bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral cavernoma: an emerging long‐term consequence of external beam radiation in childhood
Authors: Liu Y. , Preston R. , Thomas S. M. , Brackenridge A. , Carroll P. V.
Published: December 2009

The long‐term effects of cranial external beam radiotherapy are emerging as survival rates for cerebral tumours improve. Cerebral cavernoma are a recognized consequence of cranial irradiation. Endocrinologists managing the life‐long complications of hypopituitarism associated with irradiation need to be aware and vigilant of the risks of cavernoma formation, in particular in the population with a history of childhood irradiation. We present three cases of young patients who were diagnosed with cerebral cavernoma many years after childhood irradiation treatment and review the current literature on this condition. We discuss implications for endocrine practice as rising numbers of patients survive childhood cancer and irradiation and are now attending adult endocrine services for long‐term management of secondary hypopituitarism.
d3‐GHR genotype does not explain heterogeneity in GH responsiveness in hypopituitary adults
Authors: Moyes V. J. , Walker D. M. , Owusu‐Antwi S. , Maher K. T. , Metherell L. , Akker S. A. , Monson J. P. , Clark A. J. L. , Drake W. M.
Published: December 2009

Objective  Heterogeneity in growth hormone (GH) responsiveness in adult hypopituitary patients receiving recombinant human GH (rhGH) is poorly understood; doses vary up to fourfold between individuals. Deletion of exon 3 in the GH receptor (d3‐GHR) has been linked to enhanced rhGH responsiveness in children. We investigated the role of the d3‐GHR polymorphism in determining adult rhGH responsiveness.

Methods  One hundred and ninety‐four patients treated with an identical rhGH dosing protocol in a single centre were genotyped for the d3‐GHR, and the results correlated with changes in serum IGF‐I and clinical parameters of GH responsiveness after 6 and 12 months of GH replacement therapy.

Results  Allele frequencies for homozygous full length (fl/fl), heterozygous d3 (fl/d3) and homozygous d3 (d3/d3) were 52%, 38·7% and 9·3%, respectively, and were in Hardy–Weinberg equilibrium. Baseline IGF‐I and ΔIGF‐I at 6 months were comparable between groups. ΔIGF‐I at 12 months was significantly greater in the d3/d3 group (P = 0·028). No difference was detected between fl/d3 and fl/fl groups. Regression analyses of ΔIGF‐I at 12 months and ΔIGF‐I/rhGH dose confirmed a significant relationship of d3/d3 genotype on rhGH response. There was no difference between groups in maintenance rhGH dose between genotypes.

Conclusion  Homozygosity for d3‐GHR confers a marginal increase in GH responsiveness at 12 months but without a detectable change in maintenance rhGH dose required. Both d3 alleles are required to achieve this response; given that only 10% of the population are d3 homozygotes, the d3GHR does not explain the marked heterogeneity of GH responsiveness in hypopituitary adults.
Feasibility and challenges of independent research on drugs: the Italian Medicines Agency (AIFA) experience
Authors:   Italian Medicines Agency (AIFA) Research & Development Working Group
Published: December 2009

Eur J Clin Invest 2010; 40 (1): 69–86

Key points

National Health Service (NHS) is becoming increasingly aware of the need to support independent research to answer some important questions for patient care in areas of scant commercial interest.

This article reports the main features and strategies of the independent research programme on drugs launched by the Italian Medicines Agency (AIFA) in 2005.

In the three bids launched between 2005 and 2007, a total of 151 studies have been approved for funding for a total of about 78 million Euro.

In this article we describe the Italian legislative framework under which the programme was launched, the types of research funded and discuss how the supported studies could contribute, in an international framework, to the knowledge needed on drug efficacy, effectiveness and safety.
TEM investigation of reaction zone products formed between molten Al and CoO monocrystalline substrate
Authors: MORGIEL J. , SOBCZAK N. , POMORSKA M. , RADZIWIŁŁ W. , NOWAK R. , KUDYBA A. , WOJEWODA‐BUDKA J.
Published: December 2009

The research was aimed at microstructure characterization of the reaction products formed between molten aluminium and CoO single crystal during a sessile drop wettability test performed in vacuum at 700 and 1000°C for 120 min using contact heating procedure. The solidified Al/CoO couples were sectioned and used for cutting thin foils with focused ion beam. The transmission electron microscopy and energy dispersive X‐ray spectroscopy were used for microstructure and local chemical analysis. The interaction of molten aluminium with CoO substrate at 700°C caused the formation of a corrugated 10–40 μm thick reaction zone (RZ). It consisted of aluminium matrix and Al2O3 crystallites varying in size, i.e. of ∼0.2 μm near the Al drop/RZ interface, growing up to 1–2 μm at the RZ centre and very fine nano‐crystallites near the RZ/CoO interface. The reaction of aluminium with CoO at 1000°C produced much thicker RZ of ∼280 μm characterized by layered microstructure of alternating fine crystalline Al2O3 and coarser Al13Co4 layers. Moreover, at the RZ/CoO interface the presence of a cobalt layer was also identified.
Fractal‐like behaviour of the BCC/FCC phase separation in the iron‐gold alloys
Authors: BŁACHOWSKI A. , RUEBENBAUER K. , RAKOWSKA A. , KĄC S.
Published: December 2009

