bluuebunny/crossref_metadata_2025 huggingface dataset:
Induced Atrial Tachycardia After Circumferential Pulmonary Vein Isolation of Paroxysmal Atrial Fibrillation: Electrophysiological Characteristics and Impact of Catheter Ablation on the Follow‐Up Results
Authors: CHANG SHIH‐LIN , LIN YENN‐JIANG , TAI CHING‐TAI , LO LI‐WEI , TUAN TA‐CHUAN , UDYAVAR AMEYA R. , HU YU‐FENG , CHIANG SHUO‐JU , WONGCHAROEN WANWARANG , TSAO HSUAN‐MING , UENG KWO‐CHANG , HIGA SATOSHI , LEE PI‐CHANG , CHEN SHIH‐ANN
Published: November 2008

Introduction:
Atrial tachycardia (AT), including focal and reentrant AT, can occur after circumferential pulmonary vein isolation (CPVI). The aim of this study was to investigate the electrophysiological characteristics of induced AT and its clinical outcome.

Methods and Results:
In our series of 160 patients with paroxysmal atrial fibrillation (AF), 45 ATs were induced by high‐current burst pacing after CPVI in 26 patients. All induced ATs were mapped using a three‐dimensional (3D) mapping system. Noninducibility was the endpoint of the ablation of the AT. Gap‐related AT was considered if the AT was related to the CPVI lesions. A 16‐slice multidetector computed tomography scan was performed in all patients to correlate the anatomical structure with electroanatomical mapping. Thirty‐five (78%) reentrant ATs and 10 (22%) focal ATs were identified. Of those, 34 were gap‐related ATs (24 reentrant and 10 focal ATs). Reentrant AT had more gaps in the left atrial appendage ridge than did focal AT (39.6% vs 0%, P = 0.02). Focal AT had a higher incidence of gap in the PV carina compared with reentrant AT (80% vs 10%, P < 0.001). Reentrant ATs were mostly terminated during the ablation creating the mitral and roof lines with crossing of the gaps. During a mean follow‐up of 21 ± 8 months, only one patient (0.6%) with induced mitral reentry had a recurrent AT.

Conclusion:
The location of the AT gap may be related with the complex anatomy of the LA. The induced ATs after CPVI can be eliminated by catheter ablation.
Quantitative Assessment of Left Ventricular and Left Atrial Functions by Strain Rate Imaging in Diabetic Patients with and without Hypertension
Authors: Muranaka Atsuko , Yuda Satoshi , Tsuchihashi Kazufumi , Hashimoto Akiyoshi , Nakata Tomoaki , Miura Tetsuji , Tsuzuki Masahiro , Wakabayashi Chikashi , Watanabe Naoki , Shimamoto Kazuaki
Published: November 2008

Background: Impaired left ventricular (LV) function is shown by strain rate (SR) imaging in patients with diabetes mellitus (DM). Left atrium (LA) function in patients with DM, however, has not been assessed by this method and the effect of hypertension (HT) on LV and LA functions in diabetic patients has not been fully studied. The aim of this study was to quantitatively assess LA function in diabetic patients with and without HT in combination with LV function. Methods: Conventional echocardiographic and SR imaging studies were performed in 55 subjects with normal systolic LV function (LV ejection fraction of 55% or more) and no evidence of coronary artery disease: 17 with DM (DM group), 22 who have both DM and HT (DM+HT group), and 16 age‐matched controls. SR imaging was performed from three apical views, and peak SR was measured at 12 LV segments and 5 LA segments. Mean peak systolic SR (LVs and LAs, respectively), early diastolic SR (LVe and LAe, respectively) and late diastolic SR (LVa and LAa, respectively) were calculated by averaging data in each LV and LA segment. Results: Despite no significant differences in age, LV ejection fraction and E/A ratio among the three groups, systolic blood pressure, LA dimension and LV mass index in the DM+HT group were significantly larger than those in the controls. The DM group had reduced systolic and diastolic LV functions and impaired LA reservoir and conduit functions compared with those in the controls, as shown by lower LVs (P < 0.05), LVe (P < 0.01), LAs (P < 0.01), and LAe (P < 0.05). The DM+HT group had reduced LVs (P < 0.01), LVe (P < 0.01), LAs (P < 0.01) and LAe (P < 0.01) compared with those in the controls. The DM+HT group had significantly lower LVe (P < 0.05) and LAe (P < 0.05) than did the DM group. Conclusions: SR imaging can detect impairment of LA reservoir and conduit functions as well as LV systolic and diastolic dysfunctions in patients with DM, even in the absence of LV hypertrophy and LA dilatation. Coexisting HT augments the impairment of LV diastolic and LA conduit functions in diabetic patients.
Agricultural Sustainability, Water Pollution, and Governmental Regulations: Lessons from the Sugar Creek Farmers in Ohio
Authors: Moore Richard H. , Parker Jason Shaw , Weaver Mark
Published: November 2008

