part 2 is defined as having three or more of the DSM-IV-TR diagnostic criteria of BPD, including impulsivity and anger bursts. Primary outcomes will be the frequency and severity of manic and depressive recurrences as well as severity, course and burden of borderline personality features. Secondary outcomes will be quality of life, utilizing mental healthcare and psychopathologic symptoms not primarily related to BD or BPD. Assessment will be at baseline, at the end of the intervention, and at 12 and 18 months follow-up. Discussion This will be the first randomized controlled trial of a specific intervention in patients with BD and comorbid BPD or borderline personality features. There are no recommendations in the guideline of treatment of bipolar disorders for patients with this complex comorbidity. We expect that a combined treatment aimed at mood disorder and emotion regulation will improve treatment outcomes for these patients. PMID:24912456

PDT in squamous cell carcinoma of the skin.

PubMed

Zwiebel, S; Baron, E

2011-12-01

Topical photodynamic therapy (PDT) has been demonstrated to be an effective and safe treatment option for pre-malignancies such as actinic keratoses (AK) and Bowen's disease (BD), with an increasing amount of evidence indicating good long term outcomes. Studies comparing PDT to other options such as cryotherapy and 5-fluorouracil generally demonstrate that PDT is equal to or better than these therapies with respect to patient satisfaction, cosmesis, and efficacy for AK and BD. While there are studies using squamous cell carcinoma (SCC) cells to elucidate the cellular and molecular mechanisms of PDT, this therapy is currently not indicated for treating SCC and surgery is still the first line of therapy. There has been special interest in using PDT to prevent warts, basal cell carcinoma, AK, and BD in solid organ transplant recipients, as these skin lesions are more common in immunosuppressed patients, and trials have been somewhat successful and very promising. Pain remains an obstacle for some patients and techniques such as nerve blocks, cooling packs, and hydration have been attempted to mitigate pain with an overall reduction in pain scores. Optimizing PDT is still a priority and the delivery of pro-drug as well as induction of cellular differentiation are being explored as ways to improve the efficacy of PDT. Perhaps the most interesting use of PDT in treating SCC is the potential for a tumor-specific vaccine, which is currently being developed.

The Aerosol Foam Formulation of the Fixed Combination Calcipotriene Plus Betamethasone Dipropionate Improves the Health-Related Quality of Life in Patients With Psoriasis Vulgaris: Results from the Randomized PSO-FAST Study.

PubMed

Leonardi, Craig; Bagel, Jerry; Yamauchi, Paul; Pariser, David; Xu, Zhenyi; Moller, Anders; Osterdal, Marie Louise; Stein Gold, Linda

2016-08-01

Psoriasis has a major impact on patient quality of life, similar to that seen in other chronic diseases, eg, diabetes. Health-related quality of life (HRQoL) measures are commonly included in clinical trial designs, capturing the disease burden and therapeutic success of a treatment. In the randomized, double-blind, phase III PSO-FAST (Psoriasis vulgaris, a Four-week, vehicle-controlled, efficacy And Safety Trial) study (nCT01866163), fixed combination calcipotriene (Cal) 0.005% plus betamethasone dipropionate (BD) 0.064% aerosol foam was compared with vehicle. By treatment end, 53% of patients using Cal/BD foam achieved treatment success.
To compare the impact on HRQoL of Cal/BD foam vs vehicle in patients with mild-to-severe psoriasis.
HRQoL was assessed by dermatology life-quality index (DLQI; baseline, weeks 1, 2, 4) and EQ-5D-5L (EQ-5D; baseline, week 4) questionnaires. A DLQI score of 0 (range, 0-30) indicates no effect on the patient's life; an EQ-5D utility score of 1 (range, 0-1) and an EQ-5D visual analog scale (VAS) score of 100 (range, 1-100) indicate perfect health.
426 patients were randomized (Cal/BD foam, n=323; vehicle, n=103). Baseline mean DLQI scores were 9.9 (Cal/BD foam) and 10.3 (vehicle). The impact of psoriasis on HRQoL (EQ-5D utility score) at baseline was primarily driven by pain/discomfort (Cal/BD foam: 69.9%; vehicle: 65.0%) and anxiety/depression (Cal/BD foam: 45.3%; vehicle 44.7%). There was a greater improvement from baseline in DLQI score for Cal/BD foam vs vehicle at week 4 (-7.0 vs -4.4; P<.001); increased improvement was also seen in EQ-5D scores. At week 4, 48.1% of patients using Cal/BD foam reported no effect of psoriasis on their lives (DLQI = 0/1), and of patients using Cal/BD foam with baseline DLQI scores ≥5, 81.2% achieved a ≥5-point improvement.
Cal/BD aerosol foam improved HRQoL after 4 weeks, with most patients experiencing a clinically meaningful improvement and almost 50% reporting no impairment.

J Drugs Dermatol. 2016;15(8):981-987.

Enhancing Ocean Literacy and Expertise of Diverse Populations via Graduate School Fellowship Opportunities

NASA Astrophysics Data System (ADS)

Mayo, M.; Ithier-Guzman, W.; Pyrtle, A. J.; Betzer, P.; Batson, B.; Bhansali, S.; Greene, B.; Turner, R.

2007-05-01

In 2004, the University of South Florida (USF) was granted by the National Science Foundation a Louis Stokes Alliance for Minority Participation (LSAMP) Bridge to the Doctorate (BD) site award (HRD# 0217675). As part of the Florida-Georgia Louis Stokes Alliance for Minority Participation (FGLSAMP), USF is one of thirteen institutions in an alliance that is dedicated to significantly increasing the number of underrepresented minority students who obtain undergraduate and graduate STEM degrees. The BD program at USF incorporates the goals of FGLSAMP and facilitates the recruitment of underrepresented minorities pursuing careers in the STEM fields at the graduate level. The thematic focus of the FGLSAMP USF BD program is focused on the development and application of biogeochemical sensors for marine, aquatic, environmental, remote sensing and biomedical applications. After recruitment, BD graduate fellowship recipients are provided with NSF-funded financial support for two years, and opportunities to participate in professional development workshops, seminars and short courses, as well as additional financial support to pursue and complete their doctoral studies (beyond the initial two years of NSF BD funding), in a variety of forms, including, but not limited to, Alfred P. Sloan Minority Scholarships, Florida Education Fund's McKnight Doctoral Fellowships, USF College of Graduate Studies Fellowships, USF CMS endowed fellowships, USF CMS research assistantships, and USF CMS teaching assistantships. Collectively, 3 LSAMP BD grants have been awarded at USF to support 56 underrepresented minority fellowship recipients, of which 14 are currently graduate students at the USF College of Marine Science (CMS). Since the arrival of the BD Fellowship program, the graduate community has diversified, showing an increase of over 40% in underrepresented minorities at CMS. The BD program has enhanced the research and learning environment for all CMS students, as well as fostered a nurturing community of underrepresented minority CMS graduate students committed to obtaining their doctoral degrees. As of spring 2007, a total of 4 BD fellowship recipients have obtained marine science master's degrees and are currently pursuing their doctoral degrees in the CMS. In addition, in less than two years, a BD endowment fund of more than $900,000 was established. This fund will provide financial support for at least two minority CMS graduate students in perpetuity! Lastly, in response to an identified need for increased ocean literacy among underrepresented groups, several BD fellowship recipients have engaged in activities designed to "give back" via informal and formal education and outreach opportunities within their native communities.

Influences of race and breast density on related cognitive and emotion outcomes before mandated breast density notification.

PubMed

Manning, Mark; Albrecht, Terrance L; Yilmaz-Saab, Zeynep; Shultz, Julie; Purrington, Kristen

2016-11-01

Many states have adopted laws mandating breast density (BD) notification for applicable women; however, very little is known about what women knew or felt about BD and related breast cancer (BC) risk before implementation of BD notification laws. We examined between-race differences in the extent to which having dense breasts was associated with women's related BD cognition and emotion, and with health care providers' communication about BD. We received surveys between May and October of 2015 assessing health care provider (HCP) communication about BD, BD-related knowledge, BD-related anxiety and BC worry from 182 African American (AA) and 113 European American (EA) women in the state of Michigan for whom we had radiologists' assessments of BD. Whereas having dense breasts was not associated with any BD-related cognition or emotion, there were robust effects of race as follows: EA women were more likely to have been told about BD by a HCP, more likely to know their BD status, had greater knowledge of BD and of BC risk, and had greater perceptions of BC risk and worry; AA women had greater BD-related anxieties. EA women's greater knowledge of their own BD status was directly related to the increased likelihood of HCP communication about BD. However, HCP communication about BD attenuated anxiety for AA women only. We present the only data of which we are aware that examines between-race differences in the associations between actual BD, HCP communication and BD related cognition and emotion before the implementation of BD notification laws. Our findings suggest that the BD notification laws could yield positive benefits for disparities in BD-related knowledge and anxiety when the notifications are followed by discussions with health care providers. Copyright © 2016 Elsevier Ltd. All rights reserved.

The relationship between lifestyle factors and clinical symptoms of bipolar disorder patients in a Chinese population.

PubMed

Huang, Jia; Yuan, Cheng Mei; Xu, Xian Rong; Wang, Yong; Hong, Wu; Wang, Zuo Wei; Su, You Song; Hu, Ying Yan; Cao, Lan; Wang, Yu; Chen, Jun; Fang, Yi Ru

2018-05-06

There is evidence that bipolar disorder (BD) patients with an unhealthy lifestyle have a worse course of illness. This study was designed to examine the extent to which lifestyle could influence the severity of clinical symptoms associated with BD. A total of 113 BD patients were recruited in this study. The lifestyle information including data on dietary patterns, physical activity, and sleep quality were collected using a self-rated questionnaire. The results showed that the consumption of whole grain, seafood, and dairy products were significantly negatively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score. The consumption of sugar, soft drinks, and alcohol as well as being a current smoker were positively correlated with the severity of clinical symptoms. Multiple linear regression and binary logistic regression analyses demonstrated an independent negative correlation between both whole grain and dairy product consumption with the HAMD-17 score. The results from the current study suggested that lifestyle factors, especially dietary patterns, might be associated with clinical symptoms of BD. The association between the consumption of specific foods and severity of depressive symptoms may offer some useful information and further understanding of the role of lifestyle factors in the development of BD. Copyright © 2018. Published by Elsevier B.V.

Performance and lipid profiles of native chickens fed diet containing skipjack fish oil as by-product of fish canning factory

NASA Astrophysics Data System (ADS)

Leke, J. R.; Mandey, J. S.; Laihad, J. T.; Tinangon, R. M.; Tangkau, L.; Junus, C.

2018-01-01

The study was conducted to determine the use of fish oil as by-product of fish canning factory in diet on the performance and lipid profiles of native chickens. The experiment used 100 native chicken with an average initial body weight of 48,9 gram (sd + 9.9), was used in this study for 8 weeks experiment. These were arranged by a completely randomized design with 5 treatments, 5 replications and 4 hens in replication each. The diets were: R0 = 100% Based Diet (BD) + 0% Fish Oil (FO); R1 = 98.5% BD + 1.5% FO; R2 = 98% BD + 2% FO; R3 = 97.5% BD + 2.5% FO; R4 = 97 % BD + 3% FO. Feed and water were provided ad libitum. Variables were performance parameters and lipid profiles. Results showed that fish oil inclusion in diets were significantly increased feed intake, body weight gain, carcass percentage, liver, breast and thigh weight, and decreased blood cholesterol, carbohydrate and meat cholesterol, and also tended to decrease abdominal fat. However, there were no affected on feed conversion, water, protein, fat and ash of breast meat. It can be concluded that the use of fish oil in diet up to 3% could improved performance parameters of native chickens.

The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness.

PubMed

Zink, Davor N; Miller, Justin B; Caldwell, Jessica Z K; Bird, Christopher; Banks, Sarah J

2018-06-01

Tests of visuospatial function are often administered in comprehensive neuropsychological evaluations. These tests are generally considered assays of parietal lobe function; however, the neural correlates of these tests, using modern imaging techniques, are not well understood. In the current study we investigated the relationship between three commonly used tests of visuospatial function and lobar cortical thickness in each hemisphere. Data from 374 patients who underwent a neuropsychological evaluation and MRI scans in an outpatient dementia clinic were included in the analysis. We examined the relationships between cortical thickness, as assessed with Freesurfer, and performance on three tests: Judgment of Line Orientation (JoLO), Block Design (BD) from the Fourth edition of the Wechsler Adult Intelligence Scale, and Brief Visuospatial Memory Test-Revised Copy Trial (BVMT-R-C) in patients who showed overall average performance on these tasks. Using a series of multiple regression models, we assessed which lobe's overall cortical thickness best predicted test performance. Among the individual lobes, JoLO performance was best predicted by cortical thickness in the right temporal lobe. BD performance was best predicted by cortical thickness in the right parietal lobe, and BVMT-R-C performance was best predicted by cortical thickness in the left parietal lobe. Performance on constructional tests of visuospatial function appears to correspond best with underlying cortical thickness of the parietal lobes, while performance on visuospatial judgment tests appears to correspond best to temporal lobe thickness. Future research using voxel-wise and connectivity techniques and including more diverse samples will help further understanding of the regions and networks involved in visuospatial tests.

Females and males are highly similar in language performance and cortical activation patterns during verb generation.

PubMed

Allendorfer, Jane B; Lindsell, Christopher J; Siegel, Miriam; Banks, Christi L; Vannest, Jennifer; Holland, Scott K; Szaflarski, Jerzy P

2012-10-01

To test the existence of sex differences in cortical activation during verb generation when performance is controlled for. Twenty male and 20 female healthy adults underwent functional magnetic resonance imaging (fMRI) using a covert block-design verb generation task (BD-VGT) and its event-related version (ER-VGT) that allowed for intra-scanner recordings of overt responses. Task-specific activations were determined using the following contrasts: BD-VGT covert generation>finger-tapping; ER-VGT overt generation>repetition; ER-VGT overt>covert generation. Lateral cortical regions activated during each contrast were used for calculating language lateralization index scores. Voxelwise regressions were used to determine sex differences in activation, with and without controlling for performance. Each brain region showing male/female activation differences for ER-VGT overt generation>repetition (isolating noun-verb association) was defined as a region of interest (ROI). For each subject, the signal change in each ROI was extracted, and the association between ER-VGT activation related to noun-verb association and performance was assessed separately for each sex. Males and females performed similarly on language assessments, had similar patterns of language lateralization, and exhibited similar activation patterns for each fMRI task contrast. Regression analysis controlling for overt intra-scanner performance either abolished (BD-VGT) or reduced (ER-VGT) the observed differences in activation between sexes. The main difference between sexes occurred during ER-VGT processing of noun-verb associations, where males showed greater activation than females in the right middle/superior frontal gyrus (MFG/SFG) and the right caudate/anterior cingulate gyrus (aCG) after controlling for performance. Better verb generation performance was associated with increased right caudate/aCG activation in males and with increased right MFG/SFG activation in females. Males and females exhibit similar activation patterns during verb generation fMRI, and controlling for intra-scanner performance reduces or even abolishes sex differences in language-related activation. These results suggest that previous findings of sex differences in neuroimaging studies that did not control for task performance may reflect false positives. Copyright © 2011 Elsevier Srl. All rights reserved.

Identification of functional features of synthetic SINEUPs, antisense lncRNAs that specifically enhance protein translation

PubMed Central

Kozhuharova, Ana; Sharma, Harshita; Ohyama, Takako; Fasolo, Francesca; Yamazaki, Toshio; Cotella, Diego; Santoro, Claudio; Zucchelli, Silvia; Gustincich, Stefano; Carninci, Piero

2018-01-01

SINEUPs are antisense long noncoding RNAs, in which an embedded SINE B2 element UP-regulates translation of partially overlapping target sense mRNAs. SINEUPs contain two functional domains. First, the binding domain (BD) is located in the region antisense to the target, providing specific targeting to the overlapping mRNA. Second, the inverted SINE B2 represents the effector domain (ED) and enhances translation. To adapt SINEUP technology to a broader number of targets, we took advantage of a high-throughput, semi-automated imaging system to optimize synthetic SINEUP BD and ED design in HEK293T cell lines. Using SINEUP-GFP as a model SINEUP, we extensively screened variants of the BD to map features needed for optimal design. We found that most active SINEUPs overlap an AUG-Kozak sequence. Moreover, we report our screening of the inverted SINE B2 sequence to identify active sub-domains and map the length of the minimal active ED. Our synthetic SINEUP-GFP screening of both BDs and EDs constitutes a broad test with flexible applications to any target gene of interest. PMID:29414979

Comorbid obsessive-compulsive disorder with bipolar disorder: A distinct form?

PubMed

Ozdemiroglu, Filiz; Sevincok, Levent; Sen, Gulnur; Mersin, Sanem; Kocabas, Oktay; Karakus, Kadir; Vahapoglu, Fatih

2015-12-30

We examined whether the patients with Bipolar Disorder (BD) and Obsessive-Compulsive Disorder (OCD) comorbidity may represent a distinct form of BD. The subjects diagnosed with BD (n=48), OCD (n=61), and BD with OCD (n=32) were compared in terms of several socio-demographic and clinical characteristics. Previous history of suicidal attempts was more likely to be higher in BD-OCD group compared to the other two groups. A more episodic course of OCD, higher rates of rapid cycling, and the seasonality were found in BD-OCD patients. The frequency of bipolar II and NOS subtypes was more prevalent in patients with BD-OCD than in OCD patients. The first diagnosed illness was BD in the majority of BD-OCD cases. It was found that first affective episode was major depression in half of BD-OCD patients. Age at onset of BD was found to be earlier in BD-OCD group compared to pure BD patients. Bipolarity may not have a specific effect on the phenomenology of OC symptoms. The episodic course of OCD, seasonality, rapid cycling, earlier onset of BD, and impulsivity in BD-OCD patients may be indicative for a distinct form of BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biodegradable Stents: An Evolution in Management of Benign Intestinal Strictures.

PubMed

Jain, Deepanshu; Mahmood, Ejaz; Singhal, Shashideep

2017-04-01

Benign intestine strictures secondary to postoperative narrowing or inflammatory bowel disease can be managed surgically or conservatively. Some patients may not be suitable surgical candidates and some patients may choose not to have repeat surgery. Biodegradable (BD) stents offer a prolonged dilatory effect before gradual degradation and obviates the need of a second procedure for stent removal. BD stents have high technical success rates (mean, 94.4%; median, 100%; range, 86% to 100%) but widely variable clinical success rates (range, 45% to 100%). Stent migration is the most commonly reported complication (mean, 22.2%; range, 0% to 36%). In the future, with better understanding of the factors contributing to stent migration, improvement in present stent design and better anchoring techniques, the stent migration rate is expected to decrease and improve clinical outcome. The role of prophylactic BD stent placement to prevent stricture development postintestine surgery is an intriguing idea and needs to be explored. As of now, the use of BD stents is a reasonable option for patients with dilatation resistant intestinal strictures who are unfit for surgery or refuse to have surgical treatment.

Aripiprazole augmentation in managing comorbid obsessive-compulsive disorder and bipolar disorder: a case with suicidal attempts.

PubMed

Lai, Jianbo; Lu, Qiaoqiao; Zhang, Peng; Xu, Tingting; Xu, Yi; Hu, Shaohua

2017-01-01

Comorbid obsessive-compulsive disorder (OCD) and bipolar disorder (BD) have long been an intractable problem in clinical practice. The increased risk of manic/hypomanic switch hinders the use of antidepressants for managing coexisting OCD symptoms in BD patients. We herein present a case of a patient with BD-OCD comorbidity, who was successfully treated with mood stabilizers and aripiprazole augmentation. The young female patient reported recurrent depressive episodes and aggravating compulsive behaviors before hospitalization. Of note, the patient repetitively attempted suicide and reported dangerous driving because of intolerable mental sufferings. The preexisting depressive episode and OCD symptoms prompted the use of paroxetine, which consequently triggered the manic switching. Her diagnosis was revised into bipolar I disorder. Minimal response with mood stabilizers prompted the addition of aripiprazole (a daily dose of 10 mg), which helped to achieve significant remission in emotional and obsessive-compulsive symptoms. This case highlights the appealing efficacy of a small dose of aripiprazole augmentation for treating BD-OCD comorbidity. Well-designed clinical trials are warranted to verify the current findings.

A hybrid video codec based on extended block sizes, recursive integer transforms, improved interpolation, and flexible motion representation

NASA Astrophysics Data System (ADS)

Karczewicz, Marta; Chen, Peisong; Joshi, Rajan; Wang, Xianglin; Chien, Wei-Jung; Panchal, Rahul; Coban, Muhammed; Chong, In Suk; Reznik, Yuriy A.

2011-01-01

This paper describes video coding technology proposal submitted by Qualcomm Inc. in response to a joint call for proposal (CfP) issued by ITU-T SG16 Q.6 (VCEG) and ISO/IEC JTC1/SC29/WG11 (MPEG) in January 2010. Proposed video codec follows a hybrid coding approach based on temporal prediction, followed by transform, quantization, and entropy coding of the residual. Some of its key features are extended block sizes (up to 64x64), recursive integer transforms, single pass switched interpolation filters with offsets (single pass SIFO), mode dependent directional transform (MDDT) for intra-coding, luma and chroma high precision filtering, geometry motion partitioning, adaptive motion vector resolution. It also incorporates internal bit-depth increase (IBDI), and modified quadtree based adaptive loop filtering (QALF). Simulation results are presented for a variety of bit rates, resolutions and coding configurations to demonstrate the high compression efficiency achieved by the proposed video codec at moderate level of encoding and decoding complexity. For random access hierarchical B configuration (HierB), the proposed video codec achieves an average BD-rate reduction of 30.88c/o compared to the H.264/AVC alpha anchor. For low delay hierarchical P (HierP) configuration, the proposed video codec achieves an average BD-rate reduction of 32.96c/o and 48.57c/o, compared to the H.264/AVC beta and gamma anchors, respectively.

Carpal Tunnel Syndrome in Behçet's Disease.

PubMed

Lee, Jungsoo; Cho, Suhyun; Kim, Do Young; Zheng, Zhenlong; Park, Hoon; Bang, Dongsik

2015-07-01

Behçet's disease (BD) is a chronic inflammatory disease characterized by orogenital ulcers, skin and ocular lesions, in addition to articular, vascular, and neurologic symptoms. Carpal tunnel syndrome (CTS), can also occur in BD patients secondary to inflammation in the connective tissues, vessels, and tendons, as well as nerve involvement in BD itself. However, reports of patients who have CTS in BD are rare. The aim of this study was to evaluate the clinical characteristics of CTS in BD patients. Retrospective analysis of the medical records of 1750 BD patients, and 14 (0.8%) BD patients who were diagnosed with CTS was performed at the BD Specialty Clinic of Severance Hospital. Patient demographics, disease activity/severity for both diseases, and the clinical characteristics of CTS in BD were recorded and analyzed. All 14 BD patients with CTS were women. Twelve patients (85.7%) were diagnosed with active BD. The CTS was mild in 8 patients (57.2%), moderate in 3 patients (21.4%), and severe in 3 patients (21.4%). Ten patients (71.4%) had BD prior to the diagnosis of CTS, and these 10 patients all had active BD. CTS can occur as a result of the inflammation associated with BD and can also be the presenting symptom of nerve involvement in BD. CTS can also develop as the initial symptom of BD. Therefore, a higher degree of suspicion should be maintained for CTS in patients with BD and vice versa; however, the exact relationship is uncertain.

Imperfect pathogen detection from non-invasive skin swabs biases disease inference

USGS Publications Warehouse

DiRenzo, Graziella V.; Grant, Evan H. Campbell; Longo, Ana; Che-Castaldo, Christian; Zamudio, Kelly R.; Lips, Karen

2018-01-01

1. Conservation managers rely on accurate estimates of disease parameters, such as pathogen prevalence and infection intensity, to assess disease status of a host population. However, these disease metrics may be biased if low-level infection intensities are missed by sampling methods or laboratory diagnostic tests. These false negatives underestimate pathogen prevalence and overestimate mean infection intensity of infected individuals. 2. Our objectives were two-fold. First, we quantified false negative error rates of Batrachochytrium dendrobatidis on non-invasive skin swabs collected from an amphibian community in El Copé, Panama. We swabbed amphibians twice in sequence, and we used a recently developed hierarchical Bayesian estimator to assess disease status of the population. Second, we developed a novel hierarchical Bayesian model to simultaneously account for imperfect pathogen detection from field sampling and laboratory diagnostic testing. We evaluated the performance of the model using simulations and varying sampling design to quantify the magnitude of bias in estimates of pathogen prevalence and infection intensity. 3. We show that Bd detection probability from skin swabs was related to host infection intensity, where Bd infections < 10 zoospores have < 95% probability of being detected. If imperfect Bd detection was not considered, then Bd prevalence was underestimated by as much as 16%. In the Bd-amphibian system, this indicates a need to correct for imperfect pathogen detection caused by skin swabs in persisting host communities with low-level infections. More generally, our results have implications for study designs in other disease systems, particularly those with similar objectives, biology, and sampling decisions. 4. Uncertainty in pathogen detection is an inherent property of most sampling protocols and diagnostic tests, where the magnitude of bias depends on the study system, type of infection, and false negative error rates. Given that it may be difficult to know this information in advance, we advocate that the most cautious approach is to assume all errors are possible and to accommodate them by adjusting sampling designs. The modeling framework presented here improves the accuracy in estimating pathogen prevalence and infection intensity.

Human β-Defensin 1 and β-Defensin 3 (Mouse Ortholog mBD14) Function as Full Endogenous Agonists at Select Melanocortin Receptors.

PubMed

Ericson, Mark D; Singh, Anamika; Tala, Srinivasa R; Haslach, Erica M; Dirain, Marvin L S; Schaub, Jay W; Flores, Viktor; Eick, Natalie; Lensing, Cody J; Freeman, Katie T; Smeester, Branden A; Adank, Danielle N; Wilber, Stacey L; Speth, Robert; Haskell-Luevano, Carrie

2018-04-26

β-Defensin 3 (BD3) was identified as a ligand for the melanocortin receptors (MCRs) in 2007, although the pharmacology activity of BD3 has not been clearly elucidated. Herein, it is demonstrated that human BD3 and mouse BD3 are full micromolar agonists at the MCRs. Furthermore, mouse β-defensin 1 (BD1) and human BD1 are also MCR micromolar agonists. This work identifies BD1 as an endogenous MCR ligand and clarifies the controversial role of BD3 as a micromolar agonist.

Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study.

PubMed

Altamura, A C; Salvadori, Daniele; Madaro, Donato; Santini, Annalisa; Mundo, Emanuela

2003-09-01

The literature on the use of quetiapine for the treatment of bipolar disorder (BD) is limited to case reports, and there are no systematic studies on the efficacy of quetiapine in the prophylactic treatment of BD. The aim of the present study was to compare the efficacy of flexible doses of quetiapine and well established mood stabilizers in the maintenance treatment of BD. Twenty-eight DSM-IV BD outpatients were consecutively recruited into the study and were randomized to receive one of two open-label treatments, with quetiapine or classical mood stabilizers at flexible doses for 12 months. Clinical assessment was carried out using BPRS, CGI, YMRS and the 21-item HAM-D at baseline (T0) and every 2 months until the end of the study. ANOVAs with repeated measures were applied to the rating scale scores considering the time and the treatment group as main factors. All patients experienced a significant improvement on the BPRS, CGI and HAM-D scores, with no significant side-effects and a good compliance. This study should be considered preliminary given the small sample size investigated and the open-label design. If these results will be replicated on larger samples and in controlled studies, there could be relevant implications for the use of quetiapine as an alternative maintenance treatment for BD.

Transcriptomic analysis of submergence-tolerant and sensitive Brachypodium distachyon ecotypes reveals oxidative stress as a major tolerance factor

PubMed Central

Rivera-Contreras, Irma Karla; Zamora-Hernández, Teresa; Huerta-Heredia, Ariana Arlene; Capataz-Tafur, Jacqueline; Barrera-Figueroa, Blanca Estela; Juntawong, Piyada; Peña-Castro, Julián Mario

2016-01-01

When excessive amounts of water accumulate around roots and aerial parts of plants, submergence stress occurs. To find the integrated mechanisms of tolerance, we used ecotypes of the monocot model plant Brachypodium distachyon to screen for genetic material with contrasting submergence tolerance. For this purpose, we used a set of previously studied drought sensitive/tolerant ecotypes and the knowledge that drought tolerance is positively associated with submergence stress. We decided to contrast aerial tissue transcriptomes of the ecotype Bd21 14-day-old plants as sensitive and ecotype Bd2-3 as tolerant after 2 days of stress under a long-day photoperiod. Gene ontology and the grouping of transcripts indicated that tolerant Bd2-3 differentially down-regulated NITRATE REDUCTASE and ALTERNATIVE OXIDASE under stress and constitutively up-regulated HAEMOGLOBIN, when compared with the sensitive ecotype, Bd21. These results suggested the removal of nitric oxide, a gaseous phytohormone and concomitant reactive oxygen species as a relevant tolerance determinant. Other mechanisms more active in tolerant Bd2-3 were the pathogen response, glyoxylate and tricarboxylic acid cycle integration, and acetate metabolism. This data set could be employed to design further studies on the basic science of plant tolerance to submergence stress and its biotechnological application in the development of submergence-tolerant crops. PMID:27282694

The association between school exam grades and subsequent development of bipolar disorder.

PubMed

Pedersen, Steffie Damgaard; Østergaard, Søren Dinesen; Petersen, Liselotte

2018-03-13

Prior studies have indicated that both high and low school grades are associated with development of bipolar disorder (BD), but these studies have not adjusted for parental history of mental disorder, which is a likely confounder. Furthermore, the association between school grades and bipolar I disorder (BD-I) has not been studied. Therefore, we aimed to study the association between school exam grades and subsequent development of BD and BD-I while adjusting for parental history of mental disorder. We conducted a register-based nationwide cohort study following 505 688 individuals born in Denmark between 1987 and 1995. We investigated the association between school exam grades and development of BD or BD-I with a Cox model adjusting for family history of mental disorder and other potential confounders. During follow-up, 900 individuals were diagnosed with BD and 277 of these with BD-I. The risk for BD and BD-I was significantly increased for individuals not having completed the exams at term [adjusted hazard ratio (aHR) for BD (aHR=1.71, 95% CI: 1.43-2.04) and for BD-I (aHR=1.57, 95% CI: 1.13-2.19)]. Also, having low exam grades in mathematics was associated with increased risk of both BD (aHR=2.41, 95% CI: 1.27-4.59) and BD-I (aHR=2.71, 95% CI: 1.41-5.21). Females with very high exam grades in Danish (percentile group>97.7) had a significantly increased risk of BD-I (aHR=2.49, 95% CI: 1.19-5.23). The potential to develop BD seems to affect the school results of individuals negatively even before BD is diagnosed - with females having the potential to develop BD-I as a possible exception.

Temporal sequencing of nicotine dependence and bipolar disorder in the national epidemiologic survey on alcohol and related conditions (NESARC)

PubMed Central

Martínez-Ortega, José M.; Goldstein, Benjamin I.; Gutiérrez-Rojas, Luis; Sala, Regina; Wang, Shuai; Blanco, Carlos

2013-01-01

Bipolar disorder (BD) and nicotine dependence (ND) often co-occur. However, the mechanisms underlying this association remain unclear. We aimed to examine, for the first time in a national and representative sample, the magnitude and direction of the temporal relationship between BD and ND; and to compare, among individuals with lifetime ND and BD, the sociodemographic and clinical characteristics of individuals whose onset of ND preceded the onset of BD (ND-prior) with those whose onset of ND followed the onset of BD (BD-prior). The sample included individuals with lifetime BD type I or ND (n=7958) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n=43093). Survival analyses and logistic regression models were computed to study the temporal association between ND and BD, and to compare ND-prior (n=135) and BD-prior (n=386) individuals. We found that ND predicted the onset of BD and BD also predicted the onset of ND. Furthermore, the risk of developing one disorder following the other one was greatest early in the course of illness. Most individuals with lifetime ND and BD were BD-prior (72.6%). BD-prior individuals had an earlier onset of BD and a higher number of manic episodes. By contrast, ND-prior individuals had an earlier onset of both daily smoking and ND, and an increased prevalence of alcohol use disorder. In conclusion, ND and BD predict the development of each other. The phenomenology and course of ND and BD varied significantly depending on which disorder had earlier onset. PMID:23582710

The influence of social support on psychological distress in Canadian adults with bipolar disorder.

PubMed

Warren, Christie D; Fowler, Ken; Speed, David; Walsh, Anna

2018-05-08

Individuals with bipolar I disorder (BD-I) and bipolar II disorder (BD-II) are at higher risk for experiencing high levels of psychological distress and low levels of social support. The primary objectives of this study were to examine perceived social support and psychological distress among Canadian adults with self-reported BD-I or BD-II as diagnosed by a health professional and explore the relationship between types of social support and psychological distress within this sample. Using a cross-sectional, national datafile, 563 Canadian male and female adults (20-64 years) who reported being diagnosed with BD-I or BD-II were investigated using the Social Provisions Scale (SPS), and the Kessler Psychological Distress Scale (K10). It was observed that while the BD-I or BD-II sample had significantly lower SPS scores and significantly higher K10 scores than the overall Canadian sample, age and support in the form of reassurance of worth and social integration were associated with decreased psychological distress. Further, a diagnosis of BD-I and BD-II was found to moderate the effect of social support on psychological distress. Despite the limitations, which include self-reported diagnosis of BD-I and BD-II and potential exclusion of those who are not diagnosed but have BD-I or BD-II, these findings suggest that reassurance of worth and social integration may act as protective factors for psychological distress among individuals with BD-I or BD-II.

Affective temperaments are associated with specific clusters of symptoms and psychopathology: a cross-sectional study on bipolar disorder inpatients in acute manic, mixed, or depressive relapse.

PubMed

Iasevoli, Felice; Valchera, Alessandro; Di Giovambattista, Emanuela; Marconi, Massimo; Rapagnani, Maria Paola; De Berardis, Domenico; Martinotti, Giovanni; Fornaro, Michele; Mazza, Monica; Tomasetti, Carmine; Buonaguro, Elisabetta F; Di Giannantonio, Massimo; Perugi, Giulio; de Bartolomeis, Andrea

2013-11-01

The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder. Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data. The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states. Cross-sectional design; sample size. Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described. © 2013 Elsevier B.V. All rights reserved.

Reinforcing effects of sigma-receptor agonists in rats trained to self-administer cocaine.

PubMed

Hiranita, Takato; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L

2010-02-01

sigma-Receptor (sigmaR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of sigmaR ligands in rats trained to self-administer cocaine (0.032-1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/inj cocaine, or by the sigmaR agonists, 1,3-di-(2-tolyl)guanidine (DTG; 1.0 mg/kg/inj) or 2-(4-morpholinethyl) 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084; 0.32 mg/kg/inj), when substituted for cocaine. Lower response rates were maintained at higher and lower doses of the compounds. No dose of the sigmaR antagonists [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047), N-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD 1063)] maintained responding appreciably above levels obtained when responding had no consequences. Presession treatment with sigmaR agonists dose-dependently shifted the cocaine self-administration dose-effect curve leftward. The dopamine-uptake inhibitor, (-)-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (WIN 35,428), dose-dependently shifted the DTG and PRE-084 self-administration dose-effect curves leftward. Treatment with the sigmaR antagonists dose-dependently decreased response rates maintained by DTG or PRE-084, but did not affect cocaine self-administration. Response rates maintained by maximally effective DTG or PRE-084 doses were decreased by sigmaR antagonists at lower doses than those that decreased response rates maintained by food reinforcement. Although sigmaR antagonists block some cocaine-induced effects, the lack of effect on cocaine self-administration suggests that the primary reinforcing effects of cocaine do not involve direct effects at sigmaRs. However, the self-administration of sigmaR agonists in cocaine-trained subjects, facilitation of cocaine self-administration by sigmaR-agonist pretreatment, and the facilitation of sigmaR-agonist self-administration by WIN 35,428, together suggest enhanced abuse-related effects resulting from concomitant dopaminergically mediated actions and sigmaR-mediated actions of the drugs.

Reinforcing Effects of σ-Receptor Agonists in Rats Trained to Self-Administer Cocaine

PubMed Central

Hiranita, Takato; Soto, Paul L.; Tanda, Gianluigi

2010-01-01

σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer cocaine (0.032–1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/inj cocaine, or by the σR agonists, 1,3-di-(2-tolyl)guanidine (DTG; 1.0 mg/kg/inj) or 2-(4-morpholinethyl) 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084; 0.32 mg/kg/inj), when substituted for cocaine. Lower response rates were maintained at higher and lower doses of the compounds. No dose of the σR antagonists [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047), N-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD 1063)] maintained responding appreciably above levels obtained when responding had no consequences. Presession treatment with σR agonists dose-dependently shifted the cocaine self-administration dose-effect curve leftward. The dopamine-uptake inhibitor, (−)-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428), dose-dependently shifted the DTG and PRE-084 self-administration dose-effect curves leftward. Treatment with the σR antagonists dose-dependently decreased response rates maintained by DTG or PRE-084, but did not affect cocaine self-administration. Response rates maintained by maximally effective DTG or PRE-084 doses were decreased by σR antagonists at lower doses than those that decreased response rates maintained by food reinforcement. Although σR antagonists block some cocaine-induced effects, the lack of effect on cocaine self-administration suggests that the primary reinforcing effects of cocaine do not involve direct effects at σRs. However, the self-administration of σR agonists in cocaine-trained subjects, facilitation of cocaine self-administration by σR-agonist pretreatment, and the facilitation of σR-agonist self-administration by WIN 35,428, together suggest enhanced abuse-related effects resulting from concomitant dopaminergically mediated actions and σR-mediated actions of the drugs. PMID:19892920

Design and realization of the baseband processor in satellite navigation and positioning receiver

NASA Astrophysics Data System (ADS)

Zhang, Dawei; Hu, Xiulin; Li, Chen

2007-11-01

The content of this paper is focused on the Design and realization of the baseband processor in satellite navigation and positioning receiver. Baseband processor is the most important part of the satellite positioning receiver. The design covers baseband processor's main functions include multi-channel digital signal DDC, acquisition, code tracking, carrier tracking, demodulation, etc. The realization is based on an Altera's FPGA device, that makes the system can be improved and upgraded without modifying the hardware. It embodies the theory of software defined radio (SDR), and puts the theory of the spread spectrum into practice. This paper puts emphasis on the realization of baseband processor in FPGA. In the order of choosing chips, design entry, debugging and synthesis, the flow is presented detailedly. Additionally the paper detailed realization of Digital PLL in order to explain a method of reducing the consumption of FPGA. Finally, the paper presents the result of Synthesis. This design has been used in BD-1, BD-2 and GPS.

Effectiveness of the Dader Method for pharmaceutical care in patients with bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar I disorder (BD-I) is a chronic mental illness characterized by the presence of one or more manic episodes, or both depressive and manic episodes, usually separated by asymptomatic intervals. Pharmacists can contribute to the management of BD-I, mainly with the use of effective and safe drugs, and improve the patient’s life quality through pharmaceutical care. Some studies have shown the effect of pharmaceutical care in the achievement of therapeutic goals in different illnesses; however, to our knowledge, there is a lack of randomized controlled trials designed to assess the effect of pharmacist intervention in patients with BD. The aim of this study is to assess the effectiveness of the Dader Method for pharmaceutical care in patients with BD-I. Methods/design Randomized, controlled, prospective, single-center clinical trial with duration of 12 months will be performed to compare the effect of Dader Method of pharmaceutical care with the usual care process of patients in a psychiatric clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been discharged or referred from outpatients service of the San Juan de Dios Clinic (Antioquia, Colombia) will be included. Patients will be randomized into the intervention group who will receive pharmaceutical care provided by pharmacists working in collaboration with psychiatrists, or into the control group who will receive usual care and verbal-written counseling regarding BD. Study outcomes will be assessed at baseline and at 3, 6, 9, and 12 months after randomization. The primary outcome will be to measure the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits. Effectiveness, safety, adherence, and quality of life will be assessed as secondary outcomes. Statistical analyses will be performed using two-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; a P value <0.05 will be considered as statistically significant. Discussion As far as we know, this is the first randomized controlled trial to assess the effect of the Dader Method for pharmaceutical care in patients with BD-I and it could generate valuable information and recommendations about the role of pharmacists in the improvement of therapeutic goals, solution of drug-related problems, and adherence. Trial registration Registration number NCT01750255 on August 6, 2012. First patient randomized on 24 November 2011. PMID:24885673

Spatiotemporal pattern of bacillary dysentery in China from 1990 to 2009: what is the driver behind?

PubMed

Xu, Zhiwei; Hu, Wenbiao; Zhang, Yewu; Wang, Xiaofeng; Tong, Shilu; Zhou, Maigeng

2014-01-01

Little is known about the spatiotemporal pattern of bacillary dysentery (BD) in China. This study assessed the geographic distribution and seasonality of BD in China over the past two decades. Data on monthly BD cases in 31 provinces of China from January 1990 to December 2009 obtained from Chinese Center for Disease Control and Prevention, and data on demographic and geographic factors, as well as climatic factors, were compiled. The spatial distributions of BD in the four periods across different provinces were mapped, and heat maps were created to present the seasonality of BD by geography. A cosinor function combined with Poisson regression was used to quantify the seasonal parameters of BD, and a regression analysis was conducted to identify the potential drivers of morbidity and seasonality of BD. Although most regions of China have experienced considerable declines in BD morbidity over the past two decades, Beijing and Ningxia still had high BD morbidity in 2009. BD morbidity decreased more slowly in North-west China than other regions. BD in China mainly peaked from July to September, with heterogeneity in peak time between regions. Relative humidity was associated with BD morbidity and peak time, and latitude was the major predictor of BD amplitude. The transmission of BD was heterogeneous in China. Improved sanitation and hygiene in North-west China, and better access to clean water and food in the big floating population in some metropolises could be the focus of future preventive interventions against BD. BD control efforts should put more emphasis on those dry areas in summer.

Business Re-Engineering: Lessons Learned from the U.S. Army Corps of Engineers Modernization Program

DTIC Science & Technology

1992-06-01

and Management, Vol 7, 1984. Yang, Dori "Boeing Knocks Down the Wall Between the Dreamers and the Doers", Business Week, 28 Oct 1991, p. 12 0 . "The...Management (CIM) Initiative that have lead to a number of tools such as Activity Based Costing (ABC) and IDEF that may be used as building blocks for a re...Tung X. Bui 646-2630 AS/BD DD FORM 1473.84 MAR 83 APR edition may be used until exhausted SECURITY CLASSIFICATION OF THIS PAGE All other editions are

Nigeria`s Escravos gas project starts up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nwokoma, M.

Nigeria`s Escravos gas project, Delta state, officially began late last year. The project -- 6,650 b/d of LPG and 1,740 b/d of condensate from 165 MMscfd of gas -- is the first attempt to rid Nigeria of incessant flares that have lit the Delta skies. Operator Chevron Nigeria Ltd. believes that the Escravos project will enable the joint venture to utilize a significant portion of the gas reserves, thus reducing gas flaring. The paper describes the background of the project, the gas fields, transport pipeline, process design, construction, and start-up.

Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study.

PubMed

Cyprien, Fabienne; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Olié, Emilie; Le Bars, Emmanuelle; Bonafé, Alain; Mura, Thibault; Jollant, Fabrice; Courtet, Philippe; Artero, Sylvaine

2016-12-01

Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders. CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity. FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations. Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men. Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.

PubMed

Soehner, Adriane M; Bertocci, Michele A; Manelis, Anna; Bebko, Genna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Birmaher, Boris; Phillips, Mary L

2016-11-15

Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP. Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed. Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group ⁎ sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only. Cross-sectional design and small sample size. Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial distribution of Batrachochytrium dendrobatidis in South American caecilians.

PubMed

Lambertini, Carolina; Becker, C Guilherme; Bardier, Cecilia; da Silva Leite, Domingos; Toledo, Luís Felipe

2017-04-20

The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) is linked to population declines in anurans and salamanders globally. To date, however, few studies have attempted to screen Bd in live caecilians; Bd-positive caecilians have only been reported in Africa and French Guiana. Here, we performed a retrospective survey of museum preserved specimens to (1) describe spatial patterns of Bd infection in Gymnophiona across South America and (2) test whether areas of low climatic suitability for Bd in anurans predict Bd spatial epidemiology in caecilians. We used quantitative PCR to detect Bd in preserved caecilians collected over a 109 yr period, and performed autologistic regressions to test the effect of bioclimatic metrics of temperature and precipitation, vegetation density, and elevation on the likelihood of Bd occurrence. We detected an overall Bd prevalence of 12.4%, with positive samples spanning the Uruguayan savanna, Brazil's Atlantic Forest, and the Amazon basin. Our autologistic models detected a strong effect of macroclimate, a weaker effect of vegetation density, and no effect of elevation on the likelihood of Bd occurrence. Although most of our Bd-positive records overlapped with reported areas of high climatic suitability for the fungus in the Neotropics, many of our new Bd-positive samples extend far into areas of poor suitability for Bd in anurans. Our results highlight an important gap in the study of amphibian chytridiomycosis: the potential negative impact of Bd on Neotropical caecilians and the hypothetical role of caecilians as Bd reservoirs.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

PubMed

Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

2013-12-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone

PubMed Central

RIVERA, CÉSAR; MONSALVE, FRANCISCO; SALAS, JUAN; MORÁN, ANDREA; SUAZO, IVÁN

2013-01-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H2O (n=3), distilled water without the drug and alveolar bone damage; BD/H2O/PRP (n=3), BD and PRP; BD/H2O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects. PMID:24250728

Cofacial boron dipyrromethene (Bodipy) dimers: synthesis, charge delocalization, and exciton coupling.

PubMed

Benniston, Andrew C; Copley, Graeme; Harriman, Anthony; Howgego, David; Harrington, Ross W; Clegg, William

2010-03-19

A series of compounds containing two boron dipyrromethene (Bodipy) units has been synthesized and fully characterized in which the spacer between the two Bodipy groups is varied from dibenzothiophene (BD1), to dibenzofuran (BD2), to 9,9-dimethylxanthene (BD3), and finally to diphenyl ether (BD4 and BD5). For BD1-BD4 the Bodipy units adopt, to varying degrees, cofacial conformations that allow for systematic variations of both the mutual orientation and the mean separation of the two Bodipy residues. In the remaining dimer, BD5, the Bodipy units are well-separated and cannot come into close proximity. Single-crystal X-ray structures have been determined for BD1-BD3 and reveal that the "bite angle" between the two Bodipy residues decreases progressively along the series with individual values of 41.33(5) degrees, 36.95(6) degrees, and 8.57(3) degrees. Detailed (1)H and (19)F NMR studies for BD3 and BD4 show the methylene protons to be diastereotopic due to restricted rotation of the two Bodipy groups. For BD4 conformational rocking is invoked to explain the variable-temperature NMR spectra, whereby the methyl and methylene groups become inequivalent. Cyclic voltammetry indicates reversible oxidation and reduction of the Bodipy groups. However, the close proximity of the Bodipy groups in BD3 and BD4 results in two well-resolved waves in the anodic region, and slight splitting of the cathodic wave. Peak splitting is attributed to charge delocalization. Spectroelectrochemical measurements at a fixed oxidative potential reveal an optical intervalence charge-transfer (IVCT) absorption band. This IVCT band is attributed to electron exchange between the cofacially arranged neutral and mono-oxidized Bodipy units. Various levels of exciton coupling are observed for BD1-BD4, but not BD5 since here the Bodipy groups remain isolated.

Introduction of an automated user-independent quantitative volumetric magnetic resonance imaging breast density measurement system using the Dixon sequence: comparison with mammographic breast density assessment.

PubMed

Wengert, Georg Johannes; Helbich, Thomas H; Vogl, Wolf-Dieter; Baltzer, Pascal; Langs, Georg; Weber, Michael; Bogner, Wolfgang; Gruber, Stephan; Trattnig, Siegfried; Pinker, Katja

2015-02-01

The purposes of this study were to introduce and assess an automated user-independent quantitative volumetric (AUQV) breast density (BD) measurement system on the basis of magnetic resonance imaging (MRI) using the Dixon technique as well as to compare it with qualitative and quantitative mammographic (MG) BD measurements. Forty-three women with normal mammogram results (Breast Imaging Reporting and Data System 1) were included in this institutional review board-approved prospective study. All participants were subjected to BD assessment with MRI using the following sequence with the Dixon technique (echo time/echo time, 6 milliseconds/2.45 milliseconds/2.67 milliseconds; 1-mm isotropic; 3 minutes 38 seconds). To test the reproducibility, a second MRI after patient repositioning was performed. The AUQV magnetic resonance (MR) BD measurement system automatically calculated percentage (%) BD. The qualitative BD assessment was performed using the American College of Radiology Breast Imaging Reporting and Data System BD categories. Quantitative BD was estimated semiautomatically using the thresholding technique Cumulus4. Appropriate statistical tests were used to assess the agreement between the AUQV MR measurements and to compare them with qualitative and quantitative MG BD estimations. The AUQV MR BD measurements were successfully performed in all 43 women. There was a nearly perfect agreement of AUQV MR BD measurements between the 2 MR examinations for % BD (P < 0.001; intraclass correlation coefficient, 0.998) with no significant differences (P = 0.384). The AUQV MR BD measurements were significantly lower than quantitative and qualitative MG BD assessment (P < 0.001). The AUQV MR BD measurement system allows a fully automated, user-independent, robust, reproducible, as well as radiation- and compression-free volumetric quantitative BD assessment through different levels of BD. The AUQV MR BD measurements were significantly lower than the currently used qualitative and quantitative MG-based approaches, implying that the current assessment might overestimate breast density with MG.

Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study.

PubMed

Paul, C; Stein Gold, L; Cambazard, F; Kalb, R E; Lowson, D; Bang, B; Griffiths, C E M

2017-01-01

Fixed combination calcipotriol 50 μg/g (Cal) plus betamethasone 0.5 mg/g (BD) foam has been developed as a new treatment option for patients with psoriasis. The randomized, parallel-group, investigator-blinded Phase III, 12-week PSO-ABLE study compared the efficacy and safety of Cal/BD foam with Cal/BD gel. Patients aged ≥18 years with mild-to-severe psoriasis were randomized 4:4:1:1 to once-daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle (NCT02132936). The primary efficacy endpoint was the proportion of patients who were clear/almost clear with a ≥ 2 grade improvement according to the physician's global assessment of disease severity (i.e. treatment success) at week 4 for Cal/BD foam vs. week 8 for Cal/BD gel. Secondary efficacy endpoints included: proportion of patients achieving at least a 75% reduction in modified psoriasis area and severity index (mPASI75), and time to treatment success (TTTS). Safety was monitored throughout. A total of 463 patients were randomized: Cal/BD foam (n = 185), Cal/BD gel (n = 188), foam vehicle (n = 47), gel vehicle (n = 43); overall completion rate was 90%. Cal/BD foam achieved higher treatment success rates (38% vs. 22%; P < 0.001) and mPASI75 (52% vs. 35%; P < 0.001) by week 4 than Cal/BD gel by week 8. Median TTTS with Cal/BD foam was 6 weeks; this could not be determined for Cal/BD gel as 50% treatment success was not achieved (P < 0.001). Adverse drug reactions were reported in 14 (7.6%) Cal/BD aerosol foam patients and 7 (3.7%) Cal/BD gel patients; all were single events except for itch with Cal/BD aerosol foam (n = 5; 2.7%) and worsening psoriasis with Cal/BD gel (n = 3; 1.6%). Cal/BD aerosol foam showed significantly greater efficacy after 4 weeks, than 8 weeks of treatment with Cal/BD gel, with similar tolerability. © 2016 European Academy of Dermatology and Venereology.

Spatiotemporal Pattern of Bacillary Dysentery in China from 1990 to 2009: What Is the Driver Behind?

PubMed Central

Wang, Xiaofeng; Tong, Shilu; Zhou, Maigeng

2014-01-01

Background Little is known about the spatiotemporal pattern of bacillary dysentery (BD) in China. This study assessed the geographic distribution and seasonality of BD in China over the past two decades. Methods Data on monthly BD cases in 31 provinces of China from January 1990 to December 2009 obtained from Chinese Center for Disease Control and Prevention, and data on demographic and geographic factors, as well as climatic factors, were compiled. The spatial distributions of BD in the four periods across different provinces were mapped, and heat maps were created to present the seasonality of BD by geography. A cosinor function combined with Poisson regression was used to quantify the seasonal parameters of BD, and a regression analysis was conducted to identify the potential drivers of morbidity and seasonality of BD. Results Although most regions of China have experienced considerable declines in BD morbidity over the past two decades, Beijing and Ningxia still had high BD morbidity in 2009. BD morbidity decreased more slowly in North-west China than other regions. BD in China mainly peaked from July to September, with heterogeneity in peak time between regions. Relative humidity was associated with BD morbidity and peak time, and latitude was the major predictor of BD amplitude. Conclusions The transmission of BD was heterogeneous in China. Improved sanitation and hygiene in North-west China, and better access to clean water and food in the big floating population in some metropolises could be the focus of future preventive interventions against BD. BD control efforts should put more emphasis on those dry areas in summer. PMID:25093593

Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data.

PubMed

Cui, Lu; Wang, Yu; Liu, Zhihong; Chen, Hongzhuan; Wang, Hao; Zhou, Xinxin; Xu, Jun

2015-11-23

Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed.

Fairness in optimizing bus-crew scheduling process.

PubMed

Ma, Jihui; Song, Cuiying; Ceder, Avishai Avi; Liu, Tao; Guan, Wei

2017-01-01

This work proposes a model considering fairness in the problem of crew scheduling for bus drivers (CSP-BD) using a hybrid ant-colony optimization (HACO) algorithm to solve it. The main contributions of this work are the following: (a) a valid approach for cases with a special cost structure and constraints considering the fairness of working time and idle time; (b) an improved algorithm incorporating Gamma heuristic function and selecting rules. The relationships of each cost are examined with ten bus lines collected from the Beijing Public Transport Holdings (Group) Co., Ltd., one of the largest bus transit companies in the world. It shows that unfair cost is indirectly related to common cost, fixed cost and extra cost and also the unfair cost approaches to common and fixed cost when its coefficient is twice of common cost coefficient. Furthermore, the longest time for the tested bus line with 1108 pieces, 74 blocks is less than 30 minutes. The results indicate that the HACO-based algorithm can be a feasible and efficient optimization technique for CSP-BD, especially with large scale problems.

Substance Use Disorders and Suicide Attempts in Bipolar Subtypes

PubMed Central

Sublette, M. Elizabeth; Carballo, Juan J.; Moreno, Carmen; Galfalvy, Hanga C.; Brent, David A.; Birmaher, Boris; Mann, J. John; Oquendo, Maria A.

2009-01-01

1. Abstract Bipolar disorder (BD) is associated with high rates of suicide attempt and completion. Substance use disorders (SUD) have been identified as potent risk factors for suicidal behavior in BD. However, little is known concerning differences between BD subtypes with regard to SUD as a risk factor for suicidal behavior. We studied previous suicidal behavior in adults with a major depressive episode in context of BD type I (BD-I; N=96) or BD type II (BD-II; N=42), with and without history of SUD. Logistic regressions assessed the association between SUD and suicide attempt history by BD type, and exploratory analyses examined the effects of other clinical characteristics on these relationships. SUD were associated with suicide attempt in BD-I but not BD-II, an effect not attributable to sample size differences. The higher suicide attempt rate associated with alcoholism in BD-I was mostly explained by higher aggression scores, and earlier age of BD onset increased the likelihood that alcohol use disorder would be associated with suicide attempt(s). The higher suicide attempt rate associated with other drug use disorders in BD-I was collectively explained by higher impulsivity, hostility, and aggression scores. The presence of both alcohol and drug use disorders increased odds of a history of suicide attempt in a multiplicative fashion: 97% of BD-I who had both comorbid drug and alcohol use disorders had made a suicide attempt. A critical next question is how to target SUD and aggressive traits for prevention of suicidal behavior in BD-I. PMID:18590916

Identification of sociodemographic and clinical factors associated with the levels of human β-defensin-1 and human β-defensin-2 in the human milk of Han Chinese.

PubMed

Wang, Xiao-Fang; Cao, Rui-Ming; Li, Jing; Wu, Jing; Wu, Sheng-Mei; Chen, Tong-Xin

2014-03-14

Human milk provides infants with various immune molecules. The objective of the present study was to measure human β-defensin-1 (hBD-1) and human β-defensin-2 (hBD-2) levels in the colostrum and mature milk of healthy Han Chinese, to identify factors regulating milk hBD-1 and hBD-2 expression and to explore the potential protective effect of milk hBD-1 and hBD-2 on infants. A total of 100 mothers and their babies were recruited into the study. Sociodemographic characteristics and other factors were obtained by a questionnaire. Babies were followed up for a period of 6 months. Colostrum samples (n 100) and mature milk samples (n 82) were collected by hand expression. The hBD-1 and hBD-2 concentrations were measured by ELISA. The hBD-1 and hBD-2 levels differed in the colostrum and mature milk. In the colostrum, the concentration ranges of hBD-1 and hBD-2 were 1·04-12·81 μg/ml and 0·31-19·12 ng/ml, respectively. In mature milk, the hBD-1 and hBD-2 levels were 1·03-31·76 ng/ml and 52·65-182·29 pg/ml, respectively. Several independent factors influence their production. The multivariable analysis showed a strong association between pre-pregnancy BMI and hBD-1 levels in the colostrum (P=0·001), mode of delivery was significantly associated with hBD-2 levels in the colostrum (P=0·006) and gestational age was significantly associated with hBD-1 levels in mature milk (P= 0·010). During the first 6 months of life, the incidence rate of upper respiratory infection was found to be less in the high-colostrum hBD-1 group than in the low-colostrum hBD-1 group (χ²=4·995, P=0·025). The present study suggested that the abundance of hBD-1 in the colostrum may have a protective function against upper respiratory infection for infants younger than 6 months.

26 CFR 1.468B - Designated settlement funds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Designated settlement funds. 1.468B Section 1... (CONTINUED) INCOME TAXES Taxable Year for Which Deductions Taken § 1.468B Designated settlement funds. A designated settlement fund, as defined in section 468B(d)(2), is taxed in the manner described in § 1.468B-2...

Different patterns of language activation in post-stroke aphasia are detected by overt and covert versions of the verb generation fMRI task

PubMed Central

Allendorfer, Jane B.; Kissela, Brett M.; Holland, Scott K.; Szaflarski, Jerzy P.

2012-01-01

Summary Background Post-stroke language functions depend on the relative contributions of the dominant and non-dominant hemispheres. Thus, we aimed to identify the neural correlates of overt and covert verb generation in adult post-stroke aphasia. Material/Methods Sixteen aphasic LMCA stroke patients (SPs) and 32 healthy controls (HCs) underwent language testing followed by fMRI while performing an overt event-related verb generation task (ER-VGT) isolating activations related to noun-verb semantic processing or to articulation and auditory processing, and a covert block design verb generation task (BD-VGT). Results BD-VGT activation patterns were consistent with previous studies, while ER-VGT showed different patterns in SPs relative to HCs including less left-hemispheric involvement during semantic processing and predominantly right-sided activation related to articulation and auditory processing. ER-VGT intra-scanner performance was positively associated with activation during semantic associations in the left middle temporal gyrus for HCs (p=0.031) and left middle frontal gyrus for SPs (p=0.042). Increased activation in superior frontal/cingulate gyri was associated with better intra-scanner performance (p=0.020). Lesion size negatively impacted verbal fluency tested with Controlled Oral Word Association Test (p=0.0092) and the Semantic Fluency Test (p=0.033) and trended towards a negative association with verb generation performance on the event-related verb generation task (p=0.081). Conclusions Greater retention of pre-stroke language skills is associated with greater involvement of the left hemisphere with different cortical recruitment patterns observed in SPs versus HCs. Post-stroke verbal fluency may depend more upon the structural and functional integrity of the dominant left hemisphere language network rather than the shift to contralateral homologues. PMID:22367124

WAIS-IV Seven-Subtest Short Form: Validity and Clinical Use in Schizophrenia.

