bluuebunny/crossref_metadata_2025 huggingface dataset:
A Synaptic Function Approach to Investigating Complex Psychiatric Diseases
Authors: Earls Laurie R. , Zakharenko Stanislav S.
Published: August 2013

The 22q11 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans and presents with a complex and variable psychiatric phenotype. Patients show cognitive impairment and have a higher probability of psychiatric disorders. As much as 30% of patients with 22q11DS suffer from schizophrenia, the strongest association between any mutation and the disease. Schizophrenia is a complex psychiatric disease that affects multiple brain regions, giving rise to a constellation of seemingly unrelated symptoms including hallucinations, social withdrawal, and memory deficits. Synaptic or neuronal malfunctions within certain physiological circuits appear to be at the core of these symptoms. Understanding disease at the synaptic level requires genetic model systems where intact neural circuits can be interrogated for functional deficits. Because of the overlap between 22q11DS and schizophrenia, models of 22q11DS may be key genetic tools for investigating both diseases. Here we discuss the advantages of using a synaptic function approach to studying mouse models of 22q11DS, review recent findings, and discuss them in the broader context of 22q11DS and schizophrenia.
Headhunters and the ‘ideal’ executive body
Authors: Meriläinen Susan , Tienari Janne , Valtonen Anu
Published: August 2013

In this article, we adopt a critical perspective to study how executive search practices reproduce particular understandings of the ‘ideal’ executive body. We show how this disadvantages not only women but also men who are considered not to fit the ‘ideal’, and further demonstrate how search practices are embodied: how aesthetics, the senses and a sensorial way of knowing permeate the practices through which candidates are evaluated. We identify discourses on embodied co-presence, capabilities and voice in search consultants’ talk, and specify how notions of the ‘ideal’ executive body and embodied search practices become intertwined. We offer this contribution to the discussion on the body, gender and management and to research on executive search practice.
All-cause mortality and suicide within 8 days after emergency department discharge
Authors: Rafnsson Vilhjalmur , Gunnarsdottir Oddny S.
Published: August 2013

Aim: The aim of the study was to evaluate the association of death within 8–30 days after discharge home from the emergency department with a non-causative diagnosis in a prospective cohort study. Methods: The 227,097 visits to the emergency department were filed by personal identification number and included information on gender, age, admission, discharge, and diagnosis. The visits were classified by main diagnosis at discharge into those with non-causative diagnosis and those with other diagnoses. Mortality per 100,000 within 8, 15 and 30 days and the corresponding hazard ratio (HR) and 95% confidence intervals (CI) were calculated for all causes of death and for selected causes of death in a time-dependent analysis. Results: The HRs of all causes of death for patients with a non-causative diagnosis were 0.64 (95% CI 0.41–1.01) within 8 days, 0.70 (95% CI 0.50–0.99) within 15 days, and 0.82 (95% CI 0.65–1.04) within 30 days as compared to those with a causative diagnosis. The HRs within 30 days among those with a non-causative diagnosis at discharge were 1.48 (95% CI 1.03–2.13) for malignant neoplasm, 3.72 (95% CI 1.44–9.60) for suicide, and 0.50 (95% CI 0.32–0.79) for diseases of the circulatory system. Conclusion: Death within 8 days after discharge home from the ED is a rare event. Death of patients that occur shortly after discharge who had received a non-causative diagnosis as the main diagnosis may indicate a misjudgement of the patients’ condition at that time.
Stuck between the past and the future: Conditional cash transfer programme development and policy feedbacks in Brazil and Argentina
Authors: Fenwick Tracy Beck
Published: August 2013

Do policy feedbacks interact with transnational policy ideas? How do they impact domestic policy development? Using a qualitative research method based on a comparison of two poverty alleviation strategies in Latin America, this article asserts that in all likelihood, if a previously implemented policy initiative was ‘locked-in’ through domestic policy experimentation and resultant state-building and interest group policy effects, it will not easily be replaced by alternative, transnational policy ideas that appear on the radar screen of national policymakers at a later date. However, if transnational policy ideas and models can draw on or build upon already established ideational and symbolic beliefs, they can actually be used to further the motivations of key political actors and societal interests – here, diffusion opens up great reform opportunities and opens the door to further policy institutionalization.
Hobbes’s commitment to society as a product of sovereignty: A basis for a Hobbesian sociology
Authors: Wickham Gary
Published: August 2013

There is a commitment in Thomas Hobbes’s work which is largely neglected by sociology, a commitment to society as a product of sovereignty. Hobbes makes this commitment in line with his strident opposition to the scholastic idea of the dominance of reason in nature. For Hobbes, society is not based on natural reason. Drawing on his distinctive Epicurean anthropology, he argues that the small amount of reason that nature supplies to humans is enough to give them a limited capacity for sociability – enough, that is, to achieve a rudimentary level of self-preservation – but not nearly enough to produce society. He builds this argument directly against the scholastic argument that nature in fact supplies to humans so much reason that, were they to apply it in the manner in which nature intends, they would achieve a perfect society. In forging his particular direction against the scholastics, Hobbes draws mostly on his Epicurean political philosophy, whereby the rule of a strong authority, the sovereign, disciplines the wills of subjects in order to properly balance their passions, to the extent that a distinct domain of peace and security is created and maintained, a domain he mostly calls simply ‘society’. His account of society is normative in only one respect, a very important respect – its dedication to the fundamental importance of peace and security.
The risk of cutaneous adverse reactions among patients with the HLA-A* 31:01 allele who are given carbamazepine, oxcarbazepine or eslicarbazepine: a perspective review
Authors: Kaniwa Nahoko , Saito Yoshiro
Published: August 2013

