bluuebunny/crossref_metadata_2025_split huggingface dataset:
Animal models to guide clinical drug development in ADHD: lost in translation?
Authors: Wickens Jeffery R , Hyland Brian I , Tripp Gail 
Published: April 2011

We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention‐deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open‐field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6‐hydroxydopamine‐lesioned (6‐OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6‐OHDA‐lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.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
Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways
Authors: Gomez O , Sanchez‐Rodriguez A , Le MQU , Sanchez‐Caro C , Molina‐Holgado F , Molina‐Holgado E 
Published: April 2011

BACKGROUND AND PURPOSE The endogenous cannabinoid system participates in oligodendrocyte progenitor differentiation in vitro. To determine the effect of synthetic cannabinoids on oligodendrocyte differentiation, we exposed differentiating cultures of oligodendrocytes with cannabinoid CB1, CB2 and CB1/CB2 receptor agonists and antagonists. The response of the PI3K/Akt and the mammalian target of rapamycin (mTOR) signalling pathways were studied as effectors of cannabinoid activity.EXPERIMENTAL APPROACH Purified oligodendrocyte progenitor cells (OPC) obtained from primary mixed glial cell cultures were treated for 48 h with CB1, CB2 and CB1/CB2 receptor agonists (ACEA, JWH133 and HU210, respectively) in the presence or absence of the antagonists AM281 (CB1 receptor) and AM630 (CB2 receptor). Moreover, inhibitors of the phosphatidylinositol 3‐kinase (PI3K)/Akt and mTOR pathways (LY294002 and rapamycin, respectively) were used to study the involvement of these pathways on cannabinoid‐induced OPC maturation.KEY RESULTS ACEA, JWH133 and HU‐210 enhanced OPC differentiation as assessed by the expression of stage specific antigens and myelin basic protein (MBP). Moreover, this effect was blocked by the CB receptor antagonists. ACEA, JWH133 and HU210 induced a time‐dependent phosphorylation of Akt and mTOR, whereas the inhibitors of PI3K/Akt (LY294002) or of mTOR (rapamycin) reversed the effects of HU‐210 on oligodendrocyte differentiation and kinase activation.CONCLUSIONS AND IMPLICATIONS Activation of cannabinoid CB1 or CB2 receptors with selective agonists accelerated oligodendrocyte differentiation through the mTOR and Akt signalling pathways.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
Non‐invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice
Authors: Wang Qin , Luan Wei , Goz Vadim , Burakoff Steven J. , Hiotis Spiros P. 
Published: April 2011

AbstractBackground: Maintenance of complex transgenic colonies and labour‐intensive techniques pose significant challenges in work involving mouse models for hepatocellular carcinoma (HCC). Other animal models of unusual species are generally impractical for research purposes.Aims: To develop a highly reproducible orthotopic mouse model for HCC based on the murine α‐foetoprotein (AFP), producing cell line Hepa1‐6 and to monitor liver tumour progression via in vivo imaging, and measurement of plasma AFP.Methods: Intrahepatic tumour was induced following subcapsular implantation of 10+6 Hepa1‐6 cells into C57L/J mice. AFP production was examined in vitro and in vivo using immunoblotting. Three confirmatory non‐invasive imaging modalities were applied to follow tumour progression over time including ultrasound biomicroscopy (UBM), micromagnetic resonance imaging (microMRI), and bioluminescence.Results: α‐foetoprotein expression was confirmed both in vitro and in vivo, with increasing levels in the plasma as tumours progressed. UBM, microMRI and bioluminescence detected intrahepatic tumours to a 2 mm resolution by day 14. Sequential imaging studies demonstrated an intrahepatic pattern of disease progression with an observed median survival of 29 days. Immunosuppression of tumour‐bearing mice led to a greater tumour size and decreased survival.Conclusions: Intrahepatic implantation of Hepa1‐6 as a mouse model for HCC is a highly reproducible in vivo system with tumour biology analogous to human disease and is regulated by the presence of an intact host immune system. Tumour progression may be monitored in vivo by UBM, microMRI and bioluminescence. Plasma AFP increases over time, allowing redundancy in non‐invasive means of following tumour progression.
The critical care nurse's role in End‐of‐Life care: issues and challenges
Authors: Efstathiou Nikolaos , Clifford Collette 
Published: April 2011

