bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure
Authors: Watson Elizabeth , Fargali Samira , Okamoto Haruka , Sadahiro Masato , Gordon Ronald E , Chakraborty Tandra , Sleeman Mark W , Salton Stephen R
Published: October 2009

Background

Previous studies of mixed background mice have demonstrated that targeted deletion ofVgfproduces a lean, hypermetabolic mouse that is resistant to diet-, lesion-, and genetically-induced obesity. To investigate potential mechanism(s) and site(s) of action of VGF, a neuronal and endocrine secreted protein and neuropeptide precursor, we further analyzed the metabolic phenotypes of two independent VGF knockout lines on C57Bl6 backgrounds.

Results

Unlike hyperactive VGF knockout mice on a mixed C57Bl6-129/SvJ background, homozygous mutant mice on a C57Bl6 background were hypermetabolic with similar locomotor activity levels toVgf+/Vgf+mice, during day and night cycles, indicating that mechanism(s) other than hyperactivity were responsible for their increased energy expenditure. InVgf-/Vgf-knockout mice, morphological analysis of brown and white adipose tissues (BAT and WAT) indicated decreased fat storage in both tissues, and decreased adipocyte perimeter and area in WAT. Changes in gene expression measured by real-time RT-PCR were consistent with increased fatty acid oxidation and uptake in BAT, and increased lipolysis, decreased lipogenesis, and brown adipocyte differentiation in WAT, suggesting that increased sympathetic nervous system activity inVgf-/Vgf-mice may be associated with or responsible for alterations in energy expenditure and fat storage. In addition, uncoupling protein 1 (UCP1) and UCP2 protein levels, mitochondrial number, and mitochondrial cristae density were upregulated inVgf-/Vgf-BAT. Using immunohistochemical and histochemical techniques, we detected VGF in nerve fibers innervating BAT andVgfpromoter-driven reporter expression in cervical and thoracic spinal ganglia that project to and innervate the chest wall and tissues including BAT. Moreover, VGF peptide levels were quantified by radioimmunoassay in BAT, and were found to be down-regulated by a high fat diet. Lastly, despite being hypermetabolic, VGF knockout mice were cold intolerant.

Conclusion

We propose that VGF and/or VGF-derived peptides modulate sympathetic outflow pathways to regulate fat storage and energy expenditure.
A multi-component model of the dynamics of salt-induced hypertension in Dahl-S rats
Authors: McLoone Violeta I , Ringwood John V , Van Vliet Bruce N
Published: October 2009

Background

In humans, salt intake has been suggested to influence blood pressure (BP) on a wide range of time scales ranging from several hours or days to many months or years. Detailed time course data collected in the Dahl salt-sensitive rat strain suggest that the development of salt-induced hypertension may consist of several distinct phases or components that differ in their timing and reversibility. To better understand these components, the present study sought to model the dynamics of salt-induced hypertension in the Dahl salt sensitive (Dahl-S) rat using 3 sets of time course data.

Results

The first component of the model ("Acute-Reversible") consisted of a linear transfer function to account for the rapid and reversible effects of salt on BP (ie. acute salt sensitivity, corresponding with a depressed slope of the chronic pressure natriuresis relationship). For the second component ("Progressive-Irreversible"), an integrator function was used to represent the relatively slow, progressive, and irreversible effect of high salt intake on BP (corresponding with a progressive salt-induced shift of the chronic pressure natriuresis relationship to higher BP levels). A third component ("Progressive-Reversible") consisted of an effect of high salt intake to progressively increase the acute salt-sensitivity of BP (ie. reduce the slope of the chronic pressure natriuresis relationship), amounting to a slow and progressive, yet reversible, component of salt-induced hypertension. While the 3 component model was limited in its ability to follow the BP response to rapid and/or brief transitions in salt intake, it was able to accurately follow the slower steady state components of salt-induced BP changes. This model exhibited low values of mean absolute error (1.92 ± 0.23, 2.13 ± 0.37, 2.03 ± 0.3 mmHg for data sets 1 - 3), and its overall performance was significantly improved over that of an initial model having only 2 components. The 3 component model performed well when applied to data from hybrids of Dahl salt sensitive and Dahl salt resistant rats in which salt sensitivity varied greatly in its extent and character (mean absolute error = 1.11 ± 0.08 mmHg).

