bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine receptors regulate NMDA receptor surface expression in prefrontal cortex neurons
Authors: Gao Can , Wolf Marina E.
Published: July 2008

Interactions between dopamine (DA) and glutamate systems in the prefrontal cortex (PFC) are important in addiction and other psychiatric disorders. Here, we examined DA receptor regulation of NMDA receptor surface expression in postnatal rat PFC neuronal cultures. Immunocytochemical analysis demonstrated that surface expression (synaptic and non‐synaptic) of NR1 and NR2B on PFC pyramidal neurons was increased by the D1 receptor agonist SKF 81297 (1 μM, 5 min). Activation of protein kinase A (PKA) did not alter NR1 distribution, indicating that PKA does not mediate the effect of D1 receptor stimulation. However, the tyrosine kinase inhibitor genistein (50 μM, 30 min) completely blocked the effect of SKF 81297 on NR1 and NR2B surface expression. Protein cross‐linking studies confirmed that SKF 81297 (1 μM, 5 min) increased NR1 and NR2B surface expression, and further showed that NR2A surface expression was not affected. Genistein blocked the effect of SKF 81297 on NR1 and NR2B. Surface‐expressed immunoreactivity detected with a phospho‐specific antibody to tyrosine 1472 of NR2B also increased after D1 agonist treatment. Our results show that tyrosine phosphorylation plays an important role in the trafficking of NR2B‐containing NMDA receptors in PFC neurons and the regulation of their trafficking by DA receptors.
Does a solitary lobar collapse give pressure–lung volume relationship similar to that found in acute respiratory distress syndrome? A porcine experimental study
Authors: Koefoed‐Nielsen Jacob , Hansen Lars Kjærsgaard , Larsson Anders
Published: July 2008

Background:  The underlying pathophysiology causing different shapes of static pressure–lung volume (PV) curves is not fully elucidated. In this study the aim was to examine the influence of a solitary lobar collapse on inflation–deflation PV curves. The hypothesis was that a lobar collapse would induce the same changes in the PV‐curve as those found in experimental acute lung injury (ALI) and in acute respiratory distress syndrome (ARDS).

Methods:  In four mechanically ventilated, anaesthetized pigs, the right lower lobe was collapsed by selective lavage and exsufflation. End‐expiratory lung volume and static inflation–deflation PV curves of the respiratory system, the chest wall and the lung were obtained before formation of the collapse. After creation of the collapse, the same measurements were performed in the non‐collapsed lung and in the whole lung including the lobar collapse. In two animals computed tomography was performed to verify the lobar collapse.

Results:  The solitary lobar collapse changed the PV curve by inducing a significant hysteresis and a right shift of lower inflexion point (LIP) on the inflation limb, but had minimal influence on the deflation limb. After creation of the lobar collapse, LIP was found at the pressure at which the collapse started to expand.

Conclusions:  PV curves of lungs with solitary lobar collapse are similar to those found in ALI/ARDS. Inspiratory LIP indicated start of recruitment, and expiratory curves did not indicate the pressure at which collapse occurred.
Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome
Authors: Patrick Neary J. , Roberts Andy D. W. , Leavins Nina , Harrison Michael F. , Croll James C. , Sexsmith James R.
Published: July 2008

This study examined the effects of maximal incremental exercise on cerebral oxygenation in chronic fatigue syndrome (CFS) subjects. Furthermore, we tested the hypothesis that CFS subjects have a reduced oxygen delivery to the brain during exercise. Six female CFS and eight control (CON) subjects (similar in height, weight, body mass index and physical activity level) performed an incremental cycle ergometer test to exhaustion, while changes in cerebral oxy‐haemoglobin (HbO2), deoxy‐haemoglobin (HHb), total blood volume (tHb = HbO2 + HHb) and O2 saturation [tissue oxygenation index (TOI), %)] was monitored in the left prefrontal lobe using a near‐infrared spectrophotometer. Heart rate (HR) and rating of perceived exertion (RPE) were recorded at each workload throughout the test. Predicted VO2peak in CFS (1331 ± 377 ml) subjects was significantly (P ≤ 0·05) lower than the CON group (1990 ± 332 ml), and CFS subjects achieved volitional exhaustion significantly faster (CFS: 351 ± 224 s; CON: 715 ± 176 s) at a lower power output (CFS: 100 ± 39 W; CON: 163 ± 34 W). CFS subjects also exhibited a significantly lower maximum HR (CFS: 154 ± 13 bpm; CON: 186 ± 11 bpm) and consistently reported a higher RPE at the same absolute workload when compared with CON subjects. Prefrontal cortex HbO2, HHb and tHb were significantly lower at maximal exercise in CFS versus CON, as was TOI during exercise and recovery. The CFS subjects exhibited significant exercise intolerance and reduced prefrontal oxygenation and tHb response when compared with CON subjects. These data suggest that the altered cerebral oxygenation and blood volume may contribute to the reduced exercise load in CFS, and supports the contention that CFS, in part, is mediated centrally.
The significance of the personal within disability geography
Authors: Worth Nancy
Published: August 2008

Drawing on in‐depth qualitative data, this article critically examines disability geography as a subfield where the personal is highly valued. The value and the risks inherent in this personal approach will be evaluated, including the usefulness of being an ‘insider’ and the difficulties of being reflexive and critically making use of one's positionality. The article concludes with reflections regarding how disability geography can confront its marginal status, appealing to researchers who claim no experience of disability while also supporting and encouraging those with personal experiences of disability to participate in the field.
Revealing and Resolving Patient Safety Defects: The Impact of Leadership WalkRounds on Frontline Caregiver Assessments of Patient Safety
Authors: Frankel Allan , Grillo Sarah Pratt , Pittman Mary , Thomas Eric J. , Horowitz Lisa , Page Martha , Sexton Bryan
Published: July 2008

Objective. To evaluate the impact of rigorous WalkRounds on frontline caregiver assessments of safety climate, and to clarify the steps and implementation of rigorous WalkRounds.

