bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative role of endogenous leucotrienes and platelet‐activating factor in ischaemia–reperfusion‐mediated tissue injury
Authors: Bitencourt Claudia S. , Bessi Valérie L. , Huynh David N. , Ménard Liliane , Lefebvre Julie S. , Lévesque Tania , Hamdan Leila , Sohouhenou Fanny , Faccioli Lucia H. , Borgeat Pierre , Marleau Sylvie 
Published: November 2013

AbstractInsufficient oxygen delivery to organs leads to tissue dysfunction and cell death. Reperfusion, although vital to organ survival, initiates an inflammatory response that may both aggravate local tissue injury and elicit remote organ damage. Polymorphonuclear neutrophil (PMN) trafficking to remote organs following ischaemia/reperfusion (I/R) is associated with the release of lipid mediators, including leucotriene (LT) B4, cysteinyl‐LTs (CysLTs) and platelet‐activating factor (PAF). Yet, their potentially cooperative role in regulating I/R‐mediated inflammation has not been thoroughly assessed. The present study aimed to determine the cooperative role of lipid mediators in regulating PMN migration, tissue oedema and injury using selective receptor antagonists in selected models of I/R and dermal inflammation. Our results show that rabbits, pre‐treated orally with BIIL 284 and/or WEB 2086 and MK‐0571, were protected from remote tissue injury following I/R or dermal inflammation in an additive or synergistic manner when the animals were pre‐treated with two drugs concomitantly. The functional selectivity of the antagonists towards their respective agonists was assessed in vitro, showing that neither BIIL 284 nor WEB 2086 prevented the inflammatory response to IL‐8, C5a and zymosan‐activated plasma stimulation. However, these agonists elicited LTB4 biosynthesis in isolated rabbit PMNs. Similarly, a cardioprotective effect of PAF and LTB4 receptor antagonists was shown following myocardial I/R in mice. Taken together, these results underscore the intricate involvement of LTB4 and PAF in each other's responses and provide further evidence that targeting both LTs and PAF receptors provides a much stronger anti‐inflammatory effect, regulating PMN migration and oedema formation.
The Mediating Effect of Chronic Pain on the Relationship Between Obesity and Physical Function and Disability in Older Adults
Authors: Fowler‐Brown Angela , Wee Christina C. , Marcantonio Edward , Ngo Long , Leveille Suzanne 
Published: November 2013

ObjectivesTo determine the extent to which bodily pain mediates the effect of obesity on disability and physical function.DesignCross‐sectional analysis.SettingPopulation‐based sample of residents in the greater Boston area.ParticipantsCommunity‐dwelling adults aged 70 and older (N = 736).MeasurementsBody mass index (BMI), obtained from measured height and weight, was categorized as normal weight (19.0–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥30.0 kg/m2). Main outcome measures were the Physical Component Summary of the Medical Outcomes Study 12‐item Short‐Form Survey (PCS), activity of daily living (ADL) disability, and Short Physical Performance Battery (SPPB) score. Chronic pain was assessed according to the number of weight‐bearing joint sites that had pain (hips, knees, feet and pain all over).ResultsOlder obese adults had greater ADL disability and lower SPPB and PCS scores than their nonobese counterparts, although in sex‐stratified adjusted analyses, obesity was adversely associated with outcomes only in women. Obesity was associated with greater number of pain sites; and more pain sites were associated with greater odds of disability. Mediation analysis suggests that pain is a significant mediator (22–44%) of the adverse effect of obesity on disability and physical function in women.ConclusionBodily pain may be an important treatable mediator of the adverse effect of obesity on disability and physical function in women.
“You're Being Paged!” Outcomes of a Nursing Home On‐Call Role‐Playing and Longitudinal Curriculum
Authors: Yuasa Misuzu , Bell Christina L. , Inaba Michiko , Tamura Bruce K. , Ahsan Samina , Saunders Valisa , Masaki Kamal 
Published: November 2013

