bluuebunny/crossref_metadata_2025 huggingface dataset:
Action research and public relations: Dialogue, peer learning, and the issue of alcohol
Authors: Pieczka Magda , Wood Emma
Published: May 2013

This article presents an action research project that transformed dialogic techniques used in, policy making and community development into an innovative approach to education about alcohol. The project was developed by a group of teenage volunteers, the AlcoLOLs, and two public relations researchers, tested in a local school, presented at the Scottish Parliament to policy stakeholders concerned with alcohol, and subsequently extended to a number of schools across the city of Edinburgh (Scotland).

The article contributes to public relations research by offering a detailed analytical account of dialogue as a method of inquiry and a mechanism for change. The article also introduces the concept of extended epistemology as a fresh perspective on the phenomenon of relationship and relationship management. Finally, the article argues that action research has the transformative potential for the development of academic knowledge in the field and as an approach to education and training of practitioners.
Clinical Supervision Among Family Physicians
Authors: Torppa Martina A. , Toivola Kristiina , Ruskoaho Juho , Pitkälä Kaisu H.
Published: May 2013

Background: Clinical supervision (CS) is not an established support system among physicians. Family physicians (FPs) have used Balint groups as a form of clinical supervision. In all, not much is known about the prevalence of physicians’ attendance to or needs for CS. Objective: We studied what proportion of FPs compared with other physicians have attended or report they would need CS and whether having patients who request certain tests or medicines is associated with FPs’ attendance to or need for CS. Design: A postal survey for all working-aged Finnish physicians was performed in 2008. Special questions concerning CS (eg, Balint) and patients’ requests were included. Results: Response rate for the survey was 74% (N = 13 708). Special questions were responded by 10 559 physicians of whom 1252 were FPs. FPs had attended CS more often than other physicians (42% vs 29%, P < .001). Of FPs, 25% reported a need for CS with no availability of it. FPs experienced with or needing for CS were more often than other FPs females, had participated in continuing medical education, and reported that patients with requests have increased in recent years. Conclusion: Both experience of CS and a need for CS with no availability are common among Finnish FPs. Experiences of patients with requests may reflect a need for CS among FPs. Studies on the content, significance and effectiveness CS among FPs are needed.
Subcellular mislocalization of the transcription factor NF-E2 in erythroid cells discriminates prefibrotic primary myelofibrosis from essential thrombocythemia
Authors: Aumann Konrad , Frey Anna-Verena , May Annette M. , Hauschke Dieter , Kreutz Clemens , Marx Jan P. , Timmer Jens , Werner Martin , Pahl Heike L.
Published: May 2013

Key Points

The transcription factor NF-E2 is mislocalized in patients with primary myelofibrosis. Immunohistochemical staining for NF-E2 distinguishes essential thrombocythemia from primary myelofibrosis.
Comparative transcriptome analysis and marker development of two closely related Primrose species (Primula poissonii and Primula wilsonii)
Authors: Zhang Lu , Yan Hai-Fei , Wu Wei , Yu Hui , Ge Xue-Jun
Published: May 2013

Background

Primula species are important early spring garden plants with a centre of diversity and speciation in the East Himalaya-Hengduan Mountains in Western China. Studies on population genetics, speciation and phylogeny of Primula have been impeded by a lack of genomic resources. In the present study, we sequenced the transcriptomes of two closely related primrose species, Primula poissonii and Primula wilsonii, using short reads on the Illumina Genome Analyzer platform.

