bluuebunny/crossref_metadata_2025 huggingface dataset:
Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages
Authors: del Sol Antonio , Araúzo-Bravo Marcos J , Amoros Dolors , Nussinov Ruth
Published: May 2007

Background

Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways.

Results

We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples (the Gα
s
subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization.

Conclusion

Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulation of inter-modular linkages.
Somatostatin Receptor Subtype-2-Deficient Mice with Diet-Induced Obesity Have Hyperglycemia, Nonfasting Hyperglucagonemia, and Decreased Hepatic Glycogen Deposition
Authors: Singh Vandana , Grötzinger Carsten , Nowak Krzysztof W. , Zacharias Sylvia , Göncz Eva , Pless Gesine , Sauer Igor M. , Eichhorn Ines , Pfeiffer-Guglielmi Brigitte , Hamprecht Bernd , Wiedenmann Bertram , Plöckinger Ursula , Strowski Mathias Z.
Published: May 2007

Hypersecretion of glucagon contributes to abnormally increased hepatic glucose output in type 2 diabetes. Somatostatin (SST) inhibits murine glucagon secretion from isolated pancreatic islets via somatostatin receptor subtype-2 (sst2). Here, we characterize the role of sst2 in controlling glucose homeostasis in mice with diet-induced obesity. Sst2-deficient (sst2−/−) and control mice were fed high-fat diet for 14 wk, and the parameters of glucose homeostasis were monitored. Hepatic glycogen and lipid contents were quantified enzymatically and visualized histomorphologically. Enzymes regulating glycogen and lipid synthesis and breakdown were measured by real-time PCR and/or Western blot. Gluconeogenesis and glycogenolysis were determined from isolated primary hepatocytes and glucagon or insulin secretion from isolated pancreatic islets. Nonfasting glucose, glucagon, and fasting nonesterified fatty acids of sst2−/− mice were increased. Inhibition of glucagon secretion from sst2-deficient pancreatic islets by glucose or somatostatin was impaired. Insulin less potently reduced blood glucose concentration in sst2-deficient mice as compared with wild-type mice. Sst2-deficient mice had decreased nonfasting hepatic glycogen and lipid content. The activity/expression of enzymes controlling hepatic glycogen synthesis of sst2−/− mice was decreased, whereas enzymes facilitating glycogenolysis and lipolysis were increased. Somatostatin and an sst2-selective agonist decreased glucagon-induced glycogenolysis, without influencing de novo glucose production using cultured primary hepatocytes. This study demonstrates that ablation of sst2 leads to hyperglucagonemia. Increased glucagon concentration is associated with impaired glucose control in sst2−/− mice, resulting from decreased hepatic glucose storage, increased glycogen breakdown, and reduced lipid accumulation. Sst2 may constitute a therapeutic target to lower hyperglucagonemia in type 2 diabetes.
Pig Conceptuses Secrete Estrogen and Interferons to Differentially Regulate Uterine STAT1 in a Temporal and Cell Type-Specific Manner
Authors: Joyce Margaret M. , Burghardt Robert C. , Geisert Rodney D. , Burghardt James R. , Hooper R. Neil , Ross Jason W. , Ashworth Morgan D. , Johnson Greg A.
Published: May 2007

Conceptus trophectoderm and uterine luminal epithelial cells interact via endocrine, paracrine, and autocrine modulators to mediate pregnancy recognition and implantation. Pig conceptuses not only release estrogens for pregnancy recognition but also secrete interferons during implantation. Because interferon-stimulated genes are increased by interferons secreted for pregnancy recognition in ruminants, we asked whether the interferon-stimulated gene, STAT1, is up-regulated in pig endometrium by conceptus estrogens and/or interferons. STAT1 expression in response to day of pregnancy, estrogen injection, and intrauterine infusion of conceptus secretory proteins in pigs indicated 1) estrogen increases STAT1 in luminal epithelial cells, 2) conceptus secretory proteins that contain interferons increase STAT1 in stroma, 3) STAT1 increases in close proximity to the conceptus, and 4) early estrogen results in conceptus death and no STAT1 in stroma. The interactions of estrogen and interferons to regulate cell-type-specific expression of STAT1 highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.
A unified method to find active forces and passive wrench of some parallel manipulators with n SPS active legs and a passive leg
Authors: Lu Y , Hu B
Published: May 2007

A unified analysis approach is proposed for solving the active force and the passive wrench of some parallel manipulators with n SPS-type active legs and an unactuated passive leg. Firstly, some mathematical formulae for solving the force transformation matrix and active force and passive wrench are derived, and many possible types of the unactuated passive constrained legs are synthesized. Secondly, three parallel manipulators with three to five SPS-type active legs and a different passive leg are presented to illustrate as how to solve their inverse kinematics, force matrix, active forces, and passive wrench, and singularity by using the force matrix. Thirdly, some examples are given, and solving results have been verified by the simulation mechanism approach.
Large eddy simulations of variable property turbulent flow in horizontal and vertical channels with buoyancy and heat transfer effects
Authors: Lee J S , Pletcher R H
Published: May 2007