Data Sources/Study Setting. Primary outcome variables were baseline and post WalkRounds safety climate scores from the Safety Attitudes Questionnaire (SAQ). Secondary outcomes were safety issues elicited through WalkRounds. Study period was August 2002 to April 2005; seven hospitals in Massachusetts agreed to participate; and the project was implemented in all patient care areas.

Study Design. Prospective study of the impact of rigorously applied WalkRounds on frontline caregivers assessments of safety climate in their patient care area. WalkRounds were conducted weekly and according to the seven‐step WalkRounds Guide. The SAQ was administered at baseline and approximately 18 months post‐WalkRounds implementation to all caregivers in patient care areas.

Results. Two of seven hospitals complied with the rigorous WalkRounds approach; hospital A was an academic teaching center and hospital B a community teaching hospital. Of 21 patient care areas, SAQ surveys were received from 62 percent of respondents at baseline and 60 percent post WalkRounds. At baseline, 10 of 21 care areas (48 percent) had safety climate scores below 60 percent, whereas post‐WalkRounds three care areas (14 percent) had safety climate scores below 60 percent without improving by 10 points or more. Safety climate scale scores in hospital A were 62 percent at baseline and 77 percent post‐WalkRounds (t=2.67, p=.03), and in hospital B were 46 percent at baseline and 56 percent post WalkRounds (t=2.06, p=.06). Main safety issues by category were equipment/facility (A [26 percent] and B [33 percent]) and communication (A [24 percent] and B [18 percent]).

Conclusions. WalkRounds implementation requires significant organizational will; sustainability requires outstanding project management and leadership engagement. In the patient care areas that rigorously implemented WalkRounds, frontline caregiver assessments of patient safety increased. SAQ results such as safety climate scores facilitate the triage of quality improvement efforts, and provide consensus assessments of frontline caregivers that identify themes for improvement.
Force Characteristics of In Vivo Tissue‐engineered Myocardial Constructs Using Varying Cell Seeding Densities
Authors: Birla Ravi , Dhawan Vikas , Huang Yen‐Chih , Lytle Ian , Tiranathanagul Khajohn , Brown David
Published: July 2008

Abstract:  Experiments have been successfully performed culminating in functional, vascularized, three‐dimensional cardiac muscle tissue. Past experience in tissue engineering has led us to the understanding that cell seeding density plays a critical role in the formation and function of both in vitro and in vivo engineered tissues. Therefore, to improve upon the mechanics of this model and to facilitate the formation of myocardial tissue with improved functional performance, we sought to optimize the seeding density of cardiomyocytes in these constructs. Neonatal cardiac myocytes were isolated from 2‐day‐old Fischer 344 rat hearts. Silicone chambers containing fibrin gel were seeded with varying numbers of cardiac cells (1, 5, 10, and 20 million). Control chambers were prepared using fibrin gel alone. All of the chambers were then implanted around the femoral vessels of isogenic rats. Six constructs per cell seeding density group were implanted. Histological and immunohistochemical evaluation was performed via hematoxylin and eosin, von Gieson, and α‐sarcomeric actin staining protocols. Linear contractile force measurements were obtained for each construct following 4 weeks of in vivo implantation. After an implantation period of 4 weeks, the newly formed cardiac constructs contained within the chambers were harvested. The femoral vessels within the constructs were found to be patent in all cases. With direct electrical stimulation, the constructs were able to generate an average active force that varied depending on their seeding density. Constructs with seeding densities of 1, 5, 10, and 20 million cells produced an average active force of 208, 241, 151, and 108 µN, respectively. The control constructs did not generate any active force on electrical stimulation. This study demonstrates the in vivo survival, vascularization, organization, and function of transplanted myocardial cells. It is also apparent that cell seeding density plays a direct role in the force generation and mechanical properties of these engineered constructs. Among different groups using varying cell seeding densities, we found that the group with 5 million cells generated maximum active force.
In Vitro Assessment of Dialysis Membrane as an Endotoxin Transfer Barrier: Geometry, Morphology, and Permeability
Authors: Henrie Michael , Ford Cheryl , Andersen Marion , Stroup Eric , Diaz‐Buxo Jose , Madsen Ben , Britt David , Ho Chih‐Hu
Published: July 2008

