bluuebunny/crossref_metadata_2025 huggingface dataset:
Questioning urban modernity
Authors: Dibazar Pedram , Lindner Christoph , Meissner Miriam , Naeff Judith
Published: August 2013

This critical introduction to the special issue examines the place and significance of urban modernity as a concept in contemporary urban studies. It draws on postcolonial theory to demonstrate that the relation between the city and modernity developed within the western tradition of urban thinking has produced a geographically and historically uneven conceptualisation of urban modernity. This conceptualisation not only involves dynamics of othering, in which cities are differentiated hierarchically, but also obscures a vast array of possible understandings of contemporary urban living. The aim of this introduction is to question this way of thinking about urban modernity in light of globalisation and 21st-century transformations of urban space. It argues that it is crucial, now more than ever, to render the concept of urban modernity attentive to the lived experience of contemporary cities worldwide.
Pudong: The shanzhai global city
Authors: de Kloet Jeroen , Scheen Lena
Published: August 2013

Shanghai’s Pudong financial district is known for its spectacular skyline, which Michelle Huang has referred to as ‘a copy of a global city’ – a reading that this article pushes further. What does this ‘copy of a global city’ tell us about the intricate relationships between globalisation, capitalism and urbanity? Whereas Koolhaas proposed the notion of the ‘generic city’ to grasp the future Asian city, this article argues that his reading reifies the conservative premise that globalisation equals homogenisation. Although Abbas’ concept of the ‘fake’ comes closer to what we see emerging in Asia, it simultaneously reifies the problematic idea of an authentic original. Instead, the article proposes reading Pudong as a shanzhai version of the global city: meaning the culture of Chinese pirated, ‘fake’ products. By linking the notion of shanzhai to that of the global city, it aims to recuperate the locality, fluidity and peculiarity of the global city.
Yes my name is Ahmet, but please don’t target me. Islamic marketing: Marketing IslamTM?
Authors: Süerdem Ahmet
Published: August 2013

The coupling of consumerism with Islamic cultural movements is cherished as providing counterevidence to Orientalist stereotypes. Although this coupling may be celebrated like the cultural recognition of Muslims, this commentary highlights some reserves against a premature conclusion for the emancipatory role of the Islamic consumerism. Liaising marketing and Islamic may be a dangerous liaison articulating an important discursive function related to the production of profits, ideology, power, and identity. Critical consumer studies up to now have emphasized the role of everyday religious and cultural practices as a form of resistance against the disciplinary role of modern institutions, state, and administrative apparatus. However, the disciplinary role of populist cultural movements has been relatively underemphasized. A critical position should keep its distance to rigid dichotomizations depicting popular as excluded subalterns struggling against the technologies of domination. The relations between the popular and domination are not so clear cut if we evoke that truth games perform within a matrix of complex relations between the self and structure. Branding neo-populist Islamist movements as more “humane”, ethical ways of modernity tend to reduce complex political societal strategies struggling for cultural hegemony simply to a moralizing discourse. These movements tend to create an emulation of community and charity rather than the decommodification of the sociality dissected and atomized by neoliberal commodification. Public display of conspicuous charity and morality serves more to branding of Islam rather than the modesty of Islam. Marketing an emulated Islamic identity for self-branding of Muslims and excommunicating the internal other can be as dangerous as Orientalist ideology.
Rudiments of a value praxeology
Authors: Arnould Eric J.
Published: August 2013

This commentary complements Karababa and Kjeldgaard's fine review paper. It discusses how a practice theory of value might be developed. It suggest value is one outcome of practices. And it draws attention to how value producing practices might differ depending upon what regime of value dominates. It encourages us to think that value producing practices critical to consumer culture differ from those in other cultural contexts.
Error Augmentation Enhancing Arm Recovery in Individuals With Chronic Stroke
Authors: Abdollahi Farnaz , Case Lazarro Emily D. , Listenberger Molly , Kenyon Robert V. , Kovic Mark , Bogey Ross A. , Hedeker Donald , Jovanovic Borko D. , Patton James L.
Published: August 2013

Background. Neurorehabilitation studies suggest that manipulation of error signals during practice can stimulate improvement in coordination after stroke. Objective. To test visual display and robotic technology that delivers augmented error signals during training, in participants with stroke. Methods. A total of 26 participants with chronic hemiparesis were trained with haptic (via robot-rendered forces) and graphic (via a virtual environment) distortions to amplify upper-extremity (UE) tracking error. In a randomized crossover design, the intervention was compared with an equivalent amount of practice without error augmentation (EA). Interventions involved three 45-minute sessions per week for 2 weeks, then 1 week of no treatment, and then 2 additional weeks of the alternate treatment. A therapist provided a visual cursor using a tracking device, and participants were instructed to match it with their hand. Haptic and visual EA was used with blinding of participant, therapist, technician-operator, and evaluator. Clinical measures of impairment were obtained at the beginning and end of each 2-week treatment phase as well as at 1 week and at 45 days after the last treatment. Results. Outcomes showed a small, but significant benefit to EA training over simple repetitive practice, with a mean 2-week improvement in Fugl-Meyer UE motor score of 2.08 and Wolf Motor Function Test of timed tasks of 1.48 s. Conclusions. This interactive technology may improve UE motor recovery of stroke-related hemiparesis.
Getting started with research: ‘Carrying out your research project’
Authors: Browne Jacinta E
Published: August 2013

