bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise in the Prevention and Treatment of Adolescent Depression: A Promising but Little Researched Intervention
Authors: Dunn Andrea L. , Weintraub Philippe
Published: August 2008

Despite a dramatic increase in the number of treatment studies for adolescent major depressive disorder in the past 15 years, the majority being clinical trials of medications and cognitive behavioral therapy, response rates have been modest and remission rates low. Moreover, most positive responders posttreatment have many residual symptoms, significant functional impairment, and high rates of relapse. There is a need for the development of new, more effective interventions to treat this severe, chronic condition that usually persists into adulthood with poor long-term outcomes. Findings from preliminary treatment studies suggest that exercise may have the potential to be efficacious as a monotherapy or as part of a combined treatment for adolescent major depressive disorder. This review summarizes the findings and analyzes the design flaws of randomized trials of exercise to treat adolescent depression, offering recommendations on how to design more methodologically sound studies with an emphasis on subject selection criteria; issues related to control conditions, types of diagnostic interviews, and measures needed to establish the diagnosis of depression; types of exercise treatments; and appropriate outcome measures. Future studies of exercise to treat and prevent adolescent major depressive disorder need to be comparable to state-of-the-art treatment studies of pharmacotherapy and cognitive behavioral therapy in this population to more accurately determine its efficacy and potential public health benefits.
Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein specification in vertebrates
Authors: Chun Chang Z. , Kaur Sukhbir , Samant Ganesh V. , Wang Ling , Pramanik Kallal , Garnaas Maija K. , Li Keguo , Field Lyndsay , Mukhopadhyay Debabrata , Ramchandran Ramani
Published: August 2008

In vertebrates, molecular mechanisms dictate angioblasts' migration and subsequent differentiation into arteries and veins. In this study, we used a microarray screen to identify a novel member of the sucrose nonfermenting related kinase (snrk-1) family of serine/threonine kinases expressed specifically in the embryonic zebrafish vasculature and investigated its function in vivo. Using gain- and loss-of-function studies in vivo, we show that Snrk-1 plays an essential role in the migration, maintenance, and differentiation of angioblasts. The kinase function of Snrk-1 is critical for migration and maintenance, but not for the differentiation of angioblasts. In vitro, snrk-1 knockdown endothelial cells show only defects in migration. The snrk-1 gene acts downstream or parallel to notch and upstream of gridlock during artery-vein specification, and the human gene compensates for zebrafish snrk-1 knockdown, suggesting evolutionary conservation of function.
Molecular evolution of the keratin associated protein gene family in mammals, role in the evolution of mammalian hair
Authors: Wu Dong-Dong , Irwin David M , Zhang Ya-Ping
Published: August 2008

Background

Hair is unique to mammals. Keratin associated proteins (KRTAPs), which contain two major groups: high/ultrahigh cysteine and high glycine-tyrosine, are one of the major components of hair and play essential roles in the formation of rigid and resistant hair shafts.

Results

The KRTAP family was identified as being unique to mammals, and near-complete KRTAP gene repertoires for eight mammalian genomes were characterized in this study. An expanded KRTAP gene repertoire was found in rodents. Surprisingly, humans have a similar number of genes as other primates despite the relative hairlessness of humans. We identified several new subfamilies not previously reported in the high/ultrahigh cysteine KRTAP genes. Genes in many subfamilies of the high/ultrahigh cysteine KRTAP genes have evolved by concerted evolution with frequent gene conversion events, yielding a higher GC base content for these gene sequences. In contrast, the high glycine-tyrosine KRTAP genes have evolved more dynamically, with fewer gene conversion events and thus have a lower GC base content, possibly due to positive selection.

Conclusion

Most of the subfamilies emerged early in the evolution of mammals, thus we propose that the mammalian ancestor should have a diverse KRTAP gene repertoire. We propose that hair content characteristics have evolved and diverged rapidly among mammals because of rapid divergent evolution of KRTAPs between species. In contrast, subfamilies of KRTAP genes have been homogenized within each species due to concerted evolution.
Stable high volumetric production of glycosylated human recombinant IFNalpha2b in HEK293 cells
Authors: Loignon Martin , Perret Sylvie , Kelly John , Boulais Denise , Cass Brian , Bisson Louis , Afkhamizarreh Fatemeh , Durocher Yves
Published: August 2008

Background

Mammalian cells are becoming the prevailing expression system for the production of recombinant proteins because of their capacity for proper protein folding, assembly, and post-translational modifications. These systems currently allow high volumetric production of monoclonal recombinant antibodies in the range of grams per litre. However their use for large-scale expression of cytokines typically results in much lower volumetric productivity.