Abstract:  High‐flux dialysis membranes used with bicarbonate dialysis fluid increase the risk of back diffusion of bacterial endotoxin into the blood during hemodialysis. Endotoxin transfer of various synthetic fiber membranes was tested with bacterial culture filtrates using an in vitro system testing both diffusive and convective conditions. Membranes were tested in a simulated dialysis mode with endotoxin challenge material (∼420 EU/mL) added to the dialysis fluid, with saline used to model both blood and dialysis fluid. Samples were taken of both blood and dialysis fluid, and analyzed using a kinetic turbidimetric Limulus amoebocyte lysate assay. Endotoxin was found in all of the blood circuit samples, except for the Fresenius Optiflux F200NRe and thick‐wall membranes. All membranes tested removed ∼95% of the endotoxin from solution, with the residual ∼5% recirculating within the dialysis fluid compartment. Endotoxin distribution through the fiber membrane was examined using a fluorescent‐labeled endotoxin conjugate. Fluorescence images indicate that adsorption occurs throughout the membrane wall, with the greatest concentration of endotoxin located at the inner lumen. Contact angle analysis was able to show that all membranes exhibit a more hydrophilic lumen and a more hydrophobic outer surface except for the polyethersulfone membranes, which were of equal hydrophobicity. Resulting data indicate that fiber geometry plays an important role in the ability of the membrane to inhibit endotoxin transfer, and that both adsorption and filtration are methods by which endotoxin is retained and removed from the dialysis fluid circuit.
Hydrogel‐based Engineered Skeletal Muscle Grafts Normalize Heart Function Early After Myocardial Infarction
Authors: Giraud Marie‐Noëlle , Ayuni Erick , Cook Stéphane , Siepe Matthias , Carrel Thierry P. , Tevaearai Hendrik T.
Published: July 2008

Abstract:  Tissue engineering represents an attractive approach for the treatment of congestive heart failure. The influence of the differentiation of myogenic graft for functional recovery is not defined. We engineered a biodegradable skeletal muscle graft (ESMG) tissue and investigated its functional effect after implantation on the epicardium of an infarcted heart segment. ESMGs were synthesized by mixing collagen (2 mg/mL), Matrigel (2 mg/mL), and rat skeletal muscle cells (106). Qualitative and quantitative aspects of ESMGs were optimized. Two weeks following coronary ligation, the animals were randomized in three groups: ESMG glued to the epicardial surface with fibrin (ESMG, n = 7), fibrin alone (fibrin, n = 5), or sham operation (sham, n = 4). Echocardiography, histology, and immunostaining were performed 4 weeks later. A cohesive three‐dimensional tissular structure formed in vitro within 1 week. Myoblasts differentiated into randomly oriented myotubes. Four weeks postimplantation, ESMGs were vascularized and invaded by granulation tissue. Mean fractional shortening (FS) was, however, significantly increased in the ESMG group as compared with preimplantation values (42 ± 6 vs. 33 ± 5%, P < 0.05) and reached the values of controlled noninfarcted animals (control, n = 5; 45 ± 3%; not significant). Pre‐ and postimplantation FS did not change over these 4 weeks in the sham group and the fibrin‐treated animals. This study showed that it is possible to improve systolic heart function following myocardial infarction through implantation of differentiated muscle fibers seeded on a gel‐type scaffold despite a low rate of survival.
Spongy Polyethersulfone Membrane for Hepatocyte Cultivation: Studies on Human Hepatoma C3A Cells
Authors: Kinasiewicz Andrzej , Śmietanka Anna , Dudziński Konrad , Chwojnowski Andrzej , Gajkowska Barbara , Weryński Andrzej
Published: July 2008

Abstract:  There are different types of membranes used for hepatocyte cultivation. In our studies, spongy polyethersulfone (PES) membranes were examined as a support for hepatic cell cultivation in vitro. The extended surface of the membranes allows to introduce a high cell number especially in three‐dimensional gel structure. Scanning electron microscopy analysis indicated that C3A cells used in our experiments grew well on PES membranes forming microvilli characteristic for normal hepatocytes. Analysis of cell viability proved that spongy PES membrane is well tolerated by J774 macrophages and did not stimulate nitric oxide synthesis. Bile canalicular structures were observed in fluorescence microscopy after F‐actin staining with tetramethyl rhodamine iso‐thiocyanate (TRITC)‐phalloidin. The C3A cells showed high affinity to the PES membranes and adhered to almost 90% during the initial 24 h of incubation. Albumin production increased during static culture from the value of 805.2 ± 284.4 (ng/24 h/initial 106 cells) during the first days, to 2017.6 ± 505.9 (ng/24 h/initial 106 cells) after 10 days of culture. In conclusion, the spongy PES membranes can be used as scaffold for hepatocyte cultivation, especially for the creation of three‐dimensional environments.
COOLIA CANARIENSIS SP. NOV. (DINOPHYCEAE), A NEW NONTOXIC EPIPHYTIC BENTHIC DINOFLAGELLATE FROM THE CANARY ISLANDS1
Authors: Fraga Santiago , Penna Antonella , Bianconi Irene , Paz Beatriz , Zapata Manuel
Published: July 2008

A new photosynthetic dinoflagellate species, Coolia canariensis S. Fraga sp. nov., is described based on samples taken from tidal ponds on the rocky shore of the Canary Islands, northeast Atlantic Ocean. Its morphology was studied by LM and SEM. It is almost spherical and has a thick smooth theca with many scattered pores. Plate 1′ is the biggest of the epithecal plates, and 7″ is twice as wide as it is long. Phylogeny inferred from the D1/D2 regions of the LSU nuclear rDNA of three strains of C. canariensis and several strains of other Coolia species, C. monotis, C. sp., showed that C. canariensis strains clustered in a well‐supported clade distinct from the other species. No toxins were detected using mouse bioassay, liquid chromatography with Fluorescence detection (LC‐FLD) or liquid chromatography‐mass spectrometry (LC‐MS). Its pigment composition is of the peridinin type of dinoflagellates. Together with this new species, many other strains of C. monotis from the Atlantic Ocean and Mediterranean Sea have been analyzed for toxin presence, and no evidence of toxin production related to yessotoxins (YTXs) was found, as was previously suggested for C. monotis from Australia.
Brain Diffusion Abnormalities in Children With Fetal Alcohol Spectrum Disorder
Authors: Lebel Catherine , Rasmussen Carmen , Wyper Katy , Walker Lindsay , Andrew Gail , Yager Jerome , Beaulieu Christian
Published: July 2008

Background:  Children with fetal alcohol spectrum disorder (FASD) have a variety of cognitive, behavioral, and neurological impairments, including structural brain damage. Despite the importance of white matter connections for proper brain function, little is known about how these connections, and the deep gray matter structures that act as relay stations, are affected in children with FASD. The purpose of this study was to use diffusion tensor imaging, an advanced magnetic resonance imaging technique, to examine microstructural differences of white and deep gray matter in children with FASD.