PubMed

Bulzacka, Ewa; Meyers, John E; Boyer, Laurent; Le Gloahec, Tifenn; Fond, Guillaume; Szöke, Andrei; Leboyer, Marion; Schürhoff, Franck

2016-09-01

This study assesses the psychometric properties of Ward's seven-subtest short form (SF) for WAIS-IV in a sample of adults with schizophrenia (SZ) and schizoaffective disorder. Seventy patients diagnosed with schizophrenia or schizoaffective disorder were administered the full version of the WAIS-IV. Four different versions of the Ward's SF were then calculated. The subtests used were: Similarities, Digit Span, Arithmetic, Information, Coding, Picture Completion, and Block Design (BD version) or Matrix Reasoning (MR version). Prorated and regression-based formulae were assessed for each version. The actual and estimated factorial indexes reflected the typical pattern observed in schizophrenia. The four SFs correlated significantly with their full-version counterparts, but the Perceptual Reasoning Index (PRI) correlated below the acceptance threshold for all four versions. The regression-derived estimates showed larger differences compared to the full form. The four forms revealed comparable but generally low clinical category agreement rates for factor indexes. All SFs showed an acceptable reliability, but they were not correlated with clinical outcomes. The WAIS-IV SF offers a good estimate of WAIS-IV intelligence quotient, which is consistent with previous results. Although the overall scores are comparable between the four versions, the prorated forms provided a better estimation of almost all indexes. MR can be used as an alternative for BD without substantially changing the psychometric properties of the SF. However, we recommend a cautious use of these abbreviated forms when it is necessary to estimate the factor index scores, especially PRI, and Processing Speed Index. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Artificial intelligence modeling of cadmium(II) biosorption using rice straw

NASA Astrophysics Data System (ADS)

Nasr, Mahmoud; Mahmoud, Alaa El Din; Fawzy, Manal; Radwan, Ahmed

2017-05-01

The biosorption efficiency of Cd2+ using rice straw was investigated at room temperature (25 ± 4 °C), contact time (2 h) and agitation rate (5 Hz). Experiments studied the effect of three factors, biosorbent dose BD (0.1 and 0.5 g/L), pH (2 and 7) and initial Cd2+ concentration X (10 and 100 mg/L) at two levels "low" and "high". Results showed that, a variation in X from high to low revealed 31 % increase in the Cd2+ biosorption. However, a discrepancy in pH and BD from low to high achieved 28.60 and 23.61 % increase in the removal of Cd2+, respectively. From 23 factorial design, the effects of BD, pH and X achieved p value equals to 0.2248, 0.1881 and 0.1742, respectively, indicating that the influences are in the order X > pH > BD. Similarly, an adaptive neuro-fuzzy inference system indicated that X is the most influential with training and checking errors of 10.87 and 17.94, respectively. This trend was followed by "pH" with training error (15.80) and checking error (17.39), after that BD with training error (16.09) and checking error (16.29). A feed-forward back-propagation neural network with a configuration 3-6-1 achieved correlation ( R) of 0.99 (training), 0.82 (validation) and 0.97 (testing). Thus, the proposed network is capable of predicting Cd2+ biosorption with high accuracy, while the most significant variable was X.

Functional characterization of cinnamyl alcohol dehydrogenase and caffeic acid O-methyltransferase in Brachypodium distachyon

PubMed Central

2013-01-01

Background Lignin is a significant barrier in the conversion of plant biomass to bioethanol. Cinnamyl alcohol dehydrogenase (CAD) and caffeic acid O-methyltransferase (COMT) catalyze key steps in the pathway of lignin monomer biosynthesis. Brown midrib mutants in Zea mays and Sorghum bicolor with impaired CAD or COMT activity have attracted considerable agronomic interest for their altered lignin composition and improved digestibility. Here, we identified and functionally characterized candidate genes encoding CAD and COMT enzymes in the grass model species Brachypodium distachyon with the aim of improving crops for efficient biofuel production. Results We developed transgenic plants overexpressing artificial microRNA designed to silence BdCAD1 or BdCOMT4. Both transgenes caused altered flowering time and increased stem count and weight. Downregulation of BdCAD1 caused a leaf brown midrib phenotype, the first time this phenotype has been observed in a C3 plant. While acetyl bromide soluble lignin measurements were equivalent in BdCAD1 downregulated and control plants, histochemical staining and thioacidolysis indicated a decrease in lignin syringyl units and reduced syringyl/guaiacyl ratio in the transgenic plants. BdCOMT4 downregulated plants exhibited a reduction in total lignin content and decreased Maule staining of syringyl units in stem. Ethanol yield by microbial fermentation was enhanced in amiR-cad1-8 plants. Conclusion These results have elucidated two key genes in the lignin biosynthetic pathway in B. distachyon that, when perturbed, may result in greater stem biomass yield and bioconversion efficiency. PMID:23902793

The involuntary nature of binge drinking: goal directedness and awareness of intention

PubMed Central

Doñamayor, Nuria; Strelchuk, Daniela; Baek, Kwangyeol; Banca, Paula

2017-01-01

Abstract Binge drinking represents a public health issue and is a known risk factor in the development of alcohol use disorders. Previous studies have shown behavioural as well as neuroanatomical alterations associated with binge drinking. Here, we address the question of the automaticity or involuntary nature of the behaviour by assessing goal‐directed behaviour and intentionality. In this study, we used a computational two‐step task, designed to discern between model‐based/goal‐directed and model‐free/habitual behaviours, and the classic Libet clock task, to study intention awareness, in a sample of 31 severe binge drinkers (BD) and 35 matched healthy volunteers. We observed that BD had impaired goal‐directed behaviour in the two‐step task compared with healthy volunteers. In the Libet clock task, BD showed delayed intention awareness. Further, we demonstrated that alcohol use severity, as reflected by the alcohol use disorders identification test, correlated with decreased conscious awareness of volitional intention in BD, although it was unrelated to performance on the two‐step task. However, the time elapsed since the last drinking binge influenced the model‐free scores, with BD showing less habitual behaviour after longer abstinence. Our findings suggest that the implementation of goal‐directed strategies and the awareness of volitional intention are affected in current heavy alcohol users. However, the modulation of these impairments by alcohol use severity and abstinence suggests a state effect of alcohol use in these measures and that top‐down volitional control might be ameliorated with alcohol use cessation. PMID:28419776

Widespread presence of the pathogenic fungus Batrachochytrium dendrobatidis in wild amphibian communities in Madagascar

PubMed Central

Bletz, Molly C.; Rosa, Gonçalo M.; Andreone, Franco; Courtois, Elodie A.; Schmeller, Dirk S.; Rabibisoa, Nirhy H. C.; Rabemananjara, Falitiana C. E.; Raharivololoniaina, Liliane; Vences, Miguel; Weldon, Ché; Edmonds, Devin; Raxworthy, Christopher J.; Harris, Reid N.; Fisher, Matthew C.; Crottini, Angelica

2015-01-01

Amphibian chytridiomycosis, an emerging infectious disease caused by the fungus Batrachochytrium dendrobatidis (Bd), has been a significant driver of amphibian declines. While globally widespread, Bd had not yet been reported from within Madagascar. We document surveys conducted across the country between 2005 and 2014, showing Bd's first record in 2010. Subsequently, Bd was detected in multiple areas, with prevalence reaching up to 100%. Detection of Bd appears to be associated with mid to high elevation sites and to have a seasonal pattern, with greater detectability during the dry season. Lineage-based PCR was performed on a subset of samples. While some did not amplify with any lineage probe, when a positive signal was observed, samples were most similar to the Global Panzootic Lineage (BdGPL). These results may suggest that Bd arrived recently, but do not exclude the existence of a previously undetected endemic Bd genotype. Representatives of all native anuran families have tested Bd-positive, and exposure trials confirm infection by Bd is possible. Bd's presence could pose significant threats to Madagascar's unique “megadiverse” amphibians. PMID:25719857

Clinical Implications of DSM-IV Subtyping of Bipolar Disorders in Referred Children and Adolescents

ERIC Educational Resources Information Center

Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Pari, Cinzia; Pfanner, Chiara; Berloffa, Stefano; Toni, Cristina

2007-01-01

Objective: According to DSM-IV, bipolar disorders (BDs) include four subtypes, BD I, BD II, cyclothymic disorder, and BD not otherwise specified (NOS). We explore the clinical implications of this subtyping in a naturalistic sample of referred youths with BD I, BD II, and BD-NOS. Method: The sample consisted of 217 patients, 135 males and 82…

Historical amphibian declines and extinctions in Brazil linked to chytridiomycosis

PubMed Central

Carvalho, Tamilie; Becker, C. Guilherme

2017-01-01

The recent increase in emerging fungal diseases is causing unprecedented threats to biodiversity. The origin of spread of the frog-killing fungus Batrachochytrium dendrobatidis (Bd) is a matter of continued debate. To date, the historical amphibian declines in Brazil could not be attributed to chytridiomycosis; the high diversity of hosts coupled with the presence of several Bd lineages predating the reported declines raised the hypothesis that a hypervirulent Bd genotype spread from Brazil to other continents causing the recent global amphibian crisis. We tested for a spatio-temporal overlap between Bd and areas of historical amphibian population declines and extinctions in Brazil. A spatio-temporal convergence between Bd and declines would support the hypothesis that Brazilian amphibians were not adapted to Bd prior to the reported declines, thus weakening the hypothesis that Brazil was the global origin of Bd emergence. Alternatively, a lack of spatio-temporal association between Bd and frog declines would indicate an evolution of host resistance in Brazilian frogs predating Bd's global emergence, further supporting Brazil as the potential origin of the Bd panzootic. Here, we Bd-screened over 30 000 museum-preserved tadpoles collected in Brazil between 1930 and 2015 and overlaid spatio-temporal Bd data with areas of historical amphibian declines. We detected an increase in the proportion of Bd-infected tadpoles during the peak of amphibian declines (1979–1987). We also found that clusters of Bd-positive samples spatio-temporally overlapped with most records of amphibian declines in Brazil's Atlantic Forest. Our findings indicate that Brazil is post epizootic for chytridiomycosis and provide another piece to the puzzle to explain the origin of Bd globally. PMID:28179514

Historical amphibian declines and extinctions in Brazil linked to chytridiomycosis.

PubMed

Carvalho, Tamilie; Becker, C Guilherme; Toledo, Luís Felipe

2017-02-08

The recent increase in emerging fungal diseases is causing unprecedented threats to biodiversity. The origin of spread of the frog-killing fungus Batrachochytrium dendrobatidis ( Bd ) is a matter of continued debate. To date, the historical amphibian declines in Brazil could not be attributed to chytridiomycosis; the high diversity of hosts coupled with the presence of several Bd lineages predating the reported declines raised the hypothesis that a hypervirulent Bd genotype spread from Brazil to other continents causing the recent global amphibian crisis. We tested for a spatio-temporal overlap between Bd and areas of historical amphibian population declines and extinctions in Brazil. A spatio-temporal convergence between Bd and declines would support the hypothesis that Brazilian amphibians were not adapted to Bd prior to the reported declines, thus weakening the hypothesis that Brazil was the global origin of Bd emergence. Alternatively, a lack of spatio-temporal association between Bd and frog declines would indicate an evolution of host resistance in Brazilian frogs predating Bd 's global emergence , further supporting Brazil as the potential origin of the Bd panzootic. Here, we Bd -screened over 30 000 museum-preserved tadpoles collected in Brazil between 1930 and 2015 and overlaid spatio-temporal Bd data with areas of historical amphibian declines. We detected an increase in the proportion of Bd -infected tadpoles during the peak of amphibian declines (1979-1987). We also found that clusters of Bd -positive samples spatio-temporally overlapped with most records of amphibian declines in Brazil's Atlantic Forest. Our findings indicate that Brazil is post epizootic for chytridiomycosis and provide another piece to the puzzle to explain the origin of Bd globally. © 2017 The Author(s).

The role of industry influence in sinus balloon dilation: Trends over time.

PubMed

Gadkaree, Shekhar K; Rathi, Vinay K; Gottschalk, Esther; Feng, Allen L; Phillips, Katie M; Scangas, George A; Metson, Ralph

2018-05-08

Balloon dilation (BD) is a controversial alternative to conventional sinus surgery. The role of industry on practice patterns remains unknown. The aim of this study was to determine whether industry payments from BD manufacturers influence practice patterns for otolaryngologists and evaluate how these payments change over time. Retrospective cohort study using Medicare Provider Utilization and Payment (PUP) Data and Center for Medicare and Medicaid Services Open Payments (OP) general payment datasets. A total of 294 otolaryngologists identified in the PUP dataset who performed BD procedures from January 1, 2013, to December 31, 2015, were cross-referenced in the OP dataset from January 1, 2014, to December 31, 2016, for BD manufacturer payments. Payments to surgeons performing BD stratified by amount, type, and number of procedures performed were primary outcome measures. Of the 294 otolaryngologists reporting BD procedures, 223 (76%) received payments from a company that manufactures BD devices. Receipt of $2,500 in BD payments was associated with performance of one additional BD procedure, and consulting fees were most positively associated with performing additional BD procedures (P = 0.006). The providers receiving the most in BD payments were more likely to continue to receive the most in payments, regardless of number of BD procedures performed. Performing more BD procedures did not correlate with decrease in other sinus procedures. Payments to otolaryngologists from manufacturers of sinus BD devices are associated with the performance of an increased number of such procedures. Surgeons should consider the impact of interactions with industry when evaluating patients for BD procedures. 4. Laryngoscope, 00:000-000, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

American tertiary clinic-referred bipolar II disorder versus bipolar I disorder associated with hastened depressive recurrence.

PubMed

Dell'Osso, Bernardo; Shah, Saloni; Do, Dennis; Yuen, Laura D; Hooshmand, Farnaz; Wang, Po W; Miller, Shefali; Ketter, Terence A

2017-12-01

Bipolar disorder (BD) is a chronic, frequently comorbid condition characterized by high rates of mood episode recurrence and suicidality. Little is known about prospective longitudinal characterization of BD type II (BD II) versus type I (BD I) in relation to time to depressive recurrence and recovery from major depressive episode. We therefore assessed times to depressive recurrence/recovery in tertiary clinic-referred BD II versus I patients. Outpatients referred to Stanford BD Clinic during 2000-2011 were assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and with Clinical Monitoring Form during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of bipolar subtype in recovered (euthymic ≥8 weeks) and depressed patients were assessed. Kaplan-Meier analyses assessed the relationships between bipolar subtype and longitudinal depressive severity, and Cox proportional hazard analyses assessed the potential mediators. BD II versus BD I was less common among 105 recovered (39.0 vs. 61.0%, p = 0.03) and more common among 153 depressed (61.4 vs. 38.6%, p = 0.006) patients. Among recovered patients, BD II was associated with 6/25 (24.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics and hastened depressive recurrence (p = 0.015). Among depressed patients, BD II was associated with 8/25 (33.0%) baseline unfavorable illness characteristics/mood symptoms/psychotropics, but only non-significantly associated with delayed depressive recovery. BD II versus BD I was significantly associated with current depression and hastened depressive recurrence, but only non-significantly associated with delayed depressive recovery. Research on bipolar subtype relationships with depressive recurrence/recovery is warranted to enhance clinical management of BD patients.

Low doses of dextromethorphan attenuate morphine-induced rewarding via the sigma-1 receptor at ventral tegmental area in rats.

PubMed

Chen, Shiou-Lan; Hsu, Kuei-Ying; Huang, Eagle Yi-Kung; Lu, Ru-Band; Tao, Pao-Luh

2011-09-01

Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20 mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5 mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3 mg/kg, i.p.). When BD1047 (5 nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Treatment of CHP in LEED® for Building Design and Construction: New Construction and Major Renovations

EPA Pesticide Factsheets

This factsheet introduces CHP and its benefits to architects and engineers, and summarizes how CHP is treated under the LEED® for Building Design and Construction: New Construction and Major Renovations (LEED BD+C: New Construction) rating system.

Enhanced bioactive properties of BiodentineTM modified with bioactive glass nanoparticles.

PubMed

Corral Nuñez, Camila; Covarrubias, Cristian; Fernandez, Eduardo; Oliveira, Osmir Batista de

2017-01-01

To prepare nanocomposite cements based on the incorporation of bioactive glass nanoparticles (nBGs) into BiodentineTM (BD, Septodent, Saint-Maur-des-Fosses Cedex, France) and to assess their bioactive properties. nBGs were synthesised by the sol-gel method. BD nanocomposites (nBG/BD) were prepared with 1 and 2% nBGs by weight; unmodified BD and GC Fuji IX (GIC, GC Corporation, Tokyo, Japan) were used as references. The in vitro ability of the materials to induce apatite formation was assessed in SBF by X-ray diffraction (XRD), attenuated total reflectance with Fourier transform infrared spectroscopy (ATR-FTIR), and scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis. BD and nBG/BD were also applied to dentine discs for seven days; the morphology and elemental composition of the dentine-cement interface were analysed using SEM-EDX. One and two percent nBG/BD composites accelerated apatite formation on the disc surface after short-term immersion in SBF. Apatite was detected on the nBG/BD nanocomposites after three days, compared with seven days for unmodified BD. No apatite formation was detected on the GIC surface. nBG/BD formed a wider interfacial area with dentine than BD, showing blockage of dentine tubules and Si incorporation, suggesting intratubular precipitation. The incorporation of nBGs into BD improves its in vitro bioactivity, accelerating the formation of a crystalline apatite layer on its surface after immersion in SBF. Compared with unmodified BD, nBG/BD showed a wider interfacial area with greater Si incorporation and intratubular precipitation of deposits when immersed in SBF.

A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate aerosol foam versus gel for the topical treatment of plaque psoriasis.

PubMed

Foley, Peter; Garrett, Sinead; Ryttig, Lasse

2018-01-24

Calcipotriol 50 µg/g and betamethasone 0.5 mg/g dipropionate (Cal/BD) aerosol foam formulation provides greater effectiveness and improved patient preference compared with traditional Cal/BD formulations for the topical treatment of plaque psoriasis. To determine the cost-effectiveness of Cal/BD foam compared with Cal/BD gel from the Australian perspective. A Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD foam and gel for the treatment of people with plaque psoriasis. Treatment effectiveness, safety, and utilities were based on a randomized control trial, resource use was informed by expert opinion, and unit costs were obtained from public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios. All costs were reported in 2017 Australian Dollars. The model showed that patients using Cal/BD foam had more QALYs and higher costs over 1 year compared with patients using Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4 weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated with an incremental cost of $15,091 per QALY gained. Cal/BD foam is the most cost-effective Cal/BD formulation for the topical treatment of patients with plaque psoriasis.

Mannans and endo-β-mannanases (MAN) in Brachypodium distachyon: expression profiling and possible role of the BdMAN genes during coleorhiza-limited seed germination

PubMed Central

González-Calle, Virginia; Barrero-Sicilia, Cristina; Carbonero, Pilar; Iglesias-Fernández, Raquel

2015-01-01

Immunolocalization of mannans in the seeds of Brachypodium distachyon reveals the presence of these polysaccharides in the root embryo and in the coleorhiza in the early stages of germination (12h), decreasing thereafter to the point of being hardly detected at 27h. Concurrently, the activity of endo-β-mannanases (MANs; EC 3.2.1.78) that catalyse the hydrolysis of β-1,4 bonds in mannan polymers, increases as germination progresses. The MAN gene family is represented by six members in the Brachypodium genome, and their expression has been explored in different organs and especially in germinating seeds. Transcripts of BdMAN2, BdMAN4 and BdMAN6 accumulate in embryos, with a maximum at 24–30h, and are detected in the coleorhiza and in the root by in situ hybridization analyses, before root protrusion (germination sensu stricto). BdMAN4 is not only present in the embryo root and coleorhiza, but is abundant in the de-embryonated (endosperm) imbibed seeds, while BdMAN2 and BdMAN6 are faintly expressed in endosperm during post-germination (36–42h). BdMAN4 and BdMAN6 transcripts are detected in the aleurone layer. These data indicate that BdMAN2, BdMAN4 and BdMAN6 are important for germination sensu stricto and that BdMAN4 and BdMAN6 may also influence reserve mobilization. Whether the coleorhiza in monocots and the micropylar endosperm in eudicots have similar functions, is discussed. PMID:25922488

Me Power

ERIC Educational Resources Information Center

Poeske, Jack; And Others

1975-01-01

Describes a health curriculum created by two sixth grade teachers. The program they designed includes exercises to help students build up their self image, and study units on smoking, alcohol, drugs, and nutrition. (BD)

Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241

PubMed Central

Zhang, Liaoyuan; Guo, Zewang; Chen, Jiebo; Xu, Quanming; Lin, Hui; Hu, Kaihui; Guan, Xiong; Shen, Yaling

2016-01-01

Serratia sp. T241, a newly isolated xylose-utilizing strain, produced three 2,3-butanediol (2,3-BD) stereoisomers. In this study, three 2,3-butanediol dehydrogenases (BDH1-3) and one glycerol dehydrogenase (GDH) involved in 2,3-BD isomers formation by Serratia sp. T241 were identified. In vitro conversion showed BDH1 and BDH2 could catalyzed (3S)-acetoin and (3R)-acetoin into (2S,3S)-2,3-BD and meso-2,3-BD, while BDH3 and GDH exhibited the activities from (3S)-acetoin and (3R)-acetoin to meso-2,3-BD and (2R,3R)-2,3-BD. Four encoding genes were assembled into E. coli with budA (acetolactate decarboxylase) and budB (acetolactate synthase), responsible for converting pyruvate into acetoin. E. coli expressing budAB-bdh1/2 produced meso-2,3-BD and (2S,3S)-2,3-BD. Correspondingly, (2R,3R)-2,3-BD and meso-2,3-BD were obtained by E. coli expressing budAB-bdh3/gdh. These results suggested four enzymes might contribute to 2,3-BD isomers formation. Mutants of four genes were developed in Serratia sp. T241. Δbdh1 led to reduced concentration of meso-2,3-BD and (2S,3S)-2,3-BD by 97.7% and 87.9%. (2R,3R)-2,3-BD with a loss of 73.3% was produced by Δbdh3. Enzyme activity assays showed the decrease of 98.4% and 22.4% by Δbdh1 and Δbdh3 compared with the wild strain. It suggested BDH1 and BDH3 played important roles in 2,3-BD formation, BDH2 and GDH have small effects on 2,3-BD production by Serratia sp. T241. PMID:26753612

Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241.

PubMed

Zhang, Liaoyuan; Guo, Zewang; Chen, Jiebo; Xu, Quanming; Lin, Hui; Hu, Kaihui; Guan, Xiong; Shen, Yaling

2016-01-12

Serratia sp. T241, a newly isolated xylose-utilizing strain, produced three 2,3-butanediol (2,3-BD) stereoisomers. In this study, three 2,3-butanediol dehydrogenases (BDH1-3) and one glycerol dehydrogenase (GDH) involved in 2,3-BD isomers formation by Serratia sp. T241 were identified. In vitro conversion showed BDH1 and BDH2 could catalyzed (3S)-acetoin and (3R)-acetoin into (2S,3S)-2,3-BD and meso-2,3-BD, while BDH3 and GDH exhibited the activities from (3S)-acetoin and (3R)-acetoin to meso-2,3-BD and (2R,3R)-2,3-BD. Four encoding genes were assembled into E. coli with budA (acetolactate decarboxylase) and budB (acetolactate synthase), responsible for converting pyruvate into acetoin. E. coli expressing budAB-bdh1/2 produced meso-2,3-BD and (2S,3S)-2,3-BD. Correspondingly, (2R,3R)-2,3-BD and meso-2,3-BD were obtained by E. coli expressing budAB-bdh3/gdh. These results suggested four enzymes might contribute to 2,3-BD isomers formation. Mutants of four genes were developed in Serratia sp. T241. Δbdh1 led to reduced concentration of meso-2,3-BD and (2S,3S)-2,3-BD by 97.7% and 87.9%. (2R,3R)-2,3-BD with a loss of 73.3% was produced by Δbdh3. Enzyme activity assays showed the decrease of 98.4% and 22.4% by Δbdh1 and Δbdh3 compared with the wild strain. It suggested BDH1 and BDH3 played important roles in 2,3-BD formation, BDH2 and GDH have small effects on 2,3-BD production by Serratia sp. T241.

Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors

PubMed Central

Yang, Weilian; Wu, Gong; Huo, Tianyao; Tjarks, Werner; Ciesielski, Michael; Fenstermaker, Robert A.; Ross, Brain D.; Wikstrand, Carol J.; Riley, Kent J.; Binns, Peter J.

2010-01-01

In the present study, we have evaluated a boronated dendrimer-epidermal growth factor (BD-EGF) bioconjugate as a molecular targeting agent for boron neutron capture therapy (BNCT) of the human EGFR gene-transfected F98 rat glioma, designated F98EGFR. EGF was chemically linked to a heavily boronated polyamidoamine dendrimer (BD) by means of the heterobifunctional reagent, mMBS. Biodistribution studies were carried out at 6 h and 24 h following intratumoral (i.t.) injection or intracerebral (i.c.) convection enhanced delivery (CED) of 125I-labeled or unlabeled BD-EGF (40 μg 10B/10 μg EGF) to F98 glioma bearing rats. At 24 h. there was 43% more radioactivity in EGFR(+) tumors following CED compared to i.t. injection, and a doubling of the tumor boron concentration (22.3 μg/g vs. 11.7 μg/g). CED of BD-EGF resulted in a 7.2× increase in the volume of distribution within the infused cerebral hemisphere and a 1.9× increase in tumor uptake of BD-EGF compared with i.t. injection. Based on these favorable bio-distribution data, BNCT was carried out at the Massachusetts Institute of Technology nuclear reactor 14 days following i.c. tumor implantation and 24 h. after CED of BD-EGF. These animals had a MST of 54.1 ± 4.7 days compared to 43.0 ± 2.8 days following i.t. injection. Rats that received BD-EGF by CED in combination with i.v. boronophenylalanine (BPA), which has been used in both experimental and clinical studies, had a MST of 86.0 ± 28.1 days compared to 39.8 ± 1.6 days for i.v. BPA alone (P < 0.01), 30.9 ± 1.4 days for irradiated controls and 25.1 ± 1.0 days for untreated controls (overall P < 0.0001). These data have demonstrated that the efficacy of BNCT was significantly increased (P < 0.006), following i.c CED of BD-EGF compared to i.t injection, and that the survival data were equivalent to those previously reported by us using the boronated anti-human-EGF mAb, C225 (cetuximab). PMID:19588228

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity.

PubMed

McMullin, Ryan P; Wittner, Ben S; Yang, Chuanwei; Denton-Schneider, Benjamin R; Hicks, Daniel; Singavarapu, Raj; Moulis, Sharon; Lee, Jeongeun; Akbari, Mohammad R; Narod, Steven A; Aldape, Kenneth D; Steeg, Patricia S; Ramaswamy, Sridhar; Sgroi, Dennis C

2014-03-14

There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway.

A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity

PubMed Central

2014-01-01

Introduction There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis. Methods We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets. Results In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency. Conclusions A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway. PMID:24625110

Expression of beta-defensins pBD-1 and pBD-2 along the small intestinal tract of the pig: lack of upregulation in vivo upon Salmonella typhimurium infection.

PubMed

Veldhuizen, Edwin J A; van Dijk, Albert; Tersteeg, Monique H G; Kalkhove, Stefanie I C; van der Meulen, Jan; Niewold, Theo A; Haagsman, Henk P

2007-01-01

Defensins are antimicrobial peptides that play an important role in the innate immune response in the intestine. Up to date, only one beta-defensin (pBD-1), has been described in pig, which was found to be expressed at low levels in the intestine. We set-up a quantitative PCR method to detect the gene expression of pBD-1 and a newly discovered porcine beta-defensin, pBD-2. Expression of pBD-1 mRNA increased from the proximal to the distal part of the intestine whereas pBD-2 expression decreased. The main gene expression sites for pBD-2 were kidney and liver, whereas pBD-1 was mainly expressed in tongue. The porcine small intestinal segment perfusion (SISP) technique was used to investigate effects of Salmonella typhimurium DT104 on intestinal morphology and pBD-1 and pBD-2 mRNA levels in vivo. The early responses were studied 2, 4 and 8 h post-infection in four separate jejunal and ileal segments. Immunohistochemistry showed invasion of the mucosa by Salmonella and changes in intestinal morphology. However, no concomitant changes in expression of either pBD-1 or pBD-2 were observed. We conclude that at least two defensins are differentially expressed in the intestine of pigs, and that expression of both defensins is not altered by S. typhimurium under these conditions.

Biomarker Discovery by Modeling Behçet's Disease with Patient-Specific Human Induced Pluripotent Stem Cells.

PubMed

Son, Mi-Young; Kim, Young-Dae; Seol, Binna; Lee, Mi-Ok; Na, Hee-Jun; Yoo, Bin; Chang, Jae-Suk; Cho, Yee Sook

2017-01-15

Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. In this study, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells. Based on comparative transcriptome analysis using our BD model cells, we identified eight novel BD-specific genes, AGTR2, CA9, CD44, CXCL1, HTN3, IL-2, PTGER4, and TSLP, which were differentially expressed in BD patients compared with healthy controls or patients with other immune diseases. The use of CXCL1 as a BD biomarker was further validated at the protein level using both a BD iPSC-HPC-based assay system and BD patient serum samples. Furthermore, we show that our BD iPSC-HPC-based drug screening system is highly effective for testing CXCL1 BD biomarkers, as determined by monitoring the efficacy of existing anti-inflammatory drugs. Our results shed new light on the usefulness of patient-specific iPSC technology in the development of a benchmarking platform for disease-specific biomarkers, phenotype- or target-driven drug discovery, and patient-tailored therapies.

Heterogeneous occupancy and density estimates of the pathogenic fungus Batrachochytrium dendrobatidis in waters of North America

USGS Publications Warehouse

Chestnut, Tara E.; Anderson, Chauncey; Popa, Radu; Blaustein, Andrew R.; Voytek, Mary; Olson, Deanna H.; Kirshtein, Julie

2014-01-01

Biodiversity losses are occurring worldwide due to a combination of stressors. For example, by one estimate, 40% of amphibian species are vulnerable to extinction, and disease is one threat to amphibian populations. The emerging infectious disease chytridiomycosis, caused by the aquatic fungus Batrachochytrium dendrobatidis (Bd), is a contributor to amphibian declines worldwide. Bd research has focused on the dynamics of the pathogen in its amphibian hosts, with little emphasis on investigating the dynamics of free-living Bd. Therefore, we investigated patterns of Bd occupancy and density in amphibian habitats using occupancy models, powerful tools for estimating site occupancy and detection probability. Occupancy models have been used to investigate diseases where the focus was on pathogen occurrence in the host. We applied occupancy models to investigate free-living Bd in North American surface waters to determine Bd seasonality, relationships between Bd site occupancy and habitat attributes, and probability of detection from water samples as a function of the number of samples, sample volume, and water quality. We also report on the temporal patterns of Bd density from a 4-year case study of a Bd-positive wetland. We provide evidence that Bd occurs in the environment year-round. Bd exhibited temporal and spatial heterogeneity in density, but did not exhibit seasonality in occupancy. Bd was detected in all months, typically at less than 100 zoospores L−1. The highest density observed was ∼3 million zoospores L−1. We detected Bd in 47% of sites sampled, but estimated that Bd occupied 61% of sites, highlighting the importance of accounting for imperfect detection. When Bd was present, there was a 95% chance of detecting it with four samples of 600 ml of water or five samples of 60 mL. Our findings provide important baseline information to advance the study of Bd disease ecology, and advance our understanding of amphibian exposure to free-living Bd in aquatic habitats over time.

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats

PubMed Central

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-01-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke. PMID:29399121

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

PubMed

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-02-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder.

PubMed

Chang, Kiki; Garrett, Amy; Kelley, Ryan; Howe, Meghan; Sanders, Erica Marie; Acquaye, Tenah; Bararpour, Layla; Li, Sherrie; Singh, Manpreet; Jo, Booil; Hallmayer, Joachim; Reiss, Allan

2017-11-01

Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD. We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene. While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD. Copyright © 2017. Published by Elsevier B.V.

Enhanced bioactive properties of BiodentineTM modified with bioactive glass nanoparticles

PubMed Central

CORRAL NUÑEZ, Camila; COVARRUBIAS, Cristian; FERNANDEZ, Eduardo; de OLIVEIRA, Osmir Batista

2017-01-01

Abstract Objective To prepare nanocomposite cements based on the incorporation of bioactive glass nanoparticles (nBGs) into BiodentineTM (BD, Septodent, Saint-Maur-des-Fosses Cedex, France) and to assess their bioactive properties. Material and Methods nBGs were synthesised by the sol-gel method. BD nanocomposites (nBG/BD) were prepared with 1 and 2% nBGs by weight; unmodified BD and GC Fuji IX (GIC, GC Corporation, Tokyo, Japan) were used as references. The in vitro ability of the materials to induce apatite formation was assessed in SBF by X-ray diffraction (XRD), attenuated total reflectance with Fourier transform infrared spectroscopy (ATR-FTIR), and scanning electron microscopy (SEM) with energy dispersive X-ray (EDX) analysis. BD and nBG/BD were also applied to dentine discs for seven days; the morphology and elemental composition of the dentine-cement interface were analysed using SEM-EDX. Results One and two percent nBG/BD composites accelerated apatite formation on the disc surface after short-term immersion in SBF. Apatite was detected on the nBG/BD nanocomposites after three days, compared with seven days for unmodified BD. No apatite formation was detected on the GIC surface. nBG/BD formed a wider interfacial area with dentine than BD, showing blockage of dentine tubules and Si incorporation, suggesting intratubular precipitation. Conclusions The incorporation of nBGs into BD improves its in vitro bioactivity, accelerating the formation of a crystalline apatite layer on its surface after immersion in SBF. Compared with unmodified BD, nBG/BD showed a wider interfacial area with greater Si incorporation and intratubular precipitation of deposits when immersed in SBF. PMID:28403358

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study.

PubMed

Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

2016-01-01

Behçet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ∩ "OB vs C" ∩ "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behçet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.

Widespread occurrence of the chytrid fungus batrachochytrium dendrobatidis on oregon spotted frogs (rana pretiosa)

USGS Publications Warehouse

Pearl, C.A.; Bowerman, J.; Adams, M.J.; Chelgren, N.D.

2009-01-01

The pathogen Batrachochytrium dendrobatidis (Bd) has been associated with amphibian declines in multiple continents, including western North America. We investigated Bd prevalence in Oregon spotted frog (Rana pretiosa), a species that has declined across its range in the Pacific Northwest. Polymerase chain reaction analysis of skin swabs indicated that Bd was prevalent within populations (420 of 617 juvenile and adults) and widespread among populations (36 of 36 sites) where we sampled R. pretiosa in Oregon and Washington. We rarely detected Bd in R. pretiosa larvae (2 of 72). Prevalence of Bd in postmetamorphic R. pretiosa was inversely related to frog size. We found support for an interactive effect of elevation and sampling date on Bd: prevalence of Bd generally increased with date, but this effect was more pronounced at lower elevations. We also found evidence that the body condition of juvenile R. pretiosa with Bd decreased after their first winter. Our data indicate that some Oregon spotted frog populations are currently persisting with relatively high Bd prevalence, but the risk posed by Bd is unknown. ?? 2010 International Association for Ecology and Health.

Emotional Response Inhibition in Bipolar Disorder: A Functional Magnetic Resonance Imaging Study of Trait- and State-Related Abnormalities

PubMed Central

Hummer, Tom A.; Hulvershorn, Leslie A.; Karne, Harish S.; Gunn, Abigail D.; Wang, Yang; Anand, Amit

2018-01-01

Background Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. Methods One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. Results The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. Conclusions These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment. PMID:22871393

Serogrouping of Halophilic Bdellovibrios from Chesapeake Bay and Environs by Immunodiffusion and Immunoelectrophoresis

PubMed Central

Schoeffield, Andrew J.; Falkler, William A.; Desai, Darshana; Williams, Henry N.

1991-01-01

Little has been reported on the serological relationship of halophilic bdellovibrios (Bd). Immunodiffusion analysis performed with rabbit or mouse Bd antisera developed against eight halophilic Bd isolates and one terrestrial Bd isolate, when reacted with soluble antigen preparations of 45 isolates of halophilic Bd, allowed separation into seven serogroups, which were distinct from the terrestrial isolate. Soluble antigen preparations of prey bacteria, Vibrio parahaemolyticus P-5 (P-5) and Escherichia coli ML 35 (ML 35), exhibited no reactivity with the antisera by immunodiffusion. Immunoelectrophoresis revealed the presence of three distinct antigens in homologous reactions and one shared antigen in heterologous Bd reactions. Shared antigens were noted between halophilic and terrestrial Bd, in addition to between halophilic Bd strains, indicating the possible existence of an antigen(s) which may be shared among all Bd. Again, no shared antigen was noted when P-5 or ML 35 was allowed by immunoelectrophoresis to react with the antisera. Prey susceptibility testing of the seven distinct groups of halophilic Bd, using 20 test prey, produced essentially identical spectra for each group, indicating that this was not a useful technique in delineating the Bd. While immunoelectrophoresis was able to demonstrate an antigen common to all Bd tested, immunodiffusion was able to delineate strains on the basis of a “serogroup specific” antigen. This suggests that immunological tools may serve as important means to study the taxonomy of halophilic Bd, as well as in the formation of a clearer taxonomic picture of the genus Bdellovibrio. Images PMID:16348597

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder.

PubMed

McCormack, C; Green, M J; Rowland, J E; Roberts, G; Frankland, A; Hadzi-Pavlovic, D; Joslyn, C; Lau, P; Wright, A; Levy, F; Lenroot, R K; Mitchell, P B

2016-03-01

Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Amphibian-killing chytrid in Brazil comprises both locally endemic and globally expanding populations.

PubMed

Jenkinson, T S; Betancourt Román, C M; Lambertini, C; Valencia-Aguilar, A; Rodriguez, D; Nunes-de-Almeida, C H L; Ruggeri, J; Belasen, A M; da Silva Leite, D; Zamudio, K R; Longcore, J E; Toledo, F L; James, T Y

2016-07-01

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is the emerging infectious disease implicated in recent population declines and extinctions of amphibian species worldwide. Bd strains from regions of disease-associated amphibian decline to date have all belonged to a single, hypervirulent clonal genotype (Bd-GPL). However, earlier studies in the Atlantic Forest of southeastern Brazil detected a novel, putatively enzootic lineage (Bd-Brazil), and indicated hybridization between Bd-GPL and Bd-Brazil. Here, we characterize the spatial distribution and population history of these sympatric lineages in the Brazilian Atlantic Forest. To investigate the genetic structure of Bd in this region, we collected and genotyped Bd strains along a 2400-km transect of the Atlantic Forest. Bd-Brazil genotypes were restricted to a narrow geographic range in the southern Atlantic Forest, while Bd-GPL strains were widespread and largely geographically unstructured. Bd population genetics in this region support the hypothesis that the recently discovered Brazilian lineage is enzootic in the Atlantic Forest of Brazil and that Bd-GPL is a more recently expanded invasive. We collected additional hybrid isolates that demonstrate the recurrence of hybridization between panzootic and enzootic lineages, thereby confirming the existence of a hybrid zone in the Serra da Graciosa mountain range of Paraná State. Our field observations suggest that Bd-GPL may be more infective towards native Brazilian amphibians, and potentially more effective at dispersing across a fragmented landscape. We also provide further evidence of pathogen translocations mediated by the Brazilian ranaculture industry with implications for regulations and policies on global amphibian trade. © 2016 John Wiley & Sons Ltd.

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanamala, Naveena, E-mail: wqu1@cdc.gov; Hatfield, Meghan K., E-mail: wla4@cdc.gov; Farcas, Mariana T., E-mail: woe7@cdc.gov

2013-10-15

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-basedmore » D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.« less

Cortico-Cortical interactions between and within three cortical auditory areas specialized for time-domain signal processing

PubMed Central

Tang, Jie; Suga, Nobuo

2009-01-01

In auditory cortex of the mustached bat, the FF (F means frequency modulation), dorsal fringe (DF) and ventral fringe (VF) areas consist of “combination-sensitive” neurons tuned to the pair of an emitted biosonar pulse and its echo with a specific delay (best delay: BD). The DF and VF areas are hierarchically at a higher level than the FF area. Focal electric stimulation of the FF area evokes “centrifugal” BD shifts of DF neurons, i.e., shifts away from the BD of the stimulated FF neurons, whereas stimulation of the DF neurons evokes “centripetal” BD shifts of FF neurons, i.e., shifts toward the BD of the stimulated DF neurons. In our current studies, we found that the feed forward projection from FF neurons evokes centrifugal BD shifts of VF neurons, that the feedback projection from VF neurons evokes centripetal BD shifts of FF neurons, that the contralateral projection from DF neurons evokes centripetal BD shifts of DF neurons, and that the centripetal BD shifts evoked by the DF and VF neurons are 2.5 times larger than the centrifugal BD shifts evoked by the FF neurons. The centrifugal BD shifts shape the selective neural representation of a specific target-distance, whereas the centripetal BD shifts expand the representation of the selected specific target-distance to focus on the processing of the target information at a specific distance. The centrifugal and centripetal BD shifts evoked by the feed forward and feedback projections promote finer analysis of a target at shorter distances. PMID:19494145

Discovery and characterization of Coturnix chinensis avian β-defensin 10, with broad antibacterial activity.

PubMed

Ma, Deying; Lin, Lijuan; Zhang, Kexin; Han, Zongxi; Shao, Yuhao; Wang, Ruiqin; Liu, Shengwang

2012-04-01

A novel avian β-defensin (AvBD), AvBD10, was discovered in the liver and bone marrow tissues from Chinese painted quail (Coturnix chinensis) in the present study. The complete nucleotide sequence of quail AvBD10 contains a 207-bp open reading frame that encodes 68 amino acids. The quail AvBD10 was expressed widely in all the tissues from quails except the tongue, crop, breast muscle, and thymus and was highly expressed in the bone marrow. In contrast to the expression pattern of AvBD10 in tissues from quail, the chicken AvBD10 was expressed in all 21 tissues from the layer hens investigated, with a high level of expression in the kidney, lung, liver, bone marrow, and Harderian glands. Recombinant glutathione S-transferase (GST)-tagged AvBD10s of both quail and chicken were produced and purified by expression of the two cDNAs in Escherichia coli, respectively. In addition, peptide according to the respective AvBD10s sequence was synthesized, named synthetic AvBD10s. As expected, both recombinant GST-tagged AvBD10s and synthetic AvBD10s of quail and chicken exhibited similar bactericidal properties against most bacteria, including Gram-positive and Gram-negative forms. However, no significant bactericidal activity was found for quail recombinant GST-tagged AvBD10 against Salmonella choleraesuis or for chicken recombinant GST-tagged AvBD10 against Proteus mirabilis. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Unlocking the story in the swab: A new genotyping assay for the amphibian chytrid fungus Batrachochytrium dendrobatidis.

PubMed

Byrne, Allison Q; Rothstein, Andrew P; Poorten, Thomas J; Erens, Jesse; Settles, Matthew L; Rosenblum, Erica Bree

2017-11-01

One of the most devastating emerging pathogens of wildlife is the chytrid fungus, Batrachochytrium dendrobatidis (Bd), which affects hundreds of amphibian species around the world. Genomic data from pure Bd cultures have advanced our understanding of Bd phylogenetics, genomic architecture and mechanisms of virulence. However, pure cultures are laborious to obtain and whole-genome sequencing is comparatively expensive, so relatively few isolates have been genetically characterized. Thus, we still know little about the genetic diversity of Bd in natural systems. The most common noninvasive method of sampling Bd from natural populations is to swab amphibian skin. Hundreds of thousands of swabs have been collected from amphibians around the world, but Bd DNA collected via swabs is often low in quality and/or quantity. In this study, we developed a custom Bd genotyping assay using the Fluidigm Access Array platform to amplify 192 carefully selected regions of the Bd genome. We obtained robust sequence data for pure Bd cultures and field-collected skin swabs. This new assay has the power to accurately discriminate among the major Bd clades, recovering the basic tree topology previously revealed using whole-genome data. Additionally, we established a critical value for initial Bd load for swab samples (150 Bd genomic equivalents) above which our assay performs well. By leveraging advances in microfluidic multiplex PCR technology and the globally distributed resource of amphibian swab samples, noninvasive skin swabs can now be used to address critical spatial and temporal questions about Bd and its effects on declining amphibian populations. © 2017 John Wiley & Sons Ltd.

The differences in temperament-character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I and II.

PubMed

Izci, Filiz; Fındıklı, Ebru Kanmaz; Zincir, Serkan; Zincir, Selma Bozkurt; Koc, Merve Iris

2016-01-01

The primary aim of this study was to compare the differences in temperament-character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I (BD-I) and bipolar disorder II (BD-II). Fifty-two BD-I patients and 49 BD-II patients admitted to Erenköy Mental and Neurological Disease Training and Research Hospital psychiatry clinic and fifty age- and sex-matched healthy control subjects were enrolled in this study. A structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders, Temperament and Character Inventory, Barrett Impulsiveness Scale-11 (BIS-11), Hamilton Depression Inventory Scale, Young Mania Rating Scale, and Bipolar Disorder Functioning Questionnaire (BDFQ) were administered to patients and to control group. No statistically significant difference in sociodemographic features existed between the patient and control groups (P>0.05). Thirty-eight subjects (37.62%) in the patient group had a suicide attempt. Twenty-three of these subjects (60.52%) had BD-I, and 15 of these subjects (39.47%) had BD-II. Suicide attempt rates in BD-I and II patients were 60.52% and 39.47%, respectively (P<0.05). Comparison of BD-I and II patients with healthy control subjects revealed that cooperativeness (C), self-directedness (Sdi), and self-transcendence (ST) scores were lower and novelty seeking (NS1 and NS2), harm avoidance (HA4), and reward dependence (RD2) subscale scores were higher in patients with BD-I. When BD-I patients were compared with BD-II patients, BIS-11 (attention) scores were higher in patients with BD-II and BIS-11 (motor and nonplanning impulsivity) scores were higher in patients with BD-I. According to BDFQ, relations with friends, participation in social activities, daily activities and hobbies, and occupation subscale scores were lower and taking initiative subscale scores were higher in patients with BD-I. Social withdrawal subscale scores were higher in patients with BD-II. In our study, NS, HA, and RD scores that may be found high in suicide attempters and Sdi scores that may be found low in suicide attempters were as follows: NS1, NS2, HA4, and RD2 subscale scores were high and Sdi scores were low in patients with BD-I, suggesting a higher rate of suicide attempts in this group of patients. In addition, C and Sdi scores that indicate a predisposition to personality disorder were significantly lower in patients with BD-I than patients with BD-II and healthy controls, suggesting a higher rate of personality disorder comorbidity in patients with BD-I. Higher impulsivity and suicidality rates and poorer functionality in patients with BD-I also suggest that patients with BD-I may be more impulsive and more prone to suicide and have poorer functionality in some areas.

The differences in temperament–character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I and II

PubMed Central

Izci, Filiz; Fındıklı, Ebru Kanmaz; Zincir, Serkan; Zincir, Selma Bozkurt; Koc, Merve Iris

2016-01-01

Background The primary aim of this study was to compare the differences in temperament–character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I (BD-I) and bipolar disorder II (BD-II). Methods Fifty-two BD-I patients and 49 BD-II patients admitted to Erenköy Mental and Neurological Disease Training and Research Hospital psychiatry clinic and fifty age- and sex-matched healthy control subjects were enrolled in this study. A structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders, Temperament and Character Inventory, Barrett Impulsiveness Scale-11 (BIS-11), Hamilton Depression Inventory Scale, Young Mania Rating Scale, and Bipolar Disorder Functioning Questionnaire (BDFQ) were administered to patients and to control group. Results No statistically significant difference in sociodemographic features existed between the patient and control groups (P>0.05). Thirty-eight subjects (37.62%) in the patient group had a suicide attempt. Twenty-three of these subjects (60.52%) had BD-I, and 15 of these subjects (39.47%) had BD-II. Suicide attempt rates in BD-I and II patients were 60.52% and 39.47%, respectively (P<0.05). Comparison of BD-I and II patients with healthy control subjects revealed that cooperativeness (C), self-directedness (Sdi), and self-transcendence (ST) scores were lower and novelty seeking (NS1 and NS2), harm avoidance (HA4), and reward dependence (RD2) subscale scores were higher in patients with BD-I. When BD-I patients were compared with BD-II patients, BIS-11 (attention) scores were higher in patients with BD-II and BIS-11 (motor and nonplanning impulsivity) scores were higher in patients with BD-I. According to BDFQ, relations with friends, participation in social activities, daily activities and hobbies, and occupation subscale scores were lower and taking initiative subscale scores were higher in patients with BD-I. Social withdrawal subscale scores were higher in patients with BD-II. Conclusion In our study, NS, HA, and RD scores that may be found high in suicide attempters and Sdi scores that may be found low in suicide attempters were as follows: NS1, NS2, HA4, and RD2 subscale scores were high and Sdi scores were low in patients with BD-I, suggesting a higher rate of suicide attempts in this group of patients. In addition, C and Sdi scores that indicate a predisposition to personality disorder were significantly lower in patients with BD-I than patients with BD-II and healthy controls, suggesting a higher rate of personality disorder comorbidity in patients with BD-I. Higher impulsivity and suicidality rates and poorer functionality in patients with BD-I also suggest that patients with BD-I may be more impulsive and more prone to suicide and have poorer functionality in some areas. PMID:26848266

Intra prediction using face continuity in 360-degree video coding

NASA Astrophysics Data System (ADS)

Hanhart, Philippe; He, Yuwen; Ye, Yan

2017-09-01

This paper presents a new reference sample derivation method for intra prediction in 360-degree video coding. Unlike the conventional reference sample derivation method for 2D video coding, which uses the samples located directly above and on the left of the current block, the proposed method considers the spherical nature of 360-degree video when deriving reference samples located outside the current face to which the block belongs, and derives reference samples that are geometric neighbors on the sphere. The proposed reference sample derivation method was implemented in the Joint Exploration Model 3.0 (JEM-3.0) for the cubemap projection format. Simulation results for the all intra configuration show that, when compared with the conventional reference sample derivation method, the proposed method gives, on average, luma BD-rate reduction of 0.3% in terms of the weighted spherical PSNR (WS-PSNR) and spherical PSNR (SPSNR) metrics.

Treatment Satisfaction, Product Perception, and Quality of Life in Plaque Psoriasis Patients Using Betamethasone Dipropionate Spray 0.05%

PubMed Central

Fowler, Joseph F.; Del Rosso, James Q.; Pakunlu, Refika I.

2017-01-01

Objective: To assess patient-reported satisfaction, efficacy, and tolerability associated with the use of betamethasone dipropionate spray 0.05% when applied twice daily in subjects with moderate plaque psoriasis. Design: This was an open-label, multicenter study involving 45 patients with moderate plaque psoriasis, with the aim of evaluating patient-reported outcomes with betamethasone dipropionate spray 0.05%. Patients treated all affected areas twice daily with betamethasone dipropionate (BD) spray 0.05% for 28 days per label instructions. Measurements: Outcome measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), Dermatology Life Quality Index (DLQI), Investigators Global Assessment (IGA), and Total Sign Score (TSS). In addition, the lesions were photographed at baseline (Day 1) and on Day 8, Day 14, and Day 29. Results: The results indicated that BD spray 0.05% treatment is associated with improved quality of life. BD spray 0.05% also led to improved IGA and TSS values and a reduction in the percentage of body surface area affected. Conclusion: In subjects with moderate plaque psoriasis, BD spray 0.05% demonstrated good levels of patient satisfaction and quality of life measures, in combination with improvements in the global assessment of disease and the level of itching experienced by subjects. PMID:29399255

Cognitive processing in bipolar disorder conceptualized using the Interactive Cognitive Subsystems (ICS) model.

PubMed

Lomax, C L; Barnard, P J; Lam, D

2009-05-01

There are few theoretical proposals that attempt to account for the variation in affective processing across different affective states of bipolar disorder (BD). The Interacting Cognitive Subsystems (ICS) framework has been recently extended to account for manic states. Within the framework, positive mood state is hypothesized to tap into an implicational level of processing, which is proposed to be more extreme in states of mania. Thirty individuals with BD and 30 individuals with no history of affective disorder were tested in euthymic mood state and then in induced positive mood state using the Question-Answer task to examine the mode of processing of schemas. The task was designed to test whether individuals would detect discrepancies within the prevailing schemas of the sentences. Although the present study did not support the hypothesis that the groups differ in their ability to detect discrepancies within schemas, we did find that the BD group was significantly more likely than the control group to answer questions that were consistent with the prevailing schemas, both before and after mood induction. These results may reflect a general cognitive bias, that individuals with BD have a tendency to operate at a more abstract level of representation. This may leave an individual prone to affective disturbance, although further research is required to replicate this finding.

Comorbidity of obsessive-compulsive disorder in recovered inpatients with bipolar disorder.

PubMed

Krüger, S; Bräunig, P; Cooke, R G

2000-03-01

To determine the frequency of obsessive-compulsive disorder (OCD) in inpatient subjects with bipolar disorder (BD) and to examine the clinical characteristics of BD subjects with OCD. The sample consisted of 143 inpatient subjects with DSM-III-R BD-I and BD-NOS (BD-II), recovered from a current episode of either depression or mania. Demographic and clinical variables were obtained on the day of admission. Current comorbid conditions including OCD were determined by the Structured Clinical Interview for DSM-III-R Ifollowing recovery from the acute affective episode. The frequency of current OCD was 7% (N = 10). All BD subjects with OCD were BD-II, were male, and had a diagnosis of current dysthymia. They had fewer episodes and a higher incidence of prior suicide attempts than bipolar subjects without OCD. None of the bipolar subjects with OCD fulfilled criteria for cyclothymia. Our findings suggest that BD-II, OCD, dysthymia, and suicidality cluster together in some subjects with BD. We discuss the clinical implications of our findings.

Human β-defensin 3 has immunosuppressive activity in vitro and in vivo

PubMed Central

Semple, Fiona; Webb, Sheila; Li, Hsin-Ni; Patel, Hetal B; Perretti, Mauro; Jackson, Ian J; Gray, Mohini; Davidson, Donald J; Dorin, Julia R

2010-01-01

β-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition β-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human β defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary Mφ. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-α and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-γ stimulation of Mφ and in vivo, hBD3 significantly reduces the LPS-induced TNF-α level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation. PMID:20104491

Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo.

PubMed

Semple, Fiona; Webb, Sheila; Li, Hsin-Ni; Patel, Hetal B; Perretti, Mauro; Jackson, Ian J; Gray, Mohini; Davidson, Donald J; Dorin, Julia R

2010-04-01

Beta-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition beta-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human beta defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary Mphi. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-gamma stimulation of Mphi and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.

Body awareness and mindfulness: validation of the Spanish version of the Scale of Body Connection.

PubMed

del C Quezada-Berumen, Lucía; González-Ramírez, Mónica T; Cebolla, Ausias; Soler, Joaquim; Garcia-Campayo, Javier

2014-01-01

To assess the psychometric properties and the factor structure of the Spanish version of the Scale of Body Connection (SBC) in a community population of meditators and non-meditators and to investigate the relationships among mindfulness, body awareness and body dissociation. Design. Validation study. Sampling. An internet-based commercial system was used to recruit the sample. Instruments. In addition to the SBC, the Five Facet Mindfulness Questionnaire (FFMQ) and the Depression, Anxiety, and Stress Scale (DASS-21) were administered. A sample of 578 subjects responded to all of the items in the protocol. A total of 55.2% of respondents had some previous experience with meditation. A Scree plot showed a two-factor solution involving the Body Awareness (BA) and Body Dissociation (BD) subscales. This study differed from the original validation study in the lack of independence of the subscales; they were correlated in the present study (r=-.11). Internal consistency for BA was α: .86, and for BD, the α was .62. Test-retest reliability was assessed in a subsample (N=67) and was r=.679 for BA and r=.765 for BD. Hierarchical multiple regression analyses showed that mindfulness practice and the FFMQ factors of Observing and Describing were positive predictors of BA. Describing, Acting with awareness and Non-judging negatively predicted BD, and Observing positively predicted BD. The study confirms the adequacy of the psychometric properties of the Spanish version of the SBC for use in community samples. The relationship between SBC and mindfulness is discussed in light of previous research.

Investigation of the influence of coadsorbent dye upon the interfacial structure of dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Honda, M.; Yanagida, M.; Han, L.; Miyano, K.

2014-11-01

The interface between Ru(tcterpy)(NCS)3TBA2 [black dye (BD); tcterpy = 4,4',4″-tricarboxy-2,2':6',2″-terpyridine, NCS = thiocyanato, TBA = tetrabutylammonium cation] and nanocrystalline TiO2, as found in dye-sensitized solar cells, is investigated by soft-X-ray synchrotron radiation and compared with the adsorption structure of cis-Ru(Hdcbpy)2(NCS)2TBA2 (N719; dcbpy = 4,4'-dicarboxy-2,2'-bipyridine) on TiO2 to elucidate the relationship between the adsorption mode of BD and the photocurrent with and without coadsorbed indoline dye D131. The depth profile is characterized with X-ray photoelectron spectroscopy and S K-edge X-ray absorption fine structure using synchrotron radiation. Both datasets indicate that one of the isothiocyanate groups of BD interacts with TiO2 via its S atom when the dye is adsorbed from a single-component solution. In contrast, the interaction is slightly suppressed when D131 is coadsorbed, indicated by the fact that the presence of D131 changes the adsorption mode of BD. Based upon these results, the number of BD dye molecules interacting with the substrate is shown to decrease by 10% when D131 is coadsorbed, and the dissociation is shown to be related to the short-circuit photocurrent in the 600-800 nm region. The design of a procedure to promote the preferential adsorption of D131 therefore leads to an improvement of the short-circuit current and conversion efficiency.

Delayed sleep phase: An important circadian subtype of sleep disturbance in bipolar disorders.

PubMed

Steinan, Mette Kvisten; Morken, Gunnar; Lagerberg, Trine V; Melle, Ingrid; Andreassen, Ole A; Vaaler, Arne E; Scott, Jan

2016-02-01

Theoretical models of Bipolar Disorder (BD) highlight that sleep disturbances may be a marker of underlying circadian dysregulation. However, few studies of sleep in BD have reported on the most prevalent circadian sleep abnormality, namely Delayed Sleep Phase (DSP). A cross-sectional study of 404 adults with BD who met published clinical criteria for insomnia, hypersomnia or DSP, and who had previously participated in a study of sleep in BD using a comprehensive structured interview assessment. About 10% of BD cases with a sleep problem met criteria for a DSP profile. The DSP group was younger and had a higher mean Body Mass Index (BMI) than the other groups. Also, DSP cases were significantly more likely to be prescribed mood stabilizers and antidepressant than insomnia cases. An exploratory analysis of selected symptom item ratings indicated that DSP was significantly more likely to be associated with impaired energy and activity levels. The cross-sectional design precludes examination of longitudinal changes. DSP is identified by sleep profile, not by diagnostic criteria or objective sleep records such as actigraphy. The study uses data from a previous study to identify and examine the DSP group. The DSP group identified in this study can be differentiated from hypersomnia and insomnia groups on the basis of clinical and demographic features. The association of DSP with younger age, higher BMI and impaired energy and activity also suggest that this clinical profile may be a good proxy for underlying circadian dysregulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Expression of host defense peptides in the intestine of Eimeria-challenged chickens.

PubMed

Su, S; Dwyer, D M; Miska, K B; Fetterer, R H; Jenkins, M C; Wong, E A

2017-07-01

Avian coccidiosis is caused by the intracellular protozoan Eimeria, which produces intestinal lesions leading to weight gain depression. Current control methods include vaccination and anticoccidial drugs. An alternative approach involves modulating the immune system. The objective of this study was to profile the expression of host defense peptides such as avian beta-defensins (AvBDs) and liver expressed antimicrobial peptide 2 (LEAP2), which are part of the innate immune system. The mRNA expression of AvBD family members 1, 6, 8, 10, 11, 12, and 13 and LEAP2 was examined in chickens challenged with either E. acervulina, E. maxima, or E. tenella. The duodenum, jejunum, ileum, and ceca were collected 7 d post challenge. In study 1, E. acervulina challenge resulted in down-regulation of AvBD1, AvBD6, AvBD10, AvBD11, AvBD12, and AvBD13 in the duodenum. E. maxima challenge caused down-regulation of AvBD6, AvBD10, and AvBD11 in the duodenum, down-regulation of AvBD10 in the jejunum, but up-regulation of AvBD8 and AvBD13 in the ceca. E. tenella challenge showed no change in AvBD expression in any tissue. In study 2, which involved challenge with only E. maxima, there was down-regulation of AvBD1 in the ileum, AvBD11 in the jejunum and ileum, and LEAP2 in all 3 segments of the small intestine. The expression of LEAP2 was further examined by in situ hybridization in the jejunum of chickens from study 2. LEAP2 mRNA was expressed similarly in the enterocytes lining the villi, but not in the crypts of control and Eimeria challenged chickens. The lengths of the villi in the Eimeria challenged chickens were less than those in the control chickens, which may in part account for the observed down-regulation of LEAP2 mRNA quantified by PCR. Overall, the AvBD response to Eimeria challenge was not consistent; whereas LEAP2 was consistently down-regulated, which suggests that LEAP2 plays an important role in modulating an Eimeria infection. Published by Oxford University Press on behalf of Poultry Science Association 2017.

Exciplex formation and excited state deactivation of difluoroborondipyrromethene (Bodipy) dyads.