Carbamazepine is a drug that is widely used for the treatment of epilepsy, trigeminal neuralgia and bipolar disorder. This drug is also known to cause cutaneous adverse drug reactions (cADRs) in up to 10% of patients. The recent progress in pharmacogenetics has revealed that human leukocyte antigen (HLA) genotypes are associated with a susceptibility to the cADRs caused by particular drugs. For carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis, very strong associations with HLA-B*15:02 have been found mainly in patients of Southeastern Asian origin. In some countries, prescreening HLA-B*15:02 allele has already been put to practical use as a biomarker to avoid the life-threatening adverse drug reactions. In this review, another risk factor for carbamazepine-induced cADRs is discussed, namely HLA-A*31:01. We compare the strength of the association between HLA-A*31:01 and carbamazepine-induced cADRs based on reports for various ethnic populations; discuss the difference between the HLA-A*31:01 and HLA-B*15:02 biomarkers and the usefulness of prescreening HLA-A*31:01 to detect patients at high risk for carbamazepine-induced cADRs; and refer to points that remain to be resolved.
Can we mend a broken engagement?
Authors: Johnston Ron
Published: August 2013

Murphy’s (2013) argument for greater engagement by academic geographers in the discourses and debates underpinning foreign policy is critiqued. Contemporary academic culture means that few geographers undertake the sorts of research and writing that Murphy wishes to see increased. Even within that context, it is hard to identify what his hoped-for grand regional narratives might look like; his expectation that they could be both empirically grounded and authoritative is questioned.
A different kind of difference
Authors: McKinnon Katharine
Published: August 2013

This commentary explores the implications of identifying an Antipodean economic geography distinct from an apparent Anglo-American hegemony. I explore Wray et al.’s (2013) proposal that there is a different kind of ‘edginess’ to the work produced by those on the underside of the world. Using an example from fieldwork in the highlands of northern Thailand, I suggest that identifying with perspectives of the so-called periphery, and striving to see those perspectives as, in fact, central is a crucial part of critical knowledge production.
A survey of pharmacological and nonpharmacological treatment of functional gastrointestinal disorders
Authors: Lahner Edith , Bellentani Stefano , Bastiani Rudy De , Tosetti Cesare , Cicala Michele , Esposito Gianluca , Arullani Paolo , Annibale Bruno ,   Study Group Primary Care in Gastroenterology of the Italian Society of Gastroenterology
Published: August 2013

Background

Treatment of functional gastrointestinal disorders (FGIDs) is based on symptoms relieve by conventional drugs, but increasingly complementary and alternative medicine (CAM) is used.

Objective

This survey aimed to investigate the current treatments used by FGIDs patients.

Methods

A total of 25 Italian gastroenterologists interviewed outpatients on gastrointestinal symptoms and treatments (pharmacological, CAM, diet/dietary supplements) used during the last year to relieve FGIDs. Consecutive adults with FGIDs according to Rome III were included.

Results

Of the 199 patients, 81% used conventional drugs, 64.3% diet/dietary supplements, and 48.7% CAM. Conventional drugs, diet/dietary supplements, or CAM as exclusive treatment were used by 24.6, 6, and 2.5% of patients, respectively. Two‐thirds used more than one treatment: 34.7% conventional drugs, CAM, and diet/dietary supplements, 17.1% conventional drugs and diet/dietary supplements, 10.1% diet and CAM, and 5% conventional drugs and CAM. Benefits and adverse effects were similar for conventional drugs and nonpharmacological treatments. Males (OR 2.4) without lower GI symptoms (OR 5.4) used more frequently exclusive pharmacological treatment of FGIDs.

Conclusions

Conventional drugs are the preferred treatment for FGID. CAM and dietary modifications are more likely used as an adjunct to rather than instead of conventional drugs. Adverse effects occurred in all treatments.
Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells
Authors: Li Bin E. , Gan Tao , Meyerson Matthew , Rabbitts Terence H. , Ernst Patricia
Published: August 2013

Key Points

MLL1 does not require interaction with menin to maintain hematopoietic stem cell homeostasis. Menin and MLL1 are both critical during B-cell differentiation, but largely through distinct pathways.
Epidemiology of cancer-associated venous thrombosis
Authors: Timp Jasmijn F. , Braekkan Sigrid K. , Versteeg Henri H. , Cannegieter Suzanne C.
Published: August 2013

Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increased mortality compared with cancer patients without. This may be explained by the more aggressive type of malignancies associated with this condition. It is hypothesized that thromboprophylaxis in cancer patients might improve prognosis and quality of life by preventing thrombotic events. However, anticoagulant treatment leads to increased bleeding, particularly in this patient group, so in case of proven benefit of thromboprophylaxis, only patients with a high risk of venous thrombosis should be considered. This review describes the literature on incidence of and risk factors for cancer-associated venous thrombosis, with the aim to provide a basis for identification of high-risk patients and for further development and refinement of prediction models. Furthermore, knowledge on risk factors for cancer-related venous thrombosis may enhance the understanding of the pathophysiology of thrombosis in these patients.
Genetic loss of SH2B3 in acute lymphoblastic leukemia
Authors: Perez-Garcia Arianne , Ambesi-Impiombato Alberto , Hadler Michael , Rigo Isaura , LeDuc Charles A. , Kelly Kara , Jalas Chaim , Paietta Elisabeth , Racevskis Janis , Rowe Jacob M. , Tallman Martin S. , Paganin Maddalena , Basso Giuseppe , Tong Wei , Chung Wendy K. , Ferrando Adolfo A.
Published: August 2013

Key Points

SH2B3 is a recessive tumor suppressor gene with germline and somatic mutations in ALL.
A note on complete convergence of weighted sums for array of rowwise AANA random variables
Authors: Wang Xinghui , Shen Aiting , Li Xiaoqin
Published: August 2013

In this paper, we consider complete convergence and complete moment convergence of weighted sums for an array of rowwise AANA random variables. The main result of the paper generalizes the Baum-Katz theorem on AANA random variables. Our results extend and improve the corresponding ones of Wang et al. (Abstr. Appl. Anal. 2012:315138, 2012).

MSC:60B10, 60F15.
Antioxidants cause rapid expansion of human adipose-derived mesenchymal stem cells via CDK and CDK inhibitor regulation
Authors: Sun Li-Yi , Pang Cheng-Yoong , Li Dian-Kun , Liao Chia-Hsin , Huang Wei-Chao , Wu Chao-Chuan , Chou Yi-Yo , Li Wei Wu , Chen Shin-Yuan , Liu Hwan-Wun , Chang Yao-Jen , Cheng Ching-Feng
Published: August 2013

Background

Antioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs)in vitro, although the detailed mechanism(s) and potential side effects are not fully understood.

In this study, human ADMSCs cultured in ImF-A medium supplemented with antioxidants (N-acetyl-l-cysteine and ascorbic acid-2-phosphate) and fibroblast growth factor 2 (FGF-2) were compared with ADMSCs cultured with FGF-2 alone (ImF) or with FGF-2 under 5% pO2conditions (ImF-H).

Results

During log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions.

Conclusion

Antioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.
Cysteine-rich domain of scavenger receptor AI modulates the efficacy of surface targeting and mediates oligomeric Aβ internalization
Authors: Huang Fong-Lee , Shiao Young-Ji , Hou Sheue-Jane , Yang Cheng-Ning , Chen Yi-Jen , Lin Chao-Hsiung , Shie Feng-Shiun , Tsay Huey-Jen
Published: August 2013

Background

Insufficient clearance of soluble oligomeric amyloid-β peptide (oAβ) in the central nervous system leads to the synaptic and memory deficits in Alzheimer's disease (AD). Previously we have identified scavenger receptor class A (SR-A) of microglia mediates oligomeric amyloid-β peptide (oAβ) internalization by siRNA approach. SR-A is a member of cysteine-rich domain (SRCR) superfamily which contains proteins actively modulating the innate immunity and host defense, however the functions of the SRCR domain remain unclear. Whether the SRCR domain of SR-AI modulates the receptor surface targeting and ligand internalization was investigated by expressing truncated SR-A variants in COS-7 cells. Surface targeting of SR-A variants was examined by live immunostaining and surface biotinylation assays. Transfected COS-7 cells were incubated with fluorescent oAβ and acetylated LDL (AcLDL) to assess their ligand-internalization capabilities.

Result

Genetic ablation of SR-A attenuated the internalization of oAβ and AcLDL by microglia. Half of oAβ-containing endocytic vesicles was SR-A positive in both microglia and macrophages. Clathrin and dynamin in SR-AI-mediated oAβ internalization were involved. The SRCR domain of SR-AI is encoded by exons 10 and 11. SR-A variants with truncated exon 11 were intracellularly retained, whereas SR-A variants with further truncations into exon 10 were surface-targeted. The fusion of exon 11 to the surface-targeted SR-A variant lacking the SRCR domain resulted in the intracellular retention and the co-immunoprecipitation of Bip chaperon of the endoplasmic reticulum. Surface-targeted variants were N-glycosylated, whereas intracellularly-retained variants retained in high-mannose states. In addition to the collagenous domain, the SRCR domain is a functional binding domain for oAβ and AcLDL. Our data suggest that inefficient folding of SR-AI variants with truncated SRCR domain was recognized by the endoplasmic reticulum associated degradation which leads to the immature N- glycosylation and intracellular retention.

Conclusion

The novel functions of the SRCR domain on regulating the efficacy of receptor trafficking and ligand binding may lead to possible approaches on modulating the innate immunity in Alzheimer’s disease and atherosclerosis.
CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes
Authors: Rusconi Francesca , Thakur Hrishikesh , Li Jinliang , Kapiloff Michael S
Published: August 2013

Background

CIP4 is a scaffold protein that regulates membrane deformation and tubulation, organization of the actin cytoskeleton, endocytosis of growth factor receptors, and vesicle trafficking. Although expressed in the heart, CIP4 has not been studied with regards to its potential function in cardiac myocytes.