Methods:  Subjects were 24 children aged 5–13 years previously diagnosed with FASD and 95 healthy children over the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region‐of‐interest analysis was used to assess 4 deep gray matter structures. Fractional anisotropy, an indicator of white matter integrity, and mean diffusivity, a measure of the average water diffusion, were assessed in all 14 brain structures.

Results:  Diffusion tensor imaging revealed significant differences of diffusion parameters in several areas of the brain, including the genu and splenium of the corpus callosum, cingulum, corticospinal tracts, inferior fronto‐occipital fasciculus, inferior and superior longitudinal fasciculi, globus pallidus, putamen, and thalamus. Reduced white and gray matter volumes, as well as total brain volume, were observed in the FASD group.

Conclusions:  These results demonstrate diffusion abnormalities in FASD beyond the corpus callosum and suggest that several specific white matter regions, particularly commissural and temporal connections, and deep gray matter areas of the brain are sensitive to prenatal alcohol exposure.
Errors in patient specimen collection: application of statistical process control
Authors: Dzik Walter Sunny , Beckman Neil , Selleng Kathleen , Heddle Nancy , Szczepiorkowski Zbigniew , Wendel Silvano , Murphy Michael
Published: July 2008

BACKGROUND: Errors in the collection and labeling of blood samples for pretransfusion testing increase the risk of transfusion‐associated patient morbidity and mortality. Statistical process control (SPC) is a recognized method to monitor the performance of a critical process. An easy‐to‐use SPC method was tested to determine its feasibility as a tool for monitoring quality in transfusion medicine.

STUDY DESIGN AND METHODS: SPC control charts were adapted to a spreadsheet presentation. Data tabulating the frequency of mislabeled and miscollected blood samples from 10 hospitals in five countries from 2004 to 2006 were used to demonstrate the method. Control charts were produced to monitor process stability.

RESULTS: The participating hospitals found the SPC spreadsheet very suitable to monitor the performance of the sample labeling and collection and applied SPC charts to suit their specific needs. One hospital monitored subcategories of sample error in detail. A large hospital monitored the number of wrong‐blood‐in‐tube (WBIT) events. Four smaller‐sized facilities, each following the same policy for sample collection, combined their data on WBIT samples into a single control chart. One hospital used the control chart to monitor the effect of an educational intervention.

CONCLUSION: A simple SPC method is described that can monitor the process of sample collection and labeling in any hospital. SPC could be applied to other critical steps in the transfusion processes as a tool for biovigilance and could be used to develop regional or national performance standards for pretransfusion sample collection. A link is provided to download the spreadsheet for free.
Survival after blood transfusion
Authors: Kamper‐Jørgensen Mads , Ahlgren Martin , Rostgaard Klaus , Melbye Mads , Edgren Gustaf , Nyrén Olof , Reilly Marie , Norda Rut , Titlestad Kjell , Tynell Elsa , Hjalgrim Henrik
Published: July 2008

BACKGROUND: Long‐term survival of transfusion recipients has rarely been studied. This study examines short‐ and long‐term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population.

STUDY DESIGN AND METHODS: Population‐based cohort study of transfusion recipients in Denmark and Sweden followed for up to 20 years after their first blood transfusion. Main outcome measure was all‐cause mortality.

RESULTS: A total of 1,118,261 transfusion recipients were identified, of whom 62.0 percent were aged 65 years or older at the time of their first registered transfusion. Three months after the first transfusion, 84.3 percent of recipients were alive. One‐, 5‐, and 20‐year posttransfusion survival was 73.7, 53.4, and 27.0 percent, respectively. Survival was slightly poorer in men than in women, decreased with increasing age, and was worst for recipients transfused at departments of internal medicine. The first 3 months after the first transfusion, the standardized mortality ratio (SMR) was 17.6 times higher in transfusion recipients than in the general population. One to 4 years after first transfusion, the SMR was 2.1 and even after 17 years the SMR remained significantly 1.3‐fold increased.