PubMed

Benniston, Andrew C; Copley, Graeme; Lemmetyinen, Helge; Tkachenko, Nikolai V

2010-06-07

Two series of geometrically-related dyads are discussed based on the difluoroborondipyrromethene (Bodipy) unit, and incorporating covalently attached hydroquinone/quinone groups. These units are anchored directly, or via a phenylene spacer, to the Bodipy core at the meso position in one series (BD-MHQ, BD-MQ, BD-MPHQ, BD-MPQ), but for the second series the attachment site is the 2-position (BD-SHQ, BD-SQ, BD-SPHQ, BD-SPQ). The compounds show various levels of fluorescence depending on the oxidation state of the appended group and the substitution pattern. In non-polar solvents such as toluene, diethyl ether and dichlorobenzene, the S(1) state deactivation of the Bodipy unit in BD-SPQ and BD-MPQ is dominated by (1, 3)exciplex formation, which has not been reported for Bodipy derivatives so far. In the latter molecule, the decay of the exciplex is divided between population of the Bodipy triplet state (13 %-21 %) and ground state reformation. This partitioning is not seen for the side-on substituted derivative, BD-SPQ, and only ground state reformation is observed following decay of the exciplex. This difference in behavior is explained by the radical-pair inter-system-crossing mechanism, which more effectively operates in BD-MPQ because of the orthogonality of the donor-acceptor units. In the more polar solvent CH(3)CN all the quinone derivatives show fast formation of the charge-separated state (k(CS)) followed by slower charge recombination (k(CR)). The ratio k(CS)/k(CR)

Distinguishing between Unipolar Depression and Bipolar Depression: Current and Future Clinical and Neuroimaging Perspectives

PubMed Central

de Almeida, Jorge Renner Cardoso; Phillips, Mary Louise

2012-01-01

Differentiating bipolar disorder (BD) from recurrent unipolar depression (UD) is a major clinical challenge. Main reasons for this include the higher prevalence of depressive relative to hypo/manic symptoms during the course of BD illness and the high prevalence of subthreshold manic symptoms in both BD and UD depression. Identifying objective markers of BD might help improve accuracy in differentiating between BD and UD depression, to ultimately optimize clinical and functional outcome for all depressed individuals. Yet, only eight neuroimaging studies to date directly compared UD and BD depressed individuals. Findings from these studies suggest more widespread abnormalities in white matter connectivity and white matter hyperintensities in BD than UD depression, habenula volume reductions in BD but not UD depression, and differential patterns of functional abnormalities in emotion regulation and attentional control neural circuitry in the two depression types. These findings suggest different pathophysiologic processes, especially in emotion regulation, reward and attentional control neural circuitry in BD versus UD depression. This review thereby serves as a “call to action” to highlight the pressing need for more neuroimaging studies, using larger samples sizes, comparing BD and UD depressed individuals. These future studies should also include dimensional approaches, studies of at risk individuals, and more novel neuroimaging approaches, such as, connectivity analysis and machine learning. Ultimately, these approaches might provide biomarkers to identify individuals at future risk for BD versus UD, and biological targets for more personalized treatment and new treatment developments for BD and UD depression. PMID:22784485

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions

PubMed Central

Moreno, Carmen; Hasin, Deborah S.; Arango, Celso; Oquendo, Maria A.; Vieta, Eduard; Liu, Shangmin; Grant, Bridget F.; Blanco, Carlos

2012-01-01

Objectives To compare the clinical features and course of major depressive episodes (MDE) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001–2002), a nationally representative face-to-face survey of more than 43,000 adults in the United States, including 5,695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Results Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent—and number of depressive symptoms per MDE were higher—among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDE, had the worst quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about 10 years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Conclusions Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications. PMID:22548900

Functional characterization of NADPH-cytochrome P450 reductase from Bactrocera dorsalis: Possible involvement in susceptibility to malathion

PubMed Central

Huang, Yong; Lu, Xue-Ping; Wang, Luo-Luo; Wei, Dong; Feng, Zi-Jiao; Zhang, Qi; Xiao, Lin-Fan; Dou, Wei; Wang, Jin-Jun

2015-01-01

NADPH cytochrome P450 reductase (CPR) is essential for cytochrome P450 catalysis, which is important in the detoxification and activation of xenobiotics. In this study, two transcripts of Bactrocera dorsalis CPR (BdCPR) were cloned, and the deduced amino-acid sequence had an N-terminus membrane anchor for BdCPR-X1 and three conserved binding domains (FMN, FAD, and NADP), as well as an FAD binding motif and catalytic residues for both BdCPR-X1 and BdCPR-X2. BdCPR-X1 was detected to have the high expression levels in adults and in Malpighian tubules, fat bodies, and midguts of adults, but BdCPR-X2 expressed lowly in B. dorsalis. The levels of BdCPRs were similar in malathion-resistant strain compared to susceptible strain. However, injecting adults with double-stranded RNA against BdCPR significantly reduced the transcript levels of the mRNA, and knockdown of BdCPR increased adult susceptibility to malathion. Expressing complete BdCPR-X1 cDNA in Sf9 cells resulted in high activity determined by cytochrome c reduction and these cells had higher viability after exposure to malathion than control. The results suggest that BdCPR could affect the susceptibility of B. dorsalis to malathion and eukaryotic expression of BdCPR would lay a solid foundation for further investigation of P450 in B. dorsalis. PMID:26681597

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

PubMed

Moreno, Carmen; Hasin, Deborah S; Arango, Celso; Oquendo, Maria A; Vieta, Eduard; Liu, Shangmin; Grant, Bridget F; Blanco, Carlos

2012-05-01

To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative face-to-face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent-and number of depressive symptoms per MDE was higher-among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications. © 2012 John Wiley and Sons A/S.

Preparation of polyclonal antibody against porcine beta defensin 2 and identification of its distribution in tissues of pig.

PubMed

Bao, Y Y; Li, L; Zhang, H; Gao, C Y; Xiao, C B; Li, C L

2015-12-29

Porcine β-defensin 2 (pBD2) is an antimicrobial peptide in pigs that plays an important role in the immune system by preventing bacterial invasion. To produce an anti-pBD2 antibody, which is not commercially available, we expressed and purified a soluble, his-tagged version of pBD2 (his-pBD2). Purified pBD2 was injected into New Zealand white rabbits to generate polyclonal antiserum. Anti-pBD2 antibodies were purified by ammonium sulfate precipitation, followed by diethylaminoethyl cellulose ion-exchange chromatography. The purified polyclonal antibody showed high sensitivity, with a titer as high as 204,800 by enzyme-linked immunosorbent assay, and it also showed high specificity for both his-pBD2 and native pBD2, as assessed by western blotting. Furthermore, immunohistochemistry analysis using the purified antibody revealed that pBD2 protein is distributed in the tongue, liver, kidney, small intestine, and large intestine of pigs. These results indicate that the prepared polyclonal antibody will be a useful tool for further studies of the function and mechanism of pBD2.

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

PubMed Central

Yanamala, Naveena; Hatfield, Meghan K.; Farcas, Mariana T.; Schwegler-Berry, Diane; Hummer, Jon A.; Shurin, Michael R.; Birch, M. Eileen; Gutkin, Dmitriy W.; Kisin, Elena; Kagan, Valerian E.; Bugarski, Aleksandar D.; Shvedova, Anna A.

2015-01-01

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. PMID:23886933

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

PubMed

Galimberti, Daniela; Prunas, Cecilia; Paoli, Riccardo A; Dell'Osso, Bernardo; Fenoglio, Chiara; Villa, Chiara; Palazzo, Carlotta; Cigliobianco, Michela; Camuri, Giulia; Serpente, Maria; Scarpini, Elio; Altamura, A Carlo

2014-11-01

Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Systematic Review of Cognitive Function in Euthymic Bipolar Disorder and Pre-Surgical Temporal Lobe Epilepsy.

PubMed

Bostock, Emmanuelle C S; Kirkby, Kenneth C; Garry, Michael I; Taylor, Bruce V M

2017-01-01

Bipolar disorder (BD) and temporal lobe epilepsy (TLE) overlap in domains including epidemiology, treatment response, shared neurotransmitter involvement and temporal lobe pathology. Comparison of cognitive function in both disorders may indicate temporal lobe mediated processes relevant to BD. This systematic review examines neuropsychological test profiles in euthymic bipolar disorder type I (BD-I) and pre-surgical TLE and compares experimental designs used. A search of PubMed, PsychINFO, and Scopus using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. Inclusion criteria were comparison group or pre- to post-surgical patients; reported neuropsychological tests; participants aged 18-60 years. Fifty six studies met criteria: 27 BD-I; 29 TLE. Deficits in BD-I compared to healthy controls (HC) were in executive function, attention span and verbal memory. Deficits in TLE compared to HC were in executive function and memory. In the pre- to post-surgical comparisons, verbal memory in left temporal lobe (LTL) and, less consistently, visuospatial memory in right temporal lobe (RTL) epilepsy declined following surgery. BD-I studies used comprehensive test batteries in well-defined euthymic patients compared to matched HC groups. TLE studies used convenience samples pre- to post-surgery, comparing LTL and RTL subgroups, few included comparisons to HC (5 studies). TLE studies typically examined a narrow range of known temporal lobe-mediated neuropsychological functions, particularly verbal and visuospatial memory. Both disorders exhibit deficits in executive function and verbal memory suggestive of both frontal and temporal lobe involvement. However, deficits in TLE are measured pre- to post-surgery and not controlled at baseline pre-surgery. Further research involving a head-to-head comparison of the two disorders on a broad range of neuropsychological tests is needed to clarify the nature and extent of cognitive deficits and potential overlaps.

Association between genetic variation in the myo-inositol monophosphatase 2 (IMPA2) gene and age at onset of bipolar disorder.

PubMed

Tomioka, Yoko; Jiménez, Esther; Salagre, Estela; Arias, Bárbara; Mitjans, Marina; Ruiz, Victoria; Sáiz, Pilar; García-Portilla, María Paz; de la Fuente, Lorena; Gomes-da-Costa, Susana Patricia; Bobes, Julio; Vieta, Eduard; Benabarre, Antoni; Grande, Iria

2018-05-01

The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that early-onset BD (EO-BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD. 235 bipolar patients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18. The analyses showed that in the genotype distribution rs1020294 (p = .01) and rs1250171 (p = .01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p = .002; OR = 9.57, CI95%[2.37-38.64]). The results also showed that EO-BD tended to experience more alcohol misuse (p = .003; OR = .197, CI95%[.07-.58]) compared to LO-BD. Our results provide evidence for genetic differences between EO-BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications. Copyright © 2018 Elsevier B.V. All rights reserved.

Behcet disease combined with Sjogren syndrome: A unique case report and literature review.

PubMed

Ju, Fang-He; Xu, Ting-Zhen; Hong, Hui-Hua; Mao, He; Wang, Meng; Wang, Zhen

2018-03-01

Behcet disease(BD) and Sjogren syndrome(SS) are separate conditions that rarely concomitantly affect an individual. In theory,mild symptoms of patients with BD or SS are easy to igore and,thus,remain undiagnosed. There,it is reasonable to believe there may be some clinical cases of combined diseases that go undiscovered and which needs to be taken seriously. In addition,it has been suggested that herpes simplex virus(HSV) types 1 and 2 are associated with BD,but have not been shown to be correlated to the direct pathogenesis of BD. The role of HSV in BD needs more research and attention. Here,we report a young woman who had both BD and SS. The first symptom of the disease was fever. However,the HSV type 1 IgG and HSV type 2 IgM antibody results were positive in our case and,which rendered this case unique. BD and SS concomitantly affect the individual,and BD was the acute type. IV methylprednisolone was used for 9 days and then oral glucocorticoids was used to instead,and the treatment works very well. BD and SS can concomitantly affect an individual,and we believe that HSV-2 may be directly related to the pathogenesis of BD. The nature of BD as an auto-inflammatory disorder, autoimmune disorder, or both, is controversial. If we can find more patients who combined affected these two disease, it might helpful for us to understand the nature of BD. For patients with clinical diagnosis of BD or SS,we need to be alert that it may combinded the other disease. Long term follow up and detailed inspection are important means to avoid undiscovered.

Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53

PubMed Central

Yue, Hong; Wang, Liming; Jin, Jessica; Ghosh, Santosh K.; Kawsar, Hameem I.; Zender, Chad; Androphy, Elliot J.; Weinberg, Aaron; McCormick, Thomas S.; Jin, Ge

2016-01-01

Human β-defensin-3 (hBD3) is an epithelial cell-derived innate immune regulatory molecule overexpressed in oral dysplastic lesions and fosters a tumor-promoting microenvironment. Expression of hBD3 is induced by the epidermal growth factor receptor signaling pathway. Here we describe a novel pathway through which the high-risk human papillomavirus type-16 (HPV-16) oncoprotein E6 induces hBD3 expression in mucosal keratinocytes. Ablation of E6 by siRNA induces the tumor suppressor p53 and diminishes hBD3 in HPV-16 positive CaSki cervical cancer cells and UM-SCC-104 head and neck cancer cells. Malignant cells in HPV-16-associated oropharyngeal cancer overexpress hBD3. HPV-16 E6 induces hBD3 mRNA expression, peptide production and gene promoter activity in mucosal keratinocytes. Reduction of cellular levels of p53 stimulates hBD3 expression, while activation of p53 by doxorubicin inhibits its expression in primary oral keratinocytes and CaSki cells, suggesting that p53 represses hBD3 expression. A p53 binding site in the hBD3 gene promoter has been identified by using electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP). In addition, the p63 protein isoform ΔNp63α, but not TAp63, stimulated transactivation of the hBD3 gene and was co-expressed with hBD3 in head and neck cancer specimens. Therefore, high-risk HPV E6 oncoproteins may stimulate hBD3 expression in tumor cells to facilitate tumorigenesis of HPV-associated head and neck cancer. PMID:27034006

Awareness of Breast Density and Its Impact on Breast Cancer Detection and Risk

PubMed Central

Rhodes, Deborah J.; Radecki Breitkopf, Carmen; Ziegenfuss, Jeanette Y.; Jenkins, Sarah M.; Vachon, Celine M.

2015-01-01

Purpose Legislation mandating disclosure of breast density (BD) information has passed in 21 states; however, actual awareness of BD and knowledge of its impact on breast cancer detection and risk are unknown. Methods We conducted a national cross-sectional survey administered in English and Spanish using a probability-based sample of screening-age women, with oversampling of Connecticut, the only state with BD legislation in effect for > 1 year before the survey. Results Of 2,311 women surveyed, 65% responded. Overall, 58% of women had heard of BD, 49% knew that BD affects breast cancer detection, and 53% knew that BD affects cancer risk. After multivariable adjustment, increased BD awareness was associated with white non-Hispanic race/ethnicity (Hispanic v white non-Hispanic: odds ratio [OR], 0.23; P < .001), household income (OR, 1.07 per category increase; P < .001), education (OR, 1.19 per category increase; P < .001), diagnostic evaluation after a mammogram (OR, 2.64; P < .001), and postmenopausal hormone therapy (OR, 1.69; P = .002). Knowledge of the masking effect of BD was associated with higher household income (OR, 1.10; P < .001), education (OR, 1.22; P = .01), prior breast biopsy (OR, 2.16; P < .001), and residing in Connecticut (Connecticut v other states: OR, 3.82; P = .003). Connecticut residents were also more likely to have discussed their BD with a health care provider (67% v 43% for residents of other US states; P = .001). Conclusion Disparities in BD awareness and knowledge exist by race/ethnicity, education, and income. BD legislation seems to be effective in increasing knowledge of BD impact on breast cancer detection. These findings support continued and targeted efforts to improve BD awareness and knowledge among women eligible for screening mammography. PMID:25732156

Awareness of breast density and its impact on breast cancer detection and risk.

PubMed

Rhodes, Deborah J; Radecki Breitkopf, Carmen; Ziegenfuss, Jeanette Y; Jenkins, Sarah M; Vachon, Celine M

2015-04-01

Legislation mandating disclosure of breast density (BD) information has passed in 21 states; however, actual awareness of BD and knowledge of its impact on breast cancer detection and risk are unknown. We conducted a national cross-sectional survey administered in English and Spanish using a probability-based sample of screening-age women, with oversampling of Connecticut, the only state with BD legislation in effect for > 1 year before the survey. Of 2,311 women surveyed, 65% responded. Overall, 58% of women had heard of BD, 49% knew that BD affects breast cancer detection, and 53% knew that BD affects cancer risk. After multivariable adjustment, increased BD awareness was associated with white non-Hispanic race/ethnicity (Hispanic v white non-Hispanic: odds ratio [OR], 0.23; P < .001), household income (OR, 1.07 per category increase; P < .001), education (OR, 1.19 per category increase; P < .001), diagnostic evaluation after a mammogram (OR, 2.64; P < .001), and postmenopausal hormone therapy (OR, 1.69; P = .002). Knowledge of the masking effect of BD was associated with higher household income (OR, 1.10; P < .001), education (OR, 1.22; P = .01), prior breast biopsy (OR, 2.16; P < .001), and residing in Connecticut (Connecticut v other states: OR, 3.82; P = .003). Connecticut residents were also more likely to have discussed their BD with a health care provider (67% v 43% for residents of other US states; P = .001). Disparities in BD awareness and knowledge exist by race/ethnicity, education, and income. BD legislation seems to be effective in increasing knowledge of BD impact on breast cancer detection. These findings support continued and targeted efforts to improve BD awareness and knowledge among women eligible for screening mammography. © 2015 by American Society of Clinical Oncology.

In silico aided metabolic engineering of Klebsiella oxytoca and fermentation optimization for enhanced 2,3-butanediol production.

PubMed

Park, Jong Myoung; Song, Hyohak; Lee, Hee Jong; Seung, Doyoung

2013-09-01

Klebsiella oxytoca naturally produces a large amount of 2,3-butanediol (2,3-BD), a promising bulk chemical with wide industrial applications, along with various byproducts. In this study, the in silico gene knockout simulation of K. oxytoca was carried out for 2,3-BD overproduction by inhibiting the formation of byproducts. The knockouts of ldhA and pflB genes were targeted with the criteria of maximization of 2,3-BD production and minimization of byproducts formation. The constructed K. oxytoca ΔldhA ΔpflB strain showed higher 2,3-BD yields and higher final concentrations than those obtained from the wild-type and ΔldhA strains. However, the simultaneous deletion of both genes caused about a 50 % reduction in 2,3-BD productivity compared with K. oxytoca ΔldhA strain. Based on previous studies and in silico investigation that the agitation speed during 2,3-BD fermentation strongly affected cell growth and 2,3-BD synthesis, the effect of agitation speed on 2,3-BD production was investigated from 150 to 450 rpm in 5-L bioreactors containing 3-L culture media. The highest 2,3-BD productivity (2.7 g/L/h) was obtained at 450 rpm in batch fermentation. Considering the inhibition of acetoin for 2,3-BD production, fed-batch fermentations were performed using K. oxytoca ΔldhA ΔpflB strain to enhance 2,3-BD production. Altering the agitation speed from 450 to 350 rpm at nearly 10 g/L of acetoin during the fed-batch fermentation allowed for the production of 113 g/L 2,3-BD, with a yield of 0.45 g/g, and for the production of 2.1 g/L/h of 2,3-BD.

No apparent association between bipolar disorder and cancer in a large epidemiological study of outpatients in a managed care population.

PubMed

Kahan, Natan R; Silverman, Barbara; Liphshitz, Irena; Waitman, Dan-Andrei; Ben-Zion, Itzhak; Ponizovsky, Alexander M; Weizman, Abraham; Grinshpoon, Alexander

2018-03-01

An association between bipolar disorder (BD) and cancer risk has been reported. The purpose of this study was to investigate this association through linkage analysis of a national HMO database and a national cancer registry. All members of the Leumit Health Services (LHS) HMO of Israel from 2000 to 2012 were included. Members with a recorded diagnosis of BD and a record of at least one written or dispensed prescription for pharmacotherapy for treatment of BD were classified as patients with BD. We linked the LHS population with the Israel National Cancer Registry database to capture all cases of cancer reported. Standardized incidence ratios (SIRs) for cancer in the BD population as compared with non-BD LHS members were calculated. A total of 870 323 LHS members were included in the analysis; 3304 of whom met the criteria for inclusion in the BD arm. We identified 24 515 and 110 cancer cases among members without BD and with BD, respectively. Persons with BD were no more likely than other HMO members to be diagnosed with cancer during the follow-up period [SIR, males=0.91, 95% confidence interval (CI): 0.66-1.22; SIR, females=1.15, 95% CI: 0.89-1.47]. Sensitivity analysis using different criteria for positive BD classification (lithium treatment alone or registered physician diagnosis) had no effect on the estimate of cancer risk. A nonstatistically significant association between breast cancer and BD among women was observed (SIR=1.24, 95% CI: 0.79-1.86). These findings do not corroborate previously reported associations between BD and elevated cancer risk.

Association of Anxiety Symptoms in Offspring of Bipolar Parents with Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype

PubMed Central

Park, Min-Hyeon; Sanders, Erica; Howe, Meghan; Singh, Manpreet; Hallmayer, Joachim; Kim, Eunjoo

2015-01-01

Abstract Objective: Offspring of parents with bipolar disorder (BD) have been shown to be at high risk for BD. Anxiety symptoms, even at subclinical levels, have been associated with increased risk for BD in these youth. The s-allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been implicated in the pathophysiology of both BD and anxiety disorders and has been associated with pharmacological treatment response and increased risk for antidepressant side effects. Therefore, we aimed to explore 1) whether anxiety symptoms in offspring of BD parents were associated with presence of the 5-HTTLPR s-allele and 2) whether anxiety symptoms in the offspring of BD parents according to the 5-HTTLPR genotypes are related to antianxiety medication status. Methods: A total of 64 offspring of BD parents (mean age: 13.7 years) and 51 healthy controls (HC) (mean age: 13.7 years) were compared genetically and on the Multidimensional Anxiety Scale for Children (MASC). Results: Offspring of BD parents showed higher levels of overall anxiety than did the HC group. Only antianxiety medication naïve offspring of BD parents were found to have an association between 5-HTTLPR genotypes and anxiety symptoms. The antianxiety medication naïve offspring of BD parents with the s-allele showed higher level of overall anxiety than offspring of BD parents with the l/l genotype. No significant differences in anxiety symptoms or their association with the 5-HTTLPR genotype were found in the HC group. Conclusions: This study indicated that there may be an association between 5-HTTLPR genotypes and anxiety symptoms in offspring of BD parents, and that antianxiety medication status may affect anxiety symptoms in the offspring of BD patients according to genotype. PMID:26218602

Cool temperatures reduce antifungal activity of symbiotic bacteria of threatened amphibians--implications for disease management and patterns of decline.

PubMed

Daskin, Joshua H; Bell, Sara C; Schwarzkopf, Lin; Alford, Ross A

2014-01-01

Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is a widespread disease of amphibians responsible for population declines and extinctions. Some bacteria from amphibians' skins produce antimicrobial substances active against Bd. Supplementing populations of these cutaneous antifungal bacteria might help manage chytridiomycosis in wild amphibians. However, the activity of protective bacteria may depend upon environmental conditions. Biocontrol of Bd in nature thus requires knowledge of how environmental conditions affect their anti-Bd activity. For example, Bd-driven amphibian declines have often occurred at temperatures below Bd's optimum range. It is possible these declines occurred due to reduced anti-Bd activity of bacterial symbionts at cool temperatures. Better understanding of the effects of temperature on chytridiomycosis development could also improve risk evaluation for amphibian populations yet to encounter Bd. We characterized, at a range of temperatures approximating natural seasonal variation, the anti-Bd activity of bacterial symbionts from the skins of three species of rainforest tree frogs (Litoria nannotis, Litoria rheocola, and Litoria serrata). All three species declined during chytridiomycosis outbreaks in the late 1980s and early 1990s and have subsequently recovered to differing extents. We collected anti-Bd bacterial symbionts from frogs and cultured the bacteria at constant temperatures from 8 °C to 33 °C. Using a spectrophotometric assay, we monitored Bd growth in cell-free supernatants (CFSs) from each temperature treatment. CFSs from 11 of 24 bacteria showed reduced anti-Bd activity in vitro when they were produced at cool temperatures similar to those encountered by the host species during population declines. Reduced anti-Bd activity of metabolites produced at low temperatures may, therefore, partially explain the association between Bd-driven declines and cool temperatures. We show that to avoid inconsistent antifungal activity, bacteria evaluated for use in chytridiomycosis biocontrol should be tested over a range of environmental temperatures spanning those likely to be encountered in the field.

The neurobiology of adaptation to seasons: Relevance and correlations in bipolar disorders.

PubMed

Maruani, Julia; Anderson, George; Etain, Bruno; Lejoyeux, Michel; Bellivier, Frank; Geoffroy, Pierre A

2018-06-25

Bipolar disorders (BDs) are severe and common psychiatric disorders. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. In addition, infradian fluctuations of mood, social activity, weight and sleep patterns are very frequent in BD. Disease course with a seasonal pattern (SP) occurs in approximately 25% of depressive and 15% of manic episodes, which is coupled to a more severe disease symptomatology. The pathophysiological mechanisms of seasonal effects in BD await clarification, with likely important clinical consequences. This review aims at synthesizing available data regarding the underlying pathophysiological mechanisms of seasonality in BD patients, with implications for future research directions in the study of seasonality in BD. Three factors are suggested to play significant roles in BD with SP, namely the suprachiasmatic nuclei, as well as the melatonergic and photoperiodism systems. It is proposed that BD with SP may be considered as a complex disorder resulting from the interaction of clock gene vulnerabilities and biological clock neuroplasticity, with environmental factors, such as the response to light. Light seems to play a key role in BD with SP, mainly due to two seasonal signaling pathways: a light to cortex serotonin transporter pathway, as well as a pathway connecting light to melatonin synthesis. This provides a theoretical framework for BD with SP, including for future research and clinical management. The review proposes that future research should explore markers of seasonality in BD, such as plasma melatonin, sleep-wake rhythms (with actigraphy) and genetic or epigenetic variants within the melatonin synthesis pathway. The role of light in driving BD with SP is an active area of research. Seasonality may also be intimately linked to wider aspects of BD, including via interactions with the gut microbiome, the gut-liver axis, cholesterol regulation, aspects of metabolic syndrome, vitamin D, decreased longevity, suicide risk and medication treatment targets. Further research on the role of seasonality in BD is likely to clarify the etiology, course and treatment of BD more widely.

DNA Extraction Method Affects the Detection of a Fungal Pathogen in Formalin-Fixed Specimens Using qPCR.

PubMed

Adams, Andrea J; LaBonte, John P; Ball, Morgan L; Richards-Hrdlicka, Kathryn L; Toothman, Mary H; Briggs, Cheryl J

2015-01-01

Museum collections provide indispensable repositories for obtaining information about the historical presence of disease in wildlife populations. The pathogenic amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has played a significant role in global amphibian declines, and examining preserved specimens for Bd can improve our understanding of its emergence and spread. Quantitative PCR (qPCR) enables Bd detection with minimal disturbance to amphibian skin and is significantly more sensitive to detecting Bd than histology; therefore, developing effective qPCR methodologies for detecting Bd DNA in formalin-fixed specimens can provide an efficient and effective approach to examining historical Bd emergence and prevalence. Techniques for detecting Bd in museum specimens have not been evaluated for their effectiveness in control specimens that mimic the conditions of animals most likely to be encountered in museums, including those with low pathogen loads. We used American bullfrogs (Lithobates catesbeianus) of known infection status to evaluate the success of qPCR to detect Bd in formalin-fixed specimens after three years of ethanol storage. Our objectives were to compare the most commonly used DNA extraction method for Bd (PrepMan, PM) to Macherey-Nagel DNA FFPE (MN), test optimizations for Bd detection with PM, and provide recommendations for maximizing Bd detection. We found that successful detection is relatively high (80-90%) when Bd loads before formalin fixation are high, regardless of the extraction method used; however, at lower infection levels, detection probabilities were significantly reduced. The MN DNA extraction method increased Bd detection by as much as 50% at moderate infection levels. Our results indicate that, for animals characterized by lower pathogen loads (i.e., those most commonly encountered in museum collections), current methods may underestimate the proportion of Bd-infected amphibians. Those extracting DNA from archived museum specimens should ensure that the techniques they are using are known to provide high-quality throughput DNA for later analysis.

Multiple glutathione S-transferase genes: identification and expression in oriental fruit fly, Bactrocera dorsalis.

PubMed

Hu, Fei; Dou, Wei; Wang, Jing-Jing; Jia, Fu-Xian; Wang, Jin-Jun

2014-02-01

The oriental fruit fly, Bactrocera dorsalis (Hendel), is widely distributed in Asia-Pacific regions, where it is a serious pest of a wide range of tropical and subtropical fruit and vegetable crops. In this study, 17 cDNA encoding glutathione S-transferases (GSTs) in B. dorsalis were sequenced and characterised. Phylogenetic analysis revealed that 16 GSTs belonged to five different cytosolic classes, including four in delta, eight in epsilon, two in omega, one in theta, and one in zeta. The remaining GST (BdGSTu1) was unclassified. RT-qPCR assay showed that the relative expression levels of five GST genes were significantly higher in larval stages than in adulthood. Tissue-specific expression analysis found that BdGSTe3, BdGSTe9 and BdGSTd5 were expressed highly in the midgut, BdGSTe4, BdGSTe6, BdGSTd6 and BdGSTz2 were higher in the fat body, and six GSTs were higher in Malpighian tubules. RT-qPCR confirmed that the expressions of nine GST genes were increased by malathion exposure at various times and doses, while BdGSTe4, BdGSTe9 and BdGSTt1 were increased by β-cypermethrin exposure. The increases in GST gene expression levels after malathion and β-cypermethrin exposure in B. dorsalis might increase the ability of this species to detoxify other insecticides and xenobiotics. © 2013 Society of Chemical Industry.

13 CFR 124.204 - How does SBA process applications for 8(a) BD program admission?

Code of Federal Regulations, 2011 CFR

2011-01-01

... admission? (a) The AA/BD is authorized to approve or decline applications for admission to the 8(a) BD... from ANC-owned applicants and review them for completeness before sending them to the AA/BD for further... admittance. (e) The decision of the AA/BD to approve or deny an application will be in writing. A decision to...

13 CFR 124.204 - How does SBA process applications for 8(a) BD program admission?

Code of Federal Regulations, 2013 CFR

2013-01-01

... admission? (a) The AA/BD is authorized to approve or decline applications for admission to the 8(a) BD... information relates. (d) An applicant must be eligible as of the date the AA/BD issues a decision. The...) The decision of the AA/BD to approve or deny an application will be in writing. A decision to deny...

A pesticide paradox: Fungicides indirectly increase fungal infections

USGS Publications Warehouse

Rohr, Jason R.; Brown, Jenise; Battaglin, William A.; McMahon, Teagan A.; Reylea, Rick A.

2017-01-01

There are many examples where the use of chemicals have had profound unintended consequences, such as fertilizers reducing crop yields (paradox of enrichment) and insecticides increasing insect pests (by reducing natural biocontrol). Recently, the application of agrochemicals, such as agricultural disinfectants and fungicides, has been explored as an approach to curb the pathogenic fungus, Batrachochytrium dendrobatidis (Bd), which is associated with worldwide amphibian declines. However, the long-term, net effects of early-life exposure to these chemicals on amphibian disease risk have not been thoroughly investigated. Using a combination of laboratory experiments and analysis of data from the literature, we explored the effects of fungicide exposure on Bd infections in two frog species. Extremely low concentrations of the fungicides azoxystrobin, chlorothalonil, and mancozeb were directly toxic to Bd in culture. However, estimated environmental concentrations of the fungicides did not reduce Bd on Cuban tree frog (Osteopilus septentrionalis) tadpoles exposed simultaneously to any of these fungicides and Bd, and fungicide exposure actually increased Bd-induced mortality. Additionally, exposure to any of these fungicides as tadpoles resulted in higher Bd abundance and greater Bd-induced mortality when challenged with Bd post-metamorphosis, an average of 71 d after their last fungicide exposure. Analysis of data from the literature revealed that previous exposure to the fungicide itraconazole, which is commonly used to clear Bd infections, made the critically endangered booroolong frog (Litoria booroolongensis) more susceptible to Bd. Finally, a field survey revealed that Bd prevalence was positively associated with concentrations of fungicides in ponds. Although fungicides show promise for controlling Bd, these results suggest that, if fungicides do not completely eliminate Bd or if Bd recolonizes, exposure to fungicides has the potential to do more harm than good. To ensure that fungicide applications have the intended consequence of curbing amphibian declines, researchers must identify which fungicides do not compromise the pathogen resistance mechanisms of amphibians.

The pathogen Batrachochytrium dendrobatidis disturbs the frog skin microbiome during a natural epidemic and experimental infection

PubMed Central

Jani, Andrea J.; Briggs, Cheryl J.

2014-01-01

Symbiotic microbial communities may interact with infectious pathogens sharing a common host. The microbiome may limit pathogen infection or, conversely, an invading pathogen can disturb the microbiome. Documentation of such relationships during naturally occurring disease outbreaks is rare, and identifying causal links from field observations is difficult. This study documented the effects of an amphibian skin pathogen of global conservation concern [the chytrid fungus Batrachochytrium dendrobatidis (Bd)] on the skin-associated bacterial microbiome of the endangered frog, Rana sierrae, using a combination of population surveys and laboratory experiments. We examined covariation of pathogen infection and bacterial microbiome composition in wild frogs, demonstrating a strong and consistent correlation between Bd infection load and bacterial community composition in multiple R. sierrae populations. Despite the correlation between Bd infection load and bacterial community composition, we observed 100% mortality of postmetamorphic frogs during a Bd epizootic, suggesting that the relationship between Bd and bacterial communities was not linked to variation in resistance to mortal disease and that Bd infection altered bacterial communities. In a controlled experiment, Bd infection significantly altered the R. sierrae microbiome, demonstrating a causal relationship. The response of microbial communities to Bd infection was remarkably consistent: Several bacterial taxa showed the same response to Bd infection across multiple field populations and the laboratory experiment, indicating a somewhat predictable interaction between Bd and the microbiome. The laboratory experiment demonstrates that Bd infection causes changes to amphibian skin bacterial communities, whereas the laboratory and field results together strongly support Bd disturbance as a driver of bacterial community change during natural disease dynamics. PMID:25385615

Utilization of plant-derived recombinant human β-defensins (hBD-1 and hBD-2) for averting salmonellosis.

PubMed

Patro, Sunita; Maiti, Soumitra; Panda, Santosh Kumar; Dey, Nrisingha

2015-04-01

We describe the use of plant-made β-defensins as effective antimicrobial substances for controlling salmonellosis, a deadly infection caused by Salmonella typhimurium (referred to further as S. typhi). Human β-defensin-1 (hBD-1) and -2 (hBD-2) were expressed under the control of strong constitutive promoters in tobacco plants, and bio-active β-defensins were successfully extracted. In the in vitro studies, enriched recombinant plant-derived human β-defensin-1 (phBD-1) and -2 (phBD-2) obtained from both T1 and T2 transgenic plants showed significant antimicrobial activity against Escherichia coli and S. typhi when used individually and in various combinations. The 2:1 peptide combination of phBD-1:phBD-2 with peptides isolated from T1-and T2-generation plants reduced the growth of S. typhi by 96 and 85 %, respectively. In vivo studies employing the mouse model (Balb/c) of Salmonella infection clearly demonstrated that the administration of plant-derived defensins individually and in different combinations enhanced the mean survival time of Salmonella-infected animals. When treatment consisted of the 2:1 phBD-1:phBD-2 combination, approximately 50 % of the infected mice were still alive at 206 h post-inoculation; the lowest number of viable S. typhi was observed in the liver and spleen of infected animals. We conclude that plant-made recombinant β-defensins (phBD-1 and phBD-2) are promising antimicrobial substances and have the potential to become additional tools against salmonellosis, particularly when used in combination.

Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives.

PubMed

Cardoso de Almeida, Jorge Renner; Phillips, Mary Louise

2013-01-15

Differentiating bipolar disorder (BD) from recurrent unipolar depression (UD) is a major clinical challenge. Main reasons for this include the higher prevalence of depressive relative to hypo/manic symptoms during the course of BD illness and the high prevalence of subthreshold manic symptoms in both BD and UD depression. Identifying objective markers of BD might help improve accuracy in differentiating between BD and UD depression, to ultimately optimize clinical and functional outcome for all depressed individuals. Yet, only eight neuroimaging studies to date have directly compared UD and BD depressed individuals. Findings from these studies suggest more widespread abnormalities in white matter connectivity and white matter hyperintensities in BD than UD depression, habenula volume reductions in BD but not UD depression, and differential patterns of functional abnormalities in emotion regulation and attentional control neural circuitry in the two depression types. These findings suggest different pathophysiologic processes, especially in emotion regulation, reward, and attentional control neural circuitry in BD versus UD depression. This review thereby serves as a call to action to highlight the pressing need for more neuroimaging studies, using larger samples sizes, comparing BD and UD depressed individuals. These future studies should also include dimensional approaches, studies of at-risk individuals, and more novel neuroimaging approaches, such as connectivity analysis and machine learning. Ultimately, these approaches might provide biomarkers to identify individuals at future risk for BD versus UD and biological targets for more personalized treatment and new treatment developments for BD and UD depression. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Unusual Resistance of Avian Defensin AvBD7 to Proteolytic Enzymes Preserves Its Antibacterial Activity

PubMed Central

Bailleul, Geoffrey; Kravtzoff, Amanda; Joulin-Giet, Alix; Lecaille, Fabien; Labas, Valérie; Meudal, Hervé; Loth, Karine; Teixeira-Gomes, Ana-Paula; Gilbert, Florence B.; Coquet, Laurent; Jouenne, Thierry; Brömme, Dieter; Schouler, Catherine; Landon, Céline; Lalmanach, Gilles; Lalmanach, Anne-Christine

2016-01-01

Defensins are frontline peptides of mucosal immunity in the animal kingdom, including birds. Their resistance to proteolysis and their ensuing ability to maintain antimicrobial potential remains questionable and was therefore investigated. We have shown by bottom-up mass spectrometry analysis of protein extracts that both avian beta-defensins AvBD2 and AvBD7 were ubiquitously distributed along the chicken gut. Cathepsin B was found by immunoblotting in jejunum, ileum, caecum, and caecal tonsils, while cathepsins K, L, and S were merely identified in caecal tonsils. Hydrolysis product of AvBD2 and AvBD7 incubated with a panel of proteases was analysed by RP-HPLC, mass spectrometry and antimicrobial assays. AvBD2 and AvBD7 were resistant to serine proteases and to cathepsins D and H. Conversely cysteine cathepsins B, K, L, and S degraded AvBD2 and abolished its antibacterial activity. Only cathepsin K cleaved AvBD7 and released Ile4-AvBD7, a N-terminal truncated natural peptidoform of AvBD7 that displayed antibacterial activity. Besides the 3-stranded antiparallel beta-sheet typical of beta-defensins, structural analysis of AvBD7 by two-dimensional NMR spectroscopy highlighted the restricted accessibility of the C-terminus embedded by the N-terminal region and gave a formal evidence of a salt bridge (Asp9-Arg12) that could account for proteolysis resistance. The differential susceptibility of avian defensins to proteolysis opens intriguing questions about a distinctive role in the mucosal immunity against pathogen invasion. PMID:27561012

Bipolar II disorder as a risk factor for postpartum depression.

PubMed

Mandelli, Laura; Souery, Daniel; Bartova, Lucie; Kasper, Siegfried; Montgomery, Stuart; Zohar, Joseph; Mendlewicz, Julien; Serretti, Alessandro

2016-11-01

There is evidence for a bipolar diathesis in postpartum depression (PPD) and women presenting with a first PPD frequently receive a diagnosis of bipolar type II disorder (BD-II). However formal evidence for an association between BD-II and PPD has not yet been reported. In the present study we tested a potential association between BD-II and PPD. Parous women with a diagnosis of bipolar type I disorder (BD-I) (n=93), BD-II (n=36) or major depressive disorder (MDD) (n=444) were considered in the present study. All women were retrospectively evaluated for history of PPD (DSM-IV criteria) and other clinical and socio-demographic features. Women with a history of PDD (n=139, 24%) were younger, younger at illness onset and had more family history for BD compared to women without history of PPD (n=436, 75.9%). Half of BD-II women reported PPD (50%), compared to less than one-third of BD-I and MDD women (respectively 27.5% and 21.6%) (p=0.004). Limitations include the retrospective assessment of PPD and no available data about the timing of postpartum episodes, illness onset or psychiatric care before or after childbirth, and the number of postpartum episodes. BD-II may confer a remarkable risk for PPD, which may be even higher than that of women affected by BD-I disorder. Careful monitoring of BD-II women during the pregnancy and postpartum period, as well as assessment of bipolar features in women with a PPD without a current diagnosis of BD are recommended. Copyright © 2016 Elsevier B.V. All rights reserved.

Executive functioning deficits among adults with Bipolar Disorder (types I and II): A systematic review and meta-analysis.

PubMed

Dickinson, Tania; Becerra, Rodrigo; Coombes, Jacqui

2017-08-15

Executive functioning (EF) deficits contribute to a significant proportion of the burden of disease associated with bipolar disorder (BD). Yet, there is still debate in the literature regarding the exact profile of executive functioning in BD. The purpose of the present project was to assess whether EF deficits exist among adults suffering BD, and whether these deficits (if apparent) differ by BD subtype. A systematic search identified relevant literature. Randomised controlled trials that used neuropsychological assessment to investigate EF among adults 16-65 years) with a remitted DSM diagnosis of BD (type I or II) were included. Studies were published between 1994 and 2015. A systematic review and meta-analysis were undertaken. For individual studies, standardised mean differences (Cohen's d) and 95% confidence intervals were calculated and represented in forest plots to illustrate differences in executive performance between groups. Summary effects were produced and tests of heterogeneity employed to assess the dispersion and generalisability of results. Thirty-six studies met criteria for inclusion. Six domains of EF were identified: Set-shifting (SS), inhibition (INH), planning (PLA), verbal fluency (VF), working memory (WM), and attention (ATT). BD1s performed worse than HCs in all domains. BD2s demonstrated impairment in VF, WM, SS, and ATT. The results were mixed for comparisons between BD1s and BD2s, but revealed that BD2s can experience similar (or sometimes greater) EF impairment. Only a limited number of studies that included BD2 samples were available for inclusion in the current study. Subgroup analysis to elucidate potential moderators of within-study variance was not undertaken. This is the first systematic review and meta-analysis to have compared the EF of remitted BD1s, BD2s, and HCs. The results provided useful insight into the EF profile of patients with BD, and offered commentary as to some of the contradictory results reported in the literature. A standardised methodological protocol for assessment of EF in BD was proposed. The information in this review could enhance our understanding of EF impairment inherent in BD, and the methods and efficacy with which clinicians assess and treat this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Mindfulness based cognitive therapy may improve emotional processing in bipolar disorder: pilot ERP and HRV study.

PubMed

Howells, Fleur M; Laurie Rauch, H G; Ives-Deliperi, Victoria L; Horn, Neil R; Stein, Dan J

2014-06-01

Emotional processing in bipolar disorder (BD) is impaired. We aimed to measure the effects of mindfulness based cognitive-behavioral therapy (MBCT) in BD on emotional processing, as measured by event related potentials (ERP) and by heart rate variability (HRV). ERP and HRV were recorded during the completion of a visual matching task, which included object matching, affect matching, and affect labeling. Individuals with BD (n = 12) were compared with controls (n = 9) to obtain baseline data prior to the individuals with BD undergoing an 8-week MBCT intervention. ERP and HRV recording was repeated after the MBCT intervention in BD. Participants with BD had exaggerated ERP N170 amplitude and increased HRV HF peak compared to controls, particularly during the affect matching condition. After an 8-week MBCT intervention, participants with BD showed attenuation of ERP N170 amplitude and reduced HRV HF peak. Our findings support findings from the literature emphasizing that emotional processing in BD is altered, and suggesting that MBCT may improve emotional processing in BD.

Bipolar disorder comorbidity in patients with a primary diagnosis of OCD.

PubMed

Saraf, Gayatri; Paul, Imon; Viswanath, Biju; Narayanaswamy, Janardhanan C; Math, Suresh Bada; Reddy, Y C Janardhan

2017-03-01

Bipolar disorder (BD) is considered to be a common comorbid condition in subjects with obsessive-compulsive disorder (OCD), but there is limited literature on the prevalence of BD and its clinical correlates in those with a primary diagnosis of OCD. We studied the prevalence of BD in a sample of consecutively registered outpatients attending a specialty OCD clinic in India over a period of 13 months. One hundred and seventy-one patients with a primary diagnosis of OCD were assessed systematically using structured and semi-structured instruments. The prevalence of lifetime BD in OCD was 4%. The OCD + BD group had an episodic course of OCD and higher rate of lifetime suicide attempts. BD may not be as highly prevalent in OCD as reported in literature. Those with OCD seem to have only a marginally higher risk for developing BD than the general population. A diagnosis of BD seems to have a pathoplastic effect on the course of OCD. Patients with OCD-BD comorbidity have to be specifically assessed for suicide risk.

Distribution limits of Batrachochytrium dendrobatidis: a case study in the Rocky Mountains, USA

USGS Publications Warehouse

Hossack, Blake R.; Muths, Erin L.; Anderson, Chauncey W.; Kirshtein, Julie D.; Corn, P. Stephen

2009-01-01

Knowledge of the environmental constraints on a pathogen is critical to predicting its dynamics and effects on populations. Batrachochytrium dendrobatidis (Bd), an aquatic fungus that has been linked with widespread amphibian declines, is ubiquitous in the Rocky Mountains. As part of assessing the distribution limits of Bd in our study area, we sampled the water column and sediments for Bd zoospores in 30 high-elevation water bodies that lacked amphibians. All water bodies were in areas where Bd has been documented from neighboring, lower-elevation areas. We targeted areas lacking amphibians because existence of Bd independent of amphibians would have both ecologic and management implications. We did not detect Bd, which supports the hypothesis that it does not live independently of amphibians. However, assuming a detection sensitivity of 59.5% (based on sampling of water where amphibians tested positive for Bd), we only had 95% confidence of detecting Bd if it was in > or =16% of our sites. Further investigation into potential abiotic reservoirs is needed, but our results provide a strategic step in determining the distributional and environmental limitations of Bd in our study region.

Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes.

PubMed

Forti, Adriana; Garcia, Eduardo Garcia; Yu, Maria B; Jimenez, Maria C; Brodows, Robert G; Oliveira, Juliana H

2008-09-01

To evaluate whether exenatide administered before breakfast and dinner (BD) or before lunch and dinner (LD) provided similar glycemic control in Latin American patients with type 2 diabetes mellitus (T2DM) who consume a small breakfast. In this open-label, 2-arm study, patients taking metformin, sulfonylureas, and/or thiazolidinediones were randomized to exenatide before BD or before LD (5-mug exenatide for 4 weeks, then 10-microg exenatide for 8 weeks). Treatment assignment was determined by a computer-generated random sequence using an interactive response system. Patients were eligible for study inclusion if they consumed <15% of their total caloric intake at breakfast. The primary endpoint was HbA(1c) change from baseline to endpoint. Secondary endpoints included fasting serum glucose (FSG) level, 7-point SMBG profile, and safety. Clinicaltrials.gov Identifier: NCT00359879. 377 participants (55% female, age 54 +/- 10 years, weight 82 +/- 15 kg, BMI 31 +/- 4 kg/m(2), HbA(1c) 8.4 +/- 0.9%; mean +/- SD) from Brazil and Mexico were randomized to study treatment. HbA(1c) reduction with exenatide administration before BD was non-inferior to administration before LD (mean difference between (LD-BD) treatments: 0.14%; 95% CI -0.04 to 0.32%, p=0.120). Both treatments resulted in statistically significant HbA(1c) reductions at endpoint (BD -1.2% and LD -1.1%, respectively, p<0.001). In Brazil, the non-inferiority criteria were met for HbA(1c) reduction between treatment arms (-0.12%; CI -0.37 to 0.13%, p=0.344), whereas in Mexico, there was a difference favoring exenatide administration before BD (0.41%; CI 0.16 to 0.66%, p=0.002). At endpoint, there were no statistical significant differences between the BD and LD arms in mean change in FSG (0.50 mmol/L; CI -0.02 to 1.02 mmol/L, p=0.058) and daily mean change in SMBG (0.19 mmol/L; CI -0.17 to 0.54 mmol/L, p=0.295). The rates of symptomatic hypoglycemia (5.2 events/patient-year vs. 6.1 events/patient-year) and nausea (23% vs. 25%), were similar between the BD and LD arms, respectively. A limitation of the study design was that caloric intake of patients and meal times were not monitored. In T2DM patients who consume a small breakfast, exenatide administration before breakfast or lunch resulted in significant improvement in glycemic control.

A Comparative Metabolomic Evaluation of Behcet’s Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid

PubMed Central

Kim, Jungyeon; Hwang, Jiwon; Kim, Kyoung Heon; Cha, Hoon-Suk

2015-01-01

Behcet’s disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis. PMID:26270538

Batrachochytrium dendrobatidis infection dynamics in the Columbia spotted frog Rana luteiventris in north Idaho, USA.

PubMed

Russell, Danelle M; Goldberg, Caren S; Waits, Lisette P; Rosenblum, Erica Bree

2010-11-01

The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) is contributing to amphibian declines worldwide. Temperature plays an important role in both pathogen growth and host immune function, but little is known about seasonal dynamics of Bd infection in north temperate regions. Our objective was to increase understanding of Bd disease ecology by investigating patterns of Bd infection of Columbia spotted frogs Rana luteiventris across seasons, age classes, and sexes in north Idaho, USA. We collected skin swabs from 223 R. luteiventris in spring, summer, and fall 2009 at 7 ponds in the Palouse region and quantified Bd zoospores for each sample using quantitative PCR. Across seasons, Bd prevalence of adults was higher in summer than in spring or fall, suggesting that individuals may be clearing low-level infections over the summer. Among age classes, all but one late stage tadpole (Gosner stage 43-45) tested negative for Bd. Conversely, 100% of metamorphs tested positive for Bd and had the highest Bd loads of all age classes, suggesting they may be the most vulnerable age class. Adult R. luteiventris had high infection prevalence (> 60%) in all seasons, indicating that Bd infection is maintained within populations and that adults likely serve as disease reservoirs across seasons. Among adults, we also found weak evidence for females having higher infection prevalence than males. Further laboratory and field studies are needed to determine whether there are individual and population impacts from Bd on R. luteiventris and other amphibians in north Idaho.

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

PubMed

Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

2016-01-01

Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8.

PubMed

McElroy, Susan L; Winham, Stacey J; Cuellar-Barboza, Alfredo B; Colby, Colin L; Ho, Ada Man-Choi; Sicotte, Hugues; Larrabee, Beth R; Crow, Scott; Frye, Mark A; Biernacka, Joanna M

2018-02-02

Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.

Why does Amphibian Chytrid (Batrachochytrium dendrobatidis) not occur everywhere? An exploratory study in Missouri ponds.

PubMed

Strauss, Alex; Smith, Kevin G

2013-01-01

The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is a globally emerging pathogen that has caused widespread amphibian population declines, extirpations, and extinctions. However, Bd does not occur in all apparently suitable amphibian populations, even within regions where it is widespread, and it is often unclear why Bd occurs in some habitats but not others. In this study, we rigorously surveyed the amphibian and invertebrate biodiversity of 29 ponds in Missouri, screened resident amphibian larvae (Rana (Lithobates) sp.) for Bd infection, and characterized the aquatic physiochemical environment of each pond (temperature pH, conductivity, nitrogen, phosphorus, and chlorophyll-a). Our goal was to generate hypotheses toward answering the question, "Why does Bd not occur in all apparently suitable habitats?" Bd occurred in assayed amphibians in 11 of the 29 ponds in our study area (38% of ponds). We found no significant relationship between any single biotic or abiotic variable and presence of Bd. However, multivariate analyses (nonmetric multidimensional scaling and permutational tests of dispersion) revealed that ponds in which Bd occurred were a restricted subset of all ponds in terms of amphibian community structure, macroinvertebrate community structure, and pond physiochemistry. In other words, Bd ponds from 6 different conservation areas were more similar to each other than would be expected based on chance. The results of a structural equation model suggest that patterns in the occurrence of Bd among ponds are primarily attributable to variation in macroinvertebrate community structure. When combined with recent results showing that Bd can infect invertebrates as well as amphibians, we suggest that additional research should focus on the role played by non-amphibian biota in determining the presence, prevalence, and pathogenicity of Bd in amphibian populations.

Is Chytridiomycosis an Emerging Infectious Disease in Asia?

PubMed Central

Swei, Andrea; Rowley, Jodi J. L.; Rödder, Dennis; Diesmos, Mae L. L.; Diesmos, Arvin C.; Briggs, Cheryl J.; Brown, Rafe; Cao, Trung Tien; Cheng, Tina L.; Chong, Rebecca A.; Han, Ben; Hero, Jean-Marc; Hoang, Huy Duc; Kusrini, Mirza D.; Le, Duong Thi Thuy; McGuire, Jimmy A.; Meegaskumbura, Madhava; Min, Mi-Sook; Mulcahy, Daniel G.; Neang, Thy; Phimmachak, Somphouthone; Rao, Ding-Qi; Reeder, Natalie M.; Schoville, Sean D.; Sivongxay, Niane; Srei, Narin; Stöck, Matthias; Stuart, Bryan L.; Torres, Lilia S.; Tran, Dao Thi Anh; Tunstall, Tate S.; Vieites, David; Vredenburg, Vance T.

2011-01-01

The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has caused dramatic amphibian population declines and extinctions in Australia, Central and North America, and Europe. Bd is associated with >200 species extinctions of amphibians, but not all species that become infected are susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of the world, such as in Australia, USA, and throughout Central and South America, causing population and species collapse. The mechanism behind the rapid global emergence of the disease is poorly understood, in part due to an incomplete picture of the global distribution of Bd. At present, there is a considerable amount of geographic bias in survey effort for Bd, with Asia being the most neglected continent. To date, Bd surveys have been published for few Asian countries, and infected amphibians have been reported only from Indonesia, South Korea, China and Japan. Thus far, there have been no substantiated reports of enigmatic or suspected disease-caused population declines of the kind that has been attributed to Bd in other areas. In order to gain a more detailed picture of the distribution of Bd in Asia, we undertook a widespread, opportunistic survey of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea. Survey sites spanned 15 countries, approximately 36° latitude, 111° longitude, and over 2000 m in elevation. Bd prevalence was very low throughout our survey area (2.35% overall) and infected animals were not clumped as would be expected in epizootic events. This suggests that Bd is either newly emerging in Asia, endemic at low prevalence, or that some other ecological factor is preventing Bd from fully invading Asian amphibians. The current observed pattern in Asia differs from that in many other parts of the world. PMID:21887238

Why Does Amphibian Chytrid (Batrachochytrium dendrobatidis) Not Occur Everywhere? An Exploratory Study in Missouri Ponds

PubMed Central

Strauss, Alex; Smith, Kevin G.

2013-01-01

The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is a globally emerging pathogen that has caused widespread amphibian population declines, extirpations, and extinctions. However, Bd does not occur in all apparently suitable amphibian populations, even within regions where it is widespread, and it is often unclear why Bd occurs in some habitats but not others. In this study, we rigorously surveyed the amphibian and invertebrate biodiversity of 29 ponds in Missouri, screened resident amphibian larvae (Rana (Lithobates) sp.) for Bd infection, and characterized the aquatic physiochemical environment of each pond (temperature pH, conductivity, nitrogen, phosphorus, and chlorophyll-a). Our goal was to generate hypotheses toward answering the question, “Why does Bd not occur in all apparently suitable habitats?” Bd occurred in assayed amphibians in 11 of the 29 ponds in our study area (38% of ponds). We found no significant relationship between any single biotic or abiotic variable and presence of Bd. However, multivariate analyses (nonmetric multidimensional scaling and permutational tests of dispersion) revealed that ponds in which Bd occurred were a restricted subset of all ponds in terms of amphibian community structure, macroinvertebrate community structure, and pond physiochemistry. In other words, Bd ponds from 6 different conservation areas were more similar to each other than would be expected based on chance. The results of a structural equation model suggest that patterns in the occurrence of Bd among ponds are primarily attributable to variation in macroinvertebrate community structure. When combined with recent results showing that Bd can infect invertebrates as well as amphibians, we suggest that additional research should focus on the role played by non-amphibian biota in determining the presence, prevalence, and pathogenicity of Bd in amphibian populations. PMID:24086681

Differential gene expression profiles of β-defensins in the crop, intestine, and spleen using a necrotic enteritis model in 2 commercial broiler chicken lines.

PubMed

Hong, Y H; Song, W; Lee, S H; Lillehoj, H S

2012-05-01

Changes in the expression levels of avian β-defensin (AvBD) mRNA were evaluated in necrotic enteritis (NE) disease model in 2 genetically disparate commercial broiler chicken lines: Ross and Cobb. The NE was initiated in the gut by a previously established co-infection model using oral Eimeria maxima infection followed by a Clostridium perfringens challenge. Among the 14 AvBD types examined, there was a tissue-specific expression of AvBD transcripts: AvBD1, AvBD7, and AvBD9 in the crop; AvBD8, AvBD10, and AvBD13; in the intestine and AvBD1 and AvBD7 in the spleen. The 2 different commercial broiler chicken lines showed differential gene expression patterns of AvBD transcripts following co-infection with E. maxima and C. perfringens, with R-line chickens generally showing higher expression levels than the C strain. Both chicken strains showed enhanced gene expression levels of proinflammatory cytokines, such as IL-1β, IL-6, IL-17F, and TNFSF15 in spleen, and TNFSF15 in intestine, whereas IL-17F was significantly increased only in the intestine of R-line chickens following NE infection. Although the exact nature of interactions between defensins and cytokines in determining the outcome of host innate immune responses to the pathogens of NE remains to be investigated, the differences in gene expression levels of β-defensins and proinflammatory cytokines in the intestine, crop, and spleen could explain the predisposed disease resistance and susceptibility to NE in the 2 commercial broiler chicken lines.

σ-1 receptor stimulation protects against pressure-induced damage through InsR-MAPK signaling in human trabecular meshwork cells

PubMed Central

Meng, Bo; Li, Hongyi; Sun, Xian; Qu, Wei; Yang, Binbin; Cheng, Fang; Shi, Liping; Yuan, Huiping

2017-01-01

The purpose of the present study was to investigate the protective effect of the σ-1 receptor (Sig-1R) agonist (+)-pentazocin (PTZ) on pressure-induced apoptosis and death of human trabecular meshwork cells (hTMCs). The expression levels of Sig-1R and insulin receptor (InsR) were examined in hTMCs. Cells were cultured under a pressure of 0, 20, 40, 60 and 80 mmHg for 48 h, and under 80 mmHg for 44 h, after which the cells were treated with (+)-PTZ (20 µM), N-(2-(3,4-dichlorophenyl)ethyl)-N-methyl-2-(dimethylamino) ethylamine (BD-1063; 20 µM) administered 30 min prior to (+)-PTZ, or BD-1063 (20 µM) and then exposed to 80 mmHg again until the 48 h time-point. The changes of the cells were observed by optical and electron microscopy, the apoptosis and death of hTMCs were detected by ethidium bromide/acridine orange dual staining assay and the expression of Sig-1R and InsR by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The phosphorylation of extracellular signal-regulated kinase (ERK), an important downstream protein of the InsR-mitogen-activated protein kinases (MAPK) signaling pathway, was also detected by western blot analysis when (+)-PTZ and BD-1063 were added to the 80 mmHg-treated cells. Sig-1Rs and InsRs were expressed in hTMCs. The apoptosis and death of hTMCs increased from 40 mmHg with 50% cell death when the pressure was at 80 mmHg and the structure of the cells noticeably changed. The expression of Sig-1R and InsR increased along with the elevation of pressure. (+)-PTZ decreased the apoptosis and death of hTMCs and increased the expression of Sig-1R and InsR, and the phosphorylation of ERK. Such effects were blocked by BD-1063. The present study suggested that Sig-1R agonist (+)-PTZ can protect hTMCs from pressure-induced apoptosis and death by activating InsR and the MAPK signal pathway. PMID:28560459

Differences in Butadiene Adduct Formation between Rats and Mice Not Due to Selective Inhibition of CYP2E1 by Butadiene Metabolites

PubMed Central

Pianalto, Kaila M.; Hartman, Jessica H.; Boysen, Gunnar; Miller, Grover P.

2013-01-01

CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EB-diol). The dose response of DNA and protein adducts derived from BD metabolites increase linearly at low BD exposures and then saturate at higher exposures in rats, but not mice. It was hypothesized that differences in adduct formation between rodents reflect more efficient BD oxidation in mice than rats. Herein, we assessed whether BD-derived metabolites selectively inhibit rat but not mouse CYP2E1 activity using B6C3F1 mouse and Fisher 344 rat liver microsomes. Basal CYP2E1 activities toward 4-nitrophenol were similar between rodents. Through IC50 studies, EB was the strongest inhibitor (IC50 54 μM, mouse; 98 μM, rat), BD-diol considerably weaker (IC50 1200 μM, mouse; 1000 μM, rat), and DEB inhibition nonexistent (IC50 >25 mM). Kinetic studies showed that in both species EB and BD-diol inhibited 4-nitrophenol oxidation through two-site mechanisms in which inhibition constants reflected trends observed in IC50 studies. None of the reactive epoxide metabolites inactivated CYP2E1 irreversibly. Thus, there was no selective inhibition or inactivation of rat CYP2E1 by BD metabolites relative to mouse Cyp2e1, and it can be inferred that CYP2E1 activity toward BD between rodent species would similarly not be impacted by the presence of BD metabolites. Inhibition of CYP2E1 by BD metabolites is then not responsible for the reported species difference in BD metabolism, formation of BD-derived DNA and protein adducts, mutagenicity and tumorigenesis. PMID:24021170

Differences in butadiene adduct formation between rats and mice not due to selective inhibition of CYP2E1 by butadiene metabolites.