Agricultural sustainability requires that farmers must face an entanglement of regulations regarding not only conservation measures but also water quality. These entail learning the intricacies of conservation measures and water qualities as legally defined by the USDA and Environmental Protection Agency (EPA) as well as dealing with the bureaucracy of multiple agencies and paperwork. The lessons from the Sugar Creek Watershed in Ohio, classified as Ohio's second most polluted watershed, include proactive behavior based on a partnership between farmers and university researchers. The farmers had to confront the regulations of the EPA and in so doing insisted on high‐density sampling to find out whether their own farms had polluted the watershed. The researchers who teamed with them were unexpectedly led into new headwaters and participatory research areas. The farmers were able to improve their profitability while decreasing pollution levels through innovative and culturally based solutions. This case, presently endorsed as a model by both the EPA and the USDA, is being replicated in Ohio and has the potential for replication in other states and countries.
The Southern Model of Broiler Production and Its Global Implications
Authors: Constance Douglas H.
Published: November 2008

This paper introduces the concept of the Southern Model of broiler production as the preferred organizational form in the global agrifood system. A synthesis of existing works on the broiler industry combined with new information documenting its global diffusion is used to develop the concept of the Southern Model. The analysis of events supports a flexible accumulation over flexible specialization interpretation of the globalization of the Southern Model. The investigation of the historical development and diffusion of the Southern Model warrants special attention from researchers concerned with the socioeconomic implications of the global restructuring of the agrifood system.
How many well vs. unwell days can you expect over 10 years, once you become depressed?
Authors: Furukawa T. A. , Yoshimura R. , Harai H. , Imaizumi T. , Takeuchi H. , Kitamura T. , Takahashi K.
Published: November 2008

Objective:  Prognostic studies of major depression have mainly focused on episode remission and relapse, and only a limited number of studies have examined long‐term course of depressive symptomatology at threshold and subthreshold levels.

Method:  The Group for Longitudinal Affective Disorders Study has conducted prospective serial assessments of a cohort of heretofore untreated major depressive episodes for 10 years under naturalistic conditions.

Results:  Of the 94 patients in the cohort, the follow‐up rate was 70% of the 11 280 person‐months. Around 77% of the follow‐up months were spent in euthymia, 16% in subthreshold depression and 7% in major depression. Duration of the index episode before reaching recovery was the only significant predictor of the ensuing well time.

Conclusion:  On average, patients with major depression starting treatment today may expect to spend three quarters of the next decade in euthymia but the remaining one quarter in subthrehold or threshold depression.
Regional gray matter reduction and theory of mind deficit in the early phase of schizophrenia: a voxel‐based morphometric study
Authors: Herold R. , Feldmann Á. , Simon M. , Tényi T. , Kövér F. , Nagy F. , Varga E. , Fekete S.
Published: November 2008

Objective:  We tested the association between theory of mind (ToM) performance and structural changes in the brains of patients in the early course of schizophrenia.

Method:  Voxel‐based morphometry (VBM) data of 18 patients with schizophrenia were compared with those of 21 controls. ToM skills were assessed by computerized faux pas (FP) tasks.

Results:  Patients with schizophrenia performed significantly worse in FP tasks than healthy subjects. VBM revealed significantly reduced gray matter density in certain frontal, temporal and subcortical regions in patients with schizophrenia. Poor FP performance of schizophrenics correlated with gray matter reduction in the left orbitofrontal cortex and right temporal pole.

Conclusion:  Our data indicate an association between poor ToM performance and regional gray matter reduction in the left orbitofrontal cortex and right temporal pole shortly after the onset of schizophrenia.
Differential effects of bone graft substitutes on regeneration of bone marrow
Authors: Schwartz Z. , Doukarsky‐Marx T. , Nasatzky E. , Goultschin J. , Ranly D. M. , Greenspan D. C. , Sela J. , Boyan B. D.
Published: November 2008

Background: This study used a rat tibial marrow ablation model to test the hypothesis that bone remodeling within the medullary canal varies with bone graft materials of different chemical compositions and structural properties, impacting marrow cavity restoration. Bone graft materials were selected based on their relative resorption or degradation in vivo and their osteogenic properties.

Methods: Following ablation of the right tibial marrow in male Sabra‐strain rats, materials were implanted in the proximal marrow cavity: poly‐d,l‐lactide‐co‐glycolide 75 : 25 (PLGA); coralline‐hydroxyapatite (HA), calcium‐sulfate (CaSO4), collagen–HA–tricalcium phosphate granules, anorganic bovine bone mineral, demineralized bone matrix (DBM), 45S5 Bioglass (BG), PLGA with BG 50 : 50, PLGA : BG 80 : 20, and PLGA and PLGA:BG 50 : 50 plus bone marrow (BM). Control tibias were ablated but received no implants. At 2 (endosteal bone healing), 4 (marrow cavity remodeling) and 8 weeks (marrow restoration), six to eight animals per group were euthanized and tibias processed for histomorphometry of proximal and distal medullary canals.

Results: Control tibias showed primary bone in proximal and distal medullary canals at 2 weeks, with trabeculae surrounded by cellular marrow. At 4 and 8 weeks, control trabeculae were thinned and marrow had more fat cells. In the treated tibias, trabecular bone volume (TBV) varied with time and was material specific. Most implants supported comparable TBV at 2 weeks. Sites with CaSO4 or DBM exhibited decreased TBV with time whereas trabecular bone was retained in proximal tibias containing other materials, closely juxtaposed to the implants. TBV did not always correlate directly with implant volume, but changes in BM volume were correlated inversely with TBV. Addition of BM increased marrow restoration in sites containing PLGA; however, BM reduced restoration of marrow when added to PLGA : BG. Although the presence of implants in the proximal tibia resulted in retention of trabecular bone, there was a time‐dependent reduction in TBV in distal canals; the rate and extent of the distal TBV reduction were implant dependent.