Aim: The purpose of this article is to discuss the challenges critical care nurses face when looking after patients needing End‐of‐Life (EoL) care in critical care environments. Background: Critical care nurses frequently provide care to patients who fail to respond to treatments offered to support and prolong life. The dying phase for individuals in critical care settings, commonly after withholding/withdrawing treatment, is very short posing great demands on critical care nurses to provide physical and emotional support to both patients and their families. Despite the existence of recognized care planning frameworks that may help nurses in providing EoL care, these are not used by all units and many nurses rely on experience to inform practice. A number of aspects such as communication, patient/family‐centred decision‐making, continuity of care, emotional/spiritual support and support for health professionals have been indicated as contributing factors towards the provision of effective EoL care. These are considered from the perspective of critical care nursing. Conclusion: Skills development in key aspects of care provision may improve the provision of EoL care for critical care patients and their families. Relevance to clinical practice: Critical care nurses have an essential role in the provision of effective EoL care; however, this dimension of their role needs further exploration. It is noted that educational opportunities need to be provided for critical care nurses to increase the knowledge on planning and delivering EoL care. To inform this evaluation of current EoL care provision in critical care is necessary to address a knowledge deficit of the needs of nurses who seek to support patients and their families at a critical time.
‘The patient is my space’: hermeneutic investigation of the nurse‐patient relationship in critical care
Authors: Vouzavali Foteini JD , Papathanassoglou Elizabeth DE , Karanikola Maria NK , Koutroubas Anna , Patiraki Elisabeth I , Papadatou Danai 
Published: April 2011

Background: The nurse‐patient relationship has been postulated to lie at the core of nursing care. However, it is unclear how this concept applies in critical care, as a great majority of critically ill patients are unable to communicate. Aims: Through a phenomenological hermeneutical perspective, we aimed to explore intensive care nurses' perceptions and meanings regarding their interpersonal relationship with critically ill individuals. Methods: A Heideggerian hermeneutical approach was used to design the study and analyse the data, which were collected through repetitive interviews with 12 intensive care nurses. Results: Critical care nurses report to experience deep relationships with patients, which seem to be mediated by the ongoing contact with patients' bodies. These relationships evoke intense feelings of love, empathy and care and affect how nurses perceive and make sense of their role and their world. The identified core theme of their experience is entitled ‘syncytium’, which describes a network of closely connected cells. According to participants' perceptions, nurse and patient affect each other reciprocally and are mutually dependent upon each other. In Heideggerian terms patients provide nurses with opportunities to experience ‘authentic care’ and they participate in their ‘being‐in‐the‐world’, thus they are central in nurses' meanings about their role and existence. Other elicited themes that account for the perceived nurse‐patient relationship include the spatiality/temporality of the relationship, nurses' perceptions and meanings attributed to their role and nurses' perceptions of death. Conclusions: Critical care nurses appear to experience their relationships with patients intensely. These relationships are invested with meanings and elicit powerful feelings over a shared course with patients. Patients are central in nurses' meaning‐making process and role perception. Relevance to clinical practice: These findings have implications for the educational preparation of critical care nurses and their psychological support.
The Risks of High Ultrafiltration Rate in Chronic Hemodialysis: Implications for Patient Care
Authors: Flythe Jennifer E. , Brunelli Steven M. 
Published: April 2011

AbstractAs dialytic practice has evolved, hemodialysis (HD) adequacy has come to be defined in terms of small molecule clearance. A growing body of evidence suggests that fluid dynamics, specifically ultrafiltration rate (UFR), bear clinical and physiological significance and should perhaps play a more central role in titrating HD therapy. Three recent studies have shown an independent association between higher UFR and mortality. Further work is needed to determine whether this relationship represents a direct toxic effect of rapid fluid perturbations or whether this association is a consequence of confounding on the basis of large interdialytic weight gain, as each would prompt a different therapeutic response. This mounting evidence builds the case that fluid management should play a more central role in the dialytic prescription and that more individualized approaches to fluid management should be encouraged.
The Risks and Benefits of Implementing Glycemic Control Guidelines in Frail Older Adults with Diabetes Mellitus
Authors: Lee Sei J. , Boscardin W. John , Stijacic Cenzer Irena , Huang Elbert S. , Rice‐Trumble Kathy , Eng Catherine 
Published: April 2011