Results

We now show using RNA interference that CIP4 expression in neonatal rat ventricular myocytes is required for the induction of non-mitotic, hypertrophic growth by the α-adrenergic agonist phenylephrine, the IL-6 cytokine leukemia inhibitor factor, and fetal bovine serum, as assayed using morphometry, immunocytochemistry for the hypertrophic marker atrial natriuretic factor and [3H]leucine incorporation for de novo protein synthesis. This requirement was consistent with the induction of CIP4 expression by hypertrophic stimulation. The inhibition of myocyte hypertrophy by CIP4 small interfering oligonucleotides (siRNA) was rescued by expression of a recombinant CIP4 protein, but not by a mutant lacking the N-terminal FCH domain responsible for CIP4 intracellular localization.

Conclusions

These results imply that CIP4 plays a significant role in the intracellular hypertrophic signal transduction network that controls the growth of cardiac myocytes in heart disease.
Association analysis between variants in KISS1 gene and litter size in goats
Authors: An Xiaopeng , Ma Teng , Hou Jinxing , Fang Fang , Han Peng , Yan Yan , Zhao Haibo , Song Yunxuan , Wang Jiangang , Cao Binyun
Published: August 2013

Background

Kisspeptins are the peptide products ofKISS1gene, which operate via the G - protein-coupled receptor GPR54. These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the hypothalamic–pituitary– gonadal (HPG) axis. The present study detected the polymorphisms of caprineKISS1gene in three goat breeds and investigated the associations between these genetic markers and litter size.

Results

Three goat breeds (n = 680) were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron–exon boundaries and the proximal flanking regions ofKISS1gene by DNA sequencing and PCR–RFLP. Eleven novel SNPs (g.384G>A, g.1147T>C, g.1417G>A, g.1428_1429delG, g.2124C>T, g.2270C>T, g.2489T>C, g.2510G>A, g.2540C>T, g.3864_3865delCA and g.3885_3886insACCCC) were identified. It was shown that Xinong Saanen and Guanzhong goat breeds were in Hardy-Weinberg disequilibrium atg.384G>Alocus (P< 0.05). Bothg.2510G>Aandg.2540C>Tloci were closely linked in Xinong Saanen (SN), Guanzhong (GZ) and Boer (BG) goat breeds (r2> 0.33). The g.384G>A, g.2489T>C, g.2510G>A and g.2540C>T SNPs were associated with litter size (P<0.05). Individuals withAATTAATTcombinative genotype of SN breed (SC) andTTAATTcombinative genotype of BG breed (BC) had higher litter size than those with other combinative genotypes in average parity. The results extend the spectrum of genetic variation of the caprineKISS1gene, which might contribute to goat genetic resources and breeding.

Conclusions

This study explored the genetic polymorphism ofKISS1gene, and indicated that four SNPs may play an important role in litter size. Their genetic mechanism of reproduction in goat breeds should be further investigated. The female goats with SC1 (AATTAATT) and BC7 (TTAATT) had higher litter size than those with other combinative genotypes in average parity and could be used for the development of new breeds of prolific goats. Further research on a large number of animals is required to confirm the link with increased prolificacy in goats.
Can a routine follow-up blood culture be justified in Klebsiella pneumoniaebacteremia? a retrospective case–control study
Authors: Kang Chang Kyung , Kim Eu Suk , Song Kyoung-Ho , Kim Hong Bin , Kim Taek Soo , Kim Nak-Hyun , Kim Chung-Jong , Choe Pyoeng Gyun , Bang Ji-Hwan , Park Wan Beom , Park Kyoung Un , Park Sang Won , Kim Nam-Joong , Kim Eui-Chong , Oh Myoung-don
Published: August 2013

Background

The need for mandatory confirmation of negative conversion in Klebsiella pneumoniae bacteremia (KpB) has not been adequately addressed. We conducted a retrospective case–control study of adult patients with KpB over a 5-year period in two tertiary-care hospitals to determine the risk factors for persistent bacteremia and to reevaluate the necessity of follow-up blood culture in KpB.

Methods

Persistent KpB is defined as the finding of K. pneumoniae in more than two separate blood-culture samples for longer than a two-day period in a single episode. The case- and control-groups were patients with persistent and non-persistent KpB, respectively, and they were matched 1-to-3 according to age and gender.

Results

Among 1068 KpB episodes analyzed after excluding polymicrobial infection and repeated KpB, follow-up blood cultures were performed in 862 cases (80.7%), 62 of which (7.2%) were persistent. Independent risk factors for persistence were intra-abdominal infection, higher Charlson’s comorbidity weighted index score, prior solid organ transplantation, and unfavorable treatment response, which was defined as positivity for at least two parameters among fever, leukocytosis, and no decrease of C-reactive protein on the second day after initial culture. A proposed scoring system using four variables, namely, intra-abdominal infection, nosocomial KpB, fever and lack of C-reactive protein decrease, the last two being assessed on the second day after the initial blood culture, showed that only 4.9% of the patients with no risk factors or with only intra-abdominal infection had persistent KpB.

