bluuebunny/crossref_metadata_2025 huggingface dataset:
Sulphide quinone reductase contributes to hydrogen sulphide metabolism in murine peripheral tissues but not in the CNS
Authors: Linden DR , Furne J , Stoltz GJ , Abdel‐Rehim MS , Levitt MD , Szurszewski JH
Published: September 2011

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) is gaining acceptance as a gaseous signal molecule. However, mechanisms regarding signal termination are not understood. We used stigmatellin and antimycin A, inhibitors of sulphide quinone reductase (SQR), to test the hypothesis that the catabolism of H2S involves SQR.

EXPERIMENTAL APPROACH H2S production and consumption were determined in living and intact mouse brain, liver and colonic muscularis externa using gas chromatography and HPLC. Expressions of SQR, ethylmalonic encephalopathy 1 (Ethe1) and thiosulphate transferase (TST; rhodanese) were determined by RT‐PCR and immunohistochemistry.

KEY RESULTS In the colonic muscularis externa, H235S was catabolized to [35S]‐thiosulphate and [35S]‐sulphate, and stigmatellin reduced both the consumption of H235S and formation of [35S]‐thiosulphate. Stigmatellin also enhanced H2S release by the colonic muscularis externa. In the brain, catabolism of H235S to [35S]‐thiosulphate and [35S]‐sulphate, which was stigmatellin‐insensitive, partially accounted for H235S consumption, while the remainder was captured as unidentified 35S that was probably bound to proteins. Levels of mRNA encoding SQR were higher in the colonic muscularis externa and the liver than in the brain.

CONCLUSIONS AND IMPLICATIONS These data support the concept that termination of endogenous H2S signalling in the colonic muscularis externa occurs via catabolism to thiosulphate and sulphate partially via a mechanism involving SQR. In the brain, it appears that H2S signal termination occurs partially through protein sequestration and partially through catabolism not involving SQR. As H2S has beneficial effects in animal models of human disease, we suggest that selective inhibition of SQR is an attractive target for pharmaceutical development.
A novel compound PTIQ protects the nigral dopaminergic neurones in an animal model of Parkinson's disease induced by MPTP
Authors: Son Hyo Jin , Lee Ji Ae , Shin Nari , Choi Ji Hyun , Seo Jai Woong , Chi Dae Yoon , Lee Cheol Soon , Kim Eun‐Mee , Choe Han , Hwang Onyou
Published: September 2011

BACKGROUND AND PURPOSE In Parkinson's disease, the dopaminergic neurones in the substantia nigra undergo degeneration. While the exact mechanism for the degeneration is not completely understood, neuronal apoptosis and neuroinflammation are thought to be key contributors. We have recently established that MMP‐3 plays crucial roles in dopaminergic cell death and microglial activation.

EXPERIMENTAL APPROACH We tested the effects of 7‐hydroxy‐6‐methoxy‐2‐propionyl‐1,2,3,4‐tetrahydroisoquinoline (PTIQ) on expression of MMP‐3 and inflammatory molecules and dopaminergic cell death in vitro and in an animal model of Parkinson's disease, and Parkinson's disease‐related motor deficits. The pharmacokinetic profile of PTIQ was also evaluated.

KEY RESULTS PTIQ effectively suppressed the production of MMP‐3 induced in response to cellular stress in the dopaminergic CATH.a cell line and prevented the resulting cell death. In BV‐2 microglial cells activated with lipopolysaccharide, PTIQ down‐regulated expression of MMP‐3 along with IL‐1β, TNF‐α and cyclooxygenase‐2 and blocked nuclear translocation of NF‐κB. In the mouse model of Parkinson's disease ,induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), PTIQ attenuated the associated motor deficits, prevented neurodegeneration and suppressed microglial activation in the substantia nigra. Pharmacokinetic analysis showed it was relatively stable against liver microsomal enzymes, did not inhibit the cytochrome p450 isozymes or the hERG ion channel, exhibited no cytotoxicity on liver cells or lethality when administered at 1000 mg kg−1 and entered the brain rather rapidly yielding a 28% brain:plasma ratio after i.p. injection.

CONCLUSIONS AND IMPLICATIONS These results suggest PTIQ has potential as a candidate drug for disease‐modifying therapy for Parkinson's disease.
Tri‐Leaflet Valve Design With a Purge Flow for Heart‐Assist Devices: An In Vitro Optimization Study
Authors: Timmel Tobias , Seshadri Santhosh , Goubergrits Leonid , Affeld Klaus , Kertzscher Ulrich
Published: September 2011