CONCLUSION: The survival and relative mortality patterns among blood transfusion recipients were characterized with unprecedented detail and precision. Our results are relevant to assessments of the consequences of possible transfusion‐transmitted disease as well as for cost‐benefit estimation of new blood safety interventions.
Commercial Mortgage‐Backed Securities (CMBS) and Market Efficiency with Respect to Costly Information
Authors: Christopoulos Andreas D. , Jarrow Robert A. , Yildirim Yildiray
Published: July 2008

Commercial mortgage‐backed securities (CMBS) are complex asset‐backed securities trading in markets that do not currently use derivatives pricing technology. This lack of usage is due to the complexity of the modeling exercise, and only the recent and costly availability of historical data. As such, CMBS markets provide a natural environment for the testing of market efficiency with respect to this costly information. Using this information, this article develops a CMBS pricing model to provide a joint test of the model and market efficiency. Backtesting our pricing model for 4 years, although there is some evidence of abnormal trading profits, we cannot reject the efficiency of the CMBS markets.
Modeling Long Memory in REITs
Authors: Cotter John , Stevenson Simon
Published: July 2008

One stylized feature of financial volatility impacting the modeling process is long memory. This article examines long memory for alternative risk measures, observed absolute and squared returns for Daily Equity real estate investment trust (REITs) and compares the findings for a market equity index. The article utilizes a variety of tests for long memory finding evidence that REIT volatility does display persistence. Trading volume is found to be strongly associated with long memory. Results suggest differences in the findings with regard to REITs in comparison to the broader equity sector.
Priority setting for research on aquatic resources: an application of modified economic surplus analysis to natural resource systems
Authors: Briones Roehlano M. , Dey Madan M. , Ahmed A. K. M. Mahfuzuddin , Prein Mark , Stobutzki Ilona
Published: July 2008

In contrast to research on farming systems, research on natural resource systems seldom applies rigorous priority setting techniques, mainly due to difficulties associated with estimating research impact ex ante for such systems. This article presents a replicable approach to priority setting that addresses these difficulties. Assessment is based on multiple criteria, combining economic surplus analysis with subjective scoring, based on information drawn from a cross‐country survey of expert opinion. The approach is applied to the WorldFish Center, a global agricultural research organization focusing on living aquatic resources, both farmed and wild. The exercise demonstrates the relevance of conventional evaluation techniques to fisheries research based on a practical application of its impact pathways.
DNA‐hydrolysing activity of IgG antibodies from the sera of patients with diseases caused by different bacterial infections
Authors: Parkhomenko Taisiya A. , Odintsova Elena S. , Buneva Valentina N. , Kunder Elena V. , Zhyltsov Ivan V. , Senkovich Sergey A. , Generalov Igor I. , Nevinsky Georgy A.
Published: July 2008

DNase autoantibodies (Abs) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases with insignificant disturbances of the immune status does not contain the DNase Abs. Here we have analysed for the first time the DNase activity in the patients with diseases caused by several bacterial infections. Several rigid criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of patients with bacterial diseases but not from healthy donors. The relative activity of IgGs has been shown to vary extensively between the diseases analysed and from patient to patient, but most of the preparations had detectable levels of the DNase activity. On average, the catalytic activities were significantly lower than in patients with autoimmune pathologies and increased in the following order: streptococcal infection (erysipelas) < urogenital chlamydiosis associated with arthritis (Reiter’s disease) < meningococcal meningitis < shigellosis < suppurative surgical infections caused by Staphylococcus aureus < suppurative surgical infections caused by epidermal staphylococci < urogenital ureaplasmosis associated with reactive arthritis. While intact IgGs possessed this catalytic activity, separated light chains of polyclonal Abs appeared to be even more active in the hydrolysis of DNA.
Cytosolic renin is targeted to mitochondria and inducesapoptosis in H9c2 rat cardiomyoblasts
Authors: Wanka Heike , Keßler Nicole , Ellmer Janett , Endlich Nicole , Peters Barbara S. , Clausmeyer Susanne , Peters Jörg
Published: July 2008

One important goal in cardiology is to prevent necrotic cell death in the heart. Necrotic cell death attracts neutrophils and monocytes into the injured myocardium. The consequences are fibrosis, remodelling and cardiac failure. The renin‐angiotensin system promotes the development of cardiac failure. Recently, alternative renin transcripts have been identified lacking the signal sequence for a cotranslational transport to the endoplasmatic reticulum. These transcripts encode for a cytosolic renin with unknown functions. The expression of this alternative transcript increases after myocardial infarction. We hypothesized that cytosolic renin plays a role in survival and death of cardiomyocytes. To test this hypothesis, we overexpressed secretory or cytosolic renin in H9c2 cardiomyblasts and determined the rate of proliferation, necrosis and apoptosis. Proliferation rate, as indicated by BrdU incorporation into DNA, was reduced by secretory and cytosolic renin (cells transfected with control vector: 0.33 ± 0.06; secretory renin: 0.12 ± 0.02; P < 0.05; cytosolic renin: 0.15 ± 0.03; P < 0.05). Necrosis was increased by secretory renin but decreased by cytosolic renin (LDH release after 10 days from cells transfected with control vector: 68.5 ± 14.9; secretory renin: 100.0 ± 0; cytosolic renin: 25.5 ± 5.3% of content, each P < 0.05). Mitochondrial apoptosis, as indicated by phosphatidylserin translocation to the outer membrane, was unaffected by secretory renin but increased by cytosolic renin (controls: 23.8 ± 3.9%; secretory renin: 22.1 ± 4.7%; cytoplasmatic renin: 41.2 ± 3.8%; P < 0.05). The data demonstrate that a cytosolic renin exists in cardiomyocytes, which in contradiction to secretory renin protects from necrosis but increases apoptosis. Non‐secretory cytosolic renin can be considered as a new target for cardiac failure.
Development of a murine model to evaluate the effect of vernix caseosa on skin barrier recovery
Authors: Oudshoorn Marion H. M. , Rissmann Robert , Van Der Coelen Dennis , Hennink Wim E. , Ponec Maria , Bouwstra Joke A.
Published: August 2008

