bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of antidepressant treatment on gene expression profile in mouse brain: cell type‐specific transcription profiling using laser microdissection and microarray analysis
Authors: Boehm C. , Newrzella D. , Herberger S. , Schramm N. , Eisenhardt G. , Schenk V. , Sonntag‐Buck V. , Sorgenfrei O.
Published: March 2006

A gene expression study of mice treated with the tricyclic antidepressant amitriptyline was performed. To enable the detection of cell type‐specific expression changes, laser‐microdissected nucleus accumbens was analysed after 4 and 28 days of treatment. After 4 days of treatment no significantly regulated genes could be detected in this study. In contrast, 95 genes exhibited different expression levels in animals treated for 28 days with amitrityline compared with sham animals. This observation reflects the long‐term effects and adaptation processes observed in patients treated with this drug. Among the regulated genes are receptors belonging to the dopamine‐dependent signalling cascade, ion channels (mainly voltage‐dependent potassium and calcium channels) potentially involved in signalling cascades and neuropeptides. The results support the hypothesis that the therapeutic effect of this antidepressant is much more complex and not confined to a reuptake inhibition of neurotransmitters. Paradigms inducing only weak expression changes, which may be limited to certain cell types within the highly complex brain structure, can therefore be reliably investigated by applying a cell type‐specific expression profiling technique based on laser microdissection and subsequent RNA amplification followed by DNA microarray analysis.
Lipocalin‐type prostaglandin D synthase is up‐regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides
Authors: Mohri Ikuko , Taniike Masako , Okazaki Issei , Kagitani‐Shimono Kuriko , Aritake Kosuke , Kanekiyo Takahisa , Yagi Takashi , Takikita Shoichi , Kim Hyung‐Suk , Urade Yoshihiro , Suzuki Kinuko
Published: March 2006

Lipocalin‐type prostaglandin (PG) D synthase (L‐PGDS) is a dually functional protein, acting both as a PGD2‐synthesizing enzyme and as an extracellular transporter of various lipophilic small molecules. L‐PGDS is expressed in oligodendrocytes (OLs) in the central nervous system and is up‐regulated in OLs of the twitcher mouse, a model of globoid cell leukodystrophy (Krabbe's disease). We investigated whether up‐regulation of L‐PGDS is either unique to Krabbe's disease or is a more generalized phenomenon in lysosomal storage disorders (LSDs), using LSD mouse models of Tay–Sachs disease, Sandhoff disease, GM1 gangliosidosis and Niemann–Pick type C1 disease. Quantitative RT‐PCR revealed that L‐PGDS mRNA was up‐regulated in the brains of all these mouse models. In addition, strong L‐PGDS immunoreactivity was observed in OLs, but not in either astrocytes or microglia in these models. Thus, up‐regulation of L‐PGDS appears to be a common response of OLs in LSDs. Moreover, surface plasmon resonance analyses revealed that L‐PGDS binds GM1 and GM2 gangliosides, accumulated in neurons in the course of LSD, with high affinities (KD = 65 and 210 nm, respectively). This suggests that L‐PGDS may play a role in scavenging harmful lipophilic substrates in LSD.
Archaeal diversity and geochemical energy yields in a geothermal well on Vulcano Island, Italy
Authors: ROGERS K. L. , AMEND J. P.
Published: March 2006

The archaeal diversity in a shallow geothermal well on Vulcano Island, Italy was characterized using culture‐independent 16S rDNA sequence analysis. Environmental DNA was extracted from 56 °C well water, and the 16S ribosomal RNA gene was amplified with archaea‐specific primers. Restriction fragment length polymorphism (RFLP) analysis of ∼250 clones revealed 35 unique patterns, which were sequenced and analyzed. These yielded 17 operational taxonomic units, of which 13, 3, and 1 were unique cren‐, eury‐, and korarchaeotal sequences, respectively. The majority of the crenarchaeotal phylotypes formed a novel, deeply‐branching clade that includes sequences from other hydrothermal environments, but no cultured representatives. Three phylotypes represent novel lineages in the Thermoproteales and two phylotypes represent a novel genus of Euryarchaeota. One euryarchaeotal phylotype was nearly identical (99%) to Palaeococcus helgesonii, an aerotolerant, hyperthermophilic fermenter previously isolated from the same well. To place this diverse archaeal community in the geochemical framework of this ecosystem, we calculate values of Gibbs free energy of 145 organic and inorganic redox reactions at in situ conditions. Energy yields ranged from 0 to 125 kJ per mole of electrons transferred. The most exergonic organic reactions were organic carbon oxidation with O2 (>100 kJ/mol e−), followed by oxidation with (61–93 kJ/mol e−), Fe(III) (43–60 kJ/mol e−), and S0/ (6–27 kJ/mol e−) as terminal electron acceptors. Overall, energy yields from inorganic reactions were similar to those of the organic reactions considered, but were less systematic with respect to terminal electron acceptor. The oxidation of methane coupled with Fe(III) reduction yielded the most energy (123 kJ/mol e−). However, the most exergonic inorganic reactions were predominantly O2, , or reduction. Reduction of , S0, CO2, and CO yielded significantly less energy (0–18 kJ/mol e−). Metabolisms of the cultured organisms identified in the Pozzo Istmo archaeal clone library were exergonic. However, most of the archaeal diversity remains uncultured and energetic calculations reveal an extensive suite of potential lithotrophic and heterotrophic metabolisms that could be exploited by these novel organisms.
Ethnic Differences in Birth Outcomes in England*
Authors: Dearden Lorraine , Mesnard Alice , Shaw Jonathan
Published: March 2006