Results

We obtained 55,284 and 55,011 contigs with N50 values of 938 and 1,085 for P. poissonii and P. wilsonii, respectively, and 6,654 pairs of putative orthologs were identified between the two species. Estimations of non-synonymous/synonymous substitution rate ratios for these orthologs indicated that 877 of the pairs may be under positive selection (Ka/Ks > 0.5), and functional enrichment analysis revealed that significant proportions of the orthologs were in the categories DNA repair, stress resistance, which may provide some hints as to how the two closely related Primula species adapted differentially to extreme environments, such as habitats characterized by aridity, high altitude and high levels of ionizing radiation. It was possible for the first time to estimate the divergence time between the radiated species pair, P. poissonii and P. wilsonii; this was found to be approximately 0.90 ± 0.57 Mya, which falls between the Donau and Gunz glaciation in the Middle Pleistocene. Primers based on 54 pairs of orthologous SSR-containing sequences between the two Primula species were designed and verified. About half of these pairs successfully amplified for both species. Of the 959 single copy nuclear genes shared by four model plants (known as APVO genes), 111 single copy nuclear genes were verified as being present in both Primula species and exon-anchored and intron-spanned primers were designed for use.

Conclusion

We characterized the transcriptomes for the two Primula species, and produced an unprecedented amount of genomic resources for these important garden plants. Evolutionary analysis of these two Primula species not only revealed a more precise divergence time, but also provided some novel insights into how differential adaptations occurred in extreme habitats. Furthermore, we developed two sets of genetic markers, single copy nuclear genes and nuclear microsatellites (EST-SSR). Both these sets of markers will facilitate studies on the genetic improvement, population genetics and phylogenetics of this rapidly adapting taxon.
Expression of Toll-like receptors 2 and 9 in cells of dog jejunum and colon naturally infected with Leishmania infantum
Authors: Figueiredo Maria M , Amorim Izabela FG , Pinto Aldair JW , Barbosa Vítor S , de Jesus Pinheiro Lucélia , Deoti Beatriz , Faria Ana MC , Tafuri Wagner L
Published: May 2013

Background

Infection with parasite protozoa is a long-term health issue in tropical and subtropical regions throughout the world. The Toll-like receptor (TLR) signaling pathway is one of the first-responding defense systems against Leishmania. The aim of this study was to investigate the expression of TLR2 and TLR9 in jejunum and colon and its correlation with CD11c, CD11b, and CD14 receptors used as markers for dendritic cells and macrophages.

Methods

Twenty four dogs infected with Leishmania infantum were used in this study. Cytometry was carried out in lamina propria cells from jejunum and colon using markers for TLR2, TLR9, CD11b, CD11c and CD14.

Results

Cellular inflammatory exudate was diffuse in the mucosa and submucosa, predominately comprising mononuclear cells: plasma cells, macrophages, and lymphocytes. Despite the parasite load, microscopy showed no erosion was evident in the epithelial mucosa layers. The colon harbored more parasites than the jejunum. Flow cytometry revealed higher frequency of TLR2+ and CD11c+ dendritic cells in the colon than in the jejunum. Conversely, TLR9-expressing cells were more frequent in jejunum. Moreover, frequency of macrophages (CD11b+ and CD14+) expressing simultaneity TLR9 were lower in the colon than in jejunum, while CD11c+ cells predominated in the colon. Despite of the negative ELISA serum results, IL-10 and TNF-α were higher in jejunum than colon of infected animals. However, IL-4 was higher in colon than jejunum of infected animals. A higher expression these cytokines were demonstrated in infected dogs compared to uninfected dogs.

Conclusions

There was no correlation between clinical signs and pathological changes and immunological and parasitological findings in the gastrointestinal tract in canine visceral leishmaniasis. However, jejunum showed a lower parasite load with increased frequency and expression of CD11b, TLR9, CD14/CD11b/TLR9 receptors and IL-10 and TNF-α cytokines. Conversely, the colon showed a higher parasite load along with increased frequency and expression of TLR2, CD11c receptors, and IL-4 cytokine. Thus, Leishmania infantum is able to interfere in jejunum increased expression of TLR2, TLR9, CD11b, CD14, CD14/CD11b/TLR9 receptors, IL-10, and TNF-α; and in colon increased expression of CD11c, TLR2, TLR9, CD11b, CD14 e, CD14/CD11b/TLR9 receptors, IL-10, and TNF-α.
The cell morphogenesis ANGUSTIFOLIA (AN) gene, a plant homolog of CtBP/BARS, is involved in abiotic and biotic stress response in higher plants
Authors: Gachomo Emma W , Jimenez-Lopez Jose C , Smith Sarah R , Cooksey Anthony B , Oghoghomeh Oteri M , Johnson Nicholas , Baba-Moussa Lamine , Kotchoni Simeon O
Published: May 2013