This paper gives an overview of the considerations and practical aspects of carrying out a research project, which may be of use to those beginning their research career or simply carrying out a research project for the first time as part of an academic qualification. It outlines practical steps for consideration in the day-to-day management of a research project and highlights areas which require particular consideration for a project to be completed successfully.
Management of interstitial pregnancy – a case managed with ultrasound guidance and a review of literature
Authors: Aich Abhijit , Budithi Srividhya , Kumar Bidyut
Published: August 2013

Interstitial pregnancy is a rare form of ectopic pregnancy. Interstitial pregnancy refers to an ectopic pregnancy implanted in the interstitial portion of the tube. This is the segment of Fallopian tube traversing the muscular wall of the uterus, beginning at the tubal ostium and proceeding superiorly and laterally away from the uterine cavity to join the isthmic portion of the tube arising from the fundus. The interstitial portion, being a relatively thicker portion of the tube, has a greater capacity to expand before rupture takes place. Therefore, such pregnancies may present late and rupture can result in life-threatening haemorrhage, particularly because of the high vascularity of this region. Diagnosis is difficult and treatment has not been standardized. A high index of suspicion is required to diagnose this type of pregnancy. Access to high-resolution transvaginal ultrasonography and highly sensitive quantitative β-hCG assays has increased early detection and appropriate management. A wide array of treatment methods have been tried for the management of this condition. The optimum therapeutic option depends on variables related to each individual case.
Renal cell carcinoma in polycystic kidney disease: Use of contrast-enhanced ultrasound for characterization and review of the literature
Authors: Navaratne Subhachandra , Huang Dean Y , Sellars Maria E , Sidhu Paul S
Published: August 2013

We describe a case of renal cell carcinoma (RCC) in a patient with autosomal dominant polycystic kidney disease (ADPKD), seen on B-mode sonography, confirmed with the use of contrast-enhanced ultrasound (CEUS) and demonstrated on computed tomography (CT). RCC in ADPKD is described but is rare, no more frequent than in the general population, although often sought on imaging. CEUS may be used in patients with ADPKD when a complicating carcinoma is suspected on the B-mode examination in lieu of imaging strategies that use nephrotoxic contrast agents.
Fetal intra-abdominal umbilical vein varix: a case report
Authors: Kalumbi Chimwemwe , Crowson Richard , Soydemir Fatimah , Butcher Tracy
Published: August 2013

The incidence of the fetal intra-abdominal umbilical vein varix condition is very rare. Its significance in pregnancy is still unknown, but it has been associated with fetal hydrops, IUGR and still birth. However, in most isolated cases, the outcome is good. A 31-year-old primigravida was referred to the antenatal clinic at 28 weeks of gestation as her uterus was measuring small for gestational age. Her anomaly scan at 20 weeks was normal. The scan at 28 weeks showed growth below the lower 10th centile with normal liquor volume and umbilical Doppler wave velocity. However, an intra-abdominal ovoid structure measuring 28 mm × 10 mm was seen superior to the fetal bladder. Color flow Doppler revealed venous flow in continuity with the umbilical vein. A diagnosis of umbilical varix was made. The venous flow was present throughout the lesion, suggesting the absence of thrombi. There was no evidence of fetal hydrops. Subsequent scans at 32, 34 and 36 weeks showed no increase in size of the umbilical varix and progressive fetal growth, although growth remained below the lower 10th centile with normal Doppler results and liquor volume. The patient had an uneventful emergency cesarean section at 37 weeks for failed induction of labor and reduced fetal movements. Postnatal assessment and a follow-up neonatal cardiac echo scan were normal. Our case supports the new emerging evidence that pregnancy outcome in cases of isolated fetal umbilical vein varix is generally good. Caution must be exercised against unnecessary early induction and costly preterm births.
The importance of visceral fat mass in obese pregnant women and relation with pregnancy outcomes
Authors: Balani Jyoti , Hyer Steve , Johnson Antoinette , Shehata Hassan
Published: August 2013

Background

Maternal obesity is a well established risk factor for gestational diabetes but it is not known if the pattern of maternal fat distribution predicts adverse pregnancy outcomes.

Methods

Body composition was assessed by bioimpedance using Inbody 720® in 302 consecutive obese pregnant women attending a weight management clinic. The relation of visceral fat mass and total percentage body fat with the development of gestational diabetes and perinatal outcomes was evaluated.

