bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease
Authors: Singh Prabhleen , Ricksten Sven‐Erik , Bragadottir Gudrun , Redfors Bengt , Nordquist Lina
Published: November 2012

Acute kidney injury (AKI) is a major burden on health systems and may arise from multiple initiating insults, including ischaemia‐reperfusion injury, cardiovascular surgery, radiocontrast administration and sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase, with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end‐stage renal disease.

Although the mechanisms for the development of AKI and progression to CKD remain poorly understood, initial impairment of oxygen balance likely constitutes a common pathway, causing renal tissue hypoxia and ATP starvation that, in turn, induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop diuretics, atrial natriuretic peptide and inhibitors of inducible nitric oxide synthase, substances that target kidney oxygen consumption and regulators of renal oxygenation, such as nitric oxide and heme oxygenase‐1.
Adaptation of spherical multicellular magnetotactic prokaryotes to the geochemically variable habitat of an intertidal zone
Authors: Zhou Ke , Zhang Wen‐Yan , Pan Hong‐Miao , Li Jin‐Hua , Yue Hai‐Dong , Xiao Tian , Wu Long‐Fei
Published: November 2012

A combination of microscopic, molecular and biogeochemical methods was used to study the structure, phylogenetics and vertical distribution of spherical multicellular magnetotactic prokaryotes (MMPs) of intertidal sediments in theYellowSea. TheseMMPswere 5.5 μm in diameter and composed of approximately 15–30 cells. They synthesized bullet‐shaped magnetites in chains or clusters. Phylogenetic analysis of 16S rRNAgene sequences suggested that theseMMPsrepresent a novel species affiliated to theDeltaproteobacteria.To study their vertical distribution and the relationship to geochemical parameters, sediment cores were collected after the redox potential was measuredin situ. The sediments were composed of yellow, grey and black layers from the surface to depth. The sphericalMMPswere concentrated near the grey‐black layer transition at a depth of 8–12 cm, while coccoid‐shaped magnetotactic bacteria near the yellow‐grey layer transition at a depth of 3–5 cm. The intertidalMMPsshowed a deeper distribution at more reduced environments than coccoid‐shaped magnetotactic bacteria, andMMPsin lagoon sediments. Additionally theMMPswere concentrated significantly in layers with high proportion of fine sand and total organic carbon, rich in leachable iron but poor in nitrate. These results show an adaptation of sphericalMMPsto the peculiar intertidal sediment habitat.
Should oral misoprostol be used to prevent postpartum haemorrhage in home‐birth settings in low‐resource countries? A systematic review of the evidence
Authors: Hundley VA , Avan BI , Sullivan CJ , Graham WJ
Published: November 2012

Background

Using misoprostol to prevent postpartum haemorrhage (PPH) in home‐birth settings remains controversial.

Objectives

To review the safety and effectiveness of oral misoprostol in preventing PPH in home‐birth settings.

Search strategy

The Cochrane Library, PubMed, and POPLINE were searched for articles published until 31 March 2012.

Selection criteria

Studies, conducted in low‐resource countries, comparing oral misoprostol with a placebo or no treatment in a home‐birth setting. Studies of misoprostol administered by other routes were excluded.

Data collection and analysis

Data were extracted by two reviewers and independently checked for accuracy by a third. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data were sythesised and meta‐analysis was performed where appropriate.

Main results

Ten papers describing two randomised and four non randomised trials. Administration of misoprostol was associated with a significant reduction in the incidence of PPH (RR 0.58, 95% CI 0.38–0.87), additional uterotonics (RR 0.34, 95% CI 0.16–0.73), and referral for PPH (RR 0.49, 95% CI 0.37–0.66). None of the studies was large enough to detect a difference in maternal mortality, and none reported neonatal mortality. Shivering and pyrexia were the most common side effects.

Author's conclusions

The finding that the distribution of oral misoprostol through frontline health workers is effective in reducing the incidence of PPH could be a significant step forwards in reducing maternal deaths in low‐resource countries. However, given the limited number of high‐quality studies in this review, further randomised controlled trials are required to confirm the association, particularly in different implementation settings. Adverse effects have not been systematically captured, and there has been limited consideration of the potential for inappropriate or inadvertent use of misoprostol. Further evidence is needed to inform the development of implementation and safety guidelines on the routine availability of misoprostol.
Changes in snuff and smoking habits in Swedish pregnant women and risk for small for gestational age births
Authors: Baba S , Wikström A‐K , Stephansson O , Cnattingius S
Published: November 2012

Objective

To examine associations between antenatal exposure to Swedish oral moist snuff (which includes essentially only nicotine) and to smoking and risks of small‐for‐gestational‐age (SGA) births and to compare risks among women who stopped or continued using snuff or smoking during pregnancy.