The objective of this study is to assess the effect of a purge flow on valves of pulsatile heart‐assist devices. Clinical applications of these devices are still limited because of frequent thromboembolic complications. These complications often originate at the valves and the unavoidable flow separation regions that are found behind the leaflets. The flow separations cause a long residence time of blood that is considered particularly detrimental. To solve this problem, a valve with a purge flow is proposed. A purge flow is a jet, which is separated from the main blood flow and directed behind the leaflets into the sinus to flush it. Even though the purge flow does not prevent a flow separation, it shortens the residence time of the blood in the sinus. Thus, the purge flow improves the periodic washout of the blood in the region of flow separation. The complex purge flow was investigated in a tri‐leaflet valve. The geometrical parameters of the valve were varied systematically. A statistical technique—the Taguchi method—was used to reduce the number of investigated models to 12. The flows through the resulting valve models were numerically simulated and analyzed. The evaluated models with the best results were subsequently investigated experimentally using different methods: hemodynamic tests in a valve tester and flow visualization using the dye washout method. It was shown that the purge flow can effectively wash out the sinus. Therefore, the purge flow valve reduces the potential of a thrombus formation normally associated with the valve.
Stability of Therapeutic Albumin Solutions Used for Molecular Adsorbent Recirculating System‐Based Liver Dialysis
Authors: De Bruyn Tom , Meijers Björn , Evenepoel Pieter , Laub Ruth , Willems Ludo , Augustijns Patrick , Annaert Pieter
Published: September 2011

Mounting evidence suggests beneficial effects of albumin dialysis‐based liver support in patients suffering from acute‐on‐chronic liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological liver support device, based on the exchange of albumin‐bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion‐exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF‐DCF [Red Cross], and Sigma‐Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin‐associated esterase‐like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher Kd) after the 1–7‐h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (Bmax) increased about twofold. For albumin obtained from CAF‐DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase‐like activities associated with these albumins were either maintained or enhanced (up to 2.5‐fold in case of Sigma albumin) following 7‐h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier‐specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure.
Modified Ear Canal Ablation and Lateral Bulla Osteotomy for Management of Otitis Media in an Alpaca
Authors: Sumner Julia P. , Mueller Tami , Clapp Kemba S. , Darien Benjamin J. , Forrest Lisa J. , Colopy Sara A.
Published: September 2011

Objective

To report surgical treatment of severe otitis media in an alpaca by a modification of a subtotal ear canal ablation and lateral bulla osteotomy technique used in dogs.

Study Design

Case report.

Animals

An 11‐week‐old female alpaca cria.

Methods

The cria had a 2‐week history of right otitis media, nonresponsive to medical treatment, as well as right facial nerve paralysis, and a melting corneal ulcer of the right eye. Otitis media was confirmed by computed tomography. Right subtotal ear canal ablation and lateral bulla osteotomy were performed using a modification of a technique reported in dogs.

Results

There were no surgical complications and the alpaca was discharged from the hospital 5 days later. At 10 months, moderate motor function had been restored to the pinna with the ear standing partially erect. The otitis had resolved, and the alpaca was reportedly well integrated into the herd.

Conclusion

Subtotal ear canal ablation and lateral bulla osteotomy, a technique modified from that performed in dogs, were successful in providing complete clinical resolution of otitis media in an alpaca.
Storage time of blood products and transfusion‐related acute lung injury
Authors: Middelburg Rutger A. , Borkent Barbara , Jansen Mart , van de Watering Leo M.G. , Wiersum‐Osselton Johanna C. , Schipperus Martin R. , Beckers Erik A.M. , Briët Ernest , van der Bom Johanna G.
Published: September 2011

BACKGROUND: Besides white blood cell antibodies in plasma‐rich products, another cause of transfusion‐related acute lung injury (TRALI) could be release of biologically active substances during storage of cellular blood products. We aimed to investigate the association of storage time and risk of TRALI for different product types.

STUDY DESIGN AND METHODS: We compared storage time of blood products transfused within 6 hours before the onset of TRALI to storage time of a representative sample of all blood products transfused in the Netherlands. Generalized linear models were used to correct for confounding variables.

RESULTS: Platelets (PLTs) in plasma transfused to TRALI patients were stored for 0.7 (95% confidence interval [CI], 0.073 to 1.3) days longer than those transfused to controls. The relative risk of TRALI, after receiving PLTs stored for 4 or 5 days, compared to 3 days or less, was 5.8 (95% CI, 0.99 to 110) and increased to 6.3 (95% CI, 1.1 to 118) after more than 5 days (i.e., 6 or 7 days).