Results

Women developing gestational diabetes (Group 1; n = 72) were older, had higher body mass indices and greater central obesity (waist:hip ratio, visceral fat mass) compared with those remaining normoglycaemic. Visceral fat mass, but not percentage body fat, correlated with fasting glucose in all patients ( r = 0.2, p < 0.001) and particularly those in Group 1 ( r = 0.35, p = 0.002). Visceral fat mass, but not percentage body fat, also correlated strongly with glycaemia, particularly in Group 1 ( r = 0.47, p < 0.0001). Visceral fat mass also showed a weak but significant correlation with baby weight ( r = 0.17, p = 0.01).

Discussion

Central obesity, as assessed by early pregnancy waist:hip ratio and particularly by visceral fat mass, is a predictor of gestational diabetes in addition to classical risk factors and may help identify those obese patients at increased risk of complications.
RETRACTED: Nut consumption with risk of hypertension and type 2 diabetes mellitus: A meta-analysis of prospective cohort studies
Authors: Guo Kai , Jiang Yibo , Zhou Zhiwen , Li Yigang
Published: August 2013

Background

The consumption of nuts was reported to be associated with risk of hypertension and type 2 diabetes mellitus (T2DM), but the results were inconclusive. The aim of this study was to systematically examine longitudinal studies investigating nut intake in relation to risk of hypertension and T2DM.

Methods

A systematic search of the PubMed and EMBASE databases to 31 March 2013 was performed. Reference lists of retrieved articles were also screened. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Q and I2statistics were used to examine between-study heterogeneity.

Results

A total of nine prospective cohort studies (three for hypertension and six for T2DM) were identified. Using random effects models, we found that based on the highest vs lowest analysis, nut consumption were inversely associated with risk of hypertension (SRR = 0.84, 95% CI: 0.76–0.93, pheterogeneity = 0.831, I2 = 0%). Dose-response analyses indicated that nut consumption at more than two servings/wk, but not ne serving/wk, had a preventative role in the hypertension. In addition, nut consumption was not associated with risk of T2DM (SRRs = 0.98, 95% CI: 0.84–1.15; pheterogeneity = 0.008, I2 = 67.7%) on the basis of the highest vs lowest analysis. This null association was also shown in the dose-response analysis.

Conclusion

In our meta-analysis, nut consumption is found to be inversely associated with hypertension risk but is not associated with the risk of T2DM.
Memoirs, confessions and apologies: the last chapter of Byzantine autobiography
Authors: Angold Michael
Published: August 2013

Two issues are addressed here: the status of Byzantine autobiography and the state of Byzantine literary culture in its last years. Autobiographical information was mostly a device used at all levels of Byzantine literature for immediacy, emphasis and to suggest personal involvement. It continued to function in this way in the last years of Byzantium, but there was also a degree of experimentation, as it extended its range into satire and comedy and, in the hands of Theodore Agallianos evolved from the rhetoric of apologia into fully-fledged autobiography.
Days of those made like me: retrospective pleasure, sexual knowledge, and C. P. Cavafy’s homobiographics
Authors: Papanikolaou Dimitris
Published: August 2013

This article begins with a comparison between the anonymous Roman d’un inverti (1894/5) and Cavafy’s poem ‘Na μείνει’, and then proceeds to read Cavafy’s private notes and key erotic poems in the context of late nineteenth- and twentieth-century discourses about non-normative sexuality. During that period, and in a discursive domain dominated by sexological case studies, the deviant sexual life story was published in order to titillate, check, control and medicalize. In Cavafy’s texts we see, instead, a network of homosexual life stories proposed as a platform for the conceptualization of novel sexual, aesthetic and social technologies, as well as a new ethics of contact.
Deregulation of ETS1 and FLI1 contributes to the pathogenesis of diffuse large B-cell lymphoma
Authors: Bonetti Paola , Testoni Monica , Scandurra Marta , Ponzoni Maurilio , Piva Roberto , Mensah Afua A. , Rinaldi Andrea , Kwee Ivo , Tibiletti Maria Grazia , Iqbal Javeed , Greiner Timothy C. , Chan Wing-Chung , Gaidano Gianluca , Piris Miguel A. , Cavalli Franco , Zucca Emanuele , Inghirami Giorgio , Bertoni Francesco
Published: August 2013

Key Points

A recurrent gain of a region of chromosome 11 (11q24.3) occurs in up to one-quarter of cases of diffuse large B-cell lymphoma. ETS1 and FLI1 genes are overexpressed and determine proliferation, survival, and differentiation arrest of the lymphoma cells.
Genetically coupled receptor–ligand pair NKp80-AICL enables autonomous control of human NK cell responses
Authors: Klimosch Sascha N. , Bartel Yvonne , Wiemann Stefan , Steinle Alexander
Published: August 2013