Design

Population‐based cohort study.

Setting

Sweden.

Population

All live singleton births in Sweden 1999–2010.

Methods

Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis.

Main outcome measures

SGA birth, also stratified into preterm (≤36 weeks of gestation) and term (≥37 weeks of gestation) SGA births.

Results

Compared with non‐tobacco users in early pregnancy, snuff users and above all smokers in early pregnancy had increased risks of SGA births: adjusted ORs (95% CI) were 1.26 (1.09–1.46) and 2.55 (2.43–2.67), respectively). Snuff use had, if anything, a stronger association with preterm SGA than term SGA, whereas the opposite was true for smoking. Compared with non‐tobacco users, women who stopped using snuff before their first visit to antenatal care had no increased risks of preterm or term SGA, and women who stopped using snuff later during pregnancy had no increased risk of term SGA. Smoking cessation early in pregnancy was associated with a larger reduction in risk than smoking cessation later in pregnancy.

Conclusions

As both smoking and snuff use influence risk of SGA, both nicotine but above all tobacco combustion products are involved in the mechanisms by which maternal smoking increases the risk of SGA.
Age‐related impairment of endothelial progenitor cell migration correlates with structural alterations of heparan sulfate proteoglycans
Authors: Williamson Kate A. , Hamilton Andrew , Reynolds John A. , Sipos Peter , Crocker Ian , Stringer Sally E. , Alexander Yvonne M.
Published: November 2012

Aging poses one of the largest risk factors for the development of cardiovascular disease. The increased propensity toward vascular pathology with advancing age maybe explained, in part, by a reduction in the ability of circulating endothelial progenitor cells to contribute to vascular repair and regeneration. Although there is evidence to suggest that colony forming unit‐Hill cells and circulating angiogenic cells are subject to age‐associated changes that impair their function, the impact of aging on human outgrowth endothelial cell (OEC) function has been less studied. We demonstrate that OECs isolated from cord blood or peripheral blood samples from young and old individuals exhibit different characteristics in terms of their migratory capacity. In addition, age‐related structural changes were discovered in OEC heparan sulfate (HS), a glycocalyx component that is essential in many signalling pathways. An age‐associated decline in the migratory response of OECs toward a gradient of VEGF significantly correlated with a reduction in the relative percentage of the trisulfated disaccharide, 2‐O‐sulfated‐uronic acid, N, 6‐O‐sulfated‐glucosamine (UA[2S]‐GlcNS[6S]), within OEC cell surface HS polysaccharide chains. Furthermore, disruption of cell surface HS reduced the migratory response of peripheral blood‐derived OECs isolated from young subjects to levels similar to that observed for OECs from older individuals. Together these findings suggest that aging is associated with alterations in the fine structure of HS on the cell surface of OECs. Such changes may modulate the migration, homing, and engraftment capacity of these repair cells, thereby contributing to the progression of endothelial dysfunction and age‐related vascular pathologies.
Ultrasonographic markers and preoperative CA‐125 to distinguish between borderline ovarian tumors and stage I ovarian cancer
Authors: Zacharakis Dimitrios , Thomakos Nikolaos , Biliatis Ioannis , Rodolakis Alexandros , Simou Maria , Daskalakis Georgios , Bamias Aris , Antsaklis Aris
Published: November 2012

Objective

Preoperative evaluation of ovarian masses has become increasingly important for optimal planning of treatment. The aim of this study was to assess the role of preoperative serum cancer antigen 125 (CA‐125) levels in correlation with ultrasonographic features in order to distinguish between borderline ovarian tumors (BOTs) and stage I epithelial ovarian carcinoma (EOC).

Design

Retrospective study.

Setting

Tertiary University Hospital.

Population

We reviewed all women with BOTs and stage I EOC from January 2000 to December 2010. Data from 165 women (66 BOTs and 99 stage I EOC) were analyzed.

Methods

Multivariable logistic regression with stepwise selection of variables was used to determine which clinical variables, ultrasound features and CA‐125 level were independently associated with invasiveness.

Main outcome measures

Utility of ultrasonographic markers and CA‐125 in the preoperative differential diagnosis between BOTs and stage I EOC.

Results

Women with CA‐125 > 100 IU mL−1 had almost three times greater likelihood of belonging in the EOC group [odds ratio (OR) 3.02; confidence interval (CI) 95%: 1.13–8.12]. Furthermore, the presence of large solid component (≥20% of the tumor comprised of solid components) was associated with 4.25 times greater odds of it to representing ovarian cancer rather than a BOT (OR 4.25; 95% CI: 2.05–8.82). In contrast, the presence of papillary projections was associated with a 73% lower likelihood of EOC (OR 0.27; 95% CI: 0.13–0.58).