Conclusions: Thus, although many materials can support bone formation in the marrow cavity, bone quality, quantity, and physical relationship to the implant, and its rate of resorption differ in a material‐dependent manner, resulting in differences in the restoration of marrow.

Clinical relevance: Bone graft materials should be selected not only for their ability to support new bone formation but also for their impact on the remodeling phase of bone healing.
Immediate functional loading of TiOblast dental implants in full‐arch edentulous maxillae: a 3‐year prospective study
Authors: Collaert Bruno , De Bruyn Hugo
Published: November 2008

Introduction: Immediate functional loading of dental implants for full‐arch restoration is a patient‐friendly approach, shown to be feasible with a good long‐term prognosis in a completely edentulous mandible. For the complete restoration of the maxilla, acceptable long‐term clinical follow‐up is lacking or based on case reports rather than on prospective studies.

Objectives: This prospective mono‐centre study reports the 3‐year outcome of immediately functionally loaded Astra Tech Dental implants in completely edentulous maxillae based on clinical survival and success based on radiographical assessment of bone level.

Material and methods: One hundred and ninety‐five Astra Tech TiOblast surface fixtures were installed in 25 consecutively treated patients (age range: 42–76 years), of whom eight were smokers, 12 had a confirmed history of periodontitis and six had poor bone quality normally deemed for delayed loading. Fixtures and abutments were inserted in a one‐stage procedure and functionally loaded within 24 h with a 10‐unit provisional glass‐fibre or metal‐reinforced screw‐retained restoration. After 6 months, each implant was checked for stability using a manual torque of 20 N cm and the provisional restoration was replaced by a 10–12‐unit screw‐retained metal–ceramic or metal–resin cantilever bridge. Bone level was assessed radiographically from the day of surgery up to 3 years and used to calculate mean bone loss at the patient level and individual implant success.

Results: No failures occurred in implants or prostheses, the total survival rate being 100%. Mean marginal bone loss was 0.58 mm (SD 0.58); 0.6 mm (SD 0.53); 0.63 (SD 0.61); and 0.72 (SD 0.63) after 6 and 12 months, and 2 and 3 years, respectively, yielding a 100% success at the patient level. Wilcoxon's signed ranks test showed only statistically significant bone loss between baseline and 6 months and a steady‐state condition during all other intervals. At the individual fixture level, 82% lost <1 mm marginal bone between baseline and 1 year. After 3 years, 86% have <1.5 mm total bone loss and can be considered a success. The fixtures expressing more bone loss were all inserted in smokers.

Conclusion: Immediate loading of a full‐arch maxillary bridgework on 7–9 Astra Tech TiOblast implants is a predictable treatment option with 100% fixture survival and stable bone‐to‐implant contact up to 3 years. The steady state in bone remodelling is indicative of a good long‐term prognosis in non‐smokers but smokers seem to be more prone to bone loss.
Marginal accuracy of combined tooth–implant‐supported fixed dental prostheses after in vitro stress simulation
Authors: Boeckler Arne F. , Morton Dean , Kraemer Stephan , Geiss‐Gerstdorfer Juergen , Setz Juergen M.
Published: November 2008

Objectives: Caries, periodontal disease, and peri‐implant inflammation caused by deficient marginal adaptation of fixed prostheses are reasons for clinical failure of combined tooth–implant‐supported fixed dental prostheses (TISFDP). This in vitro study examined the marginal accuracy in TISFDP after simulated stress in an artificial oral environment.

Materials and methods: Twelve three‐unit TISFDPs were fabricated using a high noble alloy on models containing a human premolar with an artificial periodontium and an implant. Four three‐unit tooth‐supported prostheses (TSFDP) represented the control group. The experimental TISFDPs (four per group) were luted with three different cements: group 1, zinc phosphate; group 2, glass ionomer; group 3, self‐adhesive resin. The specimens were mechanically loaded (1.2 million cycles/50 N) and thermally cycled (8000 cycles with 5/55°C). The vertical marginal gap was measured before and after cementation, after chewing simulation and after thermal cycling by light microscopy (× 560). The results were subjected to statistical analysis (t‐test/one‐way analysis of variance/Bonferroni).

Results: Significant increase (P≤0.05) in the marginal gap was found after cementation within the experimental TISFDPs (implants, 11.7–18.7 μm; teeth, 13.4–24.2 μm) and the control TSFDPs (28.5 μm). Comparison of groups 1 and 2 revealed significant differences for the teeth while comparison of the implants showed significant differences among all groups. Chewing simulation and thermal cycling caused statistically insignificant changes in the marginal gaps of the experimental as well as the control TSFDPs.

Conclusion: The cementation of the TISFDPs with different luting materials caused a specific enlargement of the marginal gap in teeth and implants. Subsequent to simulated oral stress in an artificial oral environment, no significant changes of the marginal accuracy could be found.
Matrix metalloproteinase‐8 concentration in shallow crevices associated with the extent of periodontal disease
Authors: Passoja Anna , Ylipalosaari Merja , Tervonen Tellervo , Raunio Taina , Knuuttila Matti
Published: November 2008

Objective: The aim of this study was to analyse the association between matrix metalloproteinase‐8 (MMP‐8) concentration in shallow, mostly non‐bleeding gingival crevices, and the extent of periodontal disease.