Background

ANGUSTIFOLIA (AN), one of the CtBP family proteins, plays a major role in microtubule-dependent cell morphogenesis. Microarray analysis of mammalian AN homologs suggests that AN might function as a transcriptional activator and regulator of a wide range of genes. Genetic characterization ofANmutants suggests that AN might be involved in multiple biological processes beyond cell morphology regulation.

Results

Using a reverse genetic approach, we provide in this paper the genetic, biochemical, and physiological evidence for ANGUSTIFOLIA’s role in other new biological functions such as abiotic and biotic stress response in higher plants. The T-DNA knockoutan-t1mutant exhibits not only all the phenotypes of previously describedangustifolianull mutants, but also copes better than wild type under dehydration and pathogen attack. The stress tolerance is accompanied by a steady-state modulation of cellular H2O2content, malondialdehyde (MDA) derived from cellular lipid peroxidation, and over-expression of stress responsive genes. Our results indicate that ANGUSTIFOLIA functions beyond cell morphology control through direct or indirect functional protein interaction networks mediating other biological processes such as drought and pathogen attacks.

Conclusions

Our results indicate that theANGUSTIFOLIAgene participates in several biochemical pathways controlling cell morphogenesis, abiotic, and biotic stress responses in higher plants. Our results suggest that thein vivofunction of plant ANGUSTIFOLIA has been overlooked and it needs to be further studied beyond microtubule-dependent cell morphogenesis.
Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study
Authors: Kuramoto Takanori , Umegaki Eiji , Nouda Sadaharu , Narabayashi Ken , Kojima Yuichi , Yoda Yukiko , Ishida Kumi , Kawakami Ken , Abe Yosuke , Takeuchi Toshihisa , Inoue Takuya , Murano Mitsuyuki , Tokioka Satoshi , Higuchi Kazuhide
Published: May 2013

Background

Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects.

Methods

Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment.

Results

There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031).

Conclusion

Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole.

Trial registration

This study was registered in the UMIN Clinical Trials Registry (Registry ID number;UMIN000008114)
Pulmonary actinomycosis during the first decade of 21st century: cases of 94 patients
Authors: Kim So Ri , Jung Lae Young , Oh In-Jae , Kim Young-Chul , Shin Kyeong-Cheol , Lee Min Ki , Yang Sei-Hoon , Park Hee Sun , Kim Mi-Kyung , Kwak Jin Young , Um Soo-Jung , Ra Seung Won , Kim Woo Jin , Kim Seungsoo , Choi Eu-Gene , Lee Yong Chul
Published: May 2013

Background

Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces. Both improving oral hygiene and early application of antibiotics to the case of suspicious pulmonary infections result in changes in incidences and presentations of pulmonary actinomycosis. However, there are little reports dealt with the recent clinical characteristics of pulmonary actinomycosis. This study aimed to review the characteristics of pulmonary actinomycosis occurred during the first decade of 21st century.

Methods

This retrospective study was performed on 94 subjects with pulmonary actinomycosis diagnosed pathologically from January 2000 to December 2010 in 13 hospitals in Korea.

Results

The data of the study showed that pulmonary actinomycosis occurs frequently in middle to old-aged males (mean age; 57.7 years old) and that the most common symptoms are cough, hemoptysis, and sputum production. Various radiologic features such as the consolidation with central low attenuation (74.5%) and no regional predominance were also observed. Most of patients recovered completely with medical and/or surgical treatment, reaching approximately 98% cure rate.