Turbulent combined flow of forced and natural convection was investigated using large eddy simulations for horizontal and vertical channels with significant heat transfer. The walls were maintained at constant temperatures, one heated and the other cooled, at temperature ratios of 1.01, 1.99, and 3.00, respectively. Results showed that with increasing the Grashof number, large-scale turbulent motions emerged near the wall, resulting in significant changes in turbulent intensities for the horizontal channel flow case. Aiding and opposing flows, however, for the vertical channel, emerge near the heated and cooled walls, respectively, while the pressure gradient drives the mean flow upwards. Buoyancy effects on the mean velocity, temperature, and turbulent intensities were observed near the walls. In the aiding flow, the turbulent intensities and heat transfer were suppressed and the flow was relaminarized at large values of the Grash of number. In the opposing flow, however, turbulence was enhanced with increasing velocity fluctuations.
The C-terminal domain of RNA Pol II helps ensure that editing precedes splicing of the GluR-B transcript
Authors: Ryman Kicki , Fong Nova , Bratt Eva , Bentley David L. , Öhman Marie
Published: May 2007

The C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) influences many steps in the synthesis of an mRNA and helps control the final destiny of the mature transcript. ADAR2 edits RNA by converting adenosine to inosine within double-stranded or structured RNA. Site-selective A-to-I editing often occurs at sites near exon/intron borders, where it depends on intronic sequences for substrate recognition. It is therefore essential that editing precedes splicing. We have investigated whether there is coordination between ADAR2 editing and splicing of the GluR-B pre-mRNA. We show that the CTD is required for efficient editing at the R/G site one base upstream of a 5′-splice site. The results suggest that the CTD enhances editing at the R/G site by preventing premature splicing that would remove the intronic recognition sites for ADAR2. Editing at the GluR-B Q/R site, 24 bases upstream of the intron 11 5′-splice site, stimulates splicing at this intron. Furthermore, unlike previously studied introns, the CTD actually inhibits excision of intron 11, which includes the complementary recognition sequences for the Q/R editing site. In summary, these results show that the CTD and ADAR2 function together to enforce the order of events that allows editing to precede splicing, and they furthermore suggest a new role for the CTD as a coordinator of two interdependent pre-mRNA processing events.
Local Anaesthetic Infusion with Elastomeric Pump After Arthroscopic Subacromial Decompression
Authors: Little Kevin , Pillai Anand , Fazzi Umberto , Storey Neil
Published: May 2007

INTRODUCTION

The use of extended local anaesthesia for postoperative pain has previously been reported, and has several advantages over other methods, including ease of placement, safety, reliability, lower cost and effective analgesia. We present our experience with a portable elastomeric infusion device in patients undergoing arthroscopic subacromial decompression, and make a case for its potential to allow same-day discharge.

PATIENTS AND METHODS

Forty patients undergoing arthroscopic subacromial decompression were followed-up. At the end of the procedure, an epidural catheter connected to a portable elastomeric local anaesthetic infusion system was inserted into the subacromial space. All patients were electively admitted for overnight stay postoperatively and assessed using a visual analogue scale (VAS) to evaluate their level of pain.

RESULTS

No patient reported severe pain at any stage. None of the patients required any parenteral opiate analgesia with the pump in situ.

CONCLUSIONS

These findings suggest that the use of this elastomeric infusion device following shoulder surgery allows safe and early discharge of patients with decreased need for parenteral opiate analgesia.
Impact of HIV and AIDS on Surgical Practice
Authors: Dua RS , Wajed SA , Winslet MC
Published: May 2007

INTRODUCTION

Surgical intervention has become a common component in the management of patients infected with the human immunodeficiency virus (HIV) or suffering from the clinical consequences of acquired immunodeficiency syndrome (AIDS). We investigated the evolution of this involvement at a tertiary referral centre for this condition over a 16-year period.

PATIENTS AND METHODS

Detailed retrospective examination of the medical records of HIV-positive patients treated at the Royal Free Hospital between 1986 and 2002 was undertaken. Clinical, pathological and operative details of those patients who underwent surgical intervention were recorded.

RESULTS

Of the 2100 cases reviewed, 477 patients underwent a combined total of 772 surgical procedures. Of the 772 operations, 95 (12.3%) were performed as emergencies. Anorectal surgery represented the highest group with a total of 195 procedures (25.26%) being undertaken. The majority of patients (59%) had AIDS at the time of surgery, and 27.04% had a significant co-existing medical problem. Overall postoperative complication rate was 10.1%, with the risk being significantly greater in those undergoing intra-abdominal surgery and emergency procedures.