Conclusions

Though persistent KpB is uncommon, follow-up blood culture was performed in as many as 80% of the cases in this study. A more careful clinical assessment is warranted to reduce the cost and patient inconvenience involved in follow-up blood culture.
MicroRNA-433 negatively regulates the expression of thymidylate synthase (TYMS) responsible for 5-fluorouracil sensitivity in HeLa cells
Authors: Gotanda Keisuke , Hirota Takeshi , Matsumoto Nozomi , Ieiri Ichiro
Published: August 2013

Background

Thymidylate synthase (TYMS) is an important folate-dependent enzyme in DNA synthesis and an important target for cancer chemotherapy. High TYMS expression levels in tumors are generally associated with resistance to 5-fluorouracil (5-FU). The cause of the variability in TYMS expression is still not fully understood, however, only a small proportion of the TYMS expression can be explained by TYMS genetic polymorphisms. The purpose of this study is to identify novel microRNAs (miRNAs) which regulate the expression of TYMS and to determine whether miRNAs binding to the 3′-untranslated region (UTR) of TYMS mRNA affect the proliferation of HeLa cells treated with 5-FU.

Methods

An in silico search was performed to find potential binding sites of miRNAs in TYMS mRNA. The efficacy of predicted miRNAs at the 3′-UTR of TYMS mRNA was evaluated using a dual-luciferase reporter assay. TYMS mRNA and protein expression in HeLa cells was quantified with real-time RT-PCR and Western blotting, respectively. The effects of miR-433 on cell proliferative activity were determined by WST-8 assay.

Results

The overexpression of miR-433 was associated with significantly decreased reporter activity in the plasmid containing the 3′-UTR of TYMS mRNA (P < 0.01). The levels of TYMS mRNA and protein in HeLa cells were significantly decreased by the overexpression of miR-433 (P < 0.05). Furthermore, miR-433 increased inhibition of cell proliferation in HeLa cells treated with 5-FU at over 2.0 μM.

Conclusion

The results indicate that miR-433 post-transcriptionally regulates the expression of TYMS mRNA and protein, and increases sensitivity to 5-FU in HeLa cells. This is the first report showing that a miRNA regulating TYMS expression has a significant impact on sensitivity to 5-FU treatment.
10-year trend in quantity and quality of pediatric randomized controlled trials published in mainland China: 2002–2011
Authors: Yang Chun-Song , Zhang Ling-Li , Zeng Li-Nan , Liang Yi , Han Lu , Lin Yun-Zhu
Published: August 2013

Background

Quality assessment of pediatric randomized controlled trials (RCTs) in China is limited. The aim of this study was to evaluate the quantitative trends and quality indicators of RCTs published in mainland China over a recent 10-year period.

Methods

We individually searched all 17 available pediatric journals published in China from January 1, 2002 to December 30, 2011 to identify RCTs of drug treatment in participants under the age of 18 years. The quality was evaluated according to the Cochrane quality assessment protocol.

Results

Of 1287 journal issues containing 44398 articles, a total of 2.4% (1077/44398) articles were included in the analysis. The proportion of RCTs increased from 0.28% in 2002 to 0.32% in 2011. Individual sample sizes ranged from 10 to 905 participants (median 81 participants); 2.3% of the RCTs were multiple center trials; 63.9% evaluated Western medicine, 32.5% evaluated traditional Chinese medicine; 15% used an adequate method of random sequence generation; and 10.4% used a quasi-random method for randomization. Only 1% of the RCTs reported adequate allocation concealment and 0.6% reported the method of blinding. The follow-up period was from 7 days to 96 months, with a median of 7.5 months. There was incomplete outcome data reported in 8.3%, of which 4.5% (4/89) used intention-to-treat analysis. Only 0.4% of the included trials used adequate random sequence allocation, concealment and blinding. The articles published from 2007 to 2011 revealed an improvement in the randomization method compared with articles published from 2002 to 2006 (from 2.7% to 23.6%, p = 0.000).

Conclusions

In mainland China, the quantity of RCTs did not increase in the pediatric population, and the general quality was relatively poor. Quality improvements were suboptimal in the later 5 years.
The burden of pediatric diarrhea: a cross-sectional study of incurred costs and perceptions of cost among Bolivian families
Authors: Burke Rachel M , Rebolledo Paulina A , Embrey Sally R , Wagner Laura Danielle , Cowden Carter L , Kelly Fiona M , Smith Emily R , Iñiguez Volga , Leon Juan S
Published: August 2013

Background

Worldwide, acute gastroenteritis represents an enormous public health threat to children under five years of age, causing one billion episodes and 1.9 to 3.2 million deaths per year. In Bolivia, which has one of the lower GDPs in South America, an estimated 15% of under-five deaths are caused by diarrhea. Bolivian caregiver expenses related to diarrhea are believed to be minimal, as citizens benefit from universal health insurance for children under five. The goals of this report were to describe total incurred costs and cost burden associated with caregivers seeking treatment for pediatric gastroenteritis, and to quantify relationships among costs, cost burden, treatment setting, and perceptions of costs.

Methods

From 2007 to 2009, researchers interviewed caregivers (n=1,107) of pediatric patients (<5 years of age) seeking treatment for diarrhea in sentinel hospitals participating in Bolivia’s diarrheal surveillance program across three main geographic regions. Data collected included demographics, clinical symptoms, direct costs (e.g. medication, consult fees) and indirect costs (e.g. lost wages).

