bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation
Authors: Girnius Saulius K. , Lee Saem , Kambhampati Suman , Rose Michal G. , Mohiuddin Abid , Houranieh Antoun , Zimelman Abraham , Grady Terrence , Mehta Paulette , Behler Caroline , Hayes Teresa G. , Efebera Yvonne A. , Prabhala Rao H. , Han Andrew , Yellapragada Sarvari V. , Klein Catherine E. , Roodman Garson D. , Lichtenstein Alan , Munshi Nikhil C.
Published: January 2015

Once‐weekly administration of bortezomib has reduced bortezomib‐induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three‐ and four‐ drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m2 intravenously was given once‐weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co‐morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25–2·4 months). The progression‐free and overall survivals were 8 months and 46·5 months, respectively. Twenty‐four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).
Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice
Authors: van der Sluis Ronald J , Nahon Joya E , Reuwer Anne Q , Van Eck Miranda , Hoekstra Menno
Published: January 2015

Background and Purpose

Antipsychotic drugs have been shown to modulate the expression of ATP‐binding cassette transporter A1 (ABCA1), a key factor in the anti‐atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo.

Experimental Approach

Thioglycollate‐elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low‐density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol‐containing pellet and subsequently fed a Western‐type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo.

Key Results

Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP‐1 expression (−70%) and secretion (−28%) by peritoneal macrophages.

Conclusions and Implications

Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis.
Relief learning is dependent on NMDA receptor activation in the nucleus accumbens
Authors: Mohammadi Milad , Fendt Markus
Published: January 2015

Background and Purpose

Recently, we demonstrated that the nucleus accumbens (NAC) is required for the acquisition and expression of relief memory. The purpose of this study was to investigate the role of NMDA receptors within the NAC in relief learning.

Experimental Approach

The NMDA receptor antagonist 2‐amino‐5‐phosphonopentanoic acid (AP‐5) was injected into the NAC. The effects of these injections on the acquisition and expression of relief memory, as well as on the reactivity to aversive electric stimuli, were tested.

Key Results

Intra‐accumbal AP‐5 injections blocked the acquisition but not the expression of relief memory. Furthermore, reactivity to aversive electric stimuli was not affected by the AP‐5 injections.

Conclusion and Implication

The present data indicate that NMDA‐dependent plasticity within the NAC is crucial for the acquisition of relief memory.
NVP‐QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia
Authors: Coote K J , Paisley D , Czarnecki S , Tweed M , Watson H , Young A , Sugar R , Vyas M , Smith N J , Baettig U , Groot‐Kormelink P J , Gosling M , Lock R , Ethell B , Williams G , Schumacher A , Harris J , Abraham W M , Sabater J , Poll C T , Faller T , Collingwood S P , Danahay H
Published: January 2015

Background and Purpose

Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism‐based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP‐QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia.

Experimental Approach

The in vitro potency and duration of action of NVP‐QBE170 were compared with amiloride and a newer ENaC blocker, P552‐02, in primary human bronchial epithelial cells (HBECs) by short‐circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC).

Key Results

In vitro, NVP‐QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP‐QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP‐QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action.

Conclusions and Implications

NVP‐QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.
The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice
Authors: Malik Maninder , Rangel‐Barajas Claudia , Sumien Nathalie , Su Chang , Singh Meharvan , Chen Zhenglan , Huang Ren‐Qi , Meunier Johann , Maurice Tangui , Mach Robert H , Luedtke Robert R
Published: January 2015

Background and Purpose

Cognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory.

Experimental Approach

Scopolamine‐induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg−1) were used to evaluate the ability of LS‐1–137, a novel sigma (σ1) receptor‐selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration.

Key Results

LS‐1–137 is a high‐affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80‐fold selective for σ1, compared with σ2 receptors. LS‐1–137 binds with low affinity at D2‐like (D2, D3 and D4) dopamine and muscarinic receptors. LS‐1–137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS‐1–137 treatment was also found to trigger the release of brain‐derived neurotrophic factor from rat astrocytes.

Conclusions and Implications

The σ1 receptor‐selective compound LS‐1–137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor‐dependent cognitive deficits.
Schizandrin ameliorates ovariectomy‐induced memory impairment, potentiates neurotransmission and exhibits antioxidant properties
Authors: Jiang Zhong‐Jiao , Wang Chun‐Yang , Xie Xun , Yang Jing‐Fang , Huang Jun‐Ni , Cao Zhi‐Ping , Xiao Peng , Li Chu‐Hua
Published: January 2015

Background and Purpose

Schizandrin (SCH) has been reported to prevent or reduce learning and memory defects. However, it is not known whether SCH ameliorates cognitive impairments induced by oestrogen deficiency. In the present study, we investigated the effect of SCH on memory in ovariectomized (OVX) and non‐OVX rats.