Iron‐gold alloys with compositions Fe70Au30 and Fe50Au50 were prepared by arc melting. The alloys were investigated by means of the high‐resolution scanning electron microscopy (SEM‐FEG) in the as‐cast state and upon annealing in two steps, i.e. at 250°C for 24 h and subsequently at 500°C for 48 h. The alloys were composed of two phases, i.e. a BCC phase rich in iron and a FCC phase rich in gold. The single‐phase regions have equivalent diameter of about 50 nm. SEM images show self‐similar structure for the spatial distribution of the above phases on scales ranging from about 1 mm till about 100 nm. The roughness of the images has been used to estimate a fractal dimension of the phase mixture. For larger scales of the as‐cast samples one finds fractal dimension of about 1.7 for Fe70Au30 composition, i.e. very close to the dimension of typical diffusion limited aggregation (DLA) fractals. For annealed samples, dimension 1.1 was found.
The effect of carbide precipitate morphology on fracture toughness in low‐tempered steels containing Ni
Authors: KRAWCZYK J. , BAŁA P. , PACYNA J.
Published: December 2009

Nickel is known to increase the resistance to cleavage fracture of iron and decrease a ductile‐to‐brittle transition temperature. The medium‐carbon, low‐alloy martensitic steels attain the best combination of properties in low‐tempered condition, with tempered martensite, retained austenite and transition carbides in the microstructure. This paper is focused on the influence of Ni addition (from 0.35 to 4.00%) on the microstructure and fracture toughness of structural steels after tempering. In this research, four model alloys of different concentration of Ni and constant concentration of carbon and other elements were used. All samples were in as‐quenched and tempered conditions. Quenching was performed in oil at room temperature. After quenching, samples were tempered at 200°C for 2 h. The microstructure of the investigated steels was analyzed using JEM200CX transmission electron microscope. An increase of nickel content in the investigated structural steels causes a decrease of ɛ carbide concentration in their microstructure after tempering. In these steels, cementite precipitates independently in the boundaries of martensite needles and in the twin boundaries in the areas where the Fe2.4C carbide has been dissolved. These results will be used to design new technologies of tempering of structural steels with nickel addition.
Effect of annealing temperature on the structure and mechanical properties of mechanically alloyed AlMg–Nb2O5 and AlMg–ZrSi2 composites
Authors: KULA A. , BLAZ L. , KANEKO J. , SUGAMATA M.
Published: December 2009

Mechanical alloying and hot extrusion method were used for manufacturing AlMg‐based composites reinforced with addition of niobium oxide (Nb2O5) and zirconium silicide (ZrSi2) particles. High mechanical properties of the materials were found to result from heavily refined structure of composites. It was found that the composite structure was transformed at high temperature as a result of irreversible chemical reaction between disperse reinforcements and surrounding matrix. Chemical reaction for AlMg–Nb2O5 composite results in a growth of intermetallic grains of Al3Nb type and very fine oxides particles of 5–20 nm in diameter. In the annealed AlMg–ZrSi2 composite, new grains of Al3Zr, Mg2Si and Al(Mg)O are formed as a result of zirconium silicide decomposition. Hot compression tests were performed at constant true strain rate of 5.10−3 s−1 within the temperature range of 293–823 K. The high flow stress values are attributed to highly refined structure of the materials that essentially did not coarsen in spite of high deformation temperature.
Imaging using pulses: a simple and fast (>100 kHz) solution
Authors: UDALAGAMA C. , BETTIOL A.A. , WATT F.
Published: December 2009

Imaging is an important component of spectroscopy. A good imaging system is expected to work with a high‐pixel resolution using signals of high count‐rates with as little dead time as possible to deliver an image quickly and reliably. It is not uncommon for such a system to be highly specialized, expensive and to consist of many dedicated electronic components. In this work, we present a simple imaging algorithm that can be used with a pulse (TTL) data signal, such as that produced by some photomultipliers and electron detectors. This algorithm works with only a simple general purpose data acquisition computer card (NI PXI/PCI‐6259) from National Instruments residing in a computer. The system has been tested with signal rates in excess of 100 kHz to produce images at a pixel resolution of 512 × 512. The system's ability to handle such high count‐rates hinges on utilizing the buffered data collection feature on the said card, in a hitherto unreported configuration. This system now offers a simple and cost‐effective manner of incorporating high count‐rate imaging features, such as in a scanning electron microscope, into a purely spectroscopic system. Further, since the use of the NI DAQ cards are supported under other computer platforms, the current imaging formalism is readily transferrable to computer platforms such as Linux or Mac OS.
Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study
Authors: Crespo‐Leiro Maria G. , Delgado Juan F. , Paniagua Maria J. , Vázquez de Prada Jose A. , Fernandez‐Yañez Juan , Almenar Luis , Diaz‐Molina Beatriz , Roig Eulalia , Arizón Jose M. , Alonso‐Pulpón Luis , Garrido Iris P. , Sanz Maria Luisa , De La Fuente Luis , Mirabet Sonia , Manito Nicolas , Muñiz Javier
Published: December 2009

Crespo‐Leiro MG, Delgado JF, Paniagua MJ, Vázquez, de Prada JA, Fernandez‐Yañez J, Almenar L, Diaz‐Molina B, Roig E, Arizón JM, Alonso‐Pulpón L, Garrido IP, Sanz ML, de la Fuente L, Mirabet S, Manito N, Muñiz J. Prevalence and severity of renal dysfunction among 1062 heart transplant patients according to criteria based on serum creatinine and estimated glomerular filtration rate: results from the CAPRI study. Clin Transplant 2010: 24: E88–E93. © 2009 John Wiley & Sons A/S.