Conclusions

Preoperative CA‐125 > 100 IU mL−1 combined with the presence of a large solid component and the absence of papillary projections seems to improve the discriminative ability in favor of stage I EOC.
Impact of nursing care on temperature environment in preterm newborns nursed in closed convective incubators
Authors: Deguines C , Dégrugilliers L , Ghyselen L , Chardon K , Bach V , Tourneux P
Published: November 2012

Aims

Very‐low‐birth‐weight (VLBW) neonates require regular nursing procedures with frequent opening of the incubator resulting in a decrease in incubator air temperature. This study was designed to assess changes in the thermal status of VLBW neonates according to the type of nursing care and incubator openings.

Methods

Thirty‐one VLBW neonates (mean gestational age: 28.7 ± 0.3 weeks of gestation) were included. Over a 10‐day period, each opening of the incubator was recorded together with details about caregiving. Body temperature was recorded continuously, and door opening and closing events were recorded by a video camera.

Results

This study analysed 1,798 caregiving procedures with mean durations ranging from 6.2 ± 2.1 to 88.5 ± 33.4 min. Abdominal skin temperature decreased by up to 1.08°C/h for procedures such as tracheal intubation (p < 0.01). The temperature decrease was strongly correlated with the type of procedure (p < 0.01), incubator opening (p < 0.01) and procedure duration (p < 0.01). The procedure duration accounted for only 10% of the abdominal skin temperature change (p < 0.01).

Conclusions

For VLBW neonates nursed in skin temperature servo‐control incubators, the decrease in abdominal skin temperature during caregiving was correlated with the type of procedure, incubator opening modalities and procedure duration. These parameters should be considered to optimize the thermal management of VLBW neonates.
Shared physical custody after family split‐up: implications for health and well‐being in Swedish schoolchildren
Authors: Carlsund Åsa , Eriksson Ulrika , Sellström Eva
Published: November 2012

Abstract

Aim

In Sweden, shared physical custody following a parental separation has emerged as means for children to keep close relationships with both parents. Previous studies show that children benefit from regular contact with both parents, who share responsibility for their social, emotional and economic welfare. In this study, we investigate any associations between family arrangements, that is, two‐parent, single and shared physical custody families and child health outcomes and whether this association was modified by parent–child communication.

Methods

Data on 11‐ to 15‐year‐old children from the 2005/2006 and 2009/2010 Swedish Health Behaviour in School‐aged Children survey were analysed using multivariate logistic regression.

Results

Children in shared physical custody were more likely than children in two‐parent families to report multiple health complaints (OR 1.26) and low well‐being (OR 1.71). When variables of parent–child communication were entered in the model, the initial differences remained between children living in shared physical custody and those living in two‐parent families.

Conclusion

Children in shared physical custody and single‐parent families are more at risk of negative outcomes compared with children in two‐parent families. This association was not modified by parent–child communication in children in shared custody families, indicating that the communication equals that in two‐parent family children.
Mucosal healing and mortality in coeliac disease
Authors: Lebwohl B. , Granath F. , Ekbom A. , Montgomery S. M. , Murray J. A. , Rubio‐Tapia A. , Green P. H. R. , Ludvigsson J. F.
Published: November 2012

Background

Coeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery.

Aims

To determine whether persistent VA is associated with mortality in CD.

Methods

Through biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow‐up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow‐up biopsy.

Results

The mean age of CD diagnosis was 28.4; 63% were female; and the median follow‐up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow‐up biopsy was lower than that of those who did not undergo follow‐up biopsy (Hazard Ratio 0.88, 95% CI: 0.80–0.96). Of the 7648 patients who underwent follow‐up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86–1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37–3.16) or adults (HR 1.00 95% CI: 0.85–1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80–1.14).

Conclusions

Persistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow‐up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.
Prenatal stress and affective disorders in a population birth cohort
Authors: Kleinhaus Karine , Harlap Susan , Perrin Mary , Manor Orly , Margalit‐Calderon Ronit , Opler Mark , Friedlander Yehiel , Malaspina Dolores
Published: November 2012

Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit‐Calderon R, Opler M, Friedlander Y, Malaspina D. Prenatal stress and affective disorders in a population birth cohort.  Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.

Objectives:  Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort.

Methods:  Using data on 90079 offspring born in Jerusalem in 1964–1976 and linked to Israel’s psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab–Israeli war of June 1967 and incidence of mood disorders.

Results:  Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68–5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996–5.99, p = 0.054) and for all ‘other’ mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68–7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73–11.24, p < 0.0001).