Experimental Approach

A passive avoidance test was used to evaluate the effect of SCH on memory. Field EPSPs were recorded in hippocampal slices using an electrophysiological method. In OVX rats, biochemical parameters in the bilateral hippocampus were measured; these included superoxide dismutase (SOD), malondialdehyde (MDA) and AChE. Also, the number of NADPH‐diaphorase (NADPH‐d) positive neurons was counted by NADPH‐d histochemistry staining technique.

Key Results

Oral SCH improved the memory and facilitated the induction of long‐term potentiation in non‐OVX and OVX rats; this effect was more obvious in OVX rats. Similarly, SCH perfusion enhanced synaptic transmission in hippocampal slices from both non‐OVX and OVX rats. However, SCH perfusion reduced the ratio of paired‐pulse facilitation only in OVX but not in non‐OVX rats. In addition, SCH decreased AChE activity and MDA level and increased SOD activity and the number of NADPH‐d‐positive neurons in OVX rats.

Conclusions and Implications

SCH improves memory in OVX rats and its potential mechanisms may include a reduction in the loss of hippocampal NADPH‐d positive neurons, an increase of antioxidant properties and a potentiation of synaptic transmission that possibly involves to enhance cholinergic function. Overall, our findings indicate that SCH has potential as a therapeutic strategy for the cognitive dysfunctions associated with the menopause.
Attentional Processes in Low‐Socioeconomic Status Bilingual Children: Are They Modulated by the Amount of Bilingual Experience?
Authors: Ladas Aristea I. , Carroll Daniel J. , Vivas Ana B.
Published: January 2015

Recent research indicates that bilingual children are more proficient in resolving cognitive conflict than monolinguals. However, the replicability of such findings has been questioned, with poor control of participants' socioeconomic status (SES) as a possible confounding factor. Two experiments are reported here, in which the main attentional functions and pragmatic ability of 54 bilingual and 56 monolingual low‐SES children were assessed (Experiment 1: 6‐ to 12‐year‐olds; Experiment 2: 6‐ to 8‐year‐olds). A language‐switching task was also employed, to measure bilingual proficiency. Overall, the monolingual and bilingual groups did not differ significantly in any of the tasks employed, although the ability to resolve conflict was related to children's level of bilingual experience.
Ethnic Differences in Associations Among Popularity, Likability, and Trajectories of Adolescents' Alcohol Use and Frequency
Authors: Choukas‐Bradley Sophia , Giletta Matteo , Neblett Enrique W. , Prinstein Mitchell J.
Published: January 2015

Two‐part latent growth models examined associations between two forms of peer status (popularity, likability) and adolescents' alcohol use trajectories throughout high school; ethnicity was examined as a moderator. Ninth‐grade low‐income adolescents (N = 364; Mage = 15.08; 52.5% Caucasian; 25.8% African American; 21.7% Latino) completed sociometric nominations of peer status and aggression at baseline, and reported their alcohol use every 6 months. After controlling for gender, aggression, ethnicity, and socioeconomic status, popularity—but not likability—prospectively predicted alcohol use trajectories. However, these effects were moderated by ethnicity, suggesting popularity as a risk factor for alcohol use probability and frequency among Caucasian and Latino, but not African American adolescents. Results suggest that developmental correlates of peer status should be considered within cultural context.
Urinary glucocorticoid metabolites: biomarkers to classify adrenal incidentalomas?
Authors: Brossaud Julie , Ducint Dominique , Corcuff Jean‐Benoît
Published: January 2015

Objective

Total urinary cortisol metabolites represent cortisol production and metabolism. We hypothesized that to assay metabolites could add some information to the one provided by a sole cortisol assay.

Design and patients

We set up an inexpensive multiplex mass spectrometry assay to quantify cortisol metabolites. We investigated 43 patients with benign secreting (AT+) or silent (AT−) adrenal tumours compared to 48 lean (Nl) or 143 obese (Ob) subjects, and to 26 patients with a Cushing's disease (CD). The initial investigation included immunoreactive quantification of urinary free cortisol (UFC).

Results

Cortisol metabolites were overexcreted in CD but not in Ob subjects. Nl and Ob were thus pooled in a control population (Ctl). Cortisol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE) excretions were significantly increased in AT compared to Ctl subjects, whereas immunoreactive UFC was similar. A logistic regression retaining cortisol, THF, and α‐ and β‐cortolone as significant analytes allowed the construction of a receiver‐operating characteristics (ROC) curve significantly better than the curve generated by cortisol alone (area under the curve (AUC) 0·927 vs 0·729, respectively; P < 0·0001). More importantly, although there was no significant difference between Ctl vs AT− subjects for cortisol metabolites, a logistic regression retaining cortisol, allo‐THF, and α‐ and β‐cortolone as significant analytes generated a ROC curve performing significantly better than cortisol alone (AUC 0·910 vs 0·635, respectively; P < 0·0001).