Effectively handling telephone calls about nursing home (NH) residents is an important skill for healthcare professionals, but little formal training is typically provided. The objective of the current study was to describe and evaluate the effectiveness of a novel structured role‐playing didactic session followed by an on‐call NH longitudinal clinical experience. The effectiveness of the structured role‐playing didactic session was compared in different learners, including geriatric medicine fellows (n = 10), family medicine residents and faculty (n = 14), nurse practitioner students (n = 31), and other learners (n = 7). The curriculum focused on common problems encountered while caring for NH residents during on‐call periods. Learners rated themselves using an 18‐item pre/post questionnaire including five attitude and 13 skills questions, using a 1‐to‐5 Likert scale. T‐tests were used to compare means before and after sessions. Significant improvements were found in overall mean attitudes and skills scores. For all learners, the greatest improvements were seen in “comfort in managing residents at the NH,” “managing feeding or gastrostomy tube dislodgement,” “identifying different availability of medications, laboratory studies, and procedures in NH,” and “describing steps to send NH residents to the emergency department.” Geriatric medicine fellows' attitudes and skills improved significantly after the longitudinal clinical experience. The faculty survey demonstrated improved documentation, communication, and fellows' management of on‐call problems after curriculum implementation. This novel curriculum used role‐playing to provide training for on‐call management of NH residents. This curriculum has been successfully disseminated on a national geriatrics educational resource website (POGOe) and is applicable to geriatric medicine fellowships, internal medicine and family medicine residency programs, and other training programs.
Preliminary Data from an Advanced Dementia Consult Service: Integrating Research, Education, and Clinical Expertise
Authors: Catic Angela G. , Berg Andrea I. , Moran Julie A. , Knopp Julie R. , Givens Jane L. , Kiely Dan K. , Quinlan Nicky , Mitchell Susan L. 
Published: November 2013

Hospitalized individuals with advanced dementia often receive care that is of limited clinical benefit and inconsistent with preferences. An advanced dementia consultation service was designed, and a pre and post pilot study was conducted in a Boston hospital to evaluate it. Geriatricians and a palliative care nurse practitioner conducted consultations, which consisted of structured consultation, counseling and provision of an information booklet to the family, and postdischarge follow‐up with the family and primary care providers. Individuals aged 65 and older with advanced dementia who were admitted were identified, and consultations were solicited using pop‐ups programmed into the computerized provider order entry (POE) system. In the initial 3‐month period, 24 subjects received usual care. In the subsequent 3‐month period, consultations were provided to five subjects for whom they were requested. Data were obtained from the electronic medical record and proxy interviews (admission, 1 month after discharge). Mean age of the combined sample (N = 29) was 85.4, 58.6% were from nursing homes, and 86.2% of their proxies stated that comfort was the goal of care. Nonetheless, their hospitalizations were characterized by high rates of intravenous antibiotics (86.2%), more than five venipunctures (44.8%), and radiological examinations (96.6%). Acknowledging the small sample size, there were trends toward better outcomes in the intervention group, including greater proxy knowledge of the disease, better communication between proxies and providers, more advance care planning, lower rehospitalization rates, and fewer feeding tube insertions after discharge. Targeted consultation for advanced dementia is feasible and may promote greater engagement of proxies and goal‐directed care after discharge.
Use of International Classification of Diseases, Ninth Revision, Clinical Modification, Codes to Identify Inpatient Fall‐Related Injuries
Authors: Waters Teresa M. , Chandler A. Michelle , Mion Lorraine C. , Daniels Michael J. , Kessler Lori A. , Miller Stephen T. , Shorr Ronald I. 
Published: November 2013