Results

Patient populations were similar across cities in terms of gender, duration of illness, and age, but familial income varied significantly (p<0.05) when stratified on appointment type. Direct, indirect, and total costs to families were significantly higher for inpatients as compared to outpatients of urban (p<0.001) and rural (p<0.05) residence. Consult fees and indirect costs made up a large proportion of total costs. Forty-five percent of patients’ families paid ≥1% of their annual household income for this single diarrheal episode. The perception that cost was affecting family finances was more frequent among those with higher actual cost burden.

Conclusions

This study demonstrated that indirect costs due to acute pediatric diarrhea were a large component of total incurred familial costs. Additionally, familial costs associated with a single diarrheal episode affected the actual and perceived financial situation of a large number of caregivers. These data serve as a baseline for societal diarrheal costs before and immediately following the implementation of the rotavirus vaccine and highlight the serious economic importance of a diarrheal episode to Bolivian caregivers.
Validation of a Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR)
Authors: Salgueiro Monika , García-Leiva Juan Miguel , Ballesteros Javier , Hidalgo Javier , Molina Rocío , Calandre Elena P
Published: August 2013

Background

The Revised version of the Fibromyalgia Impact Questionnaire (FIQR) was published in 2009. The aim of this study was to prepare a Spanish version, and to assess its psychometric properties in a sample of patients with fibromyalgia.

Methods

The FIQR was translated into Spanish and administered, along with the FIQ, the Hospital Anxiety Depression Scale (HADS), the 36-Item Short-Form Health Survey (SF-36), and the Brief Pain Inventory (BPI), to 113 Spanish fibromyalgia patients. The administration of the Spanish FIQR was repeated a week later.

Results

The Spanish FIQR had high internal consistency (Cronbach’s α was 0.91 and 0.95 at visits 1 and 2 respectively). The test-retest reliability was good for the FIQR total score and its function and symptoms domains (intraclass correlation coefficient (ICC > 0.70), but modest for the overall impact domain (ICC = 0.51). Statistically significant correlations (p < 0.05) were also found between the FIQR and the FIQ scores, as well as between the FIQR scores and the remaining scales’ scores.

Conclusions

The Spanish version of the FIQR has a good internal consistency and our findings support its validity for assessing fibromyalgia patients. It might be a valid instrument to apply in clinical and investigational grounds.
Phospholipase D regulates the size of skeletal muscle cells through the activation of mTOR signaling
Authors: Jaafar Rami , De Larichaudy Joffrey , Chanon Stéphanie , Euthine Vanessa , Durand Christine , Naro Fabio , Bertolino Philippe , Vidal Hubert , Lefai Etienne , Némoz Georges
Published: August 2013

mTOR is a major actor of skeletal muscle mass regulation in situations of atrophy or hypertrophy. It is established that Phospholipase D (PLD) activates mTOR signaling, through the binding of its product phosphatidic acid (PA) to mTOR protein. An influence of PLD on muscle cell size could thus be suspected. We explored the consequences of altered expression and activity of PLD isoforms in differentiated L6 myotubes. Inhibition or down-regulation of the PLD1 isoform markedly decreased myotube size and muscle specific protein content. Conversely, PLD1 overexpression induced muscle cell hypertrophy, both in vitro in myotubes and in vivo in mouse gastrocnemius. In the presence of atrophy-promoting dexamethasone, PLD1 overexpression or addition of exogenous PA protected myotubes against atrophy. Similarly, exogenous PA protected myotubes against TNFα-induced atrophy. Moreover, the modulation of PLD expression or activity in myotubes showed that PLD1 negatively regulates the expression of factors involved in muscle protein degradation, such as the E3-ubiquitin ligases Murf1 and Atrogin-1, and the Foxo3 transcription factor. Inhibition of mTOR by PP242 abolished the positive effects of PLD1 on myotubes, whereas modulating PLD influenced the phosphorylation of both S6K1 and Akt, which are respectively substrates of mTORC1 and mTORC2 complexes. These observations suggest that PLD1 acts through the activation of both mTORC1 and mTORC2 to induce positive trophic effects on muscle cells. This pathway may offer interesting therapeutic potentialities in the treatment of muscle wasting.
Immunological and nutritional factors in elderly people in low-level care and their association with mortality
Authors: Woods Julie L , Iuliano-Burns Sandra , Walker Karen Z
Published: August 2013

Background

This study examines associations between markers of nutritional status and lymphocyte subsets and seeks to determine if lymphocyte profile is predictive of survival in elderly Australians residing in aged care facilities. Aged yet still ambulatory subjects (n = 88, 73% female) living in low-level care and requiring minimal assistance were studied for 143 weeks. At baseline when participants were aged (mean ± SD) 86.0 ± 5.9 years, dietary intake was determined by 3-day weighed food record, body composition was assessed by dual energy X-ray absorptiometry (DXA) and a venous blood sample was taken.

Results

At baseline assessment, study participants were consuming nutrient-poor diets and most had symptoms of chronic disease. Although overweight, 40% exhibited sarcopenia. Markers of nutritional status did not relate closely to immune cell numbers (absolute or relative), which on average were within the normal range. Men had lower numbers of CD3+CD4+ cells (CD4+ T cells), a higher proportion of CD3− CD16± CD56± (natural killer (NK) cells) and a higher ratio of NK: CD4+ T cells than women (all P < 0.05). The main age-related changes evident were decreased T cells, particularly low CD4+ T cell counts, and increased numbers of CD19+ (B-cell) and NK cells. During the 143 week duration of follow-up, about one quarter of the study participants died, with death more likely in men than women (P < 0.01). Poor survival was predicted by the presence of decreased numbers of CD4+ T cells (hazard ratio (HR) 0.919, P < 0.01) and expanded numbers of NK cells (HR 1.085, P < 0.05) in the blood, and therefore the presence of a high NK: CD4+ T cell ratio (HR 30.521, P < 0.01).