Abstract:  Chronic kidney disease (CKD) is staged on the basis of glomerular filtration rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD) in heart transplant (HT) patients is often evaluated solely in terms of serum creatinine (SCr). In a cross‐sectional, 14‐center study of 1062 stable adult HT patients aged 59.1 ± 12.5 yr (82.3% men), RD was graded as absent‐or‐mild (AoM), moderate, or severe (this last including dialysis and kidney graft) by two classifications: SCr‐RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR‐RD (eGFR cutoffs 60 and 30 mL/min/1.73 m2). SCr‐RD was AoM in 68.5% of patients, moderate in 24.9%, and severe in 6.7%; eGFR‐RD, AoM in 38.6%, moderate in 52.2%, severe in 9.2%. Among patients evaluated <2.7, 2.7‐6.2, 6.2‐9.5 and >9.5 yr post‐HT (the periods defined by time‐since‐transplant quartiles), AoM/moderate/severe RD prevalences were <2.7, SCr‐RD 74/21/5%, eGFR‐RD 47/47/6%; 2.7‐6.2, SCr‐RD 73/22/5%, eGFR‐RD 37/56/7%; 6.2–9.5, SCr‐RD 69/24/7%, eGFR‐RD 37/54/9%; >9.5, SCr‐RD 58/32/10%, eGFR‐RD 32/52/16%. The prevalence of severe RD increases with time since transplant. If the usual CKD stages are appropriate for HT patients, the need for less nephrotoxic immunosuppressants and other renoprotective measures is greater than is suggested by direct SCr‐based grading, which should be abandoned as excessively insensitive.
Secreted frizzled‐related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment
Authors: Sutton Gerard , Madigan Michele , Roufas Athena , McAvoy John
Published: December 2009

Abstract

Purpose:  To investigate the expression of Wnt signalling pathway genes in keratoconic (KC) epithelium.

Methods:  RNA was extracted from the epithelium of four KC patients undergoing corneal transplantation and five age‐matched controls. The expression of 84 genes known to be involved in the Wnt signalling pathway was tested by reverse transcription‐polymerase chain reaction (RT‐PCR) with a pathway‐targeted array (Human Wnt RT2 Profiler PCR Array, Superarray).

Results:  Using RT‐PCR arrays, LEF1, PITX2 and secreted frizzled‐related protein 1 (SFRP1) were upregulated more than twofold in KC compared with control epithelium. Only SFRP1 was significantly upregulated, ∼25‐fold compared with pooled controls (range 9.12‐fold to 98.6‐fold; P = 0.019). SFRP1 expression was associated with patient age and possibly the rate of progression of the keratoconus. Immunohistochemistry was used to assess SFRP1 protein distribution and confirm the SFRP1 microarray result (n = 3 KC and n = 2 control corneas). SFRP1 immunolablelling was seen in all KC corneas, mostly in the basal epithelium; however, control corneas showed minimal SFRP1 immunoreactivity.

Conclusion:  SFRP1 is highly upregulated in the epithelium of these KC patients, suggesting a role in the pathogenesis and progression of keratoconus. Future investigations are required to establish if SFRP1 may be a potential marker of KC progression or if manipulation of its expression can be used to therapeutic effect in this disease.
Long‐range effects of GABAergic inhibition in gerbil primary auditory cortex
Authors: Moeller Christoph K. , Kurt Simone , Happel Max F. K. , Schulze Holger
Published: December 2009

Throughout the literature, the effects of iontophoretically applied neurotransmitter agonists or antagonists on the local activity of neurons are typically studied at the site of drug application. Recently, we have demonstrated long‐range inhibitory interactions within the primary auditory cortex (AI) that are effective in complex acoustic situations. To further characterize this long‐range functional connectivity, we here report the effects of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) and the GABAA antagonist gabazine (SR 95531) on neuronal activity as a function of distance from the application site reaching beyond the diffusion radius of the applied drug. Neuronal responses to pure tone stimulation were simultaneously recorded at the application site and four additional sites, at distances between 300 and 1350 μm from the application site. We found that whereas application of GABA during best frequency (BF) stimulation in general led to a decrease, and gabazine to an increase, in neuronal activity at the application site, a considerable number of units at remote recording sites showed effects opposite to these local, drug‐induced effects. These effects were seen both in spiking activity and in amplitudes of local field potentials. At all locations, the effects varied as a function of pure tone stimulation frequency, pointing to a Mexican‐hat‐like input function resulting from thalamic inputs to the BF region of the cortical neurons and intracortical interconnections projecting to off‐BF regions of the neurons. These data demonstrate the existence of long‐range, inhibitory interactions within the gerbil AI, realized either by long‐range inhibitory projections or by long‐range excitatory projections to local inhibitory interneurons.
Ability and Trait Complex Predictors of Academic and Job Performance: A Person–Situation Approach
Authors: Kanfer Ruth , Wolf Mark B. , Kantrowitz Tracy M. , Ackerman Phillip L.
Published: December 2009

A battery of cognitive ability, knowledge, and non‐ability measures were administered to 105 college students enrolled in a cooperative school‐work program and used to predict academic and job performance. Composite scores for each domain were derived from factor analyses of 11 measures of verbal, numerical, and spatial abilities, four measures of domain knowledge, and 27 measures of personality and motivational traits, vocational interests, and self‐assessments. Both ability and non‐ability trait composites were significant predictors of academic performance, but only the non‐ability trait composites predicted job performance. Implications for the integrative assessment of individual differences and their predictive validities for performance in different active work contexts, as well as the importance of trait composites across contexts, are discussed.