ObjectivesTo compare falls and fall‐related injuries that a fall evaluator or hospital incident report identified with injuries identified according to discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes for the same set of inpatient episodes of care.DesignProspective, descriptive study.SettingSixteen adult general medical and surgical units in a major urban teaching hospital.ParticipantsAll adults who sustained a fall with injury during a 5‐year period (380 falls with injury).MeasurementsFalls that a fall evaluator or hospital incident report identified were classified according to their injury severity. Discharge abstracts provided diagnosis codes (ICD‐9‐CM) for the discharge, including fall‐related injury codes.ResultsThree hundred forty‐three inpatient falls with injury (90.2%) resulted in temporary harm to the individual; the remaining 37 falls (9.8%) resulted in more‐serious harm. Sixteen of the 37 falls with injury extending hospitalization or resulting in death were identified using Centers for Medicare and Medicaid Services (CMS)‐targeted injury code ranges combined with present‐on‐admission indicators. Of the 21 falls with injury that were not identified, nine (42.9%) lacked documentation of any injury, and seven (33.3%) identified other injuries outside the CMS‐targeted injury code ranges.ConclusionThe CMS‐targeted ICD‐9‐CM codes used to identify fall‐related injuries in claims data do not always detect the most‐serious falls.
The suitability of caffeinated drinks for children: a systematic review of randomised controlled trials, observational studies and expert panel guidelines
Authors: Ruxton C. H. S. 
Published: November 2013

AbstractBackgroundThe increased availability of caffeinated drinks raises questions about the level of caffeine that is appropriate for children, as well as the benefits and risks associated with their consumption.MethodsUsing the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, this systematic review evaluates evidence from randomised controlled trials investigating the effects of caffeine on cognition, behaviour, mood and exercise performance in children. Observational studies and expert panel guidelines are also discussed.ResultsOne hundred and nine studies were found, with 11 randomised controlled trials and 13 observational studies meeting the criteria. High caffeine intakes (e.g. >5 mg kg–1 body weight day–1) were associated with an increased risk of anxiety and withdrawal symptoms. However, smaller amounts were not linked with such effects and may benefit cognitive function and sports performance based on adult studies. The evidence suggests that children and adolescents should limit daily caffeine consumption to 2.5 mg kg–1 body weight day–1, equating to one or two cups of tea or one small cup of coffee. Lower contributors of caffeine, such as tea, may be more appropriate for children because they contribute to daily fluid intakes and provide flavonoids. By contrast, caffeinated soft drinks may be less suitable options for children as a result of their acidity, higher caffeine content, presence of added sugar (in some cases) and absence of bioactive compounds.ConclusionsMore studies are needed to determine the intakes that represent a risk and whether there may be benefits for alertness and sports performance with moderate intakes of caffeine.
The GLT‐1 (EAAT2; slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse
Authors: Bjørnsen Lars Petter , Hadera Mussie G. , Zhou Yun , Danbolt Niels C. , Sonnewald Ursula 
Published: November 2013

AbstractGlutamate is the major excitatory neurotransmitter, and is inactivated by cellular uptake catalyzed mostly by the glutamate transporter subtypes GLT‐1 (EAAT2) and GLAST (EAAT1). Astrocytes express both GLT‐1 and GLAST, while axon terminals in the neocortex only express GLT‐1. To evaluate the role of GLT‐1 in glutamate homeostasis, we injected GLT‐1 knockout (KO) mice and wild‐type littermates with [1‐13C]glucose and [1,2‐13C]acetate 15 min before euthanization. Metabolite levels were analyzed in extracts from neocortex and cerebellum and 13C labeling in neocortex. Whereas the cerebellum in GLT‐1‐deficient mice had normal levels of glutamate, glutamine, and 13C labeling of metabolites, glutamate level was decreased but labeling from [1‐13C] glucose was unchanged in the neocortex. The contribution from pyruvate carboxylation toward labeling of these metabolites was unchanged. Labeling from [1,2‐13C] acetate, originating in astrocytes, was decreased in glutamate and glutamine in the neocortex indicating reduced mitochondrial metabolism in astrocytes. The decreased amount of glutamate in the cortex indicates that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT‐1 plays a role in glutamate homeostasis in the cortex.image
Glutamate is the major excitatory neurotransmitter, and is inactivated by uptake via GLT‐1 (EAAT2) and GLAST (EAAT1) transporters, while axon terminals in the neocortex only express GLT‐1. To evaluate the role of GLT‐1 in glutamate homeostasis, we used [1‐13C]glucose and [1,2‐13C]acetate injection and NMR spectroscopy. The results indicate that glutamine transport into neurons is not sufficient to replenish glutamate lost because of neurotransmission and that GLT‐1 plays a role in glutamate homeostasis in the neocortex.
The putative multidrug resistance proteinMRP‐7 inhibits methylmercury‐associated animal toxicity and dopaminergic neurodegeneration inCaenorhabditis elegans
Authors: VanDuyn Natalia , Nass Richard 
Published: November 2013