Conclusion

Our results suggest that the slow process of development of salt-induced hypertension in Dahl-S rats over a period of many weeks can be well represented by a combination of three components that differ in their timing, reversibility, and their associated effect on the chronic pressure natriuresis relationship. These components are important to distinguish since each may represent a unique set of underlying mechanisms of salt-induced hypertension.
Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients - a longitudinal observational study
Authors: Leung Wilson Y , So Wing-yee , Stewart Derek , Lui Augustine , Tong Peter C , Ko Gary T , Kong Alice P , Ma Ronald C , Chan Francis K , Yang Xilin , Chiang Sau-chu , Chan Juliana C
Published: October 2009

Background

The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes.

Methods

This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005.

Results

Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment.

Conclusion

In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high.
Malaria treatment perceptions, practices and influences on provider behaviour: comparing hospitals and non-hospitals in south-east Nigeria
Authors: Onwujekwe Obinna , Uzochukwu Benjamin , Dike Nkem , Uguru Nkoli , Nwobi Emmanuel , Shu Elvis
Published: October 2009

Background

People seek treatment for malaria from a wide range of providers ranging from itinerant drug sellers to hospitals. However, there are lots of problems with treatment provision. Hence, factors influencing treatment provision in hospitals and non-hospitals require further investigation in order to remedy the situation.

Objectives

To examine the knowledge, pattern of treatment provision and factors influencing the behaviour of hospitals and non-hospitals in the treatment of malaria, so as to identify loci for interventions to improve treatment of the disease.

Methods

A pre-tested structured questionnaire was used to collect data from 225 providers from hospitals and non-hospitals about their malaria treatment practices and factors that influence their provision of malaria treatment services in south-east Nigeria. The data from hospitals and other providers were compared for systematic differences.

Results

73.5% of hospitals used microscopy to diagnose malaria and only 34.5.1% of non-hospitals did (p < 0.05). Majority of the respondents considered ability to pay bills (35.2%), already existing relationship (9.4%) and body mechanism (35.2%) of the patient before they provided malaria treatment services. Pressure from wholesalers to providers to repay the cost of supplied drugs was the major influence of the type of drugs provided to patients.

Conclusion

There are many challenges to appropriate provision of malaria treatment services, although challenges are less in hospitals compared to other types of non-hospitals. Improving proper diagnosis of malaria and improving the knowledge of providers about malaria are interventions that could be used to improve malaria treatment provision.
Comparison of Plasmodium falciparum allelic frequency distribution in different endemic settings by high-resolution genotyping
Authors: Schoepflin Sonja , Valsangiacomo Francesca , Lin Enmoore , Kiniboro Benson , Mueller Ivo , Felger Ingrid
Published: October 2009

Background

The diversity of genotyping markers of Plasmodium falciparum depends on transmission intensity. It has been reported that the diversity of the merozoite surface protein 2 (msp2) is greater in areas of high compared to low endemicity, however, results for msp1 were inconsistent. These previous reports relied on low resolution genotyping techniques.

Methods

In the present study, a high-resolution capillary electrophoresis-based technique was applied to genotype samples from areas of different endemicity in Papua New Guinea and Tanzania. For both endemic settings, the diversity of msp1 and msp2 was investigated; the mean multiplicity of infection (MOI) and the FST values were determined to investigate whether more accurate sizing generates different results.