PubMed

Pianalto, Kaila M; Hartman, Jessica H; Boysen, Gunnar; Miller, Grover P

2013-11-25

CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4-butanediol (EB-diol). The dose response of DNA and protein adducts derived from BD metabolites increases linearly at low BD exposures and then saturates at higher exposures in rats, but not mice. It was hypothesized that differences in adduct formation between rodents reflect more efficient BD oxidation in mice than rats. Herein, we assessed whether BD-derived metabolites selectively inhibit rat but not mouse CYP2E1 activity using B6C3F1 mouse and Fisher 344 rat liver microsomes. Basal CYP2E1 activities toward 4-nitrophenol were similar between rodents. Through IC50 studies, EB was the strongest inhibitor (IC50 54μM, mouse; 98μM, rat), BD-diol considerably weaker (IC50 1200μM, mouse; 1000μM, rat), and DEB inhibition nonexistent (IC50>25mM). Kinetic studies showed that in both species EB and BD-diol inhibited 4-nitrophenol oxidation through two-site mechanisms in which inhibition constants reflected trends observed in IC50 studies. None of the reactive epoxide metabolites inactivated CYP2E1 irreversibly. Thus, there was no selective inhibition or inactivation of rat CYP2E1 by BD metabolites relative to mouse Cyp2e1, and it can be inferred that CYP2E1 activity toward BD between rodent species would similarly not be impacted by the presence of BD metabolites. Inhibition of CYP2E1 by BD metabolites is then not responsible for the reported species difference in BD metabolism, formation of BD-derived DNA and protein adducts, mutagenicity and tumorigenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impulse oscillometry at preschool age is a strong predictor of lung function by flow-volume spirometry in adolescence.

PubMed

Lauhkonen, Eero; Riikonen, Riikka; Törmänen, Sari; Koponen, Petri; Nuolivirta, Kirsi; Helminen, Merja; Toikka, Jyri; Korppi, Matti

2018-05-01

The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally. Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years. The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV 1 and FEV 1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV 1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV 1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV 1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV 1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF 50 when expressed as %-predicted parameters. Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence. © 2018 Wiley Periodicals, Inc.

Frequency of Behçet's disease among a group of visually impaired adults.

PubMed

Uyaroglu, Oguz Abdullah; Seyhoglu, Emrah; Erden, Abdulsamet; Vahabov, Cevanşir; Babaoglu, Hakan; Armagan, Berkan; Sari, Alper; Kilic, Levent; Tatar, Olcay; Bilgen, Sule Apras; Karadag, Omer; Kalyoncu, Umut

2018-03-09

Behçet's disease (BD) is one of the reasons of acquired visual impairment among young adults. Ocular involvement is a significant cause of disability in BD. The objective of this study is to assess the prevalence of BD among a group of adults who has visual impairment. Ankara Metropolitan Municipality Education and Technology Center is one of the official institutions which records and follows the demographic data of visually impaired people in Turkey. In November 2014, there were 675 visually impaired people recorded at this center. Medical history was taken from 294 adults by phone in November and December of 2014. Participants were asked if the visual impairment had been either acquired or congenital. If the patients had BD or suspicious BD, they were recalled for detailed investigation which would be carried out by an internist, a rheumatologist and an ophthalmologist. Two hundred thirteen of 294 (72.4%) visually impaired adults were male. One hundred nine of 294 (37.1%) had acquired visual impairment. Six (5.5%) of those 109 patients had BD. Overall prevalence of BD among study group was 2.04%.The median age of people with BD was 35 years. The median age at BD diagnosis was 16.5 years and the median duration from diagnosis to visual loss was 2.5 years. BD is still one of the causes of acquired visual impairment in Turkey. In this study, BD prevalence among a visually impaired adult group was 2.04%. BD accounted for 5.5% among adults who had acquired visual impairment. In a study of 1965, BD prevalence among people with acquired blindness was 12%. However, this study was conducted at pre-immunosuppressive period. Our prevalence is obviously lower than those studies. Extended population-based studies are needed for population estimations.

Increased Intrasubject Variability in Response Time in Youths with Bipolar Disorder and At-Risk Family Members

ERIC Educational Resources Information Center

Brotman, Melissa A.; Rooney, Melissa H.; Skup, Martha; Pine, Daniel S.; Leibenluft, Ellen

2009-01-01

Intrasubject variability in response time (ISV-RT) was higher in youths with bipolar disorder (BD) and those with first-degree relatives with BD compared to youths without BD. ISV-RT may be a risk marker for BD.

Circadian Rhythm in Bipolar Disorder: A review of the literature.

PubMed

Takaesu, Yoshikazu

2018-06-05

Sleep disturbances and circadian rhythm dysfunction have been widely demonstrated in patients with bipolar disorder (BD). Irregularity of the sleep-wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes, and the irregularity of social time cues have also been well-documented in BD. Circadian rhythm dysfunction is prominent in BD compared with that in major depressive disorders, implying that circadian rhythm dysfunction is a trait marker of BD. In the clinical course of BD, the circadian rhythm dysfunctions may act as predictors for the first onset of BD and the relapse of mood episodes. Treatments focusing on sleep disturbances and circadian rhythm dysfunction in combination with pharmacological, psychosocial, and chronobiological treatments are believed to be useful for relapse prevention. Further studies are therefore warranted to clarify the relationship between circadian rhythm dysfunction and the pathophysiology of BD to develop treatment strategies for achieving recovery in BD patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Analysis of Th Cell-related Cytokine Production in Behçet Disease Patients with Uveitis Before and After Infliximab Treatment.

PubMed

Takeuchi, Masaru; Karasawa, Yoko; Harimoto, Kohzou; Tanaka, Atsushi; Shibata, Masaki; Sato, Tomohito; Caspi, Rachel R; Ito, Masataka

2017-02-01

To examine antigen-stimulated cytokine production by Behçet disease patients (BD) before and after infliximab infusion. PBMCs were obtained before and after infliximab infusion in BD patients with or without recurrent uveitis during at least 1 year of infliximab therapy, and from healthy subjects. PBMCs were cultured with IRBP, and Th-related cytokines in cultures were measured. Levels of IL-4, IL-6, IL-10 IL-17A, IL-17F, IL-31, IFN-γ, and TNFα were higher in BD before infliximab infusion than in healthy subjects, and these levels were the highest in BD with recurrent uveitis. After infliximab infusion, these cytokine levels were reduced to a greater extent in BD without recurrent uveitis than in BD with recurrence. Th-related cytokines produced by IRBP-stimulated PBMCs were elevated in BD, and infliximab infusion suppressed these cytokines to a greater extent in BD without recurrent uveitis than in those with recurrence.

Host niche may determine disease-driven extinction risk

PubMed Central

Martel, An; Haesebrouck, Freddy; Jocque, Merlijn; Brown, Tom; Green, Stephen; Vences, Miguel; Bletz, Molly C.; Pasmans, Frank

2017-01-01

The fungal pathogen Batrachochytrium dendrobatidis (Bd) drives declines and extinctions in amphibian communities. However, not all regions and species are equally affected. Here, we show that association with amphibian aquatic habitat types (bromeliad phytotelmata versus stream) across Central America results in the odds of being threatened by Bd being five times higher in stream microhabitats. This differential threat of Bd was supported in our study by a significantly lower prevalence of Bd in bromeliad-associated amphibian species compared to riparian species in Honduran cloud forests. Evidence that the bromeliad environment is less favorable for Bd transmission is exemplified by significantly less suitable physicochemical conditions and higher abundance of Bd-ingesting micro-eukaryotes present in bromeliad water. These factors may inhibit aquatic Bd zoospore survival and the development of an environmental reservoir of the pathogen. Bromeliad phytotelmata thus may act as environmental refuges from Bd, which contribute to protecting associated amphibian communities against chytridiomycosis-driven amphibian declines that threaten the nearby riparian communities. PMID:28704480

Klebsiella pneumoniae Capsule Polysaccharide Impedes the Expression of β-Defensins by Airway Epithelial Cells▿

PubMed Central

Moranta, David; Regueiro, Verónica; March, Catalina; Llobet, Enrique; Margareto, Javier; Larrate, Eider; Garmendia, Junkal; Bengoechea, José A.

2010-01-01

Human β-defensins (hBDs) contribute to the protection of the respiratory tract against pathogens. It is reasonable to postulate that pathogens have developed countermeasures to resist them. Klebsiella pneumoniae capsule polysaccharide (CPS), but not the lipopolysaccharide O antigen, mediated resistance against hBD1 and hBD2. hBD3 was the most potent hBD against Klebsiella. We investigated the possibility that as a strategy for survival in the lung, K. pneumoniae may not activate the expression of hBDs. Infection of A549 and normal human bronchial cells with 52145-ΔwcaK2, a CPS mutant, increased the expression of hBD2 and hBD3. Neither the wild type nor the lipopolysaccharide O antigen mutant increased the expression of hBDs. In vivo, 52145-ΔwcaK2 induced higher levels of mBD4 and mBD14, possible mouse orthologues of hBD2 and hBD3, respectively, than the wild type. 52145-ΔwcaK2-dependent upregulation of hBD2 occurred via NF-κB and mitogen-activated protein kinases (MAPKs) p44/42, Jun N-terminal protein kinase (JNK)-dependent pathways. The increase in hBD3 expression was dependent on the MAPK JNK. 52145-ΔwcaK2 engaged Toll-like receptors 2 and 4 (TLR2 and TLR4) to activate hBD2, whereas hBD3 expression was dependent on NOD1. K. pneumoniae induced the expression of CYLD and MKP-1, which act as negative regulators for 52145-ΔwcaK2-induced expression of hBDs. Bacterial engagement of pattern recognition receptors induced CYLD and MKP-1, which may initiate the attenuation of proinflammatory pathways. The results of this study indicate that K. pneumoniae CPS not only protects the pathogen from the bactericidal action of defensins but also impedes their expression. These features of K. pneumoniae CPS may facilitate pathogen survival in the hostile environment of the lung. PMID:20008534

Estimating Herd Immunity to Amphibian Chytridiomycosis in Madagascar Based on the Defensive Function of Amphibian Skin Bacteria

PubMed Central

Bletz, Molly C.; Myers, Jillian; Woodhams, Douglas C.; Rabemananjara, Falitiana C. E.; Rakotonirina, Angela; Weldon, Che; Edmonds, Devin; Vences, Miguel; Harris, Reid N.

2017-01-01

For decades, Amphibians have been globally threatened by the still expanding infectious disease, chytridiomycosis. Madagascar is an amphibian biodiversity hotspot where Batrachochytrium dendrobatidis (Bd) has only recently been detected. While no Bd-associated population declines have been reported, the risk of declines is high when invasive virulent lineages become involved. Cutaneous bacteria contribute to host innate immunity by providing defense against pathogens for numerous animals, including amphibians. Little is known, however, about the cutaneous bacterial residents of Malagasy amphibians and the functional capacity they have against Bd. We cultured 3179 skin bacterial isolates from over 90 frog species across Madagascar, identified them via Sanger sequencing of approximately 700 bp of the 16S rRNA gene, and characterized their functional capacity against Bd. A subset of isolates was also tested against multiple Bd genotypes. In addition, we applied the concept of herd immunity to estimate Bd-associated risk for amphibian communities across Madagascar based on bacterial antifungal activity. We found that multiple bacterial isolates (39% of all isolates) cultured from the skin of Malagasy frogs were able to inhibit Bd. Mean inhibition was weakly correlated with bacterial phylogeny, and certain taxonomic groups appear to have a high proportion of inhibitory isolates, such as the Enterobacteriaceae, Pseudomonadaceae, and Xanthamonadaceae (84, 80, and 75% respectively). Functional capacity of bacteria against Bd varied among Bd genotypes; however, there were some bacteria that showed broad spectrum inhibition against all tested Bd genotypes, suggesting that these bacteria would be good candidates for probiotic therapies. We estimated Bd-associated risk for sampled amphibian communities based on the concept of herd immunity. Multiple amphibian communities, including those in the amphibian diversity hotspots, Andasibe and Ranomafana, were estimated to be below the 80% herd immunity threshold, suggesting they may be at higher risk to chytridiomycosis if a lethal Bd genotype emerges in Madagascar. While this predictive approach rests on multiple assumptions, and incorporates only one component of hosts' defense against Bd, their culturable cutaneous bacterial defense, it can serve as a foundation for continued research on Bd-associated risk for the endemic frogs of Madagascar. PMID:28959244

Investigation of the influence of coadsorbent dye upon the interfacial structure of dye-sensitized solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honda, M., E-mail: honda.mitsunori@jaea.go.jp; Miyano, K.; Yanagida, M.

2014-11-07

The interface between Ru(tcterpy)(NCS){sub 3}TBA{sub 2} [black dye (BD); tcterpy = 4,4{sup ′},4{sup ″}-tricarboxy-2,2{sup ′}:6{sup ′},2{sup ″}-terpyridine, NCS = thiocyanato, TBA = tetrabutylammonium cation] and nanocrystalline TiO{sub 2}, as found in dye-sensitized solar cells, is investigated by soft-X-ray synchrotron radiation and compared with the adsorption structure of cis-Ru(Hdcbpy){sub 2}(NCS){sub 2}TBA{sub 2} (N719; dcbpy = 4,4{sup ′}-dicarboxy-2,2{sup ′}-bipyridine) on TiO{sub 2} to elucidate the relationship between the adsorption mode of BD and the photocurrent with and without coadsorbed indoline dye D131. The depth profile is characterized with X-ray photoelectron spectroscopy and S K-edge X-ray absorption fine structure using synchrotron radiation. Bothmore » datasets indicate that one of the isothiocyanate groups of BD interacts with TiO{sub 2} via its S atom when the dye is adsorbed from a single-component solution. In contrast, the interaction is slightly suppressed when D131 is coadsorbed, indicated by the fact that the presence of D131 changes the adsorption mode of BD. Based upon these results, the number of BD dye molecules interacting with the substrate is shown to decrease by 10% when D131 is coadsorbed, and the dissociation is shown to be related to the short-circuit photocurrent in the 600–800 nm region. The design of a procedure to promote the preferential adsorption of D131 therefore leads to an improvement of the short-circuit current and conversion efficiency.« less

A 1024×768-12μm Digital ROIC for uncooled microbolometer FPAs

NASA Astrophysics Data System (ADS)

Eminoglu, Selim

2017-02-01

This paper reports the development of a new digital microbolometer Readout Integrated Circuit (D-ROIC), called MT10212BD. It has a format of 1024 × 768 (XGA) and a pixel pitch of 12μm. MT10212BD is Mikro Tasarim's second 12μm pitch microbolometer ROIC, which is developed specifically for surface micro machined microbolometer detector arrays with small pixel pitch using high-TCR pixel materials, such as VOx and a Si. MT10212BD has an alldigital system on-chip architecture, which generates programmable timing and biasing, and performs 14-bit analog to digital conversion (ADC). The signal processing chain in the ROIC is composed of pixel bias circuitry, integrator based programmable gain amplifier followed by column parallel ADC circuitry. MT10212BD has a serial programming interface that can be used to configure the programmable ROIC features and to load the Non-Uniformity-Correction (NUC) date to the ROIC. MT10212BD has a total of 8 high-speed serial digital video outputs, which can be programmed to operate in the 2, 4, and 8-output modes and can support frames rates above 60 fps. The high-speed serial digital outputs supports data rates as high as 400 Mega-bits/s, when operated at 50 MHz system clock frequency. There is an on-chip phase-locked-loop (PLL) based timing circuitry to generate the high speed clocks used in the ROIC. The ROIC is designed to support pixel resistance values ranging from 30KΩ to 90kΩ, with a nominal value of 60KΩ. The ROIC has a globally programmable gain in the column readout, which can be adjusted based on the detector resistance value.

Affinity Map of Bromodomain Protein 4 (BRD4) Interactions with the Histone H4 Tail and the Small Molecule Inhibitor JQ1*

PubMed Central

Jung, Marie; Philpott, Martin; Müller, Susanne; Schulze, Jessica; Badock, Volker; Eberspächer, Uwe; Moosmayer, Dieter; Bader, Benjamin; Schmees, Norbert; Fernández-Montalván, Amaury; Haendler, Bernard

2014-01-01

Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family. It binds to acetylated histone tails via its tandem bromodomains BD1 and BD2 and forms a complex with the positive transcription elongation factor b, which controls phosphorylation of RNA polymerase II, ultimately leading to stimulation of transcription elongation. An essential role of BRD4 in cell proliferation and cancer growth has been reported in several recent studies. We analyzed the binding of BRD4 BD1 and BD2 to different partners and showed that the strongest interactions took place with di- and tetra-acetylated peptides derived from the histone 4 N-terminal tail. We also found that several histone 4 residues neighboring the acetylated lysines significantly influenced binding. We generated 10 different BRD4 BD1 mutants and analyzed their affinities to acetylated histone tails and to the BET inhibitor JQ1 using several complementary biochemical and biophysical methods. The impact of these mutations was confirmed in a cellular environment. Altogether, the results show that Trp-81, Tyr-97, Asn-140, and Met-149 play similarly important roles in the recognition of acetylated histones and JQ1. Pro-82, Leu-94, Asp-145, and Ile-146 have a more differentiated role, suggesting that different kinds of interactions take place and that resistance mutations compatible with BRD4 function are possible. Our study extends the knowledge on the contribution of individual BRD4 amino acids to histone and JQ1 binding and may help in the design of new BET antagonists with improved pharmacological properties. PMID:24497639

Diet and cooling interactions on physiological responses of grazing dairy cows, milk production and composition

NASA Astrophysics Data System (ADS)

Gallardo, M. R.; Valtorta, S. E.; Leva, P. E.; Gaggiotti, M. C.; Conti, G. A.; Gregoret, R. F.

2005-11-01

The objective of this trial was to evaluate the effects of diet and cooling in the holding pen before milking on rectal temperature, respiration rate and milk production and composition. Fifty-eight lactating Holstein cows were used in a factorial split-plot design, at Rafaela Experimental Station from 12 January to 3 March 2003. The treatments were combinations of two diets: control (CD) and balanced (BD) with two levels of cooling before milking: none (NSF) and a sprinkler and fans (SF). Forage:concentrate ratios for CD and BD were 81:19 and 68:32, respectively. Cows were milked twice daily. Milk production was recorded daily, and milk composition (fat, protein, lactose and urea) was analysed twice a week. The physiological data were recorded once a week, before the cattle entered the holding pen and after milking, in the afternoon. Average maximum weekly temperature humidity index was 75.4 and ranged from 61.4 to 83. There were highly significant effects of cooling on physiological responses. Milk production was affected by diet and cooling, with no interaction; the highest and lowest production of milk was 22.42 and 20.07 l/cow per day, for BD+SF and CD+NSF, respectively. Protein was affected by diet, and was higher for BD (3.17 vs. 3.08%). There were interaction effects on milk fat at the 8% level, the highest concentration being 3.65% for BD+NFS. It was concluded that under grazing conditions, cooling by sprinkler and fans before milking improves the comfort of dairy cows, and that the effects on milk production and composition are enhanced when diets are specially formulated for heat-stress periods.

Correlation Between Insight and Capacity to Consent to Research in Subjects With Bipolar Disorder Type I and Schizophrenia.

PubMed

López-Jaramillo, Carlos; Tobler, Chantal Aristizábal; Gómez, Constanza Ovalle; Triana, Jaime Escobar

2016-01-01

Schizophrenia and bipolar disorder type I (BD-I) can affect patient autonomy and capacity to consent to participate in research. Other variables associated with the autonomy of patients must be explored in order to improve the quality of the currently available tools. To evaluate the relationship between insight and the capacity to consent to participate in research in patients with BD-I and schizophrenia. A cross-sectional and longitudinal study was conducted with 120 subjects (40 subjects with schizophrenia, 40 with BD-I, and 40 healthy controls). The tools used were the Scale Assessment Insight-Expanded (SAI-E) and the MacArthur Competence Assessment Tool-Treatment (MacCAT-CR), which was first adapted culturally, and its validity and reliability assessed. The results obtained on each scale were compared and the association between them were evaluated. There is a direct correlation between the capacity to consent to research, measured using the MacCAT-CR tool, and the degree of insight, measured using the SAI-E scale, with an effect size of 1.3 for BD-I and 2.03 for schizophrenia. The results suggest that there is a correlation between the degree of insight and the capacity to consent to research in subjects with schizophrenia and BD-I. Insight should therefore be included as a relevant variable to assess the capacity to consent, and future studies should include it when researching on or designing new tools which aim at a greater respect of patient autonomy. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The Role of Th17 Cells in the Pathogenesis of Behcet's Disease.

PubMed

Nanke, Yuki; Yago, Toru; Kotake, Shigeru

2017-07-21

Behcet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. The pathogenesis of BD has not been fully elucidated; however, BD has been considered to be a typical Th1-mediated inflammatory disease, characterized by elevated levels of Th1 cytokines such as IFN-γ, IL-2, and TNF-α. Recently, some studies reported that Th17-associated cytokines were increased in BD; thus, Th17 cells and the IL17/IL23 pathway may play important roles in the pathogenesis of BD. In this chapter, we focus on the pathogenic role of Th17 cells in BD.

Differences in sensitivity to the fungal pathogen Batrachochytrium dendrobatidis among amphibian populations.

PubMed

Bradley, Paul W; Gervasi, Stephanie S; Hua, Jessica; Cothran, Rickey D; Relyea, Rick A; Olson, Deanna H; Blaustein, Andrew R

2015-10-01

Contributing to the worldwide biodiversity crisis are emerging infectious diseases, which can lead to extirpations and extinctions of hosts. For example, the infectious fungal pathogen Batrachochytrium dendrobatidis (Bd) is associated with worldwide amphibian population declines and extinctions. Sensitivity to Bd varies with species, season, and life stage. However, there is little information on whether sensitivity to Bd differs among populations, which is essential for understanding Bd-infection dynamics and for formulating conservation strategies. We experimentally investigated intraspecific differences in host sensitivity to Bd across 10 populations of wood frogs (Lithobates sylvaticus) raised from eggs to metamorphosis. We exposed the post-metamorphic wood frogs to Bd and monitored survival for 30 days under controlled laboratory conditions. Populations differed in overall survival and mortality rate. Infection load also differed among populations but was not correlated with population differences in risk of mortality. Such population-level variation in sensitivity to Bd may result in reservoir populations that may be a source for the transmission of Bd to other sensitive populations or species. Alternatively, remnant populations that are less sensitive to Bd could serve as sources for recolonization after epidemic events. © 2015 Society for Conservation Biology.

Detection of the Amphibian Chytrid Fungus Batrachochytrium dendrobatidis in Museum Specimens of Andean Aquatic Birds: Implications for Pathogen Dispersal.

PubMed

Burrowes, Patricia A; De la Riva, Ignacio

2017-04-01

The occurrence of the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) in the feet of live waterfowl has been documented, but the potential role of birds as dispersers has not been studied. We report the presence of Bd in the feet of preserved aquatic birds in the Bolivian high Andes during the time of drastic amphibian declines in the country. We sampled 48 aquatic birds from the Bolivian Andes that were preserved in museum collections. Birds were sampled for the presence of Bd DNA by swabbing, taking small pieces of tissue from toe webbing, or both. We detected Bd by DNA using quantitative PCR in 42% of the birds sampled via toe tissue pieces. This method was significantly better than swabbing at detecting Bd from bird feet. We confirmed Bd presence by sequencing Bd -positive samples and found 91-98% homology with Bd sequences from GenBank. Our study confirms that aquatic birds can carry Bd and thus may serve as potential vectors of this pathogen across large distances and complex landscapes. In addition, we recommend using DNA from preserved birds as a novel source of data to test hypotheses on the spread of chytridiomycosis in amphibians.

Gender Differences in Risk Factors for Adolescent Binge Drinking and Implications for Intervention and Prevention

PubMed Central

Dir, Allyson L.; Bell, Richard L.; Adams, Zachary W.; Hulvershorn, Leslie A.

2017-01-01

Alcohol use, particularly binge drinking (BD), is a major public health concern among adolescents. Recent national data show that the gender gap in alcohol use is lessening, and BD among girls is rising. Considering the increase in BD among adolescent girls, as well as females’ increased risk of experiencing more severe biopsychosocial negative effects and consequences from BD, the current review sought to examine gender differences in risk factors for BD. The review highlights gender differences in (1) developmental-related neurobiological vulnerability to BD, (2) psychiatric comorbidity and risk phenotypes for BD, and (3) social-related risk factors for BD among adolescents, as well as considerations for BD prevention and intervention. Most of the information gleaned thus far has come from preclinical research. However, it is expected that, with recent advances in clinical imaging technology, neurobiological effects observed in lower mammals will be confirmed in humans and vice versa. A synthesis of the literature highlights that males and females experience unique neurobiological paths of development, and although there is debate regarding the specific nature of these differences, literature suggests that these differences in turn influence gender differences in psychiatric comorbidity and risk for BD. For one, girls are more susceptible to stress, depression, and other internalizing behaviors and, in turn, these symptoms contribute to their risk for BD. On the other hand, males, given gender differences across the lifespan as well as gender differences in development, are driven by an externalizing phenotype for risk of BD, in part, due to unique paths of neurobiological development that occur across adolescence. With respect to social domains, although social and peer influences are important for both adolescent males and females, there are gender differences. For example, girls may be more sensitive to pressure from peers to fit in and impress others, while male gender role stereotypes regarding BD may be more of a risk factor for boys. Given these unique differences in male and female risk for BD, further research exploring risk factors, as well as tailoring intervention and prevention, is necessary. Although recent research has tailored substance use intervention to target males and females, more literature on gender considerations in treatment for prevention and intervention of BD in particular is warranted. PMID:29312017

Whole Exome Sequencing Identifies Rare Protein-Coding Variants in Behçet's Disease.

PubMed

Ognenovski, Mikhail; Renauer, Paul; Gensterblum, Elizabeth; Kötter, Ina; Xenitidis, Theodoros; Henes, Jörg C; Casali, Bruno; Salvarani, Carlo; Direskeneli, Haner; Kaufman, Kenneth M; Sawalha, Amr H

2016-05-01

Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent. Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches. Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein-damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10(-4) and P = 5.16 × 10(-4) , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni-corrected P = 5.63 × 10(-14) , P = 7.29 × 10(-6) , P = 1.15 × 10(-5) , and P = 6.40 × 10(-3) , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant. We used whole exome sequencing in BD for the first time and identified 2 rare putative protein-damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD. © 2016, American College of Rheumatology.

Gender Differences in Risk Factors for Adolescent Binge Drinking and Implications for Intervention and Prevention.

PubMed

Dir, Allyson L; Bell, Richard L; Adams, Zachary W; Hulvershorn, Leslie A

2017-01-01

Alcohol use, particularly binge drinking (BD), is a major public health concern among adolescents. Recent national data show that the gender gap in alcohol use is lessening, and BD among girls is rising. Considering the increase in BD among adolescent girls, as well as females' increased risk of experiencing more severe biopsychosocial negative effects and consequences from BD, the current review sought to examine gender differences in risk factors for BD. The review highlights gender differences in (1) developmental-related neurobiological vulnerability to BD, (2) psychiatric comorbidity and risk phenotypes for BD, and (3) social-related risk factors for BD among adolescents, as well as considerations for BD prevention and intervention. Most of the information gleaned thus far has come from preclinical research. However, it is expected that, with recent advances in clinical imaging technology, neurobiological effects observed in lower mammals will be confirmed in humans and vice versa . A synthesis of the literature highlights that males and females experience unique neurobiological paths of development, and although there is debate regarding the specific nature of these differences, literature suggests that these differences in turn influence gender differences in psychiatric comorbidity and risk for BD. For one, girls are more susceptible to stress, depression, and other internalizing behaviors and, in turn, these symptoms contribute to their risk for BD. On the other hand, males, given gender differences across the lifespan as well as gender differences in development, are driven by an externalizing phenotype for risk of BD, in part, due to unique paths of neurobiological development that occur across adolescence. With respect to social domains, although social and peer influences are important for both adolescent males and females, there are gender differences. For example, girls may be more sensitive to pressure from peers to fit in and impress others, while male gender role stereotypes regarding BD may be more of a risk factor for boys. Given these unique differences in male and female risk for BD, further research exploring risk factors, as well as tailoring intervention and prevention, is necessary. Although recent research has tailored substance use intervention to target males and females, more literature on gender considerations in treatment for prevention and intervention of BD in particular is warranted.

Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics.

PubMed

Versace, Amelia; Almeida, Jorge R C; Hassel, Stefanie; Walsh, Nicholas D; Novelli, Massimiliano; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2008-09-01

Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Cross-sectional, case-control, whole-brain DTI using TBSS. University research institute. Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Subjects with BD vs controls had significantly greater FA (t > 3.0, P 3.0, P

Chytrid fungus acts as a generalist pathogen infecting species-rich amphibian families in Brazilian rainforests.

PubMed

Valencia-Aguilar, Anyelet; Ruano-Fajardo, Gustavo; Lambertini, Carolina; da Silva Leite, Domingos; Toledo, Luís Felipe; Mott, Tamí

2015-05-11

The fungus Batrachochytrium dendrobatidis (Bd) is among the main causes of declines in amphibian populations. This fungus is considered a generalist pathogen because it infects several species and spreads rapidly in the wild. To date, Bd has been detected in more than 100 anuran species in Brazil, mostly in the southern portion of the Atlantic forest. Here, we report survey data from some poorly explored regions; these data considerably extend current information on the distribution of Bd in the northern Atlantic forest region. In addition, we tested the hypothesis that Bd is a generalist pathogen in this biome. We also report the first positive record for Bd in an anuran caught in the wild in Amazonia. In total, we screened 90 individuals (from 27 species), of which 39 individuals (from 22 species) were Bd-positive. All samples collected in Bahia (2 individuals), Pernambuco (3 individuals), Pará (1 individual), and Minas Gerais (1 individual) showed positive results for Bd. We found a positive correlation between anuran richness per family and the number of infected species in the Atlantic forest, supporting previous observations that Bd lacks strong host specificity; of 38% of the anuran species in the Atlantic forest that were tested for Bd infection, 25% showed positive results. The results of our study exemplify the pandemic and widespread nature of Bd infection in amphibians.

Rare esophageal ulcers related to Behçet disease: A case report.

PubMed

Jia, Ning; Tang, Yanping; Liu, Huayi; Li, Yang; Liu, Simiao; Liu, Lei

2017-11-01

The fundamental pathogenesis of Behçet disease (BD) is still unclear and controversial. Many cases of oral aphthous ulcers and genital ulcers related to BD are reported; nevertheless, idiopathic giant esophageal ulcers related to BD are rare. A rare case for esophageal ulcers related to BD is presented. In China, BD is represented with esophageal involvement which is called esophageal BD (EBD). A 56-year-old man diagnosed to the Gastroenterology Department of Integrated Traditional Chinese and Western Medicine Hospital, for multiple discrete, elliptical esophageal ulcers related to BD. The esophageal ulcers were treated with corticosteroid treatment for 12 weeks. The esophageal ulcers were cured. Our report might give further strength to avoiding the erroneous diagnosis or missed diagnosis for EBD, which is different from esophageal carcinoma, esophageal tuberculosis and esophageal Crohns disease.

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

PubMed Central

Oğuz, Ali Kemal; Yılmaz, Seda Taşır; Oygür, Çağdaş Şahap; Çandar, Tuba; Sayın, Irmak; Kılıçoğlu, Sibel Serin; Ergün, İhsan; Ateş, Aşkın; Özdağ, Hilal; Akar, Nejat

2016-01-01

Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis. PMID:26890122

Cognitive processing in bipolar disorder conceptualized using the Interactive Cognitive Subsystems (ICS) model

PubMed Central

Lomax, C. L.; Barnard, P. J.; Lam, D.

2009-01-01

Background There are few theoretical proposals that attempt to account for the variation in affective processing across different affective states of bipolar disorder (BD). The Interacting Cognitive Subsystems (ICS) framework has been recently extended to account for manic states. Within the framework, positive mood state is hypothesized to tap into an implicational level of processing, which is proposed to be more extreme in states of mania. Method Thirty individuals with BD and 30 individuals with no history of affective disorder were tested in euthymic mood state and then in induced positive mood state using the Question–Answer task to examine the mode of processing of schemas. The task was designed to test whether individuals would detect discrepancies within the prevailing schemas of the sentences. Results Although the present study did not support the hypothesis that the groups differ in their ability to detect discrepancies within schemas, we did find that the BD group was significantly more likely than the control group to answer questions that were consistent with the prevailing schemas, both before and after mood induction. Conclusions These results may reflect a general cognitive bias, that individuals with BD have a tendency to operate at a more abstract level of representation. This may leave an individual prone to affective disturbance, although further research is required to replicate this finding. PMID:18796173

The Bipolar Depression Electrical Treatment Trial (BETTER): Design, Rationale, and Objectives of a Randomized, Sham-Controlled Trial and Data from the Pilot Study Phase

PubMed Central

Pereira Junior, Bernardo de Sampaio; Nunes, Paula; Benseñor, Isabela Martins; Lotufo, Paulo Andrade; Machado-Vieira, Rodrigo; Brunoni, André R.

2015-01-01

Background. Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS. PMID:25878904

Predictors of suicide ideation among older adults with bipolar disorder.

PubMed

O'Rourke, Norm; Heisel, Marnin J; Canham, Sarah L; Sixsmith, Andrew

2017-01-01

Bipolar disorder (BD) carries the greatest risk of death by suicide of all psychiatric conditions as 25%-50% of those with BD will make one or more suicide attempt, and about 15% will intentionally end their lives. Among young adults with BD, substance misuse, medication non-adherence, age at onset, and comorbid psychiatric conditions each predict self-harm. It is currently unclear if these same factors or others predict suicide ideation among older adults with BD. We recruited a global sample of 220 older adults with BD over 19 days using socio-demographically targeted, social media advertising and online data collection (Mean = 58.50, SD = 5.42; range 50 to 81 years). Path analyses allowed us to identify direct and indirect predictors of suicide ideation among older adults with BD. Cognitive failures (perception, memory, and motor function), depressive symptoms, alcohol misuse, and dissatisfaction with life as direct predictors of suicide ideation; duration of BD symptoms and medication non-adherence emerged as indirect predictors. Of note, the significant impact of sleep on suicide ideation is indirect via depressive symptoms, cognitive failures, medication non-adherence and life dissatisfaction. As with young adults with BD, alcohol misuse and medication non-adherence emerged as significant predictors of suicide ideation. In addition, cognitive failures directly and indirectly predict suicide ideation in this sample of older adults with BD. Population aging and treatment efficacy are leading to ever growing numbers of older adults with BD. Both direct and indirect predictors of suicide ideation need to be considered in future BD research and treatment planning.

Predictors of suicide ideation among older adults with bipolar disorder

PubMed Central

Heisel, Marnin J.; Canham, Sarah L.; Sixsmith, Andrew

2017-01-01

Objectives Bipolar disorder (BD) carries the greatest risk of death by suicide of all psychiatric conditions as 25%–50% of those with BD will make one or more suicide attempt, and about 15% will intentionally end their lives. Among young adults with BD, substance misuse, medication non-adherence, age at onset, and comorbid psychiatric conditions each predict self-harm. It is currently unclear if these same factors or others predict suicide ideation among older adults with BD. Methods We recruited a global sample of 220 older adults with BD over 19 days using socio-demographically targeted, social media advertising and online data collection (Mean = 58.50, SD = 5.42; range 50 to 81 years). Path analyses allowed us to identify direct and indirect predictors of suicide ideation among older adults with BD. Results Cognitive failures (perception, memory, and motor function), depressive symptoms, alcohol misuse, and dissatisfaction with life as direct predictors of suicide ideation; duration of BD symptoms and medication non-adherence emerged as indirect predictors. Of note, the significant impact of sleep on suicide ideation is indirect via depressive symptoms, cognitive failures, medication non-adherence and life dissatisfaction. Conclusions As with young adults with BD, alcohol misuse and medication non-adherence emerged as significant predictors of suicide ideation. In addition, cognitive failures directly and indirectly predict suicide ideation in this sample of older adults with BD. Population aging and treatment efficacy are leading to ever growing numbers of older adults with BD. Both direct and indirect predictors of suicide ideation need to be considered in future BD research and treatment planning. PMID:29145409

Lifetime eating disorder comorbidity associated with delayed depressive recovery in bipolar disorder.

PubMed

Balzafiore, Danielle R; Rasgon, Natalie L; Yuen, Laura D; Shah, Saloni; Kim, Hyun; Goffin, Kathryn C; Miller, Shefali; Wang, Po W; Ketter, Terence A

2017-12-01

Although eating disorders (EDs) are common in bipolar disorder (BD), little is known regarding their longitudinal consequences. We assessed prevalence, clinical correlates, and longitudinal depressive severity in BD patients with vs. without EDs. Outpatients referred to Stanford University BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) affective disorders evaluation, and while receiving naturalistic treatment for up to 2 years, were monitored with the STEP-BD clinical monitoring form. Patients with vs. without lifetime EDs were compared with respect to prevalence, demographic and unfavorable illness characteristics/current mood symptoms and psychotropic use, and longitudinal depressive severity. Among 503 BD outpatients, 76 (15.1%) had lifetime EDs, which were associated with female gender, and higher rates of lifetime comorbid anxiety, alcohol/substance use, and personality disorders, childhood BD onset, episode accumulation (≥10 prior mood episodes), prior suicide attempt, current syndromal/subsyndromal depression, sadness, anxiety, and antidepressant use, and earlier BD onset age, and greater current overall BD severity. Among currently depressed patients, 29 with compared to 124 without lifetime EDs had significantly delayed depressive recovery. In contrast, among currently recovered (euthymic ≥8 weeks) patients, 10 with compared to 95 without lifetime EDs had only non-significantly hastened depressive recurrence. Primarily Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability. Small number of recovered patients with EDs limited statistical power to detect relationships between EDs and depressive recurrence. Further studies are warranted to explore the degree to which EDs impact longitudinal depressive illness burden in BD.

The expression of the β-defensins hBD-2 and hBD-3 is differentially regulated by NF-κB and MAPK/AP-1 pathways in an in vitro model of Candida esophagitis

PubMed Central

Steubesand, Nadine; Kiehne, Karlheinz; Brunke, Gabriele; Pahl, Rene; Reiss, Karina; Herzig, Karl-Heinz; Schubert, Sabine; Schreiber, Stefan; Fölsch, Ulrich R; Rosenstiel, Philip; Arlt, Alexander

2009-01-01

Background Candida albicans resides on epithelial surfaces as part of the physiological microflora. However, under certain conditions it may cause life-threatening infections like Candida sepsis. Human β-defensins (hBDs) are critical components of host defense at mucosal surfaces and we have recently shown that hBD-2 and hBD-3 are upregulated in Candida esophagitis. We therefore studied the role of Candidate signalling pathways in order to understand the mechanisms involved in regulation of hBD-expression by C. albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis. Results Supernatants of C. albicans or indirect coculture with C. albicans induces upregulation of hBD-2 and hBD-3 expression. PMNs strongly amplifies C. albicans-mediated induction of hBDs. By EMSA we demonstrate that C. albicans activates NF-κB and AP-1 in OE21 cells. Inhibition of these pathways revealed that hBD-2 expression is synergistically regulated by both NF-κB and AP-1. In contrast hBD-3 expression is independent of NF-κB and relies solely on an EGFR/MAPK/AP-1-dependent pathway. Conclusion Our analysis of signal transduction events demonstrate a functional interaction of epithelial cells with PMNs in response to Candida infection involving divergent signalling events that differentially govern hBD-2 and hBD-3 expression. PMID:19523197

Face validity of a pre-clinical model of operant binge drinking: just a question of speed.

PubMed

Jeanblanc, Jérôme; Sauton, Pierre; Jeanblanc, Virginie; Legastelois, Rémi; Echeverry-Alzate, Victor; Lebourgeois, Sophie; Gonzalez-Marin, Maria Del Carmen; Naassila, Mickaël

2018-06-04

Binge drinking (BD) is often defined as a large amount of alcohol consumed in a 'short' period of time or 'per occasion'. In clinical research, few researchers have included the notion of 'speed of drinking' in the definition of BD. Here, we aimed to describe a novel pre-clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long-Evans male rats, we induced BD by regularly decreasing the duration of ethanol self-administration from 1-hour to 15-minute sessions. We compared the behavioral consequences of BD with the behaviors of rats subjected to moderate drinking or heavy drinking (HD). We found that, despite high ethanol consumption levels (1.2 g/kg/15 minutes), the total amounts consumed were insufficient to differentiate HD from BD. However, consumption speed could distinguish between these groups. The motivation to consume was higher in BD than in HD rats. After BD, we observed alterations in locomotor coordination in rats that consumed greater than 0.8 g/kg, which was rarely observed in HD rats. Finally, chronic BD led to worse performance in a decision-making task, and as expected, we observed a lower stimulated dopaminergic release within nucleus accumbens slices in poor decision makers. Our BD model exhibited good face validity and can now provide animals voluntarily consuming very rapidly enough alcohol to achieve intoxication levels and thus allowing the study of the complex interaction between individual and environmental factors underlying BD behavior. © 2018 Society for the Study of Addiction.

Expression and distribution of antimicrobial peptides in the skin of healthy beagles.

PubMed

Santoro, Domenico; Bunick, David; Graves, Thomas K; Campbell, Karen L

2011-02-01

Antimicrobial peptides (AMPs) are small proteins involved in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. Our goals were to determine the distribution of AMPs and evaluate their mRNA expression in normal canine skin. Skin biopsies were taken from six healthy beagles. The relative transcript level of canine cathelicidin (cCath) and β-defensin (cBD)-1, cBD2 and cBD3 mRNA was quantified using quantitative real-time polymerase chain reaction. Indirect immunofluorescence (IIF), using polyclonal antibodies against cBD2, cBD3 and cCath, was used to evaluate protein localization in the skin of healthy dogs. The Pfaffl method, using experimentally determined primer efficiencies of amplification, was used to determine the expression level of cCath, cBD1 and cDB3 relative to cDB2. The levels of cCath, cBD3 and cBD1 mRNA were 358, 296 and 177 times higher than those of cBD2, respectively. Using IIF, cBD2 and cBD3 protein fluorescence was detected in all layers of the epidermis, whereas cCath was detected predominantly in the stratum granulosum and corneum. In addition, antimicrobial peptide detection was limited to the infundibular portion of the pilosebaceous units. We have validated useful methods to evaluate AMPs in canine skin. Further studies are needed to compare AMP expression in healthy dogs with that of dogs with inflammatory skin conditions. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Auditory processing deficits in bipolar disorder with and without a history of psychotic features.

PubMed

Zenisek, RyAnna; Thaler, Nicholas S; Sutton, Griffin P; Ringdahl, Erik N; Snyder, Joel S; Allen, Daniel N

2015-11-01

Auditory perception deficits have been identified in schizophrenia (SZ) and linked to dysfunction in the auditory cortex. Given that psychotic symptoms, including auditory hallucinations, are also seen in bipolar disorder (BD), it may be that individuals with BD who also exhibit psychotic symptoms demonstrate a similar impairment in auditory perception. Fifty individuals with SZ, 30 individuals with bipolar I disorder with a history of psychosis (BD+), 28 individuals with bipolar I disorder with no history of psychotic features (BD-), and 29 normal controls (NC) were administered a tone discrimination task and an emotion recognition task. Mixed-model analyses of covariance with planned comparisons indicated that individuals with BD+ performed at a level that was intermediate between those with BD- and those with SZ on the more difficult condition of the tone discrimination task and on the auditory condition of the emotion recognition task. There were no differences between the BD+ and BD- groups on the visual or auditory-visual affect recognition conditions. Regression analyses indicated that performance on the tone discrimination task predicted performance on all conditions of the emotion recognition task. Auditory hallucinations in BD+ were not related to performance on either task. Our findings suggested that, although deficits in frequency discrimination and emotion recognition are more severe in SZ, these impairments extend to BD+. Although our results did not support the idea that auditory hallucinations may be related to these deficits, they indicated that basic auditory deficits may be a marker for psychosis, regardless of SZ or BD diagnosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abnormal sleep duration associated with hastened depressive recurrence in bipolar disorder.

PubMed

Gershon, Anda; Do, Dennis; Satyanarayana, Satyanand; Shah, Saloni; Yuen, Laura D; Hooshmand, Farnaz; Miller, Shefali; Wang, Po W; Ketter, Terence A

2017-08-15

Abnormal sleep duration (ASD, <6 or ≥9h) is common in bipolar disorder (BD), and often persists beyond acute mood episodes. Few longitudinal studies have examined the ASD's impact upon BD illness course. The current study examined the longitudinal impact of ASD upon bipolar depressive recurrence/recovery. Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form at monthly follow-ups for up to two years of naturalistic treatment. Prevalence and clinical correlates of ASD in 93 recovered (euthymic ≥8 weeks) and 153 depressed BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between baseline ASD and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators. ASD was only half as common among recovered versus depressed BD outpatients, but was significantly associated with hastened depressive recurrence (Log-Rank p=0.007), mediated by lifetime anxiety disorder and attenuated by lifetime history of psychosis, and had only a non-significant tendency towards association with delayed depressive recovery (Log-Rank p=0.07). In both recovered and depressed BD outpatients, baseline ASD did not have significant association with any baseline BD illness characteristic. Self-reported sleep duration. Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample. Baseline ASD among recovered BD patients may be a risk marker for hastened depressive recurrence, suggesting it could be an important therapeutic target between mood episodes. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of Th17 Cells in the Pathogenesis of Behcet’s Disease

PubMed Central

Nanke, Yuki; Kotake, Shigeru

2017-01-01

Behcet’s disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. The pathogenesis of BD has not been fully elucidated; however, BD has been considered to be a typical Th1-mediated inflammatory disease, characterized by elevated levels of Th1 cytokines such as IFN-γ, IL-2, and TNF-α. Recently, some studies reported that Th17-associated cytokines were increased in BD; thus, Th17 cells and the IL17/IL23 pathway may play important roles in the pathogenesis of BD. In this chapter, we focus on the pathogenic role of Th17 cells in BD. PMID:28753995

Confronting inconsistencies in the amphibian-chytridiomycosis system: implications for disease management.

PubMed

Venesky, Matthew D; Raffel, Thomas R; McMahon, Taegan A; Rohr, Jason R

2014-05-01

Chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), is one of the largest threats to wildlife and is putatively linked to the extirpation of numerous amphibians. Despite over a decade of research on Bd, conflicting results from a number of studies make it difficult to forecast where future epizootics will occur and how to manage this pathogen effectively. Here, we emphasize how resolving these conflicts will advance Bd management and amphibian conservation efforts. We synthesize current knowledge on whether Bd is novel or endemic, whether amphibians exhibit acquired resistance to Bd, the importance of host resistance versus tolerance to Bd, and how biotic (e.g. species richness) and abiotic factors (e.g. climate change) affect Bd abundance. Advances in our knowledge of amphibian-chytrid interactions might inform the management of fungal pathogens in general, which are becoming more common and problematic globally. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

Cerebral vein thrombosis in a four year old with Behçet's disease.

PubMed

Hacihamdioglu, Duygu Ovunc; Demiriz, Murat; Sobaci, Gungor; Kocaoglu, Murat; Demirkaya, Erkan; Gok, Faysal

2014-01-01

Behçet's disease (BD) is a multisystem disorder. The main pathology in BD is vasculitis that involves arteries and veins of all calibers. Central nervous system involvement occurs in 5-10% of patients. Increased morbidity and mortality is rarely observed in children. The mean age at onset in pediatric BD is approximately 7 years. Neurologic involvement in BD is usually observed after 3-6 years. We report the case of a four-year-old Turkish boy with BD with sagittal sinus thrombosis treated with infliximab. The patient presented papilledema without neurologic signs. Although long-term efficacy evaluations are needed in this case, infliximab therapy may be a good option in childhood BD with refractory sinus thrombosis. This is the youngest case of BD with sagittal sinus thrombosis reported so far. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Performance of Bipolar Disorder Patients in Attention Testing: Comparison with Normal Controls and Among Manic, Depressive, and Euthymic Phases.

PubMed

Camelo, Evelyn V M; Mograbi, Daniel; de Assis da Silva, Rafael; Bifano, Jaqueline; Wainstok, Mayra; Silveira, Luciana Angélica Silva; Netto, Tânia; Santana, Cristina M T; Cheniaux, Elie

2017-03-01

Several studies on cognition in bipolar disorder (BD) have been developed on the last decade. Neuropsychological evaluation of attention in BD patients is fundamental since alterations in attention affect other cognitive functions. Evaluate if performance of BD patients in attention tests varies according to each phase of the disease and verify if there are differences in attention when comparing BD patients with normal controls. The study included 101 BD patients, with ages between 18 and 65 years, being 52 euthymic, 22 manic and 27 depressive, besides 30 normal controls. All subjects were evaluated though Hamilton Depression Scale, Young Mania Rating Scale and Global Assessment of Functioning, bipolar version (CGI-BP). Attention was evaluated through a neuropsychological battery. Normal controls had a better performance in selective attention tests than BD patients. No differences were found among manic, depressive and euthymic phases. Attention is markedly impaired in BD. Nevertheless, the results of this study do not imply that the severity of the attention deficit in BD patients varies according to decease phase.

Terrestrial Dispersal and Potential Environmental Transmission of the Amphibian Chytrid Fungus (Batrachochytrium dendrobatidis)

PubMed Central

Kolby, Jonathan E.; Ramirez, Sara D.; Berger, Lee; Richards-Hrdlicka, Kathryn L.; Jocque, Merlijn; Skerratt, Lee F.

2015-01-01

Dispersal and exposure to amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) is not confined to the aquatic habitat, but little is known about pathways that facilitate exposure to wild terrestrial amphibians that do not typically enter bodies of water. We explored the possible spread of Bd from an aquatic reservoir to terrestrial substrates by the emergence of recently metamorphosed infected amphibians and potential deposition of Bd-positive residue on riparian vegetation in Cusuco National Park, Honduras (CNP). Amphibians and their respective leaf perches were both sampled for Bd presence and the pathogen was detected on 76.1% (35/46) of leaves where a Bd-positive frog had rested. Although the viability of Bd detected on these leaves cannot be discerned from our quantitative PCR results, the cool air temperature, closed canopy, and high humidity of this cloud forest environment in CNP is expected to encourage pathogen persistence. High prevalence of infection (88.5%) detected in the recently metamorphosed amphibians and frequent shedding of Bd-positive residue on foliage demonstrates a pathway of Bd dispersal between aquatic and terrestrial habitats. This pathway provides the opportunity for environmental transmission of Bd among and between amphibian species without direct physical contact or exposure to an aquatic habitat. PMID:25927835

Amphibian Chytrid Fungus in Madagascar neither Shows Widespread Presence nor Signs of Certain Establishment.

PubMed

Kolby, Jonathan E; Skerratt, Lee F

2015-01-01

The global spread of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) is associated with amphibian mass mortality, population decline, and extinction. Over the past decade, concern has been expressed for the potential introduction of Bd to Madagascar, a global hotspot of amphibian biodiversity. Following years without detection, widespread Bd presence in Madagascar has now been reported (Bletz et al. 2015a), raising international conservation concern. Before reacting to this finding with a significant management response, the accuracy and context of the data warrant cautious review. Re-examination of a 10-year dataset together with results from more recent surveillance (Kolby et al. 2015) does not yet demonstrate widespread Bd presence. Detection of Bd at "positive" locations in Madagascar has been inconsistent for unknown reasons. Whether Bd is established in Madagascar (i.e. populations are self-sustaining) or instead requires continued introduction to persist also remains uncertain. The deployment of emergency conservation rescue initiatives is expected to target areas where the distribution of Bd and the risk of chytridiomycosis endangering amphibians is believed to overlap. Thus, erroneous description of Bd presence would misdirect limited conservation resources. Standardized surveillance and confirmatory surveys are now imperative to reliably characterize the distribution, potential spread, virulence and overall risk of Bd to amphibians in Madagascar.

Bipolar disorder patients have similar levels of education but lower socio-economic status than the general population.

PubMed

Schoeyen, Helle K; Birkenaes, Astrid B; Vaaler, Arne E; Auestad, Bjoern H; Malt, Ulrik F; Andreassen, Ole A; Morken, Gunnar

2011-03-01

There is conflicting evidence regarding the educational level and its importance for social and occupational functioning in bipolar disorder (BD). The aim of this study was to investigate how educational achievement relates to function in BD compared with the general population, and which clinical factors are associated with level of education. Hospitalized patients with DSM-IV BD (N=257; 69.3% BD I; 25.7% BD II; 5.1 BD NOS; 51.4% females) were consecutively recruited from mental health clinics throughout Norway and compared with a geographically matched reference sample from the general population (N=56,540) on levels of education, marital status, income, and disability benefits. Further analyses of association were carried out using logistic regression analyses. A significantly higher proportion of subjects in the BD group than in the reference group was single, had low income, or was disabled. No between-group difference was found in educational level. In the reference group education was inversely correlated with the risk of being disabled, but no such relationship was found in the BD group. Rapid cycling and recurring depressive episodes were the only clinical characteristics associated with low educational level. Acutely admitted patients might not be representative for milder forms of disease. Despite similar levels of education, BD patients had lower social and occupational function than the general population, and no association was found between education and disability for BD patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

PubMed

Chang, Kiki; Barnea-Goraly, Naama; Karchemskiy, Asya; Simeonova, Diana Iorgova; Barnes, Patrick; Ketter, Terence; Reiss, Allan L

2005-08-01

Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

Efficacy of rhBMP-2 Loaded PCL/β-TCP/bdECM Scaffold Fabricated by 3D Printing Technology on Bone Regeneration.

PubMed

Bae, Eun-Bin; Park, Keun-Ho; Shim, Jin-Hyung; Chung, Ho-Yun; Choi, Jae-Won; Lee, Jin-Ju; Kim, Chang-Hwan; Jeon, Ho-Jun; Kang, Seong-Soo; Huh, Jung-Bo

2018-01-01

This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL)/ β -tricalcium phosphate ( β -TCP) scaffold containing bone demineralized and decellularized extracellular matrix (bdECM) and human recombinant bone morphogenetic protein-2 (rhBMP-2) on bone regeneration. Scaffolds were divided into PCL/ β -TCP, PCL/ β -TCP/bdECM, and PCL/ β -TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm 3 ) and new bone areas (%). Excellent cell bioactivity was observed in the PCL/ β -TCP/bdECM and PCL/ β -TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/ β -TCP/bdECM/BMP group than in the other groups ( p < .05). Within the limitations of this study, bdECM printed PCL/ β -TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.

The prevalence of Behçet's disease in Korea: data from Health Insurance Review and Assessment Service from 2011 to 2015.

PubMed

Kim, Ji Na; Kwak, Sang Gyu; Choe, Jung-Yoon; Kim, Seong-Kyu

2017-01-01

The aim of this study is to identify the prevalence of Behçet's disease (BD) from data in the Healthcare Bigdata Hub of the Health Insurance Review & Assessment (HIRA) Service from 2011 to 2015 in Korea. This study collected information on primary and auxiliary diagnoses of BD (M352) by physicians according to the Korean Standard Classification of Diseases (KCD) codes. The prevalence of BD was assessed on the basis of age, sex, and geographical distribution. We used time series analysis, using the ARIMA model for the expected prevalence of BD from 2016 to 2025. The overall prevalence of BD was gradually increased, ranging from 32.8 to 35.7 per 100,000 population over the study period. The male to female ratio of BD ranged from 0.54:1 to 0.56:1, revealing a female predominance from 2011 to 2015. Among five districts in Korea, the prevalence in the Seoul Metropolitan district was the highest, with a slowly increasing trend for the study period, accounting for about 60.3% of total BD patients. The expected prevalence of BD patients was estimated to range from 36.9 (95% CI 35.0 - 39.0) to 44.7 (95% CI 40.2 - 49.6) between 2016 and 2025. This study found that the overall prevalence of BD is estimated to be approximately 35.0 per 100,000 population, with female predominance, and predicts gradually increased prevalence of BD in Korea.

Chemical Reactivity and Respiratory Toxicity of the α-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione and 2,3-Hexanedione

PubMed Central

Morgan, Daniel L.; Jokinen, Micheal P.; Johnson, Crystal L.; Price, Herman C.; Gwinn, William M.; Bousquet, Ronald W.; Flake, Gordon P.

2016-01-01

Occupational exposure to 2,3-butanedione (BD) vapors has been associated with severe respiratory disease leading to the use of potentially toxic substitutes. We compared the reactivity and respiratory toxicity of BD with that of two structurally-related substitutes, 2,3-pentanedione (PD) and 2,3-hexanedione (HD). Chemical reactivity of the diketones with an arginine substrate decreased with increasing chain length (BD≥PD>HD). Animals were evaluated the morning after a 2-week exposure to 0, 100, 150, or 200 ppm BD, PD, or HD (post-exposure), or 2 weeks later (recovery). Bronchial fibrosis was observed in 5/5 BD and 5/5 PD rats at 200 ppm, and in 4/6 BD and 6/6 PD rats at 150 ppm in the post-exposure groups. Following recovery, bronchial fibrosis was observed in all surviving rats exposed to 200 ppm BD (5/5) or PD (3/3), and in 2/10 BD and 7/9 PD rats exposed to 150 ppm. Bronchial fibrosis was observed only in 2/12 HD-exposed rats in the 200 ppm post-exposure group. Patchy interstitial fibrosis affected lungs of recovery groups exposed to 200 ppm PD (3/3) or BD (1/5) and 150 ppm PD (4/9) or BD (7/10) and correlated with pulmonary function deficits. BD and PD were more reactive and produced more bronchial fibrosis than HD. PMID:27025954

Global microRNA profiling of peripheral blood mononuclear cells in patients with Behçet's disease.

PubMed

Erre, Gian Luca; Piga, Matteo; Carru, Ciriaco; Angius, Andrea; Carcangiu, Laura; Piras, Marco; Sotgia, Salvatore; Zinellu, Angelo; Mathieu, Alessandro; Passiu, Giuseppe; Pescatori, Mario

2015-01-01

To explore the post-transcriptional regulation of the peripheral blood mononuclear cells (PBMCs) transcriptome by microRNAs in Behçet's disease (BD). Using TaqMan Low Density Array-based microRNAs expression profiling, the expression of 750 mature human microRNAs in PBMCs from 5 BD patients and 3 healthy controls (HC) was compared. The expression of deregulated microRNAs was then validated by quantitative real time-polymerase chain reaction (qRT-PCR), in 42 BD patients and 8 HC. In the initial screening, 13 microRNAs appeared deregulated in BD vs HC. Among them, the differential expression of miR-720 and miR-139-3p was confirmed by qRT-PCR, (p<0.05 and FDR<5%). Areas under the receiver operating characteristic curve for miR-139-3p, miR-720 and miR-139-3p+miR-720 in the validation cohort were 0.84, 0.87 and 0.92 respectively, indicating good discrimination between BD patients and HC. Post-hoc analysis showed that 9 out of 13 microRNAs from the discovery phase were significantly upregulated in active vs. quiescent BD, suggesting inflammation as a key regulator of microRNAs machinery in BD. In silico analysis revealed that several BD candidate susceptibility genes are predicted target of significantly deregulated microRNAs in active BD. A significant enrichment in microRNAs targeting elements of the Toll-like receptor (TLR) and T-cell receptor signalling pathways was also assumed. miR199-3p and miR720 deserve further confirmation as biomarkers of BD in larger studies. PBMCs from active BD displayed a unique signature of microRNAs which may be implicated in regulation of innate immunity activation and T-cell function.

Expression and Antimicrobial Function of Beta-Defensin 1 in the Lower Urinary Tract

PubMed Central

Becknell, Brian; Spencer, John David; Carpenter, Ashley R.; Chen, Xi; Singh, Aspinder; Ploeger, Suzanne; Kline, Jennifer; Ellsworth, Patrick; Li, Birong; Proksch, Ehrhardt; Schwaderer, Andrew L.; Hains, David S.; Justice, Sheryl S.; McHugh, Kirk M.

2013-01-01

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1 -/-) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1 -/- and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract. PMID:24204930

Inhibition of 1,4-butanediol metabolism in human liver in vitro.

PubMed

Lenz, Daniel; Jübner, Martin; Bender, Katja; Wintermeyer, Annette; Beike, Justus; Rothschild, Markus A; Käferstein, Herbert

2011-06-01

The conversion of 1,4-butanediol (1,4-BD) to gamma-hydroxybutyric acid (GHB), a drug of abuse, is most probably catalyzed by alcohol dehydrogenase, and potentially by aldehyde dehydrogenase. The purpose of this study was to investigate the degradation of 1,4-BD in cytosolic supernatant of human liver in vitro, and to verify involvement of the suggested enzymes by means of gas chromatography-mass spectrometry. The coingestion of 1,4-BD and ethanol (EtOH) might cause complex pharmacokinetic interactions in humans. Therefore, the effect of EtOH on 1,4-BD metabolism by human liver was examined in vitro. Additionally, the influence of acetaldehyde (AL), which might inhibit the second step of 1,4-BD degradation, was investigated. In case of a 1,4-BD intoxication, the alcohol dehydrogenase inhibitor fomepizole (4-methylpyrazole, FOM) has been discussed as an antidote preventing the formation of the central nervous system depressing GHB. Besides FOM, we tested pyrazole, disulfiram, and cimetidine as possible inhibitors of the formation of GHB from 1,4-BD catalyzed by human liver enzymes in vitro. The conversion of 1,4-BD to GHB was inhibited competitively by EtOH with an apparent K(i) of 0.56 mM. Therefore, the coingestion of 1,4-BD and EtOH might increase the concentrations and the effects of 1,4-BD itself. By contrast AL accelerated the formation of GHB. All antidotes showed the ability to inhibit the formation of GHB. In comparison FOM showed the highest inhibitory effectiveness. Furthermore, the results confirm strong involvement of ADH in 1,4-BD metabolism by human liver.