Material and Methods: Plaque, bleeding on probing (BOP), probing pocket depth (PPD) and attachment level (AL) were assessed clinically in 48 patients with chronic periodontitis. MMP‐8 concentrations in gingival crevicular fluid (GCF) from four shallow (PPD3 mm), and four diseased sites and in serum, were measured by enzyme‐linked immunosorbent assay.

Results: The mean concentration of MMP‐8 in GCF from shallow crevices was 11.8 ± 12.8 ng/ml and from diseased sites was 150.1 ± 91.8 ng/ml. In subjects with moderate to high plaque scores, a statistically significant association was found between MMP‐8 concentration from shallow crevices and the extent of AL4 mm (p=0.028) and AL6 mm (p<0.001).

Conclusion: The above association between MMP‐8 concentration in shallow crevices and attachment loss provides a new aspect to future studies of MMP‐8 as a prognostic marker for periodontal disease.
A clinical study on the effects of cordless and conventional retraction techniques on the gingival and periodontal health
Authors: Al Hamad Khaled Q. , Azar Wesam Z. , Alwaeli Hayder A. , Said Khalid N.
Published: November 2008

Aim: To investigate the influence of two cordless techniques on the periodontium in comparison with conventional cords.

Material and Methods: Dental students (n=60) with healthy gingival conditions were recruited – an expanding poly vinyl siloxane material (Magic Foam Cord®), a paste‐like material (Expasyl®), and a conventional retraction cord (Ultrapak®) were applied on the buccal aspects of three premolars of each subject. Probing depth, clinical attachment level, gingival index (GI), plaque index, mobility, bleeding, and sensitivity were assessed at baseline, and at 1 and 7 days after application. Data were analysed using Kruskal–Wallis and Mann–Whittney tests (α=0.05).

Results: The periodontal parameters were not statistically significant among the groups at all time intervals except for the GI, which was increased for all groups after 1 day. The highest was in Expasyl (p=0.011). After 7 days, the GI returned to a non‐significant level compared with baseline except for Expasyl, which was still significant (p=0.044). Expasyl induced sensitivity in four subjects. Bleeding was only induced by Ultrapak in 28.3% and 26.7% during and after retraction, respectively.

Conclusions: All techniques caused a temporary gingival inflammation; the greatest was in Expasyl, which also showed slower recovery. Cordless techniques did not induce bleeding during or after retraction.
The perilesional skin in vitiligo: a colorimetric in vivo study of 25 patients
Authors: Brazzelli V. , Muzio F. , Antoninetti M. , Villani S. , Donadini F. , Altomare A. , Borroni G.
Published: November 2008

Background: The aim of this work was to study in vivo the perilesional skin in vitiligo with a colorimetric method.

Methods: Twenty‐five patients affected by vitiligo were included. For each patient, three different areas were considered: the lesional, the perilesional and the normal skin as far as 5 cm from the nearest vitiligo spot. Skin pigmentation measurements were performed with a chromameter.

Results: The results showed that luminance L* decreased significantly in relation to increasing distance from the vitiligo spot. As expected, L* in the vitiligo spot was significantly higher than in the perilesional (P<0.0001) and normal skin (P<0.0001). There was a small difference in L* between normal skin as far as 5 cm from the nearest vitiligo spot and perilesional skin. In contrast, the pigmentation index (b*) gradually increased from lesional to perilesional to normal skin. Furthermore, the comparison of the b* value between the normal skin as far as 5 cm from the nearest vitiligo spot was higher than perilesional skin and it was statistically significant (P<0.0001).

Conclusion: Our results in vivo underline that the perilesional skin near the vitiligo spot is lighter than normal skin as far as 5 cm from the vitiligo spot.
Impact of ultraviolet radiation on the expression of marker proteins of gap and adhesion junctions in human epidermis
Authors: Gambichler Thilo , Rotterdam Sebastian , Tigges Christian , Altmeyer Peter , Bechara Falk G.
Published: November 2008

Aims/background: We aimed to investigate the impact of ultraviolet B (UVB) as well as UVA1 on the epidermal expression of specific markers of gap and adhesion junctions.

Methods: Twelve healthy subjects were enrolled in the study. The back of the subjects was irradiated with three MED‐UVB as well as three MED‐UVA1. Twenty‐four hours later, punch biopsies were taken from irradiated and non‐irradiated skin. Immunohistochemical procedures were used for the detection of connexin 43, E‐cadherin, involucrin, Ki‐67 using specific antibodies.

Results: Staining intensity of connexin 43 in UVB‐exposed skin was significantly increased when compared with non‐exposed and UVA1‐exposed sites. By contrast, staining intensity of E‐cadherin in UVB‐exposed skin was significantly decreased when compared with non‐exposed and UVA1‐exposed sites. Involucrin and Ki‐67 staining of keratinocytes was significantly increased in UVB‐exposed sites as compared with non‐exposed and UVA1‐irradiated sites.