Un ensemble de mesures relatives aux connaissances, aux aptitudes et autres dimensions furent obtenues auprès de 105 étudiants de 1° cycle impliqués dans un programme de travail scolaire coopératif, avec pour objectif de prédire les résultats universitaires et la performance au travail. Des scores composites pour chacun de ces deux domaines ont été constitués à partir d'analyses factorielles des onze mesures des aptitudes verbale, numérique et spatiale, des quatre mesures portant sur les connaissances et des 27 mesures relevant de traits de personnalité, de la motivation, des intérêts professionnels et de l'auto‐évaluation. Les scores des aptitudes et des traits de personnalité furent des prédicteurs significatifs du succès universitaire, mais seuls ces derniers ont prédit la performance au travail. On réfléchit aux conséquences sur l'évaluation synthétique des différences individuelles et leur validité prédictive de la performance dans différents contextes de travail productif, ainsi que sur l'importance des scores composites selon les situations.
Temporal features of magnetic resonance imaging and spectroscopy in non‐ketotic hyperglycemic chorea‐ballism patients
Authors: Chang K. ‐H. , Tsou J. ‐C. , Chen S. ‐T. , Ro L. ‐S. , Lyu R. ‐K. , Chang H. ‐S. , Hsu W. ‐C. , Chen C. ‐M. , Wu Y. ‐R. , Chen C. ‐J.
Published: December 2009

Background:  Non‐ketotic hyperglycemic chorea‐ballism (NKHCB) had special reversible hyperintense on T1‐weighted imaging (T1WI) lesion in comparsion to gray matter. However, the mechanism accounts for these lesions is still unclear.

Methods:  Patients diagnosed with NKHCB were recruited from 2002 to 2004. The demographic, clinical, magnetic resonance imaging (MRI), and spectroscopy (MRS) features were recorded at acute and remission phase.

Results:  In 18 patients with NKHCB, the blood sugar level at onset was significantly higher than that after being free from chorea‐ballism (419.50 ± 257.33 vs. 198.22 ± 53.97 mg/dl, P = 0.001). The serum osmolality dropped from 318.33 ± 15.21 mOsm/kg at onset to 292.50 ± 7.85 mOsm/kg after recovery (P < 0.001). All patients displayed T1 hyperintense lesions at contralateral basal ganglia at acute phase. Eight patients receiving follow‐up MRI at remission phase, all T1 hyperintense lesions at the basal ganglia regressed. The ratios between choline‐containing compounds and creatine at acute and remission phases were significant higher in lesion than in normal side, respectively (acute phase: 1.12 ± 0.23 vs. 0.72 ± 0.28, P = 0.038; remission phase: 1.23 ± 0.47 vs. 0.68 ± 0.15, P = 0.013). The lactate peaks present at 1.3 ppm on the lesion side either in acute or in remission phase of most case.

Conclusions:  The clinical, MRI, and MRS findings suggest that the mechanisms responsible for NKHCB may be a reversible ischaemia insult potentiated by hyperglycemia.
Acquired erythroderma in adults: a clinical and prognostic study
Authors: Khaled A , Sellami A , Fazaa B , Kharfi M , Zeglaoui F , Kamoun MR
Published: December 2009

Background  Erythroderma is a severe syndrome and prognostic studies are rare in the literature.

Objectives  Through a retrospective study of erythroderma in adults, we have analysed epidemiological and clinical data and precised the relevant aetiologies and survival in our patients.

Methods  This study was performed at the Department of Dermatology of Charles Nicolle Hospital of Tunis (1995–2007) including 82 cases of acquired erythroderma (>16 years). We have recorded epidemio‐clinical, biological and histological data, treatment and outcome. Clinical–histological correlation was analysed [kappa coefficient (κ)]. Follow‐up time and disease‐free survival time were calculated as were Kaplan–Meier estimates of overall survival and relapse‐free survival for some aetiologies.

Results  Erythroderma represented 0.44‰ of all dermatoses with an age of 55.13 ± 18.16 and no sex predilection. Psoriasis was the predominant aetiology (32.9%) with a median duration of 6.75 years and previous one or more episodes of erythroderma. Psoriasis was significantly associated with pruritus (P = 0.0001), pachyonychia (P = 0.00001), palmoplantar keratoderma (P = 0.0001) and hypereosinophilia (P = 0.008). The latter is then not specific for drug induced erythroderma (P = 0.004). Carbamazepine (27.8%) and penicillin (22.2%) were the most implicated drugs. Positive Clinical–histological correlation was found in 77% of cases (κ = 0.753). Relapse was seen in all aetiologies, but drug reactions and had occurred in the first 3 years in 90% of them. Mortality rate was 11.3 per 1000 patients‐years.

Conclusions  Our study illustrates the severity of erythroderma. It alters heavily the quality of life of patients which is initially altered by the pre‐existent dermatosis. It may be life threatening as mortality rate is high.
Tattoo removal by non‐professionals – medical and forensic considerations
Authors: Karsai S , Krieger G , Raulin C
Published: December 2009

Tattoos are common phenomena in the western world and the demand for their removal has become widespread in the recent years. The introduction of quality‐switched lasers has provided an effective removal method that is increasingly being exploited by tattoo studios themselves. Dermatologists, however, are frequently confronted with complications and side effects of tattoo removals that were performed by non‐professionals. The objective of this study is to assess potential risks and pitfalls of laser tattoo removal when performed by medical laymen. The methods followed are systematic and evidence‐based review of the literature. Four major problem areas were identified: rare but potentially severe allergic or toxic effects of decomposition products of the tattoo pigments; bodily harm caused by out‐of‐specification usage of the laser devices; malignant disease that is obscured within the area of a tattoo and requires meticulous dermatological diagnosis; and insufficient pre‐operative consultation of patients about the risks, side effects and realistic expectations on the therapeutic outcome. We came to a conclusion that tattoo laser removal by medical laymen is unacceptable from the point of view of patient safety and the laws need to ban this practice swiftly.
Photodynamic therapy with 5‐aminolevulinic acid in actinic cheilitis: an 18‐month clinical and histological follow‐up
Authors: Sotiriou E , Apalla Z , Chovarda E , Panagiotidou D , Ioannides D
Published: December 2009

Background  Actinic cheilitis (AC) may bear the initial and superficial changes of actinically induced squamous cell carcinoma (SCC) and may progress into fully developed SCCs. Early and effective treatment is important.