CONCLUSIONS

This is the largest study to audit the impact of HIV/AIDS in general surgical practice in the UK retrospectively. Surgery for HIV patients can be safely conducted with a low complication rate for the diagnostic and anorectal procedures that comprise the vast majority of surgery in HIV/AIDS patients. Medical treatment for patients with HIV/AIDS has developed dramatically over the last two decades. In parallel, this has resulted in a heavy, new and varied workload for general surgeons, who have also had to adapt in order to deal with the challenging spectrum of this disease.
Publicprivate partnerships in HIV vaccine trials as a contribution to the Brazilian response to the AIDS epidemic
Authors: Velho Lea , de Souza Maria Carlota
Published: May 2007

Developing countries, Brazil included, have long struggled not only with creating a strong knowledge base but also, and more importantly, with making such a knowledge base relevant to solve local problems. This article focuses on the Brazilian response to the AIDS epidemic. The case exemplifies that it is possible to articulate a multitude of social actors government, the R&D system, the manufacturing sector and the broader society to create an innovative, knowledge-based approach to a social problem. Key to the success was the fact that Brazil took ownership of its AIDS problem from the beginning and the strong commitment of all parties to the agreed strategies. Taking this context into account, the article looks at the Brazilian participation in publicprivate partnerships for HIV vaccine trials. It argues that the country prepared itself in terms of research capacity, institutional infrastructure and guidelines prior to engaging in vaccine trials partnerships. For this reason, the capacity gained by participating in international partnerships adds to the already existent knowledge and skills base, which, in turn, is ready to absorb the new knowledge.
Roundtable discussion: Do vaccine initiatives contribute to long-term capacity development?
Authors: Kambili Chrispin , Muraskin William , Mytelka Lynn K , Orsenigo Luigi
Published: May 2007

(The Guest Editors of this issue invited four experts with relevant research experience Dr. Chrispin Kambili from International AIDS Vaccine Initiative Africa; Professor William Muraskin of Queens College, CUNY, New York; Professor Lynn K. Mytelka of UNU-INTECH, Maastricht and Luigi
Orsenigo from University of Brescia and CESPRI, Bocconi University, Milan to discuss the significance of vaccine initiatives in developing countries for long-term capacity development. Following are their views.)
The Effects of Preparedness for Suicide Following the Death of a Young Adult Child
Authors: Maple Myfanwy , Plummer David , Edwards Helen , Minichiello Victor
Published: May 2007

Suicide deaths are often viewed as sudden and unexpected. Research examining bereavement responses to suicide are generally set within this conceptual framework. Twenty‐two parents were interviewed about their bereavement experience following the suicide death of a young adult son or daughter. Data analyzed using narrative methods revealed the concept of preparedness. Three distinct preparedness narratives were identified, termedturbulent‐relief,tragedy, andreflectiveplots. The data presented here highlights the way in which these different situations influence the resultant grief. Understanding preparedness for suicide assists in explaining the variety of grief responses in parents bereaved in this manner.
Ethnocultural Aspects of Suicide in Young People: A Systematic Literature Review Part 2: Risk Factors, Precipitating Agents, and Attitudes Toward Suicide
Authors: Colucci Erminia , Martin Graham
Published: May 2007

Different scholars have expressed the same regret for the lack of research on ethnocultural differences in youth suicide behavior and the need to conduct more comparative studies, necessary to develop culturally responsive prevention and intervention strategies. The authors reviewed 82 publications on youth suicide that have considered, to different degrees, the ethnicity/culture of the population studied. Part 1 of this article explored youth suicide rates and methods (SLTB, this issue), while the present paper examines risk and precipitating factors and attitudes toward suicide in young people from a cross‐cultural perspective.
Functional Expression of Ion Channels in Mesenchymal Stem Cells Derived from Umbilical Cord Vein
Authors: Park Kyoung Sun , Jung Kyoung Hwa , Kim Seung Hyun , Kim Kyung Suk , Choi Mi Ran , Kim Yangmi , Chai Young Gyu
Published: May 2007