CONCLUSIONS: While longer storage of buffy coat–derived PLTs was associated with an increased risk of TRALI, storage of plasma for up to 2 years and red blood cells for up to 35 days was not associated with the risk of TRALI.
Fundamentals, Misvaluation, and Business Investment
Authors: CHIRINKO ROBERT S. , SCHALLER HUNTLEY
Published: September 2011

Does stock market misvaluation affect business fixed investment? To answer this question, we provide evidence based on U.S. firm‐level panel data. We examine the orthogonality conditions for the investment Q and Euler equations, and our qualitative tests reject the null hypothesis that investment is unaffected by misvaluation (this result is not driven exclusively by the late 1990s). To measure the quantitative effects on investment, we introduce a measure of misvaluation into standard investment equations. Our estimates imply that a one‐standard‐deviation increase in misvaluation increases investment between 20% and 60% relative to the mean level of investment in the sample.
Mechanistic Heterogeneity of Junctional Ectopic Tachycardia in Adults
Authors: LIU CHRISTOPHER F. , IP JAMES E. , LIN ANDY C. , LERMAN BRUCE B.
Published: September 2011

Spontaneous junctional ectopic tachycardia (JET) in adults is rare, and the electrophysiologic mechanism has not been definitively established. Two patients who presented with JET, not associated with cardiac surgery, were evaluated and studied in the electrophysiology laboratory, and electrophysiologic and pharmacologic maneuvers were performed to assess the mechanisms of tachycardia. The junctional tachycardia in Patient 1 manifested characteristics consistent with a triggered mechanism, and was sensitive to adenosine. The junctional tachycardia in Patient 2 manifested characteristics consistent with abnormal automaticity, and was insensitive to adenosine. This is a rare clinical example of abnormal automaticity. These two cases demonstrate that JET may be due to multiple mechanisms, with data consistent with triggered activity and abnormal automaticity.

(PACE 2013; 36:e7–e10)
Catheter Ablation of Accessory Pathway in the Treatment of Pacemaker‐Mediated Tachycardia
Authors: ROBLEDO‐NOLASCO ROGELIO , ORTIZ‐AVALOS MARTIN , RODRIGUEZ‐DIEZ GERARDO , CASTRO‐VILLACORTA HUMBERTO
Published: September 2011

Pacemaker‐mediated tachycardia (PMT) remains a clinical problem in patients with dual‐chamber pacemaker despite technological advances. The onset mechanism of this tachycardia is sensing of retrograde atrial activation after ventricular stimulation. Repeated retrograde conduction perpetuates tachycardia. Postventricular atrial refractory period prolongation has been used for prevention of PMT, but this is not the solution in all cases. We present a case with PMT where the retrograde limb is a left accessory pathway, which is treated with radiofrequency ablation successfully. PACE 2012; 35:e84–e86)
The Management of Patients on Oral Anticoagulation Undergoing Coronary Stent Implantation: A Survey among Interventional Cardiologists from Eight European Countries
Authors: RUBBOLI ANDREA , DEWILDE WILLEM , HUBER KURT , EECKHOUT ERIC , HERZFELD ISTVÀN , VALENCIA JOSÈ , WINDECKER STEPHAN , AIRAKSINEN K. E. JUHANI , LIP GREGORY Y. H.
Published: September 2011

Purpose:
 To evaluate the current management, and adherence to recommendations, of patients on oral anticoagulation (OAC) undergoing coronary stent implantation (PCI‐S).

Methods:
 By means of a contact person who had been previously identified in 8 European countries, a questionnaire was electronically forwarded between April and July 2010 to the national institutions where PCI‐S is performed.

Results:
 A total of  202 questionnaires (median response rate: 50%, range 33–78%) was received. The prevalence of OAC patients among those undergoing PCI‐S is mostly reported 5–10% (97%). The peri‐procedural pharmacological management mostly encompasses: preprocedural OAC interruption and bridging with low‐molecular‐weight heparin (59%), intraprocedural administration of an unfractionated heparin bolus (81%), and use of glycoprotein IIb/IIIa inhibitors on an individual basis (79%). The radial approach is reported as the preferred option (58%), as well as the implantation of bare metal stents (76%). Triple therapy (warfarin, aspirin, clopidogrel) is the most frequently prescribed (80%), generally for 1 month after bare metal stent (77%) and for at least 12 months after drug‐eluting stent (60%). Throughout triple therapy, the International Normalized Ratio is mostly targeted to the lower end of the therapeutic range (77%), and gastric protection is routinely prescribed (69%), mostly by giving proton‐pump inhibitors (70%).

Conclusions:
 Among the 202 interventional cardiologists from the 8 European countries interviewed, the management of patients on OAC undergoing PCI‐S appears variable and only partially adherent to currently available recommendations. (J Interven Cardiol 2012;25:163–169)
Direct Measurement of Surface Energy of CeO2 by Differential Scanning Calorimetry
Authors: Hayun Shmuel , Ushakov Sergey V. , Navrotsky Alexandra
Published: September 2011

Surface energy of cerium oxide was measured by differential scanning calorimetry (DSC). Nanocrystalline CeO2 samples were synthesized by a nonaqueous sol–gel method and their surface and interfacial areas were determined from nitrogen adsorption, X‐ray diffraction, and electron microscopy measurements. Three samples were repeatedly heated in a differential scanning calorimeter and the excess enthalpy was obtained from the difference in DSC traces between first heating, during which coarsening occurred, and second heating. Surface enthalpy was calculated from excess enthalpy and from changes in surface and interfacial areas. The measured surface enthalpy for CeO2, 1.2 ± 0.2 J/m2, is consistent with values from oxide melt solution calorimetry on samples with different surface areas. This is the first successful measurement of surface energy using scanning calorimetry.
Personality, fear of childbirth and cesarean delivery on demand
Authors: HANDELZALTS JONATHAN E. , FISHER SHIMRIT , LURIE SAMUEL , SHALEV AMIR , GOLAN ABRAHAM , SADAN OSCAR
Published: September 2011