Abstract:  The aim of this study was twofold, that is the generation of a reliable model for skin barrier disruption and repair and to evaluate recovery of damaged skin after application of vernix caseosa (VC). VC was selected as its wound healing properties were suggested previously, but never clearly demonstrated. Five different levels of barrier disruption in mice, accomplished by tape‐stripping, were evaluated. Disruption models such as moderate, severe #1 and #2 (transepidermal water loss (TEWL) of 31 ± 2, 59 ± 4 and 66 ± 3 g/m2/h, respectively) showed complete recovery within 72 h. However, not all corneocytes were removed after tape‐stripping. Additionally, models such as severe #3 and #4 (TEWL of 73 ± 5 and 79 ± 6 g/m2/h, respectively) with a more severe disruption were evaluated. After tape‐stripping, all corneocytes were removed and the remaining epidermis was intact. However, model #3 still showed complete recovery within 72 h. With model #4, a crust was formed and almost complete recovery (approximately 90%) was obtained within only 8 days. The effect of VC application on recovery of disrupted skin was evaluated with model #3 and #4. Model #3 showed that application of VC predominantly influenced initial recovery and is therefore merely appropriate to study the effect of formulations in the initial recovery period. Topical application of VC on model #4 considerably increased initial and long‐term recovery. Moreover, VC application promoted rapid formation of stratum corneum and prevented epidermal thickening. These observations not only confirm the ability of VC to enhance barrier recovery, but also suggest potential use of this treatment clinically.
Nothing ‘FISH’y about the rhesus macaque sex ratio
Authors: Hung Pei‐Hsuan , Froenicke Lutz , Lyons Leslie A. , VandeVoort Catherine A.
Published: July 2008

Background  The rhesus macaque is an important model to study the effects of environmental toxicants on human reproduction. While the offspring sex ratio is one of the measurements in reproductive studies, this ratio has not been established for rhesus macaques.

Methods  The birth data for the last 23 years at the California National Primate Research Center are reported to determine the post‐zygotic sex ratio. The percentage of X‐ and Y‐bearing sperm was evaluated in four males by fluorescence in situ hybridization and by quantitative real‐time polymerase chain reaction (QRT‐PCR) to determine the pre‐zygotic sex ratio.

Results  The total birth data showed a male‐to‐female offspring sex ratio of 1.03, and the observed ratio of Y‐ and X‐bearing spermatozoa was 1.01. The QRT‐PCR failed to provide precise and consistent results.

Conclusions  The offspring sex ratio and sperm X:Y ratio data provide a reference for future studies of the reproductive toxicology in rhesus macaques.
Pediatric hepatic hemangiosarcoma in a rhesus macaque (Macaca mulatta)
Authors: Mejía A.F. , Gierbolini L. , Jacob B. , Westmoreland S.V.
Published: July 2008

Background  Pediatric hepatic angiosarcoma is a rare condition in children with poor prognosis. Microscopically this neoplasm has a particular ‘Kaposi‐form’ arrangement. Hemangiosarcoma in non‐human primates is a rare finding.

Methods  Gross and microscopic examination of a 3‐year‐old rhesus were performed. Immunohistochemistry was used to characterize the hepatic hemangiosarcoma.

Results  The gross necropsy revealed hemoabdomen and a 4 × 3 × 3 cm mass in the liver with multiple smaller masses throughout the hepatic parenchyma. Histopathology confirmed a poorly differentiated hemangiosarcoma. Other organs submitted were free of metastases.

Conclusions  Hemangiosarcoma in non‐human primates has been rarely reported. Diagnosis was confirmed by expression of endothelial‐specific markers CD31 and vWF by immunohistochemistry. Due to the young age of this monkey and the particular solid pattern throughout the mass this neoplasm resembles pediatric hepatic angiosarcoma in humans.
Early cessation of breastfeeding to prevent postnatal transmission of HIV: a recommendation in need of guidance
Authors: De Paoli Marina M , Mkwanazi Ntombizodumo B , Richter Linda M , Rollins Nigel
Published: July 2008

Aim: Early and rapid cessation of breastfeeding has been recommended by WHO to reduce mother‐to‐child transmission of HIV. This study assessed how HIV‐infected mothers planned and experienced breastfeeding cessation as part of an HIV prevention strategy and how counsellors facilitated this process.

Methods: A qualitative study was conducted among HIV‐infected mothers and counsellors from local clinics and an intervention research project in Durban, South Africa.

Results: Mothers enrolled in the research setting reported many success stories in contrast to mothers attending routine services. Consistent counselling and ongoing support from counsellors facilitated this, though specific advice on how to stop breastfeeding and introduce complementary feeds was inadequate amongst both sets of counsellors. Few mothers had a plan for what they were actually going to do on the day when they had decided to stop breastfeeding. Their primary motivation for wanting to rapidly stop breastfeeding, even with the difficulties involved, was to avoid infecting their child with HIV. Both counsellors and HIV‐infected mothers expressed concern about practical issues, including social consequences, associated with early cessation. Mothers who had stopped breastfeeding offered some, albeit limited, recommendations to assist and guide other women.

Conclusion: The experiences of HIV‐infected mothers planning for and stopping breastfeeding early illustrate the complexity of this recommendation and demonstrate that counsellors are ill‐prepared to support mothers accomplish this safely. Guidance that acknowledges the cultural context and psychological stresses is urgently needed to direct policy, training and service delivery.
A 2‐year school‐based exercise programme in pre‐pubertal boys induces skeletal benefits in lumbar spine
Authors: Alwis Gayani , Linden Christian , Ahlborg Henrik G. , Dencker Magnus , Gardsell Per , Karlsson Magnus K.
Published: July 2008

Aim: The aim of this study was to evaluate if a general school‐based exercise intervention programme in pre‐pubertal boys would render site‐specific benefits in bone mineral accrual and gain in femoral neck structure.