Objective  To assess the clinical and histological long‐term outcome in AC after two ALA‐PDT sessions.

Methods  Patients with histologically proven grade 1 and 2 AC received two ALA‐PDT sessions at 2 weeks interval. Subjects with complete clinical response at 3 months were evaluated further clinically and histologically at months 6, 12 and 18. Long‐term study outcome was defined as clinical and histological AC recurrence among patients with complete clinical response 3 months after treatment. Cosmetic outcome was assessed by the investigators at the final follow‐up visit at 18 months.

Results  Of the 40 patients enrolled, 38 completed the study. Complete clinical response at 3 months was achieved in 26 patients. At 6 months, clinical and histological recurrence occurred in three patients and at 12 months, one more patient showed clinical and histological recurrence. At 18 months, overall clinical recurrence rate was 15.38% (4/26), while overall histological recurrence rate was 34.61% (9/26). Cosmetic outcome was rated as excellent in more than 80% of evaluated cases.

Conclusion  PDT represents a moderately effective treatment modality in AC. Optimization of treatment procedure and protocols is still needed for higher response rates to be achieved. Moreover, the high treatment cost should be given consideration. Further long‐term follow‐up studies are needed for assessment of clinical and histological very late recurrences that could be expected after PDT.
D3dopamine receptor signals to activation of phospholipase D through a complex with Rho
Authors: Everett P. Benjamin , Senogles Susan E.
Published: December 2009

J. Neurochem. (2009)112, 963–971.

Dopamine acts through a family of G protein‐coupled receptors to exert its myriad effects. The D3Dopamine receptor is one member of the D2‐like dopamine receptors. We have previously demonstrated in human embryonic kidney (HEK293) cells that D3receptor stimulation of phospholipase D (PLD) activity is pertussis toxin insensitive [Everett and Senogles.Neurosci. Lett.371 (2004), 34]. We hypothesized that a low molecular weight G protein was involved in the agonist‐mediated activation of PLD. When the D3receptor was coexpressed with RhoA in HEK293 cells, agonist‐induced stimulation of PLD activity was increased. However, co‐expression of Rac or Cdc42 with the D3receptor did not change the PLD activity. As well, expression of a dominant‐negative construct of RhoA, N19 Rho completely ablated D3receptor‐mediated PLD activation, when co‐expressed with the D3receptor in HEK293 cells. In contrast, expression of dominant‐negative constructs of Rac or Cdc42 had no effect. Treatment of HEK293 cells transfected with the D3receptor and treated with a D3preferring agonistR(+)‐hydroxy(dipropylamino)tetralin hydrobromide, results in an agonist‐induced physical complex of D3receptor and either endogenous Rho or transfected hemaglutinin (HA)‐RhoA that can be detected by immunoprecipitation and western blotting. Treatment of cells transfected with D3receptor withR(+)‐hydroxy(dipropylamino)tetralin hydrobromide also results in agonist‐dependent Rho activation, as measured by a Rho effector pull‐down assay. The data suggest that D3receptor/RhoA association and activation is necessary for D3receptor‐mediated PLD activation.
Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia
Authors: Son Tae Gen , Camandola Simonetta , Arumugam Thiruma V. , Cutler Roy G. , Telljohann Richard S. , Mughal Mohamed R. , Moore Tyson A. , Luo Weiming , Yu Qian‐Sheng , Johnson Delinda A. , Johnson Jeffrey A. , Greig Nigel H. , Mattson Mark P.
Published: December 2009

J. Neurochem. (2010) 112, 1316–1326.

Many phytochemicals function as noxious agents that protect plants against insects and other damaging organisms. However, at subtoxic doses, the same phytochemicals may activate adaptive cellular stress response pathways that can protect cells against a variety of adverse conditions. We screened a panel of botanical pesticides using cultured human and rodent neuronal cell models, and identified plumbagin as a novel potent activator of the nuclear factor E2‐related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. In vitro, plumbagin increases nuclear localization and transcriptional activity of Nrf2, and induces the expression of the Nrf2/ARE‐dependent genes, such as heme oxygenase 1 in human neuroblastoma cells. Plumbagin specifically activates the Nrf2/ARE pathway in primary mixed cultures from ARE‐human placental alkaline phosphatase reporter mice. Exposure of neuroblastoma cells and primary cortical neurons to plumbagin provides protection against subsequent oxidative and metabolic insults. The neuroprotective effects of plumbagin are abolished by RNA interference‐mediated knockdown of Nrf2 expression. In vivo, administration of plumbagin significantly reduces the amount of brain damage and ameliorates‐associated neurological deficits in a mouse model of focal ischemic stroke. Our findings establish precedence for the identification and characterization of neuroprotective phytochemicals based upon their ability to activate adaptive cellular stress response pathways.
Parental Investment in Children: Differential Pathways of Parental Education and Mental Health*
Authors: YAMAUCHI CHIKAKO
Published: December 2009