Conclusion

Cortisol metabolite excretion is modified in AT, including AT−, patients even without modification of UFC. Clinical usefulness of these biomarkers has to be investigated in prospective studies following up patients with AT.
How many marmoset (Primates: Cebidae: Callitrichinae) genera are there? A phylogenetic analysis based on multiple morphological systems
Authors: Garbino Guilherme S. T.
Published: January 2015

The marmosets, tribe Callitrichini, are the most speciose clade in the subfamily Callitrichinae, containing 21 species. However, there is no consensus among molecular and morphological systematists as to how many genera should be recognized for the group. To test the morphological support for the alternative generic classifications, this study presents a comprehensive phylogenetic analysis. It is the first such analysis to include all 21 species and employ continuous and discrete osteological, pelage and tegument, karyological and vocal characters. This dataset was combined with nucleotide sequences from two mitochondrial and four nuclear regions. Separate analyses showed that, among morphological datasets, osteological characters were best at solving relationships at more inclusive levels, whilst pelage characters were most informative at the interspecific level. This suggests the presence of different transformation rates for the two character sets. When a single most parsimonious tree was obtained using the 83‐character matrix, three main clades were identified, supporting the division of the marmosets into three genera:Callithrix,CebuellaandMico. The total evidence analysis that included an additional 3481 molecular characters corroborated most of the morphology‐based clades and also supported a three‐genus classification of the marmosets. This is the first morphological study to support an Amazonian marmoset clade (Cebuella + Mico), which is also strongly supported in exclusively molecular phylogenies, and to synonimizeCallibellaunderMico.
Conservation Traps and Long‐Term Species Persistence in Human‐Dominated Systems
Authors: Cardador Laura , Brotons Lluís , Mougeot François , Giralt David , Bota Gerard , Pomarol Manel , Arroyo Beatriz
Published: January 2015

Major conservation efforts in human‐dominated systems, such as farmland, have focused on the establishment of subsidies and compensation promoting low‐impact management practices to reverse the impacts of conservation threats in the short term (reactive approaches). In this study, we discuss how a different way of framing conservation policy (proactive approaches) could lead to fundamentally different long‐term conservation outcomes. We define proactive approaches as those not necessarily including measures directly addressing the threats affecting biodiversity, but promoting transitions from current scenarios in which species are threatened to new states in which the threat is no longer present. We illustrate reactive and proactive approaches using as a case study two contrasting conservation frameworks for a vulnerable farmland bird, the Montagu's harrier (Circus pygargus) in northeastern Spain. This example shows that reactive approaches can lead to “conservation traps,” which we defined as situations where the application of biologically focused actions in response to conservation problems results in an unsustainable need to perpetuate the implementation of those actions. Our aim is to offer a fresh perspective on biodiversity conservation in human‐dominated systems and to stimulate alternative, more holistic approaches in conservation promoting transitions to new states not requiring long‐term active and costly conservation action.
Concerns of ABO incompatible and crossmatch‐positive potential donors and recipients about participating in kidney exchanges
Authors: Rodrigue James R. , Leishman Ruthanne , Vishnevsky Tanya , Evenson Amy , Mandelbrot Didier A.
Published: January 2015

Kidney paired exchanges (KPEs) have increased, yet are still underutilized. This study aimed to develop tools for assessing KPE concerns, identify predictors of KPE concerns, and describe common KPE concerns among potential living donors (LDs) and intended recipients. Incompatible former potential LDs (n = 135) and intended recipients (n = 83) retrospectively completed questionnaires to assess KPE concerns. Healthcare system distrust also was assessed. A minority (n = 48 or 36.5% of potential LDs; n = 25 or 30.1% of intended recipients) had pursued KPE participation. Of those who pursued KPE participation, 11 (22.9%) and 6 (24.0%) completed KPE donation or transplantation, respectively. The questionnaires for potential LDs and recipients showed good internal consistency and preliminary convergent validity. LDs and patients less willing to pursue KPE reported more KPE concerns. Common KPE concerns for both potential LDs and recipients were related to perceived Distrust/Inequity and Inconvenience/Cost. Multivariate predictors of more KPE concerns were as follows: male gender (t = 4.5, p < 0.001) and more healthcare system distrust (t = 2.5, p = 0.01) for potential LDs; black race (t = 2.1, p = 0.04) and more healthcare system distrust (t = 2.3, p = 0.03) for intended recipients. These findings underscore the importance of addressing concerns potential LDs and patients have about KPE if the true potential of KPE is to be realized.
Multivariable risk of developing new onset diabetes after transplant—results from a single‐center study of 481 adult, primary kidney transplant recipients
Authors: Gaynor Jeffrey J. , Ciancio Gaetano , Guerra Giselle , Sageshima Junichiro , Hanson Lois , Roth David , Goldstein Michael J. , Chen Linda , Kupin Warren , Mattiazzi Adela , Tueros Lissett , Flores Sandra , Barba Luis J. , Lopez Adrian , Rivas Jose , Ruiz Phillip , Vianna Rodrigo , Burke George W.
Published: January 2015

Background

Understanding the relative contributions of baseline demographics and immunosuppressive therapy on NODAT risk may help in developing preventive strategies.