Conclusions:  A time‐limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.
Students working with multiple conflicting documents on a scientific issue: Relations between epistemic cognition while reading and sourcing and argumentation in essays
Authors: Bråten Ivar , Ferguson Leila E. , Strømsø Helge I. , Anmarkrud Øistein
Published: November 2012

Background

There is burgeoning research within educational psychology on both epistemic cognition and multiple‐documents literacy, as well as on relationships between the two constructs.

Aim

To examine relationships between epistemic cognition concerning the justification of knowledge claims and sourcing and argumentation skills.

Sample

Participants were 51 Norwegian undergraduates.

Method

Three dimensions of justification were identified in think‐aloud protocols based on students' reading of six documents presenting conflicting claims on the controversial scientific issue of cell phone radiation and health risks: justification by authority, personal justification and justification by multiple sources. Hierarchical multiple regression analyses were performed to examine the unique predictability of these dimensions for essay performance after removing variance associated with prior knowledge about the topic of the documents.

Results

After controlling for topic knowledge, justification by multiple sources uniquely predicted students' sourcing and argumentation in essays that they wrote after reading the documents, with students trying to justify knowledge claims by corroborating across several sources of information more likely to include explicit source citations, link sources and contents, and display better, more integrated argumentation in their essays.

Conclusion

Findings are considered in the light of a theoretical framework for multiple‐documents literacy adapted to the domain of science, and both theoretical and educational implications are discussed.
Individuals’ Innovation Response Behaviour: A Framework of Antecedents and Opportunities for Future Research
Authors: Goepel Monique , Hölzle Katharina , zu Knyphausen‐Aufseß Dodo
Published: November 2012

Innovation response behaviour is defined as individuals’ novelty‐supporting or novelty‐impeding action when navigating innovation initiatives through the organization. A typology of innovation response behaviour is developed, distinguishing between active and passive modes of conduct for novelty‐supporting and novelty‐impeding behaviour, respectively. The antecedents of innovation response behaviour are delineated based on West and Farr's five‐factor model of individual innovation. Moreover, we argue that within organizational contexts, individuals often fail to implement their ideas due to innovation barriers, perceived as factors that are beyond their control. Based on the theory of planned behaviour, we reveal how these barriers influence individuals’ intentional and exhibited innovation response behaviour. Propositions about proximal and distal antecedents of individuals’ innovation response behaviour are derived. Proposing a research framework to study the organizational process of innovation from an actor‐based perspective, this paper intends to link existing research on individual innovation with the process of innovation at the organizational level, explicitly accounting for the socio‐political dynamics and arising managerial problems associated with successful innovation implementation within organizational realities. Implications for research in innovation management are discussed and avenues for future research outlined.
Thematic Ideation – Antecedents and Consequences of Individuals’ Thematic Similarity Recognition
Authors: Froehlich Julia K. , Hoegl Martin
Published: November 2012

Work on thematic thinking, an individual's preference for basing decisions and cognitive processes on thematic similarity, has been developed recently. These preferences also build the basis for idea generation (thematic ideation) and evaluation processes. Research results indicate that there are inter‐individual differences in these preferences. We apply these findings from the field of cognition to the business context and theoretically develop and empirically test a set of antecedents and consequences of thematic thinking. Results indicate that experience and positive affect are positively related to thematic thinking. The consequences that were examined, adaptation and creativity, showed relations which were reverse to the ones hypothesized based on related prior literature. Counter‐intuitively, adaptation is positively related to thematic thinking, while creativity is negatively related. We discuss theoretical and managerial implications and highlight avenues for future research on thematic thinking.
Phylogeny of the sabertoothed felids (Carnivora: Felidae: Machairodontinae)
Authors: Christiansen Per
Published: November 2012