Hybrid Approach for Biliary Interventions Employing MRI-Guided Bile Duct Puncture with Near-Real-Time Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wybranski, Christian, E-mail: Christian.Wybranski@uk-koeln.de; Pech, Maciej; Lux, Anke

ObjectiveTo assess the feasibility of a hybrid approach employing MRI-guided bile duct (BD) puncture for subsequent fluoroscopy-guided biliary interventions in patients with non-dilated (≤3 mm) or dilated BD (≥3 mm) but unfavorable conditions for ultrasonography (US)-guided BD puncture.MethodsA total of 23 hybrid interventions were performed in 21 patients. Visualization of BD and puncture needles (PN) in the interventional MR images was rated on a 5-point Likert scale by two radiologists. Technical success, planning time, BD puncture time and positioning adjustments of the PN as well as technical success of the biliary intervention and complication rate were recorded.ResultsVisualization even of third-order non-dilated BDmore » and PN was rated excellent by both radiologists with good to excellent interrater agreement. MRI-guided BD puncture was successful in all cases. Planning and BD puncture times were 1:36 ± 2.13 (0:16–11:07) min. and 3:58 ± 2:35 (1:11–9:32) min. Positioning adjustments of the PN was necessary in two patients. Repeated capsular puncture was not necessary in any case. All biliary interventions were completed successfully without major complications.ConclusionA hybrid approach which employs MRI-guided BD puncture for subsequent fluoroscopy-guided biliary intervention is feasible in clinical routine and yields high technical success in patients with non-dilated BD and/or unfavorable conditions for US-guided puncture. Excellent visualization of BD and PN in near-real-time interventional MRI allows successful cannulation of the BD.« less

Burden of maternal bipolar disorder on at-risk offspring: a controlled study on family planning and maternal care.

PubMed

Moreno, Doris Hupfeld; Bio, Danielle Soares; Petresco, Sandra; Petresco, Denise; Gutt, Elisa Kijner; Soeiro-de-Souza, Márcio Gerhardt; Moreno, Ricardo Alberto

2012-12-20

Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. BD mothers were less likely to have stable unions (45.5%; p<0.01) or to live with the biological father of their children (33.3%; p<0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p=0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. Copyright © 2012 Elsevier B.V. All rights reserved.

Binge drinking among Brazilian students: a gradient of association with socioeconomic status in five geo-economic regions.

PubMed

Sanchez, Zila M; Locatelli, Danilo P; Noto, Ana R; Martins, Silvia S

2013-01-01

Socioeconomic status (SES) may be directly associated with binge drinking (BD) and country inequality. The aims of this study were to describe the characteristics of BD among high school students in Brazil and the association of BD with students' socioeconomic status in the five different Brazilian macro-regions. A national cross sectional survey was carried out using a multistage probabilistic sample of 17,297 high school students aged 14-18 years drawn from 789 public and private schools in each of the 27 Brazilian state capitals. Self-report data about BD behaviors and SES were analyzed via weighted logistic regressions and a funnel plot. Almost 32% of the students engaged in BD in the past-year. Being in the highest SES stratum doubled the risk of BD among students in all five Brazilian macro-regions. There was a gradient in the association between past-year BD and socioeconomic status: as SES increased; the chance of having recently engaged in BD also increased. In Brazilian capitals as a whole, being a boy versus being a girl (adjusted odds ratio - aOR=1.40 [95%CI 1.26; 1.58]), being older (aOR=1.47 [95%CI 1.40; 1.55]) and attending private versus public schools (aOR=1.39 [95%CI 1.18; 1.62]) were associated with greater risk for BD. Contrary to what is observed in developed countries, students living in Brazilian capitals may be at an increased risk of BD when they belong to the highest socioeconomic status. There might be similar associations between high SES and BD among adolescents growing up in other emerging economies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder

PubMed Central

Vasconcelos-Moreno, Mirela Paiva; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Sartori, Juliana; Eisele, Bárbara; Ferrari, Pamela; Fijtman, Adam; Rüegg, Joëlle; Gassen, Nils Christian; Kapczinski, Flávio; Rein, Theo; Kauer-Sant’Anna, Márcia

2015-01-01

Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness. PMID:25522387

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris.

PubMed

Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Akbulak, Ozge; Uzuncakmak, Tugba Kevser; Demirkan, Serkan; Akdeniz, Necmettin

2017-12-01

Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

PubMed Central

Wilcox, Holly C.; Fullerton, Janice M.; Glowinski, Anne L.; Benke, Kelly; Kamali, Masoud; Hulvershorn, Leslie A.; Stapp, Emma K.; Edenberg, Howard J.; Roberts, Gloria M.P.; Ghaziuddin, Neera; Fisher, Carrie; Brucksch, Christine; Frankland, Andrew; Toma, Claudio; Shaw, Alex D.; Kastelic, Elizabeth; Miller, Leslie; McInnis, Melvin G.; Mitchell, Philip B.; Nurnberger, John I.

2018-01-01

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability. PMID:29173741

Utility of the sendai consensus guidelines for branch-duct intraductal papillary mucinous neoplasms: a systematic review.

PubMed

Goh, Brian K P; Tan, Damien M Y; Ho, Mac M F; Lim, Tony K H; Chung, Alexander Y F; Ooi, London L P J

2014-07-01

The Sendai Consensus Guidelines (SCG) was formulated in 2006 to guide the management of intraductal papillary mucinous neoplasms (IPMN). The main area of controversy is the criteria for selection of branch duct (BD)-IPMN for resection. Although these guidelines have gained widespread acceptance, there is limited data to date supporting its use. This systematic review is performed to evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN. Studies evaluating the clinical utility of the SCG in surgically resected neoplasms were identified. The SCG were retrospectively applied to all resected neoplasms in these studies. BD-IPMNs which met the criteria for resection were termed SCG+ve and those for surveillance were termed SCG-ve. Twelve studies were included, of which, 9 were suitable for pooled analysis. There were 690 surgically resected BD-IPMNs, of which, 24% were malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG-ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52% and the NPV of SCG-ve neoplasms ranged from 90 to 100%. Overall, there were 150/501 (29.9%) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90%) of benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive) BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single study. When the results from this single study were excluded, 170/171 (99%) of SCG-ve BD-IPMNs were benign. The results of this review confirm the limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant BD-IPMN was low and some malignant lesions may be missed based on these guidelines.

Lipid peroxidation biomarkers in adolescents with or at high-risk for bipolar disorder.

PubMed

Scola, Gustavo; McNamara, Robert K; Croarkin, Paul E; Leffler, Jarrod M; Cullen, Kathryn R; Geske, Jennifer R; Biernacka, Joanna M; Frye, Mark A; DelBello, Melissa P; Andreazza, Ana C

2016-03-01

Prior work suggests that adult bipolar disorder (BD) is associated with increased oxidative stress and inflammation. This exploratory study examined markers of lipid and protein oxidation and inflammation in adolescents with and at varying risk for BD type I (BD-I). Blood was obtained from four groups of adolescents (9-20 years of age): (1) healthy comparison subjects with no personal or family history of psychiatric disorders (n=13), (2) subjects with no psychiatric diagnosis and at least one parent with BD-I ('high-risk', n=15), (3) subjects with at least one parent with BD-I and a diagnosis of depressive disorder not-otherwise-specified ('ultra-high-risk', n=20), and (4) first-episode patients exhibiting mixed or manic symptoms that received a diagnosis of BD-I (n=16). Plasma levels of lipid peroxidation (LPH, 4-HNE, 8-ISO), protein carbonyl, and inflammation (IL-1α-β, IL-6, IL-10, IFNγ, TNFα) were assessed using analysis of variance and covariance models. LPH was lower in adolescents with fully syndromal BD than controls, while LPH levels in the at-risk groups were between healthy controls and fully syndromal BD. Post-hoc analysis showed a non-significant increase in the (4-HNE+8-ISO)/LPH ratio suggesting a potential conversion of LPH into late-stage markers of lipid peroxidation. There were no significant differences among protein carbonyl content and inflammatory markers. In adolescents, fully syndromal BD is associated with significant reductions in LPH levels, and LPH levels decrease along the spectrum of risk for BD-I. Quantifying lipid peroxidation in longitudinal studies may help clarify the role of LPH in BD risk progression. Copyright © 2015 Elsevier B.V. All rights reserved.

Disrupting the cinnamyl alcohol dehydrogenase 1 gene (BdCAD1) leads to altered lignification and improved saccharification in Brachypodium distachyon.

PubMed

Bouvier d'Yvoire, Madeleine; Bouchabke-Coussa, Oumaya; Voorend, Wannes; Antelme, Sébastien; Cézard, Laurent; Legée, Frédéric; Lebris, Philippe; Legay, Sylvain; Whitehead, Caragh; McQueen-Mason, Simon J; Gomez, Leonardo D; Jouanin, Lise; Lapierre, Catherine; Sibout, Richard

2013-02-01

Brachypodium distachyon (Brachypodium) has been proposed as a model for grasses, but there is limited knowledge regarding its lignins and no data on lignin-related mutants. The cinnamyl alcohol dehydrogenase (CAD) genes involved in lignification are promising targets to improve the cellulose-to-ethanol conversion process. Down-regulation of CAD often induces a reddish coloration of lignified tissues. Based on this observation, we screened a chemically induced population of Brachypodium mutants (Bd21-3 background) for red culm coloration. We identified two mutants (Bd4179 and Bd7591), with mutations in the BdCAD1 gene. The mature stems of these mutants displayed reduced CAD activity and lower lignin content. Their lignins were enriched in 8-O-4- and 4-O-5-coupled sinapaldehyde units, as well as resistant inter-unit bonds and free phenolic groups. By contrast, there was no increase in coniferaldehyde end groups. Moreover, the amount of sinapic acid ester-linked to cell walls was measured for the first time in a lignin-related CAD grass mutant. Functional complementation of the Bd4179 mutant with the wild-type BdCAD1 allele restored the wild-type phenotype and lignification. Saccharification assays revealed that Bd4179 and Bd7591 lines were more susceptible to enzymatic hydrolysis than wild-type plants. Here, we have demonstrated that BdCAD1 is involved in lignification of Brachypodium. We have shown that a single nucleotide change in BdCAD1 reduces the lignin level and increases the degree of branching of lignins through incorporation of sinapaldehyde. These changes make saccharification of cells walls pre-treated with alkaline easier without compromising plant growth. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults.

PubMed

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-08-01

Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report that their symptoms started in childhood, suggesting that BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition both in children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7-26 years) and HC participants (n = 87; ages 7-25 years). Complementary analyses investigated errors for child and adult faces. A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred both for child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target - that is, for cognitive remediation to improve BD youths' emotion recognition abilities. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Facial emotion recognition in childhood-onset bipolar I disorder: an evaluation of developmental differences between youths and adults

PubMed Central

Wegbreit, Ezra; Weissman, Alexandra B; Cushman, Grace K; Puzia, Megan E; Kim, Kerri L; Leibenluft, Ellen; Dickstein, Daniel P

2015-01-01

Objectives Bipolar disorder (BD) is a severe mental illness with high healthcare costs and poor outcomes. Increasing numbers of youths are diagnosed with BD, and many adults with BD report their symptoms started in childhood, suggesting BD can be a developmental disorder. Studies advancing our understanding of BD have shown alterations in facial emotion recognition in both children and adults with BD compared to healthy comparison (HC) participants, but none have evaluated the development of these deficits. To address this, we examined the effect of age on facial emotion recognition in a sample that included children and adults with confirmed childhood-onset type-I BD, with the adults having been diagnosed and followed since childhood by the Course and Outcome in Bipolar Youth study. Methods Using the Diagnostic Analysis of Non-Verbal Accuracy, we compared facial emotion recognition errors among participants with BD (n = 66; ages 7–26 years) and HC participants (n = 87; ages 7–25 years). Complementary analyses investigated errors for child and adult faces. Results A significant diagnosis-by-age interaction indicated that younger BD participants performed worse than expected relative to HC participants their own age. The deficits occurred for both child and adult faces and were particularly strong for angry child faces, which were most often mistaken as sad. Our results were not influenced by medications, comorbidities/substance use, or mood state/global functioning. Conclusions Younger individuals with BD are worse than their peers at this important social skill. This deficit may be an important developmentally salient treatment target, i.e., for cognitive remediation to improve BD youths’ emotion recognition abilities. PMID:25951752

Brain activation during self- and other-reflection in bipolar disorder with a history of psychosis: Comparison to schizophrenia

PubMed Central

Zhang, Liwen; Opmeer, Esther M.; Ruhé, Henricus G.; Aleman, André; van der Meer, Lisette

2015-01-01

Objectives Reflecting on the self and on others activates specific brain areas and contributes to metacognition and social cognition. The aim of the current study is to investigate brain activation during self- and other-reflection in patients with bipolar disorder (BD). In addition, we examined whether potential abnormal brain activation in BD patients could distinguish BD from patients with schizophrenia (SZ). Methods During functional magnetic resonance imaging (fMRI), 17 BD patients, 17 SZ patients and 21 healthy controls (HCs) performed a self-reflection task. The task consisted of sentences divided into three conditions: self-reflection, other-reflection and semantic control. Results BD patients showed less activation in the posterior cingulate cortex (PCC) extending to the precuneus during other-reflection compared to HCs (p = 0.028 FWE corrected on cluster-level within the regions of interest). In SZ patients, the level of activation in this area was in between BD patients and HCs, with no significant differences between patients with SZ and BD. There were no group differences in brain activation during self-reflection. Moreover, there was a positive correlation between the PCC/precuneus activation during other-reflection and cognitive insight in SZ patients, but not in BD patients. Conclusions BD patients showed less activation in the PCC/precuneus during other-reflection. This may support an account of impaired integration of emotion and memory (evaluation of past and current other-related information) in BD patients. Correlation differences of the PCC/precuneus activation with the cognitive insight in patients with BD and SZ might reflect an important difference between these disorders, which may help to further explore potentially distinguishing markers. PMID:26106544

Brain activation during self- and other-reflection in bipolar disorder with a history of psychosis: Comparison to schizophrenia.

PubMed

Zhang, Liwen; Opmeer, Esther M; Ruhé, Henricus G; Aleman, André; van der Meer, Lisette

2015-01-01

Reflecting on the self and on others activates specific brain areas and contributes to metacognition and social cognition. The aim of the current study is to investigate brain activation during self- and other-reflection in patients with bipolar disorder (BD). In addition, we examined whether potential abnormal brain activation in BD patients could distinguish BD from patients with schizophrenia (SZ). During functional magnetic resonance imaging (fMRI), 17 BD patients, 17 SZ patients and 21 healthy controls (HCs) performed a self-reflection task. The task consisted of sentences divided into three conditions: self-reflection, other-reflection and semantic control. BD patients showed less activation in the posterior cingulate cortex (PCC) extending to the precuneus during other-reflection compared to HCs (p = 0.028 FWE corrected on cluster-level within the regions of interest). In SZ patients, the level of activation in this area was in between BD patients and HCs, with no significant differences between patients with SZ and BD. There were no group differences in brain activation during self-reflection. Moreover, there was a positive correlation between the PCC/precuneus activation during other-reflection and cognitive insight in SZ patients, but not in BD patients. BD patients showed less activation in the PCC/precuneus during other-reflection. This may support an account of impaired integration of emotion and memory (evaluation of past and current other-related information) in BD patients. Correlation differences of the PCC/precuneus activation with the cognitive insight in patients with BD and SZ might reflect an important difference between these disorders, which may help to further explore potentially distinguishing markers.

Behçet's disease departs the 'Silk Road': a case report and brief review of literature with geographical comparison.

PubMed

Ahmed, Zohair; Rossi, Maria L; Yong, Sherri; Martin, Daniel K; Walayat, Saqib; Cashman, Michael; Tsoraides, Steven; Dhillon, Sonu

2016-01-01

Behçet's disease (BD) is a chronic multisystem inflammatory disease most prevalent in Eastern Asia and along the Mediterranean basin, an area referred to as the 'Silk Road'. The diagnosis of BD is largely based on the International Study Group (ISG) criteria, which are more specific than sensitive. ISG criteria do not include intestinal manifestations, a feature more commonly seen in the West. Intestinal BD is one of several findings that are not typically seen along the 'Silk Road'. Herein we report a rare case of intestinal BD and compare Western versus traditional BD. A 25-year-old male with a history of painful oral aphthous ulcers, pericarditis, and diffuse papulopustular rash presented to the emergency department with two terminal ileal perforations. Pathology demonstrated mucosal necrosis with active inflammation and no chronic inflammatory changes. Post-surgical laboratory studies showed an elevated c-reactive protein of 35.57 mg/dL, erythrocyte sedimentation rate of 82 mm/h, and a positive anti-Saccharomyces cerevisiae antibody. Rheumatological workup including ANA, RF, PR3 antibody, MPO antibody, ANCA, SSA and SSB, Smith antibody, SCL-70, and anti-Jo-1 antibodies were all negative. His pericarditis symptoms improved with colchicine and prednisone prior to discharge. Our patient did not meet the current ISG criteria for traditional BD; however, he clearly showed findings typically seen in Western patients with BD, which include intestinal manifestations, cardiac involvement, and lack of pathergy reaction and ocular changes. Our investigation demonstrates that the clinical manifestations common to this disorder vary among geographic and ethnic populations. Commonly used criteria for the diagnosis of BD may not be sensitive for some populations, such as Western BD, potentially leading to underdiagnoses and mismanagement. Recognition and select inclusion of these differences may be one way to assist with diagnosing Western BD in the future. As our knowledge of BD continues to evolve, so must the population-specific criteria used to define BD.

Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo

Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infectedmore » by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.« less

The relative influence of individual risk factors for attempted suicide in patients with bipolar I versus bipolar II disorder.

PubMed

Bobo, William V; Na, Peter J; Geske, Jennifer R; McElroy, Susan L; Frye, Mark A; Biernacka, Joanna M

2018-01-01

To compare the relative influence (RI) of individual predictors for lifetime attempted suicide between adults with bipolar I (BDBD-I) and bipolar II disorder (BDBD-II). We conducted an analysis of data from 1465 enrollees in the Mayo Clinic Bipolar Disorder Biobank. Demographic and clinical variables and history of attempted suicide were ascertained using standardized questionnaires. Height and weight were assessed to determine body mass index (BMI); obesity was defined as BMI ≥30kg/m 2 . The frequencies of these variables were compared between persons with and without self-reported lifetime suicide attempts both overall, and within BD-I and BD-II subgroups. Gradient boosting machine (GBM) models were used to quantify the RI of study variables on the risk of lifetime attempted suicide. Nearly one-third of patients reported having a lifetime suicide attempt. Attempted suicide rates were higher in patients with BD-I than BD-II, but absolute differences were small. Lifetime attempted suicide was associated with female sex, BD-I subtype, psychiatric and substance use comorbidities, binge eating behavior, lifetime history of rapid cycling, other indicators of adverse illness course, and early age of bipolar illness onset in the entire cohort. Differences in the rank-ordering of RI for predictors of attempted suicide between BD-I and BD-II patients were modest. Rapid cycling was a strong risk factor for attempted suicide, particularly in men with BD-I. Actively psychotic or suicidal patients needing psychiatric hospitalization were initially excluded, but were approached after these acute psychiatric problems resolved. The prevalence of lifetime attempted suicide was significantly higher in BD-I than BD-II in this large, cross-sectional cohort. Predictors of attempted suicide were similar in BD-I and BD-II subgroups. Copyright © 2017. Published by Elsevier B.V.

Harnessing the potential of community-based participatory research approaches in bipolar disorder.

PubMed

Michalak, Erin E; Jones, Steven; Lobban, Fiona; Algorta, Guillermo Perez; Barnes, Steven J; Berk, Lesley; Berk, Michael; Hole, Rachelle; Lapsley, Sara; Maxwell, Victoria; Milev, Roumen; McManamy, John; Murray, Greg; Tohen, Mauricio; Tse, Samson; Sanchez de Carmona, Manuel; Johnson, Sheri L

2016-12-01

Despite the rapid growth in the sophistication of research on bipolar disorder (BD), the field faces challenges in improving quality of life (QoL) and symptom outcomes, adapting treatments for marginalized communities, and disseminating research insights into real-world practice. Community-based participatory research (CBPR)-research that is conducted as a partnership between researchers and community members-has helped address similar gaps in other health conditions. This paper aims to improve awareness of the potential benefits of CBPR in BD research. This paper is a product of the International Society for Bipolar Disorders (ISBD) Taskforce on Community Engagement which includes academic researchers, healthcare providers, people with lived experience of BD, and stakeholders from BD community agencies. Illustrative examples of CBPR in action are provided from two established centres that specialize in community engagement in BD research: the Collaborative RESearch Team to study psychosocial issues in BD (CREST.BD) in Canada, and the Spectrum Centre for Mental Health Research in the United Kingdom. We describe the philosophy of CBPR and then introduce four core research areas the BD community has prioritized for research: new treatment approaches, more comprehensive outcome assessments, tackling stigma, and enhanced understanding of positive outcomes. We then describe ways in which CBPR is ideal for advancing each of these research areas and provide specific examples of ways that CBPR has already been successfully applied in these areas. We end by noting potential challenges and mitigation strategies in the application of CBPR in BD research. We believe that CBPR approaches have significant potential value for the BD research community. The observations and concerns of people with BD, their family members, and supports clearly represent a rich source of information. CBPR approaches provide a collaborative, equitable, empowering orientation to research that builds on the diversity of strengths amongst community stakeholders. Despite the potential merits of this approach, CBPR is as yet not widely used in the BD research field, representing a missed opportunity.

Modulation of human beta-defensin-1 (hBD-1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity.

PubMed

Ryan, Lisa K; Dai, Jihong; Yin, Zhiwei; Megjugorac, Nicholas; Uhlhorn, Victoria; Yim, Sunghan; Schwartz, Kyell D; Abrahams, Joshua M; Diamond, Gill; Fitzgerald-Bocarsly, Patricia

2011-08-01

hBD comprise a family of antimicrobial peptides that plays a role in bridging the innate and adaptive immune responses to infection. The expression of hBD-2 increases upon stimulation of numerous cell types with LPS and proinflammatory cytokines. In contrast, hBD-1 remains constitutively expressed in most cells in spite of cytokine or LPS stimulation; however, its presence in human PDC suggests it plays a role in viral host defense. To examine this, we characterized the expression of hBD-1 in innate immune cells in response to viral challenge. PDC and monocytes increased production of hBD-1 peptide and mRNA as early as 2 h following infection of purified cells and PBMCs with PR8, HSV-1, and Sendai virus. However, treatment of primary NHBE cells with influenza resulted in a 50% decrease in hBD-1 mRNA levels, as measured by qRT-PCR at 3 h following infection. A similar inhibition occurred with HSV-1 challenge of human gingival epithelial cells. Studies with HSV-1 showed that replication occurred in epithelial cells but not in PDC. Together, these results suggest that hBD-1 may play a role in preventing viral replication in immune cells. To test this, we infected C57BL/6 WT mice and mBD-1((-/-)) mice with mouse-adapted HK18 (300 PFU/mouse). mBD-1((-/-)) mice lost weight earlier and died sooner than WT mice (P=0.0276), suggesting that BD-1 plays a role in early innate immune responses against influenza in vivo. However, lung virus titers were equal between the two mouse strains. Histopathology showed a greater inflammatory influx in the lungs of mBD-1((-/-)) mice at Day 3 postinfection compared with WT C57BL/6 mice. The results suggest that BD-1 protects mice from influenza pathogenesis with a mechanism other than inhibition of viral replication.

Predicting psychosis across diagnostic boundaries: Behavioral and computational modeling evidence for impaired reinforcement learning in schizophrenia and bipolar disorder with a history of psychosis.

PubMed

Strauss, Gregory P; Thaler, Nicholas S; Matveeva, Tatyana M; Vogel, Sally J; Sutton, Griffin P; Lee, Bern G; Allen, Daniel N

2015-08-01

There is increasing evidence that schizophrenia (SZ) and bipolar disorder (BD) share a number of cognitive, neurobiological, and genetic markers. Shared features may be most prevalent among SZ and BD with a history of psychosis. This study extended this literature by examining reinforcement learning (RL) performance in individuals with SZ (n = 29), BD with a history of psychosis (BD+; n = 24), BD without a history of psychosis (BD-; n = 23), and healthy controls (HC; n = 24). RL was assessed through a probabilistic stimulus selection task with acquisition and test phases. Computational modeling evaluated competing accounts of the data. Each participant's trial-by-trial decision-making behavior was fit to 3 computational models of RL: (a) a standard actor-critic model simulating pure basal ganglia-dependent learning, (b) a pure Q-learning model simulating action selection as a function of learned expected reward value, and (c) a hybrid model where an actor-critic is "augmented" by a Q-learning component, meant to capture the top-down influence of orbitofrontal cortex value representations on the striatum. The SZ group demonstrated greater reinforcement learning impairments at acquisition and test phases than the BD+, BD-, and HC groups. The BD+ and BD- groups displayed comparable performance at acquisition and test phases. Collapsing across diagnostic categories, greater severity of current psychosis was associated with poorer acquisition of the most rewarding stimuli as well as poor go/no-go learning at test. Model fits revealed that reinforcement learning in SZ was best characterized by a pure actor-critic model where learning is driven by prediction error signaling alone. In contrast, BD-, BD+, and HC were best fit by a hybrid model where prediction errors are influenced by top-down expected value representations that guide decision making. These findings suggest that abnormalities in the reward system are more prominent in SZ than BD; however, current psychotic symptoms may be associated with reinforcement learning deficits regardless of a Diagnostic and Statistical Manual of Mental Disorders (5th Edition; American Psychiatric Association, 2013) diagnosis. (c) 2015 APA, all rights reserved).

Effect of oxygen mass transfer rate on the production of 2,3-butanediol from glucose and agro-industrial byproducts by Bacillus licheniformis ATCC9789.

PubMed

Rebecchi, Stefano; Pinelli, Davide; Zanaroli, Giulio; Fava, Fabio; Frascari, Dario

2018-01-01

2,3-Butanediol (BD) is a largely used fossil-based platform chemical. The yield and productivity of bio-based BD fermentative production must be increased and cheaper substrates need to be identified, to make bio-based BD production more competitive. As BD bioproduction occurs under microaerobic conditions, a fine tuning and control of the oxygen transfer rate (OTR) is crucial to maximize BD yield and productivity. Very few studies on BD bioproduction focused on the use of non-pathogenic microorganisms and of byproducts as substrate. The goal of this work was to optimize BD bioproduction by the non-pathogenic strain Bacillus licheniformis ATCC9789 by (i) identifying the ranges of volumetric and biomass-specific OTR that maximize BD yield and productivity using standard sugar and protein sources, and (ii) performing a preliminary evaluation of the variation in process performances and cost resulting from the replacement of glucose with molasses, and beef extract/peptone with chicken meat and bone meal, a byproduct of the meat production industry. OTR optimization with an expensive, standard medium containing glucose, beef extract and peptone revealed that OTRs in the 7-15 mmol/L/h range lead to an optimal BD yield (0.43 ± 0.03 g/g) and productivity (0.91 ± 0.05 g/L/h). The corresponding optimal range of biomass-specific OTR was equal to 1.4-7.9 [Formula: see text], whereas the respiratory quotient ranged from 1.8 to 2.5. The switch to an agro-industrial byproduct-based medium containing chicken meat and bone meal and molasses led to a 50% decrease in both BD yield and productivity. A preliminary economic analysis indicated that the use of the byproduct-based medium can reduce by about 45% the BD production cost. A procedure for OTR optimization was developed and implemented, leading to the identification of a range of biomass-specific OTR and respiratory quotient to be used for the scale-up and control of BD bioproduction by Bacillus licheniformis . The switch to a byproduct-based medium led to a relevant decrease in BD production cost. Further research is needed to optimize the process of BD bioproduction from the tested byproduct-based medium.

Investigation on the correlation between energy deposition and clustered DNA damage induced by low-energy electrons.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2018-05-01

This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment. Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated with about 90% of total clustered DNA damage are below 150 eV. The simple clustered DNA damage, which is constituted of the combination of SSBs and adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the spectra of the energy depositions correlating with them are similar for different primary energies. One type of simple clustered DNA damage is the combination of a SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB + BD to total simple clustered DNA damage reaches up to about 84% for the considered primary energies. In all forms of SSB + BD, the SSB + BD including only one base damage is dominant (above 80%). In addition, for the considered primary energies, there is no obvious difference between the average energy depositions for a fixed complexity of SSB + BD determined by the number of base damage, but average energy depositions increase with the complexity of SSB + BD. In the complex clustered DNA damage constituted by the combination of DSBs and BD around them, a relatively simple type is a DSB combining adjacent BD, marked as DSB + BD, and it is of substantial contribution (on average up to about 82%). The spectrum of DSB + BD is given mainly by the DSB in combination with different numbers of base damage, from 1 to 5. For the considered primary energies, the DSB combined with only one base damage contributes about 83% of total DSB + BD, and the average energy deposition is about 106 eV. However, the energy deposition increases with the complexity of clustered DNA damage, and therefore, the clustered DNA damage with high complexity still needs to be considered in the study of radiation biological effects, in spite of their small contributions to all clustered DNA damage.

[Predicting bipolar disorder: what can we learn from prospective cohort studies?].

PubMed

Geoffroy, P A; Leboyer, M; Scott, J

2015-02-01

Bipolar disorder (BD) is a life course illness; and there is increasing awareness of the many personal, social and economic consequences of the illness in older adults. However, it is important to emphasize that BD usually begins in late adolescence or early adulthood and 75 % cases have a first episode in this age period. This early onset and the associated level of disability mean that BD is the 4th leading cause of global disease burden in adolescents and young adults. Internationally, mental health services are increasingly striving to diagnose and treat BD as early as possible to try to prevent poor outcomes. In addition, researchers are using methods employed previously in psychosis studies as these may help us to recognise the earliest manifestations of BD. If it is possible to identify sub-threshold and 'ultra high risk' syndromes for BD, this might lead to new interventions that could target the prevention of first episodes of mania. One approach to understanding these risk syndromes is to examine prospective community cohort studies and BD offspring studies. This paper reviews prospective cohort studies that identify robust risk factors in early illness onset, which was defined as age at onset of BD between 15-25 years. We found that although > 50 % of individuals who developed BD had developed a putative BD prodrome prior to 14 years of age, this usually began with non-specific symptoms that overlap with similar presentations for those who later develop psychosis or severe depression. However, there are some features that seem to better identify groups with a BD "at-risk" syndrome. This syndrome is frequently composed of several factors such as mood lability, depressive episodes, prior anxiety, sleep and/or conduct disorders, attention and concentration impairment, altered energy patterns, and a family history of mania and/or depression. The course of these early predictors suggests the precursor syndromes are composed of mini-clusters of symptoms many of which are episodic and change over time. During the early phases of BD, most of the affective disturbances reported were depressive in polarity and started during adolescence, there were few manic or mixed or psychotic episodes with an onset before puberty. The pathogenesis of BD demonstrates a gradual progression from non-specific to more specific symptoms and then to frank BD features. Prospective community and offspring BD cohort studies are approaches that together can help us understand the evolution of BD and allow us to define the developmental pathways. Further, identifying subjects with BD "at-risk" syndrome using a clinical staging model may allow benign interventions to be used as first-line treatment - such as neuroprotective agents like essential fatty acids; second line treatments, with a less benign risk to benefit ratio should be reserved for severe or resistant cases. Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

A systematic review of neuropsychological studies involving young binge drinkers.

PubMed

Carbia, Carina; López-Caneda, Eduardo; Corral, Montserrat; Cadaveira, Fernando

2018-07-01

Binge drinking (BD) is a public health concern with serious implications for brain development. This review is the first in which neuropsychological studies of healthy young BDs are synthesized following PRISMA guidelines. We conducted a literature search in PsycINFO, Web of Science, and PubMed. Articles were screened using strict inclusion criteria. Two authors independently assessed the methodological quality. Of the 27 studies included, 14 (52%) were of intermediate quality, 7 (26%) of poor quality and 6 (22%) of high quality. BD is associated with deficits in verbal memory and executive functions, principally poor inhibitory control. Tentatively, BD may be related to deficits in cognitive flexibility and monitoring of information in working memory. Further studies are needed to determine potential impairments in prospective memory and decision-making. BDs do not seem to show difficulties in planning, short-term memory, attention, processing speed or visuospatial construction. The evidence does not seem to support greater vulnerability in females. Future longitudinal studies should identify the characteristics of extreme trajectories, explore recovery deficits and design intervention programs. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 27406 - Airworthiness Directives; Bombardier, Inc. Model BD-100-1A10 (Challenger 300) Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... BD- 100 Time Limits/Maintenance Checks. The actions described in this service information are... Challenger 300 BD-100 Time Limits/Maintenance Checks. (1) For the new tasks identified in Bombardier TR 5-2... Requirements,'' in Part 2 of Chapter 5 of Bombardier Challenger 300 BD-100 Time Limits/ Maintenance Checks...

Rodent bone densitometer on the International Space Station: Instrument design and performance

NASA Astrophysics Data System (ADS)

Vellinger, John C.; Barton, Kenneth; Faget, Paul; Todd, Paul; Boland, Eugene

2016-07-01

The study of bone loss dynamics, mechanisms and countermeasures has been a publicly stated purpose of biomedical research aboard the International Space Station. Rodent research has always played a major role in terrestrial laboratories studying bone loss. The "gold standard" for assessing bone loss in human patients has been dual-energy x-ray absorptiometry (DEXA). DEXA is also widely applied to the study of bone loss in laboratory animals, so this technology has been added to the ISS inventory of analytical tools in the form of the ISS Bone Densitometer (BD) designed, constructed, tested and integrated by Techshot, Inc. (Greenville, Indiana, USA). The BD is a re-packaged COTS device known as PIXImus (GE-Lunar, USA), which was installed on ISS in November 2014 after launching on SpaceX-4. To facilitate operations in microgravity and to meet spaceflight facility and safety requirements the commercial x-ray source, control electronics and imaging system were modified and packaged by Techshot into a drawer that fits into a single EXPRESS Locker replacement. A space-rated "Exam Box" is also supplied for containment of the anesthetized subject during transfer into the BD and during exposure. The commercial software package controls four paired-energy exposures, 80 and 35 kV, and applies DEXA algorithms to the fluorescence images and displays bone mineral density (BMD), bone mineral content, lean mass, fat mass, total mass and per cent fat. The BD is therefore also a means for measuring mass and body composition making it a versatile tool for many types of rodent studies on orbit. The BD has been operated multiple times on orbit, and its performance has not differed significantly from its performance on the ground. It has been shown to measure body mass with a precision of +/- 0.1 g and on-orbit accuracy of -0.3 g. It is expected to detect BMD losses of approximately 2%. The image data are stored in a manner that allows post-test data analysis especially including the identification of a region of interest (ROI) by the investigator who wishes to assess BMD changes in femur only or spine only, for example. This research was supported by the Center for Advancement of Science in Space (CASIS) and NASA Contract NNJ13GA01C.

Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?

PubMed

Erdem, Hakan; Pay, Salih; Musabak, Ugur; Simsek, Ismail; Dinc, Ayhan; Pekel, Aysel; Sengul, Ali

2007-08-01

In our previous studies, we found higher synovial fluid (SF) levels of angiogenic ELR(+) CXC chemokines such as CXCL1, CXCL5, CXCL6 and CXCL8, which play an important role in neutrophil migration and angiogenesis, and more abundant synovial CXCR2 chemokine receptor expression in patients with rheumatoid arthritis (RA) than those with Behçet's disease (BD), familial Mediterranean fever and osteoarthritis (OA). As a continuation of our previous studies, we investigated synovial levels of angiostatic non-ELR CXC chemokines (CXCL4, CXCL9 and CXCL10) in patients with RA, BD, spondyloarthritis (SpA), and OA. Seventy (17 RA, 15 BD, 19 SpA, and 19 OA) patients were enrolled in the study. The levels of CXCL4, CXCL9, and CXCL10 were measured by ELISA. The SF levels of CXCL4 in patients with RA were higher than those of the patients with BD, SpA, and OA (P = 0.007, P = 0.022, and P = 0.017, respectively). No difference was found with respect to CXCL4 levels among the BD, SpA, and OA patients. The synovial CXCL9 levels of patients with RA and SpA were found to be higher than those of the patients with OA (P = 0.002 and P = 0.005, respectively), while no statistically significant difference was detected among the other groups. With regard to SF CXCL10 levels, patients with RA had higher levels as compared to patients with OA (P = 0.002), but no significant difference was found among the other groups. CXCL9 correlated with CXCL4 and CXCL10 (P < 0.05 for both) in patients with RA. No correlation was found in other parameters. The angiostatic non-ELR CXC chemokines were expressed in synovial inflammation. We proposed that angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR (+) CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA. In addition, as CXCL-9 and CXCL-10 play crucial role in inflammation characterized by Th1 polarization, we suggested that they may contribute to the commencement and the perpetuation of synovitis seen in these groups of arthritides.

Behcet's disease in Budd-Chiari syndrome.

PubMed

Desbois, Anne Claire; Rautou, Pierre Emmanuel; Biard, Lucie; Belmatoug, Nadia; Wechsler, Bertrand; Resche-Rigon, Mathieu; Zarrouk, Virginie; Fantin, Bruno; de Chambrun, M Pineton; Cacoub, Patrice; Valla, Dominique; Saadoun, David; Plessier, Aurélie

2014-01-01

Behcet's disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD. We investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD. Male gender (p = 0.003), North African origin (P = 0.007) and inferior vena cava obstruction (P < 0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p = 0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P = 0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P = 0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment. This study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD.

Differentiating between bipolar and unipolar depression in functional and structural MRI studies.

PubMed

Han, Kyu-Man; De Berardis, Domenico; Fornaro, Michele; Kim, Yong-Ku

2018-03-28

Distinguishing depression in bipolar disorder (BD) from unipolar depression (UD) solely based on clinical clues is difficult, which has led to the exploration of promising neural markers in neuroimaging measures for discriminating between BD depression and UD. In this article, we review structural and functional magnetic resonance imaging (MRI) studies that directly compare UD and BD depression based on neuroimaging modalities including functional MRI studies on regional brain activation or functional connectivity, structural MRI on gray or white matter morphology, and pattern classification analyses using a machine learning approach. Numerous studies have reported distinct functional and structural alterations in emotion- or reward-processing neural circuits between BD depression and UD. Different activation patterns in neural networks including the amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC), and striatum during emotion-, reward-, or cognition-related tasks have been reported between BD and UD. A stronger functional connectivity pattern in BD was pronounced in default mode and in frontoparietal networks and brain regions including the PFC, ACC, parietal and temporal regions, and thalamus compared to UD. Gray matter volume differences in the ACC, hippocampus, amygdala, and dorsolateral prefrontal cortex (DLPFC) have been reported between BD and UD, along with a thinner DLPFC in BD compared to UD. BD showed reduced integrity in the anterior part of the corpus callosum and posterior cingulum compared to UD. Several studies performed pattern classification analysis using structural and functional MRI data to distinguish between UD and BD depression using a supervised machine learning approach, which yielded a moderate level of accuracy in classification. Copyright © 2018 Elsevier Inc. All rights reserved.

Bipolar disorder in children and adolescents: international perspective on epidemiology and phenomenology.

PubMed

Soutullo, César A; Chang, Kiki D; Díez-Suárez, Azucena; Figueroa-Quintana, Ana; Escamilla-Canales, Inmaculada; Rapado-Castro, Marta; Ortuño, Felipe

2005-12-01

There is considerable skepticism outside the US over the prevalence of pediatric bipolar disorder (BD). We wished to evaluate the epidemiology of BD in children and adolescents in non-US samples. We reviewed studies on the prevalence of BD in children and adolescents in international samples. We also describe our sample of 27 children with BD at the University of Navarra. There are important and frequently overlooked differences in the definition of BD between the International Classification of Diseases 10th edition (ICD-10) and DSM-IV and methodological differences in epidemiological studies that may partially explain international differences in prevalence of pediatric BD. The prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%. In Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania 0.9%. Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of adolescents in Finland had BD. In our clinic, the prevalence of DSM-IV BD in children 5-18 years old is 4%, and of any mood disorders 27%. There are also data from Brazil, India and Turkey with varying results. Relative lack of data, ICD-10 and DSM-IV differences in diagnostic criteria, different levels of recognition of Child and Adolescent Psychiatry as a true specialty in Europe, clinician bias against BD, an overdiagnosis of the disorder in USA and/or a true higher prevalence of pediatric BD in USA may explain these results. US-International differences may be a methodological artifact and research is needed in this field.

Conversion from bipolar disorder not otherwise specified (BP-NOS) to bipolar I or II in youth with family history as a predictor of conversion.

PubMed

Martinez, Molly S; Fristad, Mary A

2013-06-01

Bipolar disorder-not otherwise specified (BD-NOS) is an imprecise, heterogeneous diagnosis that is unstable in youth. This study reports rates of conversion from BD-NOS to BD-I or II in children aged 8-12, and investigates the impact of family history of bipolar disorder and depression on conversion. As part of the Multi-Family Psychoeducational Psychotherapy (MF-PEP) study, 27 children (6-12 years of age) diagnosed with BD-NOS at baseline were reassessed every 6 months over an 18-month period. Family history of bipolar disorder and depression was assessed at baseline. One-third of the sample converted from BD-NOS to BD-I or II over 18-months. Having a first-degree relative with symptoms of bipolar disorder and having a loaded pedigree for diagnosis of depression each were associated with conversion from BD-NOS to BD-I or II (odds ratio range: 1.09-3.14; relative risk range: 1.06-2.34). This study had very low power (range: 10-45) given the small sample size, precluding statistical significance of non-parametric Fisher's Exact test findings. This study replicates the previous finding of a high rate of conversion from BD-NOS to BD-I or II among youth, and suggests conversion is related to symptoms of bipolar disorder or depression diagnoses in the family history. Additional research is warranted in a larger sample with a longer follow-up period. Copyright © 2012 Elsevier B.V. All rights reserved.

Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics.

PubMed

Clements, C; Morriss, R; Jones, S; Peters, S; Roberts, C; Kapur, N

2013-12-01

Bipolar disorder (BD) has been reported to be associated with high risk of suicide. We aimed to investigate the frequency and characteristics of suicide in people with BD in a national sample. Suicide in BD in England from 1996 to 2009 was explored using descriptive statistics on data collected by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI). Suicide cases with a primary diagnosis of BD were compared to suicide cases with any other primary diagnosis. During the study period 1489 individuals with BD died by suicide, an average of 116 cases/year. Compared to other primary diagnosis suicides, those with BD were more likely to be female, more than 5 years post-diagnosis, current/recent in-patients, to have more than five in-patient admissions, and to have depressive symptoms. In BD suicides the most common co-morbid diagnoses were personality disorder and alcohol dependence. Approximately 40% were not prescribed mood stabilizers at the time of death. More than 60% of BD suicides were in contact with services the week prior to suicide but were assessed as low risk. Given the high rate of suicide in BD and the low estimates of risk, it is important that health professionals can accurately identify patients most likely to experience poor outcomes. Factors such as alcohol dependence/misuse, personality disorder, depressive illness and current/recent in-patient admission could characterize a high-risk group. Future studies need to operationalize clinically useful indicators of suicide risk in BD.

Binocular pattern deprivation interferes with the expression of proteins involved in primary visual cortex maturation in the cat.

PubMed

Laskowska-Macios, Karolina; Nys, Julie; Hu, Tjing-Tjing; Zapasnik, Monika; Van der Perren, Anke; Kossut, Malgorzata; Burnat, Kalina; Arckens, Lutgarde

2015-08-14

Binocular pattern deprivation from eye opening (early BD) delays the maturation of the primary visual cortex. This delay is more pronounced for the peripheral than the central visual field representation within area 17, particularly between the age of 2 and 4 months [Laskowska-Macios, Cereb Cortex, 2014]. In this study, we probed for related dynamic changes in the cortical proteome. We introduced age, cortical region and BD as principal variables in a 2-D DIGE screen of area 17. In this way we explored the potential of BD-related protein expression changes between central and peripheral area 17 of 2- and 4-month-old BD (2BD, 4BD) kittens as a valid parameter towards the identification of brain maturation-related molecular processes. Consistent with the maturation delay, distinct developmental protein expression changes observed for normal kittens were postponed by BD, especially in the peripheral region. These BD-induced proteomic changes suggest a negative regulation of neurite outgrowth, synaptic transmission and clathrin-mediated endocytosis, thereby implicating these processes in normal experience-induced visual cortex maturation. Verification of the expression of proteins from each of the biological processes via Western analysis disclosed that some of the transient proteomic changes correlate to the distinct behavioral outcome in adult life, depending on timing and duration of the BD period [Neuroscience 2013;255:99-109]. Taken together, the plasticity potential to recover from BD, in relation to ensuing restoration of normal visual input, appears to rely on specific protein expression changes and cellular processes induced by the loss of pattern vision in early life.

Donor Brain Death Exacerbates Complement-Dependent Ischemia Reperfusion Injury in Transplanted Hearts

PubMed Central

Atkinson, Carl; Floerchinger, Bernhard; Qiao, Fei; Casey, Sarah; Williamson, Tucker; Moseley, Ellen; Stoica, Serban; Goddard, Martin; Ge, Xupeng; Tullius, Stefan G.; Tomlinson, Stephen

2013-01-01

Background Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia reperfusion injury (IRI) post-transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on post transplant cardiac IRI. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts, and addressed the clinical relevance of these studies by analysis of human heart biopsies from BD and domino (living) donors. Methods and Results Hearts from living or brain dead donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours post-transplant for injury, inflammation and complement deposition, and allografts monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated IRI and graft rejection as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, inflammatory chemokine and cytokine levels, complement deposition, and decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared to controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared to grafts from living donors. Conclusions BD exacerbates post-transplant cardiac IRI in mice and humans, and decreases survival of mouse allografts. Further, targeted complement inhibition in recipient mice ameliorates BD-exacerbated IRI. PMID:23443736

Evaluation of the BD Max Cdiff assay for the detection of toxigenic Clostridium difficile in human stool specimens.

PubMed

Putsathit, Papanin; Morgan, Justin; Bradford, Damien; Engelhardt, Nelly; Riley, Thomas V

2015-02-01

The Becton Dickinson (BD) PCR-based GeneOhm Cdiff assay has demonstrated a high sensitivity and specificity for detecting Clostridium difficile. Recently, the BD Max platform, using the same principles as BD GeneOhm, has become available in Australia. This study aimed to investigate the sensitivity and specificity of BD Max Cdiff assay for the detection of toxigenic C. difficile in an Australian setting. Between December 2013 and January 2014, 406 stool specimens from 349 patients were analysed with the BD Max Cdiff assay. Direct and enrichment toxigenic culture were performed on bioMérieux ChromID C. difficile agar as a reference method. isolates from specimens with discrepant results were further analysed with an in-house PCR to detect the presence of toxin genes. The overall prevalence of toxigenic C. difficile was 7.2%. Concordance between the BD Max assay and enrichment culture was 98.5%. The sensitivity, specificity, positive predictive value and negative predictive value for the BD Max Cdiff assay were 95.5%, 99.0%, 87.5% and 99.7%, respectively, when compared to direct culture, and 91.7%, 99.0%, 88.0% and 99.4%, respectively, when compared to enrichment culture. The new BD Max Cdiff assay appeared to be an excellent platform for rapid and accurate detection of toxigenic C. difficile.

Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.

PubMed

Bilham, Kirstin; Boyd, Amy C; Preston, Stephen G; Buesching, Christina D; Newman, Chris; Macdonald, David W; Smith, Adrian L

2017-04-06

The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers.

Intestinal Behçet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis?

PubMed Central

Kim, Duk Hwan

2016-01-01

Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor α antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision. PMID:26632379

Differential patterns of Batrachochytrium dendrobatidis infection in relict amphibian populations following severe disease-associated declines.

PubMed

Whitfield, Steven M; Alvarado, Gilbert; Abarca, Juan; Zumbado, Hector; Zuñiga, Ibrahim; Wainwright, Mark; Kerby, Jacob

2017-09-20

Global amphibian biodiversity has declined dramatically in the past 4 decades, and many amphibian species have declined to near extinction as a result of emergence of the amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd). However, persistent or recovering populations of several amphibian species have recently been rediscovered, and such populations may illustrate how amphibian species that are highly susceptible to chytridiomycosis may survive in the presence of Bd. We conducted field surveys for Bd infection in 7 species of Costa Rican amphibians (all species that have declined to near extinction but for which isolated populations persist) to characterize infection profiles in highly Bd-susceptible amphibians post-decline. We found highly variable patterns in infection, with some species showing low prevalence (~10%) and low infection intensity and others showing high infection prevalence (>80%) and either low or high infection intensity. Across sites, infection rates were negatively associated with mean annual precipitation, and infection intensity across sites was negatively associated with mean average temperatures. Our results illustrate that even the most Bd-susceptible amphibians can persist in Bd-enzootic ecosystems, and that multiple ecological or evolutionary mechanisms likely exist for host-pathogen co-existence between Bd and the most Bd-susceptible amphibian species. Continued monitoring of these populations is necessary to evaluate population trends (continuing decline, stability, or population growth). These results should inform efforts to mitigate impacts of Bd on amphibians in the field.

Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives

PubMed Central

Kanske, P; Schönfelder, S; Forneck, J; Wessa, M

2015-01-01

Deficient emotion regulation has been proposed as a crucial pathological mechanism in bipolar disorder (BD). We therefore investigated emotion regulation impairments in BD, the related neural underpinnings and their etiological relevance for the disorder. Twenty-two euthymic patients with bipolar-I disorder and 17 unaffected first-degree relatives of BD-I patients, as well as two groups of healthy gender-, age- and education-matched controls (N=22/17, respectively) were included. Participants underwent functional magnetic resonance imaging while applying two different emotion regulation techniques, reappraisal and distraction, when presented with emotional images. BD patients and relatives showed impaired downregulation of amygdala activity during reappraisal, but not during distraction, when compared with controls. This deficit was correlated with the habitual use of reappraisal. The negative connectivity of amygdala and orbitofrontal cortex (OFC) observed during reappraisal in controls was reversed in BD patients and relatives. There were no significant differences between BD patients and relatives. As being observed in BD patients and unaffected relatives, deficits in emotion regulation through reappraisal may represent heritable neurobiological abnormalities underlying BD. The neural mechanisms include impaired control of amygdala reactivity to emotional stimuli and dysfunctional connectivity of the amygdala to regulatory control regions in the OFC. These are, thus, important aspects of the neurobiological basis of increased vulnerability for BD. PMID:25603413

Emission analysis on the effect of nanoparticles on neat biodiesel in unmodified diesel engine.

PubMed

Pandian, Amith Kishore; Ramakrishnan, Ramesh Bapu Bathey; Devarajan, Yuvarajan

2017-10-01

Biodiesels derived from the mahua seeds are established as a promising alternative for the diesel fuel owing to its non-edible nature and improved properties. TiO 2 nanoparticle in powder form is added to neat mahua oil biodiesel (BD100) to examine its effect on emission characteristics. TiO 2 nanoparticle is chosen as an additive owing to its catalytic effect, higher surface energy, and larger surface to volume ratio. TiO 2 nanoparticle with an average size of 60 nm was synthesized by sol-gel route. TiO 2 nanoparticles are added with mahua biodiesel (BD100) at 100 and 200 ppm. Mahua oil biodiesel doped with 100 and 200 ppm of TiO 2 nanoparticles are referred as BD100T100 and BD100T200. A constant speed diesel engine is employed for the experimental trail. Engine is fueled with diesel, BD100, BD100T100, and BD100T200, respectively. Experimental result confirmed that the modified fuels (BD100T200 and BD100T100) showed a significant reduction in all the emissions. Further, the addition of TiO 2 nanoparticle (200 ppm) to mahua biodiesel gave respective reduction of 9.3, 5.8, 6.6, and 2.7% in carbon monoxide, hydrocarbon, nitrogen oxide, and smoke emissions when compared to neat mahua biodiesel.

A psychometric evaluation of the clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C16) in patients with bipolar disorder.

PubMed

Bernstein, Ira H; Rush, A John; Suppes, Trisha; Trivedi, Madhukar H; Woo, Ada; Kyutoku, Yasushi; Crismon, M Lynn; Dennehy, Ellen; Carmody, Thomas J

2009-06-01

The clinician-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-C16) has been extensively evaluated in patients with major depressive disorder (MDD). This report assesses the psychometric properties of the QIDS-C16 in outpatients with bipolar disorder (BD, N = 405) and MDD (N = 547) and in bipolar patients in the depressed phase only (BD-D) (N = 99) enrolled in the Texas Medication Algorithm Project (TMAP) using classical test theory (CTT) and the Samejima graded item response theory (IRT) model. Values of coefficient alpha were very similar in BD, MDD, and BD-D groups at baseline (alpha = 0.80-0.81) and at exit (alpha = 0.82-0.85). The QIDS-C16 was unidimensional for all three groups. MDD and BD-D patients (n = 99) had comparable symptom levels. The BD-D patients (n = 99) had the most, and bipolar patients in the manic phase had the least depressive symptoms at baseline. IRT analyses indicated that the QIDS-C16 was most sensitive to the measurement of depression for both MDD patients and for BD-D patients in the average range. The QIDS-C16 is suitable for use with patients with BD and can be used as an outcome measure in trials enrolling both BD and MDD patients. John Wiley & Sons, Ltd

Elevated Choline-Containing Compound Levels in Rapid Cycling Bipolar Disorder.

PubMed

Cao, Bo; Stanley, Jeffrey A; Passos, Ives Cavalcante; Mwangi, Benson; Selvaraj, Sudhakar; Zunta-Soares, Giovana B; Soares, Jair C

2017-10-01

Previous studies have found increased levels of choline-containing compounds (ie, glycerophosphocholine plus phosphocholine (GPC+PC)) in bipolar disorder using in vivo proton magnetic resonance spectroscopy ( 1 H MRS), especially in bipolar I disorder (BD-I). Increased levels of GPC+PC suggest alterations in the membrane phospholipids metabolism in bipolar disorder. Rapid cycling (RC) bipolar disorder is considered as a severe course of bipolar disorder, but it is unclear whether rapid cycling bipolar disorder is linked to highly altered membrane phospholipid metabolism. The purpose of this study was to investigate whether the regional extent of elevated GPC+PC were greater in BD-I patients with rapid cycling compared to BD-I patients without rapid cycling and healthy controls. Using a multi-voxel 1 H MRS approach at 3 Tesla with high spatial resolution and absolute quantification, GPC+PC levels from the anterior cingulate cortex (ACC), caudate and putamen of 16 RC BD-I, 34 non-RC BD-I and 44 healthy controls were assessed. We found significantly elevated GPC+PC levels in ACC, putamen and caudate of RC BD-I patients compared to healthy controls (P<0.005) and in ACC compared to non-RC BD-I patients (P<0.05). These results suggest greater alteration of membrane phospholipid metabolisms in rapid cycling BD-I compared to non-rapid-cycling BD-I.

Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients

PubMed Central

Rao, Jagadeesh Sridhara; Kellom, Matthew; Reese, Edmund Arthur; Rapoport, Stanley Isaac; Kim, Hyung-Wook

2012-01-01

Background Dysregulated glutamate, serotonin and dopamine neurotransmission has been reported in bipolar disorder (BD) and schizophrenia (SZ), but the underlying mechanisms of dysregulation are not clear. We hypothesized that they involve alterations in excitatory amino acid transporters (EAATs), the serotonin reuptake transporter (SERT), and the dopamine reuptake transporter (DAT). Methods To test this hypothesis, we determined protein and mRNA levels of EAAT subtypes 1–4, of the SERT and of the DAT in postmortem frontal cortex from BD (n=10) and SZ (n=10) patients and from healthy control (n=10) subjects. Results Compared to control levels, protein and mRNA levels of EAAT1 were increased significantly in cortex from both BD and SZ patients. EAAT2 protein and mRNA levels were decreased significantly in BD but not in SZ cortices. EAAT3 and EAAT 4 protein and mRNA levels were significantly higher in SZ but not in BD compared with control. DAT protein and mRNA levels were decreased significantly in both BD and SZ cortex. There was no significant change in SERT expression in either BD or SZ. Conclusions The altered EAATs and DAT expression could result in altered glutamatergic and hyperdopaminergic function in BD and SZ. Differently altered EAATs involved in glutamatergic transmission could be therapeutic targets for treating BD and SZ. PMID:21925739

Family Functioning, Social Impairment, and Symptoms Among Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

Keenan-Miller, Danielle; Peris, Tara; Axelson, David; Kowatch, Robert A.; Miklowitz, David J.

2012-01-01

Objective: Impaired social functioning is common among youth with bipolar disorder (BD), emerges in multiple settings, and persists over time. However, little is known about factors associated with poor peer and family functioning in the early-onset form of BD. Using a sample of adolescents with BD I or II, we examined which symptoms of BD,…

Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

ERIC Educational Resources Information Center

Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

2012-01-01

Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

Headache in Behçet's disease.

PubMed

Aykutlu, E; Baykan, B; Akman-Demir, G; Topcular, B; Ertas, M

2006-02-01

The aim of this study was to investigate the characteristics of headache in patients with Behçet's disease (BD) seeking neurological consultation. Consecutive patients with BD seen within 1 year at the neuro-Behçet's out-patient clinic were studied using an electronic database according to the classification criteria of the International Headache Society. During a 12-month period 118 BD patients were admitted, and 98 had headaches. Migraine was the most common type of primary headache diagnosed in 45 patients (46.4%) in the whole headache group, followed by tension-type headache (TTH) in 26 cases (26.8%). Thirty-seven patients had secondary headaches mainly due to cerebral venous thrombosis or parenchymal neurological involvement of BD. Of these patients, 15 had both primary and secondary headaches. The primary headaches of 13 patients were exacerbated with systemic BD flare-ups, and four patients had migraine attacks triggered only by systemic BD activation which showed a good response to the treatment of systemic inflammation. The majority of the headaches of patients with BD do not indicate any neurological involvement; they are usually due to migraine or TTH. In a minority of patients, migraine associated with systemic inflammation of BD is notable.

Facial recognition deficits as a potential endophenotype in bipolar disorder.

PubMed

Vierck, Esther; Porter, Richard J; Joyce, Peter R

2015-11-30

Bipolar disorder (BD) is considered a highly heritable and genetically complex disorder. Several cognitive functions, such as executive functions and verbal memory have been suggested as promising candidates for endophenotypes. Although there is evidence for deficits in facial emotion recognition in individuals with BD, studies investigating these functions as endophenotypes are rare. The current study investigates emotion recognition as a potential endophenotype in BD by comparing 36 BD participants, 24 of their 1st degree relatives and 40 healthy control participants in a computerised facial emotion recognition task. Group differences were evaluated using repeated measurement analysis of co-variance with age as a covariate. Results revealed slowed emotion recognition for both BD and their relatives. Furthermore, BD participants were less accurate than healthy controls in their recognition of emotion expressions. We found no evidence of emotion specific differences between groups. Our results provide evidence for facial recognition as a potential endophenotype in BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Community Structure and Function of Amphibian Skin Microbes: An Experiment with Bullfrogs Exposed to a Chytrid Fungus.

PubMed

Walke, Jenifer B; Becker, Matthew H; Loftus, Stephen C; House, Leanna L; Teotonio, Thais L; Minbiole, Kevin P C; Belden, Lisa K

2015-01-01

The vertebrate microbiome contributes to disease resistance, but few experiments have examined the link between microbiome community structure and disease resistance functions. Chytridiomycosis, a major cause of amphibian population declines, is a skin disease caused by the fungus, Batrachochytrium dendrobatidis (Bd). In a factorial experiment, bullfrog skin microbiota was reduced with antibiotics, augmented with an anti-Bd bacterial isolate (Janthinobacterium lividum), or unmanipulated, and individuals were then either exposed or not exposed to Bd. We found that the microbial community structure of individual frogs prior to Bd exposure influenced Bd infection intensity one week following exposure, which, in turn, was negatively correlated with proportional growth during the experiment. Microbial community structure and function differed among unmanipulated, antibiotic-treated, and augmented frogs only when frogs were exposed to Bd. Bd is a selective force on microbial community structure and function, and beneficial states of microbial community structure may serve to limit the impacts of infection.