This paper uses the Millennium Cohort Study to look at ethnic differences in birth outcomes for a cohort of English children born in 2000 and 2001. There is an increasingly large literature showing that longer gestation and higher birthweight are positively associated with cognitive and non‐cognitive outcomes later in life, so understanding sources of ethnic differences in these outcomes and identifying factors that may influence birth outcomes has a lot of potential policy interest. This paper shows that even after controlling for background characteristics in a number of ways, there still remain unexplained differences in both gestation and birthweight outcomes across broad ethnic groups. It also suggests, however, that there may be potential policy levers that could be used to narrow this ethnic gap in birth outcomes, such as reducing the proportion of underweight Asian mothers and overweight Black mothers and increasing ethnic minority attendance at antenatal classes.
UNRESOLVED ISSUES IN DIALYSIS: Revisiting the Hemodialysis Dose
Authors: Leypoldt John K. , Cheung Alfred K.
Published: March 2006

An adequate dose of hemodialysis is currently defined by the Kidney Disease Outcomes Quality Initiative (K/DOQI) and European guidelines as a delivered single‐pool urea Kt/V (spKt/V) of 1.2 and 1.4, respectively. Results from several studies, in particular the Hemodialysis (HEMO) study, have largely supported the legitimacy of these guidelines, although they may need to be altered or amended for certain patient subgroups. This review discusses several potential changes to current guidelines based on recent clinical outcome studies. The following questions are addressed: 1) Should the dialysis dose for low molecular weight water‐soluble solutes (i.e., urea) be normalized by the body distribution volume for urea? 2) Should spKt/V or equilibrated Kt/V (eKt/V) be used for routine monitoring of the hemodialysis dose? 3) Should the dialysis dose for small solutes be dependent on gender? 4) Should the dialysis dose for middle molecules be used in clinical practice? 5) What should be the dialysis dose when using hemodialysis treatment strategies that are more frequent than thrice weekly?
UNRESOLVED ISSUES IN DIALYSIS: Revisiting the Peritoneal Dialysis Dose
Authors: Moran John , Correa‐Rotter Ricardo
Published: March 2006

The question of the minimum dose for adequate peritoneal dialysis has been settled following the publication of two randomized controlled studies and a number of nonrandomized studies. This review summarizes these studies, concluding that these studies support a weekly total Kt/V of 1.7 as the minimum dose, with careful observation for symptoms or signs of uremia and adjustment of the clearance as indicated.
UNRESOLVED ISSUES IN DIALYSIS: Dialysis‐Related Amyloidosis: Late Finding or Hidden Epidemic?
Authors: Dember Laura M. , Jaber Bertrand L.
Published: March 2006

Dialysis‐related amyloidosis is a complication of end‐stage renal disease (ESRD) that results from retention of β2‐microglobulin (β2M) and its deposition as amyloid fibrils into osteoarticular tissue. The clinical manifestations usually develop after several years of dialysis dependence and include carpal tunnel syndrome, destructive arthropathy, and bone cysts and fractures. High‐flux membranes, daily dialysis, and hemofiltration all would be expected to delay the onset of dialysis‐related amyloidosis because, to varying degrees, each increases the clearance of β2M from the plasma. Thus what is currently a late complication of ESRD might become an even later complication as dialysis practices change. The significance of histologically evident but clinically silent β2M amyloid, detectable not only in osteoarticular tissue but also in blood vessels, is unclear. Accumulating evidence that amyloidogenic proteins have direct and specific effects on cell processes irrespective of the extent of amyloid deposition raises the possibility that early, clinically silent β2M amyloid deposits have unrecognized importance.
UNRESOLVED ISSUES IN DIALYSIS: Extracorporeal Strategies for the Removal of Middle Molecules
Authors: Winchester James F. , Audia Patrick F.
Published: March 2006

Uremic toxins with a molecular weight of less than 500 Da are classified as small nitrogenous waste products. They are highly water soluble, relatively homogeneous, and have no protein binding. Other uremic retention toxins differ significantly from the small nitrogenous metabolite class in molecular weight, heterogeneity, protein binding, and hydrophobicity. The European Uremic Toxin Work Group subdivided molecules into two categories: protein‐bound solutes and middle molecules. Middle molecules were defined as toxins in the molecular weight range of 500–60,000 Da, which exceeds the molecular weight of 2000 Da defined in the original middle molecule hypothesis. Under this new proposed definition, most of these middle molecules are low molecular weight peptides and proteins (LMWPs). This concise review focuses on LMWPs. The metabolism of LMWPs is described, including molecular weight, physical conformation, and charge. Factors influencing dialytic removal of LMWPs such as membrane characteristics, protein–membrane interactions, and solute removal mechanisms, as well as strategies to enhance clearance of these compounds are discussed.
UNRESOLVED ISSUES IN DIALYSIS: Inflammatory Biomarkers and Cardiovascular Risk: Association or Cause and Effect?
Authors: Rao Madhumathi , Jaber Bertrand L. , Balakrishnan Vaidyanathapuram S.
Published: March 2006