Mesenchymal stem cells have the ability to renew and differentiate into various lineages of mesenchymal tissues. We used undifferentiated human mesenchymal-like stem cells from human umbilical cord vein (hUC-MSCs), a cell line which contains several mesenchymal cell markers. We characterized functional ion channels in cultured hUC-MSCs with whole-cell patch clamp and reverse transcription-polymerase chain reaction (RT-PCR). Three types of outward current were found in these cells: the Ca2+-activated K+ channel (IKCa), a transient outward K+ current (Ito), and a delayed rectifier K+ current (IKDR). IKCa and IKDR were totally suppressed by tetraethylammonium, and IKCa was sensitive to a specific blocker, iberiotoxin. Ito was inhibited by 4-aminopyridine. Another type of inward rectifier K+ current (Kir) was also detected in approximately 5% of hUC-MSCs. Elevation of external potassium ion concentration increased the Kir current amplitude and positively shifted its reversal potential. In addition, inward Na+ current (INa) was found in these cells (∼30%); the current was blocked by tetrodotoxin and verapamil. In the RT-PCR analysis, Kv1.1, Kv4.2, Kv1.4, Kir2.1, heag1, MaxiK, hNE-Na, and TWIK-1 were detected. These results suggested that multiple functional ion channel currents, IKCa, IKDR, Ito, INa, and Kir, are expressed in hUC-MSCs.

Disclosure of potential conflicts of interest is found at the end of this article.
Behaviour of geogrid-reinforced load transfer platforms for embankment on rammed aggregate piers
Authors: Abdullah C. H. , Edil T. B.
Published: May 2007

A test embankment was constructed over soft ground to evaluate the performance of different types of load transfer platform (LTP) supported on rammed aggregate piers (called ‘geopiers’). Three types of LTP were constructed in accordance with the recommended design for each: a geosynthetic-reinforced LTP with two layers of geogrid (catenary LTP), a geosynthetic-reinforced LTP with three or more layers of geogrid (beam LTP), and a reinforced concrete LTP. The results indicate that the differential settlement between the geopiers and the matrix soil is relatively small in all LTP sections, with the smallest in the beam LTP. The tensile strain in the geogrid was approximately 60% of the allowable design strain of 5% in the beam LTP. In the catenary LTP, the tensile strain in the geogrid was approximately 20% of the allowable design strain of 6%, although the differential settlement was larger than the beam LTP. The total and differential settlements observed indicate that the use of less stiff geopier columns together with LTPs provides an attractive option for supporting low embankments on soft ground with tolerable total and differential settlements. The presence of LTPs and the supporting columns also tend to reduce the lateral movement of the foundation soil. The cost analysis of the different LTPs indicates that construction costs for geosynthetic-reinforced LTPs are likely to vary with locality; however, it appears that beam LTPs offer a less costly approach, with enhanced performance.
Metal retention in geosynthetic clay liners following permeation by different mining solutions
Authors: Lange K. , Rowe R. K. , Jamieson H.
Published: May 2007

The leaching of hazardous metals and metalloids from mine tailings is a significant problem facing the mining industry. Although, in the past, geosynthetic clay liners (GCLs) have primarily been employed as leachate barriers in landfills, recent times have seen an increase in the variety of their applications, including applications in the mining industry. The capacity of GCLs to attenuate metals and metalloids (As, Al, Cd, Cu, Fe, Mn, Ni, Sr, Zn) from mine acidic rock drainage (ARD) water and a neutral-pH, As-rich water associated with gold mine tailings (GMT) was evaluated. Water-prehydrated GCLs were permeated with GMT and ARD for short (2 and 5 pore volumes, PV) and long (21 PV) periods. The long-term hydraulic conductivity of the GCLs increased from 1.6 × 10-11 m/s (water for 5 PV) to 5.0 × 10-11 m/s and 1.3 × 10-10 m/s after permeation with the GMT and ARD waters, respectively (21 PV). The distribution of metals within the GCL was quantified in order to differentiate between metals associated with precipitated compounds, soluble complexes in porewater, and sorbed metals. Metals sorbed to the GCL are reported in micrograms of metal per gram of bentonite (ppm), and are indicative of the GCL's sorption capacity for a barrier system. Significant differences existed between the soil tested at 2 PV 5 PV and 21 PV It was only at 5 PV that the precipitation of the ferrihydrite occurred in the ARD samples, and gypsum occurred in the GMT samples. These minerals were responsible for retention of metals in addition to the cation exchange of the GCL.
Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients
Authors: Manco Melania , Fernández-Real José M. , Valera-Mora Maria E. , Déchaud Henri , Nanni Giuseppe , Tondolo Vincenzo , Calvani Menotti , Castagneto Marco , Pugeat Michel , Mingrone Geltrude
Published: May 2007

OBJECTIVE—Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.

RESEARCH DESIGN AND METHODS—Ten glucose-normotolerant, fertile, obese women (BMI >40 kg/m2, aged 38.66 ± 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method.