Community Structure and Function of Amphibian Skin Microbes: An Experiment with Bullfrogs Exposed to a Chytrid Fungus

PubMed Central

Walke, Jenifer B.; Becker, Matthew H.; Loftus, Stephen C.; House, Leanna L.; Teotonio, Thais L.; Minbiole, Kevin P. C.; Belden, Lisa K.

2015-01-01

The vertebrate microbiome contributes to disease resistance, but few experiments have examined the link between microbiome community structure and disease resistance functions. Chytridiomycosis, a major cause of amphibian population declines, is a skin disease caused by the fungus, Batrachochytrium dendrobatidis (Bd). In a factorial experiment, bullfrog skin microbiota was reduced with antibiotics, augmented with an anti-Bd bacterial isolate (Janthinobacterium lividum), or unmanipulated, and individuals were then either exposed or not exposed to Bd. We found that the microbial community structure of individual frogs prior to Bd exposure influenced Bd infection intensity one week following exposure, which, in turn, was negatively correlated with proportional growth during the experiment. Microbial community structure and function differed among unmanipulated, antibiotic-treated, and augmented frogs only when frogs were exposed to Bd. Bd is a selective force on microbial community structure and function, and beneficial states of microbial community structure may serve to limit the impacts of infection. PMID:26445500

Prospective Predictors of Body Dissatisfaction in Young Adults: 10-year Longitudinal Findings

PubMed Central

Quick, Virginia; Eisenberg, Marla E.; Bucchianeri, Michaela M.; Neumark-Sztainer, Dianne

2014-01-01

This study identified longitudinal risk factors for body dissatisfaction (BD) over a 10-year period from adolescence to young adulthood. Participants (N = 2134; age at baseline: M =15.0, SD =1.6 years) provided two waves of survey data. A 6-step hierarchical linear regression analysis examined the predictive contribution of Time 1 BD, weight status, demographics, family and peer environmental factors, and psychological factors. Among females, Asian race/ethnicity, low self-esteem, greater BD, and higher body mass index during adolescence contributed significantly to predicting greater BD at 10-year follow up (R2 = 0.27). Among males, demographics (i.e., Asian, other-mixed ethnicity, education attainment), depressive symptoms, greater BD, higher body mass index, more parent communication, and less peer weight teasing during adolescence contributed to BD at follow-up (R2 = 0.27). Findings indicate who may be at greatest risk for BD in young adulthood and the types of factors that should be addressed during adolescence. PMID:25045599

Effect of burdock extract on physical performance and physiological fatigue in mice

PubMed Central

CHEN, Wen-Chyuan; HSU, Yi-Ju; LEE, Mon-Chien; LI, Hua Shuai; HO, Chun-Sheng; HUANG, Chi-Chang; CHEN, Fu-An

2017-01-01

Burdock (BD) is a common vegetable with many pharmacological properties. However, few studies have examined the effect of BD on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of BD on fatigue and ergogenic functions following physical challenge in mice. Methods: Male ICR mice were divided into four groups to receive either vehicle, or BD at 348.5, 697 or 1,742.5 mg/kg/day, by daily oral gavage for 4 weeks. Exercise performance and fatigue were evaluated from forelimb grip strength, exhaustive swimming time, and post-exercise levels of physical fatigue-related biomarkers serum lactate, ammonia, glucose, and creatine kinase (CK). Results: BD supplementation elevated endurance and grip strength in a dose-dependent manner. It also significantly decreased lactate, ammonia, and CK levels after physical challenge. In addition, BD supplementation had few subchronic toxic effects. Conclusions: Supplementation with BD has a wide spectrum of bioactive effects, including health promotion, performance improvement, and fatigue reduction. PMID:28890521

Serum ghrelin levels in patients with Behcet’s disease

PubMed Central

Erden, Ilker; Demir, Betül; Cicek, Demet; Dertlioğlu, Selma Bakar; Aydin, Suleyman; Ozturk, Savas

2016-01-01

Introduction Behcet’s disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology. Aim To measure serum ghrelin levels in BD patients and healthy controls and to investigate its association with metabolic syndrome (MetS). Material and methods Thirty BD patients and 30 healthy individuals were enrolled in the study. Ghrelin levels were measured in blood samples using ELISA. Results The mean serum ghrelin level in BD patients (28.57 ±14.04) was significantly lower compared to healthy controls (40.72 ±23.21) (p = 0.01). The mean serum ghrelin level in BD patients who had MetS (24.18 ±12.73) was lower compared to BD patients who did not have MetS (30.77 ±14.45), but this difference was not significant (p > 0.05). Conclusions Ghrelin levels were lower in BD patients compared to healthy controls. There was no association between reduced ghrelin levels and MetS; however, there was a negative correlation between ghrelin levels and disease activity. PMID:28035223

Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease.

PubMed

Hisamatsu, Tadakazu; Hayashida, Mari

2017-07-01

Behçet's disease (BD) is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.

Body dissatisfaction levels and gender differences in attentional biases toward idealized bodies.

PubMed

Cho, Ara; Lee, Jang-Han

2013-01-01

Attentional bias toward idealized bodies (men: muscular; women: thin) may cause upward comparisons and increase body dissatisfaction (BD). We investigated attentional biases of 39 men and 41 women with high and low BD toward muscular male bodies and thin female bodies. An eye-tracker measured gaze durations and fixation frequencies while exposing participants to images of thin, normal, muscular, and fat bodies of the same gender. Results revealed longer and more frequent attention toward muscular bodies in high BD men, and toward thin bodies in high BD women. High BD men and women also rated muscular and thin bodies as more attractive than those with low BD. Although men attended to muscular and women attended to thin bodies, both showed an attentional bias toward body types they rated as more attractive. These findings could provide indirect evidence in explaining the relationship between BD and the social comparison theory with attentional bias. Copyright © 2012 Elsevier Ltd. All rights reserved.

NMR Fragment Screening Hit Induces Plasticity of BRD7/9 Bromodomains.

PubMed

Wang, Na; Li, Fudong; Bao, Hongyu; Li, Jie; Wu, Jihui; Ruan, Ke

2016-08-03

The complex biology associated with inhibition of bromodomain and extra-terminal (BET) domains by chemical probes has attracted increasing attention, and there is a need to identify non-BET bromodomain (BD) inhibitors. Several potent inhibitors of the BRD9 BD have recently been discovered, with anticancer and anti-inflammation activity. However, its paralogue, BRD7 BD, remains unexploited. Here, we identified new chemotypes targeting BRD7 BD by using NMR fragment-based screening. BRD7/9 BDs exhibit similar patterns of chemical-shift perturbation upon the titration of hit compound 1. The crystal structure revealed that 1 repels the Y222 group of BRD9 BD in a similar way to that for butyryllysine, but not acetyllysine and known inhibitors. Hit 1 induced less rearrangement of residue F161 of BRD9 BD than acetyllysine, butyryllysine, and crotonyllysine. Our study provides structural insight into a new generation of butyryllysine mimics for probing the function of BRD7/9 BD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The clinical significance of creativity in bipolar disorder

PubMed Central

Murray, Greg; Johnson, Sheri L.

2012-01-01

Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity–BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype. PMID:20579791

Study of the Algorithm of Backtracking Decoupling and Adaptive Extended Kalman Filter Based on the Quaternion Expanded to the State Variable for Underwater Glider Navigation

PubMed Central

Huang, Haoqian; Chen, Xiyuan; Zhou, Zhikai; Xu, Yuan; Lv, Caiping

2014-01-01

High accuracy attitude and position determination is very important for underwater gliders. The cross-coupling among three attitude angles (heading angle, pitch angle and roll angle) becomes more serious when pitch or roll motion occurs. This cross-coupling makes attitude angles inaccurate or even erroneous. Therefore, the high accuracy attitude and position determination becomes a difficult problem for a practical underwater glider. To solve this problem, this paper proposes backing decoupling and adaptive extended Kalman filter (EKF) based on the quaternion expanded to the state variable (BD-AEKF). The backtracking decoupling can eliminate effectively the cross-coupling among the three attitudes when pitch or roll motion occurs. After decoupling, the adaptive extended Kalman filter (AEKF) based on quaternion expanded to the state variable further smoothes the filtering output to improve the accuracy and stability of attitude and position determination. In order to evaluate the performance of the proposed BD-AEKF method, the pitch and roll motion are simulated and the proposed method performance is analyzed and compared with the traditional method. Simulation results demonstrate the proposed BD-AEKF performs better. Furthermore, for further verification, a new underwater navigation system is designed, and the three-axis non-magnetic turn table experiments and the vehicle experiments are done. The results show that the proposed BD-AEKF is effective in eliminating cross-coupling and reducing the errors compared with the conventional method. PMID:25479331

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease

PubMed Central

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-01-01

Background: The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. Materials and Methods: We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Results: Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Conclusion: Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy. PMID:26538777

No Definite Association between Human Parvovirus B19 Infection and Behçet Disease.

PubMed

Habibagahi, Mojtaba; Habibagahi, Zahra; Saidmardani, Said-Mostafa; Sadeghian, Faezeh

2015-11-01

The etiology of the Behçet disease (BD) has remained obscured. There have been studies to show the association of BD to infections like herpes simplex, hepatitis, and parvovirus B19 however, the findings are rather controversial. We selected 55 patients with the best matched symptoms of BD and measured the loads of B19 DNA in their plasma by quantitative real time PCR and verified their seropositivity by ELISA. All findings were compared to the results from 42 healthy persons. Patients showed a wide spectrum of BD symptoms. Serologic studies showed high prevalence of B19 IgG among the tested patients which was not statistically different with the healthy population (72.7% vs. 85.7%, respectively). Similarly, the prevalence of B19 IgM between patients and controls was not different (18% vs. 11.9%, respectively). No correlation was found between the presence of anti-B19 antibodies and the clinical observations. Only one person from the patient and control groups had detectable levels of B19 DNA without any difference or correlation with the disease symptoms. Our data could not establish an association between B19 parvovirus infection and Behçet disease, although there have been reports of such correlation. Nevertheless, there might be indirect relation in genetically susceptible individuals after viral infections. More studies on designed animal models and surveys on patients should be done to resolve this controversy.

Study of the algorithm of backtracking decoupling and adaptive extended Kalman filter based on the quaternion expanded to the state variable for underwater glider navigation.

PubMed

Huang, Haoqian; Chen, Xiyuan; Zhou, Zhikai; Xu, Yuan; Lv, Caiping

2014-12-03

High accuracy attitude and position determination is very important for underwater gliders. The cross-coupling among three attitude angles (heading angle, pitch angle and roll angle) becomes more serious when pitch or roll motion occurs. This cross-coupling makes attitude angles inaccurate or even erroneous. Therefore, the high accuracy attitude and position determination becomes a difficult problem for a practical underwater glider. To solve this problem, this paper proposes backing decoupling and adaptive extended Kalman filter (EKF) based on the quaternion expanded to the state variable (BD-AEKF). The backtracking decoupling can eliminate effectively the cross-coupling among the three attitudes when pitch or roll motion occurs. After decoupling, the adaptive extended Kalman filter (AEKF) based on quaternion expanded to the state variable further smoothes the filtering output to improve the accuracy and stability of attitude and position determination. In order to evaluate the performance of the proposed BD-AEKF method, the pitch and roll motion are simulated and the proposed method performance is analyzed and compared with the traditional method. Simulation results demonstrate the proposed BD-AEKF performs better. Furthermore, for further verification, a new underwater navigation system is designed, and the three-axis non-magnetic turn table experiments and the vehicle experiments are done. The results show that the proposed BD-AEKF is effective in eliminating cross-coupling and reducing the errors compared with the conventional method.

Epidemiological and clinical variables related with the predominant polarity on bipolar disorder: A systematic review.

PubMed

García-Jiménez, Jesús; Álvarez-Fernández, Marisol; Aguado-Bailón, Lidia; Gutiérrez-Rojas, Luis

2017-08-14

Current classification of bipolar disorder (BD) in type i or type ii, however useful, may be insufficient to provide relevant clinical information in some patients. As a result, complementary classifications are being proposed, like the predominant polarity (PP) based, which is defined as a clear tendency in the patient to present relapses in the manic or depressive poles. We carried out a search in PubMed and Web of Science databases, following the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses -PRISMA- guidelines, to identify studies about BD reporting PP. The search is updated to June 2016. Initial search revealed 907 articles, of which 16 met inclusion criteria. Manic PP was found to be associated with manic onset, drug consumption prior to onset and a better response to atypical antipsychotics and mood stabilisers. Depressive PP showed an association with depressive onset, more relapses, prolonged acute episodes, a greater suicide risk and a later diagnosis of BD. Depressive PP was also associated with anxiety disorders, mixed symptoms, melancholic symptoms and a wider use of quetiapine and lamotrigine. Few prospective studies. Variability in some results. PP may be useful as a supplement to current BD classifications. We have found consistent data on a great number of studies, but there is also contradictory information regarding PP. Further studies are needed, ideally of a prospective design and with a unified methodology. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

Team-based learning on a third-year pediatric clerkship improves NBME subject exam blood disorder scores.

PubMed

Saudek, Kris; Treat, Robert

2015-01-01

Purpose At our institution, speculation amongst medical students and faculty exists as to whether team-based learning (TBL) can improve scores on high-stakes examinations over traditional didactic lectures. Faculty with experience using TBL developed and piloted a required TBL blood disorders (BD) module for third-year medical students on their pediatric clerkship. The purpose of this study is to analyze the BD scores from the NBME subject exams before and after the introduction of the module. Methods We analyzed institutional and national item difficulties for BD items from the NBME pediatrics content area item analysis reports from 2011 to 2014 before (pre) and after (post) the pilot (October 2012). Total scores of 590 NBME subject examination students from examinee performance profiles were analyzed pre/post. t-Tests and Cohen's d effect sizes were used to analyze item difficulties for institutional versus national scores and pre/post comparisons of item difficulties and total scores. Results BD scores for our institution were 0.65 (±0.19) compared to 0.62 (±0.15) nationally (P=0.346; Cohen's d=0.15). The average of post-consecutive BD scores for our students was 0.70(±0.21) compared to examinees nationally [0.64 (±0.15)] with a significant mean difference (P=0.031; Cohen's d=0.43). The difference in our institutions pre [0.65 (±0.19)] and post [0.70 (±0.21)] BD scores trended higher (P=0.391; Cohen's d=0.27). Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above national norms. Conclusions Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above national norms.

The relationship between stressful life events and Axis I diagnoses among adolescent offspring of probands with bipolar and non-bipolar psychiatric disorders and healthy controls

PubMed Central

Pan, Lisa A.; Goldstein, Tina R.; Rooks, Brian T.; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S.; Sakolsky, Dara J.; Hafeman, Daniella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J.; Axelson, David; Brent, David A.; Birmaher, Boris

2018-01-01

Background Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Scale(SLES) among three groups of adolescent offspring of probands: with bipolar(BD), with non-BD psychiatric disorders, and healthy control(HC). Furthermore, we examined the relationship between stressful life events and presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent or independent), and positive, negative, and neutral (neither positive or negative). Method Offspring of probands with BD aged 13–18 years(N=269), demographically-matched offspring of probands with non-BD Axis I disorders(N=88), and HC probands(N=81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002–2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current offspring Axis I diagnoses after adjusting for confounds. Results After adjusting for demographic and clinical between-group differences(in probands and offspring), offspring of BD probands had greater independent and neutral life events compared with HC offspring and greater number of more severe stressful life events than HC offspring, but not non-BD offspring. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events. Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both BD and non-BD affected probands regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Conclusions Offspring of BD probands have greater exposure to independent and neutral life events than HC offspring. Greater frequency and severity of stressful life events was associated with Axis I disorder in offspring of both BD and non-BD affected probands. PMID:28199068

Widespread occurrence of bd in French Guiana, South America.

PubMed

Courtois, Elodie A; Gaucher, Philippe; Chave, Jérôme; Schmeller, Dirk S

2015-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is a purported agent of decline and extinction of many amphibian populations worldwide. Its occurrence remains poorly documented in many tropical regions, including the Guiana Shield, despite the area's high amphibian diversity. We conducted a comprehensive assessment of Bd in French Guiana in order to (1) determine its geographical distribution, (2) test variation of Bd prevalence among species in French Guiana and compare it to earlier reported values in other South American anuran species (http://www.bd-maps.net; 123 species from 15 genera) to define sentinel species for future work, (3) track changes in prevalence through time and (4) determine if Bd presence had a negative effect on one selected species. We tested the presence of Bd in 14 species at 11 sites for a total of 1053 samples (306 in 2009 and 747 in 2012). At least one Bd-positive individual was found at eight out of 11 sites, suggesting a wide distribution of Bd in French Guiana. The pathogen was not uniformly distributed among the studied amphibian hosts, with Dendrobatidae species displaying the highest prevalence (12.4%) as compared to Bufonidae (2.6 %) and Hylidae (1.5%). In contrast to earlier reported values, we found highest prevalence for three Dendrobatidae species and two of them displayed an increase in Bd prevalence from 2009 to 2012. Those three species might be the sentinel species of choice for French Guiana. For Dendrobates tinctorius, of key conservation value in the Guiana Shield, smaller female individuals were more likely to be infected, suggesting either that frogs can outgrow their chytrid infections or that the disease induces developmental stress limiting growth. Generally, our study supports the idea that Bd is more widespread than previously thought and occurs at remote places in the lowland forest of the Guiana shield.

Co-Infection by Chytrid Fungus and Ranaviruses in Wild and Harvested Frogs in the Tropical Andes

PubMed Central

Warne, Robin W.; LaBumbard, Brandon; LaGrange, Seth; Vredenburg, Vance T.; Catenazzi, Alessandro

2016-01-01

While global amphibian declines are associated with the spread of Batrachochytrium dendrobatidis (Bd), undetected concurrent co-infection by other pathogens may be little recognized threats to amphibians. Emerging viruses in the genus Ranavirus (Rv) also cause die-offs of amphibians and other ectotherms, but the extent of their distribution globally, or how co-infections with Bd impact amphibians are poorly understood. We provide the first report of Bd and Rv co-infection in South America, and the first report of Rv infections in the amphibian biodiversity hotspot of the Peruvian Andes, where Bd is associated with extinctions. Using these data, we tested the hypothesis that Bd or Rv parasites facilitate co-infection, as assessed by parasite abundance or infection intensity within individual adult frogs. Co-infection occurred in 30% of stream-dwelling frogs; 65% were infected by Bd and 40% by Rv. Among terrestrial, direct-developing Pristimantis frogs 40% were infected by Bd, 35% by Rv, and 20% co-infected. In Telmatobius frogs harvested for the live-trade 49% were co-infected, 92% were infected by Bd, and 53% by Rv. Median Bd and Rv loads were similar in both wild (Bd = 101.2 Ze, Rv = 102.3 viral copies) and harvested frogs (Bd = 103.1 Ze, Rv = 102.7 viral copies). While neither parasite abundance nor infection intensity were associated with co-infection patterns in adults, these data did not include the most susceptible larval and metamorphic life stages. These findings suggest Rv distribution is global and that co-infection among these parasites may be common. These results raise conservation concerns, but greater testing is necessary to determine if parasite interactions increase amphibian vulnerability to secondary infections across differing life stages, and constitute a previously undetected threat to declining populations. Greater surveillance of parasite interactions may increase our capacity to contain and mitigate the impacts of these and other wildlife diseases. PMID:26726999

Characteristics of six small heat shock protein genes from Bactrocera dorsalis: Diverse expression under conditions of thermal stress and normal growth.

PubMed

Dou, Wei; Tian, Yi; Liu, Hong; Shi, Yan; Smagghe, Guy; Wang, Jin-Jun

2017-11-01

To explore the functions of small heat shock proteins (sHsps) in relation to thermal stress and development in Bactrocera dorsalis (Hendel), one of the most economically important pest species attacking a wide range of fruits and vegetables, six full-length cDNAs of sHsp genes (BdHsp17.7, 18.4, 20.4, 20.6, 21.6 and 23.8) were cloned, and the expression patterns in different developmental stages and tissues, as well as in response to both thermal and 20-hydroxyecdysone (20E) exposures, were examined using real time quantitative PCR. The open reading frames (ORFs) of six sHsps are 453, 489, 537, 543, 567 and 630bp in length, encoding proteins with molecular weights of 17.7, 18.4, 20.4, 20.6, 21.6 and 23.8kDa, respectively. BdHsp18.4 and BdHsp20.4 maintained lower expression levels in both eggs and larvae, whereas remarkably up-regulated after the larval-pupal transformation, suggesting that these two sHsps may be involved in metamorphosis. Significant tissue specificity exists among sHsps: the highest expression of BdHsp20.6 and BdHsp23.8 in the Malpighian tubules and ovary, respectively, versus a peak in the fat body for others. BdHsp20.4 and BdHsp20.6 were significantly up-regulated by thermal stress. In contrast, BdHsp18.4 and BdHsp23.8 reacted only to heat stress. BdHsp17.7 and BdHsp21.6 were insensitive to both heat and cold stresses. The degree of sHsps response depends on intensity of 20E treatment, i.e., dose and time. These results strongly suggest functional differentiation within the sHsp subfamily in B. dorsalis. The physiological function of sHsp members under thermal stress and normal growth remains the subjects of further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Widespread Occurrence of Bd in French Guiana, South America

PubMed Central

Courtois, Elodie A.; Gaucher, Philippe; Chave, Jérôme; Schmeller, Dirk S.

2015-01-01

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is a purported agent of decline and extinction of many amphibian populations worldwide. Its occurrence remains poorly documented in many tropical regions, including the Guiana Shield, despite the area’s high amphibian diversity. We conducted a comprehensive assessment of Bd in French Guiana in order to (1) determine its geographical distribution, (2) test variation of Bd prevalence among species in French Guiana and compare it to earlier reported values in other South American anuran species (http://www.bd-maps.net; 123 species from 15 genera) to define sentinel species for future work, (3) track changes in prevalence through time and (4) determine if Bd presence had a negative effect on one selected species. We tested the presence of Bd in 14 species at 11 sites for a total of 1053 samples (306 in 2009 and 747 in 2012). At least one Bd-positive individual was found at eight out of 11 sites, suggesting a wide distribution of Bd in French Guiana. The pathogen was not uniformly distributed among the studied amphibian hosts, with Dendrobatidae species displaying the highest prevalence (12.4%) as compared to Bufonidae (2.6 %) and Hylidae (1.5%). In contrast to earlier reported values, we found highest prevalence for three Dendrobatidae species and two of them displayed an increase in Bd prevalence from 2009 to 2012. Those three species might be the sentinel species of choice for French Guiana. For Dendrobates tinctorius, of key conservation value in the Guiana Shield, smaller female individuals were more likely to be infected, suggesting either that frogs can outgrow their chytrid infections or that the disease induces developmental stress limiting growth. Generally, our study supports the idea that Bd is more widespread than previously thought and occurs at remote places in the lowland forest of the Guiana shield. PMID:25902035

Bipolar disorder and complementary medicine: current evidence, safety issues, and clinical considerations.

PubMed

Sarris, Jerome; Lake, James; Hoenders, Rogier

2011-10-01

Bipolar disorder (BD) is a debilitating syndrome that is often undiagnosed and undertreated. Population surveys show that persons with BD often self-medicate with complementary and alternative medicine (CAM) or integrative therapies in spite of limited research evidence supporting their use. To date, no review has focused specifically on nonconventional treatments of BD. The study objectives were to present a review of nonconventional (complementary and integrative) interventions examined in clinical trials on BD, and to offer provisional guidelines for the judicious integrative use of CAM in the management of BD. PubMed, CINAHL,(®) Web of Science, and Cochrane Library databases were searched for human clinical trials in English during mid-2010 using Bipolar Disorder and CAM therapy and CAM medicine search terms. Effect sizes (Cohen's d) were also calculated where data were available. Several positive high-quality studies on nutrients in combination with conventional mood stabilizers and antipsychotic medications in BD depression were identified, while branched-chain amino acids and magnesium were effective (small studies) in attenuating mania in BD. In the treatment of bipolar depression, evidence was mixed regarding omega-3, while isolated studies provide provisional support for a multinutrient formula, n-acetylcysteine, and l-tryptophan. In one study, acupuncture was found to have favorable but nonsignificant effects on mania and depression outcomes. Current evidence supports the integrative treatment of BD using combinations of mood stabilizers and select nutrients. Other CAM or integrative modalities used to treat BD have not been adequately explored to date; however, some early findings are promising. Select CAM and integrative interventions add to established conventional treatment of BD and may be considered when formulating a treatment plan. It is hoped that the safety issues and clinical considerations addressed in this article may encourage the practice of safety-conscious and evidence-based integrative management of BD.

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts.

PubMed

Wilcox, Holly C; Fullerton, Janice M; Glowinski, Anne L; Benke, Kelly; Kamali, Masoud; Hulvershorn, Leslie A; Stapp, Emma K; Edenberg, Howard J; Roberts, Gloria M P; Ghaziuddin, Neera; Fisher, Carrie; Brucksch, Christine; Frankland, Andrew; Toma, Claudio; Shaw, Alex D; Kastelic, Elizabeth; Miller, Leslie; McInnis, Melvin G; Mitchell, Philip B; Nurnberger, John I

2017-12-01

Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Behçet's disease.

PubMed

Lee, Kwang Hoon; Chung, Hae-Shin; Kim, Hyoung Sup; Oh, Sang-Ho; Ha, Moon-Kyung; Baik, Ja-Hyun; Lee, Sungnack; Bang, Dongsik

2003-07-01

To identify and recombine a protein of the human dermal microvascular endothelial cell (HDMEC) that specifically reacts with anti-endothelial cell antibody (AECA) in the serum of patients with Behçet's disease (BD), and to evaluate the usefulness of this protein in BD. The proteomics technique, with 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry, was used to identify and recombine HDMEC antigen. Western blotting and enzyme-linked immunosorbent assay (ELISA) of recombinant protein isolated by gene cloning were performed on serum from healthy controls, patients with BD, and patients with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, and Wegener's granulomatosis). Eighteen of 40 BD patients had serum IgM antibody to HDMEC antigen. The purified protein that reacted with AECA in BD patient sera was found to be alpha-enolase by 2-dimensional gel electrophoresis followed by immunoblotting and MALDI-TOF mass spectrometry. Recombinant alpha-enolase protein was isolated and refined by gene cloning. On Western blots, AECA-positive IgM from the sera of patients with active BD reacted strongly with recombinant human alpha-enolase. BD patient sera positive for anti-alpha-enolase did not react with human gamma-enolase. On dot-blotting, reactivity to human alpha-enolase was detected only in the IgM-positive group. Fifteen of the 18 AECA-positive sera that were positive for the HDMEC antigen showed reactivity to recombinant alpha-enolase IgM antibody by ELISA. The alpha-enolase protein is the target protein of serum AECA in BD patients. This is the first report of the presence of IgM antibodies to alpha-enolase in endothelial cells from the serum of BD patients. Although further studies relating this protein to the pathogenesis of BD will be necessary, alpha-enolase and its antibody may prove useful in the development of new diagnostic and treatment modalities in BD.

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. © Copyright 2017 Physicians Postgraduate Press, Inc.

Bipolar obsessive-compulsive disorder and personality disorders.

PubMed

Maina, Giuseppe; Albert, Umberto; Pessina, Enrico; Bogetto, Filippo

2007-11-01

Relatively few systematic data exist on the clinical impact of bipolar comorbidity in obsessive-compulsive disorder (OCD) and no studies have investigated the influence of such a comorbidity on the prevalence and pattern of Axis II comorbidity. The aim of the present study was to explore the comorbidity of personality disorders in a group of patients with OCD and comorbid bipolar disorder (BD). The sample consisted of 204 subjects with a principal diagnosis of OCD (DSM-IV) and a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score>or=16 recruited from all patients consecutively referred to the Anxiety and Mood Disorders Unit, Department of Neuroscience, University of Turin over a period of 5 years (January 1998-December 2002). Diagnostic evaluation and Axis I comorbidities were collected by means of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Personality status was assessed by using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II). Socio-demographic and clinical features (including Axis II comorbidities) were compared between OCD patients with and without a lifetime comorbidity of BD. A total of 21 patients with OCD (10.3%) met DSM-IV criteria for a lifetime BD diagnosis: 4 (2.0%) with BD type I and 17 (8.3%) with BD type II. Those without a BD diagnosis showed significantly higher rates of male gender, sexual and hoarding obsessions, repeating compulsions and lifetime comorbid substance use disorders, when compared with patients with BD/OCD. With regard to personality disorders, those with BD/OCD showed higher prevalence rates of Cluster A (42.9% versus 21.3%; p=0.027) and Cluster B (57.1% versus 29.0%; p=0.009) personality disorders. Narcissistic and antisocial personality disorders were more frequent in BD/OCD. Our results point towards clinically relevant effects of comorbid BD on the personality profiles of OCD patients, with higher rates of narcissistic and antisocial personality disorders in BD/OCD patients.

Prospective progression from high-prevalence disorders to bipolar disorder: Exploring characteristics of pre-illness stages.

PubMed

Ratheesh, Aswin; Cotton, Susan M; Betts, Jennifer K; Chanen, Andrew; Nelson, Barnaby; Davey, Christopher G; McGorry, Patrick D; Berk, Michael; Bechdolf, Andreas

2015-09-01

Identification of risk factors within precursor syndromes, such as depression, anxiety or substance use disorders (SUD), might help to pinpoint high-risk stages where preventive interventions for Bipolar Disorder (BD) could be evaluated. We examined baseline demographic, clinical, quality of life, and temperament measures along with risk clusters among 52 young people seeking help for depression, anxiety or SUDs without psychosis or BD. The risk clusters included Bipolar At-Risk (BAR) and the Bipolarity Index as measures of bipolarity and the Ultra-High Risk assessment for psychosis. The participants were followed up for 12 months to identify conversion to BD. Those who converted and did not convert to BD were compared using Chi-Square and Mann Whitney U tests. The sample was predominantly female (85%) and a majority had prior treatment (64%). Four participants converted to BD over the 1-year follow up period. Having an alcohol use disorder at baseline (75% vs 8%, χ(2)=14.1, p<0.001) or a family history of SUD (67% vs 12.5%, χ(2)=6.0, p=0.01) were associated with development of BD. The sub-threshold mania subgroup of BAR criteria was also associated with 12-month BD outcomes. The severity of depressive symptoms and cannabis use had high effects sizes of association with BD outcomes, without statistical significance. The small number of conversions limited the power of the study to identify associations with risk factors that have previously been reported to predict BD. However, subthreshold affective symptoms and SUDs might predict the onset of BD among help-seeking young people with high-prevalence disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder.

PubMed

Hassel, Stefanie; Almeida, Jorge R; Frank, Ellen; Versace, Amelia; Nau, Sharon A; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

2009-11-01

The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BD individuals. Small sample size of predominantly medicated BD individuals. This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD.

Nothing a Hot Bath Won't Cure: Infection Rates of Amphibian Chytrid Fungus Correlate Negatively with Water Temperature under Natural Field Settings

PubMed Central

2011-01-01

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10–50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75–100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications. There must be quite a few things a hot bath won't cure, but I don't know many of them - Sylvia Plath, “The Bell Jar” (1963). PMID:22205950

Neurocognitive functioning in individuals with bipolar disorder and their healthy siblings: a preliminary study

PubMed Central

Bauer, Isabelle E.; Wu, Mon-Ju; Frazier, T.W.; Mwangi, Benson; Spiker, Danielle; Zunta-Soares, Giovana B.; Soares, Jair C.

2016-01-01

Background Cognitive deficits have been consistently reported in individuals with bipolar disorder (BD). The cognitive profile of siblings of individuals with BD is, however, less clearly established possibly due to the heterogeneity of neuropsychological measures used in previous studies. The aim of this exploratory study was to assess the cognitive function of siblings of individuals with BD and compare it with that of their first-degree relatives suffering with BD, and healthy controls (HC) using the Cambridge Neuropsychological Test Automated Battery (CANTAB) - a comprehensive and validated computerized cognitive battery. Methods We recruited 23 HC (33.52±10.29 years, 8 males), 27 individuals with BD (34.26±10.19 years, 9 males, 25 BDI, 1BDII and 1 BD-NOS), and 15 of their biologically related siblings (37.47±13.15 years, 4 males). Siblings had no current or lifetime history of mental disorders. Participants performed the CANTAB and completed questionnaires assessing mood and global functioning. Multivariate analyses compared CANTAB measures across the three participant groups. Results Individuals with BD and their siblings were less accurate in a task of sustained attention (Rapid Visual Processing) when compared to HC. Further, individuals with BD displayed pronounced deficits in affective processing (Affective Go/No-Go) compared to HC. There were no cognitive differences between siblings and individuals with BD. After correcting for current depressive symptoms, these results did not reach statistical significance. Conclusions Subthreshold depressive symptoms may be associated with reduced sustained attention in healthy siblings of BD patients. This preliminary result needs to be corroborated by large-scale, longitudinal studies assessing the relationship between cognition and mood in vulnerable individuals. PMID:27179338

DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects.

PubMed

Polesello, Vania; Zupin, Luisa; Di Lenarda, Roberto; Biasotto, Matteo; Pozzato, Gabriele; Ottaviani, Giulia; Gobbo, Margherita; Crovella, Sergio; Segat, Ludovica

2017-01-01

The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP. We analysed three DEFB1 polymorphisms at 5' UTR, -52G>A (rs1799946), -44C>G (rs1800972), -20G>A (rs11362) and two DEFB1 polymorphisms at 3'UTR, c*5G>A (rs1047031), c*87A>G (rs1800971), with the aim of correlating these genetic variants and hBD-1 salivary level in a group of OLP patients and in healthy subjects. We also evaluated hBD-1 salivary concentrations, using ELISA, in OLP and healthy controls. We compared hBD-1 concentrations in OLP and healthy subjects: hBD-1 concentration was significantly higher in OLP patients respect to control. When considering the correlation between DEFB1 polymorphisms genotypes and hBD-1 expression levels, significant results were obtained for SNPs -52G>A (p=0.03 both in OLP patients and healthy individuals) and -44C>G (p=0.02 in OLP patients). hBD-1 production was different between OLP and healthy subjects (not age-matched with OLP). DEFB1 gene polymorphisms, -52G>A and -44C>G, correlated with hBD-1 salivary concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calcium Channel Genes Associated with Bipolar Disorder Modulate Lithium's Amplification of Circadian Rhythms

PubMed Central

McCarthy, Michael J.; LeRoux, Melissa; Wei, Heather; Beesley, Stephen; Kelsoe, John R.; Welsh, David K.

2015-01-01

Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells. We used fluorescent dyes to measure Ca2+ changes in BD and control fibroblasts after lithium treatment, and bioluminescent reporters to measure Per2∷luc rhythms in fibroblasts from BD patients, human controls, and mice while pharmacologically or genetically manipulating calcium channels. Longitudinal expression of LTCC genes (CACNA1C, CACNA1D and CACNB3) was then measured over 12-24 hr in BD and control cells. Our results indicate that independently of LTCCs, lithium stimulated intracellular Ca2+ less effectively in BD vs. control fibroblasts. In longitudinal studies, pharmacological inhibition of LTCCs or knockdown of CACNA1A, CACNA1C, CACNA1D and CACNB3 altered circadian rhythm amplitude. Diltiazem and knockdown of CACNA1C or CACNA1D eliminated lithium's ability to amplify rhythms. Knockdown of CACNA1A or CACNB3 altered baseline rhythms, but did not affect rhythm amplification by lithium. In human fibroblasts, CACNA1C genotype predicted the amplitude response to lithium, and the expression profiles of CACNA1C, CACNA1D and CACNB3 were altered in BD vs. controls. We conclude that in cells from BD patients, calcium signaling is abnormal, and that LTCCs underlie the failure of lithium to amplify circadian rhythms. PMID:26476274

An investigation of mental imagery in bipolar disorder: Exploring "the mind's eye".

PubMed

Di Simplicio, Martina; Renner, Fritz; Blackwell, Simon E; Mitchell, Heather; Stratford, Hannah J; Watson, Peter; Myers, Nick; Nobre, Anna C; Lau-Zhu, Alex; Holmes, Emily A

2016-12-01

Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non-clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders. Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non-clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non-emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery. (i) Compared to non-clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and "real" negative images (prospective imagery task), and higher self-involvement (picture-word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained-across all groups, imagery differences were associated with affective lability and anxiety. Compared to non-clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD-rather, imagery may reflect a transdiagnostic marker of emotional psychopathology. © 2016 Medical Research Council. Bipolar Disorders Published by John Wiley & Sons Ltd.

Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma Staging.

PubMed

Saldanha, Gerald; Yarrow, Jeremy; Pancholi, Jay; Flatman, Katarina; Teo, Kah Wee; Elsheik, Somaia; Harrison, Rebecca; O'Riordan, Marie; Bamford, Mark

2018-06-01

Histomorphologic prognostic biomarkers that can be measured using only an hematoxylin and eosin stain are very attractive because they are simple and cheap. We conceived an entirely novel biomarker of this type, the Breslow density (BD), which measures invasive melanoma cell density at the site where Breslow thickness (BT) is measured. This study assessed BD's prognostic value. In this study, BD was measured in 1329 melanoma patients. Measurement accuracy and precision was assessed using intraclass correlation coefficient (ICC). Survival was assessed with a primary end-point of melanoma-specific survival (MSS) and also overall survival and metastasis-free survival. We found that BD measurement was accurate compared with gold standard image analysis (ICC, 0.84). Precision was excellent for 3 observers with different experience (ICC, 0.93) and for an observer using only written instructions (ICC, 0.93). BD was a highly significant predictor in multivariable analysis for overall survival, MSS, and metastasis-free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD together had best explanatory capability. A BD cut point of ≥65% was trained in 970 melanomas and validated in 359. This cut point showed promise as a novel way to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a targeted burden score. This was a validated as an adjunct to American Joint Committee on Cancer stage. In summary, BD can be measured accurately and precisely. It demonstrated independent prognostic value and explained MSS better than BT alone. Notably, we demonstrated ways that BD could be used with American Joint Committee on Cancer version 8 staging.

The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication.

PubMed

Sundaresh, Aparna; Wu, Ching-Lien; Chinnadurai, Raj Kumar; Rajkumar, Ravi Philip; Mariaselvam, Christina Mary; LeMaoult, Joël; Krishnamoorthy, Rajagopal; Leboyer, Marion; Negi, Vir Singh; Tamouza, Ryad

2018-05-08

Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection. Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC. Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.

Interactions between amphibians' symbiotic bacteria cause the production of emergent anti-fungal metabolites

PubMed Central

Loudon, Andrew H.; Holland, Jessica A.; Umile, Thomas P.; Burzynski, Elizabeth A.; Minbiole, Kevin P. C.; Harris, Reid N.

2014-01-01

Amphibians possess beneficial skin bacteria that protect against the disease chytridiomycosis by producing secondary metabolites that inhibit the pathogen Batrachochytrium dendrobatidis (Bd). Metabolite production may be a mechanism of competition between bacterial species that results in host protection as a by-product. We expect that some co-cultures of bacterial species or strains will result in greater Bd inhibition than mono-cultures. To test this, we cultured four bacterial isolates (Bacillus sp., Janthinobacterium sp., Pseudomonas sp. and Chitinophaga arvensicola) from red-backed salamanders (Plethodon cinereus) and cultured isolates both alone and together to collect their cell-free supernatants (CFS). We challenged Bd with CFSs from four bacterial species in varying combinations. This resulted in three experimental treatments: (1) CFSs of single isolates; (2) combined CFSs of two isolates; and (3) CFSs from co-cultures. Pair-wise combinations of four bacterial isolates CFSs were assayed against Bd and revealed additive Bd inhibition in 42.2% of trials, synergistic inhibition in 42.2% and no effect in 16.6% of trials. When bacteria isolates were grown in co-cultures, complete Bd inhibition was generally observed, and synergistic inhibition occurred in four out of six trials. A metabolite profile of the most potent co-culture, Bacillus sp. and Chitinophaga arvensicola, was determined with LC-MS and compared with the profiles of each isolate in mono-culture. Emergent metabolites appearing in the co-culture were inhibitory to Bd, and the most potent inhibitor was identified as tryptophol. Thus mono-cultures of bacteria cultured from red-backed salamanders interacted synergistically and additively to inhibit Bd, and such bacteria produced emergent metabolites when cultured together, with even greater pathogen inhibition. Knowledge of how bacterial species interact to inhibit Bd can be used to select probiotics to provide amphibians with protection against Bd. PMID:25191317

Disinhibition of the extracellular-signal-regulated kinase restores the amplification of circadian rhythms by lithium in cells from bipolar disorder patients.

PubMed

McCarthy, Michael J; Wei, Heather; Landgraf, Dominic; Le Roux, Melissa J; Welsh, David K

2016-08-01

Bipolar disorder (BD) is characterized by depression, mania, and circadian rhythm abnormalities. Lithium, a treatment for BD stabilizes mood and increases circadian rhythm amplitude. However, in fibroblasts grown from BD patients, lithium has weak effects on rhythm amplitude compared to healthy controls. To understand the mechanism by which lithium differentially affects rhythm amplitude in BD cells, we investigated the extracellular-signal-regulated kinase (ERK) and related signaling molecules linked to BD and circadian rhythms. In fibroblasts from BD patients, controls and mice, we assessed the contribution of the ERK pathway to lithium-induced circadian rhythm amplification. Protein analyses revealed low phospho-ERK1/2 (p-ERK) content in fibroblasts from BD patients vs. Pharmacological inhibition of ERK1/2 by PD98059 attenuated the rhythm amplification effect of lithium, while inhibition of two related kinases, c-Jun N-terminal kinase (JNK), and P38 did not. Knockdown of the transcription factors CREB and EGR-1, downstream effectors of ERK1/2, reduced baseline rhythm amplitude, but did not alter rhythm amplification by lithium. In contrast, ELK-1 knockdown amplified rhythms, an effect that was not increased further by the addition of lithium, suggesting this transcription factor may regulate the effect of lithium on amplitude. Augmentation of ERK1/2 signaling through DUSP6 knockdown sensitized NIH3T3 cells to rhythm amplification by lithium. In BD fibroblasts, DUSP6 knockdown reversed the BD rhythm phenotype, restoring the ability of lithium to increase amplitude in these cells. We conclude that the inability of lithium to regulate circadian rhythms in BD may reflect reduced ERK activity, and signaling through ELK-1. Published by Elsevier B.V.

Multisite evaluation of the BD™ Stem Cell Enumeration (SCE) Kit for CD34+ cell enumeration on the BD FACSCanto II™ and BD FACSCalibur™ flow cytometers

PubMed Central

Preti, Robert A; Chan, Wai Shun; Kurtzberg, Joanne; Dornsife, Ronna E.; Wallace, Paul K.; Furlange, Rosemary; Lin, Anna; Omana-Zapata, Imelda; Bonig, Halvard; Tonn, Thorsten

2018-01-01

Background Evaluation of the BD™ Stem Cell Enumeration (SCE) Kit was conducted at four clinical sites with flow cytometry CD34+ enumeration, to assess agreement between two investigational methods, the BD FACSCanto™ II and BD FACSCalibur™ systems, and the predicate method (Beckman Coulter Stem-Kit™ reagents). Methods Leftover and delinked specimens (n = 1,032) from clinical flow cytometry testing were analyzed on the BD FACSCanto II (n = 918) and BD FACSCalibur (n = 905) in normal and mobilized blood, frozen and thawed bone marrow, and leucopheresis and cord blood anticoagulated with CPD, ACD-A, heparin, and EDTA alone or in combination. Fresh leucopheresis analysis addressed site equivalency for sample preparation, testing, and analysis. Results The mean relative bias showed agreement within predefined parameters for the BD FACSCanto II (−2.81 to 4.31 ±7.1) and BD FACSCalibur (−2.69 to 5.2 ±7.9). Results are reported as absolute and relative differences compared to the predicate for viable CD34+, percentage of CD34+ in CD45+, and viable CD45+ populations (or gates). Bias analyses of the distribution of the predicate low, mid, and high bin values were done using BD FACSCanto II optimal gating and BD FACSCalibur manual gating for viable CD34+, percentage of CD34+ in CD45+, and viable CD45+. Bias results from both investigational methods show agreement. Deming regression analyses showed a linear relationship with R2 >0.92 for both investigational methods. Discussion In conclusion, the results from both investigational methods demonstrated agreement and equivalence with the predicate method for enumeration of absolute viable CD34+, percentage of viable CD34+ in CD45+, and absolute viable CD45+ populations. PMID:24927716

A common variant of staphylococcal cassette chromosome mec type IVa in isolates from Copenhagen, Denmark, is not detected by the BD GeneOhm methicillin-resistant Staphylococcus aureus assay.

PubMed

Bartels, Mette Damkjaer; Boye, Kit; Rohde, Susanne Mie; Larsen, Anders Rhod; Torfs, Herbert; Bouchy, Peggy; Skov, Robert; Westh, Henrik

2009-05-01

Rapid tests for detection of methicillin-resistant Staphylococcus aureus (MRSA) carriage are important to limit the transmission of MRSA in the health care setting. We evaluated the performance of the BD GeneOhm MRSA real-time PCR assay using a diverse collection of MRSA isolates, mainly from Copenhagen, Denmark, but also including international isolates, e.g., USA100-1100. Pure cultures of 349 MRSA isolates representing variants of staphylococcal cassette chromosome mec (SCCmec) types I to V and 103 different staphylococcal protein A (spa) types were tested. In addition, 53 methicillin-susceptible Staphylococcus aureus isolates were included as negative controls. Forty-four MRSA isolates were undetectable; of these, 95% harbored SCCmec type IVa, and these included the most-common clone in Copenhagen, spa t024-sequence type 8-IVa. The false-negative MRSA isolates were tested with new primers (analyte-specific reagent [ASR] BD GeneOhm MRSA assay) supplied by Becton Dickinson (BD). The ASR BD GeneOhm MRSA assay detected 42 of the 44 isolates that were false negative in the BD GeneOhm MRSA assay. Combining the BD GeneOhm MRSA assay with the ASR BD GeneOhm MRSA assay greatly improved the results, with only two MRSA isolates being false negative. The BD GeneOhm MRSA assay alone is not adequate for MRSA detection in Copenhagen, Denmark, as more than one-third of our MRSA isolates would not be detected. We recommend that the BD GeneOhm MRSA assay be evaluated against the local MRSA diversity before being established as a standard assay, and due to the constant evolution of SCCmec cassettes, a continuous global surveillance is advisable in order to update the assay as necessary.

Behçet's disease and hereditary periodic fever syndromes: casual association or causal relationship?

PubMed

Espinosa, G; Arostegui, J I; Plaza, S; Rius, J; Cervera, R; Yagüe, J; Font, J

2005-01-01

Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean fever (FMF) and TNF receptor-associated periodic syndrome (TRAPS), respectively. A higher prevalence of Behçet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF TRAPS and BD could be genetically related. We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes. The heterozygous MEFV mutation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF 1A gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation. Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.

Genome-wide identification, phylogenetic analysis, and expression profiles of ATP-binding cassette transporter genes in the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).

PubMed

Xiao, Lin-Fan; Zhang, Wei; Jing, Tian-Xing; Zhang, Meng-Yi; Miao, Ze-Qing; Wei, Dan-Dan; Yuan, Guo-Rui; Wang, Jin-Jun

2018-03-01

The ATP-binding cassette (ABC) is the largest transporter gene family and the genes play key roles in xenobiotic resistance, metabolism, and development of all phyla. However, the specific functions of ABC gene families in insects is unclear. We report a genome-wide identification, phylogenetic, and transcriptional analysis of the ABC genes in the oriental fruit fly, Bactrocera dorsalis (Hendel). We identified a total of 47 ABC genes (BdABCs) from the transcriptomic and genomic databases of B. dorsalis and classified these genes into eight subfamilies (A-H), including 7 ABCAs, 7 ABCBs, 9 ABCCs, 2 ABCDs, 1 ABCE, 3 ABCFs, 15 ABCGs, and 3 ABCHs. Comparative phylogenetic analysis of the ABCs suggests an orthologous relationship between B. dorsalis and other insect species in which these genes have been related to pesticide resistance and essential biological processes. Comparison of transcriptome and relative expression patterns of BdABCs indicated diverse multifunctions within different B. dorsalis tissues. The expression of 4, 10, and 14 BdABCs from 18 BdABCs was significantly upregulated after exposure to LD 50 s of malathion, avermectin, and beta-cypermethrin, respectively. The maximum expression level of most BdABCs (including BdABCFs, BdABCGs, and BdABCHs) occurred at 48h post exposures, whereas BdABCEs peaked at 24h after treatment. Furthermore, RNA interference-mediated suppression of BdABCB7 resulted in increased toxicity of malathion against B. dorsalis. These data suggest that ABC transporter genes might play key roles in xenobiotic metabolism and biosynthesis in B. dorsalis. Copyright © 2017 Elsevier Inc. All rights reserved.

Nothing a hot bath won't cure: infection rates of amphibian chytrid fungus correlate negatively with water temperature under natural field settings.

PubMed

Forrest, Matthew J; Schlaepfer, Martin A

2011-01-01

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10-50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75-100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications.There must be quite a few things a hot bath won't cure, but I don't know many of them--Sylvia Plath, "The Bell Jar" (1963).

Potential metabolomic biomarkers for reliable diagnosis of Behcet's disease using gas chromatography/ time-of-flight-mass spectrometry.

PubMed

Ahn, Joong Kyong; Kim, Jungyeon; Hwang, Jiwon; Song, Juhwan; Kim, Kyoung Heon; Cha, Hoon-Suk

2018-05-01

Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform. Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HCs) were performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (PLS-DA) model are R 2 X of 0.246, R 2 Y of 0.913 and Q 2 of 0.852, respectively, indicating strong explanation and prediction capabilities of the model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The PLS_DA model showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set. This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS. Copyright © 2017. Published by Elsevier SAS.

RVX-297- a novel BD2 selective inhibitor of BET bromodomains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kharenko, Olesya A., E-mail: olesya@zenithepigenetics.com; Gesner, Emily M.; Patel, Reena G.

Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. Wemore » demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains. - Highlights: • A novel inhibitor of BET bromodomains, RVX-297 is described. • The differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography are described. • RVX-297 preferentially binds to the BD2 domains of the BET bromodomains. • The structural and thermodynamic properties of the BD2 selective binding of RVX-297 are characterized.« less

A dual mechanism involved in membrane and nucleic acid disruption of AvBD103b, a new avian defensin from the king penguin, against Salmonella enteritidis CVCC3377.

PubMed

Teng, Da; Wang, Xiumin; Xi, Di; Mao, Ruoyu; Zhang, Yong; Guan, Qingfeng; Zhang, Jun; Wang, Jianhua

2014-10-01

The food-borne bacterial gastrointestinal infection is a serious public health threat. Defensins are evolutionarily conserved innate immune components with broad-spectrum antibacterial activity that do not easily induce resistance. AvBD103b, an avian defensin with potent activity against Salmonella enteritidis, was isolated from the stomach contents of the king penguin (Aptenodytes patagonicus). To elucidate further the antibacterial mechanism of AvBD103b, its effect on the S. enteritidis CVCC3377 cell membrane and intracellular DNA was researched. The cell surface hydrophobicity and a N-phenyl-1-naphthylamine uptake assay demonstrated that AvBD103b treatment increased the cell surface hydrophobicity and outer membrane permeability. Atomic absorption spectrometry, ultraviolet spectrophotometry, flow cytometry, and transmission electron microscopy (TEM) indicated that AvBD103b treatment can lead to the release of the cellular contents and cell death through damage of the membrane. DNA gel retardation and circular dichroism analysis demonstrated that AvBD103b interacted with DNA and intercalated into the DNA base pairs. A cell cycle assay demonstrated that AvBD103b affected cellular functions, such as DNA synthesis. Our results confirmed that AvBD103b exerts its antibacterial activity by damaging the cell membrane and interfering with intracellular DNA, ultimately causing cell death, and suggested that AvBD103b may be a promising candidate as an alternative to antibiotics against S. enteritidis.

Developmental differences according to age at onset in juvenile bipolar disorder.

PubMed

Masi, Gabriele; Perugi, Giulio; Millepiedi, Stefania; Mucci, Maria; Toni, Cristina; Bertini, Nicoletta; Pfanner, Chiara; Berloffa, Stefano; Pari, Cinzia

2006-12-01

This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

Short-Term Exposure to Warm Microhabitats Could Explain Amphibian Persistence with Batrachochytrium dendrobatidis

PubMed Central

Daskin, Joshua H.; Alford, Ross A.; Puschendorf, Robert

2011-01-01

Environmental conditions can alter the outcomes of symbiotic interactions. Many amphibian species have declined due to chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), but many others persist despite high Bd infection prevalence. This indicates that Bd's virulence is lower, or it may even be a commensal, in some hosts. In the Australian Wet Tropics, chytridiomycosis extirpated Litoria nannotis from high-elevation rain forests in the early 1990 s. Although the species is recolonizing many sites, no population has fully recovered. Litoria lorica disappeared from all known sites in the early 1990 s and was thought globally extinct, but a new population was discovered in 2008, in an upland dry forest habitat it shares with L. nannotis. All frogs of both species observed during three population censuses were apparently healthy, but most carried Bd. Frogs perch on sun-warmed rocks in dry forest streams, possibly keeping Bd infections below the lethal threshold attained in cooler rain forests. We tested whether short-term elevated temperatures can hamper Bd growth in vitro over one generation (four days). Simulating the temperatures available to frogs on strongly and moderately warmed rocks in dry forests, by incubating cultures at 33°C for one hour daily, reduced Bd growth below that of Bd held at 15°C constantly (representing rain forest habitats). Even small decreases in the exponential growth rate of Bd on hosts may contribute to the survival of frogs in dry forests. PMID:22028834

Short-term exposure to warm microhabitats could explain amphibian persistence with Batrachochytrium dendrobatidis.

PubMed

Daskin, Joshua H; Alford, Ross A; Puschendorf, Robert

2011-01-01

Environmental conditions can alter the outcomes of symbiotic interactions. Many amphibian species have declined due to chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), but many others persist despite high Bd infection prevalence. This indicates that Bd's virulence is lower, or it may even be a commensal, in some hosts. In the Australian Wet Tropics, chytridiomycosis extirpated Litoria nannotis from high-elevation rain forests in the early 1990 s. Although the species is recolonizing many sites, no population has fully recovered. Litoria lorica disappeared from all known sites in the early 1990 s and was thought globally extinct, but a new population was discovered in 2008, in an upland dry forest habitat it shares with L. nannotis. All frogs of both species observed during three population censuses were apparently healthy, but most carried Bd. Frogs perch on sun-warmed rocks in dry forest streams, possibly keeping Bd infections below the lethal threshold attained in cooler rain forests. We tested whether short-term elevated temperatures can hamper Bd growth in vitro over one generation (four days). Simulating the temperatures available to frogs on strongly and moderately warmed rocks in dry forests, by incubating cultures at 33°C for one hour daily, reduced Bd growth below that of Bd held at 15°C constantly (representing rain forest habitats). Even small decreases in the exponential growth rate of Bd on hosts may contribute to the survival of frogs in dry forests.

Cerebral Oximetry as an Auxiliary Diagnostic Tool in the Diagnosis of Brain Death.

PubMed

Tatli, O; Bekar, O; Imamoglu, M; Gonenc Cekic, O; Aygun, A; Eryigit, U; Karaca, Y; Sahin, A; Turkmen, S; Turedi, S

2017-10-01

To investigate the efficacy of cerebral oximetry (CO) as an auxiliary diagnostic tool in brain death (BD). This observational case-control study was performed on patients with suspected BD. Patients with diagnosis of BD confirmed by the brain death committee were enrolled as the BD group and other patients as the non-BD group. CO monitoring was performed at least 6 h, and cerebral tissue oxygen saturation (ScO 2 ) parameters were compared. Mean ScO 2 level in the BD group was lower than non-brain-dead patients: mean difference for right lobe = 6.48 (95% confidence interval [CI] 0.08-12.88) and for left lobe = 6.09 (95% CI -0.22-12.41). Maximum ScO 2 values in the BD group were significantly lower than the non-BD group: mean difference for right lobe = 8.20 (95% CI 1.64-14.77) and for left lobe = 9.54 (95% CI 3.06-16.03). The area under the curve for right lobe maximum ScO 2 was 0.69 (95% CI 0.55-0.81) and for left lobe was 0.72 (95% CI 0.58-0.84). Maximum ScO 2 in brain-dead patients at CO monitoring is significantly low. However, this cannot be used to differentiate brain-dead and non-brain-dead patients. CO monitoring is therefore not an appropriate auxiliary diagnostic tool for confirming BD. Copyright © 2017 Elsevier Inc. All rights reserved.

Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders.

PubMed

Geoffroy, Pierre Alexis; Etain, Bruno; Franchi, Jean-Arthur Micoulaud; Bellivier, Frank; Ritter, Philipp

2015-01-01

Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate the routine use of melatonin-agonists in the treatment of BD.

The effect of brain death and coma on gastric myoelectrical activity.

PubMed

Bor, Canan; Bordin, Dmitry; Demirag, Kubilay; Uyar, Mehmet

2016-05-01

Gastrointestinal motility problems and delayed gastric emptying in patients admitted to intensive care units are important because they can contribute to different problems. Herein we aimed to measure the changes in gastric myoelectrical activity with electrogastrography (EGG) following brain death (BD) and compare the results to those from patients in a deep coma without BD. Fifteen patients with BD and nine in a deep coma with a Glasgow Coma Score from 3 to 8 were included. An enteral nutrition solution was given via a nasogastric tube between 45 min of fasting and the postprandial periods. The mean dominant frequency (MnDF), normal gastric slow wave ratio (%), tachygastria and bradygastria (%), power ratio (PR: dominant power after test meal/fasting), and dominant frequency instability coefficient were evaluated. The median of MnDF was determined 3.20±0.6 (BD) vs 3.05±0.5 (control), p>0.05. Patients with BD displayed tachygastria, particularly during the fasting state, with this disturbance decreasing during the postprandial period (from 41% to 15%). However, none of the differences between the groups were statistically significant. PR was pathologic in 4/15 (26.7%) patients in the BD group and 4/9 (44.4%) patients in the control group (p=0.288). Patients with coma or BD bouth might have gastric myoelectrical activity disturbances. BD does not show more severe disturbance than coma wihouth BD. EGG might be useful as a non-invasive and easy-to-use technology; however, it needs further improvement.

Attachment styles and psychopathology among adolescent children of parents with bipolar disorder.

PubMed

Erkan, Mustafa; Gencoglan, Salih; Akguc, Leyla; Ozatalay, Esin; Fettahoglu, Emine Cigil

2015-04-16

The aim of this study was to compare attachment styles and psychopathology in adolescent children of parents with bipolar disorder (BD) with a healthy control group. We studied 25 adolescents who had at least 1 parent with BD (BD group) and 28 adolescents who had no parents with BD (control group). The adolescent participants were between the ages of 12 and 17 years. We used the Adolescent Relationship Scales Questionnaire (A-RSQ) for the adolescents in the BD vs. control groups, and we used the Schedule for Affective Disorders and Schizophrenia for School-age Children - present and lifetime version (K-SADS-PL). We used the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Clinician Version for each parent of adolescents in the BD and control groups to rule out psychopathologies. Attachment styles of participants were assessed according to A-RSQ, dismissing attachment style scores of adolescents in BD group were found significantly higher compared to the healthy control group (p<0.05). As a result of the assessments, 12 adolescents (48%) out of 25 in the BD group and 5 adolescents (18%) out of 28 in the control group were given DSM-IV Axis I diagnosis, which is a statistically significant result (p<0.05). However, when psychiatric diagnoses were assessed separately, the difference was not statistically significant. We found that the adolescent children of parents with BD have increased risk of developing mental illnesses, and that these adolescents adopt dismissing attachment styles.

[Evaluation of medical students knowledge on brain death].

PubMed

Bitencourt, Almir Galvão Vieira; Neves, Flávia Branco Cerqueira Serra; Durães, Larissa; Nascimento, Diego Teixeira; Neves, Nedy Maria Branco Cerqueira; Torreão, Lara de Araújo; Agareno, Sydney

2007-06-01

Because brain death (BD) is a new concept and little divulged, it’s not well accepted in general population, including doctors and Medical students. This study aims to evaluate the knowledge of a sample of Medical students on the Brazilian BD diagnosis protocol. Descriptive cross-sectional survey that evaluated students from two medical schools in Salvador-BA. We used a questionnaire composed by questions about technical and ethical knowledge contained in the Federal Council of Medicine’s Resolution nº 1480/97 that establishes the criteria for BD diagnosis. We evaluated 115 Medical students. In 14 questions about the knowledge of BD criteria, the mean of right answers were 6.7 ± 1.8, which were higher among the students that had attended some presentation on BD. Most of the students (87.4%) knew how to identify the candidates to the BD diagnosis protocol. However, only 5.2% and 16.1% of the students answered right, respectively, the clinical and complementary tests that should be accomplished during the diagnosis protocol. Facing a no-donor patient with confirmed diagnosis of BD, 66.4% referred that artificial life support should be suspended. Only 15% of the interviewed students had already evaluated a patient with BD, being this percentage higher among those who had already frequented ICU (38.2% versus 5.1%; p < 0.001). The results of this study showed a limited knowledge of the evaluated students on BD diagnosis criteria, mainly in relation to the practical approach of this condition.

