bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive animal models of mania: hits, misses and future directions
Authors: Young Jared W , Henry Brook L , Geyer Mark A 
Published: March 2011

Mania has long been recognized as aberrant behaviour indicative of mental illness. Manic states include a variety of complex and multifaceted symptoms that challenge clear clinical distinctions. Symptoms include over‐activity, hypersexuality, irritability and reduced need for sleep, with cognitive deficits recently linked to functional outcome. Current treatments have arisen through serendipity or from other disorders. Hence, treatments are not efficacious for all patients, and there is an urgent need to develop targeted therapeutics. Part of the drug discovery process is the assessment of therapeutics in animal models. Here we review pharmacological, environmental and genetic manipulations developed to test the efficacy of therapeutics in animal models of mania. The merits of these models are discussed in terms of the manipulation used and the facet of mania measured. Moreover, the predictive validity of these models is discussed in the context of differentiating drugs that succeed or fail to meet criteria as approved mania treatments. The multifaceted symptomatology of mania has not been reflected in the majority of animal models, where locomotor activity remains the primary measure. This approach has resulted in numerous false positives for putative treatments. Recent work highlights the need to utilize multivariate strategies to enable comprehensive assessment of affective and cognitive dysfunction. Advances in therapeutic treatment may depend on novel models developed with an integrated approach that includes: (i) a comprehensive battery of tests for different aspects of mania, (ii) utilization of genetic information to establish aetiological validity and (iii) objective quantification of patient behaviour with translational cross‐species paradigms.LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
The endocannabinoid system and cancer: therapeutic implication
Authors: Guindon Josée , Hohmann Andrea G 
Published: March 2011

The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others). The main active ingredient of cannabis, Δ9‐tetrahydrocannabinol (Δ9‐THC), produces its effects through activation of CB1 and CB2 receptors. CB1 receptors are expressed at high levels in the central nervous system (CNS), whereas CB2 receptors are concentrated predominantly, although not exclusively, in cells of the immune system. Endocannabinoids are endogenous lipid‐signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG). Here we review the relationship between the endocannabinoid system and anti‐tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer. This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed. Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis‐like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients. Further basic research on anti‐cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted.LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
An assessment of oral health promotion programmes in the United Kingdom
Authors: Passalacqua A. , Reeves A. O. , Newton T. , Hughes R. , Dunne S. , Donaldson N. , Wilson N. 
Published: March 2011

AbstractBackground:  Improving oral health and reducing tooth decay is a key area for action, both in the United Kingdom (UK) and overseas. The World Health Organization (WHO) has highlighted the unique advantage schools have in promoting oral health.Aim:  We summarise current oral health promotion strategies in the United Kingdom and estimate the spread of their use as well as their impact on oral health and influence on the oral health‐related knowledge and behaviour in a patient population.Methods:  A structured overview of published papers, government publications, official government websites and policy reports. A cross‐sectional study of patients referred for a tooth extraction in one dental surgery in south‐east London. Statistical methods consisted of logistic and ordinal regressions to model the likelihood of exposure to oral health promotion and of obtaining higher levels of knowledge of oral health issues, respectively. Linear regression was used to model the level of oral health and knowledge of oral health issues.Results:  We found three main promotion programmes, namely, National Healthy Schools (NHS), Sure Start and Brushing for life plus a small number of local initiatives. Sure Start targets disadvantaged areas, but is limited. In our observational study, 34% of the patients reported exposure to a settings‐based oral health education programme: Sure Start (5%), NHS (7%) and other (22%). This exposure was not influenced by age or gender, but an association with education was detected. Although oral health promotion was not found to influence the actual knowledge of oral health issues, it was found to influence some oral health‐related attitudes and perceptions.Conclusions:  Participation in an oral health promotion programme was found to be significantly associated with the patients’ education, their belief that they can prevent oral disease and the subjective perception of their own oral health. The WHO principles need to be embedded across all schools to achieve a true national oral health promotion programme for the United Kingdom. The National Healthy Schools programme provides the perfect platform.
Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain
Authors: Freitas Tiago P. , Rezin Gislaine T. , Fraga Daiane B. , Moretti Morgana , Vieira Julia S. , Gomes Lara M. , Borges Lislaine S. , Valvassori Samira S. , Quevedo João , Streck Emilio L. 
Published: March 2011