Results and Conclusion

The results of the present study confirmed previous reports of a higher mean MOI for both marker genes and increased genetic diversity in areas of higher endemicity as estimated by the total number of distinct alleles for msp2. For msp1 a minor increase in diversity was observed. Measures of between population variance in allele frequencies (FST) indicated little genetic differentiation for both marker genes between the two populations from different endemic settings. MOI adjusted for the probability of multiple infections sharing the same allele was estimated by using the msp2 allele frequency distribution and the distribution of observed numbers of concurrent infections. For the high-resolution typing technique applied in this study, this adjustment made little difference to the estimated mean MOI compared to the observed mean MOI.
Robust algorithm for arrhythmia classification in ECG using extreme learning machine
Authors: Kim Jinkwon , Shin Hang Sik , Shin Kwangsoo , Lee Myoungho
Published: October 2009

Background

Recently, extensive studies have been carried out on arrhythmia classification algorithms using artificial intelligence pattern recognition methods such as neural network. To improve practicality, many studies have focused on learning speed and the accuracy of neural networks. However, algorithms based on neural networks still have some problems concerning practical application, such as slow learning speeds and unstable performance caused by local minima.

Methods

In this paper we propose a novel arrhythmia classification algorithm which has a fast learning speed and high accuracy, and uses Morphology Filtering, Principal Component Analysis and Extreme Learning Machine (ELM). The proposed algorithm can classify six beat types: normal beat, left bundle branch block, right bundle branch block, premature ventricular contraction, atrial premature beat, and paced beat.

Results

The experimental results of the entire MIT-BIH arrhythmia database demonstrate that the performances of the proposed algorithm are 98.00% in terms of average sensitivity, 97.95% in terms of average specificity, and 98.72% in terms of average accuracy. These accuracy levels are higher than or comparable with those of existing methods. We make a comparative study of algorithm using an ELM, back propagation neural network (BPNN), radial basis function network (RBFN), or support vector machine (SVM). Concerning the aspect of learning time, the proposed algorithm using ELM is about 290, 70, and 3 times faster than an algorithm using a BPNN, RBFN, and SVM, respectively.

Conclusion

The proposed algorithm shows effective accuracy performance with a short learning time. In addition we ascertained the robustness of the proposed algorithm by evaluating the entire MIT-BIH arrhythmia database.
Association of serum levels of lipid and its novel constituents with the different stages of esophageal carcinoma
Authors: Diao Yutao , Li Hao , Li Huiqing , Zhou Yingzhi , Ma Qing , Wang Yan , Li Dong
Published: October 2009

Background

The aim of the study was to evaluate the association of immunoglobulin G type of autoantibodies to oxidized low-density lipoprotein (oxLDL-lgG) and oxLDL-lgM with the progression of esophageal squamous cell carcinoma (ESSC).

Methods

Residents from Feicheng, China aged 40 to 69 years were screened for esophageal lesions in a screening program conducted during the period of January 2008 to December 2006. There were 33 controls with normal esophageal squamous epithelium cells, 37 patients with basal cell hyperplasia, 47 with esophageal squamous cell dysplasia, and 43 with ESCC. All the participants were diagnosed by biopsy and histopathological examination. Adiponectin, oxidized low-density lipoprotein (oxLDL), autoantibodies against oxLDL (oxLDL-ab), OxLDL-lgG, and OxLDL-lgM were determined by enzyme linked immunosorbent assay (ELISA). Total cholesterol, High-density lipoprotein (HDL), triglyceride, serum albumin, and blood pressure were co-estimated. Analysis of covariance for lipid levels was used to control the influence of covariates.

Results

The level of oxLDL-lgM increased gradually along with esophageal carcinoma progression. The oxLDL-lgM levels in the ESCC group were the highest after possible covariates were controlled. Binary logistic regression showed that oxLDL-lgM had a positive correlation with the development of esophageal carcinoma, while oxLDL and oxLDL-ab had a negative correlation with ESSC. No significant association between the levels of oxLDL-lgG and adiponectin and the different stages of ESSC was observed.

Conclusion

The present study shows that the decreased oxLDL and oxLDL-ab and the elevated oxLDL-lgM serum levels may relate to the development and progression of ESSC.
Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E2
Authors: Herrerias Aida , Torres Rosa , Serra Mariona , Marco Alberto , Pujols Laura , Picado César , de Mora Fernando
Published: October 2009

Background

Prostaglandin E2 (PGE2), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE2.