This article examines pathways through which parental characteristics might affect children’s cognitive and behavioural outcomes. Using the 2004 Longitudinal Study of Australian Children, I show that more educated and mentally healthier parents are likely to have children with better outcomes. Educated parents are more frequently engaged in education‐oriented activities with their children, whereas mentally healthier parents exhibit more favourable parenting practices. To the extent that these results reflect causal relationships, they suggest that parental education and mental health affect children’s outcomes through different pathways.
Neuropeptide Y Signaling in the Central Nucleus of Amygdala Regulates Alcohol‐Drinking and Anxiety‐Like Behaviors of Alcohol‐Preferring Rats
Authors: Zhang Huaibo , Sakharkar Amul J. , Shi Guangbin , Ugale Rajesh , Prakash Anand , Pandey Subhash C.
Published: December 2009

Background: The neuropeptide Y (NPY) system of the central nucleus of amygdala (CeA) has been shown to be involved in anxiety and alcoholism. In this study, we investigated the molecular mechanisms by which NPY in the CeA regulates anxiety and alcohol drinking behaviors using alcohol‐preferring (P) rats as an animal model.

Methods: Alcohol‐preferring rats were bilaterally cannulated targeting the CeA and infused with artificial cerebrospinal fluid (aCSF) or NPY. Alcohol drinking and anxiety‐like behaviors were assessed by the 2‐bottle free‐choice paradigm and light/dark box (LDB) exploration test, respectively. The levels of NPY and related signaling proteins were determined by the gold immunolabeling procedure. The mRNA levels of NPY were measured by in situ RT‐PCR. Double‐immunofluorescence labeling was performed to observe the colocalization of NPY and Ca2+/calmodulin‐dependent protein kinase IV (CaMK IV).

Results: We found that NPY infusion into the CeA produced anxiolytic effects, as measured by the LDB exploration test, and also decreased alcohol intake in P rats. NPY infusion into the CeA significantly increased levels of CaMK IV and phosphorylated cAMP responsive element‐binding (pCREB) protein and increased mRNA and protein levels of NPY, but produced no changes in protein levels of CREB or the catalytic α‐subunit of protein kinase A (PKA‐Cα) in the CeA. We also observed that alcohol intake produced anxiolytic effects in P rats in the LDB test and also increased NPY expression and protein levels of pCREB and PKA‐Cα without modulating protein levels of CREB or CaMK IV, in both the CeA and medial nucleus of amygdala. In addition, we found that CaMK IV‐positive cells were co‐localized with NPY in amygdaloid structures of P rats.

Conclusions: These results suggest that NPY infusion may increase the expression of endogenous NPY in the CeA, which is most likely attributable to an increase in CaMK IV‐dependent CREB phosphorylation and this molecular mechanism may be involved in regulating anxiety and alcohol drinking behaviors of P rats.
Calcium is a key constituent for maintaining the in vitro properties of platelets suspended in the bicarbonate‐containing additive solution M‐sol with low plasma levels
Authors: Wagner Stephen J. , Skripchenko Andrey , Myrup Andrew , Thompson‐Montgomery Dedeene , Awatefe Helen , Moroff Gary
Published: December 2009

BACKGROUND: Commercially available additive solutions (ASs) require 30% to 35% plasma for optimal storage of platelets (PLTs). PLTs suspended in M‐sol, a bicarbonate‐based experimental platelet additive solution (PAS), maintain in vitro PLT properties during storage with low levels of plasma (≤5%).

STUDY DESIGN AND METHODS: Four different formulations of M‐sol were prepared at the optimal pH (6.1): M‐sol, M‐sol without calcium, M‐sol without citric acid, and M‐sol without calcium and citric acid. Apheresis PLT units (100% plasma) were equally divided into five 50‐mL aliquots in PL732 containers, centrifuged, and resuspended to prepare units suspended in the four different PASs (95%) with 5% plasma and 1 unit in 100% plasma. Units (n = 10) were stored under standard conditions and assayed for in vitro properties on Days 1, 5, and 7. The data were analyzed by analysis of variance for repeated measures (n = 10, p < 0.001).

RESULTS: On Day 5 of storage, PLTs suspended in the M‐sol formulation containing calcium but lacking citric acid had similar pH, extent of shape change (ESC) values, and percentage of CD62‐positive PLTs and greater hypotonic shock response (HSR) and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma. In contrast, PLTs suspended in the M‐sol formulation lacking calcium had lesser ESC values, greater percentage of CD62‐positive PLTs, and similar HSR values and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma on Day 5 (p < 0.001).

CONCLUSIONS: Calcium plays an important role in maintaining CD62‐negative PLTs and relatively high ESC in 5% plasma. The removal of citric acid from M‐sol may improve PLT storage properties with low plasma levels.
Therapeutic efficacy of platelet transfusion in patients with acute leukemia: an evaluation of methods
Authors: Apelseth Torunn O. , Bruserud Øystein , Wentzel‐Larsen Tore , Hervig Tor
Published: December 2009

BACKGROUND: Clinical effect of platelet (PLT) transfusion is monitored by measures of PLT viability (PLT recovery and survival) and functionality. In this study we evaluate and compare transfusion effect measures in patients with chemotherapy‐induced thrombocytopenia due to treatment of acute leukemia.

STUDY DESIGN AND METHODS: Forty transfusions (28 conventional gamma‐irradiated and 12 pathogen‐inactivated photochemical‐treated PLT concentrates [PCs]) were investigated. PC quality was analyzed immediately before transfusion. Samples were collected from thrombocytopenic patients at 1 and 24 hours for PLT increments and thromboelastography (TEG) with assessments of bleeding score and intertransfusion interval (ITI). Data were analyzed by Spearman's correlation. Patient and PC variables influencing the effect of transfusion were analyzed by use of a mixed‐effects model.