Key Points

Human NK cells contain Golgi complex–associated intracellular stores of AICL, a ligand of the activating NK receptor NKp80. Upon exposure to inflammatory cytokines, AICL surfaces on NK cells, rendering them susceptible to NKp80-mediated bystander NK cytolysis.
A simple methodology to assess endolysosomal protease activity involved in antigen processing in human primary cells
Authors: Vaithilingam Archana , Lai Nicole Y , Duong Ellen , Boucau Julie , Xu Yang , Shimada Mariko , Gandhi Malini , Le Gall Sylvie
Published: August 2013

Background

Endolysosomes play a key role in maintaining the homeostasis of the cell. They are made of a complex set of proteins that degrade lipids, proteins and sugars. Studies involving endolysosome contribution to cellular functions such as MHC class I and II epitope production have used recombinant endolysosomal proteins, knockout mice that lack one of the enzymes or purified organelles from human tissue. Each of these approaches has some caveats in analyzing endolysosomal enzyme functions.

Results

In this study, we have developed a simple methodology to assess endolysosomal protease activity. By varying the pH in crude lysate from human peripheral blood mononuclear cells (PBMCs), we documented increased endolysosomal cathepsin activity in acidic conditions. Using this new method, we showed that the degradation of HIV peptides in low pH extracts analyzed by mass spectrometry followed similar kinetics and degradation patterns as those performed with purified endolysosomes.

Conclusion

By using crude lysate in the place of purified organelles this method will be a quick and useful tool to assess endolysosomal protease activities in primary cells of limited availability. This quick method will especially be useful to screen peptide susceptibility to degradation in endolysosomal compartments for antigen processing studies, following which detailed analysis using purified organelles may be used to study specific peptides.
Genotype is an important determinant factor of host susceptibility to periodontitis in the Collaborative Cross and inbred mouse populations
Authors: Shusterman Ariel , Salyma Yasser , Nashef Aysar , Soller Morris , Wilensky Asaf , Mott Richard , Weiss Ervin I , Houri-Haddad Yael , Iraqi Fuad A
Published: August 2013

Background

Periodontal infection (Periodontitis) is a chronic inflammatory disease, which results in the breakdown of the supporting tissues of the teeth. Previous epidemiological studies have suggested that resistance to chronic periodontitis is controlled to some extent by genetic factors of the host. The aim of this study was to determine the phenotypic response of inbred and Collaborative Cross (CC) mouse populations to periodontal bacterial challenge, using an experimental periodontitis model. In this model, mice are co-infected withPorphyromonas gingivalisandFusobacterium nucleatum, bacterial strains associated with human periodontal disease. Six weeks following the infection, the maxillary jaws were harvested and analyzed for alveolar bone loss relative to uninfected controls, using computerized microtomography (microCT). Initially, four commercial inbred mouse strains were examined to calibrate the procedure and test for gender effects. Subsequently, we applied the same protocol to 23 lines (at inbreeding generations 10–18) from the newly developed mouse genetic reference population, the Collaborative Cross (CC) to determine heritability and genetic variation of control bone volume prior to infection (CBV, naïve bone volume around the teeth of uninfected mice), and residual bone volume (RBV, bone volume after infection) and loss of bone volume (LBV, the difference between CBV and RBV) following infection.

Results

BALB/CJ mice were highly susceptible (P<0.05) whereas DBA/2J, C57BL/6J and A/J mice were resistant. Six lines of the tested CC population were susceptible, whereas the remaining lines were resistant to alveolar bone loss. Gender effects on bone volume were tested across the four inbred and 23 CC lines, and found not to be significant. Based on ANOVA analyses, broad-sense heritabilities were statistically significant and equal to 0.4 for CBV and 0.2 for LBV.

Conclusions

The moderate heritability values indicate that the variation in host susceptibility to the disease is controlled to an appreciable extent by genetic factors. These results strongly support the possibility of using the Collaborative Cross, as well as developing dedicated F2 (resistant x susceptible inbred strains) resource populations, for future dissection of genetic factors in periodontitis.
Expression of SV2 isoforms during rodent brain development
Authors: Crèvecœur Julie , Foerch Patrik , Doupagne Melissa , Thielen Caroline , Vandenplas Catherine , Moonen Gustave , Deprez Manuel , Rogister Bernard
Published: August 2013

Background

SV2A, SV2B and SV2C are synaptic vesicle proteins that are structurally related to members of the major facilitator superfamily (MFS). The function and transported substrate of the SV2 proteins is not clearly defined although they are linked to neurotransmitters release in a presynaptic calcium concentration-dependent manner. SV2A and SV2B exhibit broad expression in the central nervous system while SV2C appears to be more restricted in defined areas such as striatum. SV2A knockout mice start to display generalized seizures at a late developmental stage, around post-natal day 7 (P7), and die around P15. More recently, SV2A was demonstrated to be the molecular target of levetiracetam, an approved anti-epileptic drug (AED). The purpose of this work was to precisely analyze and quantify the SV2A, SV2B and SV2C expression during brain development to understand the contribution of these proteins in brain development and their impact on epileptic seizures.