Objectives. To investigate both the psychological traits and the demographic factors associated with cesarean section on maternal demand. Design. Cross‐sectional questionnaire study. Setting. Delivery ward, Edith Wolfson Medical Center, Holon, Israel. Sample. Fifty‐nine healthy primigravida with a singleton pregnancy were recruited during 2009, of whom 28 requested and were delivered by cesarean section without obstetrical indication, whereas 31 opted for spontaneous vaginal delivery. Methods. All questionnaires were administered to the two groups at term. Various psychological (fear of childbirth questionnaire, Millon Clinical Multiaxial Inventory III, Anxiety Sensitivity Index, State‐Trait Anxiety Index and social support scale) as well as demographic variables were measured before labor and compared. A priori power calculation yielded a power of 95%. Main Outcome Measures. Fear of childbirth, various personality disorders and psychiatric clinical syndromes (29 Millon Clinical Multiaxial Inventory III scales), Anxiety Sensitivity, State Anxiety Index, social support and demographic variables. Results. Differences in age and method of conceiving (p<0.001) were found between the groups. The study group reported a higher level of fear of childbirth (p<0.001), but no differences were found in all other personality characteristics measured (29 Millon Clinical Multiaxial Inventory III scales, State‐Trait Anxiety, Anxiety Sensitivity and social support scale). The origin of the difference regarding the fear of childbirth was located to two specific questions: ‘Have you always been afraid of giving birth?’ and ‘Have you sometimes thought of the delivery as something unnatural?’ Conclusions. The only psychological variable associated with the choice for cesarean section on maternal request was the fear of childbirth.
Prospective risk of fetal death in uncomplicated monochorionic twins
Authors: FARAH NADINE , HOGAN JENNIFER , JOHNSON SUCHETA , STUART BERNARD , DALY SEAN
Published: September 2011

A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks’ gestation from July 1999 to July 2007 were included. Pregnancies with twin–twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks’ gestation and 1 in 37 after 34 weeks’ gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks’ gestation, suggesting that a policy of elective preterm delivery warrants evaluation.
Immunohistochemical analysis of matrix metalloproteinase‐9, vascular endothelial growth factor, bone sialoprotein and i‐nitric oxide synthase in calvaria vs. iliac crest bone grafts
Authors: Tetè Stefano , Zara Susi , Zizzari Vincenzo Luca , De Carlo Alessandro , Vinci Raffaele , Cataldi Amelia , Gherlone Enrico
Published: September 2011

Objectives

The aim of this study was to investigate, in parallel to clinical and histological modifications, the expression of specific proteins involved in different extraoral autologous bone grafts integration in humans.

Material and methods

Patients needing oral rehabilitation of posterior maxilla, with inadequate bone volume for implant placement, received bone grafts from calvaria (Group 1) and iliac crest (Group 2), respectively. From five patients from each group, with a total of 10 subjects, bone biopsy specimens were collected at two different experimental time points: at bone blocks withdrawal for grafting (T0), from donor sites, and after 4 months, from reconstructed sites. Samples were processed for light microscope and immunohistochemical analyses to evaluate MMP9, VEGF, BSP, iNOS expression.

Results

Morphological analysis of T0 calvaria evidenced areas of extracellular matrix, uniformly stained and organized in concentric mineralized lamellae edging few vascular canals, while T0 iliac crest showed greater cellularity compared to calvaria, with rare mineralized areas, surrounding wide bone marrow lacunae. In T1, Group 1 samples showed large areas of extracellular matrix, uniformly stained, at the same time as Group 2 samples disclosed few areas of mineralized tissue.

Although no significant differences were found in proteins expression among calvaria and iliac crest T0 samples, MMP9, VEGF and BSP expression at T1 were discovered higher in Group 1 samples than in Group 2 ones, while iNOS expression increased in Group 2 samples compared to the others. In any group, molecules expression increased passing from T0 to T1.