Objectives:Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods:Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3and 10−2M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results:Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3and 10−2M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2M.Conclusion:Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.
Differential adhesion of Streptococcus mutans to metallic brackets induced by saliva from caries‐free and caries‐active individuals
Authors: do Rosário Ademir Franco , Knop Luégya Amorin Henriques , Baboni Fernanda Brasil , Rymovicz Alinne Ulbrich Mores , Tanaka Orlando Motohiro , Rosa Edvaldo Antonio Ribeiro 
Published: March 2011

AbstractAim:  The purpose of this study was to evaluate the influence of saliva obtained from caries‐free and caries‐active individuals on the adhesion rates of Streptococcus mutans to metallic brackets.Methods:  The unstimulated whole saliva of four caries‐free (decayed, missing, or filled surfaces = 0) volunteers and four caries‐active (decayed, missing, or filled surfaces >12) patients were collected. The saliva samples from each group were mixed and clarified. Acquired pellicles were formed onto 30 metallic edgewise brackets for premolars for each saliva group. The brackets were put in contact with planktonic cells of Streptococcus mutans ATCC 25175. Adhesion rates were assessed by crystal violet retention technique.Results:  A higher streptococcal adhesion pattern (P < 0.00001) was observed on acquired pellicles formed by saliva from caries‐active donors.Conclusions:  The results showed that saliva from caries‐active patients tends to increase the mutans adhesion to surfaces, which is a point of concern for orthodontists.
Insulin resistance in equine digital vessel rings: Anin vitromodel to study vascular dysfunction in equine laminitis
Authors: VENUGOPAL C. S. , EADES S. , HOLMES E. P. , BEADLE R. E. 
Published: March 2011

SummaryReasons for performing study:One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels.Hypothesis and objectives:Insulin resistance can be induced in palmar digital vessels by continued exposure to insulinin vitro. The objective was to evaluate thisin vitromodel for future studies.Methods:Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3‐kinase) and PD‐098059 (to block MAP‐kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min.Results:Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin‐incubated and wortmannin‐incubated rings.Conclusions:This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP‐kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions.Potential relevance:The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a goodin vitromodel for studying the vascular insulin resistance which may occur in equine laminitis.
In Vivo
Regulation of the Vi Antigen in Salmonella and Induction of Immune Responses with an
In Vivo
-Inducible Promoter
Authors: Janis Carole , Grant Andrew J. , McKinley Trevelyan J. , Morgan Fiona J. E. , John Victoria F. , Houghton Jenny , Kingsley Robert A. , Dougan Gordon , Mastroeni Pietro 
Published: March 2011

ABSTRACT

Salmonella enterica
serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of
S.
Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of
S.
Typhimurium carrying the whole
Salmonella
pathogenicity island 7 (SPI-7) to monitor
in vivo
Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of
in vivo
-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural
tviA
promoter with the promoter of the SPI-2 gene
ssaG
resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of
S.
Typhimurium expressing Vi under the control of the
ssaG
promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated
in vivo
and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.
Participation of CD11c
+
Leukocytes in Methicillin-Resistant Staphylococcus aureus Clearance from the Lung
Authors: Martin Francis J. , Parker Dane , Harfenist Bryan S. , Soong Grace , Prince Alice 
Published: March 2011