Conclusions: UVB significantly alters the epidermal expression of gap and adhesion junction proteins possibly indicating a role of these proteins in the regulation of UV‐induced inflammation and development and progression of skin cancer.
Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short‐term NB‐UVB phototherapy in the treatment of non‐segmental vitiligo: a left–right comparative study
Authors: Anbar Tag S. , Westerhof Wiete , Abdel‐Rahman Amal T. , Ewis Ashraf A. , El‐Khayyat Mohamed A.
Published: November 2008

Background: NB‐UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year. Skin ablation with mechanical dermabrasion with 5Fluorouracil (5FU) was introduced to treat vitiligo in 1983. This was modified replacing the mechanical dermabrasion by erbium‐YAG (ER:YAG) laser ablation and resulted in better prognosis in periungual vitiligo.

Purpose: In the present study, we are exploring the effect of the use of ER:YAG laser skin ablation and application of 5FU on the outcome of short‐term NB‐UVB therapy for patients with non‐segmental vitiligo (NSV).

Methods: This study included 50 adult patients with a total of 65‐paired symmetrical NSV lesions in different body parts. One side was treated with ER:YAG laser ablation, followed by 5FU application before simultaneous NB‐UVB therapy of both sides for a maximum period of 4 months. The outcome was then evaluated both qualitatively and quantitatively.

Results: The overall response to therapy was better using the combination therapy. Fifty patients (78.1%) experienced a moderate‐marked repigmentation response in the combination group compared with 23.4% in the mono‐therapy group. The response was significantly higher when using the combination therapy in different body parts (P value is <0.05), except for feet lesions, which were better but not statistically significant (P value=0.15). Tolerable pain during ablation or at sites of 5FU application was reported in all cases. Transient hyperpigmentation occurred in 30% of cases and 3.1% of lesions healed by a transient slate blue color. Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient.

Conclusion: We concluded that prior use of ER:YAG laser skin ablation, followed by 5FU application before NB‐UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short‐term NB‐UVB therapy and is expected to increase patient compliance.
Effect of HAART on salivary gland function in the Women’s Interagency HIV Study (WIHS)
Authors: Navazesh M , Mulligan R , Karim R , Mack WJ , Ram S , Seirawan H , Greenspan J , Greenspan D , Phelan J , Alves M ,   The Oral Substudy of the WIHS Collaborative Study Group
Published: November 2008

Objective:  To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women’s Interagency HIV Study (WIHS).

Design:  Longitudinal cohort study.

Subjects and methods:  A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow‐up oral sub‐study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands.

Main outcome measures:  Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self‐reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no).

Results:  Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non‐PI based HAART.

Conclusions:  PI‐based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.
Tyr235 of human cytosolic phosphoenolpyruvate carboxykinase influences catalysis through an anion–quadrupole interaction with phosphoenolpyruvate carboxylate
Authors: Dharmarajan Lakshmi , Case Christopher L. , Dunten Pete , Mukhopadhyay Biswarup
Published: November 2008

Tyr235 of GTP‐dependent phosphoenolpyruvate (PEP) carboxykinase is a fully invariant residue. The aromatic ring of this residue establishes an energetically favorable weak anion–quadrupole interaction with PEP carboxylate. The role of Tyr235 in catalysis was investigated via kinetic analysis of site‐directed mutagenesis‐derived variants. The Y235F change lowered the apparent Km for PEP by about six‐fold, raised the apparent Km for Mn2+ by about 70‐fold, and decreased oxaloacetate (OAA)‐forming activity by about 10‐fold. These effects were due to an enhanced anion–quadrupole interaction between the aromatic side chain at position 235, which now lacked a hydroxyl group, and PEP carboxylate, which probably increased the distance between PEP and Mn2+ and consequently affected the phosphoryl transfer step and overall catalysis. For the Y235A and Y235S changes, an elimination of the favorable edge‐on interaction increased the apparent Km for PEP by four‐ and six‐fold, respectively, and the apparent Km for Mn2+ by eight‐ and six‐fold, respectively. The pyruvate kinase‐like activity, representing the PEP dephosphorylation step of the OAA‐forming reaction, was affected by the substitutions in a similar way to the complete reaction. These observations indicate that the aromatic ring of Tyr235 helps to position PEP in the active site and the hydroxyl group allows an optimal PEP–Mn2+ distance for efficient phosphoryl transfer and overall catalysis. The Y235A and Y235S changes drastically reduced the PEP‐forming and OAA decarboxylase activities, probably due to the elimination of the stabilizing interaction between Tyr235 and the respective products, PEP and pyruvate.
Emerging pathways in genetic Parkinson’s disease: Autosomal‐recessive genes in Parkinson’s disease – a common pathway?
Authors: Fitzgerald Julia C. , Plun‐Favreau Helene
Published: November 2008

Rare, inherited mutations causing familial forms of Parkinson’s disease have provided insight into the molecular mechanisms that underlie the genetic and sporadic forms of this disease. Loss of protein function resulting from autosomal‐recessive mutations in PTEN‐induced putative kinase 1 (PINK1), Parkin and DJ‐1 has been linked to mitochondrial dysfunction, accumulation of abnormal and misfolded proteins, impaired protein clearance and oxidative stress. Accumulating evidence suggests that wild‐type PINK1, Parkin and DJ‐1 may be key components of neuroprotective signalling cascades that run in parallel, interact via cross talk or converge in a common pathway.
Complex gangliosides are apically sorted in polarized MDCK cells and internalized by clathrin‐independent endocytosis
Authors: Crespo Pilar M. , von Muhlinen Natalia , Iglesias‐Bartolomé Ramiro , Daniotti Jose L.
Published: November 2008