Conclusion

These findings suggested that, even though clinically both extraoral sources of autologous bone could be considered suitable for grafting in case of large oral rehabilitation, some differences might be detected microscopically and biologically. Calvaria bone graft seemed to enhance not only the quantity of bone tissue at the defect site, but also its quality, better than iliac crest bone do. Then, while both grafts appeared to promote a suitable neoangiogenesis, as showed by morphological analysis and by MMP9 and VEGF expression, in terms of new bone formation and lack of occurrence of inflammatory events, calvaria could be considered a more suitable donor site for bone grafts.
Disease ontogeny overshadows effects of climate and species interactions on population dynamics in a nonnative forest disease complex
Authors: Garnas Jeffrey R. , Houston David R. , Ayres Matthew P. , Evans Celia
Published: September 2011

Biotic threats to trees often arise from interactions among two or more species, frequently insects and fungi, that function together to defeat host defenses, secure resources and colonize new hosts. Feedbacks among plant enemies can have large effects on host population and disease dynamics, either by promoting stabilizing negative feedbacks or contributing to positive feedbacks that can destabilize populations and permit outbreaks. Feedbacks can be rapid and direct (e.g. within trees or among years) or can arise from slowly developing changes in host resource quantity or quality at the scale of forest stands or landscapes. Climate may also influence system dynamics by altering feedbacks within or among species or through density independent effects. We evaluated major drivers of population dynamics of beech bark disease (BBD), an important forest disease in eastern deciduous forests of North America, using data from 28 study sites in the eastern United States monitored for up to 14 yr between 1979 and 1992. Both primary causal agents of BBD – the introduced felted beech scale Cryptococcus fagisuga and native fungi Neonectria spp. – showed strong simple density dependence in all study populations. Surprisingly, densities of scale insects and fungi had little or no effects on population growth rates of the other, despite their habit of living in close physical relationships. For both insects and fungi, ecologically important features of the density dependent functions (slope, carrying capacity and density independent variance) were variable across sites. Climatic effects on density‐dependent functions (and scatter around them) were evident but generally weak and variable. The most striking predictor of patterns in density dependence was duration since establishment of BBD in the region. Apparently BBD alters forests over decades in ways that strengthen self‐regulation among causal agents without eliminating or even dramatically reducing host populations.
The solar ultraviolet B radiation protection provided by shading devices with regard to its diffuse component
Authors: Kudish Avraham I. , Harari Marco , Evseev Efim G.
Published: September 2011

Background: The composition of the incident solar global ultraviolet B (UVB) radiation with regard to its beam and diffuse radiation fractions is highly relevant with regard to outdoor sun protection. This is especially true with respect to sun protection during leisure‐time outdoor sun exposure at the shore and pools, where people tend to escape the sun under shade trees or different types of shading devices, e.g., umbrellas, overhangs, etc., believing they offer protection from the erythemal solar radiation. The degree of sun protection offered by such devices is directly related to the composition of the solar global UVB radiation, i.e., its beam and diffuse fractions.

Methods: The composition of the incident solar global UVB radiation can be determined by measuring the global UVB (using Solar Light Co. Inc., Model 501A UV‐Biometer) and either of its components. The beam component of the UVB radiation was determined by measuring the normal incidence beam radiation using a prototype, tracking instrument consisting of a Solar Light Co. Inc. Model 501A UV‐Biometer mounted on an Eppley Solar Tracker Model St‐1. The horizontal beam component of the global UVB radiation was calculated from the measured normal incidence using a simple geometric correlation and the diffuse component is determined as the difference between global and horizontal beam radiations.

Results: Horizontal and vertical surfaces positioned under a horizontal overhang/sunshade or an umbrella are not fully protected from exposure to solar global UVB radiation. They can receive a significant fraction of the UVB radiation, depending on their location beneath the shading device, the umbrella radius and the albedo (reflectance) of the surrounding ground surface in the case of a vertical surface.

Conclusions: Shading devices such as an umbrella or horizontal overhang/shade provide relief from the solar global radiation and do block the solar global UVB radiation to some extent; nevertheless, a significant fraction of the solar global UVB radiation does penetrate this supposedly ‘protective or comfort zone’. As a result, it is imperative to either apply sunscreen or cover up the exposed body surfaces even when under such shading devices.
Autoimmune bullous skin diseases. Part 1: Clinical manifestations
Authors: Kneisel Andrea , Hertl Michael
Published: September 2011

Autoimmune bullous skin diseases are characterized by autoantibodies against adhesion molecules of the skin. Pemphigus is a disorder with an intraepidermal loss of adhesion and is characterized by fragile blisters and erosions. Pemphigus vulgaris often shows extensive lesions of the oral mucosa, while pemphigus foliaceus is commonly restricted to cutaneous involvement with puff pastry‐like scale formation. Paraneoplastic pemphigus is obligatorily associated with malignancies and often presents as hemorrhagic stomatitis with multiforme‐like exanthems. IgA pemphigus typically presents with pustules and annular plaques but not with mucosal involvement. The clinical spectrum of the pemphigoids includes tense blisters, urticarial plaques, and prurigo‐ like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a “cluster of jewels”‐like pattern in childhood and is more heterogeneous in adulthood. Classical epidermolysis bullosa acquisita shows extensive skin fragility. Dermatitis herpetiformis is associated with gluten‐sensitive enteropathy and manifests clinically with severe itching and papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The intention of the review is to demonstrate the heterogeneous clinical spectrum of autoimmune bullous disorders.
Mid‐upper arm circumference and weight‐for‐height to identify high‐risk malnourished under‐five children
Authors: Briend André , Maire Bernard , Fontaine Olivier , Garenne Michel
Published: September 2011