Results

First, we systematically analyzed by immunohistofluorescence, the SV2A, SV2B and SV2C expression during mouse brain development, from embryonic day 12 (E12) to P30. This semi-quantitative approach suggests a modulation of SV2A and SV2B expression in hippocampus around P7. This is the reason why we used various quantitative approaches (laser microdissection of whole hippocampus followed by qRT-PCR and western blot analysis) indicating that SV2A and SV2B expression increased between P5 and P7 and remained stable between P7 and P10. Moreover, the increase of SV2A expression in the hippocampus at P7 was mainly observed in the CA1 region while SV2B expression in this region remains stable.

Conclusions

The observed alterations of SV2A expression in hippocampus are consistent with the appearance of seizures in SV2A−/− animals at early postnatal age and the hypothesis that SV2A absence favors epileptic seizures around P7.
Association between chronic obstructive pulmonary disease and gastroesophageal reflux disease: a national cross-sectional cohort study
Authors: Kim Jinhee , Lee Jin Hwa , Kim Yuri , Kim Kyungjoo , Oh Yeon-Mok , Yoo Kwang Ha , Rhee Chin Kook , Yoon Hyoung Kyu , Kim Young Sam , Park Yong Bum , Lee Sei Won , Lee Sang Do
Published: August 2013

Background

Gastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.

Methods

Data were collected from the National Health Insurance Database of Korea. The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009. Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.

Results

The prevalence of GERD in COPD patients was 28% (39,987/141,057). Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD. Most of COPD medications except inhaled muscarinic antagonists were associated with GERD. The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).

Conclusions

The prevalence of GERD in patients with COPD was high. Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD. The presence of GERD was associated with COPD exacerbation.
Mitochondrial respiratory chain dysfunction modulates metalloproteases -1, -3 and -13 in human normal chondrocytes in culture
Authors: Cillero-Pastor Berta , Rego-Pérez Ignacio , Oreiro Natividad , Fernandez-Lopez Carlos , Blanco Francisco J
Published: August 2013

Background

Mitochondrion has an important role in the osteoarthritis (OA) pathology. We have previously demonstrated that the alteration of the mitochondrial respiratory chain (MRC) contributes to the inflammatory response of the chondrocyte. However its implication in the process of cartilage destruction is not well understood yet. In this study we have investigated the relationship between the MRC dysfunction and the regulation of metalloproteases (MMPs) in human normal chondrocytes in culture.

Methods

Human normal chondrocytes were isolated from human knees obtained form autopsies of donors without previous history of rheumatic disease. Rotenone, 3-Nitropropionic acid (NPA), Antimycin A (AA), Sodium azide and Oligomycin were used to inhibit the activity of the mitochondrial complexes I, II, III, IV and V respectively. The mRNA expression of MMPs -1, -3 and -13 was studied by real time PCR. The intracellular presence of MMP proteins was evaluated by western blot. The liberation of these proteins to the extracellular media was evaluated by ELISA. The presence of proteoglycans in tissue was performed with tolouidin blue and safranin/fast green. Immunohistochemistry was used for evaluating MMPs on tissue.

Results

Firstly, cells were treated with the inhibitors of the MRC for 24 hours and mRNA expression was evaluated. An up regulation of MMP-1 and -3 mRNA levels was observed after the treatment with Oligomycin 5 and 100 μg/ml (inhibitor of the complex V) for 24 hours. MMP-13 mRNA expression was reduced after the incubation with AA 20 and 60 μg/ml (inhibitor of complex III) and Oligomycin. Results were validated at protein level observing an increase in the intracellular levels of MMP-1 and -3 after Oligomycin 25 μg/ml stimulation [(15.20±8.46 and 4.59±1.83 vs. basal=1, respectively (n=4; *P<0.05)]. However, AA and Oligomycin reduced the intracellular levels of the MMP-13 protein (0.70±0.16 and 0.3±0.24, respectively vs. basal=1). In order to know whether the MRC dysfunction had an effect on the liberation of MMPs, their levels were evaluated in the supernatants. After 36 hours of stimulation, values were: MMP-1=18.06±10.35 with Oligomycin 25 μg/ml vs. basal=1, and MMP-3=8.49±4.32 with Oligomycin 5 μg/ml vs. basal=1 (n=5; *P<0.05). MMP-13 levels in the supernatants were reduced after AA 60 μg/ml treatment (0.50±0.13 vs. basal=1) and Oligomycin 25 μg/ml (0.41±0.14 vs. basal=1); (n=5; *P<0.05). The treatment of explants with Oligomycin, showed an increase in the positivity of MMP-1 and -3. Explants stimulated with AA or Oligomycin revealed a decrease in MMP-13 expression. Proteoglycan staining demonstrated a reduction of proteoglycan levels in the tissues treated with Oligomycin.