Methods

Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE2 or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE2, PGI2, PGD2 were also determined in bronchoalveolar lavage fluid.

Results

HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE2 and PGI2, but not PGD2, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE2 attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE2 and PGI2 production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE2 overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE2, but not in those treated with sulprostone.

Conclusion

The lung COX-2/PGE2/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE2 downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE2 to exert its protective effect.
Silver nanoparticles inhibit VEGF-and IL-1β-induced vascular permeability via Src dependent pathway in porcine retinal endothelial cells
Authors: Sheikpranbabu Sardarpasha , Kalishwaralal Kalimuthu , Venkataraman Deepak , Eom Soo Hyun , Park Jongsun , Gurunathan Sangiliyandi
Published: October 2009

The aim of this study is to determine the effects of silver nanoparticles (Ag-NP) on vascular endothelial growth factor (VEGF)-and interleukin-1 beta (IL-1β)-induced vascular permeability, and to detect the underlying signaling mechanisms involved in endothelial cells. Porcine retinal endothelial cells (PRECs) were exposed to VEGF, IL-1β and Ag-NP at different combinations and endothelial cell permeability was analyzed by measuring the flux of RITC-dextran across the PRECs monolayer. We found that VEGF and IL-1β increase flux of dextran across a PRECs monolayer, and Ag-NP block solute flux induced by both VEGF and IL-1β. To explore the signalling pathway involved VEGF- and IL-1β-induced endothelial alteration, PRECs were treated with Src inhibitor PP2 prior to VEGF and IL-1β treatment, and the effects were recorded. Further, to clarify the possible involvement of the Src pathways in endothelial cell permeability, plasmid encoding dominant negative(DN) and constitutively active(CA) form of Src kinases were transfected into PRECs, 24 h prior to VEGF and IL-1β exposure and the effects were recorded. Overexpression of DN Src blocked both VEGF-and IL-1β-induced permeability, while overexpression of CA Src rescues the inhibitory action of Ag-NP in the presence or absence of VEGF and IL-1β. Further, an in vitro kinase assay was performed to identify the presence of the Src phosphorylation at Y419. We report that VEGF and IL-1β-stimulate endothelial permeability via Src dependent pathway by increasing the Src phosphorylation and Ag-NP block the VEGF-and IL-1β-induced Src phosphorylation at Y419. These results demonstrate that Ag-NP may inhibit the VEGF-and IL-1β-induced permeability through inactivation of Src kinase pathway and this pathway may represent a potential therapeutic target to inhibit the ocular diseases such as diabetic retinopathy.
The scent of supercolonies: the discovery, synthesis and behavioural verification of ant colony recognition cues
Authors: Brandt Miriam , van Wilgenburg Ellen , Sulc Robert , Shea Kenneth J , Tsutsui Neil D
Published: October 2009

Background

Ants form highly social and cooperative colonies that compete, and often fight, against other such colonies, both intra- and interspecifically. Some invasive ants take sociality to an extreme, forming geographically massive 'supercolonies' across thousands of kilometres. The success of social insects generally, as well as invasive ants in particular, stems from the sophisticated mechanisms used to accurately and precisely distinguish colonymates from non-colonymates. Surprisingly, however, the specific chemicals used for this recognition are virtually undescribed.

Results

Here, we report the discovery, chemical synthesis and behavioural testing of the colonymate recognition cues used by the widespread and invasive Argentine ant (Linepithema humile). By synthesizing pure versions of these chemicals in the laboratory and testing them in behavioural assays, we show that these compounds trigger aggression among normally amicable nestmates, but control hydrocarbons do not. Furthermore, behavioural testing across multiple different supercolonies reveals that the reaction to individual compounds varies from colony to colony -- the expected reaction to true colony recognition labels. Our results also show that both quantitative and qualitative changes to cuticular hydrocarbon profiles can trigger aggression among nestmates. These data point the way for the development of new environmentally-friendly control strategies based on the species-specific manipulation of aggressive behaviour.