Conclusions

The results demonstrate that pulmonary actinomycosis is one of the cautious pulmonary diseases. More importantly, in cases of persistent hemoptysis or for differential diagnosis from lung malignancy, our data have revealed that surgical resection appears to be a useful intervention and that radiologic diagnosis may not provide decisive information. These findings indicate that it is important for the clinicians to include pulmonary actinomycosis as one of differential diagnoses for refractory pulmonary abnormal lesions to the current usual management.
Determinants of suboptimal hepatitis B vaccine uptake among men in the Republic of Korea: where should our efforts be focused: results from cross-sectional study
Authors: Park Boyoung , Choi Kui Son , Lee Hoo-Yeon , Kwak Min-Son , Jun Jae Kwan , Park Eun-Cheol
Published: May 2013

Background

Liver cancer is the second most-frequent cause of cancer death in Korea. Hepatitis B virus (HBV) infection is a major cause of liver cancer, and this disease is effectively prevented by HBV vaccination. This study was conducted to investigate factors associated with the lack of HBV vaccine uptake in the general adult male population in Korea.

Methods

Data of men who participated in a nationwide cross-sectional interview survey were analyzed. A total of 2,174 men 40 years of age and older were interviewed between 2006 and 2008. None of the participants was infected with HBV or was experiencing sequelae of an HBV infection.

Results

Only half (50.4%) of the men received one or more dose of the three-dose series of HBV vaccinations, and 32.5% received all three doses. Compared with men who had completed the vaccination regimen, non-vaccinated men were more likely to lack supplemental medical insurance for cancer (odds ratio = 0.66, 95% confidence interval: 0.52–0.84), have lower incomes (p-trend = 0.010), and be less educated (p-trend = 0.021). Lower education was also more prevalent in the non-vaccinated group compared with the incompletely vaccinated group. Those who had completed the vaccination regimen were likely to be more educated than those in the incompletely vaccinated group (p-trend = 0.044). The most commonly cited reason for not obtaining the HBV vaccine was lack of knowledge regarding the need for the vaccination. The number of men who cited this reason decreased as a function of education.

Conclusions

It is important to develop strategic interventions targeted at less-educated men to increase uptake of a complete three-dose series of HBV vaccinations as a primary approach to preventing liver cancer.
Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells
Authors: Tanaka Mamoru , Kataoka Hiromi , Yano Shigenobu , Ohi Hiromi , Kawamoto Keisuke , Shibahara Takashi , Mizoshita Tsutomu , Mori Yoshinori , Tanida Satoshi , Kamiya Takeshi , Joh Takashi
Published: May 2013

Background

Cisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients.

Methods

We synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl2 (L)] and [PdCl2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl2 (L)] and [PdCl2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo.

Results

CDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl2 (L)] induced DNA double-strand breaks.

Conclusion

These results indicate that [PdCl2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications.
Developmental defects of enamel in primary teeth and association with early life course events: a study of 6–36 month old children in Manyara, Tanzania
Authors: Masumo Ray , Bårdsen Asgeir , Åstrøm Anne Nordrehaug
Published: May 2013

Background

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).

Focusing 6–36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child’s early illness episodes and mothers’ perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene.

Methods

A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index.

Results

The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.2 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE.

Conclusion

Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania.
Diurnal variation of phenylalanine and tyrosine concentrations in adult patients with phenylketonuria: subcutaneous microdialysis is no adequate tool for the determination of amino acid concentrations
Authors: Grünert Sarah C , Brichta Corinna M , Krebs Andreas , Clement Hans-Willi , Rauh Reinhold , Fleischhaker Christian , Hennighausen Klaus , Sass Jörn Oliver , Schwab K Otfried
Published: May 2013

Background

Metabolic control and dietary management of patients with phenylketonuria (PKU) are based on single blood samples obtained at variable intervals. Sampling conditions are often not well-specified and intermittent variation of phenylalanine concentrations between two measurements remains unknown. We determined phenylalanine and tyrosine concentrations in blood over 24 hours. Additionally, the impact of food intake and physical exercise on phenylalanine and tyrosine concentrations was examined. Subcutaneous microdialysis was evaluated as a tool for monitoring phenylalanine and tyrosine concentrations in PKU patients.