RESULTS: PLT dose, storage time, and pathogen inactivation correlated with PLT recovery but not with PLT survival (including ITI), TEG, or clinical bleeding. Fever was negatively correlated with PLT survival but did not affect PLT recovery. After 1 and 24 hours, strong correlations were observed within measures of PLT viability and between PLT increment and the TEG value maximal amplitude (MA). Negative correlation was observed between late MA increment and clinical bleeding status after transfusion (r = −0.494, p = 0.008). PLT count increments did not correlate to clinical bleeding status.

CONCLUSIONS: PLT dose and quality of PCs are important for optimal immediate transfusion response, whereas duration of transfusion effect is influenced mainly by patient variables. The TEG value MA correlates with PLT count increments and bleeding, thus reflecting both PLT viability and functionality.
Hemodynamic Support Using the Impella 2.5 Catheter System during High‐Risk Percutaneous Coronary Intervention in a Patient with Severe Aortic Stenosis
Authors: HARJAI KISHORE J. , O’NEILL WILLIAM W.
Published: December 2009

The Impella 2.5 catheter is a percutaneously implanted left ventricular assist device cleared by the Food and Drug Administration to provide circulatory support for up to 6 hours. The presence of aortic stenosis is deemed to be a contraindication to its use, and ongoing clinical trials exclude patients with an aortic valve area of 1.5 cm2 or less. We describe a case of severe aortic stenosis with an estimated valve area of 0.9 cm2 and severe ischemic cardiomyopathy in whom the Impella catheter was successfully used for high‐risk multivessel percutaneous coronary intervention. (J Interven Cardiol 2010;23:66–69)
Case Study of the Oodi Weavers of Botswana: Challenges to Sustainability in Southern Africa
Authors: Gaskill LuAnn R. , Dingake Tshimologo
Published: December 2009

To effectively prepare future entrepreneurs and small business managers for a breadth of business endeavors, higher education is challenged to offer educational and learning experiences that help others understand the complexities and challenges of operating in a third‐world small business setting. In order to meet such needs, researchers engaged in on‐site case study development with the Oodi Weavers in Botswana, Africa. The Oodi Weavers function as a female‐based small business textile weaving cooperative offering opportunities for increased tourism, self‐sufficiency, and sustainability for a sector of the local population. Through the case presentation, readers have the opportunity to discuss the history and challenges of the Oodi Weavers from a variety of perspectives and subject matter areas.
Integral Metatheory: Beyond Specializations, Theoretical Pluralism, and Conventional Metatheory
Authors: McGregor Sue L. T.
Published: December 2009

Recent family and consumer science (FCS) conceptualizations of specialization embrace the notions of interdisciplinary specialist, integration of perspectives, integral specialist and a generalist in transdisciplinarity. These innovations open the door for a conversation around the impact of research methodologies (different from methods) on the profession’s body of knowledge. Conventional metatheory is explained, with four examples from the field of FCS. The paper then introduces the idea of integral metatheory, asking practitioners to strive for a deeper understanding of theoretical pluralism and a new form of synthesis: being able to integrate the results obtained from the integration of several theoretical perspectives. Instead of practicing from a platform of many individual theories, FCS professionals are asked to employ integral metatheory so they can consciously develop links among the theories and multiple perspectives, thereby leading to richer understandings of the complexity of the human condition.
Perceived Fairness of Pay: The Importance of Task versus Maintenance Inputs in Japan, South Korea, and Hong Kong
Authors: Kim Tae-Yeol , Weber Todd J. , Leung Kwok , Muramoto Yukiko
Published: December 2009

This study compares East Asians' evaluations of task and maintenance inputs in reward allocation decisions and examines the effects that inequity in various types of inputs and rewards have on fairness judgements. Based on a sample of 587 employees from various organizations in Hong Kong, Japan, and South Korea, we find that Hong Kong Chinese and South Korean employees are more likely to want their organizations and supervisors to emphasize maintenance inputs, while Japanese employees value task inputs in reward allocation. Results also show that there are significant country differences in fairness judgements associated with various types of inputs. For example, the positive relationship between pay level and perceived fairness of pay is significantly stronger when task contributions are high rather than low among Japanese employees but not among Hong Kong and South Korean employees. The concept of independent self-construal (similar to individualism at the societal level) seems to provide an adequate account of the country differences in choice of input preferences but not fairness judgements.
Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: type I and III collagens†
Authors: Oliveira Gisele V , Hawkins Hal K , Chinkes David , Burke Ann , Tavares Andre Luiz Pasqua , Ramos‐e‐Silva Marcia , Albrecht Thomas B , Kitten Gregory T , Herndon David N
Published: December 2009

Oliveira GV, Hawkins HK, Chinkes D, Burke A, Pasqua Tavares AL, Ramos‐e‐Silva M, Albrecht TB, Kitten GT, Herndon DN. Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: type I and III collagens.