ABSTRACT

Staphylococcus aureus
causes especially severe pulmonary infection, associated with high morbidity and mortality. In addition to the effects of specific virulence factors, it appears that the intensity of the host proinflammatory response, particularly in the initial stages of infection, contributes substantially to pulmonary damage. We tested the hypothesis that the CD11c
+
leukocytes are important in the host response to pulmonary infection with methicillin-resistant
S. aureus
(MRSA) USA300. Clodronate-induced depletion of the alveolar macrophage population resulted in increased numbers of dendritic cells (DCs) and CD4
+
cells in bronchoalveolar lavage (BAL) fluid and was associated with significantly increased mortality by 18 h following
S. aureus
inoculation but had no effect on bacterial load or polymorphonuclear leukocyte (PMN) numbers in the lung. These clodronate-treated mice also had increased expression of interleukin-17A/F (IL-17A/F) and CXCL10 but not of gamma interferon (IFN-γ) or tumor necrosis factor (TNF). Depletion of the dendritic cell population in mice expressing a CD11c-enhanced green fluorescent protein (EGFP)-diphtheria toxin receptor (DTR) transgene was associated with an increased bacterial load in the lung but not increased mortality. Both DCs and airway epithelial cells produced CXCL9, -10, and -11 in response to
S. aureus
. Pretreatment of mice with an anti-CXCR3 antibody prior to inoculation with MRSA substantially reduced CD4
+
cells and decreased pulmonary inflammation at 18 h postinfection compared to pretreatment with an IgG control. The results of these experiments suggest that CD11c
+
cells, the induction of CXCR3 ligand expression, and subsequent CD4
+
cell recruitment have an important role in the pathogenesis of severe MRSA pulmonary infection.
Common Fixed Point Theorems for Four Mappings on Cone Metric Type Space
Authors: Cvetković AleksandarS , Stanić MarijaP , Dimitrijević Sladjana , Simić Suzana 
Published: March 2011

AbstractIn this paper we consider the so called a cone metric type space, which is a generalization of a cone metric space. We prove some common fixed point theorems for four mappings in those spaces. Obtained results extend and generalize well-known comparable results in the literature. All results are proved in the settings of a solid cone, without the assumption of continuity of mappings.
Randomized, Controlled Trial of an Intervention to Enable Stroke Survivors Throughout the Los Angeles County Safety Net to “Stay With the Guidelines”
Authors: Cheng Eric M. , Cunningham William E. , Towfighi Amytis , Sanossian Nerses , Bryg Robert J. , Anderson Thomas L. , Guterman Jeffrey J. , Gross-Schulman Sandra G. , Beanes Sylvia , Jones Andrea S. , Liu Honghu , Ettner Susan L. , Saver Jeffrey L. , Vickrey Barbara G. 
Published: March 2011

Background—
Stroke is the leading cause of adult disability. Inpatient programs optimize secondary stroke prevention care at the time of hospital discharge, but such care may not be continued after hospital discharge.

Methods—
To improve the delivery of secondary stroke preventive services after hospital discharge, we have designed a chronic care model–based program called SUSTAIN (Systemic Use of STroke Averting INterventions). This care intervention includes group clinics, self-management support, report cards, decision support through care guides and protocols, and coordination of ongoing care. The first specific aim is to test, in a randomized, controlled trial, whether SUSTAIN improves blood pressure control among an analytic sample of 268 patients with a recent stroke or transient ischemic attack discharged from 4 Los Angeles County public hospitals. Secondary outcomes consist of control of other stroke risk factors, lifestyle habits, medication adherence, patient perceptions of care quality, functional status, and quality of life. A second specific aim is to conduct a cost analysis of SUSTAIN from the perspective of the Los Angeles County Department of Health Services by using direct costs of the intervention, cost equivalents of associated utilization of county system resources, and cost equivalents of the observed and predicted averted vascular events.