Methods

Phenylalanine and tyrosine concentrations of eight adult patients with PKU were determined at 60 minute intervals in serum, dried blood and subcutaneous microdialysate and additionally every 30 minutes postprandially in subcutaneous microdialysate. During the study period of 24 hours individually tailored meals with defined phenylalanine and tyrosine contents were served at fixed times and 20 min bicycle-ergometry was performed.

Results

Serum phenylalanine concentrations showed only minor variations while tyrosine concentrations varied significantly more over the 24-hour period. Food intake within the patients’ individual diet had no consistent effect on the mean phenylalanine concentration but the tyrosine concentration increased up to 300% individually. Mean phenylalanine concentration remained stable after short-term bicycle-exercise whereas mean tyrosine concentration declined significantly. Phenylalanine and tyrosine concentrations in dried blood were significantly lower than serum concentrations. No close correlation has been found between serum and microdialysis fluid for phenylalanine and tyrosine concentrations.

Conclusions

Slight diurnal variation of phenylalanine concentrations in serum implicates that a single blood sample does reliably reflect the metabolic control in this group of adult patients.Phenylalanine concentrations determined by subcutaneous microdialysis do not correlate with the patients’ phenylalanine concentrations in serum/blood.
Measuring thyroid peroxidase antibodies on the day nulliparous women present for management of miscarriage: a descriptive cohort study
Authors: Grossmann Mathis , Hoermann Rudolf , Francis Claire , Hamilton Emma J , Tint Aye , Kaitu’u-Lino Tu’uhevaha , Kuswanto Kent , Lappas Martha , Sikaris Ken , Zajac Jeffery D , Permezel Michael , Tong Stephen
Published: May 2013

Background

There has been recent evidence suggesting the presence of anti-thyroid peroxidase antibodies (TPOAb) increases the risk of miscarriage, and levothyroxine can rescue miscarriages associated with TPOAb. We propose the most clinically pragmatic cohort to screen for TPOAb are women presenting for management of a missed miscarriage and have never birthed a liveborn. We measured serum TPOAb among nulliparous women presenting for management of miscarriage, and compared levels with women who have had 2 or more livebirths (and never miscarried). Given its potential role in immunomodulation, we also measured Vitamin D levels.

Methods

We performed a prospective descriptive cohort study at a tertiary hospital (Mercy Hospital for Women, Victoria, Australia). We measured TPOAb and Vitamin D levels in serum obtained from 118 nulliparous women presenting for management of miscarriage, and 162 controls with 2 or more livebirths (and no miscarriages). Controls were selected from a serum biobank prospectively collected in the first trimester at the same hospital.

Results

Nulliparous women with 1 or more miscarriages had higher thyroid peroxidase antibody (TPOAb) levels than those with 2 or more livebirths; TPOAb in miscarriage group was 0.3 mIU/L (interquartile range [IR]: 0.2-0.7) vs 0.2 mIU/L among controls (IR 0.0-0.5; p < 0.0001). We confirmed TPOAb levels were not correlated with serum human chorionic gonadotrophin (hCG) concentrations in either the miscarriage or control groups. In contrast, thyroid stimulating hormone, fT3 and fT4 levels (thyroid hormones) either trended towards a correlation, or were significantly correlated with serum hCG levels in the two groups. Of the entire cohort that was predominantly caucasian, only 12% were Vitamin D sufficient. Low Vitamin D levels were not associated with miscarriage.

Conclusions

We have confirmed the association between miscarriage and increased TPOAb levels. Furthermore, it appears TPOAb levels in maternal blood are not influenced by serum hCG levels. Therefore, we propose the day nulliparous women present for management for miscarriage is a clinically relevant, and pragmatic time to screen for TPOAb.
Metal ion-directed solution-phase tailoring: from large-area graphene oxide into nanoscale pieces
Authors: Wang Xiansong , Huang Peng , Liu Huiyang , Li Chao , Shen Guangxia , Cui Daxiang
Published: May 2013