Methods

Using our prospectively followed cohort of 481 adult, primary kidney transplant recipients without pre‐transplant diabetes, we determined the significant baseline predictors for the hazard rate of developing NODAT via Cox stepwise regression. The multivariable influence of first BPAR (defined as a time‐dependent covariate) was also tested.

Results

Median follow‐up was 57 mo post‐transplant; the overall percentage who developed NODAT was 22.5% (108/481). Four baseline predictors of a greater NODAT hazard rate were found (by order of selection): higher BMI (p < 0.000001), planned maintenance with SRL (p = 0.0003), non‐white recipient (p = 0.0004), and older recipient age (p = 0.0004). Approximately one‐half of the 106 patients in the highest demographic risk category (BMI ≥25 kg/m2, non‐white race, and age at transplant ≥40 yr) developed NODAT; actuarial NODAT risk ranged from 10% to 30% in the lower demographic risk categories. First BPAR was also associated with significantly higher NODAT in multivariable analysis (p = 0.02)—the highly elevated NODAT rate observed during the first few months post‐transplant and following first BPAR appears to demonstrate the diabetogenic effect of using high‐dose (intravenous) corticosteroids.

Conclusions

The disturbingly high NODAT rate found among patients having multiple demographic risk factors is still an important problem that awaits a better solution.
Health‐related quality of life may improve after transplantation in pancreas–kidney recipients
Authors: Martins La Salete , Outerelo Cristina , Malheiro Jorge , Fonseca Isabel M. , Henriques António C. , Dias Leonídio S. , Rodrigues Anabela S. , Cabrita António M. , Noronha Irene L.
Published: January 2015

Pancreas–kidney transplantation (PKT) may significantly improve quality of life (HRQOL) in patients with type 1 diabetes. We have assessed the changes felt by PKT patients, using the Gastrointestinal Quality of Life Index (GIQLI) and EuroQol‐5D questionnaires. Patients were asked to compare how their HRQOL had changed from pre‐transplantation to the last visit. The 60 men and 66 women enrolled had a mean follow‐up of five yr; 84.1% with both grafts, 15.9% with one graft functioning. In all domains of EuroQol‐5D scores improved after PKT, as well as the visual analogue scale health state (from 38% to 84%, p < 0.001; effect size 3.34). In GIQLI, physical function was felt better after PKT than before (14.83 ± 3.86 vs. 7.86 ± 4.43, p < 0.001; effect size 1.68); the same was observed for psychological status, social function, and GI complaints. Concerning the burden of medical treatment, the score significantly improved (from 1.31 to 3.63, p < 0.001, effect size 2.02). The rate of unemployed patients decreased after PKT (from 50.8% to 36.5%, p < 0.001). Multivariate analysis showed that having only one functioning graft was associated with worse HRQOL scores (B = −5.157, p = 0.015). In conclusion, for all assessed domains, patients reported a significant improvement in HRQOL after PKT. Maintenance of the two grafts functioning predicted higher improvement of HRQOL scores.
“An Arena Where Meaning and Identity Are Debated and Contested on a Global Scale”: Narrative Discourses in British Museum Exhibitions, 1972–2013
Authors: Francis David
Published: January 2015

Following the so‐called narrative turn in the social sciences, museums have increasingly been conceptualized as narrative environments (MacLeod 2012). This narrative approach is characterized by a focus on museum exhibitions as spaces that tell stories rather than as repositories of knowledge (Roberts ). Despite the ubiquity of the term “narrative” in museums, relatively few studies have attempted to use literary theory to understand how these narrative spaces function. This paper attempts to apply some of the analytical models of the Russian literary theorist Mikhail Bakhtin to museum displays in order to examine how competing internal and external discourses shape exhibition narratives. This study looks at eight British Museum exhibitions beginning with Treasures of Tutankhamun in 1972 and ending with Hajj: Journey to the Heart of Islam in 2012. It explores how Bakhtin's theoretical concepts, including the “dialogic nature of discourse,” “heteroglossia” and the “carnivalesque,” can aid our critical understanding of museum displays as discursive spaces. External discourses often enter the museum unnoticed, regardless of authorial/curatorial intent, and are often impossible to keep out. However, by being critically aware of how discourse functions, museum professionals can use the techniques of literary theory to create innovative exhibitions that promote reflection and discussion about the connections between the historical past and the world in which we live today.
Clinical application of endoscopic ultrasonography for esophageal achalasia
Authors: Minami Hitomi , Inoue Haruhiro , Isomoto Hajime , Urabe Shigetoshi , Nakao Kazuhiko
Published: January 2015