RESULTS—No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P = 0.05) and postobese women (P ≤ 0.01) as was the decrease in dehydroepiandrosterone (P ≤ 0.05 and P ≤ 0.01, respectively). CBG decreased from 51.50 ± 12.76 to 34.33 ± 7.24 mg/l (P ≤ 0.01) following BPD. FCI increased from 11.15 ± 2.85 to 18.16 ± 6.82 (P ≤ 0.05). Insulin secretion decreased (52.04 ± 16.71 vs. 30.62 ± 16.32 nmol/m−2; P ≤ 0.05), and insulin sensitivity increased by 163% (P ≤ 0.0001). Serum CBG was related to BMI (r0 = 0.708; P = 0.0001), body weight (r0 = 0.643; P = 0.0001), body fat percent (r0 = 0.462; P = 0.001), C-reactive protein (r0 = 0.619; P = 0.004), and leptin (r0 = 0.579; P = 0.007) and negatively to M value (r0 = −0.603; P = 0.005).

CONCLUSIONS—After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity.
Orange Juice or Fructose Intake Does Not Induce Oxidative and Inflammatory Response
Authors: Ghanim Husam , Mohanty Priya , Pathak Ram , Chaudhuri Ajay , Sia Chang Ling , Dandona Paresh
Published: May 2007

OBJECTIVE—We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-κB (NF-κB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose.

RESEARCH DESIGN AND METHODS— Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected.

RESULTS—There was a significant increase in ROS generation by mononuclear cells (by 130 ± 18%, P < 0.001), polymorph nuclear cells (by 95 ± 22%, P < 0.01), and in NF-κB binding in mononuclear cells by 82 ± 16% (P < 0.01) over the baseline after 2 h of glucose intake. These changes were absent following fructose, orange juice, or water intake. There was significantly lower ROS generation and NF-κB binding following orange juice, fructose, and water compared with glucose (P < 0.001 for all). Furthermore, incubation of mononuclear cells in vitro with 50 mmol/l of the flavonoids hesperetin or naringenin reduced ROS generation by 52 ± 7% and 77 ± 8% (P < 0.01), respectively, while fructose or ascorbic acid did not cause any change.

CONCLUSIONS—Caloric intake in the form of orange juice or fructose does not induce either oxidative or inflammatory stress, possibly due to its flavonoids content and might, therefore, represent a potentially safe energy source.
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Topiramate Controlled Release in the Treatment of Obese Type 2 Diabetic Patients
Authors: Rosenstock Julio , Hollander Priscilla , Gadde Kishore M. , Sun Xiang , Strauss Richard , Leung Albert ,   for the OBD-202 Study Group
Published: May 2007

OBJECTIVE—This is a randomized, placebo-controlled study of the weight-loss efficacy and safety of a controlled-release (CR) formulation of topiramate in overweight and obese patients with type 2 diabetes treated with diet and exercise alone or in combination with metformin.

RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes, BMI ≥27 kg/m2, A1C >6.5 and <11.0%, treated with diet and exercise alone or in combination with metformin monotherapy were enrolled. Patients were randomized to placebo or topiramate CR titrated up to 175 mg/day. Treatment consisted of a 7-week titration phase followed by a 9-week maintenance phase.

RESULTS—A total of 111 subjects were randomized and analyzed. By the end of week 16, patients in the placebo and topiramate groups lost 2.5 and 6.0 kg, which represented 2.3 and 5.8%, respectively, of their baseline body weight (P < 0.001 vs. placebo). A1C improved from a baseline of 7.4% in the placebo and 7.6% in the topiramate groups to 7.1 and 6.7%, respectively, representing a 0.4 and 0.9% reduction from baseline, respectively (P < 0.001 vs. placebo). Topiramate also significantly reduced blood pressure and urinary albumin excretion. Adverse events were predominantly neuropsychiatric or central and peripheral nervous system related.

CONCLUSIONS—Topiramate CR treatment produced significant weight loss and meaningful improvements in A1C and blood pressure in obese patients with type 2 diabetes treated with diet and exercise or in combination with metformin. However, the central nervous system and psychiatric adverse event profile of topiramate CR makes it unsuitable for the treatment of obesity and diabetes.
Strong Association Between Time Watching Television and Blood Glucose Control in Children and Adolescents With Type 1 Diabetes
Authors: Margeirsdottir Hanna D. , Larsen Jakob R. , Brunborg Cathrine , Sandvik Leiv , Dahl-Jørgensen Knut ,   for the Norwegian Study Group for Childhood Diabetes
Published: May 2007

OBJECTIVE—To examine the relationship between blood glucose control and the time spent watching television in Norwegian children and adolescents with type 1 diabetes in a population-based study.

RESEARCH DESIGN AND METHODS—A total of 538 children and adolescents from 9 hospitals in the eastern part of Norway participated in the study; 70% of eligible subjects participated. The time spent watching television and time using a computer was recorded separately by interview together with clinical data. Mean (±SD) age was 13.1 ± 3.7 years, mean diabetes duration was 5.4 ± 3.4 years, and mean A1C was 8.6 ± 1.3% (reference range 4.1–6.4).

RESULTS—Sixty-two patients (11%) watched television <1 h daily (mean A1C 8.2 ± 0.9%), 189 patients (35%) watched television between 1 and 2 h daily (8.4 ± 1.2%), 166 patients (31%) watched television 2–3 h daily (8.7 ± 1.4%), 75 patients (14%) watched television 3–4 h daily (8.8 ± 1.2%), and 46 patients (9%) watched television ≥4 h daily (9.5 ± 1.6%). This trend was highly significant (P < 0.001). The association between television viewing and A1C remained significant, even after adjusting for age and BMI and insulin dose. No correlation between A1C and the use of a personal computer was observed.

CONCLUSIONS—Extensive television watching is associated with poor blood glucose control in children and adolescents with type 1 diabetes.
Short-Term Weight Change and the Incidence of Diabetes in Midlife
Authors: Mishra Gita D. , Carrigan Gretchen , Brown Wendy J. , Barnett Adrian G. , Dobson Annette J.
Published: May 2007

OBJECTIVE—Although there is consensus that excess adiposity is strongly associated with type 2 diabetes, its relationship with weight change is less clear. This study investigates the relative impact of BMI at baseline and short-term (2- or 3-year) weight changes on the incidence of diabetes.

RESEARCH DESIGN AND METHODS—Prospective data were collected from a population-based cohort of middle-aged women participating in the Australian Longitudinal Study on Women's Health (n = 7,239 for this report). To date, participants have completed four mailed surveys (S1, 1996; S2, 1998; S3, 2001; and S4, 2004). Generalized estimating equations were used to model binary repeated-measures data to assess the impact of BMI at S1 and weight change (S1 to S2; S2 to S3) on 3-year incidence of diabetes at S3 and S4, respectively, adjusting for sociodemographic and lifestyle factors.

RESULTS—BMI at S1 was strongly associated with the development of diabetes by S3 or S4. Compared with women who had a BMI <25 kg/m2, those with BMI ≥25 kg/m2 had higher incidence of diabetes (P < 0.0001), with odd ratios reaching 12.1 (95% CI 7.6–19.3) for women in the very obese group (BMI ≥35 kg/m2). There was no association between shorter-term weight gain or weight loss on first-reported diagnosis of diabetes (P = 0.08).

CONCLUSIONS—Because women's risk of developing type 2 diabetes in midlife is more closely related to their initial BMI (when aged 45–50 years) than to subsequent short-term weight change, public health initiatives should target the prevention of weight gain before and during early adulthood.
Diabetes Care in Extended-Care Facilities
Authors: Holt Rachel M. , Schwartz Frank L. , Shubrook Jay H.
Published: May 2007

OBJECTIVE—The American Diabetes Association (ADA) does not recognize different treatment goals for the institutionalized adult compared with the outpatient adult with diabetes, nor has it outlined specific recommendations for this population. The purpose of this study was to examine physician management of patients with type 1 and type 2 diabetes residing in extended-care facilities and to compare this management with ADA standards of care for the outpatient adult.

RESEARCH DESIGN AND METHODS—This retrospective chart review included data from 108 residents with type 1 or type 2 diabetes at 11 extended health care facilities in the Midwestern U.S. and included a review of the medical problem list, medication list, laboratory reports, and all physician and consultation notes during the study period.

RESULTS—Blood glucose was monitored in 98% of the subjects, and 38% met glucose goals. A1C goal was achieved in 67% of patients. Blood pressure was monitored in 94% of patients, with 55% meeting goal. Thirty-one percent of patients had yearly lipids checked, 37% had annual electrocardiograms, 7% had urine analyzed for microalbuminuria, 42% were on aspirin, 87% received foot exams, 42% received dilated eye exams, 89% received influenza vaccinations, and 46% received pneumoccocal vaccinations.

CONCLUSIONS—Care of the institutionalized elderly with diabetes fails to meet ADA standards of care for the outpatient adult. Separate practice guidelines are needed for people with diabetes who reside in extended care facilities in order to improve quality and consistency of care.
How Doctors Choose Medications to Treat Type 2 Diabetes
Authors: Grant Richard W. , Wexler Deborah J. , Watson Alice J. , Lester William T. , Cagliero Enrico , Campbell Eric G. , Nathan David M.
Published: May 2007

OBJECTIVE—Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second-line oral agents, and insulin).

RESULTS—Respondents reported using a median of five major considerations (interquartile range 4–6) at each stage. Frequently cited major considerations included overall assessment of the patient's health/comorbidity, A1C level, and patient's adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P < 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A1C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0–10, P < 0.001.

CONCLUSIONS—The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines.
Relationship of Physician Volume With Process Measures and Outcomes in Diabetes
Authors: Turchin Alexander , Shubina Maria , Pendergrass Merri L.
Published: May 2007

OBJECTIVE—The volume of patients cared for by an individual physician (physician volume) has been linked to improved outcomes for a number of conditions. It is not known whether a similar association exists for treatment of diabetes. In this study we aimed to determine whether physician volume is associated with improved process measures and outcomes in diabetes care.

RESEARCH DESIGN AND METHODS—This retrospective cohort study analyzed electronic medical records data for 7,120 patients with diabetes treated by 368 primary care physicians at practices affiliated with two large academic hospitals. The associations between physician volume of diabetic patients (diabetes volume) and annual A1C and LDL testing, as well as blood pressure, A1C, and LDL levels, were evaluated.

RESULTS—In multivariable analysis, absolute diabetes volume was linked to decreased odds of A1C testing (4% less for each additional patient seen; P = 0.05), and relative diabetes volume (fraction of the total patients seen who had diabetes) was associated with decreased odds of both A1C (25% less for every 10% increase in the number of diabetic patients seen annually; P = 0.03) and LDL testing (20% less for every 10% increase in the number of diabetic patients; P < 0.001). Physician volume was not significantly associated with the odds of blood pressure, A1C, or LDL control at the end of the study.

CONCLUSIONS—Higher physician volume in care of diabetic patients is associated with decreased adherence to surveillance guidelines and no measurable difference in treatment outcomes.
Safe at School: A Virginia Experience
Authors: Hellems Martha A. , Clarke William L.
Published: May 2007

OBJECTIVE—The Commonwealth of Virginia passed legislation in 1999 requiring nonmedical school personnel to assist students with the management of type 1 diabetes when school nurses were unavailable. This study was designed to determine which school personnel in Virginia currently assist type 1 diabetic students with insulin administration and management of hypoglycemia and to determine if these students are being cared for in a safe manner.

RESEARCH DESIGN AND METHODS—Parents of children with type 1 diabetes who attended public school in Virginia during the previous year and who were receiving their diabetes care at the University of Virginia diabetes clinics were asked to participate in an anonymous survey. The survey asked parents which school personnel were responsible for their child's diabetes care while at school and which persons helped with specific care tasks including blood glucose monitoring, insulin administration, and assistance with treatment of hypoglycemia. Questions were asked regarding the occurrence and treatment of hypoglycemia and any adverse effects of such treatment.

RESULTS—A total of 185 parents whose children attended 153 different schools responded, 69% of whom reported that a full-time school nurse was assigned to their child's school. In other schools, teachers, administrators, coaches, and cafeteria workers supplemented part-time nurses in assisting students with diabetes management tasks. Although hypoglycemia was not a rare event (75% of students experienced a median of five episodes per year), only one severe event requiring the use of glucagon was reported. In that case, glucagon was administered appropriately by a part-time school nurse, and the student experienced no adverse effects related to the treatment.

CONCLUSIONS—Students with type 1 diabetes can be cared for safely during the school day by a variety of trained medical and nonmedical personnel. The occurrence of one severe hypoglycemic event among 185 students suggests that as many as 3% of students could experience severe hypoglycemia in a given school year. Legislation that permits nonmedical school personnel to assist students with their diabetes management could make the diabetic children's school day safer and improve their overall glucose control.
Nonalcoholic Fatty Liver Disease and Insulin Resistance in Youth
Authors: Bloomgarden Zachary T.
Published: May 2007

Perspectives on the News commentaries are now part of a new, free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, is designating this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Materialprofile von Holzerntesystemen als Ausgangspunkt für Ökoinventare | Material Profiles of Timber-Harvesting Systems as a Basis for Life Cycle Inventories
Authors: Knechtle Norbert
Published: May 2007

A Life Cycle Assessment (LCA), based on life cycle inventories, is proposed to evaluate the eco-efficiency of timber harvesting systems. A comparison is made between timber harvesting productivity and the consumption of environment during the different stages of timber harvesting.
Dendrochronologische Auswertung fossiler Hölzer zur Rekonstruktion der nacheiszeitlichen Gletschergeschichte | Dendrochronological evaluation of fossil wood to reconstruct holocene history
Authors: Holzhauser Hanspeter
Published: May 2007

Around the middle of the 19th century, alpine glaciers advanced to their last maximum extension within the Holocene (the last 10 000 years). Some of the glaciers, especially the Great Aletsch and Gorner, penetrated deeply into wooded land and destroyed numerous trees. Not only were trees destroyed but also valuable arable land, alpine farm buildings and dwelling houses. Since this last maximum extension the retreat of the glaciers has accelerated revealing,within the glacier forefields, the remainders of trees once buried (trunks, branches and roots). Some of this fossil wood is found in the place where it grew (in situ). The wood often dates back to a time before the last glacier advance, most of it is several thousands of years old because glacial advance and retreat periods occurred repeatedly within the Holocene. This paper shows the characteristics of fossil wood and, with the help of a model, how they can be analysed to reconstruct glacial history. Using two examples, we demonstrate how glacier length variation can be exactly reconstructed with the help of dendrochronology. The first example deals with the advance of the Gorner glacier in the 14th century. This glacier reached its maximum extension around 1385. The other example deals with the advance of the Great Aletsch glacier between 1581 and 1678, the year when this glacier reached its maximum extension. Thanks to the very exact reconstruction of the change in the glacier length we can estimate the velocities of both the Gorner and Great Aletsch glaciers during the advancement periods in the 14th and 16th centuries. They range from between 7–8 and 20 m/p.a. and 7–8 and 30 m/p.a., for the Gorner glacier and the Great Aletsch glacier,respectively.
Effects of losartan on haemodynamic parameters and angiotensin receptor mRNA levels in rat heart after myocardial infarction
Authors: Yi Zhun Zhu  , Zhu Yi-Chun , Jun Li  , Schäfer Heiner , Schmidt Wolfgang , Tai Yao  , Unger Thomas
Published: May 2007

We investigated the haemodynamic parameters and the regulation of cardiac mRNA levels of the angiotensin receptor subtypes, AT1 and AT2, by the AT1-receptor antagonist losartan in rat heart during the acute phase of myocardial infarction. AT1- and AT2-receptor mRNA levels markedly increased at 30 minutes and peaked at 24 hours post myocardial infarction (12.6-fold increase for AT1- and 17.2-fold increase for AT2 compared with controls). Losartan significantly reduced mean blood pressure in sham-operated rats and decreased mean blood pressure and left ventricular end-diastolic pressure in myocardial infarction rats. However, the AT1- and AT2-receptor mRNA levels of losartan-treated rats showed a pattern similar to that of water-treated rats. The time-dependent increase of AT 1- and AT2receptor mRNA levels is associated with the early remodelling process of non-infarcted myocardium post MI and is independent of AT1-receptor blockade.
Insulin-like growth factor induces up-regulation of AT1-receptor gene expression in vascular smooth muscle cells
Authors: Müller Cornelius , Reddert Anja , Wassmann Sven , Strehlow Kerstin , Böhm Michael , Nickenig Georg
Published: May 2007

Background Insulin-like growth factor-1 (IGF-1), as well as AT1-receptor activation, plays a central role in growth processes of cardiac and vascular cells. In order to assess relevant interactions of both systems, the effect of IGF-1 on AT1-receptor expression was evaluated in vascular smooth muscle cells.

Methods and results Incubation of cultured vascular smooth muscle cells (VSMC) with IGF-1 led to a dose- and time-dependent up-regulation of AT1-receptor mRNA, as measured by Northern hybridisations. The maximal AT1-receptor overexpression of 201±70% of control levels was reached after a 24-hour incubation with 100 ng/ml IGF-1. Consequently, AT1-receptor protein expression was increased to 231±35% of control levels. Experiments under transcriptional blockade showed that AT1-receptor mRNA stability was not altered by IGF-1, suggesting that transcriptional mechanisms may be involved in IGF-1-induced AT1-receptor regulation. Preincubation with various pharmacological inhibitors revealed that IGF-1 up-regulated AT1-receptor expression via activation of p42/44 MAP kinase, whereas tyrosine phosphorylation and PI-3 kinase seemed not to participate in this regulative pathway.

Conclusions IGF-1-induced up-regulation of the AT1-receptor may be an important interaction by which cellular growth is modulated in the heart as well as in the vasculature. This may have implications for the treatment regimen of patients suffering from hypertension, cardiac hypertrophy, and coronary heart disease.
Lys 199 mutation of the human angiotensin type 1 receptor differentially affects the binding of surmountable and insurmountable non-peptide antagonists
Authors: Fierens Frederik LP , Vanderheyden Patrick ML , Gáborik Zsuzsanna , Le Minh Tam , De Backer Jean-Paul , Hunyady László , Ijzerman Adriaan , Vauquelin Georges
Published: May 2007

Many slow dissociating (insurmountable) non-peptide angiotensin type 1 receptor (AT1) antagonists contain, besides the acidic biphenyltetrazole substructure of losartan, a second acidic group to stabilise antagonist-receptor complexes. To investigate the involved basic amino-acids of the human AT1-receptor, wild-type and mutant receptors were transiently transfected in CHO-K1 cells and characterised by [3H]candesartan binding. Lys199 → Gln substitution decreased the affinity 45-fold for candesartan (95% insurmountable), 18-fold for EXP3174 (70% insurmountable), 10-fold for irbesartan (40% insurmountable) and 5-fold for losartan (surmountable). His256 → Ala substitution had only minor effects. This suggests that Lys199 is important for the tight binding of non-peptide antagonists.