Conclusions—
If SUSTAIN is effective, we will have the expertise and findings to advocate for its continued support at Los Angeles County hospitals and to disseminate the SUSTAIN program to other settings serving indigent, minority populations.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00861081.
Combined transcranial direct current stimulation and robot-assisted gait training in patients with chronic stroke: a preliminary comparison
Authors: Geroin Christian , Picelli Alessandro , Munari Daniele , Waldner Andreas , Tomelleri Christopher , Smania Nicola 
Published: March 2011

Objective: To evaluate whether robot-assisted gait training combined with transcranial direct current stimulation is more effective than robot-assisted gait training alone or conventional walking rehabilitation for improving walking ability in stroke patients. Design: Pilot randomized clinical trial. Setting: Rehabilitation unit of a university hospital. Subjects: Thirty patients with chronic stroke. Interventions: All patients received ten 50-minute treatment sessions, five days a week, for two consecutive weeks. Group 1 (n = 10) underwent a robot-assisted gait training combined with transcranial direct current stimulation; group 2 (n = 10) underwent a robot-assisted gait training combined with sham transcranial direct current stimulation; group 3 (n = 10) performed overground walking exercises. Main measures: Patients were evaluated before, immediately after and two weeks post treatment. Primary outcomes: six-minute walking test, 10-m walking test. Results: No differences were found between groups 1 and 2 for all primary outcome measures at the after treatment and follow-up evaluations. A statistically significant improvement was found after treatment in performance on the six-minute walking test and the 10-m walking test in favour of group 1 (six-minute walking test: 205.20 ± 61.16 m; 10-m walking test: 16.20 ± 7.65 s) and group 2 (six-minute walking test: 182.5 ± 69.30 m; 10-m walking test: 17.71 ± 8.20 s) compared with group 3 (six-minute walking test: 116.30 ± 75.40 m; 10-m walking test: 26.30 ± 14.10 s). All improvements were maintained at the follow-up evaluation. Conclusions: In the present pilot study transcranial direct current stimulation had no additional effect on robot-assisted gait training in patients with chronic stroke. Larger studies are required to confirm these preliminary findings.
Supporting community-based exercise in long-term neurological conditions: experience from the Long-term Individual Fitness Enablement (LIFE) project
Authors:   The LIFE group
Published: March 2011

Background: Patients with long-term neurological conditions often have low levels of physical activity and participation in exercise. Exercise referral schemes have been introduced in the UK to encourage physical activity in sedentary and clinical populations but typically exclude patients with long-term neurological conditions. We have developed and evaluated an exercise support system for people with long-term neurological disability, called the Physical Activity Support System, to enable them to use local gym facilities safely and effectively. The intervention: We describe the Physical Activity Support System for people with long-term neurological conditions and provide data on the use of this system in a phase II randomized controlled study trial. The system has five key components: access and transport advice, the fitness instructor, the gym, health professional support and how to exercise safely. Results: Ninety-nine patients with a range of long-term neurological conditions used six different community exercise facilities in Oxfordshire and Birmingham. Average gym attendance was one session per week for 12 weeks. Participants required an average of three 1-hour face-to-face physiotherapy contacts to achieve this. The average direct cost for the support system was £275. Conclusions: The scheme achieved comparable exercise participation to standard GP exercise referral schemes operating in the same centres and offers a relatively cheap, practical and feasible system for supporting people with long-term neurological conditions.
Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages
Authors: Deng Zhongbin , Pardi Ruggero , Cheadle William , Xiang Xiaoyu , Zhang Shuangyin , Shah Spandan V. , Grizzle William , Miller Donald , Mountz John , Zhang Huang-Ge 
Published: March 2011

Abstract
COP9 plays a role in plant innate immunity. The role of COP9 in mammalian innate immune responses is unknown. Here, we show that the COP9 signalosome subunit 5 (CSN5) is required for activation of proinflammatory kinases p38 and Erk and for down-regulation of the expression of genes regulated by nuclear factor E2-related factor 2. Mice with myeloid-specific CSN5 deficiency have lower mortality in polymicrobial sepsis. CSN5 is required for both Toll-like receptor (TLR) and reactive oxygen species–mediated deneddylation of Cul3, which is essential for Cul3/Keap1-mediated degradation of nuclear factor E2-related factor 2. On the basis of our results COP9 subunit CSN5 is considered to be an essential component of mammalian innate immunity.