17 CFR 249.618 - Form BD-Y2K, information required of broker-dealers pursuant to section 17 of the Securities...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form BD-Y2K, information... Exchange Members, Brokers, and Dealers § 249.618 Form BD-Y2K, information required of broker-dealers... FR 37674, July 13, 1998] Editorial Note: For Federal Register citations affecting Form BD-Y2K, see...

Transformation From a Conventional Clinical Microbiology Laboratory to Full Automation.

PubMed

Moreno-Camacho, José L; Calva-Espinosa, Diana Y; Leal-Leyva, Yoseli Y; Elizalde-Olivas, Dolores C; Campos-Romero, Abraham; Alcántar-Fernández, Jonathan

2017-12-22

To validate the performance, reproducibility, and reliability of BD automated instruments in order to establish a fully automated clinical microbiology laboratory. We used control strains and clinical samples to assess the accuracy, reproducibility, and reliability of the BD Kiestra WCA, the BD Phoenix, and BD Bruker MALDI-Biotyper instruments and compared them to previously established conventional methods. The following processes were evaluated: sample inoculation and spreading, colony counts, sorting of cultures, antibiotic susceptibility test, and microbial identification. The BD Kiestra recovered single colonies in less time than conventional methods (e.g. E. coli, 7h vs 10h, respectively) and agreement between both methodologies was excellent for colony counts (κ=0.824) and sorting cultures (κ=0.821). Antibiotic susceptibility tests performed with BD Phoenix and disk diffusion demonstrated 96.3% agreement with both methods. Finally, we compared microbial identification in BD Phoenix and Bruker MALDI-Biotyper and observed perfect agreement (κ=1) and identification at a species level for control strains. Together these instruments allow us to process clinical urine samples in 36h (effective time). The BD automated technologies have improved performance compared with conventional methods, and are suitable for its implementation in very busy microbiology laboratories. © American Society for Clinical Pathology 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Dr Jekyll and Mrs Hyde: Risky hybrid sex by amphibian-parasitizing chytrids in the Brazilian Atlantic Forests.

PubMed

Ghosh, Pria; Fisher, Matthew C

2016-07-01

In their article in this issue of Molecular Ecology, Jenkinson et al. () and colleagues address a worrying question-how could arguably the most dangerous pathogen known to science, Batrachochytrium dendrobatidis (Bd), become even more virulent? The answer: start having sex. Jenkinson et al. present a case for how the introduction into Brazil of the globally invasive lineage of Bd, BdGPL, has disrupted the relationship between native amphibians and an endemic Bd lineage, BdBrazil. BdBrazil is hypothesized to be native to the Atlantic Forest and so have a long co-evolutionary history with biodiverse Atlantic Forest amphibian community. The authors suggest that this has resulted in a zone of hybrid Bd genotypes which are potentially more likely to cause fatal chytridiomycosis than either parent lineage. The endemic-nonendemic Bd hybrid genotypes described in this study, and the evidence for pathogen translocation via the global amphibian trade presented, highlights the danger of anthropogenic pathogen dispersal. This research emphasizes that biosecurity regulations may have to refocus on lineages within species if we are to mitigate against the danger of new, possibly hypervirulent genotypes of pathogens emerging as phylogeographic barriers are breached. © 2016 John Wiley & Sons Ltd.

Amphibian chytrid fungus (Batrachochytrium dendrobatidis) in coastal and montane California, USA Anurans

USGS Publications Warehouse

Fellers, Gary M.; Cole, Rebecca A.; Reinitz, David M.; Kleeman, Patrick M.

2011-01-01

We found amphibian chytrid fungus (Bd = Batrachochytrium dendrobatidis) to be widespread within a coastalwatershed at Point Reyes National Seashore, California and within two high elevation watersheds at Yosemite NationalPark, California. Bd was associated with all six species that we sampled (Bufo boreas, B. canorus, Pseudacris regilla, Ranadraytonii, R. sierrae, and Lithobates catesbeianus). For those species sampled at 10 or more sites within a watershed, thepercentage of Bd-positive sites varied from a low of 20.7% for P. regilla at one Yosemite watershed to a high of 79.6% forP. regilla at the Olema watershed at Point Reyes. At Olema, the percent of Bd-positive water bodies declined each year ofour study (2005-2007). Because P. regilla was the only species found in all watersheds, we used that species to evaluatehabitat variables related to the sites where P. regilla was Bd-positive. At Olema, significant variables were year, length ofshoreline (perimeter), percentage cover of rooted vegetation, and water depth. At the two Yosemite watersheds, waterdepth, water temperature, and silt/mud were the most important covariates, though the importance of these three factorsdiffered between the two watersheds. The presence of Bd in species that are not declining suggests that some of theamphibians in our study were innately resistant to Bd, or had developed resistance after Bd became established.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death.

PubMed

Salih, Farid; Holtkamp, Martin; Brandt, Stephan A; Hoffmann, Olaf; Masuhr, Florian; Schreiber, Stephan; Weissinger, Florian; Vajkoczy, Peter; Wolf, Stefan

2016-08-01

We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

PubMed

Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

2017-03-01

Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

Composition of symbiotic bacteria predicts survival in Panamanian golden frogs infected with a lethal fungus

PubMed Central

Becker, Matthew H.; Walke, Jenifer B.; Cikanek, Shawna; Savage, Anna E.; Mattheus, Nichole; Santiago, Celina N.; Minbiole, Kevin P. C.; Harris, Reid N.; Belden, Lisa K.; Gratwicke, Brian

2015-01-01

Symbiotic microbes can dramatically impact host health and fitness, and recent research in a diversity of systems suggests that different symbiont community structures may result in distinct outcomes for the host. In amphibians, some symbiotic skin bacteria produce metabolites that inhibit the growth of Batrachochytrium dendrobatidis (Bd), a cutaneous fungal pathogen that has caused many amphibian population declines and extinctions. Treatment with beneficial bacteria (probiotics) prevents Bd infection in some amphibian species and creates optimism for conservation of species that are highly susceptible to chytridiomycosis, the disease caused by Bd. In a laboratory experiment, we used Bd-inhibitory bacteria from Bd-tolerant Panamanian amphibians in a probiotic development trial with Panamanian golden frogs, Atelopus zeteki, a species currently surviving only in captive assurance colonies. Approximately 30% of infected golden frogs survived Bd exposure by either clearing infection or maintaining low Bd loads, but this was not associated with probiotic treatment. Survival was instead related to initial composition of the skin bacterial community and metabolites present on the skin. These results suggest a strong link between the structure of these symbiotic microbial communities and amphibian host health in the face of Bd exposure and also suggest a new approach for developing amphibian probiotics. PMID:25788591

Branched-chain Amino Acids are associated with Metabolic Parameters in Bipolar Disorder.

PubMed

Fellendorf, F T; Platzer, M; Pilz, R; Rieger, A; Kapfhammer, H P; Mangge, H; Dalkner, N; Zelzer, S; Meinitzer, A; Birner, A; Bengesser, S A; Queissner, R; Hamm, C; Hartleb, R; Reininghaus, E Z

2018-06-14

An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual's health state, given their influence on protein synthesis and gluconeogenesis inhibition. BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analyzed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters. BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton-Depression-Scale, and Beck-Depression-Inventory-II, in male individuals. Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases, insulin resistance), health-state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

PubMed

Serretti, Alessandro; Chiesa, Alberto; Calati, Raffaella; Linotte, Sylvie; Sentissi, Othman; Papageorgiou, Konstantinos; Kasper, Siegfried; Zohar, Joseph; De Ronchi, Diana; Mendlewicz, Julien; Amital, Daniela; Montgomery, Stuart; Souery, Daniel

2013-03-01

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

PubMed Central

Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

Daily temperature change in relation to the risk of childhood bacillary dysentery among different age groups and sexes in a temperate city in China.

PubMed

Li, K; Zhao, K; Shi, L; Wen, L; Yang, H; Cheng, J; Wang, X; Su, H

2016-02-01

In recent years, many studies have found that ambient temperature is significantly associated with bacillary dysentery (BD). However, there is limited evidence on the relationship between temperature and childhood BD in temperate areas. To investigate the relationship between daily mean temperature (MT) and childhood BD in China. Data on daily MT and childhood BD between 2006 and 2012 were collected from the Bureau of Meteorology and the Centre for Disease Control and Prevention in Hefei, Anhui Province, China. A Poisson generalized linear regression model combined with a distributed lag non-linear model was used to analyse the effects of temperature on childhood BD across different age and sex subgroups. An increase in temperature was significantly associated with childhood BD, and each 1 °C increase corresponded to an increase of 1.58% [95% confidence interval (CI) 0.46-2.71%] in the number of cases of BD. Children aged 0-5 years and girls were particularly sensitive to the effects of temperature. High temperatures may increase the risk of childhood BD in Hefei. Children aged 0-5 years and girls appear to be particularly sensitive to the effects of high temperature. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The utility of the Alcohol Use Disorders Identification Test (AUDIT)for the analysis of binge drinking in university students.

PubMed

Cortés Tomás, María T; Giménez Costa, José A; Motos-Sellés, Patricia; Sancerni Beitia, María D; Cadaveira Mahía, Fernando

2017-05-01

The increasingly precise conceptualization of Binge Drinking (BD), along with the rising incidence of this pattern of intake amongst young people, make it necessary to review the usefulness of instruments used to detect it. Little evidence exists regarding effectiveness of the AUDIT, AUDIT-C and AUDIT-3 in the detection of BD. This study evaluates their utility in a sample of university students, revealing the most appropriate cut-off points for each sex. All students self-administered the AUDIT and completed a self-report of their alcohol consumption. A Two-step cluster analysis differentiated 5 groups of BD in terms of: the quantity consumed, the frequency of BD over the past six months and gender. A ROC curve adjusted cut-off points for each case. 862 university students (18-19 years-old/59.5% female), 424 (49.2%) from Valencia and 438 (50.8%) from Madrid, had cut-off points of 4 in AUDIT and 3 in AUDIT-C as a better fit. In all cases, the best classifier was AUDIT-C. Neither version properly classifies students with varying degrees of BD. All versions differentiate BD from non-BD, but none are able to differentiate between types of BD.

Mean platelet volume in ocular Behçet's disease.

PubMed

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Cınar, Yasin; Akkurt, Meltem; Sahin, Muhammed; Ozkurt, Zeynep; Sahin, Alparslan; Caça, Ihsan

2013-01-01

To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). The study population was 30 newly diagnosed ocular BD patients who presented with active uveitis. These patients had no past history of smoking, drug use, or systemic diseases including diabetes mellitus, hypertension, cardiovascular disease, and renal disease. A control group consisting of 34 healthy individuals was included for comparison. MPV measurements were performed serially upon presentation with active uveitis and at one and three month thereafter in BD group whereas only at presentation in the controls. Upon presentation with active uveitis, the mean MPV levels were 7.88 ± 1.14 femtoliters (fL) for BD group. During the posttreatment follow-up period at first and third months, BD patients demonstrated a mean MPV level of 7.71 ± 1.12 fL and 7.65 ± 1.04 fL, respectively. The mean MPV value of control group, was 8.39 ± 0.66 fL at presentation. Fluctuations in MPV values were not significant in the BD group, while there was a significant difference between the initial measurements of the BD and control groups. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment.

Charm-beauty meson bound states from B (B*)D (D*) and B (B*)D \\xAF(D\\xAF*) interaction

NASA Astrophysics Data System (ADS)

Sakai, S.; Roca, L.; Oset, E.

2017-09-01

We evaluate the s -wave interaction of pseudoscalar and vector mesons with both charm and beauty to investigate the possible existence of molecular B D , B*D , B D*, B*D*, B D ¯, B*D ¯, B D¯*, or B*D¯* meson states. The scattering amplitude is obtained implementing unitarity starting from a tree level potential accounting for the dominant vector meson exchange. The diagrams are evaluated using suitable extensions to the heavy flavor sector of the hidden gauge symmetry Lagrangians involving vector and pseudoscalar mesons, respecting heavy quark spin symmetry. We obtain bound states at energies above 7 GeV for B D (JP=0+), B*D (1+), B D* (1+), and B*D* (0+, 1+, 2+), all in isospin 0. For B D ¯ (0+), B*D ¯ (1+), B D¯* (1+), and B*D¯* (0+, 1+, 2+) we also find similar bound states in I =0 , but much less bound, which would correspond to exotic meson states with b ¯ and c ¯ quarks, and for the I =1 we find a repulsive interaction. We also evaluate the scattering lengths in all cases, which can be tested in current investigations of lattice QCD.

Effects of ANK3 variation on gray and white matter in bipolar disorder.

PubMed

Lippard, E T C; Jensen, K P; Wang, F; Johnston, J A Y; Spencer, L; Pittman, B; Gelernter, J; Blumberg, H P

2017-09-01

The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

PubMed Central

Whalley, H C; Papmeyer, M; Sprooten, E; Romaniuk, L; Blackwood, D H; Glahn, D C; Hall, J; Lawrie, S M; Sussmann, Je; McIntosh, A M

2012-01-01

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD. PMID:22760554

Emotion perception and executive functioning predict work status in euthymic bipolar disorder.

PubMed

Ryan, Kelly A; Vederman, Aaron C; Kamali, Masoud; Marshall, David; Weldon, Anne L; McInnis, Melvin G; Langenecker, Scott A

2013-12-15

Functional recovery, including return to work, in Bipolar Disorder (BD) lags behind clinical recovery and may be incomplete when acute mood symptoms have subsided. We examined impact of cognition on work status and underemployment in a sample of 156 Euthymic-BD and 143 controls (HC) who were divided into working/not working groups. Clinical, health, social support, and personality data were collected, and eight cognitive factors were derived from a battery of neuropsychological tests. The HC groups outperformed the BD groups on seven of eight cognitive factors. The working-BD group outperformed the not working-BD group on 4 cognitive factors composed of tasks of emotion processing and executive functioning including processing speed and set shifting. Emotion processing and executive tasks were predictive of BD unemployment, after accounting for number of mood episodes. Four cognitive factors accounted for a significant amount of the variance in work status among the BD participants. Results indicate that patients with BD who are unemployed/unable to work exhibit greater difficulties processing emotional information and on executive tasks that comprise a set shifting or interference resolution component as compared to those who are employed, independent of other factors. These cognitive and affective factors are suggested as targets for treatment and/or accommodations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Care satisfaction, hope, and life functioning among adults with bipolar disorder: data from the first 1000 participants in the Systematic Treatment Enhancement Program.

PubMed

Morris, Chad D; Miklowitz, David J; Wisniewski, Stephen R; Giese, Alexis A; Thomas, Marshall R; Allen, Michael H

2005-01-01

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is designed to evaluate the longitudinal outcome of patients with bipolar disorder. The STEP-BD disease-management model is built on evidence-based practices and a collaborative care approach designed to maximize specific and nonspecific treatment mechanisms. This prospective study examined the longitudinal relationships between patients' satisfaction with care, levels of hope, and life functioning in the first 1000 patients to enter STEP-BD. The study used scores from the Care Satisfaction Questionnaire, Beck Hopelessness Scale, Range of Impaired Functioning Tool, Young Mania Rating Scale, and Montgomery-Asberg Depression Rating Scale at 5 time points during a 1-year interval. Analyses tested mediational pathways between care satisfaction, hope, and life functioning, depression, and mania using mixed-effects (random and fixed) regression models. Increases in care satisfaction were associated with decreased hopelessness (P < .01) but not related to symptoms of depression or mania. Similarly, decreased hopelessness was associated with better life functioning (P < .01) but not related to symptoms of depression or mania. Depression was independently associated with poorer life functioning (P < .0001). This study provided support for the hypothesized mediational pathway between care satisfaction, hopelessness, and life functioning. Findings suggest that providing care that maximizes patient hope may be important. By so doing, patients might overcome the learned helplessness/hopelessness that often accompanies a cyclical illness and build a realistic illness-management strategy.

Co-extrusion of food grains-banana pulp for nutritious snacks: optimization of process variables.

PubMed

Mridula, D; Sethi, Swati; Tushir, Surya; Bhadwal, Sheetal; Gupta, R K; Nanda, S K

2017-08-01

Present study was undertaken to optimize the process conditions for development of food grains (maize, defatted soy flour, sesame seed)-banana based nutritious expanded snacks using extrusion processing. Experiments were designed using Box-Behnken design with banana pulp (8-24 g), screw speed (300-350 rpm) and feed moisture (14-16% w.b.). Seven responses viz. expansion ratio (ER), bulk density (BD), water absorption index (WAI), protein, minerals, iron and sensory acceptability were considered for optimizing independent parameters. ER, BD, WAI, protein content, total minerals, iron content, and overall acceptability ranged 2.69-3.36, 153.43-238.83 kg/m 3 , 4.56-4.88 g/g, 15.19-15.52%, 2.06-2.27%, 4.39-4.67 mg/100 g (w.b.) and 6.76-7.36, respectively. ER was significantly affected by all three process variables while BD was influenced by banana pulp and screw speed only. Studied process variables did not affected colour quality except 'a' value with banana pulp and screw speed. Banana pulp had positive correlation with water solubility index, total minerals and iron content and negative with WAI, protein and overall acceptability. Based upon multiple response analysis, optimized conditions were 8 g banana pulp, 350 rpm screw speed and 14% feed moisture indicating the protein, calorie, iron content and overall sensory acceptability in sample as 15.46%, 401 kcal/100 g, 4.48 mg/100 g and 7.6 respectively.

Comparison of a gratitude-based and cognitive restructuring intervention for body dissatisfaction and dysfunctional eating behavior in college women.

PubMed

Wolfe, Wendy L; Patterson, Kaitlyn

2017-01-01

Researchers have investigated the efficacy of a gratitude intervention for decreasing body dissatisfaction (BD) in an internet treatment-seeking sample and demonstrated it worked equally well to decrease BD as cognitive restructuring. We extend this research by testing the efficacy of a gratitude intervention on BD, along with common sequelae of BD: dysfunctional eating, negative mood, and depressive symptoms. Females were randomly assigned to Gratitude, Cognitive Restructuring, or Control conditions. Pre- to post-intervention period comparisons found the gratitude intervention to perform better than the other conditions at increasing body esteem, decreasing BD, reducing dysfunctional eating, and reducing depressive symptoms.

A competitive chemiluminescence enzyme immunoassay method for β-defensin-2 detection in transgenic mice.

PubMed

Yang, Xi; Zhou, Tao; Yu, Lei; Tan, Wenwen; Zhou, Rui; Hu, Yonggang

2015-03-01

A competitive chemiluminescence enzyme immunoassay (CLEIA) method for porcine β-defensin-2 (pBD-2) detection in transgenic mice was established. Several factors that affect detection, including luminol, p-iodophenol and hydrogen peroxide concentrations, as well as pH, were studied and optimized. The linear range of the proposed method for pBD-2 detection under optimal conditions was 0.05-80 ng/mL with a correlation coefficient of 0.9960. Eleven detections of a 30 ng/mL pBD-2 standard sample were performed. Reproducible results were obtained with a relative standard deviation of 3.94%. The limit of detection of the method for pBD-2 was 3.5 pg/mL (3σ). The proposed method was applied to determine pBD-2 expression levels in the tissues of pBD-2 transgenic mice, and compared with LC-MS/MS and quantitative real-time reverse-transcriptase polymerase chain reaction. This suggests that the CLEIA can be used as a valuable method to detect and quantify pBD-2. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

PubMed

Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

2017-12-01

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

Presence and prevalence of Batrachochytrium dendrobatidis in commercial amphibians in Mexico City.

PubMed

Galindo-Bustos, Miguel Angel; Hernandez-Jauregui, Dulce María Brousset; Cheng, Tina; Vredenburg, Vance; Parra-Olea, Gabriela

2014-12-01

In Mexico City, native and exotic amphibians are commonly sold through the pet trade. This study investigates the presence of Batrachochytrium dendrobatidis (Bd) in native amphibians being sold at two commercial markets and at a herpetarium in Mexico City. A total of 238 individuals (6 genera and 12 species) were tested for Bd using real-time polymerase chain reaction (PCR) analysis. There were 197 Bd-positive individuals (prevalence 82%) from five species of amphibians. Hyla eximia from the markets had very high Bd prevalence (100%; 76/76 and 99%; 88/89) but those from the herpetarium were Bd negative (0/12). Ambystoma mexicanum from the herpetarium also had a high Bd-positive prevalence (80%; 28/35). Though A. mexicanum is nearly extinct in the wild, a commercial market continues to flourish through the pet trade. Now that captive colonies of A. mexicanum are currently used for reintroduction programs, the authors recommend quarantine to reduce spread of Bd via movement of infected animals in the trade and between colonies and via disposal of wastewater from captive collections.

Disturbed resting state EEG synchronization in bipolar disorder: A graph-theoretic analysis☆

PubMed Central

Kim, Dae-Jin; Bolbecker, Amanda R.; Howell, Josselyn; Rass, Olga; Sporns, Olaf; Hetrick, William P.; Breier, Alan; O'Donnell, Brian F.

2013-01-01

Disruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting-state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (δ, θ, α, β, and γ). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto-central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity. PMID:24179795

Mercury Project

NASA Image and Video Library

1961-03-24

The Mercury-Redstone Booster Development vehicle (MR-BD) lifts off from Cape Canaveral March 24, 1961. This test flight evaluated changes incorporated in the booster designed to reduce vehicle oscillations and vibrations. The Mercury-Redstone launch vehicle was developed by Dr. Wernher von Braun and the rocket team in Huntsville, Alabama.

Review of nutritional supplements for the treatment of bipolar depression.

PubMed

Rakofsky, Jeffrey J; Dunlop, Boadie W

2014-05-01

Many patients view psychotropics with skepticism and fear and view nutritional supplements as more consistent with their values and beliefs. The purpose of this review was to critically evaluate the evidence base for nutritional supplements in the treatment of bipolar depression (BD). A literature search for all randomized, controlled clinical trials using nutritional supplements in the treatment of BD was conducted via PubMed and Ovid MEDLINE computerized database. The studies were organized into essential nutrients/minerals, nonessential nutrients, and combinations of nutritional products. Among essential nutrients/minerals, omega-3-fatty acids (O3FAs) have the strongest evidence of efficacy for bipolar depression, although some studies failed to find positive effects from O3FAs. Weak evidence supports efficacy of vitamin C whereas no data support the usefulness of folic acid and choline. Among nonessential nutrients, cytidine is the least supported treatment. Studies of N-acetylcysteine have not resolved its efficacy in treating acute depressive episodes relative to placebo. However, one study demonstrates its potential to improve depressive symptoms over time and the other, though nonsignificant, suggests it has a prophylactic effect. Studies of inositol have been mostly negative, except for 1 study. Those that were negative were underpowered but demonstrated numerically positive effects for inositol. There is no evidence that citicholine is efficacious for uncomplicated BD depression, though it may have value for comorbid substance abuse among BD patients. Finally, combination O3FA-cytidine lacks evidence of efficacy. The findings of this review do not support the routine use of nutritional supplements in the treatment or prophylaxis of BD depression. Studies with more rigorous designs are required before definitive conclusions can be made. Despite the inadequacy of the existing data, clinicians should remain open to the value of nutritional supplements: after all, lithium is a mineral too. © 2013 Wiley Periodicals, Inc.

Frequency and characteristics of individuals with seasonal pattern among depressive patients attending primary care in France.

PubMed

Azorin, Jean-Michel; Adida, Marc; Belzeaux, Raoul

2015-01-01

High rates of bipolar disorder (BD) have been found among major depressives with seasonal pattern (SP) consulting in psychiatric departments, as well as among patients seeking primary care. As SP was reported to be common in the latter, the current study was designed to assess (a) the frequency and characteristics of SP among major depressives attending primary care and (b) the prevalence and aspects of BD in this population. Among 400 patients who consulted French general practitioners (GPs) for major depression between February and December 2010, 390 could be included in the study: 167 (42.8%) met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for seasonal pattern [SP(+)], whereas 223 (57.2%) did not meet these criteria [SP(-)]. The two groups were compared on demographic, clinical, family history and temperamental characteristics. Compared to SP(-), SP(+) patients were more frequently female, married and with a later age at first depressive episode, and showed more atypical vegetative symptoms, comorbid bulimia and stimulant abuse. They also exhibited more lifetime depressive episodes, were more often diagnosed as having BD II and met more often bipolarity specifier criteria, with higher rates of bipolar temperaments and a higher BD family loading. Among SP(+) patients, 68.9% met the bipolarity specifier criteria, whereas 31.1% did not. Seasonality was not influenced by climatic conditions. The following independent variables were associated with SP: BD according to bipolarity specifier, female gender, comorbid bulimia nervosa, hypersomnia, number of depressive episodes and family history of substance abuse. Seasonal pattern is frequent among depressive patients attending primary care in France and may be indicative of hidden bipolarity. Given the risks associated with both SP and bipolarity, GPs are likely to have a major role in regard to prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

49 CFR Appendixes B-D to Part 99 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false [Reserved] B Appendixes B-D to Part 99 Transportation Office of the Secretary of Transportation EMPLOYEE RESPONSIBILITIES AND CONDUCT Appendixes B-D to Part 99 [Reserved] ...

Atomic Spectra Bibliography Databases at NIST

NASA Astrophysics Data System (ADS)

Kramida, Alexander

2010-03-01

NIST's Atomic Spectroscopy Data Center maintains three online Bibliographic Databases (BD) [http://physics.nist.gov/PhysRefData/ASBib1/index.html]: -- Atomic Energy Levels and Spectra (AEL BD), Atomic Transition Probability (ATP BD), and Atomic Spectral Line Broadening (ALB BD). This year marks new releases of these BDs -- AEL BD v.2.0, ATP BD v.9.0, and ALB DB v.3.0. These releases incorporate significant improvements in the quantity and quality of bibliographic data since the previous versions published first in 2006. The total number of papers in the three DBs grew from 20,000 to 30,000. The data search is now made easier, and the returned content is enriched with direct links to online journal articles and universal Digital Object Identifiers. Statistics show a nearly constant flow of new publications on atomic spectroscopy, about 600 new papers published each year since 1968. New papers are inserted in our BDs every two weeks on average.

Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania.

PubMed

Barbosa, Izabela G; Morato, Isabela B; Huguet, Rodrigo B; Rocha, Fabio L; Machado-Vieira, Rodrigo; Teixeira, Antônio L

2014-01-01

To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD.

Genomic epidemiology of the emerging pathogen Batrachochytrium dendrobatidis from native and invasive amphibian species in Chile.

PubMed

Valenzuela-Sánchez, A; O'Hanlon, S J; Alvarado-Rybak, M; Uribe-Rivera, D E; Cunningham, A A; Fisher, M C; Soto-Azat, C

2018-04-01

Emerging fungal diseases represent a threat to food security, animal and human health worldwide. Amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has been associated with catastrophic and well-documented amphibian population declines and extinctions. For the first time, Bd was cultured from native and non-native wild amphibians in Chile. Phylogenomic analyses revealed that Chilean isolates AVS2, AVS4 and AVS7 group within the global panzootic lineage of Bd (BdGPL) in a single highly supported clade that includes a genotype previously isolated from the United Kingdom. Our results extend the known distribution of BdGPL in South America and suggest a single and relatively recent introduction of BdGPL into the country, providing additional support to the role of anthropogenic activity in the global spread of this panzootic lineage. © 2017 Blackwell Verlag GmbH.

Cortical thickness differences between bipolar depression and major depressive disorder.

PubMed

Lan, Martin J; Chhetry, Binod Thapa; Oquendo, Maria A; Sublette, M Elizabeth; Sullivan, Gregory; Mann, J John; Parsey, Ramin V

2014-06-01

Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers. Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups. Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within the frontal and parietal lobes, and the posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6 to 9.6% (cluster-wise p-values from 1.0 e-4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5 to 8.2% (cluster-wise p-values from 1.0 e-4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group. Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Normalization of cortical bone density in children and adolescents with hyperthyroidism treated with antithyroid medication.

PubMed

Numbenjapon, N; Costin, G; Pitukcheewanont, P

2012-09-01

We assessed bone size and bone density (BD) measurements using computed tomography (CT) in children and adolescents with hyperthyroidism treated with antithyroid medication. We found that cortical BD appeared to improve at 1 year and normalize at 2 years in all tested patients. Our previous study demonstrated that cortical BD in children and adolescents with untreated hyperthyroidism was significantly decreased as compared to age-, sex- and ethnicity-matched healthy controls. The present report evaluated whether attainment of euthyroidism by medical antithyroid treatment was able to improve or normalize cortical BD in these patients. Anthropometrics and three-dimensional CT bone measurements including cross-sectional area (CSA), cortical bone area (CBA) and cortical BD at midshaft of the femur (cortical bone), and CSA and BD of L(1) to L(3) vertebrae (cancellous bone) in 15 children and adolescents after 1- and 2-year treatments with antithyroid medication were reviewed and compared to their pretreatment results. All patients were euthyroid at 1 and 2 years after medical antithyroid treatment. After adjusting for age, height, weight and Tanner stage, a significant increase in cortical BD in all patients (15/15) was found after 1 year of treatment (P < 0.001). Normalization of cortical BD was demonstrated in all tested patients (10/15) after 2 years. There were no significant changes in the other cancellous or cortical bone parameters. Cortical BD was improved at 1 year and normalized at 2 years in hyperthyroid patients rendered euthyroid with antithyroid medication.

Coincident mass extirpation of neotropical amphibians with the emergence of the infectious fungal pathogen Batrachochytrium dendrobatidis

PubMed Central

Cheng, Tina L.; Rovito, Sean M.; Wake, David B.; Vredenburg, Vance T.

2011-01-01

Amphibians highlight the global biodiversity crisis because ∼40% of all amphibian species are currently in decline. Species have disappeared even in protected habitats (e.g., the enigmatic extinction of the golden toad, Bufo periglenes, from Costa Rica). The emergence of a fungal pathogen, Batrachochytrium dendrobatidis (Bd), has been implicated in a number of declines that have occurred in the last decade, but few studies have been able to test retroactively whether Bd emergence was linked to earlier declines and extinctions. We describe a noninvasive PCR sampling technique that detects Bd in formalin-preserved museum specimens. We detected Bd by PCR in 83–90% (n = 38) of samples that were identified as positive by histology. We examined specimens collected before, during, and after major amphibian decline events at established study sites in southern Mexico, Guatemala, and Costa Rica. A pattern of Bd emergence coincident with decline at these localities is revealed—the absence of Bd over multiple years at all localities followed by the concurrent emergence of Bd in various species at each locality during a period of population decline. The geographical and chronological emergence of Bd at these localities also indicates a southbound spread from southern Mexico in the early 1970s to western Guatemala in the 1980s/1990s and to Monteverde, Costa Rica by 1987. We find evidence of a historical “Bd epidemic wave” that began in Mexico and subsequently spread to Central America. We describe a technique that can be used to screen museum specimens from other amphibian decline sites around the world. PMID:21543713

Coincident mass extirpation of neotropical amphibians with the emergence of the infectious fungal pathogen Batrachochytrium dendrobatidis.

PubMed

Cheng, Tina L; Rovito, Sean M; Wake, David B; Vredenburg, Vance T

2011-06-07

Amphibians highlight the global biodiversity crisis because ∼40% of all amphibian species are currently in decline. Species have disappeared even in protected habitats (e.g., the enigmatic extinction of the golden toad, Bufo periglenes, from Costa Rica). The emergence of a fungal pathogen, Batrachochytrium dendrobatidis (Bd), has been implicated in a number of declines that have occurred in the last decade, but few studies have been able to test retroactively whether Bd emergence was linked to earlier declines and extinctions. We describe a noninvasive PCR sampling technique that detects Bd in formalin-preserved museum specimens. We detected Bd by PCR in 83-90% (n = 38) of samples that were identified as positive by histology. We examined specimens collected before, during, and after major amphibian decline events at established study sites in southern Mexico, Guatemala, and Costa Rica. A pattern of Bd emergence coincident with decline at these localities is revealed-the absence of Bd over multiple years at all localities followed by the concurrent emergence of Bd in various species at each locality during a period of population decline. The geographical and chronological emergence of Bd at these localities also indicates a southbound spread from southern Mexico in the early 1970s to western Guatemala in the 1980s/1990s and to Monteverde, Costa Rica by 1987. We find evidence of a historical "Bd epidemic wave" that began in Mexico and subsequently spread to Central America. We describe a technique that can be used to screen museum specimens from other amphibian decline sites around the world.

Cardiovascular and psychiatric characteristics associated with oxidative stress markers among adolescents with bipolar disorder.

PubMed

Hatch, Jessica; Andreazza, Ana; Olowoyeye, Omodele; Rezin, Gislane Tezza; Moody, Alan; Goldstein, Benjamin I

2015-09-01

In the field of bipolar disorder (BD) research there is an absence of validated biomarkers and limited understanding of the biology underlying excessive and premature cardiovascular disease (CVD). Oxidative stress is a potential biomarker in both BD and CVD. To examine psychiatric and cardiovascular characteristics associated with peripheral oxidative stress markers among adolescents with BD, who are at high risk for CVD. Participants were 30 adolescents, 13-19years old, with BD and without CVD. Ultrasonography was used to evaluate vascular function and structure. Traditional CVD risk factors were also measured. Psychiatric assessments were conducted via semi-structured interview. Serum levels of oxidative stress (lipid hydroperoxides (LPH) and protein carbonylation (PC)) were assayed. Compared to published data on adults with BD, adolescents had significantly lower levels of LPH and PC (t52(11.34), p<0.0001; t58(29.68), p<0.0001, respectively). Thicker mean and maximum carotid intima media thickness was associated with greater levels of LPH (r=.455, p=.015; r=.620, p<0.0001, respectively). LPH was associated with diastolic blood pressure (r=-.488, p=0.008) and pulse pressure (r=.543, p=0.003). Mood symptoms and medication were not significantly associated with oxidative stress. Adolescents with BD have lower levels of oxidative stress compared to adults with BD, supporting prevailing illness staging theories for BD. Oxidative stress is robustly associated with a proxy measure of atherosclerosis and may explain in part the increased risk of CVD in BD. Copyright © 2015 Elsevier Inc. All rights reserved.

Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study

PubMed Central

Shi, Xian-Feng; Kondo, Douglas G; Sung, Young-Hoon; Hellem, Tracy L; Fiedler, Kristen K; Jeong, Eun-Kee; Huber, Rebekah S; Renshaw, Perry F

2015-01-01

Objectives To compare the concentrations of high-energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC). Methods We used in vivo phosphorus-31 magnetic resonance spectroscopy (31P-MRS) at 3 Tesla to measure phosphocreatine (PCr), beta-nucleoside triphosphate (β-NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs. Results Analysis of covariance, including age as a covariate, revealed differences in PCr (p = 0.037), Pi (p = 0.017), and PCr/Pi (p = 0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post-hoc Tukey–Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p = 0.038) and medicated BD (24%; p = 0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p = 0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p = 0.013) and with medicated BD (39%; p = 0.002). No differences in β-NTP or pH were observed. Conclusions Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n-acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD. PMID:22816670

Physical and mental health burden in cases of bipolar disorder classified as current, former, or non-tobacco smokers.

PubMed

Icick, R; Gard, S; Barde, M; Carminati, M; Desage, A; Guillaume, S; Scott, J; Bellivier, F

2017-01-15

Tobacco smoking increases the global burden of bipolar disorder (BD). We examined markers of physical and mental health that are associated with tobacco smoking, controlling for confounders that have not always been considered in previous studies of BD. Over 600 individuals with BD I or II referred to the French Network for bipolar disorder (FACE-BD) who completed standardized assessments, and could be reliably classified as current (CS) or former smokers (FS), were compared with those who were never smokers (NS) on: BD symptom load and psychiatric comorbidities; prevalence of alcohol and substance use disorders (ASUD); medication usage; functioning and physical health parameters. The bivariate and multivariate analyses took into account age and gender. 300 cases (49%) were CS, 78 (13%) FS and 238 (39%) had never smoked. Rates were similar across genders regardless of BD subtype. Compared with NS, CS were more likely to have an ASUD (Odds Ratio (OR) 5.18), BD I (OR 2.09), and lower abdominal obesity (OR 0.97), and FS were more likely to have an ASUD (OR 6.32) and higher abdominal obesity (OR 1.03). The sample comprised of white Europeans; the FS subgroup was relatively small and we did not apply any statistical correction for the bivariate analyses. The increased risk of physical and mental health burden in CS and FS compared to NS represents avoidable morbidity in BD. This study offers support to the argument that individuals with BD should be routinely offered support to prevent or stop tobacco smoking. Copyright © 2016 Elsevier B.V. All rights reserved.

BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer

PubMed Central

JIANG, JIAHUA; THYAGARAJAN-SAHU, ANITA; LOGANATHAN, JAGADISH; ELIAZ, ISAAC; TERRY, COLIN; SANDUSKY, GEORGE E.; SLIVA, DANIEL

2012-01-01

We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers. PMID:22842551

Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction

PubMed Central

Jia, Yun-Fang; Choi, YuBin; Ayers-Ringler, Jennifer R.; Biernacka, Joanna M.; Geske, Jennifer R.; Lindberg, Daniel R.; McElroy, Susan L.; Frye, Mark A.; Choi, Doo-Sup; Veldic, Marin

2017-01-01

While downregulation of excitatory amino acid transporter 2 (EAAT2), the main transporter removing glutamate from the synapse, has been recognized in bipolar disorder (BD), the underlying mechanisms of downregulation have not been elucidated. BD is influenced by environmental factors, which may, via epigenetic modulation of gene expression, differentially affect illness presentation. This study thus focused on epigenetic DNA methylation regulation of SLC1A2, encoding for EAAT2, in BD with variable environmental influences of addiction. High resolution melting PCR (HRM-PCR) and thymine–adenine (TA) cloning with sequence analysis were conducted to examine methylation of the promoter region of the SLC1A2. DNA was isolated from blood samples drawn from BD patients (N = 150) with or without addiction to alcohol, nicotine, or food, defined as binge eating, and matched controls (N = 32). In comparison to controls, the SLC1A2 promoter region was hypermethylated in BD without addiction but was hypomethylated in BD with addiction. After adjusting for age and sex, the association of methylation levels with nicotine addiction (p = 0.0009) and binge eating (p = 0.0002) remained significant. Consistent with HRM-PCR, direct sequencing revealed increased methylation in CpG site 6 in BD, but decreased methylation in three CpG sites (6, 48, 156) in BD with alcohol and nicotine addictions. These results suggest that individual point methylation within the SLC1A2 promoter region may be modified by exogenous addiction and may have a potential for developing clinically valuable epigenetic biomarkers for BD diagnosis and monitoring. PMID:28785205

Differential SLC1A2 Promoter Methylation in Bipolar Disorder With or Without Addiction.

PubMed

Jia, Yun-Fang; Choi, YuBin; Ayers-Ringler, Jennifer R; Biernacka, Joanna M; Geske, Jennifer R; Lindberg, Daniel R; McElroy, Susan L; Frye, Mark A; Choi, Doo-Sup; Veldic, Marin

2017-01-01

While downregulation of excitatory amino acid transporter 2 (EAAT2), the main transporter removing glutamate from the synapse, has been recognized in bipolar disorder (BD), the underlying mechanisms of downregulation have not been elucidated. BD is influenced by environmental factors, which may, via epigenetic modulation of gene expression, differentially affect illness presentation. This study thus focused on epigenetic DNA methylation regulation of SLC1A2 , encoding for EAAT2, in BD with variable environmental influences of addiction. High resolution melting PCR (HRM-PCR) and thymine-adenine (TA) cloning with sequence analysis were conducted to examine methylation of the promoter region of the SLC1A2 . DNA was isolated from blood samples drawn from BD patients ( N = 150) with or without addiction to alcohol, nicotine, or food, defined as binge eating, and matched controls ( N = 32). In comparison to controls, the SLC1A2 promoter region was hypermethylated in BD without addiction but was hypomethylated in BD with addiction. After adjusting for age and sex, the association of methylation levels with nicotine addiction ( p = 0.0009) and binge eating ( p = 0.0002) remained significant. Consistent with HRM-PCR, direct sequencing revealed increased methylation in CpG site 6 in BD, but decreased methylation in three CpG sites (6, 48, 156) in BD with alcohol and nicotine addictions. These results suggest that individual point methylation within the SLC1A2 promoter region may be modified by exogenous addiction and may have a potential for developing clinically valuable epigenetic biomarkers for BD diagnosis and monitoring.

Distribution and pathogenicity of Batrachochytrium dendrobatidis in boreal toads from the grand teton area of western wyoming

USGS Publications Warehouse

Murphy, P.J.; St-Hilaire, S.; Bruer, S.; Corn, P.S.; Peterson, C.R.

2009-01-01

The pathogen Batrachochytrium dendrobatidis (Bd), which causes the skin disease chytridiomycosis, has been linked to amphibian population declines and extinctions worldwide. Bd has been implicated in recent declines of boreal toads, Bufo boreas boreas, in Colorado but populations of boreal toads in western Wyoming have high prevalence of Bd without suffering catastrophic mortality. In a field and laboratory study, we investigated the prevalence of Bd in boreal toads from the Grand Teton ecosystem (GRTE) in Wyoming and tested the pathogenicity of Bd to these toads in several environments. The pathogen was present in breeding adults at all 10 sites sampled, with a mean prevalence of 67%. In an experiment with juvenile toadlets housed individually in wet environments, 106 zoospores of Bd isolated from GRTE caused lethal disease in all Wyoming and Colorado animals within 35 days. Survival time was longer in toadlets from Wyoming than Colorado and in toadlets spending more time in dry sites. In a second trial involving Colorado toadlets exposed to 35% fewer Bd zoospores, infection peaked and subsided over 68 days with no lethal chytridiomycosis in any treatment. However, compared with drier aquaria with dry refuges, Bd infection intensity was 41% higher in more humid aquaria and 81% higher without dry refuges available. Our findings suggest that although widely infected in nature, Wyoming toads may escape chytridiomycosis due to a slight advantage in innate resistance or because their native habitat hinders Bd growth or provides more opportunities to reduce pathogen loads behaviorally than in Colorado. ?? 2009 International Association for Ecology and Health.

Attachment Styles and Psychopathology among Adolescent Children of Parents with Bipolar Disorder

PubMed Central

Erkan, Mustafa; Gencoglan, Salih; Akguc, Leyla; Ozatalay, Esin; Fettahoglu, Emine Cigil

2015-01-01

Background The aim of this study was to compare attachment styles and psychopathology in adolescent children of parents with bipolar disorder (BD) with a healthy control group. Material/Methods We studied 25 adolescents who had at least 1 parent with BD (BD group) and 28 adolescents who had no parents with BD (control group). The adolescent participants were between the ages of 12 and 17 years. We used the Adolescent Relationship Scales Questionnaire (A-RSQ) for the adolescents in the BD vs. control groups, and we used the Schedule for Affective Disorders and Schizophrenia for School-age Children – present and lifetime version (K-SADS-PL). We used the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Clinician Version for each parent of adolescents in the BD and control groups to rule out psychopathologies. Results Attachment styles of participants were assessed according to A-RSQ, dismissing attachment style scores of adolescents in BD group were found significantly higher compared to the healthy control group (p<0.05). As a result of the assessments, 12 adolescents (48%) out of 25 in the BD group and 5 adolescents (18%) out of 28 in the control group were given DSM-IV Axis I diagnosis, which is a statistically significant result (p<0.05). However, when psychiatric diagnoses were assessed separately, the difference was not statistically significant. Conclusions We found that the adolescent children of parents with BD have increased risk of developing mental illnesses, and that these adolescents adopt dismissing attachment styles. PMID:25877235

Quantitative Proteomics of an Amphibian Pathogen, Batrachochytrium dendrobatidis, following Exposure to Thyroid Hormone

PubMed Central

Thekkiniath, Jose; Zabet-Moghaddam, Masoud; Kottapalli, Kameswara Rao; Pasham, Mithun R.; San Francisco, Susan; San Francisco, Michael

2015-01-01

Batrachochytrium dendrobatidis (Bd), a chytrid fungus, has increasingly been implicated as a major factor in the worldwide decline of amphibian populations. The fungus causes chytridiomycosis in susceptible species leading to massive die-offs of adult amphibians. Although Bd infects the keratinized mouthparts of tadpoles and negatively affects foraging behavior, these infections are non-lethal. An important morphogen controlling amphibian metamorphosis is thyroid hormone (T3). Tadpoles may be infected with Bd and the fungus may be exposed to T3 during metamorphosis. We hypothesize that exposure of Bd to T3 may induce the expression of factors associated with host colonization and pathogenicity. We utilized a proteomics approach to better understand the dynamics of the Bd-T3 interaction. Using liquid chromatography-mass spectrometry (LC-MS), we generated a data set of a large number of cytoplasmic and membrane proteins following exposure of Bd to T3. From these data, we identified a total of 263 proteins whose expression was significantly changed following T3 exposure. We provide evidence for expression of an array of proteins that may play key roles in both genomic and non-genomic actions of T3 in Bd. Additionally, our proteomics study shows an increase in several proteins including proteases and a class of uncommon crinkler and crinkler-like effector proteins suggesting their importance in Bd pathogenicity as well as those involved in metabolism and energy transfer, protein fate, transport and stress responses. This approach provides insights into the mechanistic basis of the Bd-amphibian interaction following T3 exposure. PMID:26046527

Quantitative Proteomics of an Amphibian Pathogen, Batrachochytrium dendrobatidis, following Exposure to Thyroid Hormone.

PubMed

Thekkiniath, Jose; Zabet-Moghaddam, Masoud; Kottapalli, Kameswara Rao; Pasham, Mithun R; San Francisco, Susan; San Francisco, Michael

2015-01-01

Batrachochytrium dendrobatidis (Bd), a chytrid fungus, has increasingly been implicated as a major factor in the worldwide decline of amphibian populations. The fungus causes chytridiomycosis in susceptible species leading to massive die-offs of adult amphibians. Although Bd infects the keratinized mouthparts of tadpoles and negatively affects foraging behavior, these infections are non-lethal. An important morphogen controlling amphibian metamorphosis is thyroid hormone (T3). Tadpoles may be infected with Bd and the fungus may be exposed to T3 during metamorphosis. We hypothesize that exposure of Bd to T3 may induce the expression of factors associated with host colonization and pathogenicity. We utilized a proteomics approach to better understand the dynamics of the Bd-T3 interaction. Using liquid chromatography-mass spectrometry (LC-MS), we generated a data set of a large number of cytoplasmic and membrane proteins following exposure of Bd to T3. From these data, we identified a total of 263 proteins whose expression was significantly changed following T3 exposure. We provide evidence for expression of an array of proteins that may play key roles in both genomic and non-genomic actions of T3 in Bd. Additionally, our proteomics study shows an increase in several proteins including proteases and a class of uncommon crinkler and crinkler-like effector proteins suggesting their importance in Bd pathogenicity as well as those involved in metabolism and energy transfer, protein fate, transport and stress responses. This approach provides insights into the mechanistic basis of the Bd-amphibian interaction following T3 exposure.

Effect of memantine on C-reactive protein and lipid profiles in bipolar disorder.

PubMed

Chang, Hui Hua; Chen, Po See; Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Huang, San-Yuan; Hong, Jau-Shyong; Yang, Yen Kuang; Lu, Ru-Band

2017-10-15

Balance in the immune system plays roles in bipolar disorder (BD) and its metabolic co-morbidities. Memantine is an NMDA receptor antagonist with anti-inflammatory effects. However, the effects of memantine adjunct treatment on metabolic status of BD are unclear. During the 12 weeks period, a total of 191 BD patients were enrolled and split into valproate (VPA) + placebo and VPA + memantine (5mg/day) arms. The fasting plasma levels of high-sensitivity C-reactive protein (CRP) and metabolic indices were assessed. BD patients were stratified according to their initial CRP level. A cut-off value of initial CRP level of 2322ng/mL discriminated the waist circumference in these BD patients after 12-week VPA treatment. In the high CRP (> 2322ng/mL) group, patients in the VPA + memantine arm had a significantly decreased in their CRP (p= 0.009), total cholesterol (p= 0.002), LDL (p= 0.002) levels, BMI (p= 0.001), and waist circumference (p< 0.001), compared to those in the VPA + placebo arm. However, analysis of the low CRP group did not showed the effect. We recruited BD patients in depressed states and the sample size was relative small. The effects of the fixed dose of memantine on metabolic indices were 12-week follow up in BD patients treated with VPA. BD patients with high initial CRP levels receiving memantine adjunct treatment have a reduced risk of inflammation and metabolic imbalance. Prospective studies are needed to confirm the long-term outcome for memantine adjunct therapy in BD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortisol levels in fingernails, neurocognitive performance and clinical variables in euthymic bipolar I disorder.

PubMed

Herane-Vives, Andres; Cleare, Anthony J; Chang, Chin-Kuo; de Angel, Valeria; Papadopoulos, Andrew; Fischer, Susanne; Halari, Rozmin; Cheung, Eric Y W; Young, Allan H

2017-03-27

Neurocognitive impairment has been found in bipolar patients. Hypercortisolemia is one possible cause but there has been no agreement on this. Previous sampling methods assessed only acute cortisol levels, whereas the association between cortisol and psychopathology might be better understood by investigating chronic levels. Fingernails are a novel method for measuring chronic cortisol concentration (CCC). Here, we measured CCC in euthymic bipolar disorder I (BD-I) patients and healthy controls using fingernails to investigate whether differences in CCC influenced neurocognitive performance. We also investigated whether differences in clinical illness variables influenced CCC in euthymic BD-I patients. A previous study demonstrated neurocognitive impairment in euthymic BD-I patients. The current study included a portion of this sample: 40 BD-I versus 42 matched controls who provided fingernail samples. There was no statistically significant difference in CCC between controls and BD-I (P = .09). Logistic regression analyses revealed that euthymic bipolar I subjects with more than five years of current euthymia had decreased odds of having higher fingernail cortisol concentration (>71.2 pg/mg) compared to those with less than 1.5 years (P = .04). There was no association between CCC and cognitive impairment in all domains before and after adjustment for age and sex. The current evidence suggests CCC is not a trait biomarker in euthymic BD-I (BD-I). Longer periods of stability in affective disorders are associated with lower CCC. Fingernail cortisol does not seem to be implicated in neurocognitive impairment and BD-I. Future studies may investigate CCC in different illness phases of BD-I.

State-Dependent Differences in Emotion Regulation Between Unmedicated Bipolar Disorder and Major Depressive Disorder.

PubMed

Rive, Maria M; Mocking, Roel J T; Koeter, Maarten W J; van Wingen, Guido; de Wit, Stella J; van den Heuvel, Odile A; Veltman, Dick J; Ruhé, Henricus G; Schene, Aart H

2015-07-01

Major depressive disorder (MDD) and bipolar disorder (BD) are difficult to distinguish clinically during the depressed or remitted states. Both mood disorders are characterized by emotion regulation disturbances; however, little is known about emotion regulation differences between MDD and BD. Better insight into these differences would be helpful for differentiation based on disorder-specific underlying pathophysiological mechanisms. Previous studies comparing these disorders often allowed medication use, limiting generalizability and validity. Moreover, patients with MDD and BD were mostly compared during the depressed, but not the remitted, state, while state might potentially modulate differences between MDD and BD. To investigate positive and negative emotion regulation in medication-free patients with MDD and BD in 2 mood states: depressed or remitted. A cross-sectional study conducted from May 2009 to August 2013 comparing behavioral and functional magnetic resonance imaging emotion regulation data of 42 patients with MDD, 35 with BD, and 36 healthy control (HC) participants free of psychotropic medication recruited from several psychiatric institutions across the Netherlands. A voluntary emotion regulation functional magnetic resonance imaging task using positive and negative pictures. Behavioral and functional magnetic resonance imaging blood oxygen level-dependent responses during emotion regulation. In the remitted state, only patients with BD showed impaired emotion regulation (t = 3.39; P < .001; Cohen d = 0.70), irrespective of emotion type and associated with increased dorsolateral prefrontal cortex activity compared with those with MDD and healthy control participants (P = .008). In the depressed state, patients with MDD and BD differed with regard to happy vs sad emotion regulation (t = 4.19; P < .001; Cohen d = 1.66) associated with differences in rostral anterior cingulate activity (P < .001). Patients with MDD regulated sad and happy emotions poorly compared with those with BD and healthy control participants, while they demonstrated no rostral anterior cingulate difference between happy and sad emotion regulation. In contrast, patients with BD performed worse than those with MDD on sad emotion regulation but normal on happy emotion regulation, and they demonstrated significantly less rostral anterior cingulate activity while regulating happy compared with sad emotions. Medication-free patients with MDD vs BD appear to differ in brain activations during emotion regulation, both while depressed and in remission. These different neuropathophysiological mechanisms between MDD and BD may be useful for further development of additional diagnostic tools.

Perceived stress and hair cortisol: Differences in bipolar disorder and schizophrenia.

PubMed

Streit, Fabian; Memic, Amra; Hasandedić, Lejla; Rietschel, Liz; Frank, Josef; Lang, Maren; Witt, Stephanie H; Forstner, Andreas J; Degenhardt, Franziska; Wüst, Stefan; Nöthen, Markus M; Kirschbaum, Clemens; Strohmaier, Jana; Oruc, Lilijana; Rietschel, Marcella

2016-07-01

Bipolar disorder (BD) and schizophrenia (SCZ) are psychiatric disorders with shared and distinct clinical and genetic features. In both disorders, stress increases the risk for onset or relapse and dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been reported. The latter is frequently investigated by measuring changes in the hormonal end product of the HPA axis, i.e., the glucocorticoid cortisol, whose concentration exhibits diurnal variation. The analysis of hair cortisol concentration (HCC) is a new method, which allows assessment of cumulative cortisol secretion over the preceding three months. To explore whether perceived stress and HCC: (i) differ between BD patients, SCZ patients, and controls; (ii) change over disease course; and iii) are associated with an increased genetic risk for BD or SCZ. 159 SCZ patients, 61 BD patients and 82 controls were included. Assessment included psychopathology, perceived stress, and HCC. Inpatients with an acute episode (38 BD and 77 SCZ) were assessed shortly after admission to hospital and at 3 and 6 months follow-up. Outpatients in remission and controls were assessed at one time point only. Polygenic risk scores for BD and SCZ were calculated based on results of the Psychiatric Genomic Consortium. (i) Perceived stress was higher in BD and SCZ patients compared to controls (p<0.02), and was lower in outpatients in remission compared to inpatients on admission. HCC was higher in BD patients compared to SCZ patients and controls (p<0.02), and higher in inpatients on admission than in outpatients in remission (p=0.0012). In BD patients (r=0.29; p=0.033) and SCZ patients (r=0.20; p=0.024) manic symptoms were correlated with HCC. (ii) In both BD and SCZ inpatients, perceived stress decreased over the 6 month study period (p=0.048), while HCC did not change significantly over the 6 month study period. (iii) In controls, but not in the patient groups, the genetic risk score for BD was associated with HCC (r=0.28, p=0.023). While our results are consistent with previous reports of increased perceived stress in BD and SCZ, they suggest differential involvement of the HPA axis in the two disorders. The genetic study supports this latter finding, and suggests that this effect is present below the threshold of manifest disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pathogenic fungus Batrachochytrium dendrobatidis in marbled water frog Telmatobius marmoratus: first record from Lake Titicaca, Bolivia.

PubMed

Cossel, John; Lindquist, Erik; Craig, Heather; Luthman, Kyle

2014-11-13

The pathogenic fungus Batrachochytrium dendrobatidis (Bd) has been associated with amphibian declines worldwide but has not been well-studied among Critically Endangered amphibian species in Bolivia. We sampled free-living marbled water frogs Telmatobius marmoratus (Anura: Leptodactylidae) from Isla del Sol, Bolivia, for Bd using skin swabs and quantitative polymerase chain reactions. We detected Bd on 44% of T. marmoratus sampled. This is the first record of Bd in amphibians from waters associated with Lake Titicaca, Bolivia. These results further confirm the presence of Bd in Bolivia and substantiate the potential threat of this pathogen to the Critically Endangered, sympatric Titicaca water frog T. culeus and other Andean amphibians.

Index to Benet Weapons Laboratory (LCWSL) Technical Reports - 1984.

DTIC Science & Technology

1985-07-01

construed as an official Department of the Army position unless so designated by other authorized documents. The use of trade name(s) and/or manufacture...Apr 84 System Autoloader D.E. Jones (BWL POC) ARLCB-CR-84011 Conceptual Autoloader Design B.D. Goodell Apr 84 Study for Future Armament System M.W... Design for 120mm J.E. Wildman Apr 84 Improved Conventional Armament D.E. Jones System (ICAS) Autoloader (BWL POC) ARLCB-MR-84013 Cadmium Plating vs

17 CFR 405.2 - Reports to be made by registered government securities brokers and dealers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... government securities broker or dealer shall file Part I of Form BD-Y2K (§ 249.618 of this title) prepared as..., shall file Part II of Form BD-Y2K (§ 249.618 of this title). Part II of Form BD-Y2K shall address each... registered government securities broker or dealer that was not required to file Part II of Form BD-Y2K under...

Short-term impacts of floods on enteric infectious disease in Qingdao, China, 2005-2011.

PubMed

Zhang, F; Liu, Z; Gao, L; Zhang, C; Jiang, B

2016-11-01

The current study aimed to examine the relationship between floods and the three enteric infectious diseases, namely bacillary dysentery (BD), hand-foot-mouth disease (HFMD) and other infectious diarrhoea (OID) in Qingdao, China. Relative risks (RRs) and 95% confidence intervals (CIs) of floods on BD, HFMD and OID were calculated using a quasi-Poisson generalized linear model, adjusting for daily average temperature, daily average relative humidity, and seasonal and long-term temporal trends. Two separate models within two different periods were designed. Model 1 for the summer period showed that floods were positively associated with BD for 4- to 12-day lags, with the greatest effects for 7-day (RR 1·41, 95% CI 1·22-1·62) and 11-day (RR 1·42, 95% CI 1·22-1·64) lags. Similar findings were found in model 2 for the whole study period for 5- to 12-day lags. However, HFMD and OID were not significantly associated with floods in both models. Results from this study will provide insight into the health risks associated with floods and may help inform public health precautionary measures for such disasters.

Aberrant executive attention in unaffected youth at familial risk for mood disorders.

PubMed

Belleau, Emily L; Phillips, Mary L; Birmaher, Boris; Axelson, David A; Ladouceur, Cecile D

2013-05-01

Aberrant attentional processes in individuals with mood disorders - bipolar disorder (BD) and major depressive disorder (MDD) - have been well documented. This study examined whether unaffected youth at familial risk for mood disorders would exhibit poor alerting, orienting, and executive attention relative to age-matched controls. A sample of youth (8-17 years old) having one parent with either BD or MDD (Mood-Risk, n=29) and youth having healthy parents (HC, n=27) completed the Attention Network Test-Short version (ANT-S), which assesses alerting, orienting, and executive attention. Relative to HCs, the Mood-Risk group had significantly slower reaction times on an index of executive attention, but no differences on indices of alerting or orienting. There were no differences between the two at-risk groups (i.e., youth with BD parent vs. youth with MDD parent) on any ANT-S measure. The current study is limited by its cross-sectional design, small sample size, and failure to control for familial environmental factors. The findings extend previous results indicating that altered executive attention may represent an endophenotype for mood disorders in at-risk youth. Copyright © 2012 Elsevier B.V. All rights reserved.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders

PubMed Central

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B.; Youngstrom, Eric A.; Thomas, Kathleen M.

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development. PMID:27114896

The role of infections in Behçet disease and neuro-Behçet syndrome.

PubMed

Marta, Monica; Santos, Ernestina; Coutinho, Ester; Silva, Ana Martins; Correia, João; Vasconcelos, Carlos; Giovannoni, Gavin

2015-07-01

Infections are considered an environmental trigger for exacerbations of immune-mediated diseases. We aimed to establish if common viral infections could be identified as a precipitant of Behçet disease (BD) with or without neurological involvement and to assess the variability of the immune response to common viruses. We also investigated whether cytokines and chemokines could be markers of neurological involvement. Finally, we explored if anti-basal ganglia antibodies (ABGAs) would be associated with neurological involvement in BD. Our study included 14 individuals with BD with neurological involvement (neuroBehçet syndrome - NBS), 16 individuals with BD without neurological involvement and 18 healthy controls (HC). Overall we found a tendency for increased levels of anti-viral IgG antibody levels in BD, more evident in NBS patients versus HC. Epstein-Barr viral-capsid antigen IgG titres were increased in NBS patients versus other BD patients (p=0.032). Anti-measles antibody titres induced by vaccination were similarly elevated. ABGAs were not detected in the serum of our cohort. Raised levels of serum IL-8 in some BD patients did not reflect clinical activity or severity. In conclusion, there was evidence for a polyclonal immune activation rather than a specific virus effect in the sera of individuals with BD or NBS. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of temperament on the treatment adherence of bipolar disorder type I.