The World Health Organization and UNICEF define non‐oedematous severe acute malnutrition (SAM) either by a mid‐upper arm circumference (MUAC) less than 115 mm or by a weight‐for‐height z‐score (WHZ) less than –3. The objective of this study was to assess whether there was any benefit to identify malnourished children with a high risk of death to combine these two diagnostic criteria. Data of a longitudinal study examining the relationship between anthropometry and mortality in rural Senegal and predating the development of community‐based management of SAM were used for this study. First, the receiver operating characteristic (ROC) curves of MUAC and of WHZ to predict mortality were drawn, and then the points corresponding to WHZ less than –3 and/or MUAC less than 115 mm were positioned in relation to these curves. MUAC had the highest ROC curve, which indicates that it identifies high‐risk children better than WHZ. Both points representing WHZ less than –3 and/or MUAC less than 115 mm were below the MUAC ROC curve. It is concluded that to identify high‐risk malnourished children, there is no benefit in using both WHZ less than –3 and/or MUAC less than 115 mm, and that using MUAC alone is preferable.
Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo‐flavoproteins
Authors: Torchetti Enza M. , Bonomi Francesco , Galluccio Michele , Gianazza Elisabetta , Giancaspero Teresa A. , Iametti Stefania , Indiveri Cesare , Barile Maria
Published: September 2011

A soluble form of human FAD synthase (isoform 2; hFADS2) was produced and purified to homogeneity as a recombinant His‐tagged protein. The enzyme binds 1 mole of the FAD product very tightly, although noncovalently. Complete release of FAD from the ‘as isolated’ protein requires extensive denaturation. A 75 : 25 mixture of apo/holoprotein could be prepared by treatment with mild chaotropes, allowing estimatation of the contribution made by bound FAD to the protein stability and evaluatation of whether structural rearrangements may be required for FAD release. Under turnover conditions, the enzyme catalyzes FAD assembly from ATP and FMN and, at a much lower rate, the pyrophosphorolytic hydrolysis of FAD. Several mechanistic features of both reactions were investigated in detail, along with their dependence on environmental conditions (pH, temperature, dependence on metals). Our data indicate that FAD release may represent the rate‐limiting step of the whole catalytic cycle and that the process leading to FAD synthesis, and delivery to client apoproteins may be tightly controlled.
Diameter Growth of Juvenile Trees after Gap Formation in a Bolivian Rain Forest: Responses are Strongly Species‐specific and Size‐dependent
Authors: Soliz‐Gamboa Claudia C. , Sandbrink Anne , Zuidema Pieter A.
Published: September 2011

We evaluated growth responses to gap formation for juvenile individuals of three canopy rain forest species: Peltogyne cf. heterophylla, Clarisia racemosa and Cedrelinga catenaeformis. Gaps were formed during selective logging operations 7 yr before sampling in a Bolivian rain forest. We collected wood samples for tree‐ring analyses at different distances to the stump (<10, 10–40 and >40 m) and from trees with different diameters (5–30 cm diameter at breast height [dbh]). Tree‐rings width was measured in at least two radii and converted to average diameter growth. Changes in 7‐yr median diameter growth before and after selective logging were analyzed. Diameter growth rates significantly increased by 0.7–0.8 mm/yr after gap formation for P. heterophylla and C. catenaeformis, but not for C. racemosa. We applied a multiple regression analysis to explain variation in growth responses of P. heterophylla and C. catenaeformis by distance to logging gap and tree size. For P. heterophylla we found that growth increase occurring close to logging gaps was strongest for large juvenile trees (20–25 cm dbh) and almost absent in small juveniles. For C. catenaeformis, variation in growth responses was not related to tree size or distance to gaps. Our results show that growth responses to gap formation strongly differ across species and tree sizes. This finding calls for caution in the interpretation of growth releases in tree‐ring series, as gap formation does not necessarily invoke growth responses and if such growth responses occur, their strength is species‐ and size specific.
Retrospective Review of 25 Cases of Thrombotic Thrombocytopenic Purpura in Pakistan
Authors: Sagheer Safoorah , Moiz Bushra , Usman Mohammad , Khurshid Mohammad
Published: September 2011