AbstractParkinson's disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene–environment interactions are believed to play a significant role in the vast majority ofPDcases, yet the toxicants and the associated genes involved in the neuropathology are largely ill‐defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development ofPD. Here, we report that a gene coding for the putative multidrug resistance proteinMRP‐7 inCaenorhabditis elegansmodulates whole animal andDAneuron sensitivity to MeHg. In this study, we demonstrate that genetic knockdown ofMRP‐7 results in a twofold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg‐associated animal death. Chronic exposure to low concentrations of MeHg inducesMRP‐7 gene expression, while exposures inMRP‐7 genetic knockdown animals results in a loss ofDAneuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenousMRP‐7 promoter indicate that the transporter is expressed inDAneurons. These studies show for the first time that a multidrug resistance protein is expressed inDAneurons, and its expression inhibits MeHg‐associatedDAneuron pathology.imageMethylmercury (MeHg) exposure is a risk factor for Parkinson's disease. Yet, the molecular basis for Hg transport and neurotoxicity is poorly defined. Our studies identify the first multidrug resistance protein that is targeted to dopamine (DA) neurons. We show that the transporter inhibits MeHg‐associated accumulation of Hg, intracellular toxicant‐associated stress response, and DA neurodegeneration. This model should facilitate the identification of molecular pathways and potential therapeutic targets involved in MeHg‐associated dopamine neuron pathology. hsp = heat‐shock protein.
Meaning‐in‐life in nursing‐home patients: a valuable approach for enhancing psychological and physical well‐being?
Authors: Haugan Gørill 
Published: November 2013

Aims and objectivesTo investigate the associations between meaning‐in‐life and physical, emotional, functional and social well‐being in a cognitively intact nursing‐home population.BackgroundMeaning‐in‐life is understood as an influential psychological variable that promotes health and well‐being; meaning‐in‐life has been found to be a mediating variable in both psychological and physical health.Design and methodsThe study employed a cross‐sectional design. Data were collected in 2008 and 2009 using the purpose‐in‐life test and theFACT‐G quality‐of‐life questionnaire. A total of 250 cognitively intact nursing‐home patients who met the inclusion criteria were approached and 202 attended. The hypothesised relationships between meaning and multidimensional well‐being were tested by means of structural equation modelling.ResultsThe structural equation modelling model fit well with the present data, showing significant direct relationships between meaning‐in‐life and emotional and functional well‐being, and a significant mediated influence of meaning on social and physical well‐being.ConclusionMeaning‐in‐life is associated with all dimensions of well‐being and likely plays an important role in both emotional and physical well‐being.Relevance to clinical practiceFacilitating patients' perceived meaning‐in‐life might help ease emotional distress and physical symptoms, thus fostering well‐being in cognitively intact nursing‐home patients. Therefore, advancing staff nurses' competence in facilitating meaningful involvement, connectedness, nurse–patient interaction and symptom management is important for care quality and global well‐being in nursing homes.
On the statistical model of the two-stage designs in bioequivalence assessment
Authors: Karalis Vangelis , Macheras Panos 
Published: November 2013

Abstract

Objectives
Two-stage clinical designs are currently recommended by the regulatory authorities for the assessment of bioequivalence (BE). A specific statistical methodology was recently proposed by the European Medicines Agency (EMA). The aims of this article are to elaborate on the suggested statistical design from the EMA and to compare it with the existing statistical methods reported in the literature.