With the current understanding that atherosclerosis is an inflammatory disorder, markers of the associated systemic inflammatory response have been extensively studied as predictors of cardiovascular disease. Recently the use of high‐sensitivity C‐reactive protein (hsCRP) has been proposed for risk assessment in individuals at intermediate risk of coronary heart disease. The traditional view of inflammatory biomarkers, including CRP, regards them as risk markers rather than risk factors. Either category of marker would serve a diagnostic role, monitor disease activity, and indicate the efficacy of therapy or changing prognosis. However a risk factor with a causal role would be a potential target for therapy. This review discusses the available evidence that argues for and against a causal role for inflammatory biomarkers, with specific reference to CRP, in the atherosclerotic process.
UNRESOLVED ISSUES IN DIALYSIS: Why Do Patients Sleep on Dialysis?
Authors: Gul Ambreen , Aoun Naim , Trayner Edwin M.
Published: March 2006

Sleep‐associated symptoms and excessive daytime sleepiness are felt to be more common in dialysis patients. Several surveys conducted in this patient population have identified a prevalence of sleep disturbances in up to 80% of patients. This review article summarizes common disorders associated with sleep disturbances in dialysis patients, including sleep‐disordered breathing, restless legs syndrome, and major depression. Special attention is given to pathophysiological processes and effective approaches for the prevention and timely treatment of these conditions, which in turn reduces the substantial morbidity associated with sleep disturbances.
UNRESOLVED ISSUES IN DIALYSIS: Long‐Term Management of the Tunneled Venous Catheter
Authors: Liangos Orfeas , Gul Ambreen , Madias Nicolaos E. , Jaber Bertrand L.
Published: March 2006

Despite their propensity for significant complications, tunneled central venous catheters have become a common means of vascular access in the United States for patients requiring maintenance hemodialysis for end‐stage renal disease (ESRD). Reasons for their use include advanced patient age, peripheral vascular disease (arterial and venous), late referral for creation of vascular access, and more importantly, the lack of an interdisciplinary service line on vascular access among vascular surgeons, radiologists, and nephrologists. This review article summarizes complications commonly encountered in dialysis patients who use tunneled central venous catheters for vascular access—mainly thrombosis, stenosis, and infection. Special attention is given to novel approaches for the prevention of catheter‐associated infections. Effective prevention and timely treatment of common catheter‐associated complications can reduce the substantial morbidity associated with the use of these devices. However, these measures should not detract from the goal of avoiding or limiting the long‐term use of catheters, thereby optimizing vascular access management by ensuring the timely availability of functioning arteriovenous fistulas.
UNRESOLVED ISSUES IN DIALYSIS: Dialysis Modality and Dosing Strategy in Acute Renal Failure
Authors: Palevsky Paul M.
Published: March 2006

Many fundamental aspects of the management of renal replacement therapy (RRT) in acute renal failure (ARF) remain unresolved. While data from multiple studies support the initiation of RRT, in the absence of other indications, when the BUN has reached a level of approximately 90–100 mg/dl, there are conflicting data regarding the benefit of earlier initiation of renal support. The relative efficacy of the various RRT modalities is uncertain. Despite growing utilization, a survival benefit or greater recovery of renal function has not been demonstrated for continuous renal replacement therapy (CRRT) as compared to conventional intermittent hemodialysis (IHD). Optimal dosing strategies are also poorly defined. While there is increasing evidence that more intensive renal support is associated with better outcomes in ARF, an optimal Kt/Vurea and treatment frequency for IHD remain to be established. Similarly, although data suggest that continuous venovenous hemofiltration (CVVH) should be dosed at no less than 35 ml/kg/hr (postdilution), confirmation of this dosing strategy and validation for other modalities of CRRT are required.
Interventional Nephrology in Puerto Rico
Authors: Leon Francisco Torre , Bermudez Carlos Rivera , Hernandez Victor , Silva Jose , Delpin Eduardo Santiago
Published: March 2006

Vascular access is emerging as a critical issue for hemodialysis patients in Puerto Rico. In more than 50% of the hemodialysis patients, tunneled hemodialysis catheters are the sole access for providing dialysis therapy. Most disturbing is the fact that a significant number of these catheters are nontunneled temporary catheters, sometimes placed in the subclavian vein. These facts have contributed significantly to the morbidity and mortality seen in chronic dialysis patients. In addition, many cases of early or late dysfunction of arteriovenous access are not detected and treated in a timely manner due to the lack of a comprehensive vascular access program for end‐stage renal disease (ESRD) patients. In fact, monitoring programs to identify and detect vascular access dysfunction are virtually nonexistent in many chronic dialysis units. Even when diagnosed, it is not treated in a timely fashion. Recently literature has shown that procedure‐related delays in the treatment of patients with renal disease can be minimized and nephrology care more efficiently delivered by a nephrologist trained in nephrology‐related procedures. In an effort to optimize the care of our ESRD patients, we took the initiative to develop an interventional nephrology program that effectively deals with vascular access‐related procedures in a timely manner. This approach has minimized delays, decreased hospitalizations and the use of temporary catheters, and improved the medical care of our chronic dialysis patients. So far we have performed more than 400 procedures in the 6 months since the initiation of the program. In this article we describe our initial experience with interventional nephrology in Puerto Rico.
Salvage of Problematic Peritoneal Dialysis Catheters
Authors: Asif Arif , Gadalean Florin , Vieira Cristovao F. , Hogan Renee , Leon Carlos , Merrill Donna , Ellis Renee , Amador Amarilys , Broche Osmany , Bush Barbara , Con Treras Gabriel , Pennell Phillip
Published: March 2006