Conclusion

Overall, our findings reveal the identity of specific chemicals used for colonymate recognition by the invasive Argentine ants. Although the particular chemicals used by other ants may differ, the patterns reported here are likely to be true for ants generally. As almost all invasive ants display widespread unicoloniality in their introduced ranges, our findings are particularly relevant for our understanding of the biology of these damaging invaders.
Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics
Authors: Hill Kenneth E , Clawson Susan A , Rose John W , Carlson Noel G , Greenlee John E
Published: October 2009

Background

Immunoglobulin G (IgG) antibodies reactive with intracellular neuronal proteins have been described in paraneoplastic and other autoimmune disorders. Because neurons have been thought impermeable to immunoglobulins, however, such antibodies have been considered unable to enter neurons and bind to their specific antigens during life. Cerebellar Purkinje cells - an important target in paraneoplastic and other autoimmune diseases - have been shown in experimental animals to incorporate a number of molecules from cerebrospinal fluid. IgG has also been detected in Purkinje cells studied post mortem. Despite the possible significance of these findings for human disease, immunoglobulin uptake by Purkinje cells has not been demonstrated in living tissue or studied systematically.

Methods

To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery.

Results

IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG.

Conclusion

Purkinje cells in rat organotypic cultures incorporate and clear host (rat) and non-host (human or donkey) IgG or IgM, independent of the immunoglobulin's reactivity with Purkinje cell antigens. This property permits real-time study of immunoglobulin-Purkinje cell interaction using fluorochrome IgG conjugates, and can allow Purkinje cell-specific delivery of IgG-conjugated pharmacological agents. Antibodies to intracellular Purkinje cell proteins could potentially be incorporated intracellularly to produce cell injury. Antibodies used therapeutically, including immunotoxins, may also be taken up and cause Purkinje cell injury, even if they do not recognize Purkinje cell antigens.
Localization of deformed wing virus (DWV) in the brains of the honeybee, Apis mellifera Linnaeus
Authors: Shah Karan S , Evans Elizabeth C , Pizzorno Marie C
Published: October 2009

Background

Deformed wing virus (DWV) is a positive-strand RNA virus that infects European honeybees (Apis mellifera L.) and has been isolated from the brains of aggressive bees in Japan. DWV is known to be transmitted both vertically and horizontally between bees in a colony and can lead to both symptomatic and asymptomatic infections in bees. In environmentally stressful conditions, DWV can contribute to the demise of a honeybee colony. The purpose of the current study is to identify regions within the brains of honeybees where DWV replicates using in-situ hybridization.

Results

In-situ hybridizations were conducted with both sense and antisense probes on the brains of honeybees that were positive for DWV as measured by real-time RT-PCR. The visual neuropils demonstrated detectable levels of the DWV positive-strand genome. The mushroom bodies and antenna lobe neuropils also showed the presence of the viral genome. Weaker staining with the sense probe in the same regions demonstrates that the antigenome is also present and that the virus is actively replicating in these regions of the brain.

Conclusion

These results demonstrate that in bees infected with DWV the virus is replicating in critical regions of the brain, including the neuropils responsible for vision and olfaction. Therefore DWV infection of the brain could adversely affect critical sensory functions and alter normal bee behavior.
Combined effects of hyperglycemic conditions and HIV-1 Nef: a potential model for induced HIV neuropathogenesis
Authors: Acheampong Edward A , Roschel Cassandra , Mukhtar Muhammad , Srinivasan Alagarsamy , Rafi Mohammad , Pomerantz Roger J , Parveen Zahida
Published: October 2009