Due to fascinating electronic properties and great potential in various applications, graphene has attracted great interest. Recently, much work have focused on the synthesis of different sizes and properties of graphene or graphene oxides (GOs), for example, graphene nanoribbons, nanosized graphene pieces, and nanosized triangular and hexagonal graphene sheets terminated by zigzag edges. Herein, we have demonstrated a widely available approach to fabricate the nanoscale GO pieces by directly solution-phase cutting a large-area GO sheet into nanoscale pieces via spontaneous redox reactions at room temperature. In this process, GO acts with dual functions as a model and a reducing reagent. With a typical example of silver ions, we have investigated in detail the influence of the reaction time and concentration of metal ions on yield and size of nanoscale GO pieces. Moreover, we also obtain Ag nanoparticle coating on the GO surface. Finally, a possible mechanism is suggested to explain the formation of nanoscale GO pieces.
Neurogenic factor-induced Langerhans cell activation in diabetic mice with mechanical allodynia
Authors: Dauch Jacqueline R , Bender Diane E , Luna-Wong Lucía A , Hsieh Wilson , Yanik Brandon M , Kelly Zachary A , Cheng Hsinlin T
Published: May 2013

Background

Langerhans cells (LCs) are antigen-presenting dendritic cells located in the skin. It has been reported that LC activation is associated with painful diabetic neuropathy (PDN); however, the mechanism of LC activation is still unclear.

Methods

The db/db mouse, a rodent model of PDN, was used to study the roles of LCs in the development of PDN in type 2 diabetes. Hind foot pads from db/db and control db/+ mice from 5 to 24 weeks of age (encompassing the period of mechanical allodynia development and its abatement) were collected and processed for immunohistochemistry studies. LCs were identified with immunohistochemistry using an antibody against CD207 (Langerin). The intraepidermal nerve fibers and subepidermal nerve plexus were identified by immunohistochemistry of protein gene product 9.5 (PGP 9.5) and tropomyosin-receptor kinase (Trk) A, the high affinity nerve growth factor receptor.

Results

CD207-positive LCs increased in the db/db mouse during the period of mechanical allodynia, from 8 to 10 weeks of age, in both the epidermis and subepidermal plexus. At 16 weeks of age, when mechanical allodynia diminishes, LC populations were reduced in the epidermis and subepidermal plexus. Epidermal LCs (ELCs) were positive for Trk A. Subepidermal LCs (SLCs) were positive for CD68, suggesting that they are immature LCs. Additionally, these SLCs were positive for the receptor of advanced glycation end products (RAGE) and were in direct contact with TNF-α-positive nerve fibers in the subepidermal nerve plexus during the period of mechanical allodynia. Intrathecal administration of SB203580, a p38 kinase inhibitor, significantly reduced mechanical allodynia, TNF-α expression in the subepidermal plexus, and increased both ELC and SLC populations during the period of mechanical allodynia.

Conclusions

Our data support the hypothesis that increased LC populations in PDN are activated by p38-dependent neurogenic factors and may be involved in the pathogenesis of PDN.
Clinical assessment of complementary treatment with Qishen Yiqi dripping pills on ischemic heart failure: study protocol for a randomized, double-blind, multicenter, placebo-controlled trial (CACT-IHF)
Authors: Hou Ya Zhu , Wang Shuai , Zhao Zhi Qiang , Wang Xian Liang , Li Bin , Soh Shan Bin , Mao Jing Yuan
Published: May 2013

Background

Heart failure (HF) is associated with decreased quality of life, high re-admission rate and poor prognosis. In particular, ischemic heart failure (IHF) has a worse prognosis than nonischemic HF. The use of traditional Chinese medicine (TCM) alongside Western medicine to treat HF has developed into an integrative treatment model in China. There have been small clinical trials and experimental studies to demonstrate the efficacy of TCM for treating HF; however, there is still a lack of high-quality trials. Qishen Yiqi dripping pills (QSYQ), a TCM drug, have been commonly used alongside standardized Western medicine to treat IHF. This paper describes the protocol for the clinical assessment of QSYQ in IHF patients.

Method

A randomized, double-blind, multicenter, placebo-controlled trial will assess the efficacy and safety of QSYQ in the treatment of IHF. The trial is to enroll 640 IHF patients from 32 hospitals in China. Besides their standardized Western medicine, patients will be randomized to receive treatment of either QSYQ or placebo for 6 months and follow-up monitoring for at least a further 6 months. The primary outcome is increased exercise capacity of patients, which will be measured using the 6-minute walking test (6MWT). The secondary outcomes include composite endpoints: all-cause mortality, frequency of hospitalization or emergency due to cardiovascular events, brain natriuretic peptide levels, left ventricular ejection fraction, and cardiothoracic ratio will be documented, as well as scores on the New York Heart Association classification and Minnesota quality of life index, and information obtained from the four TCM diagnostic methods. Blood lipid tests will also be administered.

Discussion

The integrative treatment model of TCM alongside Western medicine has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of QSYQ in the treatment of IHF.

Trial registration

Clinical trials.gov number: NCT01555320
Using the lymph nodal ratio to predict the risk of locoregional recurrence in lymph node-positive breast cancer patients treated with mastectomy without radiation therapy
Authors: Wu San-Gang , Chen Yong , Sun Jia-Yuan , Li Feng-Yan , Lin Qin , Lin Huan-Xin , He Zhen-Yu
Published: May 2013

Background

To evaluate the prognostic value of axillary lymph node ratio (LNR) as compared to the number of involved nodes (pN stage) in patients with axillary lymph node-positive breast cancer treated with mastectomy without radiation.

Methods

We performed a retrospective analysis of the clinical data of patients with stage II-III node-positive breast cancer (N=1068) between 1998 and 2007. Locoregional recurrence-free survival (LRFS) and overall survival (OS) were compared based on the LNR and pN staging.

Results

A total of 780 cases were classified as pN1, 183 as pN2, and 105 as pN3. With respect to LNR, 690 cases had a LNR from 0.01-0.20, 269 cases a LNR from 0.21-0.65, and 109 cases a LNR > 0.65. The median follow-up time was 62 months. Univariate analysis showed that both LNR and pN stage were prognostic factors of LRFS and OS (p<0.05). Multivariate analysis indicated that LNR was an independent prognostic factor of LRFS and OS (p<0.05). pN stage had no significant effect on LRFS or OS (p>0.05). In subgroup analysis, the LNR identified groups of patients with different survival rates based on pN stage.

Conclusions

LNR is superior to pN staging as a prognostic factor in lymph node-positive breast cancer after mastectomy, and should be used as one of the indications for adjuvant radiation therapy.
Advanced nasopharyngeal carcinoma radiotherapy with volumetric modulated arcs and the potential role of flattening filter-free beams
Authors: Zhuang Mingzan , Zhang Tuodan , Chen Zhijian , Lin Zhixiong , Li Derui , Peng Xun , Qiu Qingchun , Wu Renhua
Published: May 2013

Purpose

The purpose of this study is to investigate the dosimetric characteristics of volumetric modulated arc therapy (VMAT) with flattening filter-free (FFF) beams and assess the role of VMAT in the treatment of advanced nasopharyngeal carcinoma (NPC).

Methods

Ten cases of CT data were randomly selected from advanced NPC patients. Three treatment plans were optimized for each patient, RapidArc with FFF beams (RA-FFF), conventional beams (RA) and static gantry intensity-modulated radiation therapy (IMRT). The doses to the planning target volumes (PTVs), organs at risk (OARs), skin and normal tissue were compared. All the plans were delivered on a Varian TrueBeam linear accelerator and verified using the Delta4 phantom. Technical delivery parameters including the mean gamma score, treatment delivery time and monitor units (MUs) were also analyzed.