Gangliosides are glycosphingolipids mainly present at the outer leaflet of the plasma membrane of eukaryotic cells, where they participate in recognition and signalling activities. The synthesis of gangliosides is carried out in the lumen of the Golgi apparatus by a complex system of glycosyltransferases. After synthesis, gangliosides leave the Golgi apparatus via the lumenal surface of transport vesicles destined to the plasma membrane. In this study, we analysed the synthesis and membrane distribution of GD3 and GM1 gangliosides endogenously synthesized by Madin–Darby canine kidney (MDCK) cell lines genetically modified to express appropriate ganglioside glycosyltransferases. Using biochemical techniques and confocal laser scanning microscopy analysis, we demonstrated that GD3 and GM1, after being synthesized at the Golgi apparatus, were transported and accumulated mainly at the plasma membrane of nonpolarized MDCK cell lines. More interestingly, both complex gangliosides were found to be enriched mainly at the apical domain when these cell lines were induced to polarize. In addition, we demonstrated that, after arrival at the plasma membrane, GD3 and GM1 gangliosides were endocytosed using a clathrin‐independent pathway. Then, internalized GD3, in association with a specific monoclonal antibody, was accumulated in endosomal compartments and transported back to the plasma membrane. In contrast, endocytosed GM1, in association with cholera toxin, was transported to endosomal compartments en route to the Golgi apparatus. In conclusion, our results demonstrate that complex gangliosides are apically sorted in polarized MDCK cells, and that GD3 and GM1 gangliosides are internalized by clathrin‐independent endocytosis to follow different intracellular destinations.
Identification of two novel HLA‐DRB1 alleles, HLA‐DRB1*1214 and HLA‐DRB1*1215, in two Taiwanese individuals
Authors: Lee H. L. , Chu C. C. , Trejaut J. A. , Yang K. L. , Lin M.
Published: November 2008

Two novel HLA‐DRB1 alleles, HLA‐DRB1*1214 and HLA‐DRB1*1215, were found in Taiwan using sequence‐based typing method. DRB1*1214 differs from DRB1*120101 by two nucleotide substitutions on exon 2, causing amino acid changes at codon 37 (L→F) and codon 38 (L→V). We suggest that DRB1*1214 is the product of a gene conversion between DRB1*120101 and DRB1*140101 or DRB1*1405 and that HLA‐DRB1*1215 differs from DRB1*120201 by one single nucleotide transition at exon 2, thereby causing amino acid change at codon 37 (L→F).
An introduction of a multi‐soil‐layering system: a novel green technology for wastewater treatment in rural areas
Authors: Chen Xin , Luo An Cheng , Sato Kuniaki , Wakatsuki Toshiyuki , Masunaga Ttsugiyuki
Published: November 2008

Multi‐soil‐layering (MSL) systems are designed for municipal wastewater, livestock wastewater and polluted river water treatments. They are mainly composed of soil mixture block layers and water‐permeable layers (PL). The MSL system overcomes many of the shortcomings of conventional soil treatment systems such as easy clogging, large land requirement and low hydraulic loading rate. This paper summarizes the structure, purification mechanism and practical application of the systems for different kinds of wastewater treatment. The paper also compares MSL systems with other decentralized systems such as wetland and compact filter systems in their respective structures and treatment efficiencies. Finally, the paper gives a rough evaluation of the lifespan and cost of an MSL system based on its material composition.
Policy arguments for proprietary restitution
Authors: Swadling William
Published: November 2008

Arguments are sometimes made attempting to justify proprietary awards to unjust enrichment claimants by reference to the ‘priority’ such awards supposedly give in the defendant's insolvency. Those justifications are variously that unjust enrichment claimants do not take insolvency risks, that the defendant's creditors would otherwise receive an underserved windfall, and that unjust enrichment claimants occupy a position analogous to secured creditors. This paper shows that such arguments are flawed. To award unjust enrichment claimants' proprietary rights is not to give them priority in their defendant's insolvency but to withdraw the right from the estate available for distribution to all the unsecured creditors, whatever their order of priority. Moreover, insolvency ‘priority’ is not the only consequence of such an award. Finally, when seen for what they are, viz arguments for the award of property rights, the justifications do not, for a number of reasons, stand up.
Criminal justice and penal populism in Ireland
Authors: Campbell Liz
Published: November 2008

In constructing criminal policy the Irish legislature seems to be driven predominantly by a pragmatic and populist approach, in contrast to the rights-oriented jurisprudence of the Supreme Court. This paper describes the conflict between the courts and the legislature in relation to criminal justice matters in Ireland, particularly in the context of bail, the exclusionary rule and sentencing, and analyses the reasons for this divergence, drawing on the concept of penal populism. Although the Irish courts serve as a valuable bulwark against punitive populist policies, this paper considers if this failure to adhere to the desires of the legislature and to public opinion is anti-democratic. Furthermore, in assessing the apparent rift between the two arms of the Irish State, this paper highlights areas of criminal justice in which this conceptualisation of the legislature as punitive and the courts as rights-enforcing is unduly simplistic and possibly inaccurate.
Older people actively reconstruct their life in a care home
Authors: Cook Glenda Anne
Published: November 2008

The research reported here aimed to present the stories of care home residents through an interpretative study that was informed by a biographical approach and narrative method. Eight older people who lived in four different care homes in England participated in a sequence of up to eight narrative interviews over a six month period. The findings revealed how the older people tried to live as active biographical agents who were instrumental in shaping their own life in a care home. They were able to do this to a greater or lesser extent through the implementation of a range of resident‐led strategies.