PubMed

Buturak, Sadiye Visal; Emel, Erdogan Bakar; Koçak, Orhan Murat

2016-01-01

Treatment adherence is one of the most important factors that may determine treatment response in patients with bipolar disorders (BD). Many factors have been described to be associated with treatment adherence in BD. Temperament that can influence the course of BD will have an impact on treatment adherence. The aim of this study is to investigate temperament effect on treatment adherence in euthymic patients with BD-I. Eighty patients with BD-I participated in the study. A psychiatrist used the Structured Clinical Interview for DSM-IV Axis-I Disorders to determine the diagnosis and co-morbidities. Hamilton Depression and Young Mania Rating Scale were used to detect the remission. We used the Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire and the 4-item Morisky Medication Adherence Scale to evaluate temperament and treatment adherence, respectively. The study group was divided into two groups as "treatment adherent" and "treatment non-adherent". The cyclothymic and anxious temperament scores of the treatment non-adherent patients with BD-I were significantly higher than those of the treatment adherent group (p < 0.001, p = 0.006, respectively). Multiple linear regression analysis determined that cyclothymic temperament predicted treatment non-adherence (p = 0.009). It should be kept in mind that BD-I patients with cyclothymic temperament may be treatment non-adherent and future studies should explore whether temperament characteristics deteriorate BD-I course by disrupting treatment adherence.

Mean Platelet Volume in Ocular Behçet's Disease

PubMed Central

Türkcü, Fatih Mehmet; Cingü, Abdullah Kürşat; Yüksel, Harun; Çınar, Yasin; Akkurt, Meltem; Şahin, Muhammed; Özkurt, Zeynep; Şahin, Alparslan; Çaça, İhsan

2013-01-01

Objective. To determine whether mean platelet volume (MPV) is an indicator of disease severity in ocular Behçet's Disease (BD). Materials and Methods. The study population was 30 newly diagnosed ocular BD patients who presented with active uveitis. These patients had no past history of smoking, drug use, or systemic diseases including diabetes mellitus, hypertension, cardiovascular disease, and renal disease. A control group consisting of 34 healthy individuals was included for comparison. MPV measurements were performed serially upon presentation with active uveitis and at one and three month thereafter in BD group whereas only at presentation in the controls. Results. Upon presentation with active uveitis, the mean MPV levels were 7.88 ± 1.14 femtoliters (fL) for BD group. During the posttreatment follow-up period at first and third months, BD patients demonstrated a mean MPV level of 7.71 ± 1.12 fL and 7.65 ± 1.04 fL, respectively. The mean MPV value of control group, was 8.39 ± 0.66 fL at presentation. Fluctuations in MPV values were not significant in the BD group, while there was a significant difference between the initial measurements of the BD and control groups. Conclusion. MPV measurement in ocular BD is not a predictive laboratory test to determine the clinical improvement in early stages following classical immunosuppressive treatment. PMID:24250258

Modality-specific alterations in the perception of emotional stimuli in Bipolar Disorder compared to Healthy Controls and Major Depressive Disorder

PubMed Central

Vederman, Aaron C.; Weisenbach, Sara L.; Rapport, Lisa J.; Leon, Hadia M.; Haase, Brennan D.; Franti, Lindsay M.; Schallmo, Michael-Paul; Saunders, Erika F.H.; Kamali, Masoud M.; Zubieta, Jon-Kar; Langenecker, Scott A.; McInnis, Melvin G.

2013-01-01

Objectives Affect identification accuracy paradigms have increasingly been utilized to understand psychiatric illness including Bipolar Disorder (BD) and Major Depressive Disorder (MDD). This investigation focused on perceptual accuracy in affect identification in both visual and auditory domains among patients with BD, relative to Healthy Controls (HC) and patients with MDD. Demographic and clinical variables, in addition to medications were also investigated. Methods The visual Facial Emotion Perception Test (FEPT) and auditory Emotional Perception Test (EPT) were administered to adults with BD (n = 119) and MDD (n = 78) as well as HC (n = 66). Results Performance on the FEPT was significantly stronger than on the EPT irrespective of group. Performance on the EPT did not significantly differentiate the groups. On the FEPT, BD samples had the greatest difficulty relative to HC in identification of sad and fearful faces. BD participants also had greater difficulty identifying sad faces relative to MDD participants though not after controlling for severity of illness factors. For the BD (but not MDD) sample several clinical variables were also correlated with FEPT performance. Conclusions The findings suggest that disruptions in identification of negative emotions such as sadness and fear may be a characteristic trait of BD. However, this effect may be moderated by greater illness severity found in our BD sample. PMID:21683948

Relationship between bipolar disorder and attention deficit hyperkinetic disorder: An exploratory study.

PubMed

Jhanda, Soumya; Malhotra, Savita; Grover, Sandeep

2018-05-19

This study aimed to evaluate the impact of comorbid attention deficit hyperkinetic disorder (ADHD) on Bipolar disorder (BD). Patients aged 13-40 years with diagnosis of BD with ADHD (N = 30) were compared to those with BD without ADHD (N = 69) for clinical course, functional outcome and quality of life. Those with BD + ADHD had significantly lower age of onset of BD (p < 0.001), a significantly higher number of total lifetime episodes (p = 0.002), higher number of lifetime manic episodes (p = 0.008), higher number of hospitalizations (p = 0.004) and higher prevalence of family history of BD as compared to those with BD without ADHD (p = 0.043). BD + ADHD group had poor response to conventional mood stabilizers and significantly higher prescriptions of atypical antipsychotics (p = 0.001) and higher rates of antidepressant-induced switch. Also, BD + ADHD group had significantly lower level of functioning in personal, occupational and social domains and reduced quality of life. In the BD + ADHD group, 40% patients had persistence of ADHD into adulthood. Comorbid current ADHD had more negative impact on the course and outcome of BD, when compared with those with ADHD in the past. Comorbid ADHD has negative impact on the course and outcome of BD. Copyright © 2018 Elsevier B.V. All rights reserved.

Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.

PubMed

Urošević, Snežana; Luciana, Monica; Jensen, Jonathan B; Youngstrom, Eric A; Thomas, Kathleen M

2016-01-01

Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.

Social support and social strain in inter-episode bipolar disorder

PubMed Central

Eidelman, Polina; Gershon, Anda; Kaplan, Katherine; McGlinchey, Eleanor; Harvey, Allison G

2015-01-01

Objectives This study focused on social support and social strain and their cross-sectional associations with instabilities in sleep and social rhythms in inter-episode bipolar disorder (BD). Methods Thirty-five adults diagnosed with inter-episode BD type I and 38 healthy controls completed measures of perceived social support and social strain. Group differences in support and strain were examined. Within the BD group, instabilities in sleep and social rhythms were assessed with 28 days of daily diary and actigraphy. Correlation and regression analyses were used to examine cross-sectional and prospective associations between social support, social strain, instabilities in sleep and social rhythms, and mood symptoms. Results The BD group reported lower social support and higher social strain than the control group. Additionally, social strain was positively correlated with manic and depressive symptoms in the BD group. Furthermore, there was a cross-sectional association between social support and more stable sleep on actigraphy in the BD group, although social support did not predict future sleep instability. Conclusions These results indicate that inter-episode BD is associated with deficient social support and elevated social strain compared to controls, and that this may be due to persistent inter-episode mood symptoms. Social strain may be particularly important given its association withmanic and depressive symptoms. The results also raise the possibility that sleep instability is related to poor social support in BD. PMID:22862999

Documentation for the machine-readable version of the catalog of supplemental stars to the Bonner Durchmusterung

NASA Technical Reports Server (NTRS)

Warren, W. H., Jr.

1980-01-01

The magnetic tape version of the Bonn catalog is described. The catalog contains a listing of supplemental stars having lower case letter designations following the BD numbers after which they have been inserted. A sample catalog is also presented.

Comparison of Allergenicity at Gly m 4 and Gly m Bd 30K of Soybean after Genetic Modification.

PubMed

Tsai, Jaw-Ji; Chang, Ching-Yun; Liao, En-Chih

2017-02-15

Despite rapid growth of genetically modified (GM) crops, effective evaluations of genetic modification on allergenicity are still lacking. Gly m Bd 30K is cross-reactive with cow's milk protein casein, Gly m 4, and with birch pollen allergen Bet v 1. Here we compared the allergenicity between GM and non-GM soybeans with respect to the foci Gly m 4 and Gly m Bd 30K. Recombinant allergens of Gly m Bd 30K and Gly m 4 were generated and polyclonal antibodies raised to identify these two allergenic components in soybeans. GM soybean was first PCR-confirmed using 35S promoter. A total of 20 soybeans (half GM, half non-GM) obtained from a food market were used to assess their allergenicity based on IgE-binding and histamine release. The concentrations of Gly m Bd 30K and Gly m 4 in soybeans were then determined. Most soybean-allergic patients (9 of 10) showed IgE-positive reactions to the allergen of 30 kDa in molecular weight. That allergen turned out to be Glycine max Gly m Bd 30K based on LC-MS/MS analyses. Gly m Bd 30K is therefore the major allergen in the soybean. An increase in the transcription of both the Gly m 4 (stress-induced protein SAM22) and Gly m Bd 28K (soybean allergen precursor) was found after genetic modification. The protein concentrations of Gly m 4 and Gly m Bd 30K were not statistically significant different between non-GM and GM soybeans. There were also no statistical significances between them in the tests of IgE binding and histamine release. In conclusion, soybeans showed similar concentrations of Gly m Bd 30K and Gly m 4 regardless of genetic modification or absence thereof. The allergenicity of both Gly m Bd 30K and Gly m 4 was therefore not altered after genetic modification. Patients showing hypersensitivity to soybeans and who had pre-existing allergy to birch pollen and cow's milk casein might not further increase their allergic reactions following exposures to the GM soybeans.

Assessing the Threat of Amphibian Chytrid Fungus in the Albertine Rift: Past, Present and Future

PubMed Central

Seimon, Tracie A.; Ayebare, Samuel; Sekisambu, Robert; Muhindo, Emmanuel; Mitamba, Guillain; Greenbaum, Eli; Menegon, Michele; Pupin, Fabio; McAloose, Denise; Ammazzalorso, Alyssa; Meirte, Danny; Lukwago, Wilbur; Behangana, Mathias; Seimon, Anton; Plumptre, Andrew J.

2015-01-01

Batrachochytrium dendrobatidis (Bd), the cause of chytridiomycosis, is a pathogenic fungus that is found worldwide and is a major contributor to amphibian declines and extinctions. We report results of a comprehensive effort to assess the distribution and threat of Bd in one of the Earth’s most important biodiversity hotspots, the Albertine Rift in central Africa. In herpetological surveys conducted between 2010 and 2014, 1018 skin swabs from 17 amphibian genera in 39 sites across the Albertine Rift were tested for Bd by PCR. Overall, 19.5% of amphibians tested positive from all sites combined. Skin tissue samples from 163 amphibians were examined histologically; of these two had superficial epidermal intracorneal fungal colonization and lesions consistent with the disease chytridiomycosis. One amphibian was found dead during the surveys, and all others encountered appeared healthy. We found no evidence for Bd-induced mortality events, a finding consistent with other studies. To gain a historical perspective about Bd in the Albertine Rift, skin swabs from 232 museum-archived amphibians collected as voucher specimens from 1925–1994 were tested for Bd. Of these, one sample was positive; an Itombwe River frog (Phrynobatrachus asper) collected in 1950 in the Itombwe highlands. This finding represents the earliest record of Bd in the Democratic Republic of Congo. We modeled the distribution of Bd in the Albertine Rift using MaxEnt software, and trained our model for improved predictability. Our model predicts that Bd is currently widespread across the Albertine Rift, with moderate habitat suitability extending into the lowlands. Under climatic modeling scenarios our model predicts that optimal habitat suitability of Bd will decrease causing a major range contraction of the fungus by 2080. Our baseline data and modeling predictions are important for comparative studies, especially if significant changes in amphibian health status or climactic conditions are encountered in the future. PMID:26710251

Linking Ecology and Epidemiology to Understand Predictors of Multi-Host Responses to an Emerging Pathogen, the Amphibian Chytrid Fungus

PubMed Central

Stephens, Patrick R.; Hua, Jessica; Searle, Catherine L.; Xie, Gisselle Yang; Urbina, Jenny; Olson, Deanna H.; Bancroft, Betsy A.; Weis, Virginia; Hammond, John I.; Relyea, Rick A.; Blaustein, Andrew R.

2017-01-01

Variation in host responses to pathogens can have cascading effects on populations and communities when some individuals or groups of individuals display disproportionate vulnerability to infection or differ in their competence to transmit infection. The fungal pathogen, Batrachochytrium dendrobatidis (Bd) has been detected in almost 700 different amphibian species and is implicated in numerous global amphibian population declines. Identifying key hosts in the amphibian-Bd system–those who are at greatest risk or who pose the greatest risk for others–is challenging due in part to many extrinsic environmental factors driving spatiotemporal Bd distribution and context-dependent host responses to Bd in the wild. One way to improve predictive risk models and generate testable mechanistic hypotheses about vulnerability is to complement what we know about the spatial epidemiology of Bd with data collected through comparative experimental studies. We used standardized pathogen challenges to quantify amphibian survival and infection trajectories across 20 post-metamorphic North American species raised from eggs. We then incorporated trait-based models to investigate the predictive power of phylogenetic history, habitat use, and ecological and life history traits in explaining responses to Bd. True frogs (Ranidae) displayed the lowest infection intensities, whereas toads (Bufonidae) generally displayed the greatest levels of mortality after Bd exposure. Affiliation with ephemeral aquatic habitat and breadth of habitat use were strong predictors of vulnerability to and intensity of infection and several other traits including body size, lifespan, age at sexual maturity, and geographic range also appeared in top models explaining host responses to Bd. Several of the species examined are highly understudied with respect to Bd such that this study represents the first experimental susceptibility data. Combining insights gained from experimental studies with observations of landscape-level disease prevalence may help explain current and predict future pathogen dynamics in the Bd system. PMID:28095428

Mapping the Global Emergence of Batrachochytrium dendrobatidis, the Amphibian Chytrid Fungus

PubMed Central

Ronnenberg, Kathryn L.; Powell, Christopher I.; Walker, Susan F.; Bielby, Jon; Garner, Trenton W. J.; Weaver, George

2013-01-01

The rapid worldwide emergence of the amphibian pathogen Batrachochytrium dendrobatidis (Bd) is having a profound negative impact on biodiversity. However, global research efforts are fragmented and an overarching synthesis of global infection data is lacking. Here, we provide results from a community tool for the compilation of worldwide Bd presence and report on the analyses of data collated over a four-year period. Using this online database, we analysed: 1) spatial and taxonomic patterns of infection, including amphibian families that appear over- and under-infected; 2) relationships between Bd occurrence and declining amphibian species, including associations among Bd occurrence, species richness, and enigmatic population declines; and 3) patterns of environmental correlates with Bd, including climate metrics for all species combined and three families (Hylidae, Bufonidae, Ranidae) separately, at both a global scale and regional (U.S.A.) scale. These associations provide new insights for downscaled hypothesis testing. The pathogen has been detected in 52 of 82 countries in which sampling was reported, and it has been detected in 516 of 1240 (42%) amphibian species. We show that detected Bd infections are related to amphibian biodiversity and locations experiencing rapid enigmatic declines, supporting the hypothesis that greater complexity of amphibian communities increases the likelihood of emergence of infection and transmission of Bd. Using a global model including all sampled species, the odds of Bd detection decreased with increasing temperature range at a site. Further consideration of temperature range, rather than maximum or minimum temperatures, may provide new insights into Bd-host ecology. Whereas caution is necessary when interpreting such a broad global dataset, the use of our pathogen database is helping to inform studies of the epidemiology of Bd, as well as enabling regional, national, and international prioritization of conservation efforts. We provide recommendations for adaptive management to enhance the database utility and relevance. PMID:23463502

Emission and combustion profile study of unmodified research engine propelled with neat biofuels.

PubMed

Devarajan, Yuvarajan; Mahalingam, Arulprakasajothi; Munuswamy, Dinesh Babu; Nagappan, Beemkumar

2018-05-07

The current work focuses on the experimental investigation to analyze the combustion and emission characteristics of a direct injection diesel engine fueled with neat biodiesel (BD100) and different proportions of cyclohexanol blends as a fuel additive in various volume fractions. Cyclohexanol is dispersed into a neat biodiesel in a volume fraction of 10, 20, and 30 vol%. The biodiesel is produced from neem oil by the conventional transesterification process. The experimental results revealed that with the increased cyclohexanol fraction, the combustion was found smooth. The addition of cyclohexanol has a positive influence on various physical and chemical properties of neat biodiesel. The in-cylinder pressure is comparatively low for diesel followed by cyclohexanol and biodiesel blends when compared with neat biodiesel. This is due to shorter ignition delay period. The heat-release rate of neat biodiesel is the highest among all fuels. The overall HC emission of BD70COH30 is 12.19% lower than BD100 and 16.34% lower than diesel. The overall CO 2 emission of BD70COH30 is 13.91% higher than BD100 and 19.5% higher than diesel. The overall NO x emission of BD70COH30 is 5.31% lower than BD100 at all load engine operations. The presence of 10, 20, and 30% of cyclohexanol in biodiesel decreased smoke emissions as compared with neat biodiesel and diesel. The overall smoke emission of BD70COH30 is 19.23% lower than BD100 and 25.51% lower than diesel. The overall CO emission of cyclohexanol blended with biodiesel by 30 vol% (BD70COH30) is 17% lower than neat biodiesel and 21.8% lower than diesel. Based on the outcome of this study, neem oil biodiesel and cyclohexanol blends can be employed as a potential alternative fuel for existing unmodified diesel engines owing to its lesser emission characteristics.

A meta-analysis investigating the prevalence and moderators of migraines among people with bipolar disorder.

PubMed

Fornaro, Michele; Stubbs, Brendon

2015-06-01

Uncertainty exists regarding the prevalence and moderators of migraine comorbidity among people with bipolar disorder (BD). We conducted a meta-analysis and meta-regression to investigate the prevalence and moderators of migraine among people with BD. Two authors independently searched major electronic databases from inception till 02/2015. Articles were included that reported the prevalence of migraine in people with BD with or without a control group. A random effects meta-analysis and exploratory meta-regression were conducted. Fourteen studies were included encompassing 3976 individuals with BD (mean age 35.5 years, SD 7.6, 29% male). The overall pooled prevalence of migraine was 34.8% (95% CI=25.54-44.69). The prevalence of migraine was higher among people with BD-II (54.17%, 95% CI=31.52-75.95, n=742) compared to BD-I (32.7%, 95% CI=18.16-49.19, n=2138, z=3.97, p<0.0001). The prevalence of migraine was 33.9% (95% CI=26.02-42.44), 39.5% (95% CI=18.81-62.39) and 47.11% (95% CI=22.24-72.77) in North America, Europe and South America respectively. The prevalence of migraine was higher when classified according to recognized criteria at 47.91% (95% CI=32.51-63.5) compared to non-recognized criteria (20.0%, 95% CI=12.44-29.06, z=-8.40, p<0.0001). Meta regression suggests mean age may be a potential moderator. Migraine is common and burdensome among people with BD. People with BD-II appear to be particularly affected. Nonetheless, future research is required to better understand these relationships, with a special emphasis toward the course specifiers of comorbid migraine cases of either BD-I vs. BD-II. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation of Lactic Acid and Base Deficit Values Obtained From Arterial and Peripheral Venous Samples in a Pediatric Population During Intraoperative Care.

PubMed

Bordes, Brianne M; Walia, Hina; Sebastian, Roby; Martin, David; Tumin, Dmitry; Tobias, Joseph D

2017-12-01

Lactic acid and base deficit (BD) values are frequently monitored in the intensive care unit and operating room setting to evaluate oxygenation, ventilation, cardiac output, and peripheral perfusion. Although generally obtained from an arterial cannula, such access may not always be available. The current study prospectively investigates the correlation of arterial and peripheral venous values of BD and lactic acid. The study cohort included 48 patients. Arterial BD values ranged from -8 to 4 mEq/L and peripheral venous BD values ranged from -8 to 4 mEq/L. Arterial lactic acid values ranged from 0.36 to 2.45 μmol/L and peripheral venous lactic acid values ranged from 0.38 to 4 μmol/L. The arterial BD (-0.4 ± 2.2 mEq/L) was not significantly different from the peripheral venous BD (-0.6 ± 2.2 mEq/L). The arterial lactic acid (1.0 ± 0.5 μmol/L) was not significantly different from the peripheral venous lactic acid (1.1 ± 0.6 μmol/L). Pearson correlation coefficients demonstrated a very high correlation between arterial and peripheral venous BD ( r = .88, P < .001) and between arterial and peripheral venous lactic acid ( r = .67, P < .001). Bland-Altman plots of both pairs of measures showed that the majority of observations fell within the 95% limits of agreement. Least-squares regression indicated that a 1-unit increase in arterial BD corresponded to a 0.9-unit increase in peripheral venous BD (95% confidence interval [CI]: 0.7-1.0; P < .001) and a 1-unit increase in arterial lactic acid corresponded to a 0.9-unit increase in peripheral venous lactic acid (95% CI: 0.6-1.2; P < .001). These data demonstrate that there is a clinically useful correlation between arterial and peripheral venous lactic acid and BD values.

Supersaturation of Calcipotriene and Betamethasone Dipropionate in a Novel Aerosol Foam Formulation for Topical Treatment of Psoriasis Provides Enhanced Bioavailability of the Active Ingredients.

PubMed

Lind, Marianne; Nielsen, Kim Troensegaard; Schefe, Line Hollesen; Nørremark, Kasper; Eriksson, André Huss; Norsgaard, Hanne; Pedersen, Brian Thoning; Petersson, Karsten

2016-09-01

Previous studies have demonstrated the superior efficacy of a novel aerosol foam formulation of fixed combination calcipotriene 0.005% (Cal) and betamethasone dipropionate 0.064% (BD), compared with the ointment formulation. The aim of this study is to ascertain whether enhanced bioavailability of the active ingredients due to supersaturation and/or occlusive properties can explain the observed greater clinical efficacy. Solubility and evaporation experiments were conducted to examine the abilities of Cal/BD aerosol foam ingredients to create a supersaturated environment. Optical microscopy, Raman imaging and X-ray powder diffraction were used to examine the physical state of Cal and BD in the formulations after application, and determine whether a supersaturated state remained stable for clinically relevant time periods. In vitro skin penetration and ex vivo biomarker assays were conducted to compare the skin penetration and bioavailability of Cal and BD from the aerosol foam and ointment formulations, respectively. Occlusive properties were examined via transepidermal water loss. Solubility studies showed that Cal and BD solubility increased with increasing dimethyl ether (DME) content. Both active ingredients are completely dissolved in the final aerosol foam formulation. DME rapidly evaporates after spraying, and the amount was reduced to 0.5% of the initial amount after 2 min. This led to the formation of a supersaturated environment, where Cal and BD crystals were absent for at least 26 h after application. Cal/BD aerosol foam had significantly greater in vitro skin penetration and had increased bioavailability compared with Cal/BD ointment. Both formulations effectively occluded the skin. A stable supersaturated solution of Cal/BD in the aerosol foam leads to increased bioavailability and explains the improved clinical effect when compared to the Cal/BD ointment. The studies included in the paper are all conducted by LEO Pharma A/S or CROs on behalf of LEO Pharma A/S.

Findings from a hepatitis B birth dose assessment in health facilities in the Philippines: opportunities to engage the private sector.

PubMed

Patel, Minal K; Capeding, Rosario Z; Ducusin, Joyce U; de Quiroz Castro, Maricel; Garcia, Luzviminda C; Hennessey, Karen

2014-09-03

Hepatitis B vaccination in the Philippines was introduced in 1992 to reduce the high burden of chronic hepatitis B virus (HBV) infection in the population; in 2007, a birth dose (HepB-BD) was introduced to decrease perinatal HBV transmission. Timely HepB-BD coverage, defined as doses given within 24h of birth, was 40% nationally in 2011. A first step in improving timely HepB-BD coverage is to ensure that all newborns born in health facilities are vaccinated. In order to assess ways of improving the Philippines' HepB-BD program, we evaluated knowledge, attitudes, and practices surrounding HepB-BD administration in health facilities. Teams visited selected government clinics, government hospitals, and private hospitals in regions with low reported HepB-BD coverage and interviewed immunization and maternity staff. HepB-BD coverage was calculated in each facility for a 3-month period in 2011. Of the 142 health facilities visited, 12 (8%) did not provide HepB-BD; seven were private hospitals and five were government hospitals. Median timely HepB-BD coverage was 90% (IQR 80%-100%) among government clinics, 87% (IQR 50%-97%) among government hospitals, and 50% (IQR 0%-90%) among private hospitals (p=0.02). The private hospitals were least likely to receive supervision (53% vs. 6%-31%, p=0.0005) and to report vaccination data to the national Expanded Programme on Immunization (36% vs. 96%-100%, p<0.0001). Private sector hospitals in the Philippines, which deliver 18% of newborns, had the lowest timely HepB-BD coverage. Multiple avenues exist to engage the private sector in hepatitis B prevention including through existing laws, newborn health initiatives, hospital accreditation processes, and raising awareness of the government's free vaccine program. Copyright © 2013 World Health Organization (WHO). Published by Elsevier Ltd.. All rights reserved.

Linking Ecology and Epidemiology to Understand Predictors of Multi-Host Responses to an Emerging Pathogen, the Amphibian Chytrid Fungus.

PubMed

Gervasi, Stephanie S; Stephens, Patrick R; Hua, Jessica; Searle, Catherine L; Xie, Gisselle Yang; Urbina, Jenny; Olson, Deanna H; Bancroft, Betsy A; Weis, Virginia; Hammond, John I; Relyea, Rick A; Blaustein, Andrew R

2017-01-01

Variation in host responses to pathogens can have cascading effects on populations and communities when some individuals or groups of individuals display disproportionate vulnerability to infection or differ in their competence to transmit infection. The fungal pathogen, Batrachochytrium dendrobatidis (Bd) has been detected in almost 700 different amphibian species and is implicated in numerous global amphibian population declines. Identifying key hosts in the amphibian-Bd system-those who are at greatest risk or who pose the greatest risk for others-is challenging due in part to many extrinsic environmental factors driving spatiotemporal Bd distribution and context-dependent host responses to Bd in the wild. One way to improve predictive risk models and generate testable mechanistic hypotheses about vulnerability is to complement what we know about the spatial epidemiology of Bd with data collected through comparative experimental studies. We used standardized pathogen challenges to quantify amphibian survival and infection trajectories across 20 post-metamorphic North American species raised from eggs. We then incorporated trait-based models to investigate the predictive power of phylogenetic history, habitat use, and ecological and life history traits in explaining responses to Bd. True frogs (Ranidae) displayed the lowest infection intensities, whereas toads (Bufonidae) generally displayed the greatest levels of mortality after Bd exposure. Affiliation with ephemeral aquatic habitat and breadth of habitat use were strong predictors of vulnerability to and intensity of infection and several other traits including body size, lifespan, age at sexual maturity, and geographic range also appeared in top models explaining host responses to Bd. Several of the species examined are highly understudied with respect to Bd such that this study represents the first experimental susceptibility data. Combining insights gained from experimental studies with observations of landscape-level disease prevalence may help explain current and predict future pathogen dynamics in the Bd system.

Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology.

PubMed

Leussis, Melanie P; Madison, Jon M; Petryshen, Tracey L

2012-10-01

Bipolar disorder (BD) is a multi-factorial disorder caused by genetic and environmental influences. It has a large genetic component, with heritability estimated between 59-93%. Recent genome-wide association studies (GWAS) using large BD patient populations have identified a number of genes with strong statistical evidence for association with susceptibility for BD. Among the most significant and replicated genes is ankyrin 3 (ANK3), a large gene that encodes multiple isoforms of the ankyrin G protein. This article reviews the current evidence for genetic association of ANK3 with BD, followed by a comprehensive overview of the known biology of the ankyrin G protein, focusing on its neural functions and their potential relevance to BD. Ankyrin G is a scaffold protein that is known to have many essential functions in the brain, although the mechanism by which it contributes to BD is unknown. These functions include organizational roles for subcellular domains in neurons including the axon initial segment and nodes of Ranvier, through which ankyrin G orchestrates the localization of key ion channels and GABAergic presynaptic terminals, as well as creating a diffusion barrier that limits transport into the axon and helps define axo-dendritic polarity. Ankyrin G is postulated to have similar structural and organizational roles at synaptic terminals. Finally, ankyrin G is implicated in both neurogenesis and neuroprotection. ANK3 and other BD risk genes participate in some of the same biological pathways and neural processes that highlight several mechanisms by which they may contribute to BD pathophysiology. Biological investigation in cellular and animal model systems will be critical for elucidating the mechanism through which ANK3 confers risk of BD. This knowledge is expected to lead to a better understanding of the brain abnormalities contributing to BD symptoms, and to potentially identify new targets for treatment and intervention approaches.

Mapping the global emergence of Batrachochytrium dendrobatidis, the amphibian chytrid fungus.

PubMed

Olson, Deanna H; Aanensen, David M; Ronnenberg, Kathryn L; Powell, Christopher I; Walker, Susan F; Bielby, Jon; Garner, Trenton W J; Weaver, George; Fisher, Matthew C

2013-01-01

The rapid worldwide emergence of the amphibian pathogen Batrachochytrium dendrobatidis (Bd) is having a profound negative impact on biodiversity. However, global research efforts are fragmented and an overarching synthesis of global infection data is lacking. Here, we provide results from a community tool for the compilation of worldwide Bd presence and report on the analyses of data collated over a four-year period. Using this online database, we analysed: 1) spatial and taxonomic patterns of infection, including amphibian families that appear over- and under-infected; 2) relationships between Bd occurrence and declining amphibian species, including associations among Bd occurrence, species richness, and enigmatic population declines; and 3) patterns of environmental correlates with Bd, including climate metrics for all species combined and three families (Hylidae, Bufonidae, Ranidae) separately, at both a global scale and regional (U.S.A.) scale. These associations provide new insights for downscaled hypothesis testing. The pathogen has been detected in 52 of 82 countries in which sampling was reported, and it has been detected in 516 of 1240 (42%) amphibian species. We show that detected Bd infections are related to amphibian biodiversity and locations experiencing rapid enigmatic declines, supporting the hypothesis that greater complexity of amphibian communities increases the likelihood of emergence of infection and transmission of Bd. Using a global model including all sampled species, the odds of Bd detection decreased with increasing temperature range at a site. Further consideration of temperature range, rather than maximum or minimum temperatures, may provide new insights into Bd-host ecology. Whereas caution is necessary when interpreting such a broad global dataset, the use of our pathogen database is helping to inform studies of the epidemiology of Bd, as well as enabling regional, national, and international prioritization of conservation efforts. We provide recommendations for adaptive management to enhance the database utility and relevance.

Seasonal Pattern of Batrachochytrium dendrobatidis Infection and Mortality in Lithobates areolatus: Affirmation of Vredenburg's “10,000 Zoospore Rule”

PubMed Central

Kinney, Vanessa C.; Heemeyer, Jennifer L.; Pessier, Allan P.; Lannoo, Michael J.

2011-01-01

To fully comprehend chytridiomycosis, the amphibian disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), it is essential to understand how Bd affects amphibians throughout their remarkable range of life histories. Crawfish Frogs (Lithobates areolatus) are a typical North American pond-breeding species that forms explosive spring breeding aggregations in seasonal and semipermanent wetlands. But unlike most species, when not breeding Crawfish Frogs usually live singly—in nearly total isolation from conspecifics—and obligately in burrows dug by crayfish. Crayfish burrows penetrate the water table, and therefore offer Crawfish Frogs a second, permanent aquatic habitat when not breeding. Over the course of two years we sampled for the presence of Bd in Crawfish Frog adults. Sampling was conducted seasonally, as animals moved from post-winter emergence through breeding migrations, then back into upland burrow habitats. During our study, 53% of Crawfish Frog breeding adults tested positive for Bd in at least one sample; 27% entered breeding wetlands Bd positive; 46% exited wetlands Bd positive. Five emigrating Crawfish Frogs (12%) developed chytridiomycosis and died. In contrast, all 25 adult frogs sampled while occupying upland crayfish burrows during the summer tested Bd negative. One percent of postmetamorphic juveniles sampled were Bd positive. Zoospore equivalents/swab ranged from 0.8 to 24,436; five out of eight frogs with zoospore equivalents near or >10,000 are known to have died. In summary, Bd infection rates in Crawfish Frog populations ratchet up from near zero during the summer to over 25% following overwintering; rates then nearly double again during and just after breeding—when mortality occurs—before the infection wanes during the summer. Bd-negative postmetamorphic juveniles may not be exposed again to this pathogen until they take up residence in crayfish burrows, or until their first breeding, some years later. PMID:21423745

Perturbations in the apoptotic pathway and mitochondrial network dynamics in peripheral blood mononuclear cells from bipolar disorder patients

PubMed Central

Scaini, G; Fries, G R; Valvassori, S S; Zeni, C P; Zunta-Soares, G; Berk, M; Soares, J C; Quevedo, J

2017-01-01

Bipolar disorder (BD) is a severe psychiatric disorder characterized by phasic changes of mood and can be associated with progressive structural brain change and cognitive decline. The numbers and sizes of glia and neurons are reduced in several brain areas, suggesting the involvement of apoptosis in the pathophysiology of BD. Because the changes in mitochondrial dynamics are closely related with the early process of apoptosis and the specific processes of apoptosis and mitochondrial dynamics in BD have not been fully elucidated, we measured the apoptotic pathway and the expression of mitochondrial fission/fusion proteins from BD patients and healthy controls. We recruited 16 patients with BD type I and sixteen well-matched healthy controls and investigated protein levels of several pro-apoptotic and anti-apoptotic factors, as well as the expression of mitochondrial fission/fusion proteins in peripheral blood mononuclear cells (PBMCs). Our results showed that the levels of the anti-apoptotic proteins Bcl-xL, survivin and Bcl-xL/Bak dimer were significantly decreased, while active caspase-3 protein levels were significantly increased in PBMCs from BD patients. Moreover, we observed the downregulation of the mitochondrial fusion-related proteins Mfn2 and Opa1 and the upregulation of the fission protein Fis1 in PBMCs from BD patients, both in terms of gene expression and protein levels. We also showed a significantly decrease in the citrate synthase activity. Finally, we found a positive correlation between Mfn2 and Opa1 with mitochondrial content markers, as well as a negative correlation between mitochondrial fission/fusion proteins and apoptotic markers. Overall, data reported here are consistent with the working hypothesis that apoptosis may contribute to cellular dysfunction, brain volume loss and progressive cognitive in BD. Moreover, we show an important relationship between mitochondrial dynamics and the cell death pathway activation in BD patients, supporting the link between mitochondrial dysfunction and the pathophysiology of BD. PMID:28463235

Neural Markers in Pediatric Bipolar Disorder and Familial Risk for Bipolar Disorder.

PubMed

Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Wambach, Caroline G; Reynolds, Richard C; Chen, Gang; Towbin, Kenneth; Pine, Daniel S; Leibenluft, Ellen

2017-01-01

Bipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR). During functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth. We found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction). If replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177. Published by Elsevier Inc.

Development of a semi-continuous two-stage simultaneous saccharification and fermentation process for enhanced 2,3-butanediol production by Klebsiella oxytoca.

PubMed

Moon, S-K; Kim, D-K; Park, J M; Min, J; Song, H

2018-04-01

Klebsiella oxytoca naturally produces a large amount of 2,3-butanediol (2,3-BD), a promising chemical with wide industrial applications, along with various by-products. Previously, we have developed a metabolically engineered K. oxytoca ΔldhA ΔpflB strain to reduce the formation of by-products. To improve 2,3-BD productivity and examine the stability of K. oxytoca ΔldhA ΔpflB strain for industrial application, a semi-continuous two-stage simultaneous saccharification and fermentation (STSSF) process was developed. The STSSF with the K. oxytoca ΔldhA ΔpflB mutant using cassava as a carbon source could produce 108 ± 3·73 g (2,3- BD )  l -1 with a yield of 0·45 g (2,3- BD )  g (glucose) -1 and a productivity of 3·00 g (2,3- BD ) l -1  h -1 . No apparent changes in the final titre, yield and productivity of 2,3-BD were observed for up to 20 cycles of STSSF. Also, microbial contamination and spontaneous mutation of the host strain with potential detrimental effects on fermentation efficiency did not occur during the whole fermentation period. These results strongly underpin that the K. oxytoca ΔldhA ΔpflB mutant is stable and that the STSSF process is commercially exploitable. There is growing interest in the production of 2,3-butanediol (2,3-BD) from renewable resources by microbial fermentation because of its wide applications to specialty and commodity chemical industries. Klebsiella oxytoca usually produces 2,3-BD as a major end product during the fermentation of carbohydrates. This is the first study to provide a high-efficiency simultaneous saccharification and 2,3-BD fermentation process. Also, this study proves the stability of a metabolically engineered 2,3-BD overproducing K. oxytoca strain for industrial application. © 2018 The Society for Applied Microbiology.

Decision making in euthymic bipolar I and bipolar II disorders.

PubMed

Martino, D J; Strejilevich, S A; Torralva, T; Manes, F

2011-06-01

The main aim of this study was to compare a large population of patients with bipolar disorder (BD) types I and II strictly defined as euthymic with healthy controls on measures of decision making. An additional aim was to compare performance on a decision-making task between patients with and without a history of suicide attempt. Eighty-five euthymic patients with BD-I or BD-II and 34 healthy controls were included. All subjects completed tests to assess verbal memory, attention and executive functions, and a decision-making paradigm (the Iowa Gambling Task, IGT). Both groups of patients had worse performance than healthy controls on measures of verbal memory, attention and executive function. No significant differences were found between BD-I, BD-II and healthy controls on measures of decision making. By contrast, patients with a history of suicide attempt had lower performance in the IGT than patients without a history of suicide attempt. Patients with euthymic BD-I and BD-II had intact decision-making abilities, suggesting that this does not represent a reliable trait marker of the disorder. In addition, our results provide further evidence of an association between impairments in decision making and vulnerability to suicidal behavior.

Quantitative PCR detection of Batrachochytrium dendrobatidis DNA from sediments and water

USGS Publications Warehouse

Kirshtein, Julie D.; Anderson, Chauncey W.; Wood, J.S.; Longcore, Joyce E.; Voytek, Mary A.

2007-01-01

The fungal pathogen Batrachochytrium dendrobatidis (Bd) causes chytridiomycosis, a disease implicated in amphibian declines on 5 continents. Polymerase chain reaction (PCR) primer sets exist with which amphibians can be tested for this disease, and advances in sampling techniques allow non-invasive testing of animals. We developed filtering and PCR based quantitative methods by modifying existing PCR assays to detect Bd DNA in water and sediments, without the need for testing amphibians; we tested the methods at 4 field sites. The SYBR based assay using Boyle primers (SYBR/Boyle assay) and the Taqman based assay using Wood primers performed similarly with samples generated in the laboratory (Bd spiked filters), but the SYBR/Boyle assay detected Bd DNA in more field samples. We detected Bd DNA in water from 3 of 4 sites tested, including one pond historically negative for chytridiomycosis. Zoospore equivalents in sampled water ranged from 19 to 454 l-1 (nominal detection limit is 10 DNA copies, or about 0.06 zoospore). We did not detect DNA of Bd from sediments collected at any sites. Our filtering and amplification methods provide a new tool to investigate critical aspects of Bd in the environment. ?? Inter-Research 2007.

Creativity and executive function across manic, mixed and depressive episodes in bipolar I disorder.

PubMed

Soeiro-de-Souza, Márcio Gerhardt; Dias, Vasco Videira; Bio, Danielle Soares; Post, Robert M; Moreno, Ricardo A

2011-12-01

Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD. Copyright © 2011 Elsevier B.V. All rights reserved.

Chronotype and circadian rhythm in bipolar disorder: A systematic review.

PubMed

Melo, Matias C A; Abreu, Rafael L C; Linhares Neto, Vicente B; de Bruin, Pedro F C; de Bruin, Veralice M S

2017-08-01

Despite a complex relationship between mood, sleep and rhythm, the impact of circadian disruptions on bipolar disorder (BD) has not been clarified. The purpose of this systematic review was to define current evidence regarding chronotype and circadian rhythm patterns in BD patients. 42 studies were included, involving 3432 BD patients. Disruption of the biological rhythm was identified, even in drug-naïve BD patients and independently of mood status. Daily profiles of melatonin levels and cortisol indicated a delayed phase. Depression was more frequently associated with circadian alterations than euthymia. Few studies evaluated mania, demonstrating irregular rhythms. Evening type was more common in BD adults. Studies about the influence of chronotype on depressive symptoms showed conflicting results. Only one investigation observed the influences of chronotype in mania, revealing no significant association. Effects of psychoeducation and lithium on rhythm in BD patients were poorly studied, demonstrating no improvement of rhythm parameters. Studies about genetics are incipient. In conclusion, disruption in circadian rhythm and eveningness are common in BD. Prospective research evaluating the impact of circadian disruption on mood symptoms, metabolism, seasonality, the influence of age and the effects of mood stabilizers are needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Presence of the Amphibian Chytrid Fungus Batrachochytrium dendrobatidis in Native Amphibians Exported from Madagascar

PubMed Central

Kolby, Jonathan E.

2014-01-01

The emerging infectious disease chytridiomycosis is driven by the spread of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd), a highly virulent pathogen threatening global amphibian biodiversity. Although pandemic in distribution, previous intensive field surveys have failed to detect Bd in Madagascar, a biodiversity hotspot home to hundreds of endemic amphibian species. Due to the presence of Bd in nearby continental Africa and the ecological crisis that can be expected following establishment in Madagascar, enhanced surveillance is imperative. I sampled 565 amphibians commercially exported from Madagascar for the presence of Bd upon importation to the USA, both to assist early detection efforts and demonstrate the conservation potential of wildlife trade disease surveillance. Bd was detected in three animals via quantitative PCR: a single Heterixalus alboguttatus, Heterixalus betsileo, and Scaphiophryne spinosa. This is the first time Bd has been confirmed in amphibians from Madagascar and presents an urgent call to action. Our early identification of pathogen presence prior to widespread infection provides the necessary tools and encouragement to catalyze a swift, targeted response to isolate and eradicate Bd from Madagascar. If implemented before establishment occurs, an otherwise likely catastrophic decline in amphibian biodiversity may be prevented. PMID:24599336

Batrachochytrium dendrobatidis prevalence and haplotypes in domestic and imported pet amphibians in Japan.

PubMed

Tamukai, Kenichi; Une, Yumi; Tominaga, Atsushi; Suzuki, Kazutaka; Goka, Koichi

2014-05-13

The international trade in amphibians is believed to have increased the spread of Batrachochytrium dendrobatidis (Bd), the fungal pathogen responsible for chytridiomycosis, which has caused a rapid decline in amphibian populations worldwide. We surveyed amphibians imported into Japan and those held in captivity for a long period or bred in Japan to clarify the Bd infection status. Samples were taken from 820 individuals of 109 amphibian species between 2008 and 2011 and were analyzed by a nested-PCR assay. Bd prevalence in imported amphibians was 10.3% (58/561), while it was 6.9% (18/259) in those in private collections and commercially bred amphibians in Japan. We identified the genotypes of this fungus using partial DNA sequences of the internal transcribed spacer (ITS) region. Sequencing of PCR products of all 76 Bd-positive samples revealed 11 haplotypes of the Bd ITS region. Haplotype A (DNA Data Bank of Japan accession number AB435211) was found in 90% (52/58) of imported amphibians. The results show that Bd is currently entering Japan via the international trade in exotic amphibians as pets, suggesting that the trade has indeed played a major role in the spread of Bd.

Presence of the amphibian chytrid fungus Batrachochytrium dendrobatidis in native amphibians exported from Madagascar.

PubMed

Kolby, Jonathan E

2014-01-01

The emerging infectious disease chytridiomycosis is driven by the spread of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd), a highly virulent pathogen threatening global amphibian biodiversity. Although pandemic in distribution, previous intensive field surveys have failed to detect Bd in Madagascar, a biodiversity hotspot home to hundreds of endemic amphibian species. Due to the presence of Bd in nearby continental Africa and the ecological crisis that can be expected following establishment in Madagascar, enhanced surveillance is imperative. I sampled 565 amphibians commercially exported from Madagascar for the presence of Bd upon importation to the USA, both to assist early detection efforts and demonstrate the conservation potential of wildlife trade disease surveillance. Bd was detected in three animals via quantitative PCR: a single Heterixalus alboguttatus, Heterixalus betsileo, and Scaphiophryne spinosa. This is the first time Bd has been confirmed in amphibians from Madagascar and presents an urgent call to action. Our early identification of pathogen presence prior to widespread infection provides the necessary tools and encouragement to catalyze a swift, targeted response to isolate and eradicate Bd from Madagascar. If implemented before establishment occurs, an otherwise likely catastrophic decline in amphibian biodiversity may be prevented.

Effects of bioDensity Training and Power Plate Whole-Body Vibration on Strength, Balance, and Functional Independence in Older Adults.

PubMed

Smith, Derek T; Judge, Stacey; Malone, Ashley; Moynes, Rebecca C; Conviser, Jason; Skinner, James S

2016-01-01

Reduced strength, balance, and functional independence diminish quality of life and increase health care costs. Sixty adults (82.2 ± 4.9 years) were randomized to a control or three 12-week intervention groups: bioDensity (bD); Power Plate (PP) whole-body vibration (WBV); or bD+PP. bD involved one weekly 5-s maximal contraction of four muscle groups. PP involved two 5-min WBV sessions. Primary outcomes were strength, balance, and Functional Independence Measure (FIM). No groups differed initially. Strength significantly increased 22-51% for three muscle groups in bD and bD+PP (P < .001), with no changes in control and PP. Balance significantly improved in PP and bD+PP but not in control or bD. bD, PP, and bD+PP differentially improved FIM self-care and mobility. Strength improvements from weekly 5-min sessions of bD may impart health/clinical benefits. Balance and leg strength improvements suggest WBV beneficially impacts fall risk and incidence. Improved FIM scores are encouraging and justify larger controlled trials on bD and bD+PP efficacy.

Bipolar disorder: a neural network perspective on a disorder of emotion and motivation.

PubMed

Wessa, Michèle; Kanske, Philipp; Linke, Julia

2014-01-01

Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.

The association between social skills deficits and family history of mood disorder in bipolar I disorder.

PubMed

Fernandes, Francy B F; Rocca, Cristiana C; Gigante, Alexandre D; Dottori-Silva, Paola R; Gerchmann, Luciana; Rossini, Danielle; Sato, Rodrigo; Lafer, Beny; Nery, Fabiano G

2018-03-26

To compare social skills and related executive functions among bipolar disorder (BD) patients with a family history of mood disorders (FHMD), BD patients with no FHMD and healthy control (HCs). We evaluated 20 euthymic patients with FHMD, 17 euthymic patients without FHMD, and 31 HCs using the Social Skills Inventory (SSI) and a neuropsychological battery evaluating executive function, inhibitory control, verbal fluency and estimated intelligence. Both BD groups had lower SSI scores than controls. Scores for one subfactor of the social skills questionnaire, conversational skills and social performance, were significantly lower among patients with FHMD than among patients without FHMD (p = 0.019). Both groups of BD patients exhibited significant deficits in initiation/inhibition, but only BD patients with FHMD had deficits in verbal fluency, both compared to HC. There were no associations between social skills questionnaire scores and measures of cognitive function. Euthymic BD patients have lower social skills and executive function performance than HC. The presence of FHMD among BD patients is specifically associated with deficits in conversational and social performance skills, in addition to deficits in verbal fluency. Both characteristics might be associated with a common genetically determined pathophysiological substrate.

Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

PubMed

Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

2016-06-01

Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

Obsessive-compulsive disorder with and without bipolar disorder.

PubMed

Mahasuar, Rajnarayan; Janardhan Reddy, Y C; Math, Suresh Bada

2011-08-01

Bipolar disorder (BD) is often comorbid with obsessive-compulsive disorder (OCD). In this study, we compared clinical profile and course of subjects with a primary diagnosis of OCD with and without BD. We compared 34 subjects with primary diagnosis of OCD with BD and 57 subjects with a diagnosis of OCD without BD. Structured interview schedules, clinical rating scales, and information from clinical charts were utilized to assess patients. OCD with BD was characterized by: (i) an episodic course; (ii) a higher number of depressive episodes, greater suicidality and a higher rate of hospitalization; (iii) fewer pathological doubts and more miscellaneous compulsions; and (iv) poorer insight into obsessive-compulsive symptoms. Episodic course appears to be typical of OCD with BD. Bipolarity has a pathoplastic effect on OCD and it is possible that some forms of OCD and BD are pathophysiologically related. Bipolar OCD is associated with a higher rate of depressive episodes, higher suicidality and more frequent hospitalizations, suggesting greater morbidity. Long-term prospective follow-up studies and studies addressing pathophysiology and genetic basis are needed to understand the complexity of such comorbidity. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Association of Higher Defensin β-4 Genomic Copy Numbers with Behçet's Disease in Iraqi Patients.

PubMed

Hameed, Ammar F; Jaradat, Sameh; Al-Musawi, Bassam M; Sharquie, Khalifa; Ibrahim, Mazin J; Hayani, Raafa K; Norgauer, Johannes

2015-11-01

Behçet's disease (BD) is an immune-mediated small vessel systemic vasculitis. Human β-defensins are antimicrobial peptides associated with many inflammatory diseases and are encoded by the β-defensin family of multiple-copy genes. However, their role in BD necessitates further investigation. The aim of the present study was to investigate the possible association of BD in its various clinical forms with defensin β-4 (DEFB4) genomic copy numbers. This case-control study was conducted from January to September 2011 and included 50 control subjects and 27 unrelated Iraqi BD patients registered at Baghdad Teaching Hospital, Bagdad, Iraq. Copy numbers of the DEFB4 gene were determined using the comparative cycle threshold method by duplex real-time polymerase chain reaction technology at the Department of Dermatology of Jena University Hospital, Jena, Germany. DEFB4 genomic copy numbers were significantly higher in the BD group compared to the control group (P = 0.010). However, no statistically significant association was found between copy numbers and clinical variables within the BD group. The DEFB4 copy number polymorphism may be associated with BD; however, it is not associated with different clinical manifestations of the disease.

Presence of amphibian chytrid fungus (Batrachochytrium dendrobatidis) in rainwater suggests aerial dispersal is possible

USGS Publications Warehouse

Kolby, Jonathan E.; Sara D. Ramirez,; Lee Berger,; Griffin, Dale W.; Merlijn Jocque,; Lee F. Skerratt,

2015-01-01

Abstract Global spread of the pathogenic amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) may involve dispersal mechanisms not previously explored. Weather systems accompanied by strong wind and rainfall have been known to assist the dispersal of microbes pathogenic to plants and animals, and we considered a similar phenomenon might occur with Bd. We investigated this concept by sampling rainwater from 20 precipitation events for the presence of Bd in Cusuco National Park, Honduras: a site where high Bd prevalence was previously detected in stream-associated amphibians. Quantitative PCR analysis confirmed the presence of Bd in rainwater in one (5 %) of the weather events sampled, although viability cannot be ascertained from molecular presence alone. The source of the Bd and distance that the contaminated rainwater traveled could not be determined; however, this collection site was located approximately 600 m from the nearest observed perennial river by straight-line aerial distance. Although our results suggest atmospheric Bd dispersal is uncommon and unpredictable, even occasional short-distance aerial transport could considerably expand the taxonomic diversity of amphibians vulnerable to exposure and at risk of decline, including terrestrial and arboreal species that are not associated with permanent water bodies.

Characterization of Batrachochytrium dendrobatidis Inhibiting Bacteria from Amphibian Populations in Costa Rica

PubMed Central

Madison, Joseph D.; Berg, Elizabeth A.; Abarca, Juan G.; Whitfield, Steven M.; Gorbatenko, Oxana; Pinto, Adrian; Kerby, Jacob L.

2017-01-01

Global amphibian declines and extinction events are occurring at an unprecedented rate. While several factors are responsible for declines and extinction, the fungal pathogen Batrachochytrium dendrobatidis (Bd) has been cited as a major constituent in these events. While the effects of this chytrid fungus have been shown to cause broad scale population declines and extinctions, certain individuals and relict populations have shown resistance. This resistance has been attributed in part to the cutaneous bacterial microbiome. Here, we present the first study characterizing anti-Bd bacterial isolates from amphibian populations in Costa Rica, including the characterization of two strains of Serratia marcescens presenting strong anti-Bd activity. Transcriptome sequencing was utilized for delineation of shifts in gene expression of the two previously uncharacterized strains of S. marcescens grown in three different treatments comprising Bd, heat-killed Bd, and a no Bd control. These results revealed up- and down-regulation of key genes associated with different metabolic and regulatory pathways. This information will be valuable in continued efforts to develop a bacterial-based approach for amphibian protection as well as providing direction for continued mechanistic inquiries of the bacterial anti-Bd response. PMID:28293222

What your eyes tell me: Theory of mind in bipolar disorder.

PubMed

Espinós, Usue; Fernández-Abascal, Enrique García; Ovejero, Mercedes

2018-04-01

The aim of this study was to assess social- perceptual Theory of Mind in bipolar disorder (BD). 112 euthymic participants with BD I or BD II (65 with BD I and 47 with BD II) were compared to a group of 112 persons with no psychiatric diagnosis and 43 with unipolar depression (UD). They completed the task of the "Reading the Mind in the Eyes" (RMET). The results show that participants with BD, I and II, as well as the group with UD performed significantly more poorly than the control group. As for the wrong answers, BDs mostly chose positive valence stimuli, while the UD group chose negative valence items. The main limitation of this research is related to the characteristics of the cross-sectional study. It cannot detect at what time of the disorder these differences in emotion processing will appear with more intensity. As for future research, we suggest interventions to improve the deficits in ToM in bipolar persons. The use of the RMET in the first stages of BD II could help to facilitate a correct diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

45 CFR Appendixes B-D to Part 74 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false [Reserved] B Appendixes B-D to Part 74 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS..., AND COMMERCIAL ORGANIZATIONS Appendixes B-D to Part 74 [Reserved] ...

45 CFR Appendixes B-D to Part 74 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false [Reserved] B Appendixes B-D to Part 74 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS..., AND COMMERCIAL ORGANIZATIONS Appendixes B-D to Part 74 [Reserved] ...

Composition and Toxicity of Biodiesel versus Conventional Diesel

EPA Science Inventory

Increasing production of biodiesel (BD) fuel at the local, national, and global levels raise important issues related to the impact and potential adverse health outcome related to BD exposures. Studies on the toxicity of BD combustion emissions are very limited. Emission co...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reno, J.; Dalrymple, D.

Before implementing a crosslinked polymer water-control treatment, a Phillips well was producing 33 b/d of oil and 318 b/d of water. After the treatment, oil production reached 40 b/d of oil and water production decreased to 130 b/d. Water disposal costs decreased by 60% and lifting and maintenance costs were also reduced. The technological key to the improvement was a dry polymer developed for use in hostile well environments. The polymer was crosslinked with chrome (III) propionate, a crosslinker with low toxicity that produces strong, rigid gels.

Iran sets sights on 5 million b/d of crude

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-21

This paper reports that Iran, currently producing 3.2 million b/d of oil, has set a production target of 5 million b/d by March 1994. On the way to that target Iran's oil flow will climb to 4 million b/d by March 1993, says A. Moshtaqhian, director of exploration and production for National Iranian Oil Co. (NIOC). With oil reserves of about 100 million bbl, Iran will find it easy to increase productive capacity, Moshtaqhian told the Gulf Oil and Politics publication.

Isolation and identification of berberine and berberrubine metabolites by berberine-utilizing bacterium Rhodococcus sp. strain BD7100.

PubMed

Ishikawa, Kazuki; Takeda, Hisashi; Wakana, Daigo; Sato, Fumihiko; Hosoe, Tomoo

2016-05-01

Based on the finding of a novel berberine (BBR)-utilizing bacterium, Rhodococcus sp. strain BD7100, we investigated the degradation of BBR and its analog berberrubine (BRU). Resting cells of BD7100 demethylenated BBR and BRU, yielding benzeneacetic acid analogs. Isolation of benzeneacetic acid analogs suggested that BD7100 degraded the isoquinoline ring of the protoberberine skeleton. This work represents the first report of cleavage of protoberberine skeleton by a microorganism.

Differential neural correlates of autobiographical memory recall in bipolar and unipolar depression.

PubMed

Young, Kymberly D; Bodurka, Jerzy; Drevets, Wayne C

2016-11-01

Autobiographical memory (AM) recall is impaired in both bipolar depression (BD) and major depressive disorder (MDD). The current study used functional magnetic resonance imaging (fMRI) to investigate differences between healthy controls (HCs) and depressed participants with either BD or MDD as they recalled AMs that varied in emotional valence. Unmedicated adults in a current major depressive episode who met criteria for either MDD or BD and HCs (n=16/group) underwent fMRI while recalling AMs in response to emotionally valenced cue words. Control tasks involved generating examples from a given category and counting the number of risers in a letter string. Both participants with BD and those with MDD recalled fewer specific and more categorical memories than HC participants. During specific AM recall of positive memories, participants with BD showed increased hemodynamic activity in the ventrolateral prefrontal cortex, posterior cingulate cortex, anterior insula, middle temporal gyrus, parahippocampus, and amygdala relative to MDD and HC participants, as well as decreased dorsolateral prefrontal (DLPFC) activity relative to MDD participants. During specific AM recall of negative memories, participants with BD manifested decreased activity in the precuneus, amygdala, anterior cingulate, and DLPFC along with increased activity in the dorsomedial PFC relative to MDD participants. While depressed participants with BD and MDD exhibited similar depression ratings and memory deficits, the brain regions underlying successful AM recall significantly differentiated these patient groups. Differential amygdala activity during emotional memory recall (particularly increased activity in participants with BD for positive AMs) may prove useful in the differentiation of individuals with MDD and BD experiencing a depressive episode. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Head-to-head comparison of the diagnostic accuracies of BD Veritor™ System RSV and Quidel® Sofia® RSV FIA systems for respiratory syncytial virus (RSV) diagnosis.

PubMed

Kanwar, Neena; Hassan, Ferdaus; Nguyen, Ashley; Selvarangan, Rangaraj

2015-04-01

Respiratory syncytial virus (RSV) is one of the most common causes of severe lower respiratory tract disease among infants and young children. BD Veritor™ System RSV (BD) and Quidel(®) Sofia(®) RSV FIA (QD) are the new generation lateral flow digital immunoassay (DIA) tests with an instrumented read for the qualitative detection of RSV viral antigens. To compare the diagnostic accuracies of BD and QD for RSV detection using fresh nasopharyngeal aspirates and nasopharyngeal swab specimens collected in universal transport media during 2013-2014 respiratory season. The two DIA tests were performed simultaneously on randomly selected specimens on a weekly basis during the RSV season until 200 fresh remnant specimens were enrolled. Real-time RT-PCR assay results were used to compare and evaluate the performance of both RSV DIA assays. Among 200 specimens tested, RSV real-time RT-PCR assay detected RSV in 104 samples, while QD detected 84 samples and BD detected 74 samples as positive. The overall sensitivity for detection of RSV in comparison to PCR was 71.15% (61.3-79.4) for BD and 80.77% (71.6-87.6) for QD system (P=0.36). The specificity was 100% (95.2-100) for both systems. The work flow analysis revealed that the overall specimen processing time was significantly lower for BD as compared with the QD assay. In comparison with the real-time PCR, the QD system showed a higher sensitivity than that of the BD system, but the difference did not reach statistical significance (P=0.36). Both BD and QD systems were found comparable in terms of specificity. Copyright © 2015 Elsevier B.V. All rights reserved.

Cannabis use disorder is associated with greater illness severity in tobacco smoking patients with bipolar disorder.

PubMed

Lagerberg, T V; Icick, R; Andreassen, O A; Ringen, P A; Etain, B; Aas, M; Henry, C; Bjella, T D; Melle, I; Bellivier, F

2016-01-15

Cannabis use disorders (CUD) may influence the course of bipolar disorder (BD), but key confounding factors such as tobacco smoking have not been adequately addressed. This study examined whether CUD was associated with a more severe illness course in tobacco smoking BD patients. A sample of French and Norwegian tobacco smoking patients with BD I and II (N=642) was investigated. DSM-IV diagnoses and other characteristics were obtained through personal interviews using structured questionnaires. The association between CUD and illness course was assessed in regression analyses. In bivariate analyses, CUD was associated with earlier BD onset, higher frequency of manic (in BD I) and depressive episodes and hospitalizations per illness year, and a higher occurrence of psychotic episodes. After controlling for potential confounders, the relationships with earlier BD onset (B=-5.60 95% CI=-7.65 to -3.64), and increased rates of manic episodes (OR=1.93, 95% CI: 1.15 to 3.23) and hospitalizations (OR=2.93, 95% CI: 1.85 to 4.64) remained statistically significant. Despite the multivariate approach, differences between the two samples may lead to spurious findings related to hidden confounders. Substance use and mood episode information was collected retrospectively, and potential birth cohort effects could not be controlled for. Studies have found associations between tobacco smoking and poorer outcomes in BD. In this study on tobacco smoking BD patients we report an association between CUD and illness severity, suggesting that CUD exacerbates the disease evolution independently of tobacco smoking. Specific treatment and prevention programs addressing CUD in BD patients are warranted. Copyright © 2015 Elsevier B.V. All rights reserved.