Results

We have engineered a HEK293 cell clone for high level production of human recombinant glycosylated IFNα2b and developed a rapid and efficient method for its purification. This clone steadily produces more than 200 mg (up to 333 mg) of human recombinant IFNα2b per liter of serum-free culture, which can be purified by a single-step cation-exchange chromatography following media acidification and clarification. This rapid procedure yields 98% pure IFNα2b with a recovery greater than 70%. Purified IFNα2b migrates on SDS-PAGE as two species, a major 21 kDa band and a minor 19 kDa band. N-terminal sequences of both forms are identical and correspond to the expected mature protein. Purified IFNα2b elutes at neutral pH as a single peak with an apparent molecular weight of 44,000 Da as determined by size-exclusion chromatography. The presence of intramolecular and absence of intermolecular disulfide bridges is evidenced by the fact that non-reduced IFNα2b has a greater electrophoretic mobility than the reduced form. Treatment of purified IFNα2b with neuraminidase followed by O-glycosidase both increases electrophoretic mobility, indicating the presence of sialylated O-linked glycan. A detailed analysis of glycosylation by mass spectroscopy identifies disialylated and monosialylated forms as the major constituents of purified IFNα2b. Electron transfer dissociation (ETD) shows that the glycans are linked to the expected threonine at position 106. Other minor glycosylated forms and non-sialylated species are also detected, similar to IFNα2b produced naturally by lymphocytes. Further, the HEK293-produced IFNα2b is biologically active as shown with reporter gene and antiviral assays.

Conclusion

These results show that the HEK293 cell line is an efficient and valuable host for the production of biologically active and glycosylated human IFNα2b.
Serum lipid responses to psyllium fiber: differences between pre- and post-menopausal, hypercholesterolemic women
Authors: Ganji Vijay , Kuo Jennifer
Published: August 2008

Background

Cardiovascular disease is the leading cause of death in women and men. Psyllium, a soluble fiber has been known to reduce serum lipids. In this pilot study, we evaluated whether menopausal status would affect the serum lipid responses to psyllium fiber in women.

Methods

Eleven post-menopausal and eight pre-menopausal women with serum total cholesterol >200 mg/dL were included in the study. Subjects consumed their habitual diet and 15 g psyllium/d for 6 weeks. Psyllium was incorporated into cookies. Each cookie contained ≈5 g of psyllium fiber. Subjects ate one cookie in each meal.

Results

With psyllium fiber, total cholesterol concentration was significantly lower (≈5.2%, P < 0.05) in post-menopausal women but not in pre-menopausal women (≈1.3%). Also, there was a significant decrease in HDL-cholesterol in post-menopausal women (≈10.2%, P < 0.05). There were no significant changes observed in concentrations of LDL-cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B in both pre- and post-menopausal women with psyllium.

Conclusion

In this pilot study, post- and pre-menopausal, hypercholesterolemic women responded differently to psyllium fiber supplementation. Post-menopausal women would benefit from addition of psyllium to their diets in reducing the risk for heart diseases. The results of this study should be used with caution because the study was based on a small sample size.
Primary glioblastoma in the pineal region: a case report and review of the literature
Authors: Moon Kyung-Sub , Jung Shin , Jung Tae-Young , Kim In-Young , Lee Min-Cheol , Lee Kyung-Hwa
Published: August 2008

Introduction

Glioblastoma in the pineal region is extremely rare with only a few cases reported in the literature.

Case presentation

A 68-year-old man presented with a sudden deterioration manifesting as a headache, vomiting and gait disturbance. A magnetic resonance imaging study revealed a heterogeneously ring-enhanced mass in the pineal region. The mass was subtotally removed through the occipital transtentorial approach, and diagnosed as a glioblastoma.

Conclusion

We discuss the clinical course, radiological findings and treatment strategies of pineal glioblastoma with a review of the relevant literature.
Plasma Obestatin, Ghrelin, and Ghrelin/Obestatin Ratio Are Increased in Underweight Patients with Anorexia Nervosa But Not in Symptomatic Patients with Bulimia Nervosa
Authors: Monteleone Palmiero , Serritella Cristina , Martiadis Vassilis , Scognamiglio Pasquale , Maj Mario
Published: August 2008

Introduction: Peptides of the gut-brain axis have a pivotal role in the regulation of energy homeostasis. Obestatin, a sibling of ghrelin derived from preproghrelin, is thought to oppose ghrelin effects on food intake. Because changes in ghrelin levels have been associated with anorexia nervosa (AN) and bulimia nervosa (BN), the investigation of obestatin production may further contribute to understanding the role of peripheral peptides in patients with eating disorders.

Methods: In the present study, we measured circulating blood levels of obestatin and ghrelin and assessed their relationships with anthropometric and clinical measures in 20 AN patients, 21 BN patients, and 20 appropriate healthy controls.

Results: Compared with healthy women, patients with BN showed no significant differences in plasma obestatin and ghrelin concentrations and in the ghrelin/obestatin ratio, whereas underweight AN patients displayed significantly increased circulating levels of both obestatin (P < 0.009) and ghrelin (P < 0.002) and an increased ghrelin/obestatin ratio (P < 0.04). Moreover, in AN women, positive correlations emerged between the ghrelin/obestatin ratio and current body weight and body mass index.

Conclusions: Underweight AN patients are characterized by increased concentrations of ghrelin and obestatin and a higher ghrelin to obestatin ratio. No changes in circulating ghrelin or obestatin as well as in ghrelin to obestatin ratio seem to occur in acutely ill patients with BN. Although those changes likely reflect the physiological state of symptomatic AN individuals, they may also contribute to the pathophysiology of the disorder.
Interlayered Host Created by Assemblies of Monomeric Nickel Complex with Imidazole-4-acetate Chelate Ligands
Authors: Kondo Mitsuru , Amano Masaki , Iwase Takahiro , Miyazawa Makoto , Yasue Sachie , Maeda Kenji , Uchida Fumio
Published: August 2008

A new nickel(II) complex with two imidazole-4-acetate (ima) and a 1,10-phenanthroline (phen) was synthesized and characterized. The monomeric units are assembled by two NH···O–C intermolecular hydrogen bonds and π–π interactions, yielding two-dimensional layers. This complex includes six-water molecules per a nickel atom between the layers. The assembled interlayered host framework reversibly releases and reincludes water molecules.
Ortho-selective Arylation of Arylazoles with Aryl Bromides Catalyzed by Ruthenium Complexes
Authors: Oi Shuichi , Sasamoto Hiromi , Funayama Raito , Inoue Yoshio
Published: August 2008

Ortho-selective direct arylation of arylazoles with aryl bromides has been accomplished in the presence of a catalytic amount of ruthenium complexes.
DNA/α-Cyclodextrin–Rotaxane Conjugate as a New Supramolecular Material
Authors: Kuzuya Akinori , Ohnishi Toshiyuki , Komiyama Makoto
Published: August 2008

A hybrid molecule of cyclodextrin (CyD) and DNA, two major subjects in supramolecular chemistry, should open a new research field in nanoscience. By capping the end of a pseudorotaxane, formed between α-CyD and dodecylamine-modified DNA, with 1-adamantaneacetic acid, a DNA/α-CyD–rotaxane conjugate has been successfully synthesized and characterized.
Glucose interference in direct ion-sensitive electrode sodium measurements
Authors: Al-Musheifri Asila , Jones Graham R D
Published: August 2008

Circulating sodium concentration is commonly measured by both direct and indirect ion-sensitive electrode (ISE). We describe an unusual case with a high elevation of serum glucose (162 mmol/L) where direct ISE sodium measurement was 9 mmol/L higher than the indirect measurement in the absence of any cause for pseudohyponatraemia. In vitro experiments showed that very high glucose concentrations increased the sodium in direct, but not in indirect ISE measurement. This effect was insufficient to account for the entire difference between the measurements seen in the patient, indicating that other factors, for example pH and bicarbonate concentration, must also be involved. This effect may influence interpretation of sodium status in patients with gross hyperglycaemia.
Improving patients' knowledge on the relationship between HbA1c and mean plasma glucose improves glycaemic control among persons with poorly controlled diabetes
Authors: Iqbal Nosheen , Morgan Catherine , Maksoud Hisham , Idris Iskandar
Published: August 2008

Background

Recent recommendation advocates the reporting of HbA1c in terms of mean plasma glucose. We examined the impact of improving patients' interpretation of a given HbA1c value on glycaemic control.

Methods

We conducted a questionnaire survey among 111 patients attending a hospital diabetes clinic. Patients were provided with information relating to the association between HbA1c and mean plasma glucose levels. Glycaemic control among 80 patients with poor glycaemic control was assessed before and approximately seven months after such intervention.

Results

Of the respondents, 40.5% (45/111) were familiar (F) (31 type 1, 14 type 2) and 59.5% (66/111) were unfamiliar (U) (23 type 1, 43 type 2) with the term HbA1c. Following information about the interpretation of HbA1c, patients with poorly controlled diabetes (HbA1c >9%) showed a significant reduction in HbA1c levels if they were from group U (10.7% vs. 9.5%, P = 0.04) but not from group F (10.5 vs. 9.8, P = 0.28). Patients with moderately poor glycaemic control (HbA1c 7.5–9%) showed no significant change in HbA1c levels following intervention (8.3% vs. 8.2%, P = 0.57 group U; 8.3% vs. 8.2%, P = 0.79 group F).

Conclusion

Patients' knowledge of HbA1c is poor, especially among persons with type 2 diabetes. Improvement in patients' understanding of HbA1c, particularly among those with very poorly controlled diabetes with no prior knowledge of HbA1c is associated with improvement in their glycaemic control. Strategies to engage patients to know and interpret their HbA1c values should be encouraged within routine clinical practice.
2006 ISMS Practice Prize Competition—Special Section Introduction
Authors: Roberts John H. , Lilien Gary L.
Published: August 2008

We introduce the work of the finalists in the 2006 ISMS Practice Prize Competition, representing outstanding examples of rigor plus relevance in our profession. The winner, describing a collaboration between J.D. Power and Associates and U.C. Riverside, involves a sequenced program of research to understand the effect of promotional activity in the U.S. automobile market. The other three finalists address a model to calibrate the effects of corporate brand activity across three divisions at Allstate Insurance; a method for using CLV models to focus customer contact strategies at IBM; and a segmentation strategy to protect and gain customers in the face of a new entrant for the Austrian mobile telecommunications carrier, tele.ring.
Database Paper—The IRI Marketing Data Set
Authors: Bronnenberg Bart J. , Kruger Michael W. , Mela Carl F.
Published: August 2008

This paper describes a new data set available to academic researchers (at the following website: http://mktsci.pubs.informs.org ). These data are comprised of store sales and consumer panel data for 30 product categories. The store sales data contain 5 years of product sales, pricing, and promotion data for all items sold in 47 U.S. markets. In two U.S. markets, the store level data are supplemented with panel-level purchase data and cover the entire population of stores. Further information is available regarding store characteristics in these markets. We address several potential applications of these data, as well as the access protocol.

The data set described in this paper is maintained by IRI. Any fees charged by IRI for the distribution of the data set will be used for the continual maintenance and updating of the data. Scholarships to cover IRI's fees (for those who need it) are available through the INFORMS Society for Marketing Science (ISMS). Please see the website above for further details.
Sibutramine-Associated QT Interval Prolongation and Cardiac Arrest
Authors: Ernest David , Gershenzon Alexander , Corallo Carmela E , Nagappan Ramesh
Published: August 2008

Objective:

To report on a probable association between sibutramine and QT interval prolongation leading to ventricular fibrillation and cardiac arrest.

Case Summary:

A previously well 51-year-old woman with obesity but no other relevant past medical history or cardiac risk factors was prescribed sibutramine (initial dose 10 mg daily, increased to 15 mg daily after 10wk). Four months after initiation of therapy, the woman developed ventricular fibrillation and was successfully resuscitated. On admission, an electrocardiogram (ECG) demonstrated sinus tachycardia without any ischemic changes and a prolonged QTc interval (545 msec). A subsequent coronary angiogram revealed normal coronary arteries and no other abnormalities. Her QTc interval returned to normal (432 msec) by day 2 and remained within normal limits (<440 msec) thereafter. Due to a favorable neurologic recovery and the absence of any cardiac structural abnormality, the patient was readmitted for implantation of an automatic implantable cardioverter-defibrillator on day 35 and remained well from a cardiac and neurologic standpoint at a 2-year follow-up examination.

Discussion:

Sibutramine acts centrally to inhibit noradrenaline, dopamine, and serotonin reuptake, thereby sharing similar actions of other QT interval-prolonging drugs. Therefore, sibutramine might be anticipated to also share a tendency to QT interval prolongation. The current prescribing information for sibutramine does not specifically list any precautions or adverse reactions related to QT interval prolongation. QT interval prolongation associated with sibutramine in this case is considered probable based on the Naranjo probability scale.

Conclusions:

Clinicians prescribing sibutramine should monitor their patients for ECG abnormalities and be cautious in coprescribing drugs known to prolong the QT interval.
Kaolinite formation from palygorskite and sepiolite in rhizosphere soils
Authors: Khademi H. , Arocena J. M.
Published: August 2008

Palygorskite and sepiolite are fibrous clays that occur mostly in agricultural soils of arid regions. Although many investigations have examined the environmental conditions for the formation and stability of these clays, information on the transformation of these clays in the root zone (or rhizosphere) of agricultural crops is limited. In this study, changes in palygorskite and sepiolite within the rhizosphere of selected agricultural crops were determined and the ability of plants to extract Mg from these minerals compared. Alfalfa, barley, and canola were cultivated in pots under controlled conditions in a growth chamber using growth media that consisted of a mixture of Ottawa sand and clay-sized Florida palygorskite (PFl-1) or Spanish sepiolite (SepSp-1). After 100 days of cultivation, the biomass of plant roots and shoots were determined and Mg uptake measured by inductively coupled plasma analysis of the plant biomass after microwave oven digestion. The clay fraction in each pot was separated from the sand and analyzed using X-ray diffraction (XRD) and examined using transmission electron microscopy (TEM). The XRD reflection at 0.718 nm clearly indicated kaolinite in the rhizosphere after growth of the three crops. Furthermore, hexagonal kaolinite particles were observed, using TEM, and the amount of Mg extracted by the three crops was significantly greater for sepiolite than for palygorskite. Palygorskite and sepiolite kaolinization in the rhizosphere was apparently due: (1) to high acidity in the rhizosphere caused by root activity and organic matter decomposition; and (2) to fibrous clay destabilization caused by Mg uptake by plants. This study shows that kaolinite in agricultural soils of arid and semi-arid regions might be partly due to neoformation after fibrous clay dissolution and not entirely inherited from parent materials, as has been suggested in earlier literature.
Chemical and mineralogical characteristics of French green clays used for healing
Authors: Williams Lynda B. , Haydel Shelley E. , Giese Rossman F. , Eberl Dennis D.
Published: August 2008

The worldwide emergence of infectious diseases, together with the increasing incidence of antibiotic-resistant bacteria, elevate the need to properly detect, prevent, and effectively treat these infections. The overuse and misuse of common antibiotics in recent decades stimulates the need to identify new inhibitory agents. Therefore, natural products like clays, that display antibacterial properties, are of particular interest.

The absorptive properties of clay minerals are well documented for healing skin and gastrointestinal ailments. However, the antibacterial properties of clays have received less scientific attention. French green clays have recently been shown to heal Buruli ulcer, a necrotic or ‘flesh-eating’ infection caused byMycobacterium ulcerans. Assessing the antibacterial properties of these clays could provide an inexpensive treatment for Buruli ulcer and other skin infections.

Antimicrobial testing of the two clays on a broad-spectrum of bacterial pathogens showed that one clay promotes bacterial growth (possibly provoking a response from the natural immune system), while another kills bacteria or significantly inhibits bacterial growth. This paper compares the mineralogy and chemical composition of the two French green clays used in the treatment of Buruli ulcer.

Mineralogically, the two clays are dominated by 1Mdillite and Fe-smectite. Comparing the chemistry of the clay minerals and exchangeable ions, we conclude that the chemistry of the clay, and the surface properties that affect pH and oxidation state, control the chemistry of the water used to moisten the clay poultices and contribute the critical antibacterial agent(s) that ultimately debilitate the bacteria.
Low-temperature FTIR study of kaolin-group minerals
Authors: Johnston Cliff T. , Kogel Jessica Elzea , Bish David L. , Kogure Toshihiro , Murray Haydn H.
Published: August 2008

Low-temperature FTIR spectroscopy was used to characterize the v(OH) region of kaolin-group minerals including well ordered to poorly ordered kaolins from Georgia, Brazil, and England, along with samples of discrete dickite and nacrite. Low-temperature FTIR spectra were useful in resolving dickite- and nacrite-like features present in the spectra of kaolins when cooled to <30 K. These features were not resolved at room temperature and only partially resolved at liquid N2 temperature (77 K). The room-temperature and low-temperature positions of the ν(OH) bands of kaolinite, dickite, and nacrite were linearly correlated with the interatomic OH⋯O distances and this relationship served as the basis for polytype/disorder identification. Dickite or dickite-like disorder was found in high Hinckley-Index kaolinite from Keokuk, Iowa, and from Cornwall, England. Dickite- and nacrite-like features were observed in both high- and low-Hinckley-index kaolinite and the amounts of these stacking sequences generally increased with decreasing Hinckley Index.
Estradiol-Induced Enhancement of Object Memory Consolidation Involves Hippocampal Extracellular Signal-Regulated Kinase Activation and Membrane-Bound Estrogen Receptors
Authors: Fernandez Stephanie M. , Lewis Michael C. , Pechenino Angela S. , Harburger Lauren L. , Orr Patrick T. , Gresack Jodi E. , Schafe Glenn E. , Frick Karyn M.
Published: August 2008

The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen 17β-estradiol (E2). Here, we asked whether E2modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal injection of 0.2 mg/kg E2significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 h after injection. Second, we show that E2administered intraperitoneally (0.2 mg/kg) or via intrahippocampal infusion (5.0 μg/side) immediately after training in an object recognition task significantly enhances memory retention, and that the beneficial effect of intraperitoneal E2is blocked by dorsal hippocampal inhibition of ERK activation. Third, using bovine serum albumin-conjugated 17β-estradiol (BSA-E2), we demonstrate that E2binding at membrane-bound ERs can increase dorsal hippocampal ERK activation and enhance object memory consolidation in an ERK-dependent manner. Fourth, we show that this effect is independent of nuclear ERs, but is dependent on the dorsal hippocampus. By demonstrating that E2enhances memory consolidation via dorsal hippocampal ERK activation, this study is the first to identify a specific molecular pathway by which E2modulates memory and to demonstrate a novel role for membrane-bound ERs in mediating E2-induced improvements in hippocampal memory consolidation.
BACE1 Knock-Outs Display Deficits in Activity-Dependent Potentiation of Synaptic Transmission at Mossy Fiber to CA3 Synapses in the Hippocampus
Authors: Wang Hui , Song Lihua , Laird Fiona , Wong Philip C. , Lee Hey-Kyoung
Published: August 2008

β-Amyloid precursor protein cleavage enzyme 1 (BACE1) has been identified as a major neuronal β-secretase critical for the formation of β-amyloid (Aβ) peptide, which is thought responsible for the pathology of Alzheimer's disease (AD). Therefore, BACE1 is one of the key therapeutic targets that can prevent the progression of AD. Previous studies showed that knocking out the BACE1 gene prevents Aβ formation, but results in behavioral deficits and specific synaptic dysfunctions at Schaffer collateral to CA1 synapses. However, BACE1 protein is most highly expressed at the mossy fiber projections in CA3. Here, we report that BACE1 knock-out mice display reduced presynaptic function, as measured by an increase in paired-pulse facilitation ratio. More dramatically, mossy fiber long-term potentiation (LTP), which is normally expressed via an increase in presynaptic release, was eliminated in the knock-outs. Although long-term depression was slightly larger in the BACE1 knock-outs, it could not be reversed. The specific deficit in mossy fiber LTP was upstream of cAMP signaling and could be “rescued” by transiently elevating extracellular Ca2+concentration. These results suggest that BACE1 may play a critical role in regulating presynaptic function, especially activity-dependent strengthening of presynaptic release, at mossy fiber synapses.
Thyroid nodules: a review of current guidelines, practices, and prospects
Authors: Gharib H , Papini E , Paschke R
Published: August 2008

In 2006, two major society-sponsored guidelines and one major consensus statement for thyroid diagnosis and management were published by: the American Association of Clinical Endocrinologists/Associazione Medici Endocrinologi (AACE/AME); the American Thyroid Association (ATA); and the European Thyroid Association (ETA). A careful review of these guidelines reveals that despite many similarities, significant differences are also present, likely reflecting differences in practice patterns, interpretation of existing data, and availability of resources in different regions. The methodology of the guidelines is similar, but a few differences in the rating scale make a rapid comparison of the strength of both evidence and recommendations difficult for the use in current clinical practice. Some recommendations are based mostly on experts' opinion. Thus, a same recommendation may be based on a different evidence; on the other hand, sometimes the same evidence may induce a different recommendation. Therefore, efforts are needed to produce a few high-quality clinical studies to close the evidence gaps in the still controversial fields of thyroid disease and to create a joint task force of the most authoritative societies in the field of thyroid disease in order to reach a common document for clinical practice recommendations.
Safety, Efficacy, and Dosing Requirements of Bivalirudin in Patients with Heparin‐Induced Thrombocytopenia
Authors: Kiser Tyree H. , Burch Jessica C. , Klem Patrick M. , Hassell Kathryn L.
Published: August 2008

Study Objective. To evaluate the safety, efficacy, and dosing requirements of bivalirudin in patients with heparin‐induced thrombocytopenia (HIT).

Design. Retrospective cohort study.

Setting. University‐affiliated hospital.

Patients. Thirty‐seven adults with a diagnosis or history of HIT who were treated with bivalirudin between January 1, 2004, and March 31, 2007.

Measurements and Main Results. Patients had a mean ± SD age of 50 ± 16 years and weighed 80 ± 20 kg; 62% were male, 73% were Caucasian, and 95% were treated in the intensive care unit. Patients were divided into three renal function groups for assessment of bivalirudin dosing requirements: creatinine clearance (Clcr) greater than 60 ml/minute (12 patients, group 1); Clcr 30–60 ml/minute (11 patients, group 2); and Clcr lower than 30 ml/minute or receiving continuous renal replacement therapy ([RRT] 14 patients, group 3). Except for renal function, baseline demographic characteristics were similar among groups. A total of 19 (51%) of the 37 patients achieved goal activated partial thromboplastin time (aPTT) with initial mean ± SD bivalirudin doses of 0.14 ± 0.04 (median 0.15), 0.1 ± 0.07 (median 0.08), and 0.05 ± 0.05 (median 0.05) mg/kg/hour in groups 1, 2, and 3, respectively. Doses remained similar over the study period and were 0.13 ± 0.04 (median 0.15), 0.1 ± 0.06 (median 0.1), and 0.04 ± 0.02 (median 0.03) mg/kg/hour for groups 1, 2, and 3, respectively. The mean ± SD aPTT value after achieving goal range was 64 ± 9 seconds (all patients). Bivalirudin dosing requirements correlated with Clcr (r2 = 0.37, p<0.0001). Therapy duration was a mean ± SD of 11 ± 13 days (median 7 days). Systemic thrombosis and bleeding while receiving bivalirudin were also evaluated. Thrombosis occurred in one patient; clinically significant bleeding occurred in two patients.

Conclusion. Bivalirudin dosing requirements correlated with renal function; therefore, dosage reduction is required in patients with moderate or severe renal dysfunction. Starting bivalirudin at 0.15 mg/kg/hour in patients with Clcr greater than 60 ml/minute, 0.08‐0.1 mg/kg/hour in patients with Clcr 30–60 ml/minute, and 0.03‐0.05 mg/kg/hour in patients with Clcr below 30 ml/minute or receiving continuous RRT is effective at achieving goal aPTT values in most patients.
Comparison of Dosing Recommendations for Antimicrobial Drugs Based on Two Methods for Assessing Kidney Function: Cockcroft‐Gault and Modification of Diet in Renal Disease
Authors: Golik Monica V. , Lawrence Kenneth R.
Published: August 2008

Study Objectives. To quantify the difference between glomerular filtration rates (GFRs) estimated by using the Cockcroft‐Gault and Modification of Diet in Renal Disease (MDRD) equations, and to determine whether dosing recommendations for four commonly prescribed antimicrobial agents are discordant when determined by using these equations.

Design. Prospective, observational study.

Setting. Tertiary‐care medical center.

Patients. Two hundred seven consecutive adults without normal renal function but not receiving dialysis who were admitted to a non‐intensive‐care ward and had two consecutive serum creatinine concentration (Scr) values measured 20–24 hours apart.

Measurements and Main Results. The patients' mean ± SD Scr was 1.41 ± 0.95 mg/dl. Kidney function was estimated by using two versions of the four‐variable MDRD equation and four versions of the Cockcroft‐Gault equation. Mean estimated GFRs ranged from 52.3–73.1 ml/minute. Dosing for cefepime, levofloxacin, meropenem, and piperacillin‐tazobactam was determined using the two equations that had the highest level of correlation; these were the MDRD equation unadjusted for body surface area and the Cockcroft‐Gault equation adjusted for ideal body weight and Scr. When the total daily doses based on these two equations for the four antimicrobials were compared, the discordance rate was 22.8–36.3%, and statistically significant differences were observed for most of the discordant doses. When discordance was present, the MDRD equation resulted in a higher dose of the drug.