The understanding of care home life that was developed through this study offers an alternative biography for living in care homes that is not only possible but achievable. This is a biography of frail older people who are active in reconstructing their life following the move to a care home, and living lives that are meaningful, purposeful and enjoyable. This sits in contrast to the standard biography that dominates current understanding of care home life that of older people merely ‘existing’ for the most part of their days. This image provides a vision for long‐term care for older people, which is grounded in the views and aspirations of older people.
Living bereavement: an exploration of healthcare workers’ responses to loss and grief in an NHS continuing care ward for older people
Authors: Holman Cheryl
Published: November 2008

This article reports on research rooted in a work based education project and the theme of loss was chosen by the participating care staff who felt it was central to their work with dependent older people. They coined the phrase ‘living bereavement’ meaning the complex responses and grief reactions of those experiencing and bearing witness to the multiple losses endured in continuing care environments.

Aim.  The research was to identify the emotional demand of living bereavement and to explore and develop care staff’s capacity to work with it.

Methods.  Qualitative methods including participant observation and Reflective Work Groups were used to generate and analyse data over a three year period. A psychoanalytic dimension was added to the research through participation in a supervision group facilitated by a psychotherapist.

Findings.  In the article the key message from the findings, that there is an intense emotional demand in care work related to loss and grief in continuing care environments, is explained. The trajectory of living bereavement is discussed and illustrated with examples.

Implications for practice.  Some emotional aspects of the care work were glossed over or ignored which affected the way care was delivered. This may have been because the feelings were disturbing or painful to deal with. It is important to support staff working with difficult feelings so that emotional aspects of their work can be acknowledged and thought about.
Current situation of German care homes
Authors: Klein Barbara
Published: November 2008

Aim.  The aim of this paper is to explore the situation of and current developments in the German care home sector.

Background.  Germany, like other Western countries, faces demographic change and subsequently tries to develop structures and processes to achieve a care system which can tackle the increasing number of people in need of care with a variety of quality services. Policy strives to set up structures and instruments to enhance the quality of service provision.

Discussion.  Figures show that the structures in the care sector are changing in favour to increased privatization of homes, a slight increase in size and improved building structures. In order to tackle the expected changes, a mix of low and high skilled qualification and new job profiles arise in the care sector. Other changes to be observed are the development of new living arrangements and the utilization of new technologies to support the care process.

Conclusion.  This contribution looks at the socio‐demographic changes in care, the statutory developments and the structures of care homes as well as current discussions on future developments.
Development and characterization of 14 polymorphic microsatellite loci in the raccoon tick (Ixodes texanus)
Authors: DHARMARAJAN GUHA , FIKE JENNIFER A. , BEASLEY JAMES C. , RHODES JR OLIN E.
Published: November 2008

Fourteen polymorphic microsatellite loci were developed for the raccoon tick (Ixodes texanus). Three multiplexed panels comprising the loci were developed and 50 ticks collected from two infected raccoons (Procyon lotor) were genotyped. The number of alleles per locus ranged from five to 22, and single locus heterozygosities ranged from 0.46 to 0.94. Future research will further our understanding of I. texanus biology and help in elucidating the effects of life‐history variation on parasite population genetic structure, using I. texanus as a model organism.
Pharmacokinetic Interaction of the Direct Renin Inhibitor Aliskiren with Furosemide and Extended‐Release Isosorbide‐5‐Mononitrate in Healthy Subjects
Authors: Vaidyanathan Sujata , Bartlett Michael , Dieterich Hans Armin , Yeh Ching‐Ming , Antunes Ana , Howard Dan , Dole William P.
Published: November 2008