In recent years, advances in our understanding of feline relationships have cast light on their evolutionary history. In contrast, there have been no phylogenetic analyses on machairodont felids, making it difficult to develop an evolutionary hypothesis based on the recent surge of studies on their craniomandibular morphology and functional anatomy. In this paper, I provide the first phylogenetic hypothesis of machairodont relationships based on 50 craniomandibular and dental characters from a wide range of sabercats spanning more 11 Myr. Exact searches produced 19 most‐parsimonious trees, and a strict consensus was well resolved. The Machairodontinae comprise a number of basal taxa (Promegantereon, Machairodus, Nimravides, Dinofelis, Metailurus) and a well‐supported clade of primarily Plio‐Pleistocene taxa (Megantereon, Smilodon, Amphimachairodus, Homotherium, Xenosmilus) for which the name Eumachairodontia taxon novum is proposed. Previous phenetic grouping of machairodont taxa into three distinct groups, the Smilodontini, Homotherini and Metailurini, was not supported by cladistic parsimony analysis, and forcing monophyly of these groups was significantly incompatible with character distribution. Machairodonts as a clade are not characterized by saberteeth, i.e. hypertrophied, blade‐like upper canines, but by small lower canines, as well as small M1; and large P3 parastyle. True saberteeth arose later and are a synapomorphy of the Eumachairodontia.
AKT/GSK3β‐Dependent Autophagy Contributes to the Neuroprotection of Limb Remote Ischemic Postconditioning in the Transient Cerebral Ischemic Rat Model
Authors: Qi Zhi‐Feng , Luo Yu‐Min , Liu Xiang‐Rong , Wang Rong‐Liang , Zhao Hai‐Ping , Yan Feng , Song Zhao‐Jing , Luo Mei , Ji Xun‐Ming
Published: November 2012

Background

Limb remote ischemic postconditioning (RIPostC) has been recognized as an applicable strategy in protecting against cerebral ischemic injury. However, the time window for application of limb RIPostC and the mechanisms behind RIPostC are still unclear.

Aims

In this study, we investigated the protective efficacy and the role of autophagy in limb RIPostC using a transient middle cerebral artery occlusion rat model.

Results

Limb RIPostC applied in the early phase of reperfusion reduced infarct size and improved neurological function. Autophagy levels in penumbral tissues were elevated in neurons of limb RIPostC rats, with an increase in the phosphorylation of AKT and glycogen synthase kinase 3β (GSK3β). Blocking the AKT/GSK3β pathway via the AKT inhibitor LY294002 prior to limb RIPostC suppressed the RIPostC‐induced autophagy and resulted in the activation of caspase‐3 in RIPostC rats, suggesting a critical role for AKT/GSK3β‐dependent autophagy in reducing cell death after cerebral ischemia.

Conclusions

These results aid optimization of the time window for RIPostC use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIPostC.
Young nasopharyngeal cancer patients with radiotherapy and chemotherapy are most prone to ischaemic risk of stroke: a national database, controlled cohort study
Authors: Chu C.‐N. , Chen P.‐C. , Bai L.‐Y. , Muo C.‐H. , Sung F.‐C. , Chen S.‐W.
Published: November 2012

Objectives

This population‐based cohort study investigated the ischaemic stroke risk of patients with nasopharyngeal carcinoma (NPC) by treatment.

Design

Controlled cohort study.

Setting

Based on claims data of National Health Research Insurance Database in years 1996–2010.

Participants

A total of 4615 patients with nasopharyngeal carcinoma newly diagnosed in 2000–2003 were divided into three subgroups: patients received radiotherapy only, patients received both radiotherapy/chemotherapy and patients received neither radiotherapy nor chemotherapy (non‐radio/chemotherapy). They were compared with 36 919 reference persons without stroke and cancer, frequency matched with demographic characteristics.

Main outcome measures

Study subjects were followed up until 2010 to measure ischaemic stroke incidences. Risks associated with treatment and comorbidity were evaluated using Cox proportional hazards regression analysis incorporated with the competing risk of deaths.

Results

Ischaemic stroke incidence rates were ≈2‐fold higher in nasopharyngeal carcinoma patients with radiotherapy, radiotherapy/chemotherapy and non‐radio/chemotherapy than in references (13.8, 12.8 and 12.6 versus 6.07 per 1000 person‐years, respectively). The risk was much higher for 20‐ to 39‐year‐old nasopharyngeal carcinoma patients with radiotherapy/chemotherapy [hazard ratio (HR) 14.7, 95% confidence interval 9.24–23.4]. Hypertension, diabetes, hyperlipidaemia and alcoholism also enhanced the risk with hazard ratios ranging from 2.4 to 9.3. The overall adjusted ischaemic stroke risk was higher in nasopharyngeal carcinoma patients with the two types of treatment than those without, but not significant.

Conclusions

Patients with nasopharyngeal carcinoma are at an elevated risk of ischaemic stroke, without significant difference among treatment modalities. The relative risk is more prominent in younger patients. Comorbidity may enhance the risk.
Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases
Authors: Plaza Jose A. , Feldman Andrew L. , Magro Cynthia
Published: November 2012

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T‐cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co‐expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.
Prescription drug misuse among young adults: Looking across youth cultures
Authors: Kelly Brian C. , Wells Brooke E. , LeClair Amy , Tracy Daniel , Parsons Jeffrey T. , Golub Sarit A.
Published: November 2012

Introduction and Aims

Youth cultures play a key role in the social organisation of drug trends among young people; the current prescription drug misuse trend is no different. The authors evaluated whether patterns of prescription drug misuse differed across several youth cultures.

Design and Methods

Using field survey methods and time–space sampling during 2011, the authors assessed the patterns and prevalence of prescription drug misuse among young adults who are socially active in various urban youth cultures (n = 1781).

Results

The prevalence of lifetime prescription drug misuse is highest within indie rock scenes (52.5%), electronic dance music scenes (52.1%), lesbian parties (53.8%) and alt scenes (50.9%). Prescription drug misuse was lowest among young adults in hip‐hop scenes (25.0%). These findings were upheld in logistic regression analyses that accounted for demographic differences across youth cultures: indie rock scenes (adjusted odds ratio = 2.11), electronic dance music scenes (adjusted odds ratio = 2.20), lesbian parties (adjusted odds ratio = 2.30) and alt scenes (adjusted odds ratio = 2.65) all reported statistically significant (P < 0.05) higher odds of misuse than college bar scenes. Recent prescription drug misuse mirrored patterns for lifetime misuse.

Discussion and Conclusions

The differing prevalence of prescription drug misuse across distinct youth cultures suggests that the trend has not diffused equally among young people. The differing prevalence across youth cultures indicates that the most efficacious strategies for youth intervention may be targeted approaches that account for the subculturally rooted differences in attitudes and social norms.
Emerging immune therapies in type 1 diabetes and pancreatic islet transplantation
Authors: Schneider D. A. , Kretowicz A. M. , von Herrath M. G.
Published: November 2012

In type 1 diabetes (T1D) the immune system attacks insulin‐producing pancreatic β‐cells. Unfortunately, our ability to curb this pathogenic autoimmune response in a disease‐ and organ‐specific manner is still very limited due to the inchoate understanding of the exact nature and the kinetics of the immunological pathomechanisms that lead to T1D. None of the clinical immune interventions thus far, which focused primarily on new‐onset disease, were successful in producing lasting remission or curbing recurrent autoimmunity. However, these studies do provide us access to a tremendous amount of clinical data and specimens, which will aid us in revising our therapeutical approaches and defining the highly needed paradigm shift in T1D immunotherapy. Analysing the foundation and the results of the most current T1D immunotherapeutic trials, this article gives an outlook for future directions of the field.
Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double‐blind, placebo‐controlled trial
Authors: Kaku K. , Inoue S. , Matsuoka O. , Kiyosue A. , Azuma H. , Hayashi N. , Tokudome T. , Langkilde A. M. , Parikh S.
Published: November 2012

Aim

Dapagliflozin is a selective sodium‐glucose co‐transporter 2 (SGLT2) inhibitor under development as a treatment for type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of dapagliflozin monotherapy in Japanese T2DM patients with inadequate glycaemic control.

Methods

Patients (n = 279) were randomized to receive dapagliflozin (1, 2.5, 5 or 10 mg/day) or placebo once daily for 12 weeks. The primary endpoint was change from baseline in haemoglobin A1c (HbA1c) at week 12. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and proportion of patients achieving HbA1c <7.0% at week 12.

Results

Significant reductions in HbA1c were seen with all dapagliflozin doses (−0.11 to −0.44%) versus placebo (+0.37%). Reductions were also observed in FPG with dapagliflozin (−0.87 to −1.77 mmol/l [−15.61 to −31.94 mg/dl]) versus placebo (+0.62 mmol/l [+11.17 mg/dl]). No significant difference in the proportion of patients achieving HbA1c levels <7.0% was noted with dapagliflozin versus placebo. Adverse events (AEs) were more frequent with dapagliflozin (40.7–53.8%) versus placebo (38.9%) and were mostly mild/moderate in intensity. Three hypoglycaemic events were reported (1 each with placebo, dapagliflozin 2.5 mg and 10 mg). The frequency of signs and symptoms suggestive of urinary tract or genital infections was 0–3.8 and 0–1.8% respectively with dapagliflozin and 1.9 and 0% with placebo. No AEs of pyelonephritis were observed.

Conclusions

Compared with placebo, dapagliflozin significantly reduced hyperglycaemia over 12 weeks with a low risk of hypoglycaemia in Japanese T2DM patients with inadequate glycaemic control.
Distributed auditory sensory input within the mouse olfactory cortex
Authors: Varga Adrienn G. , Wesson Daniel W.
Published: November 2012

The mammalian olfactory cortex is commonly considered critical for odor information processing and perception. It is becoming increasingly apparent, however, that the olfactory cortex receives input from multiple sensory channels. Previous work from our group demonstrated the presence of auditory sensory convergence within one olfactory cortical structure, the olfactory tubercle (OT). Interestingly, anatomical evidence for auditory input into the neighboring olfactory piriform cortex (PCX) posits the possibility that auditory sensory input is a distributed property of the olfactory cortex. To address this question, we performed in vivo extracellular recordings from the OT and PCX of anesthetized mice and measured modulations in unit firing in the presence of tones. In support for auditory sensory input being a distributed feature of the olfactory cortex, we found that 29% of units sampled within the PCX display tone‐evoked responses. This population compares with that found within the OT using the same stimuli (37%). While overall tone‐evoked response magnitudes were comparable between the two structures, tone signal : noise was significantly greater within the OT than in the PCX. No effect of tone frequency (1–55 kHz) was found within either structure, with most units being narrowly tuned to a single frequency. These results suggest that a major portion of odor‐evoked output from the olfactory bulb (i.e. that entering the OT and PCX) is subject to auditory sensory input in a manner that may modulate odor information processing, odor‐guided behaviors and perception.
Conditioned enhancement of firing rates and synchrony of hippocampal neurons and firing rates of motor cortical neurons in rats
Authors: Sakurai Yoshio , Takahashi Susumu
Published: November 2012

The aim of this study was to examine the potential ability of neuronal groups to enhance their activities by conditioning without behaviors. We employed a method of neuronal operant conditioning in which increments in the firing rates and synchrony of closely neighboring neurons in the motor cortex and hippocampus were rewarded in the absence of behaviors. Rats were trained to engage in a free‐operant task in which nose‐poke behaviors were rewarded in session 1, and firing rates and synchrony above preset criteria were rewarded in sessions 2 and 3, respectively. The firing rates of motor cortical and hippocampal neuron groups were found to increase rapidly in session 2 similarly to the nose‐poke behavior in session 1. Placing contingency of reward on firing synchrony resulted in selective enhancement of firing synchrony of only hippocampal neurons in session 3. Control experiments revealed that the enhancement of neuronal firing was not attributable to increments of superstitious behaviors or excitation caused by reward delivery. Analysis of the firing rates and synchrony of individual neurons and neuron pairs in each group revealed that the firing rates and synchrony of some but not all neurons and neuron pairs increased in each group. No enhancement was observed in any neurons and neuron pairs recorded by neighboring electrodes not used for conditioning. These results suggest that neuronal operant conditioning enhances the firing rates and synchrony of only some neurons in small restricted areas. The present findings are expected to contribute to further research into neurorehabilitation and neuroprosthesis.
Bicuculline‐ and neurosteroid‐sensitive tonic chloride current in rat hypoglossal motoneurons and atypical dual effect of SR95531
Authors: Chesnoy‐Marchais Dominique
Published: November 2012

Hypoglossal motoneurons (HMs) are known to be under ‘permanent’ bicuculline‐sensitive inhibition and to show ‘transient’ synaptic γ‐aminobutyric acid (GABA)A and glycine inhibitory responses. The present paper describes a permanent bicuculline‐sensitive current that should contribute to their tonic inhibition. This current was recorded in brainstem slices superfused without any exogenous agonist and remained detectable with tetrodotoxin. It could also be blocked by the other GABAA antagonists picrotoxin (PTX) and 2‐(3‐carboxypropyl)‐3‐amino‐6‐(4 methoxyphenyl)pyridazinium bromide) (SR95531; gabazine), but persisted in the presence of a specific blocker of α5‐containing GABAA receptors. Addition of 2 μm 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridin‐3‐ol hydrochloride (THIP), known to preferentially activate GABAA receptors devoid of a γ‐subunit, induced a sustained anionic current that could be further enhanced by neurosteroids such as allopregnanolone (100 nm). Thus, HMs show a tonic inhibitory current carried by extrasynaptic γ‐free GABAA receptors, highly sensitive to neurosteroids. A second result was obtained by using SR95531 at concentrations sufficiently high to rapidly block the tonic current above the chloride equilibrium potential (ECl). Surprisingly, below ECl, SR95531 (10–40 μm) activated a sustained inward current, associated with a conductance increase, and resistant to bicuculline or PTX (100 μm). Similarly, after blockade of the bicuculline‐sensitive current, SR95531 activated an outward current above ECl. The bicuculline‐resistant anionic current activated by SR95531 could be blocked by a GABAC receptor antagonist. Thus, two types of inhibitory GABA receptors, belonging to the GABAA and GABAC families, are able to show a sustained activity in HMs and provide promising targets for neuroprotection under overexcitatory situations known to easily damage these particularly fragile neurons.
Extended‐release antiepileptic drugs: A comparison of pharmacokinetic parameters relative to original immediate‐release formulations
Authors: Leppik Ilo E. , Hovinga Collin A.
Published: November 2012