OBJECTIVES: To determine the hypo‐ and hyperglycemic outcomes associated with implementing the American Geriatrics Society (AGS) guideline for a glycosylated hemoglobin (HbA1c) level of less than 8% in frail older adults with diabetes mellitus (DM).DESIGN: Guideline implementation.SETTING: Program of All‐Inclusive Care for the Elderly.PARTICIPANTS: All participants in the before (October 2002–December 2004, n=338), early (January 2005–June 2006, n=289) and late (July 2006–December 2008, n=385) periods of guideline implementation with a diagnosis of DM and at least one HbA1c measurement.INTERVENTION: Clinician education in 2005 with annual monitoring of the proportion of each clinician's patients with DM with HbA1c less than 8%.MEASUREMENTS: Hypoglycemia (blood glucose<50 mg/dL), hyperglycemia (blood glucose>400 mg/dL), and severe hypoglycemia (emergency department (ED) visit for hypoglycemia).RESULTS: Participants in the before, early, and late periods were similar in age, race and ethnicity, comorbidities, and functional dependence. Antihyperglycemic medication use was greater in the late period, with more participants using metformin (28% before, 42% late, P<.001) and insulin (23% before, 34% late, P<.001) and achieving the AGS glycemic target of HbA1c of less than 8% (74% before, 84% late, P<.001). Episodes of hyperglycemia (per 100 person‐years) were dramatically lower in the late period (159 before, 46 late, P<.001), and episodes of hypoglycemia were similar (10.1 before, 9.3 late, P=.50). There were more episodes of severe hypoglycemia in the early period (1.1 before, 2.9 early, P=.03).CONCLUSION: Implementing the AGS glycemic control guideline for frail older adults led to fewer hyperglycemic episodes but more severe hypoglycemic episodes requiring ED visits in the early implementation period. Future glycemic control guideline implementation efforts should be coupled with close monitoring for severe hypoglycemia in the early guideline implementation period.
Electronic Nursing Documentation as a Strategy to Improve Quality of Patient Care
Authors: Kelley Tiffany F. , Brandon Debra H. , Docherty Sharron L. 
Published: April 2011

Abstract Purpose: Electronic health records are expected to improve the quality of care provided to hospitalized patients. For nurses, use of electronic documentation sources becomes highly relevant because this is where they obtain the majority of necessary patient information. Methods: An integrative review of the literature examined the relationship between electronic nursing documentation and the quality of care provided to hospitalized patients. Donabedian's quality framework was used to organize empirical literature for review. Results: To date, the use of electronic nursing documentation to improve patient outcomes remains unclear. Conclusions and Implications: Future research should investigate the day‐to‐day interactions between nurses and electronic nursing documentation for the provision of quality care to hospitalized patients. Clinical Relevance: The majority of U.S. hospital care units currently use paper‐based nursing documentation to exchange patient information for quality care. However, by 2014, all U.S. hospitals are expected to use electronic nursing documentation on patient care units, with the anticipated benefit of improved quality. However, the extent to which electronic nursing documentation improves the quality of care to hospitalized patients remains unknown, in part due to the lack of effective comparisons with paper‐based nursing documentation.
Differential adaptation to water deprivation in first‐instar nymphs of the German cockroach (Blattella germanica) and the brown‐banded cockroach (Supella longipalpa)
Authors: Melton Robert H. 
Published: April 2011

AbstractThis study compares the relative abilities of first‐instar nymphs of the german cockroach (Blattella germanica L.) and the brown‐banded cockroach (Supella longipalpa F.) to survive prolonged periods of food and/or water deprivation. S. longipalpa nymphs survived significantly longer than B. germanica nymphs when drinking water was absent, but the advantage of S. longipalpa over B. germanica disappeared if food was also absent. These results are consistent with the hypothesis that S. longipalpa is adapted to drier habitats than is B. germanica, and suggest that S. longipalpa nymphs may be more capable of producing and utilizing extra metabolic water from food than B. germanica nymphs. Evidence from the literature suggests that this species difference applies mainly to juveniles, since adults of B. germanica and S. longipalpa do not differ in ability to withstand water deprivation, regardless of food availability.
Evaluation of lytic activity of staphylococcal bacteriophage Sb‐1 against freshly isolated clinical pathogens
Authors: Kvachadze Leila , Balarjishvili Nana , Meskhi Tamila , Tevdoradze Ekaterine , Skhirtladze Natia , Pataridze Tamila , Adamia Revaz , Topuria Temur , Kutter Elizabeth , Rohde Christine , Kutateladze Mzia 
Published: April 2011

SummaryIn recent decades the increase in antibiotic‐resistant bacterial strains has become a serious threat to the treatment of infectious diseases. Drug resistance of Staphylococcus aureus has become a major problem in hospitals of many countries, including developed ones. Today the interest in alternative remedies to antibiotics, including bacteriophage treatment, is gaining new ground. Here, we describe the staphylococcal bacteriophage Sb‐1 – a key component of therapeutic phage preparation that was successfully used against staphylococcal infections during many years in the Former Soviet Union. This phage still reveals a high spectrum of lytic activity in vitro against freshly isolated, genetically different clinical samples (including methicillin‐resistant S. aureus) obtained from the local hospitals, as well as the clinics from different geographical areas. The sequence analyses of phage genome showed absence of bacterial virulence genes. A case report describes a promising clinical response after phage application in patient with cystic fibrosis and indicates the efficacy of usage of Sb‐1 phage against various staphylococcal infections.
Next‐generation sequencing of transcriptomes: a guide to RNA isolation in nonmodel animals
Authors: GAYRAL PHILIPPE , WEINERT LUCY , CHIARI YLENIA , TSAGKOGEORGA GEORGIA , BALLENGHIEN MARION , GALTIER NICOLAS 
Published: April 2011

AbstractNext Generation Sequencing technologies (NGS) are rapidly invading many evolutionary and ecological fields, such as phylogenomics, molecular evolution, population genomics and molecular ecology. Among the potential targets of NGS is transcriptome sequencing, a fast and relatively cheap way to generate massive amounts of coding sequence data, offering promising perspectives for the analysis of molecular diversity in the wild. A number of molecular ecology research groups therefore may switch from DNA‐based to RNA‐based typing in the near future. Sample preparation from natural populations, however, requires specific care and protocols when RNA is the target. Furthermore, NGS sequencing of transcriptome requires high amount of good‐quality RNA. Here we present the results of RNA extraction experiments from various samples of 39 animal species caught in the wild. We compared tissue preparation and storage conditions, evaluated and improved standard RNA extraction protocols, and achieved RNA yield and quality suitable for NGS in all cases. We derive general guidelines for the production of ready‐to‐sequence RNA in nonmodel animals sampled in the field.
Influenza A Pandemic (H1N1) 2009 Virus Outbreak in a Cat Colony in Italy
Authors: Fiorentini L. , Taddei R. , Moreno A. , Gelmetti D. , Barbieri I. , De Marco M. A. , Tosi G. , Cordioli P. , Massi P. 
Published: April 2011

SummaryIn April 2009, a novel H1N1 influenza A virus (pH1N1) was recognized as the cause of the flu pandemic in humans. Here, we report the isolation of pH1N1 virus from the lung homogenates of two cats, which died after severe respiratory symptoms. The cats belonged to a cat colony consisting of 90 caged cats and were found dead following a 2‐week period of respiratory and gastrointestinal diseases in the colony. During the outbreak, 25 cats died and 50% of the animal colony showed anorexia, depression, respiratory and gastrointestinal symptoms. Histological examination of the lungs of the two tested cats displayed lesions centred on terminal airways with epithelial bronchiolar hyperplasia and alveolar necrosis. Influenza A virus was detected in the lung tissues by immunohistochemistry and real‐time RT‐PCR (rRT‐PCR). Partial sequences of haemagglutinin (HA) genes and complete sequences of neuraminidase (NA) genes of the two isolates displayed high similarity to the pH1N1 viruses circulating in humans (99% for HA gene and 100% for NA gene). To determine whether the pandemic virus had circulated among cats, serum samples and pharyngeal swabs were collected from 38 cats of the colony. Serum samples were tested by ELISA to detect antibodies against pH1N1 nucleoprotein and by hemagglutination‐inhibition test, while pharyngeal swabs were examined by pH1N1 specific rRT‐PCR. Twenty‐one (55%) of the tested cats carried antibodies against the isolated strain and two swabs were positive for the presence of pH1N1 RNA. Our results confirm that the pH1N1 virus was able to infect cats and raise the hypothesis of the circulation of the virus within the colony being due to cat‐to‐cat transmission. The case reported here provides, to the best of the authors’ knowledge, the first description of the pH1N1 infection involving numerous cats that lived in a restricted area with limited contact with humans.
In situ analysis of multispecies biofilm formation on customized titanium surfaces
Authors: Fröjd V. , Chávez de Paz L. , Andersson M. , Wennerberg A. , Davies J.R. , Svensäter G. 
Published: April 2011

SummaryMany studies to identify surfaces that enhance the incorporation of dental implants into bone and soft‐tissue have been undertaken previously. However, to succeed in the clinical situation, an implant surface must not support development of microbial biofilms with a pathogenic potential. As a first step in investigating this, we used two‐species and three‐species biofilm models with 16S ribosomal RNA fluorescence in situ hybridization and confocal laser scanning microscopy to examine the effect of surface characteristics on biofilm formation by species that can colonize titanium implants in vivo: Streptococcus sanguinis, Actinomyces naeslundii and Lactobacillus salivarius. Surfaces blasted with Al2O3 (Sa = 1.0–2.0 μm) showed a seven‐fold higher bacterial adhesion after 2 h than turned surfaces (Sa = 0.18 μm) whereas porous surfaces, generated by anodic oxidation (Sa = 0.4 μm), showed four‐fold greater adhesion than turned surfaces. Hence, increased roughness promoted adhesion, most likely through protection of bacteria from shear forces. Chemical modification of the blasted and oxidized surfaces by incorporation of Ca2+ ions reduced adhesion compared with the corresponding non‐modified surfaces. After 14 h, biofilm growth occurred in the three‐species model but not in the two‐species consortium (containing S. sanguinis and A. naeslundii only). The biofilm biovolume on all surfaces was similar, suggesting that the influence of surface characteristics on adhesion was compensated for by biofilm development.