Methods
Monte Carlo simulations were used to simulate the conditions of a two-stage BE design. The starting sample size was either 24 or 48, whereas the coefficient of variation of the within-subject variability was equal to 20% and 40%. Several geometric mean ratio levels of the BE metric were considered. Under each condition, 1 000 000 studies were simulated.

Key findings
The overall performance, in terms of percentage of BE acceptance, is identical. The additional term, ‘sequence × stage’, suggested in the EMA method is in most cases nonsignificant. The same results were obtained regardless of the type (fixed or random) of the effect applied to the ‘subjects’ term.

Conclusions
Any BE study either finished or in progress which relies on the existing literature methodology leads to the same percentage of BE acceptance as if it was analysed with the recently proposed EMA method.
Osteoarthritis of the hand II: chemistry, pharmacokinetics and pharmacodynamics of naproxen, and clinical outcome studies
Authors: Leung Garvin J , Rainsford K D , Kean Walter F 
Published: November 2013

Abstract

Objective
This article aims to review osteoarthritis of the hand and the role of the non-steroidal anti-inflammatory drug (NSAID) naproxen on its management. We discuss the chemical and pharmacological properties of naproxen and the NSAID class, with an emphasis on its mechanism and adverse reactions. In the context of part I of this paper in characterizing hand osteoarthritis (OA), we review clinical trials that have been conducted involving hand OA and naproxen.

Key findings
The therapeutic effect of NSAIDs stems from its role on inhibiting cyclo-oxygenase (COX)-1 or COX-2 enzyme activity in the body. These enzymes play a major role in maintaining several functions in the body and due NSAIDs' inhibitory effects; many principle adverse reactions occur with the use of NSAIDs such as: gastrointestinal tract issues, cardiovascular risks, renal, hepatic, central nervous system and cutaneous. Review of clinical trials involving naproxen and hand OA show that it is significantly more efficacious when compared with placebo.

Summary
These studies, along with the finding that naproxen is of least cardiovascular risk in the NSAID class, may show that it can be part of one of the approaches in managing the condition. It is important to note that the optimal NSAID to use varies for each individual. The finding that the use of naproxen leads to the smallest increase in cardiovascular risk appeals to those at-risk individuals who suffer from OA and require pharmacological treatment for relief.
Homocysteine in dogs with systemic inflammatory response syndrome
Authors: Patterson B. E. , Barr J. W. , Fosgate G. T. , Berghoff N. , Steiner J. M. , Suchodolski J. S. , Black D. M. 
Published: November 2013

ObjectivesTo compare serum concentrations of homocysteine in healthy dogs and those fitting the criteria for systemic inflammatory response syndrome and to compare these values to commonly measured B‐vitamins.MethodsStudy dogs were classified into non‐infectious systemic inflammatory response syndrome or sepsis groups and blood was drawn on Day 1 of the patient's hospitalisation for measurement of serum homocysteine, folate and cobalamin concentrations. Homocysteine concentration was measured in 51 clinically healthy dogs to serve as the control group.ResultsA statistically significant difference was found between the homocysteine concentrations of the healthy group when compared to non‐infectious systemic inflammatory response syndrome and sepsis groups. Homocysteine values were not correlated with folate, cobalamin or APPLEfast severity scores. Homocysteine concentrations were significantly lower in sick dogs when compared to the control group, which is dissimilar to the human population.Clinical SignificanceThe clinical significance of homocysteine changes in critically ill dogs is currently unknown.