Conclusions

These results reveal that MRC dysfunction modulates the MMPs expression in human normal chondrocytes demonstrating its role in the regulation of the cartilage destruction.
Signet-ring cell carcinoma of the breast: a case report
Authors: Li Xing , Feng Yan-fen , Wei Wei-dong , Liu Peng , Xie Ze-ming , Wang Jin , Xie Xiao-ming
Published: August 2013

Signet-ring cell carcinoma (SRCC) can arise from virtually all organs. However, primary SRCC of the breast is very rare. Until 2003, SRCC was placed under ‘mucin-producing carcinomas’ and separated from other carcinomas by the World Health Organization (WHO). To date, only a few cases have been reported. A case of a 46-year-old woman with primary SRCC of the breast is presented in this report. The patient underwent a right modified radical mastectomy with axillary lymph node dissection. Characteristic features and differential diagnosis of this tumor are discussed in the light of pertinent literature.
Detection of EGFR mutations in circulating free DNA by PNA-mediated PCR clamping
Authors: Kim Hye-Ryoun , Lee Sung Yong , Hyun Dae-Sung , Lee Min Ki , Lee Hyun-Kyung , Choi Chang-Min , Yang Sei-Hoon , Kim Young-Chul , Lee Yong Chul , Kim Sun Young , Jang Seung Hun , Lee Jae Cheol , Lee Kye Young
Published: August 2013

Background

Epidermal growth factor receptor (EGFR)-activating mutations are major determinants in predicting the tumor response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). Noninvasive test for the detection of EGFR mutations is required, especially in NSCLC patients from whom tissue is not available. In this study, we assessed the feasibility of detection of EGFR mutations in free DNA circulating in plasma.

Methods

Plasma samples of 60 patients with partial response to gefitinib were analyzed to detect EGFR-activating mutations in exons 19 and 21. Forty (66.7%) of patients had tumor EGFR mutation results. EGFR mutations in plasma were detected using the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method. All clinical data and plasma samples were obtained from 11 centers of the Korean Molecular Lung Cancer Group (KMLCG).

Results

Of the 60 patients, 39 were female and the median age was 62.5 years. Forty-three patients never smoked, 53 had adenocarcinomas, and seven had other histologic types. EGFR-activating mutation was detected in plasma of 10 cases (exon 19 deletion in seven and exon 21 L858R point mutation in three). It could not be found in plasma after treatment for 2 months. When only patients with confirmed EGFR mutation in tumor were analyzed, 17% (6 of 35) of them showed positive plasma EGFR mutation and the mutation type was completely matched with that in tumor. There was no statistically significant difference in clinical parameters between patients with EGFR mutations in plasma and those without EGFR mutations.

Conclusions

The detection rate of EGFR mutations from plasma was not so high despite highly sensitive EGFR mutation test suggesting that more advances in detection methods and further exploration of characteristics of circulating free DNA are required.
Sedation in French intensive care units: a survey of clinical practice
Authors:   The SRLF Trial Group
Published: August 2013

Background

Sedation is used frequently for patients in intensive care units who require mechanical ventilation, but oversedation is one of the main side effects. Different strategies have been proposed to prevent oversedation. The extent to which these strategies have been adopted by intensivists is unknown.

Methods

We developed a six-section questionnaire that covered the drugs used, modalities of drug administration, use of sedation scales and procedural pain scales, use of written local procedures, and targeted objectives of consciousness. In November 2011, the questionnaire was sent to 1,078 intensivists identified from the French ICU Society (SRLF) database.

Results

The questionnaire was returned by 195 intensivists (response rate 18.1%), representing 135 of the 282 ICUs (47.8%) listed in the French ICU society (SRLF) database. The analysis showed that midazolam and sufentanil are the most frequently used hypnotics and opioids, respectively, administered in continuous intravenous (IV) infusions. IV boluses of hypnotics without subsequent continuous IV infusion are used occasionally (in <25% of patients) by 65% of intensivists. Anxiolytic benzodiazepines (e.g., clorazepam, alprazolam), hydroxyzine, and typical neuroleptics, via either an enteral or IV route, are used occasionally by two thirds of respondents. The existence of a written, local sedation management procedure in the ICU is reported by 55% of respondents, 54% of whom declare that they use it routinely. Written local sedation procedures mainly rely on titration of continuous IV hypnotics (90% of the sedation procedures); less frequently, sedation procedures describe alternative approaches to prevent oversedation, including daily interruption of continuous IV hypnotic infusion, hypnotic boluses with no subsequent continuous IV infusion, or the use of nonhypnotic drugs. Among the responding intensivists, 98% consider eye opening, either spontaneously or after light physical stimulation, a reasonable target consciousness level in patients with no severe respiratory failure or intracranial hypertension.