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using bothin vitroandin vivomodels. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for ourin vitrostudy. The results show thatin vitrohyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and the production of total nitrate and 8-iso-PGF2 α as reactive oxygen species (ROS) in human astrocytes leading to cell death in a dose-dependent manner. Delivery of purified recombinant HIV-1 Nef protein, or Nef expressed via HIV-1-based vectors in astrocytes showed similar results. The expression of Nef protein delivered via HIV-1 vectors in combination with hyperglycemia further augmented the production of ROS, C3, activation of caspase-3, modulation of filamentous protein (F-protein), depolarization of the mitochondria, and loss of astrocytes. To further verify the effects of hyperglycemia and HIV-1 Nef protein on CNS individually or in combination,in vivostudies were performed in streptozotocin (STZ) induced diabetic mice, by injecting HIV-1 Nef expressing viral particles into the sub-cortical region of the brain. Ourin vivoresults were similar toin vitrofindings indicating an enhanced production of caspases-3, ROS (lipid oxidation and total nitrate), and C3 in the brain tissues of these animals. Interestingly, the delivery of HIV-1 Nef protein alone caused similar damage to CNS as augmented by hyperglycemia conditions. Taken together, the data suggests that HIV-1 infected individuals with hyperglycemia could potentially be at a higher risk of developing CNS related complications.
Transparency in Nigeria's public pharmaceutical sector: perceptions from policy makers
Authors: Garuba Habibat A , Kohler Jillian C , Huisman Anna M
Published: October 2009

Background

Pharmaceuticals are an integral component of health care systems worldwide, thus, regulatory weaknesses in governance of the pharmaceutical system negatively impact health outcomes especially in developing countries [1]. Nigeria is one of a number of countries whose pharmaceutical system has been impacted by corruption and has struggled to curtail the production and trafficking of substandard drugs. In 2001, the National Agency for Food and Drug Administration and Control (NAFDAC) underwent an organizational restructuring resulting in reforms to reduce counterfeit drugs and better regulate pharmaceuticals [2]. Despite these changes, there is still room for improvement. This study assessed the perceived level of transparency and potential vulnerability to corruption that exists in four essential areas of Nigeria's pharmaceutical sector: registration, procurement, inspection (divided into inspection of ports and of establishments), and distribution.

Methods

Standardized questionnaires were adapted from the World Health Organization assessment tool and used in semi-structured interviews with key stakeholders in the public and private pharmaceutical system. The responses to the questions were tallied and converted to scores on a numerical scale where lower scores suggested greater vulnerability to corruption and higher scores suggested lower vulnerability.

Results

The overall score for Nigeria's pharmaceutical system was 7.4 out of 10, indicating a system that is marginally vulnerable to corruption. The weakest links were the areas of drug registration and inspection of ports. Analysis of the qualitative results revealed that the perceived level of corruption did not always match the qualitative evidence.

Conclusion

Despite the many reported reforms instituted by NAFDAC, the study findings suggest that facets of the pharmaceutical system in Nigeria remain fairly vulnerable to corruption. The most glaring deficiency seems to be the absence of conflict of interest guidelines which, if present and consistently administered, limit the promulgation of corrupt practices. Other major contributing factors are the inconsistency in documentation of procedures, lack of public availability of such documentation, and inadequacies in monitoring and evaluation. What is most critical from this study is the identification of areas that still remain permeable to corruption and, perhaps, where more appropriate checks and balances are needed from the Nigerian government and the international community.
Occlusion of the common femoral artery by cement after total hip arthroplasty: a case report
Authors: Reilingh Mikel L , Hartemink Koen J , Hoksbergen Arjan WJ , Saouti Rachid
Published: October 2009

Introduction

The incidence of vascular injuries after total hip arthroplasty is extremely low. In this report we describe an unusual injury to the common femoral artery.

Case presentation

A 59-year-old Caucasian woman presented with rest pain, numbness and cramps in the operated limb after hip replacement. Cement leakage under the transverse ligament had caused occlusion of the common femoral artery necessitating vascular reconstruction. She had a good functional recovery at follow-up.

Conclusion

To the best of our knowledge, this is the first well-documented case reporting this pathomechanism of vascular lesion to the femoral artery. This case report highlights the potential risk of such a limb-threatening complication, and awareness should lead to prevention by meticulous surgical technique (correct technique of pressurization) or to early detection of the lesion.
A Rasch Analysis of the Manchester Foot Pain and Disability Index
Authors: Muller Sara , Roddy Edward
Published: October 2009

Background

There is currently no interval‐level measure of foot‐related disability and this has hampered research in this area. The Manchester Foot Pain and Disability Index (FPDI) could potentially fill this gap.