Peritoneal dialysis (PD) is a markedly underutilized modality for permanent renal replacement therapy in the United States owing to a low rate of patient referral and high rate of patient dropout or transfer to hemodialysis. One cause for patient loss from PD is problematic PD catheters that often are removed rather than being subjected to simple surgical salvage procedures. We report three patients with problematic catheters and our approach to their management. The first patient developed erosion of the skin overlying the portion of the catheter between the deep and superficial cuffs after 6 months of PD. The second patient developed extrusion of the superficial cuff after 4 years of PD. The third patient demonstrated a localized abscess at the incision site for catheter insertion after 3 years of PD. Other than a mild superficial exit site infection and localized abscess in the second and third patient, respectively, there were no associated infections of the catheter tunnel and cuff or of the peritoneal cavity as determined by either clinical examination, ultrasound evidence of fluid collection, or cultures and white blood cell counts. All three cases were managed successfully by interventional nephrology on an outpatient basis and under local anesthesia without either catheter removal or placement of a new PD catheter. It was possible to continue uninterrupted PD in the first and third patients, while the second patient had temporary hemodialysis to allow for complete healing of the surgical wound. We conclude that in selected cases simple interventions can salvage problematic PD catheters and maintain patients on PD.
ASDIN Clinical Case Focus: Cause for Inadequate Clearance: Hemodialysis Catheter Migration into the Coronary Sinus
Authors: Brucculeri Michael , Licht Jonah , Serur David , Cheigh Jhoong
Published: March 2006

Complications associated with central dialysis catheters prove to be an important source of morbidity that challenge patients and clinicians alike. While thrombosis, stenosis, and infection remain the most common threats to functioning central dialysis catheters, malposition of such devices may similarly result in serious consequences. Despite advanced techniques used to confirm initial catheter placement, the very nature of these catheters entails frequent manipulation for vascular access and therefore they may migrate after repeated use. When compared with the loss of patency and infection, complications involving malposition or migration may present in a more insidious fashion, such as a gradual decline in achievable blood flow rate or observed clearance over time. We describe a patient who acutely developed both clinical and biochemical evidence of inadequate clearance after several months of suboptimal catheter function. When the central dialysis catheter was examined fluoroscopically, it was found to have migrated into the coronary sinus.
RESPONSE OF A LENTIC PERIPHYTON COMMUNITY TO NUTRIENT ENRICHMENT AT LOW N:P RATIOS1
Authors: Luttenton Mark R. , Lowe Rex L.
Published: March 2006

We examined the effect of nitrogen:phosphorus (N:P) ratios and nutrient concentrations on periphyton when nutrients (N and P) are provided in excess. A gradient of seven N:P ratios ranging from 7.5:1 to 1:7.5 and each at three absolute concentrations, was established using nutrient‐releasing substrata placed in a meso‐oligotrophic lake. Differences in total algal biovolume among nutrient ratios were significant (analysis of covariance [ANCOVA]) when P concentration was entered as the co‐variate. In addition, total algal biovolume was significantly correlated with N concentration but not P. To further evaluate the relationship between nutrient ratios and biovolume, we analyzed (using four 1‐way analysis of variances [ANOVAs]) four subsets of data defined as a series of treatments where one nutrient concentration remained relatively constant as the other changed creating different N:P ratios. Ratios of data subsets ranged from 1:1 to 7.5:1 and 1:1 to 1:7.5 with low and high concentrations of both series. Only diatom biovolume varied with ratio but these differences are most likely related to increased green algal abundance. Species richness and diversity differed among N:P ratios (ANCOVA) when P concentration was used as the co‐variate. Stigeoclonium tenue (Ag.) Gomont, which generally accounted for the increase in green algal abundance, varied with nutrient ratio (ANCOVA) when P was the co‐variate. Based on the ANCOVAs, correlations, and one‐way ANOVAs, periphyton in this system appears to be affected by N concentration but not by N:P treatment ratios under nutrient‐rich conditions. When compared with previous studies, these data also suggest that the response of periphyton to in situ treatments constructed with nutrient‐releasing substrata vary between years.
EVALUATION OF PIGMENT EXTRACTION METHODS AND A RECOMMENDED PROTOCOL FOR PERIPHYTON CHLOROPHYLL a DETERMINATION AND CHEMOTAXONOMIC ASSESSMENT1
Authors: Hagerthey Scot E. , William Louda J. , Mongkronsri Panne
Published: March 2006

Many methods have been proposed to extract and quantify algal pigments. Comparative studies have found that pigment extraction efficiency varies among solvent and mechanical disruption protocols due to differential cellular resistance, thereby, leading to potential misinterpretation of pigment data. When the type or resistance of algae are unknown, a method is required that efficiently extract pigments from all taxonomic groups. The objective of this study was to develop a simple and efficient one stage periphyton pigment extraction protocol by comparing the extractability of four solvents (acetone, methanol, methanol/acetone, and methanol/acetone/N,N‐dimethylformamide), the effects of grinding, and the effects of freeze‐drying. The best overall extraction was obtained using freeze‐dried samples extracted with methanol/acetone/DMF/water (MAD). Eighty‐six percent more chlorophyll was extracted when the sample was freeze‐dried relative to fresh/frozen samples extracted with 90% acetone. Freeze‐drying greatly improved the extraction of both polar and non‐polar (lipophilic/hydrophobic) pigments while MAD increased the extractability of polar pigments and improved peak resolution of all pigments. Chemotaxonomic assessment differed between samples that were fresh/frozen or freeze‐dried before extraction. The relative abundance of cyanobacteria was greater for freeze‐dried material compared with fresh/frozen due to the improved extractability of cyanobacterial pigments. Based on the results of this study, the traditional approach of 90% acetone as a solvent is not recommended for periphyton samples containing cyanobacteria or when the composition of the mat is unknown. The combination of freeze‐drying and MAD was sufficient for the extraction of pigments from a periphyton mat containing filamentous cyanobacteria, green algae, and diatoms.
MORPHOLOGICAL CHANGES IN MITOCHONDRIAL AND CHLOROPLAST NUCLEOIDS AND MITOCHONDRIA DURING THECHLAMYDOMONAS REINHARDTII(CHLOROPHYCEAE) CELL CYCLE1
Authors: Hiramatsu Takayoshi , Misumi Osami , Kuroiwa Tsuneyoshi , Nakamura Soichi
Published: March 2006