Endoscopic ultrasonography (EUS) has been widely used for evaluating the nature of diseases of various organs. The possibility of applying EUS for esophageal motility diseases has not been well discussed despite its versatility. At present, peroral endoscopic myotomy (POEM) for esophageal achalasia and related diseases has brought new attention to esophageal diseases because POEM provides a more direct approach to the inner structures of the esophageal wall. In the present study, we discuss the clinical utility of EUS in evaluating and treating esophageal motility diseases such as esophageal achalasia and related diseases.
Post‐Ike economic resilience along the Texas coast
Authors: Lu Ruoxi , Dudensing Rebekka M.
Published: January 2015

The economic devastation resulting from recent natural disasters has spawned intense interest in programmes that promote regional resilience. The economic impacts of Hurricane Ike (September 2008) endured long beyond the storm's landfall, compounded by a national recession. This study analyses the pattern of post‐Ike industrial growth in eight coastal counties of Texas, United States, and identifies sources of resilience and potential drivers of recovery. The results indicate that post‐disaster growth patterns differ from established growth patterns. Levels of resilience vary across industrial sectors, and service sectors tend to lead a recovery. The resilience of the hotel and restaurant sector, for instance, suggests that the presence of relief workers might immunise certain sectors against a post‐disaster economic downturn. Besides the sectors that are generally resilient, each county has its own distinct sectors that, depending on the extent of the damage suffered, tend to perform strongly after a disaster, owing to the characteristics of the respective county's economy.
Fire risk reduction through a community‐based risk assessment: reflections from Makola Market, Accra, Ghana
Authors: Oteng‐Ababio Martin , Sarpong Akwasi Owusu
Published: January 2015

This paper explores the level of vulnerability to the hazard of fire that exists in Makola Market in Accra, Ghana, and assesses how this threat can be reduced through a community‐based risk assessment. It examines the perceptions of both market‐stall occupants and primary stakeholders regarding the hazard of fire, and analyses the availability of local assets (coping strategies) with which to address the challenge. Through an evaluation of past instances of fire, as well as in‐depth key stakeholder interviews, field visits, and observations, the study produces a detailed hazard map of the market. It goes on to recommend that policymakers consider short‐to‐long‐term interventions to reduce the degree of risk. By foregrounding the essence of holistic and integrated planning, the paper calls for the incorporation of disaster mitigation measures in the overall urban planning process and for the strict enforcement of relevant building and fire safety codes by responsible public agencies.
Parents' experiences of managing their child's diabetes using an insulin pump: a qualitative study
Authors: Rankin D. , Harden J. , Noyes K. , Waugh N. , Barnard K. , Lawton J.
Published: January 2015

Aims

Continuous subcutaneous insulin infusion delivered via a pump is increasingly recommended for younger children with Type 1 diabetes. Our aims were: to understand the impact on parents who care for young children using insulin pumps; to help interpret psychological outcomes reported in quantitative research; and to inform provision of support to future parents.

Methods

We conducted in‐depth interviews with 19 parents of children (aged ≤ 12 years) with Type 1 diabetes who used an insulin pump. Data were analysed thematically.

Results

Parents reported multiple benefits from using insulin pumps, including: no longer having to administer painful injections; fewer restrictions on the frequency, timing and carbohydrate contents of snacks and meals; and improvements in family life and their child's glycaemic control. Parents liked and felt less anxious about using bolus calculators to determine insulin doses; however, parents also described undertaking additional and unanticipated work to manage their child's diabetes using a pump. This included performing more blood glucose tests to calculate insulin doses for snacks and to address their concerns that the pump increased their child's risk of hypoglycaemia. Some parents reported doing additional blood glucose checks because they could adjust pump settings to better manage hypo‐ and hyperglycaemia.

Conclusions

Parents liked and perceived benefits for their child and themselves from using an insulin pump; however, parents would benefit from being made aware of the additional work involved in using a pump and also from education and support to address concerns about hypoglycaemia. Better measures to evaluate parents' experiences are also recommended.
Difficulties in screening for peripheral neuropathies in children with diabetes
Authors: Hirschfeld G. , von Glischinski M. , Knop C. , Wiesel T. , Reinehr T. , Aksu F. , Blankenburg M. , Hirsch J. , Zernikow B.
Published: January 2015

Aims

To assess the diagnostic utility of a novel abbreviated monofilament test in comparison with the tuning fork test to detect diabetic peripheral neuropathy in children.

Methods

A total of 88 children with Type 1 diabetes mellitus were screened for diabetic peripheral neuropathy using the monofilament test and the tuning fork. Nerve conduction studies were performed according to the ‘gold standard’ for neuropathy. We assessed the diagnostic utility and inter‐rater agreement of the two screening methods.

Results

A total of 43 (49%) children (aged 6–18 years) had at least one abnormal nerve conduction study result. Diagnostic utility and inter‐rater agreement were very low for both screening methods. The monofilament test yielded a sensitivity of 18% and a specificity of 80%. The tuning fork yielded a sensitivity of 0% and a specificity of 98%.

Conclusion

The present study found that an abbreviated monofilament test has low diagnostic utility for the detection of early diabetic peripheral neuropathy because of its low reliability. The problem of reliability needs to be more thoroughly addressed in order to improve the screening procedures in diabetes management in childhood and adolescence.
Multi‐country retrospective observational study of the management and outcomes of patients with Type 2 diabetes during Ramadan in 2010 (CREED)
Authors: Babineaux S. M. , Toaima D. , Boye K. S. , Zagar A. , Tahbaz A. , Jabbar A. , Hassanein M.
Published: January 2015

Aim

To describe the characteristics and management of patients with diabetes who chose to fast during Ramadan in 2010.

Methods

This was a multi‐country, retrospective, observational study, supplemented with physician and patient questionnaires, with data captured before, during and after Ramadan. A total of 508 physicians in 13 countries enrolled 3777 patients and a total of 3394 evaluable cases were analysed. We report on the subset of patients with Type 2 diabetes, which included 3250 patients (95.8%).

Results

Oral anti‐hyperglycaemic therapy was the predominant pre‐Ramadan therapy for most patients (76.6%). The treatment regimen was modified before Ramadan for 39.3% of all patients (34.9% for patients on oral drugs alone, 47.1% for patients on injectable drugs alone). Almost all physicians (96.2%) reported providing fasting‐specific advice to patients and 62.6% report using guidelines or recommendations for the management of diabetes during Ramadan. In all, 64% of patients reported fasting everyday of Ramadan and 94.2% fasted for at least 15 days.

Conclusions

Physicians have increasingly adopted multiple approaches to the management of fasting during Ramadan, including the adoption of international and/or national guidelines, providing fasting‐specific advice and adjusting treatment regimens, such that patients are able to fast for a greater number of days without acute complications. Additional research is needed to explore physician and patient beliefs and practices to inform the evidence‐based management of diabetes while fasting, both during and outside of Ramadan, and to identify and address barriers to the universal uptake of techniques to facilitate that management.
Glycaemic control and self‐management behaviours in Type 2 diabetes: results from a 1‐year longitudinal cohort study
Authors: Houle J. , Beaulieu M.‐D. , Chiasson J.‐L. , Lespérance F. , Côté J. , Strychar I. , Bherer L. , Meunier S. , Lambert J.
Published: January 2015

Aim

To better understand the associations between changes in self‐management behaviours and glycaemic control.

Methods

We conducted a prospective observational study of 295 adult patients with Type 2 diabetes evaluated at baseline, 6 and 12 months. Four self‐management behaviours were evaluated using the Summary of Diabetes Self‐Care Activities instrument, which assesses healthy diet, physical activity, medication taking and self‐monitoring of blood glucose. Using hierarchical linear regression models, we tested whether changes in self‐management behaviours were associated with short‐term (6‐month) or long‐term (12‐month) changes in glycaemic control, after controlling for demographic and clinical characteristics.

Results

Improved diet was associated with a decrease in HbA1c level, both at 6 and 12 months. Improved medication taking was associated with short‐term improvement in glycaemic control, while increased self‐monitoring of blood glucose frequency was associated with a 12‐month improvement in HbA1c. Completely stopping exercise after being physically active at baseline was associated with a rise in HbA1c level at 6‐month follow‐up. Interaction analysis indicated that a healthy diet benefitted all participant subgroups, but that medication taking was associated with glycaemic control only for participants living in poverty and more strongly for those with lower educational levels. Finally, a higher self‐monitoring of blood glucose frequency was associated with better glycaemic control only in insulin‐treated participants.

Conclusions

Even after adjusting for potential confounders (including baseline HbA1c), increased frequency of healthy diet, medication taking and self‐monitoring of blood glucose were associated with improved HbA1c levels. These self‐management behaviours should be regularly monitored to identify patients at risk of deterioration in glycaemic control. Barriers to optimum self‐management should be removed, particularly among socio‐economically disadvantaged populations.
Effect of particle size on calcium release and elevation of pH of endodontic cements
Authors: Saghiri Mohammad Ali , Asatourian Armen , Orangi Jafar , Lotfi Mehrdad , Soukup Jason W. , Garcia‐Godoy Franklin , Sheibani Nader
Published: January 2015

Background/Aim

Elevation of pH and calcium ion release are of great importance in antibacterial activity and the promotion of dental soft and hard tissue healing process. In this study, we evaluated the effect of particle size on the elevation of pH and the calcium ion release from calcium silicate‐based dental cements.

Material and methods

Twelve plastic tubes were divided into three groups, filled with white mineral trioxide aggregate (WMTA), WMTA plus 1% methylcellulose, and nano‐modified WMTA (nano‐WMTA), and placed inside flasks containing 10 ml of distilled water. The pH values were measured using a pH sensor 3, 24, 72, and 168 h after setting of the cements. The calcium ion release was measured using an atomic absorption spectrophotometer with same sample preparation method. Data were subjected to two‐way analysis of variance (anova) followed by post hoc Tukey tests with significance level of P < 0.05.

Results

Nano‐WMTA showed significant pH elevation only after 24 h (P < 0.05) compared with WMTA, and after 3, 24, and 72 h compared with WMTA plus 1% methylcellulose (P < 0.05). Nano‐WMTA showed significantly higher calcium ion release values compared to the other two groups (P < 0.05).

Conclusions

Nano‐modification of WMTA remarkably increased the calcium ion release at all time intervals postsetting, which can significantly influence the osteogenic properties of human dental pulp cells and as a consequence enhance mineralized matrix nodule formation to achieve desirable clinical outcomes. However, the increase in pH values mainly occurred during the short time postsetting. Addition of 1% methylcellulose imposed a delay in elevation of pH and calcium ion release by WMTA.
Investigation of vacuum forming techniques for reduction of loss in mouthguard thickness: part 2—effects of sheet grooving and thermal shrinkage
Authors: Takahashi Mutsumi , Koide Kaoru , Mizuhashi Fumi , Sato Toshihide
Published: January 2015

The aim of this study was to investigate vacuum forming techniques for reduction of loss in mouthguard thickness effects of sheet grooving and thermal shrinkage of extruded sheets on molded mouthguard thickness. Mouthguards were fabricated with ethylene vinyl acetate (EVA) sheets (4.0 mm thick) using a vacuum forming machine. Sheet form was a convexing v‐shaped groove toward the back, 10–40 mm from the anterior end. The sheets were placed in the forming machine with the sheet extrusion direction either vertical or parallel to the model's centerline of right and left. Molding was performed by crimping the sheet using suction when the most descending portion of the sheet sagged downwards from the clamp, 15 mm below the basal surface. Postmolding thickness was determined using a measuring device. Measurement points were the incisal portion (incisal edge and labial surface) and molar portion (cusp and buccal surface). Differences in molded mouthguard thickness with the sheet orientation of extruded EVA sheets were analyzed by student's t‐test. The sheet in parallel axis orientation with the model's centerline yielded higher thickness than vertical orientation at the labial surface and the buccal surface. The present results suggested that addition of a groove to the sheet in conjunction with placement of the sheet with its axis of orientation parallel the centerline of the working model can effectively reduce thickness loss in the molded mouthguard with the equipment and materials used in this study.
Dewey and Video Games: From Education through Occupations to Education through Simulations
Authors: Waddington David I.
Published: January 2015

Critics like Leonard Waks argue that video games are, at best, a dubious substitute for the rich classroom experiences that John Dewey wished to create and that, at worst, they are profoundly miseducative. Using the example of Fate of the World, a climate change simulation game, David Waddington addresses these concerns through a careful demonstration of how video games can recapture some of the lost potential of Dewey's original program of education through occupations. Not only do simulation games realize most of the original goals of education through occupations, but they also solve some of the serious practical problems that Dewey's curriculum generated. Waddington concludes the essay with an analysis of Waks's critiques and some cautionary notes about why it is important to be temperate in our endorsement of educational video gaming.
Friendship and the Public Stage: Revisiting Hannah Arendt's Resistance to “Political Education”
Authors: Schutz Aaron , Sandy Marie G.
Published: January 2015

Hannah Arendt's essays about the 1957 crisis over efforts of a group of youth, the “Little Rock Nine,” to desegregate a high school in Little Rock, Arkansas, reveal a tension in her vision of the “public.” In this article Aaron Schutz and Marie Sandy look closely at the experiences of the youth desegregating the school, especially those of Elizabeth Eckford, drawing upon them to trace a continuum of forms of public engagement in Arendt's work. This ranges from arenas of “deliberative friendship,” where unique individuals collaborate on common efforts, to a more conflictual “public stage,” where groups act in solidarity to change aspects of the public world. While Arendt famously asserted in her essay “The Crisis in Education” that political capacities should not be taught in schools, it makes more sense to see this argument as focused on what she sometimes called the conflictual “public stage,” reflecting the experience of the Little Rock Nine. In contrast, Schutz and Sandy argue that Arendt's own work implies that “deliberative friendship,” as described in her essay “Philosophy and Politics” and elsewhere, should be part of everyday practices in classrooms and schools.
Glutamatergic and dopaminergic neurons in the mouse ventral tegmental area
Authors: Yamaguchi Tsuyoshi , Qi Jia , Wang Hui‐Ling , Zhang Shiliang , Morales Marisela
Published: January 2015