Objective

To assess the fit of the three subscales (function, pain, appearance) of the FPDI to the Rasch unidimensional measurement model in order to form interval‐level scores.

Methods

A two‐stage postal survey at a general practice in the UK collected data from 149 adults aged 50 years and over with foot pain. The 17 FPDI items, in three subscales, were assessed for their fit to the Rasch model. Checks were carried out for differential item functioning by age and gender.

Results

The function and pain items fit the Rasch model and interval‐level scores can be constructed. There were too few people without extreme scores on the appearance subscale to allow fit to the Rasch model to be tested.

Conclusion

The items from the FPDI function and pain subscales can be used to obtain interval level scores for these factors for use in future research studies in older adults. Further work is needed to establish the interval nature of these subscale scores in more diverse populations and to establish the measurement properties of these interval‐level scores.
Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004‐2008
Authors: Menz Hylton B
Published: October 2009

Background

In 2004, as an extension of the Enhanced Primary Care (EPC) program, the Australian Government introduced a policy of providing Medicare rebates for allied health services provided to patients with chronic or complex health conditions. The objective of this study was to evaluate the utilisation of podiatry services provided under this scheme between 2004 and 2008.

Methods

Data pertaining to the Medicare item 10962 for the calendar years 2004‐2008 were extracted from the Australian Medicare Benefits Schedule (MBS) database and cross‐tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number of consultations provided and to assess for temporal trends over the five‐year assessment period. The total cost to Medicare over this period was also determined.

Results

During the 2004‐2008 period, a total of 1,338,044 EPC consultations were provided by podiatrists in Australia. Females exhibited higher utilisation than males (63 versus 37%), and those aged over 65 years accounted for 75% of consultations. There was a marked increase in the number of consultations provided from 2004 to 2008, and the total cost of providing EPC podiatry services during this period was $62.9 M.

Conclusion

Podiatry services have been extensively utilised under the EPC program by primary care patients, particularly older women, and the number of services provided has increased dramatically between 2004 and 2008. Further research is required to determine whether the EPC program enhances clinical outcomes compared to standard practice.
PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro
Authors: Finn Richard S , Dering Judy , Conklin Dylan , Kalous Ondrej , Cohen David J , Desai Amrita J , Ginther Charles , Atefi Mohammad , Chen Isan , Fowst Camilla , Los Gerret , Slamon Dennis J
Published: October 2009

Introduction

Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines.

Methods

Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response.

Results

Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade.

Conclusions

These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991.
Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study
Authors: Roberts Russel J , Barletta Jeffrey F , Fong Jeffrey J , Schumaker Greg , Kuper Philip J , Papadopoulos Stella , Yogaratnam Dinesh , Kendall Elise , Xamplas Renee , Gerlach Anthony T , Szumita Paul M , Anger Kevin E , Arpino Paul A , Voils Stacey A , Grgurich Philip , Ruthazer Robin , Devlin John W
Published: October 2009

Introduction

While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol.

Methods

Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS.

Results

Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar.

Conclusions

Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.
Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery
Authors: Shiao Chih-Chung , Wu Vin-Cent , Li Wen-Yi , Lin Yu-Feng , Hu Fu-Chang , Young Guang-Huar , Kuo Chin-Chi , Kao Tze-Wah , Huang Down-Ming , Chen Yung-Ming , Tsai Pi-Ru , Lin Shuei-Liong , Chou Nai-Kuan , Lin Tzu-Hsin , Yeh Yu-Chang , Wang Chih-Hsien , Chou Anne , Ko Wen-Je , Wu Kwan-Dun ,   the National Taiwan University Surgical Intensive Care Unit-Associated Renal Failure (NSARF) Study Group
Published: October 2009

Introduction

Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome.