Morphological changes in the organellar nucleoids and mitochondria of livingChlamydomonas reinhardtiiDang were examined during the cell cycle under conditions of 12:12 light:dark. The nucleoids were stained with SYBR‐Green I, and the mitochondria were stained with 3,3‐dihexyloxacarbocyanine iodide. An mocG33 mutant, which contains one large chloroplast nucleoid throughout the cell cycle, was used to distinguish between the mitochondrial and chloroplast nucleoids. Changes in the total levels of organellar DNA levels were assessed by real‐time PCR. Each of the G1, S, M, and Smt,cp phases was estimated. At the start of the light period, the new daughter cells were in G1and contained about 30 mitochondrial and 10 chloroplast nucleoids, which were dispersed and had diameters of 0.1 and 0.2 μm, respectively. During the G1phase of the light period, and at the start of the S phase, both nucleoids formed short thread‐like or bead‐like structures, probably divided, and increased continuously in number, concomitantly with DNA synthesis. The nucleoids probably became smaller due to the decrease in DNA of each particle and were indistinguishable. The cells in the S and M phases contained extremely high numbers of scattered nucleoids. However, in the G1phase of the dark period, the nucleoids again formed short thread‐like or bead‐like structures, probably fused, and decreased in number. The mitochondria appeared as tangled sinuous structures that extended throughout the cytoplasm and resembled a single large mitochondrion. During the cell cycle, the numbers of mitochondrial nucleoids and sinuous structures varied relative to one another.
Advances in the Pharmacotherapy of Alcoholism: Challenging Misconceptions
Authors: Kranzler Henry R. , Koob George , Gastfriend David R. , Swift Robert M. , Willenbring Mark L.
Published: March 2006

This article highlights the proceedings of a symposium presented at the 28th Annual Scientific Meeting of the Research Society on Alcoholism in Santa Barbara, CA, June 27, 2005. The organizer and chair was Henry R. Kranzler. The presentations included: (1) Introduction, by Henry R. Kranzler; (2) Neurobiology of Alcohol Dependence: Implications for Medical Treatment, by George Koob; (3) Advances in Alcoholism Pharmacotherapy, by Henry R. Kranzler; (4) Patient Acceptance of Alcoholism Pharmacotherapy, by David R. Gastfriend; (5) System Challenges in the Adoption of Pharmacotherapy, by Robert M. Swift; and (6) Pharmacotherapy for Alcohol Dependence: Strengths, Challenges, and Future Directions, by Mark L. Willenbring.
Capturing the Moment: Innovative Approaches to Daily Alcohol Assessment
Authors: Neal Dan J. , Fromme Kim , Del Boca Frances K. , Parks Kathleen A. , King Linda P. , Pardi Ann M. , Collins R. Lorraine , Muraven Mark , Vetter Charlene , Corbin William R.
Published: March 2006

This article is a summary of a symposium presented at the 2005 Research Society on Alcoholism annual conference organized by Dan J. Neal and chaired by William R. Corbin. Event‐level data, wherein each “event” (e.g., day) is captured as its own data point, capture the complex patterns of drinking and other high‐risk behaviors in ways that the typical aggregate approach cannot. Because of their richness, methodologies that incorporate event‐level data are becoming more common in alcohol research. At least 3 distinct forms of event‐level data can be gathered: retrospective data (those collected on a single occasion, using memory aids to help each participant reconstruct all drinking events over a specific period of time), daily monitoring data (reporting on all events for that day), and momentary assessment (those recorded immediately following a drinking event or in response to a prompt from researchers). The goal of this symposium was to address many issues associated with event‐level methodology, as well as demonstrate projects that are currently implementing such innovative data collection. The 4 presentations included in this symposium were “Realizing the Promise and Avoiding the Pitfalls of Retrospective Daily Estimation Assessments of Alcohol Use” by Frances K. Del Boca; “Using Interactive Voice Response Technology to Assess the Alcohol‐Victimization Link” by Kathleen Parks, Linda King, and Ann Pardi; “Methodological Issues in Using Personal Data Assistants to Self‐monitor Alcohol Consumption” by R. Lorraine Collins, Mark Muraven, and Charlene Vetter; and “Collecting Event‐level Data Using the World Wide Web” by Dan J. Neal and Kim Fromme.
BIG News in Alcohol Addiction: New Findings on Growth Factor Pathways BDNF, Insulin, and GDNF
Authors: Janak Patricia H. , Wolf Fred W. , Heberlein Ulrike , Pandey Subhash C. , Logrip Marian. L. , Ron Dorit
Published: March 2006

In recent years, it has become clear that growth factors are not only critical for the development of the central nervous system (CNS) but may also be important contributors to other neuronal functions in the adult brain. This symposium, presented at the 2005 RSA meeting, discussed evidence to support the hypothesis that alterations in growth factor pathways produce dramatic changes in the effects of alcohol on the CNS. The 4 speakers showed that the behavioral effects of alcohol in the adult are regulated by 3 growth factors, insulin, glial cell line–derived neurotrophic factor (GDNF), and brain‐derived neurotrophic factor (BDNF). Dr. Wolf from the Heberlein laboratory presented findings obtained from genetic manipulations in Drosophila melanogaster, demonstrating that the insulin pathway controls sensitivity to the intoxicating effects of alcohol. Marian Logrip from the Ron and Janak laboratories presented evidence obtained in rodents that low concentrations of alcohol increase the expression of BDNF in the brain to regulate alcohol consumption. Dr. Pandey showed that amygdalar BDNF regulates alcohol's anxiolytic effects and preference. Finally, Dr. Janak presented evidence that increases in the expression of GDNF in the midbrain reduce alcohol self‐administration in rats.
Addressing Substance Abuse in Health Care Settings
Authors: Miller William R. , Baca Catherine , Compton Wilson M. , Ernst Denise , Manuel Jennifer K. , Pringle Beverly , Schermer Carol R. , Weiss Roger D. , Willenbring Mark L. , Zweben Allen
Published: March 2006

This article summarizes the proceedings of a roundtable discussion at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California. The chair was William R. Miller. The presentations were as follows: (1) Screening and Brief Intervention for Alcohol Problems, by Allen Zweben; (2) Three Intervention Models and Their Impact on Medical Records, by Denise Ernst; (3) Pharmacotherapies for Managing Alcohol Dependence in Health Care Settings, by Roger D. Weiss; (4) The Trauma Center as an Opportunity, by Carol R. Schermer; (5) Motivational Interviewing by Telephone and Telemedicine, by Catherine Baca; (6) Health Care as a Context for Treating Drug Abuse and Dependence, by Wilson M. Compton; and (7) Interventions for Heavy Drinking in Health Care settings: Barriers and Strategies, by Mark L. Willenbring.
Actions of Acute and Chronic Ethanol on Presynaptic Terminals
Authors: Roberto Marisa , Treistman Steven N. , Pietrzykowski Andrzej Z. , Weiner Jeff , Galindo Rafael , Mameli Manuel , Valenzuela Fernando , Zhu Ping Jun , Lovinger David , Zhang Tao A. , Hendricson Adam H. , Morrisett Richard , Siggins George Robert
Published: March 2006

This article presents the proceedings of a symposium entitled “The Tipsy Terminal: Presynaptic Effects of Ethanol” (held at the annual meeting of the Research Society on Alcoholism, in Santa Barbara, CA, June 27, 2005). The objective of this symposium was to focus on a cellular site of ethanol action underrepresented in the alcohol literature, but quickly becoming a “hot” topic. The chairs of the session were Marisa Roberto and George Robert Siggins. Our speakers were chosen on the basis of the diverse electrophysiological and other methods used to discern the effects of acute and chronic ethanol on presynaptic terminals and on the basis of significant insights that their data provide for understanding ethanol actions on neurons in general, as mechanisms underlying problematic behavioral effects of alcohol. The 5 presenters drew from their recent studies examining the effects of acute and chronic ethanol using a range of sophisticated methods from electrophysiological analysis of paired‐pulse facilitation and spontaneous and miniature synaptic currents (Drs. Weiner, Valenzuela, Zhu, and Morrisett), to direct recording of ion channel activity and peptide release from acutely isolated synaptic terminals (Dr. Treistman), to direct microscopic observation of vesicular release (Dr. Morrisett). They showed that ethanol administration could both increase and decrease the probability of release of different transmitters from synaptic terminals. The effects of ethanol on synaptic terminals could often be correlated with important behavioral or developmental actions of alcohol. These and other novel findings suggest that future analyses of synaptic effects of ethanol should attempt to ascertain, in multiple brain regions, the role of presynaptic terminals, relevant presynaptic receptors and signal transduction linkages, exocytotic mechanisms, and their involvement in alcohol's behavioral actions. Such studies could lead to new treatment strategies for alcohol intoxication, alcohol abuse, and alcoholism.
Searching for the Full Picture: Structural Equation Modeling in Alcohol Research
Authors: Schuckit Marc A. , Windle Michael , Smith Tom L. , Hesselbrock Victor , Ohannessian Christine , Averna Susan , Bauer Lance , Kramer John , Bucholz Kathleen , Sher Kenneth J.
Published: March 2006

This article summarizes the proceedings of a symposium presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. This symposium begins with a description by Michael Windle of structural equation modeling (SEM), including the assets and liabilities of this approach. Next, Marc Schuckit and Tom Smith demonstrate the application of an SEM approach to understanding the impact of a low level of response to alcohol, using data from both adolescent and adult populations. Victor Hesselbrock and colleagues next review the results when an SEM approach is used in the longitudinal study of externalizing behaviors. This is followed by a description of the application of SEM to an affect‐related model as discussed by John Kramer and Kathleen Bucholz. Finally, Kenneth Sher offers thoughts on how to place these findings into perspective.
Impact of Sex: Determination of Alcohol Neuroadaptation and Reinforcement
Authors: Wiren Kristine M. , Hashimoto Joel G. , Alele Paul E. , Devaud Leslie L. , Price Kimber L. , Middaugh Lawrence D. , Grant Kathleen A. , Finn Deborah A.
Published: March 2006

This article represents the proceedings of a symposium at the Research Society on Alcoholism meeting in Santa Barbara, California. The organizers/chairs were Kristine M. Wiren and Deborah A. Finn. Following a brief introduction by Deborah Finn, the presentations were (1) The Importance of Gender in Determining Expression Differences in Mouse Lines Selected for Chronic Ethanol Withdrawal Severity, by Kristine M. Wiren and Joel G. Hashimoto; (2) Sex Differences in Ethanol Withdrawal Involve GABAergic and Stress Systems, by Paul E. Alele and Leslie L. Devaud; (3) The Influence of Sex on Ethanol Consumption and Reward in C57BL/6 Mice, by Kimber L. Price and Lawrence D. Middaugh; and (4) Sex Differences in Alcohol Self‐administration in Cynomolgus Monkeys, by Kathleen A. Grant.
Smoking Comorbidity in Alcoholism: Neurobiological and Neurocognitive Consequences
Authors: Meyerhoff Dieter J. , Tizabi Yousef , Staley Julie K. , Durazzo Timothy C. , Glass Jennifer M. , Nixon Sara Jo
Published: March 2006

Considerable research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as on increased risk for various cancers. However, comparatively little is known about the effects of chronic smoking on brain function. Although smoking rates have decreased in the developed world (they have increased in the developing world), smoking rates have been at a persistently high level in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking and alcohol dependence, very few studies have addressed the separate and interactive effects that smoking and alcoholic drinking may have on neurobiology and brain function. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Santa Barbara, California, on June 29, 2005, postulates that the neurobiologic and neurocognitive abnormalities commonly described in studies of alcohol‐dependent individuals are modulated by concurrent abuse of tobacco products and that brain recovery in abstinent alcoholic individuals is affected by chronic smoking. Four expert speakers and a discussant from different research disciplines focus in this symposium on the description of neurobiological and neurobehavioral effects because of concomitant drinking and smoking. Understanding the potential separate effects and interactions of chronic nicotine/smoking and alcohol consumption promotes a better understanding of specific mechanisms and neurocognitive consequences of brain injury and brain recovery with abstinence. The material presented contributes useful information to ongoing discussions about treatment strategies for these comorbid disorders and valuable educational material that can be used to affect public perception about smoking and perhaps health policy.
Long‐Term Posttreatment Functioning Among Those Treated for Alcohol Use Disorders
Authors: Clifford Patrick R. , Maisto Stephen A. , Stout Robert L. , Mckay James R. , Tonigan J. Scott
Published: March 2006

This article summarizes the proceedings of a symposium that was organized and chaired by Patrick R. Clifford and presented at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California. The aims of the presentation were to focus on the prediction and explanation of longer‐term functioning following alcohol use disorders (AUD) treatment. Along these lines, Stephen A. Maisto, PhD, presented data (i.e., Project MATCH outpatient sample) on the relationship between drinking behavior in the first year following AUD outpatient treatment initiation and functioning at 3‐year follow‐up. Robert L. Stout, PhD, using data from the Extended Case Monitoring Study, analyzed long‐term drinking patterns using shorter‐term information. James R. McKay, PhD, examined the relationship between treatment services received and problem severities across a 2‐year follow‐up period. J. Scott Tonigan, PhD, served as the panel discussant.
Challenges Applying Alcohol Brief Intervention in Diverse Practice Settings: Populations, Outcomes, and Costs
Authors: Saitz Richard , Svikis Dace , D'Onofrio Gail , Kraemer Kevin L. , Perl Harold
Published: March 2006

This article summarizes the proceedings of a symposium at the 2005 Research Society on Alcoholism, Santa Barbara, California. The purpose of the symposium was to address challenges that arise in translating evidence for efficacy of alcohol brief intervention (BI) into diverse clinical settings and populations by reviewing the literature and describing 4 research studies. Dr. Saitz reviewed the limitations in evidence for efficacy of BIs and then described results of a randomized clinical trial of brief motivational intervention for medical inpatients drinking risky amounts. Dr. Svikis presented alternative methods for identifying pregnant women in prenatal care at risk for alcohol and drug problems (including nicotine and caffeine) and BIs to reduce or eliminate use. Dr. D'Onofrio discussed results of a randomized trial of the brief negotiated interview in emergency department patients. Dr. Kraemer presented results of a decision analytic and computer‐simulation model regarding the cost‐effectiveness of alcohol screening and intervention in primary care settings. Finally, Dr. Perl discussed the salient issues and suggested future directions for work in the area of alcohol BI.
Structural and Functional Modifications in Glutamateric Synapses Following Prolonged Ethanol Exposure
Authors: Chandler L. Judson , Carpenter‐Hyland Ezekiel , Hendricson Adam W. , Maldve Regina E. , Morrisett Richard A. , Zhou Feng C. , Sari Youssef , Bell Richard , Szumlinski Karen K.
Published: March 2006