Conclusions

Despite a low individual response rate, the respondents to our survey represent almost half of the ICUs in the French SRLF database. The presence of a written local sedation procedure, a cornerstone of preventing oversedation, is reported by only half of respondents; when present, it is used in for a limited number of patients. Sedation procedures mainly rely on titration of continuous IV hypnotics, but other strategies to limit oversedation also are included in sedation procedures. French intensivists no longer consider severely altered consciousness a sedation objective for most patients.
Comparative mortality risks of antipsychotic medications in community-dwelling older adults
Authors: Gerhard T. , Huybrechts K. , Olfson M. , Schneeweiss S. , Bobo W. V. , Doraiswamy P. M. , Devanand D. P. , Lucas J. A. , Huang C. , Malka E. S. , Levin R. , Crystal S.
Published: August 2013

Background

All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents.

Aims

To estimate the comparative mortality risks of commonly prescribed antipsychotic agents in older people living in the community.

Method

A retrospective, claims-based cohort study was conducted of people over 65 years old living in the community who had been newly prescribed risperidone, olanzapine, quetiapine, haloperidol, aripiprazole or ziprasidone (n = 136 393). Propensity score-adjusted Cox proportional hazards models assessed the 180-day mortality risk of each antipsychotic compared with risperidone.

Results

Risperidone, olanzapine and haloperidol showed a dose–response relation in mortality risk. After controlling for propensity score and dose, mortality risk was found to be increased for haloperidol (hazard ratio (HR) = 1.18, 95% CI 1.06–1.33) and decreased for quetiapine (HR = 0.81, 95% CI 0.73–0.89) and olanzapine (HR = 0.82, 95% CI 0.74–0.90).

Conclusions

Significant variation in mortality risk across commonly prescribed antipsychotics suggests that antipsychotic selection and dosing may affect survival of older people living in the community.
Late-Onset Exercise in Female Rat Offspring Ameliorates the Detrimental Metabolic Impact of Maternal Obesity
Authors: Bahari Hasnah , Caruso Vanni , Morris Margaret J.
Published: August 2013

Rising rates of maternal obesity/overweight bring the need for effective interventions in offspring. We observed beneficial effects of postweaning exercise, but the question of whether late-onset exercise might benefit offspring exposed to maternal obesity is unanswered. Thus we examined effects of voluntary exercise implemented in adulthood on adiposity, hormone profiles, and genes involved in regulating appetite and metabolism in female offspring. Female Sprague Dawley rats were fed either normal chow or high-fat diet (HFD) ad libitum for 5 weeks before mating and throughout gestation/lactation. At weaning, female littermates received either chow or HFD and, after 7 weeks, half were exercised (running wheels) for 5 weeks. Tissues were collected at 15 weeks. Maternal obesity was associated with increased hypothalamic inflammatory markers, including suppressor of cytokine signaling 3, TNF-α, IL-1β, and IL-6 expression in the arcuate nucleus. In the paraventricular nucleus (PVN), Y1 receptor, melanocortin 4 receptor, and TNF-α mRNA were elevated. In the hippocampus, maternal obesity was associated with up-regulated fat mass and obesity-associated gene and TNF-α mRNA. We observed significant hypophagia across all exercise groups. In female offspring of lean dams, the reduction in food intake by exercise could be related to altered signaling at the PVN melanocortin 4 receptor whereas in offspring of obese dams, this may be related to up-regulated TNF-α. Late-onset exercise ameliorated the effects of maternal obesity and postweaning HFD in reducing body weight, adiposity, plasma leptin, insulin, triglycerides, and glucose intolerance, with greater beneficial effects in offspring of obese dams. Overall, hypothalamic inflammation was increased by maternal obesity or current HFD, and the effect of exercise was dependent on maternal diet. In conclusion, even after a significant sedentary period, many of the negative impacts of maternal obesity could be improved by voluntary exercise and healthy diet.
Evidence that Orphanin FQ Mediates Progesterone Negative Feedback in the Ewe
Authors: Nestor Casey C , Coolen Lique M. , Nesselrod Gail L. , Valent Miro , Connors John M. , Hileman Stanley M. , Cheng Guanliang , Lehman Michael N. , Goodman Robert L.
Published: August 2013

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.
Activation of Neurokinin 3 Receptors Stimulates GnRH Release in a Location-Dependent but Kisspeptin-Independent Manner in Adult Mice
Authors: Gaskins Garrett T. , Glanowska Katarzyna M. , Moenter Suzanne M.
Published: August 2013