Methods: Eighty boys aged 7–9 years were included in a curriculum‐based exercise intervention programme comprising 40 min of general physical activity per school day (200 min/week) for 2 years. Fifty‐seven age‐matched boys, assigned to the general Swedish school curriculum of 60 min/week, served as controls. Bone mineral content was measured with dual X‐ray absorptiometry of the total body, the third lumbar vertebra and hip. Specific software, the hip structural analyses, evaluated the structural properties of the femoral neck. Annual changes were compared. The level of physical activity was estimated through questionnaires and accelerometers.

Results: The mean annual bone mineral content gain in third lumbar vertebra was 3.0 percentage points (p < 0.01) and in width 1.3 percentage points (p < 0.01) greater in the intervention than in the control group. The weekly duration of exercise estimated through the questionnaire correlated with gain in bone mineral content in third lumbar vertebra (r = 0.25, p = 0.005) and vertebra width (r = 0.20, p = 0.02).

Conclusion: A school‐based exercise intervention programme in pre‐pubertal boys enhances the skeletal benefits at lumbar spine.
Public provision of four‐wheeled walkers: Contingent valuation study of economic benefit
Authors: Haines Terry , Brown Cassandra , Morrison Jan
Published: July 2008

Objective:  To quantify the economic value of publicly provided four‐wheeled walkers as judged by recipients in Queensland, Australia.

Method:  Contingent valuation study using willingness‐to‐pay approach. A sample of 49 Australian older adults who received a publicly funded four‐wheeled walker in the past 3 months completed the survey via telephone. A discrete choice bidding response format with a randomly selected starting bid was employed to glean valuations.

Results:  This approach yielded only one non‐response, and one zero dollar response. The mean (standard deviation) valuation provided was $A290 ($A167), which was $A84 in excess of the price paid by the public provider agency to purchase the equipment. Starting bid was significantly associated with values provided.

Conclusion:  The current public provision program of four‐wheeled walkers is likely to generate net societal benefit. These findings coupled with arguments based on equity build a moderate case for the continuation of this program.
Determinants of work among older adults in urban China
Authors: Ling Davina C , Chi Iris
Published: July 2008

Objective:   We examined the role of personal, family and institutional factors on the work status of older adults in urban China.

Method:   The analysis was based on data from a large population survey (N = 7381) of community‐dwelling urban Chinese aged 60 years and older. Multivariate logistic regression was used to model work status.

Results:   Demographic variables such as gender, ethnicity, age and self‐perceived health status were identified as important determinants of work status. Having material assets, savings, a public pension and health insurance were all negatively correlated with remaining in the workforce, whereas earning a high income was positively correlated.

Conclusions:   Our findings have implications regarding the impact of health policy and pension reform on employment retention. While economic growth may create an incentive for some to continue working, the lack of widespread public and private old‐age support may force others to remain in the workforce out of economic necessity.
Antipsychotic use in the elderly: What doctors say they do, and what they do
Authors: Tiller John , Ames David , Brodaty Henry , Byrne Gerard , Chawla Sudarshan , Halliday Graeme , Snowdon John , Hepworth Graham , McArdle Peter , Schweitzer Isaac
Published: July 2008

Objective:  To review psychiatrists’ attitudes and actual practice on the use of typical and atypical antipsychotics in the elderly.

Methods:  Audit data were collected from 18‐old‐age psychiatry units across Australia. The attitudes of old age psychiatrists and their perceptions of the efficacy, tolerability and clinical usefulness of antipsychotics were examined.

Results:  The medications used for 321 patients were audited, and the attitudes of the 57 prescribing doctors were assessed. All available atypicals were prescribed and reported as more efficacious and clinically useful than typicals. Adverse events perceived by doctors as an obstacle to prescribing were more frequent than reported adverse event rates in product information. All diagnostic groups improved. Off‐label use comprised almost 22% in this sample.

Conclusions:  Adverse events are impediments to prescribing, more so with typical than atypical antipsychotics. All available atypicals were used and appeared effective in this elderly population.
The acute–aged care interface: Exploring the dynamics of ‘bed blocking’
Authors: Travers Catherine M , McDonnell Geoff D , Broe Gerald A , Anderson Phil , Karmel Rosemary , Duckett Stephen J , Gray Len C
Published: July 2008

Objective:  To understand the dynamics underlying ‘bed‐blocking’ in Australian public hospitals that is frequently blamed on older patients.

Methods:  Analysis of primary and secondary data of utilisation patterns of hospital and aged care services by older Australians.

Results:  A model of the dynamics at the acute–aged care interface was developed, in which the pathway into permanent high‐care Residential Aged Care (RAC) is conceptualised as competing queues for available places by applicants from the hospital, the community and from within RAC facilities. The hospital effectively becomes a safety net to accommodate people with high‐care needs who cannot be admitted into RAC in a timely manner.

Conclusion:  The model provides a useful tool to explore some of the issues that give rise to access‐block within the public hospital system. Access‐block cannot be understood by viewing the hospital system in isolation from other sectors that support the health and well‐being of older Australians.
Ethnic aged discrimination and disparities in health and social care: A question of social justice
Authors: Johnstone Megan‐Jane , Kanitsaki Olga
Published: July 2008

Older overseas‐born Australians of diverse cultural and language backgrounds experience significant disparities in their health and social care needs and support systems. Despite being identified as a ‘special needs’ group, the ethnic aged in Australia are generally underserved by local health and social care services, experience unequal burdens of disease and encounter cultural and language barriers to accessing appropriate health and social care compared to the average Australian‐born population. While a range of causes have been suggested to explain these disparities, rarely has the possibility of cultural racism been considered. In this article, it is suggested that cultural racism be named as a possible cause of ethnic aged disparities and disadvantage in health and social care. It is further suggested that unless cultural racism is named as a structural mechanism by which ethnic aged disparities in health and social care have been created and maintained, redressing them will remain difficult.
Molecular modeling and functional characterization of the monomeric primase–polymerase domain from the Sulfolobus solfataricus plasmid pIT3
Authors: Prato Santina , Vitale Rosa Maria , Contursi Patrizia , Lipps Georg , Saviano Michele , Rossi Mosé , Bartolucci Simonetta
Published: July 2008

A tri‐functional monomeric primase–polymerase domain encoded by the plasmid pIT3 from Sulfolobus solfataricus strain IT3 was identified using a structural–functional approach. The N‐terminal domain of the pIT3 replication protein encompassing residues 31–245 (i.e. Rep245) was modeled onto the crystallographic structure of the bifunctional primase–polymerase domain of the archaeal plasmid pRN1 and refined by molecular dynamics in solution. The Rep245 protein was purified following overexpression in Escherichia coli and its nucleic acid synthesis activity was characterized. The biochemical properties of the polymerase activity such as pH, temperature optima and divalent cation metal dependence were described. Rep245 was capable of utilizing both ribonucleotides and deoxyribonucleotides for de novo primer synthesis and it synthesized DNA products up to several kb in length in a template‐dependent manner. Interestingly, the Rep245 primase–polymerase domain harbors also a terminal nucleotidyl transferase activity, being able to elongate the 3′‐end of synthetic oligonucleotides in a non‐templated manner. Comparative sequence–structural analysis of the modeled Rep245 domain with other archaeal primase–polymerases revealed some distinctive features that could account for the multifaceted activities exhibited by this domain. To the best of our knowledge, Rep245 typifies the shortest functional domain from a crenarchaeal plasmid endowed with DNA and RNA synthesis and terminal transferase activity.
2,5‐diamino‐6‐ribitylamino‐4(3H)‐pyrimidinone 5′‐phosphate synthases of fungi and archaea
Authors: Römisch‐Margl Werner , Eisenreich Wolfgang , Haase Ilka , Bacher Adelbert , Fischer Markus
Published: July 2008

The pathway of riboflavin (vitamin B2) biosynthesis is significantly different in archaea, eubacteria, fungi and plants. Specifically, the first committed intermediate, 2,5‐diamino‐6‐ribosylamino‐4(3H)‐pyrimidinone 5′‐phosphate, can either undergo hydrolytic cleavage of the position 2 amino group by a deaminase (in plants and most eubacteria) or reduction of the ribose side chain by a reductase (in fungi and archaea). We compare 2,5‐diamino‐6‐ribitylamino‐4(3H)‐pyrimidinone 5′‐phosphate synthases from the yeast Candida glabrata, the archaeaon Methanocaldococcus jannaschii and the eubacterium Aquifex aeolicus. All three enzymes convert 2,5‐diamino‐6‐ribosylamino‐4(3H)‐pyrimidinone 5′‐phosphate into 2,5‐diamino‐6‐ribitylamino‐4(3H)‐pyrimidinone 5′‐phosphate, as shown by 13C‐NMR spectroscopy using [2,1′,2′,3′,4′,5′‐13C6]2,5‐diamino‐6‐ribosylamino‐4(3H)‐pyrimidinone 5′‐phosphate as substrate. The β anomer was found to be the authentic substrate, and the α anomer could serve as substrate subsequent to spontaneous anomerisation. The M. jannaschii and C. glabrata enzymes were shown to be A‐type reductases catalysing the transfer of deuterium from the 4(R) position of NADPH to the 1′ (S) position of the substrate. These results are in agreement with the known three‐dimensional structure of the M. jannaschii enzyme.
A novel 2D‐based approach to the discovery of candidate substrates for the metalloendopeptidase meprin
Authors: Ambort Daniel , Stalder Daniel , Lottaz Daniel , Huguenin Maya , Oneda Beatrice , Heller Manfred , Sterchi Erwin E.
Published: July 2008

In the past, protease‐substrate finding proved to be rather haphazard and was executed by in vitro cleavage assays using singly selected targets. In the present study, we report the first protease proteomic approach applied to meprin, an astacin‐like metalloendopeptidase, to determine physiological substrates in a cell‐based system of Madin–Darby canine kidney epithelial cells. A simple 2D IEF/SDS/PAGE‐based image analysis procedure was designed to find candidate substrates in conditioned media of Madin–Darby canine kidney cells expressing meprin in zymogen or in active form. The method enabled the discovery of hitherto unkown meprin substrates with shortened (non‐trypsin‐generated) N‐ and C‐terminally truncated cleavage products in peptide fragments upon LC‐MS/MS analysis. Of 22 (17 nonredundant) candidate substrates identified, the proteolytic processing of vinculin, lysyl oxidase, collagen type V and annexin A1 was analysed by means of immunoblotting validation experiments. The classification of substrates into functional groups may propose new functions for meprins in the regulation of cell homeostasis and the extracellular environment, and in innate immunity, respectively.