This study investigated the pharmacokinetics, safety, and tolerability of aliskiren administered alone or in combination with either the loop diuretic furosemide or an oral extended‐release formulation of isosorbide‐5‐mononitrate (ISMN). In separate studies, 22 healthy subjects (ages 18–45 years) received either ISMN 40 mg or furosemide 20 mg once‐daily for 3 days followed by a 3‐day washout. Subjects then received aliskiren 300 mg once‐daily for 7 days followed by combination therapy for 3 days. Pharmacokinetic assessments were taken at regular intervals over 24 h after dosing on the last day of each treatment period. At steady state, aliskiren AUCτ was decreased by 7% (geometric mean ratio [90% CI], 0.93 [0.84, 1.04]), and Cmax by 20% (0.80 [0.65, 0.97]) with furosemide coadministration compared with aliskiren administration alone. Aliskiren coadministration reduced furosemide AUCτ by 28% (0.72 [0.64, 0.81]) and Cmax by 49% (0.51 [0.39, 0.66]) compared with furosemide alone. Coadministration of aliskiren and ISMN was associated with only minor changes in the pharmacokinetic parameters of aliskiren (AUCτ 1.03 [0.90, 1.18]; Cmax 0.94 [0.69, 1.29]) and ISMN (AUCτ 0.88 [0.71, 1.10]; Cmax 0.94 [0.79, 1.13]). Headache and dizziness were the most common adverse events in both studies; dizziness and BP values below normal (SBP <90 and/or DBP <50 mmHg) were more frequent with aliskiren and ISMN coadministration than with either agent alone. Coadministration of aliskiren and ISMN had no clinically relevant effect on either aliskiren or ISMN pharmacokinetics. In conclusion, coadministration of aliskiren and furosemide reduced furosemide exposure and had a minor effect on aliskiren pharmacokinetics. The clinical significance of reduced systemic exposure to furosemide during coadministration of aliskiren is uncertain.
Role of Adenosine Antagonism in the Cardiorenal Syndrome
Authors: Dohadwala Mustafa M. , Givertz Michael M.
Published: November 2008

Acute decompensated heart failure (ADHF), generally related to signs and symptoms of volume overload, is one the most common reasons for hospitalization in the United States. Recently, it has been observed that the majority of patients with ADHF have baseline renal dysfunction. Moreover, heart failure (HF) treatment is limited by worsening renal function despite persistent volume overload. This connection between HF and renal dysfunction has been termed the cardiorenal syndrome and has made treatment of patients with stable and unstable HF challenging. Selective adenosine A1 receptor antagonists are novel pharmacologic agents that are currently under development to treat volume overload in HF while protecting or possibly improving renal function. In this article, we review the cardiorenal syndrome, the role of adenosine in renal function, and emerging data regarding the safety and efficacy of adenosine A1 receptor antagonists in patients with advanced HF.
Pharmacological Profile of the Selective Mitochondrial F1F0ATP Hydrolase Inhibitor BMS‐199264 in Myocardial Ischemia
Authors: Grover Gary J. , Malm Johan
Published: November 2008

The mitochondrial F1F0ATP synthase is responsible for the majority of ATP production in mammals and does this through a rotary catalytic mechanism. Studies show that the F1F0ATP synthase can switch to an ATP hydrolase, and this occurs under conditions seen during myocardial ischemia. This ATP hydrolysis causes wasting of ATP that does not produce work. The degree of ATP inefficiently hydrolyzed during ischemia may be as high as 50–90% of the total. A naturally occurring, reversible inhibitor (IF‐1) of the hydrolase activity is in the mitochondria, and it has a pH optimum of 6.8. Based on studies with the nonselective (inhibit both synthase and hydrolase activity) inhibitors aurovertin B and oligomycin B reduce the rate of ATP depletion during ischemia, showing that IF‐1 does not completely block hydrolase activity. Oligmycin and aurovertin cannot be used for treating myocardial ischemia as they will reduce ATP production in healthy tissue. We generated a focused structure–activity relationship, and several compounds were identified that selectively inhibited the F1F0ATP hydrolase activity while having no effect on synthase function. One compound, BMS‐199264 had no effect on F1F0ATP synthase function in submitochondrial particles while inhibiting hydrolase function, unlike oligomycin that inhibits both. BMS‐199264 selectively inhibited ATP decline during ischemia while not affecting ATP production in normoxic and reperfused hearts. BMS‐191264 also reduced cardiac necrosis and enhanced the recovery of contractile function following reperfusion. These data also suggest that the reversal of the synthase and hydrolase activities is not merely a chemical reaction run in reverse.
Ziprasidone in the Treatment of Affective Disorders: A Review
Authors: Rosa Adriane R , Franco Carolina , Torrent Carla , Comes Mercè , Cruz Nuria , Horga Guillermo , Benabarre Antonio , Vieta Eduard
Published: November 2008

Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and dopaminergic receptor antagonism, but also exerts effects as an inhibitor of norepinephrine reuptake. Moreover, one of the advantages of ziprasidone is its safety profile as it is not associated with clinically significant metabolic side effects and little or no effect on prolactin level or anticholinergic side effects. Most of the studies evaluating ziprasidone's efficacy and safety are short‐term double‐blind, placebo‐controlled studies in acute mania and mixed episodes. In two of them, ziprasidone was associated to significant improvement in the primary measures assessed. However, an add‐on study, lithium plus ziprasidone showed similar results than lithium monotherapy, although there was a significant advantage for the combination within the first week. In a more recent trial, ziprasidone was compared with placebo and haloperidol as monotherapies, again beating placebo. In that trial, ziprasidone appeared to be safer and better tolerated, although less likely efficacious than haloperidol. Particularly, subjects treated with ziprasidone were less likely to switch to depression. Despite the well‐studied efficacy of ziprasidone in the first weeks of treatment, there are no controlled trials that evaluate the role and efficacy of ziprasidone in long‐term treatment of bipolar disorder (BD). Overall, in the open‐label extension studies, there was a global improvement at all visits compared with baseline scores. Furthermore, ziprasidone appears to offer some antidepressant effect in patients with major depressive episode and resistant to treatment, as demonstrated in add‐on open‐label studies with ziprasidone plus selective serotonin reuptake inhibitor (SSRI).