Many antiepileptic drugs (AEDs) have short half‐lives with large fluctuations in peak‐to‐trough plasma concentrations. Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence. To address these challenges, newer formulations of these AEDs have been developed using unique extended‐release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (Cmax) at steady‐state that often contribute to AEs during treatment with immediate‐release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose‐normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([Cmax–Cmin]/Cavg) compared with the IR versions. This results in flatter concentration‐time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.
Galanin is a modulator of eccrine sweat gland secretion
Authors: Bovell Douglas L. , Holub Barbara S. , Odusanwo Olutayo , Brodowicz Bernhard , Rauch Isabella , Kofler Barbara , Lang Roland
Published: November 2012

The neuropeptide galanin has been ascribed different roles in modulating physiological functions in the skin. The present study examined the function of galanin in eccrine sweat gland physiology. We demonstrated secretion of galanin by sweat glands in vivo by radioimmunoassay of human sweat (20–192 fmol galanin/ml). Furthermore, human sweat glands expressed galanin receptors GalR2 and GalR3. Using chamber short‐circuit current (Isc) measurements showed that application of galanin to human NCL‐SG3 cells led to a significant increase in Isc, which was inhibited by the presence of chloride channel blockers and in chloride‐free Krebs solution. Additionally, application of SNAP 37889, a non‐peptidergic selective antagonist of GalR3, abolished the effect of galanin on Isc. In summary, our results show that galanin can regulate transepithelial chloride ion transport and fluid secretion by stimulating GalR3 in NCL‐SG3 cells and demonstrate a possible important extraneural function of galanin in sweat gland physiology.
Fortalezas Familiares Program: Building Sociocultural and Family Strengths in Latina Women with Depression and Their Families
Authors: Valdez Carmen R. , Abegglen Jessica , Hauser Claire T.
Published: November 2012

The purpose of this article is to describe Fortalezas Familiares (FF; Family Strengths), a community‐based prevention program designed to address relational family processes and promote well‐being among Latino families when a mother has depression. Although depression in Latina women is becoming increasingly recognized, risk and protective mechanisms associated with children's outcomes when a mother has depression are not well understood for Latino families. We begin by reviewing the literature on risk and protective psychosocial mechanisms by which maternal depression may affect Latino youth, using family systems theory and a developmental psychopathology framework with an emphasis on sociocultural factors shaping family processes. Next, we describe the theoretical basis and development of the FF program, a community‐based 12‐week intervention for Latina immigrant women with depression, other caregivers, and their children. Throughout this article, we use a case study to illustrate a Latina mother's vulnerability to depression and the family's response to the FF program. Recommendations for future research and practice include consideration of sociocultural processes in shaping both outcomes of Latino families and their response to interventions.
The Positive Aspects of Being the Parent of an LGBTQ Child
Authors: Gonzalez Kirsten A. , Rostosky Sharon S. , Odom Robert D. , Riggle Ellen D. B.
Published: November 2012

Parenting an LGBTQ (lesbian, gay, bisexual, transgender, or queer) identified child presents unique opportunities for growth and development. This study focused on self‐reported perceptions of the positive aspects of being the parent of an LGBTQ child. Participants (N = 142) were mothers (83.8%) and fathers (16.2%) of LGBTQ identified individuals who responded to an open‐ended online survey. Thematic analysis revealed five primary themes: Personal Growth (open mindedness, new perspectives, awareness of discrimination, and compassion), Positive Emotions (pride and unconditional love), Activism, Social Connection, and Closer Relationships (closer to child and family closeness). The practice implications of these findings for supporting parents in envisioning positive relationship outcomes for themselves and their children are highlighted in the discussion.
The need for decision‐support tools for a changing climate: application to inland fisheries management
Authors: Lynch A. J. , Varela‐Acevedo E. , Taylor W. W.
Published: November 2012

Large‐scale environmental impacts, such as those of climate change on fisheries, require policy and management action not only at the local level, but at regional, national and international levels. Fisheries biology and ecology, along with social, political and economic considerations, can influence policy design and implementation. Decision‐support tools can integrate these sciences to distil often complex, mechanistic and synergistic processes into a format that the public, policy makers and managers can use when designing strategies to ensure fisheries sustainability in the face of large‐scale environmental perturbations, such as climate change. Harvest management of lake whitefish, Coregonus clupeaformis (Mitchill), in the Laurentian Great Lakes provides an excellent case study to examine the value and utility of a decision‐support tool for inland fisheries management when considering the effects of climate change because this fishery is expected to be impacted by future changes in water temperature, ice cover and wind speed.