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. Because of the rarity of TTP, no comprehensive data is available in the Pakistani population. The present study aimed to review the therapeutic interventions, relapses and mortality rate in patients with TTP treated at a tertiary care hospital in Pakistan. This was a retrospective review of patients treated over a period of more than nine years (2001–2010). Medical charts were retrieved using the ICD coding system version 9 and each file was reviewed by the principal author for clinical and laboratory details, along with the therapy utilized and the outcome. Twenty‐five patients were diagnosed with TTP, including nine males (36%) and 16 females (64%) with a median age of 30 ± 18.4 years for all patients. Idiopathic TTP was seen in 17 patients (68%) and secondary causes were identified in eight (32%). Patients were treated with plasma exchange once the diagnosis of TTP was established. Only neurological and renal involvement at the time of presentation emerged as important indicators in determining the outcome and response to treatment. Most of our patients tolerated plasmapheresis very well; however, delay in starting plasmapheresis due to late presentation was a major hurdle in our set up.
Analytical Solution for Drainage and Recession from an Unconfined Aquifer
Authors: Liang Xiuyu , Zhang You‐Kuan
Published: September 2011

One‐dimensional transient groundwater flow from a divide to a river in an unconfined aquifer described by the Boussinesq equation was studied. We derived the analytical solution for the water table recession and drainage change process described with a linearized Boussinesq equation with a physically based initial condition. A method for determining the average water table in the solutions was proposed. It is shown that the solution derived in the form of infinite series can be well approximated with the simplified solution which contains only the leading term of the original solution. The solution and their simplification can be easily evaluated and used by others to study the groundwater flow problems, such as drainage and base flow estimation, in an unconfined aquifer.
Re‐imagining Infrastructure*
Authors: Gerencser Mark
Published: September 2011

A senior executive of Booz Allen Hamilton and co‐author of a business bestseller called Megacommunities argues that the United States is locked into an obsolete pattern of dealing with infrastructure investment, even as the country's population growth and technology have raced ahead. Three of America's basic “lifeline” infrastructures—energy, transportation, and water—are nearing the end of their useful operating lives and in desperate need of modernization. U.S. capital spending on infrastructure has been inadequate, amounting to less than 2% of GDP, as compared to 9% in China and 5% in India.

But if infrastructure renewal will be costly, money is not the biggest obstacle. History shows that modernizing existing infrastructures tends to be even more challenging than creating new ones because of the drag caused by legacy hardware and the associated human “software.” And so the real problems are conceptual, institutional, and political—problems whose solutions demand transformational vision and leadership that will encourage collaborative participation by both the public and private sectors.

What is lacking, then, is an oversight and coordination mechanism that restores government's traditional integrating role without creating either new monopolies or a larger, more centralized government. To that end the author issues four imperatives:

First is the need to rethink the form and function of our old infrastructures.

Second is the need for design principles that make future infrastructures robust and adaptable as technology advances, funding changes, and the needs of our citizens evolve.

Third is the need for leadership that succeeds by convening, integrating, and aligning the interests and actions of all important stakeholders.

Fourth and last is the need for a national vision for America's infra‐structure that defines the function and performance of the entire system over its total lifecycle.

A new kind of collaboration by different constituencies, which the author refers to as the creation of “megacommunities,” is held up as a way for stakeholders with conflicting interests to cooperate on compelling issues of national importance with a shared set of practices and protocols.
Reflections on Private Water Supply: Agency and Equity Issues
Authors: Hanke Steve H. , Walters Stephen J.K.
Published: September 2011

In the second of the two articles, the authors reflect on and extend their earlier work by describing recent trends in water privatization, drawing important lessons from cases where privatization efforts have failed, offering suggestions about the way privatized firms can be successfully monitored, and addressing the popular argument that “fairness” demands that water be distributed by public firms at a zero (or heavily subsidized) price.
The Upside to Fiscal Challenges: Innovative Partnerships Between Public and Private Sector
Authors: Amram Martha , Crawford Tabitha
Published: September 2011

The first U.S. public‐private partnerships, or P3s as they are now called, began over 200 years ago. These contractual arrangements between government entities and private companies for the delivery of services or facilities have long been used for water/wastewater, transportation, urban development, and the provision of social services. And the use of such partnerships is increasing because they provide an effective means for meeting public needs, maintaining a high level of public control, improving the quality of services, and increasing the cost‐effectiveness of traditional delivery methods.

Although outsourcing of public services is sometimes used to accomplish many of the same goals, P3s are likely to be a solution when public funds are not available and when:

Capital is required to upgrade the infrastructure and so achieve a lower cost, or higher quality, of services.

The contract horizon in the P3 transaction is sufficiently long for the investor/operation to recoup investment dollars and a rate of return.

City residents make payments for the service provided, creating the revenue stream for private profits.

The private partner in the P3 has a low cost of capital, often attributable largely to a large and sophisticated balance sheet.

This article uses examples of several recent P3 contracts to illustrate their role in shifting risk and increasing collaboration between the public and private sectors.
Evidence for protein‐mediated fatty acid efflux by adipocytes
Authors: Henkin A. H. , Ortegon A. M. , Cho S. , Shen W.‐J. , Falcon A. , Kraemer F. B. , Lee S.‐J. , Stahl A.
Published: September 2011

Aim:  The hormonally controlled mobilization and release of fatty acids from adipocytes into the circulation is an important physiological process required for energy homeostasis. While uptake of fatty acids by adipocytes has been suggested to be predominantly protein‐mediated, it is unclear whether the efflux of fatty acids also requires membrane proteins.