Conclusions

The NK: CD4+ T cell ratio may potentially have clinical utility for predicting longevity in elderly populations. Further studies are needed in other elderly populations to confirm this finding.
A highly divergent Encephalomyocarditis virus isolated from nonhuman primates in Singapore
Authors: Yeo Dawn Su-Yin , Lian Jing Er , Fernandez Charlene J , Lin Yueh-Nuo , Liaw Jasper Chin-Wen , Soh Moi-Lien , Lim Elizabeth Ai-Sim , Chan Kwai-Peng , Ng Mah-Lee , Tan Hwee-Cheng , Oh Serena , Ooi Eng-Eong , Tan Boon-Huan
Published: August 2013

Background

In 2001 and 2002, fatal myocarditis resulted in the sudden deaths of four, two adult and two juvenile, orang utans out of a cohort of 26 in the Singapore Zoological Gardens.

Methods

Of the four orang utans that underwent post-mortem examination, virus isolation was performed from the tissue homogenates of the heart and lung obtained from the two juvenile orang utans in Vero cell cultures. The tissue culture fluid was examined using electron microscopy. Reverse transcription and polymerase chain reaction with Encephalomyocarditis virus (EMCV)-specific primers targeting the gene regions of VP3/VP1 and 3D polymerase (3Dpol) confirmed the virus genus and species. The two EMCV isolates were sequenced and phylogenetic analyses of the virus genes performed. Serological testing on other animal species in the Singapore Zoological Gardens was also conducted.

Results

Electron microscopy of the two EMCV isolates, designated Sing-M100-02 and Sing-M105-02, revealed spherical viral particles of about 20 to 30 nm, consistent with the size and morphology of members belonging to the familyPicornaviridae. In addition, infected-Vero cells showed positive immunoflorescence staining with antiserum to EMCV. Sequencing of the viral genome showed that the two EMCV isolates were 99.9% identical at the nucleotide level, indicating a similar source of origin. When compared with existing EMCV sequences in the VP1 and 3Dpol gene regions, the nucleotide divergence were at a maximum of 38.8% and 23.6% respectively, while the amino acid divergence were at a maximum of 33.9% and 11.3% respectively. Phylogenetic analyses of VP1 and 3Dpol genes further grouped the Sing-M100-02 and Sing-M105-02 isolates to themselves, away from existing EMCV lineages. This strongly suggested that Sing-M100-02 and Sing-M105-02 isolates are highly divergent variants of EMCV. Apart from the two deceased orang utans, a serological survey conducted among other zoo animals showed that a number of other animal species had neutralizing antibodies to Sing-M105-02 isolate, indicating that the EMCV variant has a relatively wide host range.

Conclusions

The etiological agent responsible for the fatal myocarditis cases among two of the four orang utans in the Singapore Zoological Gardens was a highly divergent variant of EMCV. This is the first report of an EMCV infection in Singapore and South East Asia.
Actin filaments disruption and stabilization affect measles virus maturation by different mechanisms
Authors: Dietzel Erik , Kolesnikova Larissa , Maisner Andrea
Published: August 2013

Background

Cytoskeletal proteins are often involved in the virus life cycle, either at early steps during virus entry or at later steps during formation of new virus particles. Though actin filaments have been shown to play a role in the production of measles virus (MV), the importance of actin dynamics for virus assembly and budding steps is not known yet. Aim of this work was thus to analyze the distinctive consequences of F-actin stabilization or disruption for MV protein trafficking, particle assembly and virus release.

Results

MV infection studies in the presence of inhibitors differently affecting the actin cytoskeleton revealed that not only actin disruption but also stabilization of actin filaments interfered with MV particle release. While overall viral protein synthesis, surface expression levels of the MV glycoproteins, and cell-associated infectivity was not altered, cell-free virus titers were decreased. Interestingly, the underlying mechanisms of interference with late MV maturation steps differed principally after F-actin disruption by Cytochalasin D (CD) and F-actin stabilization by Jasplakinolide (Jaspla). While intact actin filaments were shown to be required for transport of nucleocapsids and matrix proteins (M-RNPs) from inclusions to the plasma membrane, actin dynamics at the cytocortex that are blocked by Jaspla are necessary for final steps in virus assembly, in particular for the formation of viral buds and the pinching-off at the plasma membrane. Supporting our finding that F-actin disruption blocks M-RNP transport to the plasma membrane, cell-to-cell spread of MV infection was enhanced upon CD treatment. Due to the lack of M-glycoprotein-interactions at the cell surface, M-mediated fusion downregulation was hindered and a more rapid syncytia formation was observed.

Conclusion

While stable actin filaments are needed for intracellular trafficking of viral RNPs to the plasma membrane, and consequently for assembly at the cell surface and prevention of an overexerted fusion by the viral surface glycoproteins, actin dynamics are required for the final steps of budding at the plasma membrane.
Endometrioid adenocarcinoma with simultaneous endocervical and intestinal-type mucinous differentiation: report of a rare phenomenon and the immunohistochemical profile
Authors: Buell-Gutbrod Rebecca , Sung C James , Lawrence W Dwayne , Quddus M Ruhul
Published: August 2013

Intestinal differentiation in the endometrium is rare with only case reports in the international literature. We describe a case of simultaneous endocervical and intestinal-type mucinous differentiation with goblet cells arising in a FIGO grade 1 endometrioid adenocarcinoma. The patient had no involvement of the myometrium, cervix, or extra-uterine sites. There were no intestinal metaplastic changes of the endocervical canal. The etiology of this change is unknown, although recent reports suggest an association with hyperestrogenism.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1209512176931698
Overexpression of CARM1 in breast cancer is correlated with poorly characterized clinicopathologic parameters and molecular subtypes
Authors: Cheng Hongxia , Qin Yejun , Fan Hui , Su Peng , Zhang Xiaofang , Zhang Hui , Zhou Gengyin
Published: August 2013

Background

Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. CARM1 has been reported to be associated with high grade tumors in breast cancer. It still remains unknown the expression pattern of CARM1 in breast cancer and its relationships with clinicopathological characteristics and molecular subtypes.

Methods

Two hundred forty-seven invasive breast cancer cases were collected and prepared for tissue array. There were thirty-seven tumors with benign glandular epithelium adjacent to the tumors among these cases. Molecular subtype and CARM1 expression were investigated using immunohistochemistry.

Results

Cell staining was observed in the cytoplasm and/or nucleus. Staining for CARM1 was significantly stronger in adenocarcinoma compared with adjacent benign epithelium. There is a significant correlation between CARM1 overexpression with young age, high grade, estrogen receptor (ER) and progesterone receptor (PR) negative, increased p53 expression, and high Ki-67 index. Our study demonstrated CARM1 overexpression was associated with an increase in the protein expression of HER2. Furthermore, our data indicated CARM1-overexpression rate were remarkably higher in HER2 subtype (69.6%), luminal B subtype (59.6%) and TN subtype (57.1%) compared with luminal A subtype (41.3%).

Conclusions

CARM1 expression was increased in invasive breast cancer. CARM1 overexpression was associated with poorly characterized clinicopathologic parameters and HER2 overexpression. There were significant differences between different molecular subtypes in their relationship to CARM1 overexpression. Our results support the value of using CARM1 in prognostic stratification of breast cancer patients and its potential therapeutic implications in targeting treatment.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4116338491022965
Complete genomic sequence of Epstein-Barr virus in nasopharyngeal carcinoma cell line C666-1
Authors: Tso Ken Kai-Yuen , Yip Kevin Yuk-Lap , Mak Cathy Ka-Yan , Chung Grace Tin-Yun , Lee Sau-Dan , Cheung Siu-Tim , To Ka-Fai , Lo Kwok-Wai
Published: August 2013

Background

Nasopharyngeal carcinoma is a distinct type of head and neck cancer which is consistently associated with Epstein-Barr virus (EBV). The C666-1 cell line is the only in vitro native EBV-infected NPC cell model commonly used for study of the viral-host interaction. Nevertheless, the complete EBV genome sequence in this in vitro EBV-infected NPC model has not been characterized.

Objective

To determine the complete EBV genome sequence in C666-1 cells.

Methods

The C666-1 genome was sequenced by 100-bases pair-end massive parallel sequencing. Bioinformatics analysis was performed to extract the EBV sequences and construct an EBV consensus sequence map. PCR amplification and Sanger DNA sequencing were used for sequence validation and gap filling. A phylogenetic analysis of EBV strain in C666-1 cells and other reported EBV strains was performed.

Results

A 171,317 bp complete EBV genome of C666-1 was successfully constructed (GenBank accession number: KC617875). Phylogenetic analysis of EBV genome in C666-1 revealed that the C666-1 EBV strain is closely related to the reported strains in NPC primary tumors.

Conclusion

C666-1 contains a representative NPC-associated EBV genome and might serve as an important model for studying the roles or function of viral proteins in NPC tumorigenesis.
Building limes for cultural heritage conservation in China
Authors: Dai Shi-bing
Published: August 2013

Introduction

Lime has been used as a building and decoration material for thousands of years in China. Recent research has focused on developing new air lime with higher bonding strength, grouts and restoration mortars etc. based on natural hydraulic lime, which is both chemically and mechanically more compatible with historic substances.

Results

The most applied lime in China was, and is still air lime, and the traditional slaking and preparation technique has been passed over to the modern generation for most restoration projects. Optimum dosage of Tungoil to lime-earth as damp proofing barrier lies at app. 5 wt%. A kind of patented dispersed air lime modified with additives has been developed, which can be applied as a binder for restoration of traditional lime ornaments or lime paints. Natural hydraulic lime has been introduced into China from 2008 Recently, adhesives and grouting slurries based on natural hydraulic lime have been developed and applied for refitting and cavity filling of delaminated cultural surfaces with proven satisfaction.

Conclusion

The preliminary research works show, both air lime and natural hydraulic limes through modification of latest construction chemistry achievements can meet most of restoration requirements.