Methods

A multicenter prospective observational study based on the NSARF (N ational Taiwan University S urgical ICU A ssociated R enal F ailure) Study Group database. 98 patients (41 female, mean age 66.4 ± 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006.

Results

The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality.

Conclusions

The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification.
Clinical implications of neuropsychiatric systemic lupus erythematosus
Authors: Mak Anselm , Ho Roger Chun Man , Lau Chak Sing
Published: October 2009

Systemic lupus erythematosus (SLE) is a disorder which can affect the central nervous system and result in a broad range of psychiatric syndromes such as psychosis, mood disorders, acute confusion and cognitive dysfunction. Despite the robust nomenclature of neuropsychiatric SLE (NPSLE), psychiatric syndromes in patients are often non-specific and may be secondary to concurrent non-SLE-related conditions and complications of medical therapies. Although the exact immunopathological mechanism for psychiatric presentation remains elusive, prompt exclusion of other factors contributing to the psychiatric symptoms coupled with effective assessment strategies and management with immunosuppression and psychiatric therapy are imperative. Psychiatrists and rheumatologists must work in close liaison to identify, treat and prognosticate patients with psychiatric syndromes in order to improve their quality of life, vocational aptitude and, ultimately, survival.
Article 2 of the Human Rights Act 1998 and the treatment of prisoners
Authors: Curtice Martin , Sandford John
Published: October 2009

People detained in prisons, psychiatric hospitals, police custody and immigration detention centres remain a cause of concern, particularly to professionals, politicians and the media. As the number of people detained by the state increases, Courts have been taking an increasing interest in cases in which individuals have died in state custody. Such cases are subsumed under Article 2 of the Human Rights Act 1998 – the right to life. Article 2 case law has elucidated key principles that can be applied in practice. Importantly, it imposes on states not only a negative duty not to take life intentionally or negligently, but also a positive duty to safeguard life. The inherent positive obligations have two aspects: first, there is a duty to provide an effective and impartial investigation in cases of death resulting from the activities of state officials, and second, a duty to safeguard and protect life.
Letter from America: acute in-patient psychiatry bed shortages
Authors: Sharfstein Steven S.
Published: October 2009

The number of in-patient beds for psychiatric treatment in America has declined dramatically over the past 40 years. Public and private policies have encouraged an extremely short-term, crisis-stabilisation model of treatment. This is true on both general and subspecialty units. As a result, readmissions have increased, emergency rooms are crowded, and many patients end up homeless or incarcerated in the criminal justice system. These changes have created a public health crisis in America, and are the greatest challenges that American psychiatry faces today.
Metamorphosis by Franz Kafka
Authors: Beveridge Allan
Published: October 2009

This article examines the short story Metamorphosis by the enigmatic Czech writer Franz Kafka, whose work has been the subject of extensive critical discussion. His writings have been seen in the context of existentialism, Jewish mysticism and as a warning of the advent of totalitarianism. Kafka has attracted the attention of psychoanalysts and psychiatrists, who have maintained that his life and work manifest evidence of unresolved Oedipal issues and of schizoid personality. Metamorphosis is open to a multitude of interpretations, but a potentially fruitful approach is to see parallels between the predicament of the story's main character, Gregor Samsa, and that of people with severe mental illness. The story highlights the fate of those who are judged to be different by society and how issues of alienation, impaired communication and rejection arise.
Tumor Infiltrating Lymphocytes But Not Serum Pituitary Antibodies Are Associated with Poor Clinical Outcome after Surgery in Patients with Pituitary Adenoma
Authors: Lupi Isabella , Manetti Luca , Caturegli Patrizio , Menicagli Michele , Cosottini Mirco , Iannelli Aldo , Acerbi Giovanni , Bevilacqua Generoso , Bogazzi Fausto , Martino Enio
Published: October 2009

Context: Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown.

Objective: The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome.

Design: This was a prevalence case-control study.

Patients and Setting: Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center.

Intervention: Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72).

Main Outcome Measure: Clinical response of pituitary adenoma after surgery was evaluated.

Results: Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma.

Conclusions: TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.