Methods:  We used fluorescent fatty acid efflux assays and colorimetric assays for free fatty acids and glycerol to identify inhibitors with effects on fatty acid efflux, but not lipolysis, in 3T3‐L1 adipocytes. We assessed the effect of these inhibitors on a fibroblast‐based cell line expressing fatty acid transport protein 1, hormone‐sensitive lipase and perilipin, which presumably lacks adipocyte‐specific proteins for fatty acid efflux.

Results:  We identified 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS) as an inhibitor of fatty acid efflux that did not impair lipolysis or the cellular exit of glycerol but lead to an accumulation of intracellular fatty acids. In contrast, fatty acid efflux by the reconstituted cellular model for fatty acid efflux was responsive to lipolytic stimuli, but insensitive to DIDS inhibition.

Conclusion:  We propose that adipocytes specifically express an as yet unidentified DIDS‐sensitive protein that enhances the efflux of fatty acids and therefore may lead to novel treatment approaches for obesity‐related disorders characterized by abnormal lipid fluxes and ectopic triglyceride accumulation.
Questioning quotas: applying a relational framework for diversity management practices in the United Arab Emirates
Authors: Forstenlechner Ingo , Lettice Fiona , Özbilgin Mustafa F.
Published: September 2011

The use of quota systems to improve demographic diversity in organisations is receiving mixed responses from commentators. This article demonstrates that the normative success and failure of a quota system is contingent upon the multi‐level and relational dynamics of the diversity management intervention, which uses the tool of quotas. Focusing on a quota system, which seeks to promote localisation of the workforce in the United Arab Emirates, this article presents a longitudinal case study. We analyse the multi‐level dynamics of the implementation of the quota system to show how the interdependence of these levels influenced the outcome of the quota programme. The study also accounts for the complexity of normative assessment of the quota‐based diversity intervention by illustrating how a diverse set of vested interests, a multiplicity of discourses and the interplay of schemas of change, support and resistance between managers and employees come into play.
Management of Cardiovascular Risk Factors Is Leaving the Office: Potential Impact of Telemedicine*
Authors: Krakoff Lawrence R.
Published: September 2011

J Clin Hypertens (Greenwich). 2011;13:791–794. ©2011 Wiley Periodicals, Inc.

Effective control of hypertension and the other cardiovascular risk factors has been dependent on primary medical care as provided by family practitioners and internists. The progressive reduction in availability of primary care for adult populations in the United States threatens the likelihood of better control of the risk factors and potential loss of opportunity for prevention of cardiovascular disease. Recent progress has been made in the use of home blood pressure monitoring for improvement in classification of risk for hypertensive patients. Several studies establish the feasibility of home pressure monitoring combined with telemedicine for improving control of hypertension. Some studies have explored the role of self‐care for adjustment of medication, as well. The potential growth of this strategy for effective control of hypertension with reduced need for face‐to‐face encounter time in primary care is a promising solution to the reduction in primary care providers. Management of hyperlipidemia and diabetes by telemedicine is also being explored, particularly for rural areas, but may also be effective in urban settings. Development of technology for home monitoring together with electronic communication to providers and mechanisms for education, feedback, and warnings offers a promising solution to the possible crisis in prevention of cardiovascular disease due to the loss of traditional primary care.
Sex differences in lipid profiles in relation to the progression of glucose abnormalities
Authors: CARNEVALE SCHIANCA Gian P. , FRA Gian P. , COLLI Elena , BIGLIOCCA Marcello , MELLA Roberto , SCAGLIA Elena , BARTOLI Ettore
Published: September 2011

Background:  In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM).

Methods:  An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n = 589); (ii) those with pre‐diabetes (pre‐T2DM), who were further divided into those with impaired fasting glucose (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol, triglycerides, high‐density lipoprotein–cholesterol (HDL‐C), low‐density lipoprotein–cholesterol (LDL‐C), apolipoprotein (apo) A‐I, apoB, and the apoB:apoA‐I ratio were determined in each patient. Differences in lipids between the different groups were assessed using Student’s t‐test.

Results:  Significantly higher triglyceride levels and an apoB:apoA‐I ratio were found in NGT men (P < 0.0001), along with lower HDL‐C and apoA‐I (P < 0.0001). Men in the pre‐T2DM group maintained a higher apoB:apoA‐I ratio (P < 0.05) and lower HDL‐C (P < 0.0001) compared with women. In the T2DM group, only HDL‐C was lower in men compared with women (P < 0.05).

Conclusions:  The progression of glucose intolerance from NGT to pre‐T2DM and T2DM exhibits striking sex differences regarding the lipid profile. The data demonstrate a worsening of plasma lipid composition in women who become diabetic. This could explain, at least in part, the loss of the more favorable cardiovascular risk normally associated with NGT women.