The ventral tegmental area (VTA) comprises dopamine (DA), γ‐aminobutyric acid (GABA) and glutamate (Glu) neurons. Some rat VTA Glu neurons, expressing vesicular glutamate transporter 2 (VGluT2), co‐express tyrosine hydroxylase (TH). While transgenic mice are now being used in attempts to determine the role of VGluT2/TH neurons in reward and neuronal signaling, such neurons have not been characterized in mouse tissue. By cellular detection of VGluT2 mRNA and TH immunoreactivity (TH‐IR), we determined the cellular expression of VGluT2 mRNA within VTA TH‐IR neurons in the mouse. We found that some mouse VGluT2 neurons coexpressed TH‐IR, but their frequency was lower than in the rat. To determine whether low expression of TH mRNA or TH‐IR accounts for this low frequency, we evaluated VTA cellular coexpression of TH transcripts and TH protein. Within the medial aspects of the VTA, some neurons expressed TH mRNA but lacked TH‐IR; among them a subset coexpressed VGluT2 mRNA. To determine if lack of VTA TH‐IR was due to TH trafficking, we tagged VTA TH neurons by Cre‐inducible expression of mCherry in TH::Cre mice. By dual immunofluorescence, we detected axons containing mCherry, but lacking TH‐IR, in the lateral habenula, indicating that low frequency of VGluT2 mRNA (+)/TH‐IR (+) neurons in the mouse is due to lack of synthesis of TH protein, rather than TH protein trafficking. In conclusion, VGluT2 neurons are present in the rat and mouse VTA, but they differ in the populations of VGluT2/TH and TH neurons. Under normal conditions, the translation of TH protein is suppressed in the mouse mesohabenular TH neurons.
Implication of delta opioid receptor subtype 2 but not delta opioid receptor subtype 1 in the development of morphine analgesic tolerance in a rat model of chronic inflammatory pain
Authors: Beaudry H. , Gendron L. , Morón J. A.
Published: January 2015

Opioids are well known for their robust analgesic effects. Chronic activation of mu opioid receptors (MOPs) is, however, accompanied by various unwanted effects such as analgesic tolerance. Among other mechanisms, interactions between MOPs and delta opioid receptors (DOPs) are thought to play an important role in morphine‐induced behavioral adaptations. Interestingly, certain conditions such as inflammation enhance the function of the DOP through a MOP‐dependent mechanism. Here, we investigated the role of DOPs during the development of morphine tolerance in an animal model of chronic inflammatory pain. Using behavioral approaches, we first established that repeated systemic morphine treatment induced morphine analgesic tolerance in rats coping with chronic inflammatory pain. We then observed that blockade of DOPs with subcutaneous naltrindole (NTI), a selective DOP antagonist, significantly attenuated the development of morphine tolerance in a dose‐dependent manner. We confirmed that this effect was DOP mediated by showing that an acute injection of NTI had no effect on morphine‐induced analgesia in naive animals. Previous pharmacological characterizations revealed the existence of DOP subtype 1 and DOP subtype 2. As opposed to NTI, 7‐benzylidenenaltrexone and naltriben were reported to be selective DOP subtype 1 and DOP subtype 2 antagonists, respectively. Interestingly, naltriben but not 7‐benzylidenenaltrexone was able to attenuate the development of morphine analgesic tolerance in inflamed rats. Altogether, our results suggest that targeting of DOP subtype 2 with antagonists provides a valuable strategy to attenuate the analgesic tolerance that develops after repeated morphine administration in the setting of chronic inflammatory pain.
Aging of adhesive interfaces treated with benzalkonium chloride and benzalkonium methacrylate
Authors: Sabatini Camila , Pashley David H.
Published: January 2015

Inhibition of endogenous dentin matrix metalloproteinases (MMPs) within incompletely infiltrated hybrid layers can contribute to the preservation of resin–dentin bonds. This study evaluated the bond stability of interfaces treated with benzalkonium chloride (BAC) and benzalkonium methacrylate (MBAC), and the inhibitory properties of these compounds on dentin MMP activity. Single‐component adhesive ALL‐BOND UNIVERSAL, modified with BAC or MBAC at concentrations of 0, 0.5, 1.0, and 2.0%, was used for microtensile bond strength (μTBS) evaluation after 24 h, 6 months, and 1 yr. Beams produced from human dentin were treated with 37% phosphoric acid, dipped in 0.5% BAC, 1.0% BAC, or water (control) for 60 s, and then incubated in SensoLyte generic MMP substrate to determine MMP activity. A significant decrease in the μTBS after 6 months and 1 yr was observed for the control group only. No significant differences among groups were shown at 24 h. After 6 months and 1 yr, the control group demonstrated significantly lower μTBS than all treatment groups. When applied for 60 s, 0.5% BAC inhibited total MMP activity by 31%, and 1.0% BAC inhibited total MMP activity by 54%. Both BAC and MBAC contributed to the preservation of resin–dentin bonds, probably because of their inhibitory properties of endogenous dentin proteinases.