GnRH neurons form the final common pathway for the central control of reproduction. GnRH release occurs from terminals in the external layer of the median eminence (ME) for neuroendocrine control of the pituitary, and near GnRH-GnRH fiber appositions within the preoptic area (POA). Whether or not control of GnRH secretion by neuromodulators is different in these 2 areas is unknown. Mutations in neurokinin B (NKB) or the neurokinin-3 receptor (NK3R) are linked to hypogonadotropic hypogonadism in humans, suggesting that NKB may regulate GnRH secretion. Using fast scan cyclic voltammetry through carbon-fiber microelectrodes, we examined real-time GnRH release in response to the NK3R agonist senktide in the ME and POA. Coronal brain slices were acutely prepared from adult gonad-intact GnRH-green fluorescent protein male mice, and carbon-fiber microelectrodes were placed either within green fluorescent protein-positive terminal fields of the ME or near GnRH-GnRH fiber appositions in the POA. Senktide induced GnRH release consistently in the ME but not the POA, indicating that GnRH release is differentially regulated by NKB in a location-dependent manner. Senktide also induced GnRH secretion in the ME of kisspeptin-knockout (Kiss1 knockout) mice. Interestingly, release amplitude was lower compared with wild-type mice. These data indicate regulation of GnRH release by NK3R agonists is site specific and suggest that kisspeptin is not a required mediator between NK3R activation and GnRH secretion in the ME. This information will be useful for informing future models of afferent regulation of GnRH release.
Changes in Circulating MicroRNAs Are Associated With Childhood Obesity
Authors: Prats-Puig Anna , Ortega Francisco J. , Mercader Josep M. , Moreno-Navarrete José M. , Moreno María , Bonet Nuria , Ricart Wifredo , López-Bermejo Abel , Fernández-Real José M.
Published: August 2013

Context:

Circulating microRNAs (miRNAs) are valuable biomarkers of metabolic diseases and potential therapeutic targets in this field.

Objective:

Our objective was to define the circulating pattern of miRNAs in childhood obesity.

Design, Settings, and Main Outcome Measure:

The genome-wide circulating miRNA profile was assessed by RT-PCR in 10 boys (5 lean and 5 obese children). The most relevant miRNAs were cross-sectionally validated in 85 lean versus 40 obese children (63 boys and 62 girls) and longitudinally evaluated in samples from the same children when they were ∼7 and ∼10 years old (23 boys and 22 girls).

Results:

The cross-sectional validation study disclosed that 15 specific circulating miRNAs were significantly deregulated in prepubertal obesity, including the decreased miR-221 and miR-28-3p and increased concentrations in plasma of miR-486-5p, miR-486-3p, miR-142-3p, miR-130b, and miR-423-5p (all P < .0001). The circulating concentration of these miRNAs was significantly associated with body mass index and other measures of obesity such as percent fat mass, waist, regional fat distribution and with laboratory parameters such as homeostasis model assessment of insulin resistance, high-molecular-weight adiponectin, C-reactive protein, and circulating lipids in concordance with anthropometric associations. Plasma concentrations of 10 of these circulating miRNAs changed significantly and differently during the 3-year follow-up in children who increased or decreased their normalized weight.

Conclusion:

This study provides the first evidence that circulating miRNAs are deregulated in prepubertal obese children. Thus, the very early detection of an abnormal circulating miRNA profile may be a promising strategy to identify obese children who may suffer from metabolic abnormalities.
Whole-Transcriptome Profiling of Thyroid Nodules Identifies Expression-Based Signatures for Accurate Thyroid Cancer Diagnosis
Authors: Wiseman Sam M. , Haddad Zaid , Walker Blair , Vergara Ismael A. , Sierocinski Thomas , Crisan Anamaria , Ghadessi Mercedeh , Dao Phuong , Zimmermann Benedikt , Triche Timothy J. , Erho Nicholas , Davicioni Elai
Published: August 2013

Purpose:

Due to the limitations of fine-needle aspiration biopsy (FNAB) cytopathology, many individuals who present with thyroid nodules eventually undergo thyroid surgery to diagnose thyroid cancer. The objective of this study was to use whole-transcriptome profiling to develop and validate a genomic classifier that significantly improves the accuracy of preoperative thyroid cancer diagnosis.

Materials and Methods:

Nucleic acids were extracted and amplified for microarray expression analysis on the Affymetrix Human Exon 1.0 ST GeneChips from 1-mm-diameter formalin-fixed and paraffin-embedded thyroid tumor tissue cores. A training group of 60 thyroidectomy specimens (30 cancers and 30 benign lesions) were used to assess differential expression and for subsequent generation of a genomic classifier. The classifier was validated in a blinded fashion on a group of 31 formalin-fixed and paraffin-embedded thyroid FNAB specimens.

Results:

Expression profiles of the 57 thyroidectomy training and 31 FNAB validation specimens that passed a series of quality control steps were analyzed. A genomic classifier composed of 249 markers that corresponded to 154 genes, had an overall validated accuracy of 90.0% in the 31 patient FNAB specimens and had positive and negative predictive values of 100% and 85.7%, respectively. The majority of the identified markers that made up the classifier represented non-protein-encoding RNAs.

Conclusions:

Whole-transcriptome profiling of thyroid nodule surgical specimens allowed for the development of a genomic classifier that improved the accuracy of preoperative thyroid cancer FNAB diagnosis.
Central Diabetes Insipidus: A Previously Unreported Side Effect of Temozolomide
Authors: Faje Alexander T. , Nachtigall Lisa , Wexler Deborah , Miller Karen K. , Klibanski Anne , Makimura Hideo
Published: August 2013

Context:

Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ.

Case Presentations:

A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ).

Conclusions:

Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ.