bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Cell Death in Renal Cell Carcinoma With Combination of D-Fraction and Vitamin C
Authors: Alexander Bobby , Fishman Andrew I. , Eshghi Majid , Choudhury Muhammad , Konno Sensuke
Published: January 2013

Hypothesis. Although several conventional therapeutic options for advanced renal cell carcinoma (RCC) are currently available, the unsatisfactory outcomes demand establishing more effective interventions. D-fraction (PDF), a bioactive proteoglucan of Maitake mushroom, demonstrates anticancer and immunomodulatory activities, which are also shown to be potentiated by vitamin C (VC). We thus hypothesized that a combination of PDF and VC (PDF + VC) could be an alternative approach to more effectively inhibit the growth of RCC. Study design. We examined the dose-dependent effects of PDF + VC on RCC cell viability and also performed biochemical assays to explore the growth regulatory mechanism. Methods. Human RCC, ACHN cell line, was employed and exposed to varying concentrations of PDF or VC and their combinations. Cell viability at specified times was determined by MTT assay. Lipid peroxidation assay, cell cycle analysis, and Western blot analysis were also performed. Results. PDF or VC alone led to the significant reduction in cell viability at 72 hours with PDF >500 µg/mL and VC ≥300 µM. When various combinations of PDF and VC were tested, the combination of the ineffective concentrations of PDF (300 µg/mL) and VC (200 µM) resulted in ~90% cell death in 24 hours. Lipid peroxidation assay then indicated significantly (~2.5 fold) elevated oxidative stress with this PDF + VC. Cell cycle analysis also indicated a G1 cell cycle arrest following a 6-hour PDF + VC treatment. Western blots further revealed a downregulation of Bcl2, an upregulation of Bax, and proteolytic activation of PARP (poly[ADP-ribose] polymerase) in PDF + VC-treated cells, indicating induction of apoptosis. Conclusion. The present study demonstrates that the combination of PDF and VC can become highly cytotoxic, inducing severe cell death in ACHN cells. This cytotoxic mechanism appears to be primarily attributed to oxidative stress, accompanied by a G1 cell cycle arrest. Such cell death induced by PDF + VC could be more likely linked to apoptosis, as indicated by the modulation of apoptosis regulators (Bcl2, Bax, and PARP). Therefore, as PDF and VC may work synergistically to induce apoptotic cell death, they may have clinical implications in an alternative, improved therapeutic modality for advanced RCC.
“When the sea of living memory has receded”: Cultural memory and literary narratives of the Middle Passage
Authors: Terry Jennifer
Published: January 2013

This article considers the emergence of the slave Middle Passage between Africa and the Americas as a pervasive topic and figure in modern black diasporic literature. It explores representation of the Atlantic crossing alongside broader questions about the formation and mutation of group identity based on understandings and constructions of a shared past. Three textual examples, taken from the work of David Dabydeen, John Edgar Wideman, and Toni Morrison, are used to illustrate the agency, variety, and suggestiveness of this oceanic imaginary and to highlight some specific functions of literary media. Theories of collective and cultural memory help address concerns with memorialization; the recovery of “forgotten” histories; the role of cultural production; and counter, contextual, and shifting narratives of the past.
Assessment of scapholunate instability and review of evidence for management in the absence of arthritis
Authors: Chennagiri R. J. R. , Lindau T. R.
Published: January 2013

Scapholunate ligament tear is a common wrist injury and may lead to degenerative arthritis of the wrist in the long term. We review the assessment and classification of scapholunate instability and discuss the findings from our search for evidence for the management of scapholunate instability in the absence of arthritis. Strong evidence (level 1 or 2) for management is lacking and published recommendations are largely experience-based. The choice of procedure in the absence of arthritis depends on the extent of the tear, quality of the ligament remnants, and reducibility of the joint. Prospective, randomized studies with validated outcome measures are needed to establish the efficacy of intervention on symptoms and function and its effect on the risk of future arthritis.
The wrist hyperflexion and abduction of the thumb (WHAT) test: a more specific and sensitive test to diagnose de Quervain tenosynovitis than the Eichhoff’s Test
Authors: Goubau J. F. , Goubau L. , Van Tongel A. , Van Hoonacker P. , Kerckhove D. , Berghs B.
Published: January 2013

De Quervain’s disease has different clinical features. Different tests have been described in the past, the most popular test being the Eichhoff’s test, often wrongly named as the Finkelstein’s test. Over the years, a misinterpretation has occurred between these two tests, the latter being confused with the first. To compare the Eichhoff’s test with a new test, the wrist hyperflexion and abduction of the thumb test, we set up a prospective study over a period of three years for a cohort of 100 patients (88 women, 12 men) presenting spontaneous pain over the radial side of the styloid of the radius (de Quervain tendinopathy). The purpose of the study was to compare the accuracy of the Eichhoff’s test and wrist hyperflexion and abduction of the thumb test to diagnose correctly de Quervain’s disease by comparing clinical findings using those tests with the results on ultrasound. The wrist hyperflexion and abduction of the thumb test revealed greater sensitivity (0.99) and an improved specificity (0.29) together with a slightly better positive predictive value (0.95) and an improved negative predictive value (0.67). Moreover, the study showed us that the wrist hyperflexion and abduction of the thumb test is very valuable in diagnosing dynamic instability after successful decompression of the first extensor compartment. Our results support that the wrist hyperflexion and abduction of the thumb test is a more precise tool for the diagnosis of de Quervain’s disease than the Eichhoff’s test and thus could be adopted to guide clinical diagnosis in the early stages of de Quervain’s tendinopathy.
Paediatric hand fractures
Authors: Young K. , Greenwood A. , MacQuillan A. , Lee S. , Wilson S.
Published: January 2013

This retrospective study reviews the demographics, morphology and management of paediatric hand fractures. Notes of all children with hand injuries attending a plastic surgery paediatric trauma clinic over a one-year period were reviewed. Non-bony injuries were excluded. A total of 303 fractures in 283 patients were included. Fracture incidence rose after the age of seven, peaking at 14 years of age; 76% of fractures occurred in males. Sporting injuries accounted for 47% of fractures. Physeal fractures were present in 39% of cases. Open fractures accounted for only 4% of all fractures. Management was primarily conservative. Only 5% of cases required surgical fixation; 6% of patients experienced complications.
Thumb reconstruction without formal pollicization in mirror hand deformity: a series of four cases
Authors: Al-Qattan M. M. , Al-Kahtani A. R. , Al-Sharif E. M. , Al-Otaibi N. J.
Published: January 2013

Thumb reconstruction in mirror hands is usually done by pollicization. However, objective pinch strength and power grip data in mirror hands following pollicization are lacking. Alternative thumb reconstruction techniques include doing nothing, rotation osteotomy or syndactylization of the radial digits. In this article, we report a series of four cases of mirror hand deformity where the thumb was not reconstructed by formal pollicization. Two cases had non-classic mirror hand deformity (the forearm contained a radius and an ulna) and the other two had classic ulnar dimelia. In all cases, thumb reconstruction was done by keeping one of the radial fingers in place (without pollicization) as the new thumb; and then (if required) performing a secondary osteotomy procedure to rotate the new thumb into pronation. The four cases were recalled back to the clinic for functional assessment at ages 20 years, 5 years, 4 years and 2 years, respectively. The overall hand function was considered ‘fair’ in the case with concurrent unique features, and was considered ‘excellent’ in the other three cases. It was concluded that the technique of thumb reconstruction used in the current series is an acceptable option. However, objective measurements, especially with regards to pinch strength and power grip, need to be compared with the pollicization technique.
On canonical geographies
Authors: Keighren Innes M. , Abrahamsson Christian , della Dora Veronica
Published: January 2013

Histories of geography are, by their very nature, selective enterprises. The apparent tendency of geographers to disparage particular periods of the discipline’s history, at the same time as exalting others, is characteristic of the way in which progress has been measured, relevance defined, and novelty identified. Yet, whilst other disciplines in the humanities and social sciences actively engage with their textual canons and founding figures, geographers have notoriously avoided doing so. In this paper, we consider why this has been the case and how different conceptions of canonicity have mattered to the ways in which the history of geography and its intellectual foundations have been narrated. In thinking through the significance of geography’s texts to the ways we imagine the discipline – its past, present, and future – we consider how processes of remembering and forgetting have been employed to serve certain intellectual and ideological agendas. We conclude by advocating a more serious engagement with geography’s textual legacy: one which might benefit not only disciplinary historiography but also disciplinary consciousness, and thus the future of geography itself.
Geography’s evolving traditions and textual critique
Authors: Withers Charles WJ
Published: January 2013

The commentary addresses three related matters. Since canonicity is a textual matter, we need to pay greater attention to the making and editing of texts. Since canonicity is significant in geography’s pedagogy, we need to be clear as to the purposes of our teaching it. Since canonicity is a reflection both of text and authorship, we need to understand the context to both text and its readership.
Golem geographies
Authors: Dixon Deborah , Hawkins Harriet , Straughan Elizabeth
Published: January 2013

In our response, below, we undertake a deeper engagement with one of the authors, Elizabeth Grosz, that a number of the respondents have evoked, implicitly as well as explicitly, in their response to our text and, in particular, Grosz's arguments on art as of the chaotic and of the animal. Whilst our comments on the bowerbird speak to the artistry involved in a sexuated mode of reproduction that increases biological difference, we emphasise an abyssal moment in our initial text wherein we move from a consideration of sexual selection to symbiosis and accretion as productive of diversity, terms that no longer sit quite so comfortably in the lexicon of the ‘animal’. Rather, we implicate aesthetics and an artistry across and down chemical concentration gradients.
Molecular decay of enamel matrix protein genes in turtles and other edentulous amniotes
Authors: Meredith Robert W , Gatesy John , Springer Mark S
Published: January 2013

Background

Secondary edentulism (toothlessness) has evolved on multiple occasions in amniotes including several mammalian lineages (pangolins, anteaters, baleen whales), birds, and turtles. All edentulous amniote clades have evolved from ancestors with enamel-capped teeth. Previous studies have documented the molecular decay of tooth-specific genes in edentulous mammals, all of which lost their teeth in the Cenozoic, and birds, which lost their teeth in the Cretaceous. By contrast with mammals and birds, tooth loss in turtles occurred in the Jurassic (201.6-145.5 Ma), providing an extended time window for tooth gene degradation in this clade. The release of the painted turtle and Chinese softshell turtle genomes provides an opportunity to recover the decayed remains of tooth-specific genes in Testudines.

Results

We queried available genomes of Testudines (Chrysemys picta[painted turtle],Pelodiscus sinensis[Chinese softshell turtle]), Aves (Anas platyrhynchos[duck],Gallus gallus[chicken],Meleagris gallopavo[turkey],Melopsittacus undulatus[budgerigar],Taeniopygia guttata[zebra finch]), and enamelless mammals (Orycteropus afer[aardvark],Choloepus hoffmanni[Hoffmann’s two-toed sloth],Dasypus novemcinctus[nine-banded armadillo]) for remnants of three enamel matrix protein (EMP) genes with putative enamel-specific functions. Remnants of theAMBNandENAMgenes were recovered inChrysemysand retain their original synteny. Remnants ofAMELwere recovered in both testudines, although there are no shared frameshifts. We also show that there are inactivated copies ofAMBN,AMELandENAMin representatives of divergent avian lineages including Galloanserae, Passeriformes, and Psittaciformes, and that there are shared frameshift mutations in all three genes that predate the basal split in Neognathae. Among enamelless mammals, all three EMP genes exhibit inactivating mutations inOrycteropusandCholoepus.

Conclusions

Our results highlight the power of combining fossil and genomic evidence to decipher macroevolutionary transitions and characterize the functional range of different loci involved in tooth development. The fossil record and phylogenetics combine to predict the occurrence of molecular fossils of tooth-specific genes in the genomes of edentulous amniotes, and in every case these molecular fossils have been discovered. The widespread occurrence of EMP pseudogenes in turtles, birds, and edentulous/enamelless mammals also provides compelling evidence that in amniotes, the only unique, non-redundant function of these genes is in enamel formation.
Analysis of strain relatedness using High Resolution Melting in a case of recurrent candiduria
Authors: Gago Sara , Lorenzo Belen , Gomez-Lopez Alicia , Cuesta Isabel , Cuenca-Estrella Manuel , Buitrago Maria J
Published: January 2013

Background

Several genotyping protocols have been described to study Candida albicans strains with different sensitivity values. In this study we have analyzed the genetic relatedness and the antifungal susceptibility of several Candida albicans strains isolated from a patient who from suffered recurrent candiduria for a period of five years. Strains were genotyped using Microsatellite Length Polymorphism (MLP) with three microsatellite markers (HIS 3, EF 3 and CDC 3), and a new method based on high resolution melting (HRM) was developed to analyze the microsatellite region. This method was compared with the conventional technique that uses capillary electrophoresis.

Results

MICs of the isolates showed the existence of fluconazole susceptible and resistant strains. An inter-colony test using single concentration (8 and 16 mg/l) of fluconazole revealed the coexistence of both fluconazole susceptible and resistant strains. Both genotyping analysis methods showed that all the patient’s isolates had a clonal origin. HRM analysis method developed was able to accurately establish strain relatedness and presented a discriminatory power of 0.77.

Conclusions

Although HRM analysis method presented a lower discriminatory power compared to methods based on capillary electrophoresis, it provided a more cost-effective and suitable alternative for genotyping C. albicans in a clinical laboratory.
Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes
Authors: Sheng Li , Cao Wenjie , Cha Bingbing , Chen Zhaoping , Wang Fang , Liu Jun
Published: January 2013

Objective

To investigate the association of serum osteocalcin with carotid atherosclerosis in patients with type 2 diabetes.

Methods

We performed a cross-sectional community-based study in metropolitan area. Serum total osteocalcin was measured by radioimmunoassay in 382 men and 435 postmenopausal women. The carotid artery intima-media thickness (IMT) and carotid plaques (PLQ) were measured by B-mode ultrasound.

Results

The crude mean of serum osteocalcin concentrations were 4.52±2.43 ng/ml for men and 5.75±2.92 ng/ml for postmenopausal women (P <0.001), respectively. Osteocalcin levels were associated inversely with age, fasting serum insulin, HOMA-IR, ALT, triglycerides, total cholesterol, LDL- cholesterol, CRP (all P<0.001) and positively with adiponectin and HOMA-B (all P<0.05). After multiple adjustment, the odds ratios (ORs) were substantially higher risk for carotid plaques (OR 1.77 for 1 SD decrease in osteocalcin, 95% CI 1.23-2.76, p=0.005). These associations remained significant after further adjustment for potential confounder.

Conclusions

Serum osteocalcin levels is an independent risk factor for carotid atherosclerosis in patients with type 2 diabetes.
TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression
Authors: Shmarina Galina , Pukhalsky Alexander , Petrova Nika , Zakharova Ekaterina , Avakian Lucine , Kapranov Nikolai , Alioshkin Vladimir
Published: January 2013

Background

It is well known that the disease progression in cystic fibrosis (CF) patients may be diverse in subjects with identical mutation in CFTR gene. It is quite possible that such heterogeneity is associated with TNF-α and/or LT-α gene polymorphisms since their products play a key role in inflammation. The aim of the study was to investigate the possible roles of TNF gene polymorphisms in CF disease phenotype and progression.

Methods

198 CF patients and 130 control subjects were genotyped for both TNF-α–308GA and LT-α + 252AG polymorphisms.

Results

The carriers of the TNF-α–308A allele more frequently had asthma as compared to patients homozygous for the TNF-α–308 G allele. In 9 of 108 (8.3%) of LTα + 252AA carriers, tuberculosis infection has been documented, whereas there was no case of tuberculosis among patients, either homozygous or heterozygous for LTα +252 G alleles (p = 0.01). We never observed virus hepatitis among LTα + 252GA carriers. The genotypes TNF-α–308GG – LT-α + 252AA and TNF-α–308GA – LT-α + 252AG were unfavorable with regard to liver disease development (both p < 0.05). It was also shown that neutrophil elastase activity was higher in sputum specimens from high TNF producers with genotypes TNF-α–308GA or LT-α + 252GG. In addition the carriers of such genotypes demonstrated a higher risk of osteoporosis development (p values were 0.011 and 0.017, respectively).

Conclusions

The carriers of genotypes, which are associated with higher TNF-α production, demonstrated increased frequency of asthma, higher levels of neutrophil elastase, and decrease of bone density. On the contrary, the carriers of genotypes associated with low TNF-α production showed a higher frequency of tuberculosis infection.
Association of human papillomavirus type 16 long control region mutation and cervical cancer
Authors: Pientong Chamsai , Wongwarissara Parichat , Ekalaksananan Tipaya , Swangphon Piyawut , Kleebkaow Pilaiwan , Kongyingyoes Bunkerd , Siriaunkgul Sumalee , Tungsinmunkong Kobkul , Suthipintawong Cheepsumon
Published: January 2013

Background

The variation of human papillomavirus (HPV) genes or HPV variants demonstrates different risks of cervical cancer. Mutation in the long control region (LCR) at YY1-motifs is one of the mechanisms for enhancing viral oncogene expression during the course of cancer cell progression. In Thai women, cervical cancers are almost always associated with HPV16 variant sub-lineage Asian (HPV16As); however, the mechanism involved remains elusive. The aim of this study was to understand further the oncogenic potential of HPV16As.

Methods

A total of 82 HPV16-positive specimens from Thai women were selected from formalin-fixed paraffin-embedded cervical tissues, and the full length E6 gene of each specimen was amplified and sequenced. LCRs of the HPV16As-positive cases were amplified and sequenced to analyze their polymorphisms. Transcriptional activities of the HPV16As LCRs were then compared with sub-lineage European (EUR), sub-lineage Asian-American 1 (AA1) and HPV16 prototype by insertion of the LCRs into the pGL3-Basic vector.

Results

The HPV16 DNA sequences were classified as HPV16 prototype (18.3%), Asian (As, 61%), Asian American-1 (AA1, 8.5%), European (EUR, 7.3%), Asian African-2 (AFR2, 3.7%) and Java-135C (J135C, 1.2%). The prevalence of HPV16As was 30% in low-grade squamous intraepithelial lesion (LSIL), while that in high-grade squamous intraepithelial lesion (HSIL) and squamous cell cervical carcinoma (SCC) were 63.9% and 66.7%, respectively, which demonstrates a significant association of HPV16As with the disease severity. LCR polymorphisms from 43 HPV16As positive cases were analyzed by PCR-sequencing. Thirty-eight nucleotide variation positions spanned nucleotide positions 7157–82. Ten new mutations found in the HPV16As LCRs were located predominantly at the enhancer and proximal to the 3’-end of the early promoter. The LCRs of the common HPV16As, EUR and AA1 showed 5, 13 and 23-fold higher activity than the HPV16 prototype LCR, while those of the new nucleotide variations of As showed 19 (As-sv1) and 30 (As-sv14) -fold higher activity than the HPV16 prototype.

Conclusions

HPV16As DNA sequence variation, especially at the proximal to early promoter in the LCR, enhances transcriptional activity. This could be one of the possible mechanisms for HPV16As-associated cervical cancer development.
Excretion of enterovirus 71 in persons infected with hand, foot and mouth disease
Authors: Li Jie , Lin Changying , Qu Mei , Li Xinyu , Gao Zhiyong , Zhang Xin , Liu Yuan , Huang Ying , Wang Xiaoli , Jia Lei , Li Xitai , Liu Guirong , Yan Hanqiu , Chen Lijuan , Wang Quanyi
Published: January 2013

Background

Hand, foot and mouth disease (HFMD) is a common illness in young children. It also can be seen in adults occasionally. Enterovirus 71 (EV71), a pathogen that causes not only HFMD but also neurological complications and even death, has caused many HFMD outbreaks in China. However, till now the data about the duration of EV71 shedding is very limited.

Results

A total of 136 throat swabs and fecal samples were collected from 27 children and 3 adults, which includs 7 close contacts, 9 mild cases and 14 severe cases,. The participants were divided into three groups namely, severe case group, mild case group and close contact group. All the samples were assayed with real-time polymerase chain reaction (PCR). Kruskal-Wallis Test was employed to compare the difference in duration of viral RNA shedding among three groups. The results showed that significant difference in duration of EV71 shedding was found among three groups (P < 0.01). The longest duration of EV71 shedding in fecal samples is 54 days and 30 days in throat swabs.

Conclusions

HFMD is characterized by extended excretion of EV71. Our results suggest that the duration of EV71 shedding is correlated with the severity of the disease. EV71 shedding through feces can persist more than 54 days. Prolonged virus shedding is a potential risk factor of proliferating HFMD epidemic.
Ethnobotanical study of plants used in management of livestock health problems by Afar people of Ada’ar District, Afar Regional State, Ethiopia
Authors: Giday Mirutse , Teklehaymanot Tilahun
Published: January 2013

Background

The great majority of the Afar people of Ethiopia are pastoralists, highly dependent on livestock and livestock products. Livestock productivity is, however, frequently affected by different diseases. Although many districts in the Region have veterinary clinics, they lack basic facilities. As a result, the Afar people are still dependent on local materials, mainly plants, and traditional knowledge to manage livestock health problems. However, there is a serious threat to such local resources mainly due to recurrent drought and influence of modernization. Hence there is a need for proper documentation and evaluation of the existing ethnoveterinary knowledge in the Region. This study was aimed at documenting and analysing ethnoveterinary knowledge of people in Ada’ar District of the Afar Region associated with the use of plants.

Methods

The study involved interviewing selected knowledgeable Afar people in Ada’ar District on the use of plants to manage livestock ailments. Fidelity Level (FL) values were calculated for the reported medicinal plant to estimate their healing potentials. Specimens of reported medicinal plant were collected, identified and deposited at the National Herbarium, Addis Ababa University.

Results

The study revealed 49 medicinal plants as being used by the Afar people of Ada’ar District for the treatment of various livestock ailments, the majority of which (67.3%) were shrubs. Highest number of medicinal plants was used to treat blackleg, contagious caprine pleuropneumonia (CCPP), sudden sickness and pneumonia. Leaf was the most frequently sought plant part, accounting for 47% of the reported plants. All the medicnal plants used in the District were uncultivated ones growing in semi-disturbed and disturbed habitats as remnant plants and weeds. Cissus quadrangularis and Solanum incanum were the plants scoring the highest fidelity level values for their use to treat blackleg and respiratory tract problems, respectively.

Conclusion

The study revealed that there is still rich knowledge of ethnoveterinary medicine in Ada’ar District. There was no habit of cultivating medicinal plants by people in the study area. Efforts, should, therefore, be made to protect these medicinal plants from further depletion, especially those that are scarcely availabale. Better attention should be given to medicinal plants with the highest fidelity level values as such values could indicate potencies of the plants.
Potential roles of microRNAs in regulating long intergenic noncoding RNAs
Authors: Juan Liran , Wang Guohua , Radovich Milan , Schneider Bryan P , Clare Susan E , Wang Yadong , Liu Yunlong
Published: January 2013

Background

Over 10,000 long intergenic non-coding RNAs (lincRNAs) have been identified in the human genome. Some have been well characterized and known to participate in various stages of gene regulation. In the post-transcriptional process, another class of well-known small non-coding RNA, or microRNA (miRNA), is very active in inhibiting mRNA. Though similar features between mRNA and lincRNA have been revealed in several recent studies, and a few isolated miRNA-lincRNA relationships have been observed. Despite these advances, the comprehensive miRNA regulation pattern of lincRNA has not been clarified.

Methods

In this study, we investigated the possible interaction between the two classes of non-coding RNAs. Instead of using the existing long non-coding database, we employed an ab initio method to annotate lincRNAs expressed in a group of normal breast tissues and breast tumors.

Results

Approximately 90 lincRNAs show strong reverse expression correlation with miRNAs, which have at least one predicted target site presented. These target sites are statistically more conserved than their neighboring genetic regions and other predicted target sites. Several miRNAs that target to these lincRNAs are known to play an essential role in breast cancer.

Conclusion

Similar to inhibiting mRNAs, miRNAs show potential in promoting the degeneration of lincRNAs. Breast-cancer-related miRNAs may influence their target lincRNAs resulting in differential expression in normal and malignant breast tissues. This implies the miRNA regulation of lincRNAs may be involved in the regulatory process in tumor cells.
Leptin up-regulates TLR2 in human monocytes
Authors: Jaedicke Katrin M , Roythorne Ashleigh , Padget Kay , Todryk Stephen , Preshaw Philip M , Taylor John J
Published: January 2013

Leptin-stimulated TLR2 and CD14 expression may potentiate innate immunity and inflammation, in obesity and T2DM.

The adipokine leptin elicits changes in the expression of the activation markers CD40 and CD69 in PBMCs and DCs, yet its effect on PRRs remains to be elucidated. Serum leptin concentrations are elevated in obesity and T2DM, which are both diseases associated with a proinflammatory state. We therefore investigated a possible role for leptin in monocyte TLR and CD14 expression. Leptin increased TLR2 cell-surface and mRNA expression in THP-1 and primary human monocytes. In contrast, leptin had no effect on monocyte TLR4 expression in THP-1 or primary monocytes. CD14 cell-surface and mRNA expression were increased after leptin stimulation in THP-1 monocytes. However, no change in cell-surface CD14 expression was observed after leptin treatment in primary human monocytes. Leptin also up-regulated the expression of PU.1 and EGR2, transcription factors involved in myeloid cell differentiation. Additionally, leptin potentiated Escherichia coli and Porphyromonas gingivalis LPS-induced TNF-α secretion in THP-1 monocytes. In conclusion, we show that leptin and LPS differentially influence monocyte phenotype and demonstrate, for the first time, a regulatory effect of leptin on the monocyte expression of TLR2. Leptin-stimulated TLR2 expression may potentiate innate immunity and inflammation in conditions of hyperleptinemia, such as obesity and T2DM.
Recommended IGF-I Dosage Causes Greater Fat Accumulation and Osseous Maturation Than Lower Dosage and May Compromise Long-term Growth Effects
Authors: Guevara-Aguirre Jaime , Rosenbloom Arlan L. , Guevara-Aguirre Marco , Saavedra Jannette , Procel Patricio
Published: January 2013

Context:

The maximum dose of IGF-I recommended for treatment of GH insensitivity is commonly used.

Objective:

The aim was to test the hypothesis that a lower dose is as effective as a high dose of IGF-I in growth promotion and has fewer deleterious effects.

Design and Setting:

Subjects were treated for 3 years with regular examinations including bone age and dual energy x-ray absorptiometry and for 1 year with abdominal ultrasound studies at a clinical research institute in Quito, Ecuador.

Subjects:

The study included 21 subjects ages 3.2–15.9 years with GH insensitivity due to the same splice site mutation on the GH receptor gene.

Interventions:

Subjects were allocated to receive 120 (n = 14) or 80 (n = 7) μg/kg IGF-I twice daily.

Main Outcome Measures:

Height velocity, osseous maturation, height SD scores (SDS), body composition, abdominal organ growth, and side effects were assessed.

Results:

There were no differences in growth velocity or height SDS increment by dosage, and the SDS increase was greater than in other reported series. Osseous maturation over 3 years with the high dose was nearly twice as rapid as with the lower dose (P < .001) and correlated with an increase in percentage body fat (r = .64; P < .001) and with adrenal size increase over 1 year (r = .32; P = .03). The ratio of bone age to height age was lower in the high-dose group after 3 years of treatment (P = .007).

Conclusions:

The commonly used IGF-I dosage of 120 μg/kg twice a day is excessive in comparison to a dose of 80 μg/kg twice a day, disproportionately accelerating osseous maturation, probably from the combined effects of obesity and inappropriate adrenal growth, thus likely compromising adult height potential. Moreover, the lower dose decreases direct treatment cost by one-third.
Set-Asides and Subsidies in Auctions
Authors: Athey Susan , Coey Dominic , Levin Jonathan
Published: January 2013

Set-asides and subsidies are used extensively in government procurement and resource sales. We analyze these policies in an empirical model of US Forest Service timber auctions. The model fits the data well both within the sample of unrestricted sales used for estimation, and when we predict (out-of-sample) outcomes for small business set-asides. Our estimates suggest that restricting entry substantially reduces efficiency and revenue, although it increases small business participation. An alternative policy of subsidizing small bidders would increase revenue and small bidder profit, with little efficiency cost. We explain these findings by connecting to the theory of optimal auction design. (JEL D44, H57, L73, Q23)
Evaluation of the Treatment of Vancomycin-Resistant Enterococcal Urinary Tract Infections in a Large Academic Medical Center
Authors: Heintz Brett H , Cho Stacey , Fujioka Akina , Li Jenny , Halilovic Jenana
Published: January 2013

BACKGROUND:

Vancomycin-resistant enterococci (VRE) are a common cause of nosocomial urinary tract infections (UTIs) among hospitalized patients. Clinicians need to differentiate between VRE-associated urinary colonization, asymptomatic bacteriuria, and UTIs to determine the need for treatment and length of therapy.

OBJECTIVE:

To characterize the diagnosis and management of VRE from urinary sources, including compliance with institutional treatment guidelines, and identify risk factors associated with clinical failure.

METHODS:

We performed a retrospective, single-center, cohort study among patients with VRE-positive cultures from urinary sources over a 3-year study period (July 2008-September 2011). Descriptive statistics were used to evaluate demographics, diagnostics, guideline compliance, pharmacotherapy, and outcomes. Risk factors associated with clinical failure were identified by multivariate logistic regression analysis.

RESULTS:

Two hundred sixty-nine distinct episodes of VRE met inclusion criteria among 252 patients. Forty-seven percent and 77% of episodes occurred in patients admitted to an intensive care unit and hospitalized for 7 or more days, respectively. Fifty-eight percent of the episodes were classified as asymptomatic bacteriuria or colonization. Compliance with institutional treatment guidelines for the appropriate drug, dose, and duration occurred in approximately 70% of the cases. Among noncompliant cases (n = 83), 48 (58%) were overtreated, and 35 (42%) were undertreated. Clinical failure among all cases was common, including mortality (17.1%). Factors independently associated with clinical failure determined on multivariate analysis included weight 100 kg or more (OR 5.30; 95% CI 1.42–12.21; p = 0.014), renal disease (OR 2.57; 95% CI 1.02–6.47; p = 0.048), indwelling catheter (OR 4.62; 95% CI 1.05–18.24; p = 0.046), and VRE bloodstream infection (OR 15.71; 95% CI 2.9–128.7; p < 0.001).

CONCLUSIONS:

Improved education is needed to minimize cases of overtreatment and undertreatment of VRE-associated UTIs and decrease inappropriate drug-related costs and clinical failure rates. Risk factors for clinical failure can be used to risk stratify VRE-associated UTIs and further guide treatment decisions.
A Comparison between Manual and Automated Evaluations of Tissue Microarray Patterns of Protein Expression
Authors: Alvarenga Arthur W. , Coutinho-Camillo Claudia M. , Rodrigues Bruna R. , Rocha Rafael M. , Torres Luiz Fernando B. , Martins Vilma R. , da Cunha Isabela W. , Hajj Glaucia N. M.
Published: January 2013

Tissue microarray technology enables us to evaluate the pattern of protein expression in large numbers of samples. However, manual data acquisition and analysis still represent a challenge because they are subjective and time-consuming. Automated analysis may thus increase the speed and reproducibility of evaluation. However, the reliability of automated analysis systems should be independently evaluated. Herein, the expression of phosphorylated AKT and mTOR was determined by ScanScope XT (Aperio; Vista, CA) and ACIS III (Dako; Glostrup, Denmark) and compared with the manual analysis by two observers. The percentage of labeled pixels or nuclei analysis had a good correlation between human observers and automated systems (κ = 0.855 and 0.879 for ScanScope vs. observers and κ = 0.765 and 0.793 for ACIS III vs. observers). The intensity of labeling determined by ScanScope was also correlated with that found by the human observers (correlation index of 0.946 and 0.851 for pAKT and 0.851 and 0.875 for pmTOR). However, the correlation between ACIS III and human observation varied for labeling intensity and was considered poor in some cases (correlation index of 0.718 and 0.680 for pAKT and 0.223 and 0.225 for pmTOR). Thus, the percentage of positive pixels or nuclei determination was satisfactorily performed by both systems; however, labeling intensity was better identified by ScanScope XT.
Do Business and Political Ties Differ in Cultivating Marketing Channels for Foreign and Local Firms in China?
Authors: Dong Maggie Chuoyan , Li Caroline Bingxin , Tse David K.
Published: January 2013

Despite the prominence of social ties in emerging economies, it remains unclear whether and how social ties matter in cultivating marketing channels for both local and foreign firms in China. Moreover, few studies have explicitly distinguished and examined the roles of business versus political ties. Drawing on the resource-based view and social network theory, the authors propose and test the moderating effects of political ties and business ties on channel capability–performance relationships. The findings from a survey of 342 firms indicate that the value of channel capability is conditional on political and business ties, but in opposite directions: business ties impede and political ties strengthen the effect of channel capability on firm performance. Furthermore, the moderating role of social ties is stronger for local, nonleading firms than for foreign, leading firms.
When Does Recognition Increase Charitable Behavior? Toward a Moral Identity-Based Model
Authors: Winterich Karen Page , Mittal Vikas , Aquino Karl
Published: January 2013

Each year, people in the United States donate more than $200 billion to charitable causes. Despite the lack of understanding of whether and how recognition increases charitable behavior, charities often offer it to motivate donor action. This research focuses on how the effectiveness of recognition on charitable behavior is dependent on the joint influence of two distinct dimensions of moral identity: internalization and symbolization. Three studies examining both monetary donations and volunteering behavior show that recognition increases charitable behavior among those characterized by high moral identity symbolization and low moral identity internalization. Notably, those who show high levels of moral identity internalization are uninfluenced by recognition, regardless of their symbolization. By understanding correlates of the two dimensions of moral identity among donors, nonprofits can strategically recognize potential donors to maximize donation and volunteering behavior.
When Do Transparent Packages Increase (or Decrease) Food Consumption?
Authors: Deng Xiaoyan , Srinivasan Raji
Published: January 2013

Transparent packages are pervasive in food consumption environments. Yet prior research has not systematically examined whether and how transparent packaging affects food consumption. The authors propose that transparent packaging has two opposing effects on food consumption: it enhances food salience, which increases consumption (salience effect), and it facilitates consumption monitoring, which decreases consumption (monitoring effect). They argue that the net effect of transparent packaging on food consumption is moderated by food characteristics (e.g., unit size, appearance). For small, visually attractive foods, the monitoring effect is low, so the salience effect dominates, and people eat more from a transparent package than from an opaque package. For large foods, the monitoring effect dominates the salience effect, decreasing consumption. For vegetables, which are primarily consumed for their health benefits, consumption monitoring is not activated, so the salience effect dominates, which ironically decreases consumption. The authors’ findings suggest that marketers should offer small foods in transparent packages and large foods and vegetables in opaque packages to increase postpurchase consumption (and sales).
Judging the Book by Its Cover? how Consumers Decode Conspicuous Consumption Cues in Buyer–Seller Relationships
Authors: Scott Maura L. , Mende Martin , Bolton Lisa E.
Published: January 2013

Little empirical consumer research has focused on the decoding of conspicuous symbolism, that is, the inferences consumers make about others’ conspicuous consumption. Grounded in theory on social perception and role congruity, four experiments show that consumer inferences about and behavioral intentions toward conspicuous sellers are moderated by communal and exchange relationship norms. Specifically, conspicuous consumption by a seller decreases warmth inferences and, in turn, behavioral intentions toward the seller under the communal norm; conversely, it increases competence inferences and, in turn, behavioral intentions under the exchange norm. A seller's mere wealth triggers similar inferences, suggesting that conspicuous consumption is a surrogate for actual wealth. Priming consumers with persuasion knowledge inhibits the inferential benefits resulting from conspicuousness under the exchange norm. These findings reveal the theoretically meaningful role of the consumption context by showing that consumers’ warmth and competence inferences operate differentially in commercial relationships as a result of salient communal versus exchange norms, with important consequences for consumers’ behavioral intentions.
Prestimulus Oscillatory Activity over Motor Cortex Reflects Perceptual Expectations
Authors: de Lange Floris P. , Rahnev Dobromir A. , Donner Tobias H. , Lau Hakwan
Published: January 2013

When perceptual decisions are coupled to a specific effector, preparatory motor cortical activity may provide a window into the dynamics of the perceptual choice. Specifically, previous studies have observed a buildup of choice-selective activity in motor regions over time reflecting the integrated sensory evidence provided by visual cortex. Here we ask how this choice-selective motor activity is modified by prior expectation during a visual motion discrimination task. Computational models of decision making formalize decisions as the accumulation of evidence from a starting point to a decision bound. Within this framework, expectation could change the starting point, rate of accumulation, or the decision bound. Using magneto-encephalography in human observers, we specifically tested for changes in the starting point in choice-selective oscillatory activity over motor cortex. Inducing prior expectation about motion direction biased subjects' perceptual judgments as well as the choice-selective motor activity in the 8–30 Hz frequency range before stimulus onset; the individual strength of these behavioral and neural biases were correlated across subjects. In the absence of explicit expectation cues, spontaneous biases in choice-selective activity were evident over motor cortex. These also predicted eventual perceptual choice and were, at least in part, induced by the choice on the previous trial. We conclude that both endogenous and explicitly induced perceptual expectations bias the starting point of decision-related activity, before the accumulation of sensory evidence.
Central Amygdala GluA1 Facilitates Associative Learning of Opioid Reward
Authors: Cai You-Qing , Wang Wei , Hou Yuan-Yuan , Zhang Zhi , Xie Jun , Pan Zhizhong Z.
Published: January 2013

GluA1 subunits of AMPA glutamate receptors are implicated in the synaptic plasticity induced by drugs of abuse for behaviors of drug addiction, but GluA1 roles in emotional learning and memories of drug reward in the development of drug addiction remain unclear. In this study of the central nucleus of the amygdala (CeA), which is critical in emotional learning of drug reward, we investigated how adaptive changes in the expression of GluA1 subunits affected the learning process of opioid-induced context–reward association (associative learning) for the acquisition of reward-related behavior. In CeA neurons, we found that CeA GluA1 expression was significantly increased 2 h after conditioning treatment with morphine, but not 24 h after the conditioning when the behavior of conditioned place reference (CPP) was fully established in rats. Adenoviral overexpression of GluA1 subunits in CeA accelerated associative learning, as shown by reduced minimum time of morphine conditioning required for CPP acquisition and by facilitated CPP extinction through extinction training with no morphine involved. Adenoviral shRNA-mediated downregulation of CeA GluA1 produced opposite effects, inhibiting the processes of both CPP acquisition and CPP extinction. Adenoviral knockdown of CeA GluA2 subunits facilitated CPP acquisition, but did not alter CPP extinction. Whole-cell recording revealed enhanced electrophysiological properties of postsynaptic GluA2-lacking AMPA receptors in adenoviral GluA1-infected CeA neurons. These results suggest that increased GluA1 expression of CeA AMPA receptors facilitates the associative learning of context-drug reward, an important process in both development and relapse of drug-seeking behaviors in drug addiction.
Spatiotemporal Dynamics of Functional Clusters of Neurons in the Mouse Motor Cortex during a Voluntary Movement
Authors: Hira Riichiro , Ohkubo Fuki , Ozawa Katsuya , Isomura Yoshikazu , Kitamura Kazuo , Kano Masanobu , Kasai Haruo , Matsuzaki Masanori
Published: January 2013

Functional clustering of neurons is frequently observed in the motor cortex. However, it is unknown if, when, and how fine-scale (<100 μm) functional clusters form relative to voluntary forelimb movements. In addition, the implications of clustering remain unclear. To address these issues, we conducted two-photon calcium imaging of mouse layer 2/3 motor cortex during a self-initiated lever-pull task. In the imaging session after 8–9 days of training, head-restrained mice had to pull a lever for ∼600 ms to receive a water drop, and then had to wait for >3 s to pull it again. We found two types of task-related cells in the mice: cells whose peak activities occurred during lever pulls (pull cells) and cells whose peak activities occurred after the end of lever pulls. The activity of pull cells was strongly associated with lever-pull duration. In ∼40% of imaged fields, functional clusterings were temporally detected during the lever pulls. Spatially, there were ∼70-μm-scale clusters that consisted of more than four pull cells in ∼50% of the fields. Ensemble and individual activities of pull cells within the cluster more accurately predicted lever movement trajectories than activities of pull cells outside the cluster. This was likely because clustered pull cells were more often active in the individual trials than pull cells outside the cluster. This higher fidelity of activity was related to higher trial-to-trial correlations of activities of pairs within the cluster. We propose that strong recurrent network clusters may represent the execution of voluntary movements.