Conclusion. Discordance rates for drug dosing ranged from 22.8–36.3% between the MDRD and Cockcroft‐Gault methods for estimating GFR. Although use of the MDRD equation is a well‐accepted and accurate method of estimating GFR to stage chronic kidney disease, our results demonstrated a significant difference in drug dosing regimens between the MDRD method and the Cockcroft‐Gault method.
Simvastatin‐Ezetimibe‐Induced Hepatic Failure Necessitating Liver Transplantation
Authors: Tuteja Sony , Pyrsopoulos Nikolaos T. , Wolowich William R. , Khanmoradi Kamran , Levi David M. , Selvaggi Gennaro , Weisbaum Geoffrey , Tzakis Andreas G. , Schiff Eugene R.
Published: August 2008

Serum aminotransferase elevations are a commonly known adverse effect of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin‐ezetimibe. We describe a 70‐year‐old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg‐ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work‐up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatin‐ezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work‐up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate‐to‐severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2‐year follow‐up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin‐ezetimibe‐induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatin‐ezetimibe‐induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin‐ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.
Diabetic Ketoacidosis Associated with Aripiprazole
Authors: Makhzoumi Zaineb H. , McLean Leon P. , Lee Jefferson H. , Ibe Ada I.
Published: August 2008

Metabolic adverse effects such as hyperglycemia, alterations in insulin sensitivity, and weight gain are known to be potential complications of atypical antipsychotic therapy. In certain cases, hyperglycemia may be so profound that diabetic ketoacidosis (DKA) or hyperosmolar coma may result. Aripiprazole, approved by the United States Food and Drug Administration in 2002, appears to have fewer metabolic adverse effects than other atypical antipsychotics. We describe a 44‐year‐old man with no personal or family history of diabetes mellitus who was prescribed aripiprazole for schizoaffective disorder. Two weeks after starting this therapy, the patient developed DKA, which was corrected with insulin therapy and aggressive hydration. According to the Naranjo adverse drug reaction probability scale, aripiprazole was the probable trigger of his DKA. An exhaustive search for other causes of DKA was unrevealing. Administration of aripiprazole or any other atypical antipsychotic should be terminated when impaired glucose tolerance is suspected. Vigilance regarding the potential adverse effects of this class of drugs, including new agents such as aripiprazole, is crucial to preventing potentially life‐threatening complications of hyperglycemia.
Research in Women and Special Populations
Authors:   American College of Clinical Pharmacy, Cheang Kai I. , Ott Carol , Garner Sandra , Campbell Hope , Hansen Laura , Ma Qing , Nazeri Elaheh , Gunning Karen , Wermeling Daniel
Published: August 2008

The American College of Clinical Pharmacy charged a Task Force on Research in Special Populations to review, update, and broaden its 1993 White Paper on Women as Research Subjects. Participants of the task force included pharmacy clinicians and investigators in the field. This resulting White Paper, Research in Women and Special Populations, discusses the current concepts regarding the conduct of research in women, as well as in special populations such as children, elderly, minorities, cognitively impaired, and other vulnerable populations (e.g., prisoners and refugees). For each specific population, the barriers to research participation, current guidelines and regulations, and available recommendations to address these barriers are discussed. The participation in research by these populations requires addressing special social and ethical challenges. Clinical pharmacy researchers should be cognizant of these guidelines and be an advocate for the inclusion and the rights of women and special populations in research participation.
Briefing: Agriculture and development
Authors: Mantell S. , Hove P. Van
Published: August 2008

Agriculture is closely linked to many concerns, including biodiversity loss, global warming and water availability. The recent International Assessment of Agricultural Science and Technology for Development (IAASTD) report, published on 15 April 2008, considers ways to reduce hunger and poverty, improve rural livelihoods and foster equitable and sustainable development. Sponsored by the United Nations, the World Bank and the Global Environment Facility, it represents a 3-year effort by approximately 400 experts worldwide working under the auspices of 30 governments and 30 representatives of civil society. This briefing provides a summary of the report's findings.
Assessing ‘carbon balance’ of intelligent transport schemes
Authors: Patey I. , Conquest J. , Holt A.
Published: August 2008

This paper considers how carbon costs and savings can be estimated and used as a tool, in a similar manner to the standard financial assessment tools, when assessing intelligent transport systems (ITS) schemes. This is a novel approach and one that may provide useful insights when considering investments in transport systems, especially in the light of climate change and rising energy costs. The scope and application of ITS is too broad to be considered in its entirety in one paper, so this paper considers one example—the M25 junctions 15 to 16 variable mandatory speed limit (VMSL) scheme—as a case study to determine both the carbon dioxide (CO2) costs and benefits over the life of the project. ITS can be used to reduce harmful emissions, contributing to enhanced air quality and reduced effects on climate change from CO2. The CO2 produced when constructing, operating and eventually decommissioning these schemes is, however, often overlooked. This paper considers the balance in carbon use between the building and operating of ITS-based traffic congestion management schemes and the resultant reduction in emissions from traffic. While the calculations relate to the specific example (M25 VMSL), the principals can be adopted, and further refined, for other ITS schemes.
Investigating the Relationship Between Advertising and Pricing in a Channel with Private Label Offering: A Theoretic Model
Authors: Karray Salma , Martín-Herrán Guiomar
Published: August 2008

We study the relationship between pricing and advertising decisions in a distribution channel where national brands are competing with a private label. We solve a three-stage game-theoretic model where the national brands compete on advertising and prices, and the retailer is investing in umbrella advertising for the store and is selling a private label. The obtained equilibrium strategies highlight the importance of determining the complementary or competitive roles of advertising to better understand the relationship between advertising and prices, and to better adjust strategies to varying competition levels in the marketplace. In particular, we find that advertising that expands the national brands' sales gives pricing power to manufacturers. However, persuasive advertising can create different effects on prices depending on the strength of the advertising effect and on the price competition level between the national and the store brands. For highly competitive advertising effects, the retailer should charge lower prices for the private label when it carries highly advertised national brands, increase the national brand's price that is being advertised and decrease the price of the competing national brand. The retailer's advertising leads to higher prices for the national and private labels. We consider several extensions of the base model (retail competition, asymmetric manufacturers and dynamic effects of advertising) and show that our results still hold in such settings. Marketing implications and comparative statistics are also discussed.
Letter: The Spence Commission and the Washington Consensus
Authors: Williamson John
Published: August 2008

John Williamson, the originator of the term "Washington consensus," takes issue with Dani Rodrik's contrast of the Spence report with that consensus.
Comparative Analysis of CAM Use in the U.S. Cancer and Noncancer Populations
Authors: Fouladbakhsh Judith M. , Stommel Manfred
Published: August 2008

Background: Complementary and alternative medicine (CAM) therapies are often used with conventional medical treatments, hence it is important for healthcare providers to understand factors influencing use and implications for patient care. Method: This study compared patterns and predictors of use of CAM providers, practices, and products among the U.S. cancer and noncancer population. Predisposing, enabling, and need factors in the CAM Healthcare Model were examined for ability to predict CAM use from a health service utilization perspective. A secondary analysis of the 2002 National Health Interview Survey was conducted for population estimation using STATA 9.2 software. The analysis compared CAM use by cancer survivors (N=2,262; estimated cancer population=14.3 million) and individuals without cancer (N=28,734; estimated population=191.5 million). Multinomial Logistic Regression identified between-subject differences and allowed for population comparison. Results: Data suggest that cancer survivors and noncancer populations differ in their CAM use patterns, with cancer survivors more likely to use CAM. Conclusion: While these patterns may have begun during the initial period of cancer diagnosis and treatment, they continue among long-term survivors. Predisposing, enabling, and need factors were strong predictors of CAM use in both populations.
Effect of the NaOH Concentration and Temperature on the Dissolution Mechanisms of ß-Lactoglobulin Gels in Alkali
Authors: Mercadé-Prieto Ruben , Wilson D. I. , Paterson William R.
Published: August 2008

The dissolution mechanisms of model protein gels (made from a single protein, ß- lactoglobulin) in alkali were studied at different NaOH concentrations and temperatures. A recent study has shown that the free volume within the swollen gel is a key parameter that determines the dissolution rate (Food Hydrocolloids (2007) 21:1275). This suggests that proteins diffuse in the swollen gel next to the solution before they are dissolved. We extend this hypothesis here by showing that only small oligomers (trimers and smaller), such as those formed after the cleavage of large aggregates, are likely to diffuse throughout the gel. Large aggregates (> 200 kDa) are considered to disentangle at the gel/solvent interface. Size exclusion chromatography has been used to determine the size distributions of the aggregates released from the gel matrix, and to follow the breakdown kinetics of soluble aggregates in alkaline conditions. Analysis of the dissolution process at different temperatures reveals that at low NaOH concentrations (< 0.1 M), the breakdown of large aggregates in alkali exhibits a temperature dependency different from that of the overall dissolution process. At high NaOH concentrations (> 0.3 M), where swelling is inhibited, the increase in the dissolution rate seems to be related to the destruction of cross-linked aggregates, in particular via the beta-elimination of intermolecular disulfide bonds. A previously unobserved type of dissolution behavior at 0.87 M NaOH and at high temperatures is reported.
Heat Pump Drying Kinetics of Spanish Cheese
Authors: Alves-Filho Odilio , Eikevik Trygve M.
Published: August 2008

The manchego and mallorquin cheeses are produced under controlled conditions and long time is needed to develop unique texture and flavor. This traditional manufacturing method has challenges to be addressed by new technologies. Tests were performed to verify feasibility of application of heat pump technology for cheese drying and ripening. The measured kinetic data was fitted by three models to quantify moisture removal rates. Analysis revealed that this modern technology fits well this application and that it promoted similar or higher removal rates than traditional methods. Moreover, the highly efficient heat pump thermodynamic cycle leads to added benefits related to energy, costs and environment.