Although dermal collagens appear increased in hypertrophic scars, this has not been tested in tissue samples using objective methods. We compared the expression of types I and III collagen in hypertrophic and non hypertrophic scars at 6–12 and 18–24 months after burn using a quantitative method. Among 17 patients with extensive burns, 3 patients had acute scars, 8 had hypertrophic or non hypertrophic scars at 6–12 months after burn and 6 had hypertrophic or non hypertrophic scars at 18–24 months after burn. After clinical assessment of scars using the Vancouver scale, immunohistochemistry for types I and III collagens was performed. Images were captured with a laser scanning confocal microscope and the relative amounts of types I and III collagens were determined in superficial and deep dermis. The effects of time and scar type were assessed using two‐way analysis of variance (ANOVA) and Tukey's test. Collagen III scar/normal ratios were higher in hypertrophic scars at both time points (P = 0.05). There were no differences in collagen I scar/normal ratios. Large variation was observed in scars during the acute phase regarding the expression of collagens. Easily accessed by immunohistochemistry and confocal microscopy, type III collagen deposition may help in determining scar phenotype, differentiating hypertrophic and non hypertrophic scars.
Intra‐lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo‐controlled, double‐blind study
Authors: Fernández‐Montequín José I , Valenzuela‐Silva Carmen M , Díaz Odalys González , Savigne William , Sancho‐Soutelo Natasha , Rivero‐Fernández Fidel , Sánchez‐Penton Pablo , Morejón‐Vega Lourdes , Artaza‐Sanz Heriberto , García‐Herrera Arístides , González‐Benavides Cecilio , Hernández‐Cañete Carlos M , Vázquez‐Proenza Alberto , Berlanga‐Acosta Jorge , López‐Saura Pedro A ,   for the Cuban Diabetic Foot Study Group
Published: December 2009

Fernández‐Montequín JI, Valenzuela‐Silva CM, González Díaz O, Savigne W, Sancho‐Soutelo N, Rivero‐Fernández F, Sánchez‐Penton P, Morejón‐Vega L, Artaza‐Sanz H, García‐Herrera A, González‐Benavides C, Hernández‐Cañete CM, Vázquez‐Proenza A, Berlanga‐Acosta J, López‐Saura PA, for the Cuban Diabetic Foot Study Group. Intra‐lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo‐controlled, double‐blind study.

A multicenter, double‐blind, placebo‐controlled trial was carried out to evaluate the intra‐lesional infiltration of recombinant epidermal growth factor (EGF) in Wagner's grade 3 or 4 diabetic foot ulcers (DFUs). Subjects (149) were randomised to receive EGF (75 or 25 µg) or placebo, three times per week for 8 weeks and standard good wound care. The main endpoint was granulation tissue covering ≥ 50% of the ulcer at 2 weeks. It was achieved by 19/48 controls versus 44/53 in the 75 µg group [odds ratio (OR): 7·5; 95% confidence interval (CI): 2·9–18·9] and 34/48 in the 25 µg group (OR: 3·7; 1·6–8·7). Secondary outcome variables such as end‐of‐treatment complete granulation response (28/48 controls, 46/53 with 75 µg and 34/48 with 25 µg EGF), time‐to‐complete response (controls: 5 weeks; both EGF dose groups: 3 weeks), and wound closure after follow‐up (25/48 controls, 40/53 with 75 µg and 25/48 with 25 µg EGF) were also treatment dependent. Multivariate analyses yielded that they were significantly enhanced by 75 µg EGF treatment and neuropathic versus ischemic ulcers. Most adverse events were mild and no drug‐related severe adverse reactions were reported. It was concluded that recombinant human EGF (rhEGF) local injections offer a favourable risk–benefit balance in patients with advanced DFU.
Challenging Britain's benefits system
Authors: Brien Stephen
Published: December 2009

The economic downturn has increased pressure on Britain's benefits system – a system already failing to deliver reductions in poverty or unemployment. New thinking is needed, acknowledging the economic incentives created by benefits and setting employment as a central goal for the welfare state, says Stephen Brien
Who will care? Meeting the care deficit
Authors: Ben‐Galim Dalia
Published: December 2009

As the population continues to age, more of us are becoming carers, and many must juggle responsibilities between working and caring. Innovative policy reform is fundamental if we are to meet future demand for care, explains Dalia Ben‐Galim
Serum Antioxidant Capacity is Preserved in Peritoneal Dialysis Contrary to Its Robust Depletion After Hemodialysis and Hemodiafiltration Sessions
Authors: Rysz Jacek , Stolarek Robert A , Pedzik Adrianna , Nowicki Michał , Nowak Dariusz
Published: December 2009

Renal replacement therapy (RRT) may differentially affect systemic generation of reactive oxygen species and depletion of antioxidant pools of low molecular weight molecules and proteins. This study was designed to assess the magnitude of the impairment of serum total antioxidant capacity (TAC) in relation to different RRT modalities. The study included patients on continuous ambulatory peritoneal dialysis (CAPD, N = 21), hemodialysis (HD, N = 21), hemodiafiltration (HDF, N = 20), and healthy controls (N = 33). TAC was assessed by the ferric reducing ability of plasma (FRAP) and with the 2,2‐diphenyl‐1‐picryl‐hydrazyl (DPPH) assay. In CAPD patients, predialysis FRAP and DPPH were increased: 1.46 mM and 10.5% vs. control 1.19 mM and 7.2%, respectively (P < 0.001 in each). In HD and HDF patients, the FRAP and DPPH were significantly increased before and lowered after the RRT session (P < 0.05) if compared with healthy controls. During an HD session, FRAP was decreased from pre‐HD 1.71 ± 0.29 mM to post‐HD 0.85 ± 0.20 mM (P = 0.0001). The decrease of FRAP was lower during HDF (P < 0.05 vs. HD), it decreased from pre‐HDF 1.41 ± 0.43 mM to post‐HDF 0.87 ± 0.23 mM (P = 0.0001 vs. pre‐HDF). The HD session decreased DPPH from the pre‐HD median 10.3%, interquartile range (IR) 9.3–12.0% to post‐HD 2.6% IR 2.3–3.1% (P < 0.0001). The adjustment of either urate or bilirubin up to pre‐HD levels did not restore lowered post‐HD levels of TAC. TAC remains preserved in CAPD, whereas the robust depletion of TAC, lower after HDF than HD sessions, cannot be attributed solely to the washout of dialyzable compounds.