This article summarizes the proceedings of a symposium presented at the 2005 annual meeting of the Research Society on Alcoholism in Santa Barbara, California, USA. The organizer and chair was L. Judson Chandler. The presentations were (1) Chronic Ethanol Exposure, N‐Methyl‐d‐Aspartate (NMDA) Receptor Dynamics, and Withdrawal Hyperexcitability, by Adam Hendricson, Regina Maldve, and Richard Morrisett; (2) Ethanol‐Induced Synaptic Targeting of NMDA Receptors Is Associated With Enhanced Postsynaptic Density‐95 Clustering and Spine Size, by Judson Chandler and Ezekiel Carpenter‐Hyland; (3) Presynaptic and Postsynaptic Alterations in the Nucleus Accumbens Following Chronic Alcohol Exposure, by Feng Zhou, Youssef Sari, and Richard Bell; and (4) An Active Role for Accumbens Homer2 Expression in Alcohol‐Induced Neural Plasticity, by Karen Szumlinski.
The Dynamic Nature of Mobility Disability in Older Persons
Authors: Gill Thomas M. , Allore Heather G. , Hardy Susan E. , Guo Zhenchao
Published: March 2006

OBJECTIVES:

To determine the rates of clinically meaningful transitions in mobility disability; evaluate how these transitions differ according to age, sex, and physical frailty; and depict the duration of the resulting episodes of mobility disability.

DESIGN:

Prospective cohort study.

SETTING:

General community in greater New Haven, Connecticut, from March 1998 to October 2004.

PARTICIPANTS:

Seven hundred fifty‐four community‐living older persons, aged 70 and older, who were nondisabled (i.e., required no personal assistance) in four activities of daily living.

MEASUREMENTS:

Mobility disability, defined as the inability to walk one quarter of a mile and to climb a flight of stairs, respectively without personal assistance, was assessed every month for up to 5 years.

RESULTS:

For both mobility tasks, rates per 1,000 person‐months were higher for transitions from no disability to intermittent disability (34.7 for walking one quarter of a mile and 17.4 for climbing a flight of stairs), intermittent to continuous disability (52.0 and 42.5), continuous to intermittent disability (35.4 and 31.5), and intermittent to no disability (68.6 and 85.4) than for other transitions. Older age, female sex, and physical frailty were associated with greater likelihood of transition to states of greater disability and lower likelihood of regaining independent mobility.

CONCLUSION:

Mobility disability in older persons is a highly dynamic process, characterized by frequent transitions between states of independence and disability. Programs designed to enhance independent mobility should focus not only on the prevention of mobility disability but also on the restoration and maintenance of independent mobility in older persons who become disabled.
The Effect of Emergency Department Crowding on the Management of Pain in Older Adults with Hip Fracture
Authors: Hwang Ula , Richardson Lynne D. , Sonuyi Tolulope O. , Morrison R. Sean
Published: March 2006

OBJECTIVES: To evaluate the effect of emergency department (ED) crowding on assessment and treatment of pain in older adults.

DESIGN: Retrospective review of ED records from a prospective cohort study.

SETTING: Urban, academically affiliated, tertiary medical center.

PARTICIPANTS: One hundred fifty‐eight patients, aged 50 and older, evaluated and hospitalized from the ED with hip fracture.

MEASUREMENTS: Patient‐related risk factors: age, sex, nursing home residence, ED triage status, dementia, Acute Physiology in Age and Chronic Health Evaluation II physiological score, and RAND comorbidity score. ED crowding risk factors: ED census and mean length of stay. Outcomes: documentation of pain assessment, time to pain assessment, time to pain treatment, patients reporting pain receiving analgesia, and meperidine use.

RESULTS: Mean age was 83 (range 52–101), 81.0% of patients complained of pain, mean time to pain assessment was 40 minutes (range 0–600), time to treatment was 141 minutes (range 10–525), and mean delay to treatment was 122 minutes (range 0–526). Of those with pain, 35.9% received no analgesia, 7.0% received nonopioids, and 57.0% received opioids. Of those receiving opioids, 32.8% received meperidine. ED crowding at census levels greater than 120% bed capacity was significantly associated with a lower likelihood of documentation of pain assessment (P=.05) and longer times to pain assessment (P=.01).

CONCLUSION: Older adults with hip fracture are at risk for underassessment of pain, considerable delays in analgesic administration after pain is identified, and treatment with inappropriate analgesics (e.g., meperidine) in the ED. Higher levels of ED census are significantly associated with poorer pain management.
Risk Migration and Scientific Advance: The Case of Flame‐Retardant Compounds
Authors: Alcock Ruth E , Busby Jerry
Published: March 2006

It is a common experience that attempts to mitigate a risk lead to new risks, and that risks formerly thought to be of one kind become another kind as technical knowledge evolves. This phenomenon of risk migration suggests that we should take processes over time, rather than specific risks or specific technologies, as a unit of analysis. Several of our existing models of the social management of risks—such as that of social risk amplification—are process models of a kind but are still oriented around the playing out of a particular event or issue. A case study of risk in a group of flame‐retardant compounds was used as the basis of a grounded, exploratory analysis of migration processes, the phenomena that influence them, and their consequences. This illustrated how migration naturally occurs from risks that are understood, in which risk bearers have at least some agency, to risks that are not understood and not capable of being influenced by risk bearers. It illustrated how the simultaneous improvement in measuring technology, which detects potential toxins at increasingly small concentrations, combines with intuitive models that ignore concentration to produce conditions likely to generate anxiety. And it illustrated how pressure groups and commercial interests exploit this effect. It also showed how migration makes precautionary action problematic, and how more generally it tends to undermine a society's capacity to cope with risk.