Results

All the techniques delivered adequate doses to the PTVs. RA-FFF gave the highest D
1%
(dose received by 1% of the volume), but the poorest conformity index (CI) and homogeneity index (HI) among the PTVs except for the planning target volume of involved regional lymph nodes (PTV66) CI, which showed no significant difference among three techniques. For the planning target volume of the primary nasopharyngeal tumor (PTV70), RA-FFF provided for higher mean dose than other techniques. For the planning target volume receiving 60 Gy (PTV60) and PTV66, RA delivered the lowest mean doses whereas IMRT delivered the highest mean doses. IMRT demonstrated the highest percentage of target coverage and D
99%
for PTV60. RA-FFF provided for the highest doses to the brain stem, skin and oral cavity. RA gave the highest D
1%
to the right optic nerve among three techniques while no significant differences were found between each other. IMRT delivered the highest mean doses to the parotid glands and larynx while RA delivered the lowest mean doses. Gamma analysis showed an excellent agreement for all the techniques at 3%/3mm. Significant differences in the MUs were observed among the three techniques (p < 0.001). Delivery times for RA-FFF and RA were 152 ± 7s and 153 ± 7s, respectively, nearly 70% lower than the 493 ± 24s mean time for IMRT.

Conclusions

All treatment plans met the planning objectives. The dose measurements also showed good agreement with computed doses. RapidArc technique can treat patients with advanced NPC effectively, with good target coverage and sparing of critical structures. RA has a greater dosimetric superiority than RA-FFF.
Food protein induced enterocolitis syndrome caused by rice beverage
Authors: Caminiti Lucia , Salzano Giuseppina , Crisafulli Giuseppe , Porcaro Federica , Pajno Giovanni Battista
Published: May 2013

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow’s milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option.

Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The “rice based formula” induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow’s milk substitute for the treatment of non IgE-mediated food allergy should be avoided.
Inhibition of HIV replication in vitro by clinical immunosuppressants and chemotherapeutic agents
Authors: Hawley Todd , Spear Mark , Guo Jia , Wu Yuntao
Published: May 2013

Background

Recent studies have suggested that a functional cure for HIV-1 infection, purportedly resultant from allogeneic bone marrow transplantation, may be possible. Additionally, the first such patient was treated with whole-body irradiation, immunosuppressants, and the chemotherapeutic, cytarabine. However, the precise role of the coinciding medical interventions in diminishing detectable HIV reservoirs remains unstudied.

Findings

In this article, we demonstrate that the immunosuppressants, mycophenolic acid and cyclosporine, and the chemotherapeutic, cytarabine, are potent antiretroviral agents at clinically relevant dosages. These drugs strongly inhibit HIV-1 replication in a GFP indicator T cell line and peripheral blood mononuclear cells (PBMC).

Conclusions

Our study suggests that certain clinical immunosuppressants and chemotherapeutic agents may act combinatorially to inhibit HIV infection. Additionally, chemotherapy-mediated cytotoxicity may also affect the stability of viral reservoirs. Thus, further study is needed to examine potential therapeutic value of these interventions in patients.
Strategy-aligned fuzzy approach for market segment evaluation and selection: a modular decision support system by dynamic network process (DNP)
Authors: Mohammadi Nasrabadi Ali , Hosseinpour Mohammad Hossein , Ebrahimnejad Sadoullah
Published: May 2013

In competitive markets, market segmentation is a critical point of business, and it can be used as a generic strategy. In each segment, strategies lead companies to their targets; thus, segment selection and the application of the appropriate strategies over time are very important to achieve successful business. This paper aims to model a strategy-aligned fuzzy approach to market segment evaluation and selection. A modular decision support system (DSS) is developed to select an optimum segment with its appropriate strategies. The suggested DSS has two main modules. The first one is SPACE matrix which indicates the risk of each segment. Also, it determines the long-term strategies. The second module finds the most preferred segment-strategies over time. Dynamic network process is applied to prioritize segment-strategies according to five competitive force factors. There is vagueness in pairwise comparisons, and this vagueness has been modeled using fuzzy concepts. To clarify, an example is illustrated by a case study in Iran's coffee market. The results show that success possibility of segments could be different, and choosing the best ones could help companies to be sure in developing their business. Moreover, changing the priority of strategies over time indicates the importance of long-term planning. This fact has been supported by a case study on strategic priority difference in short- and long-term consideration.
Hypothalamic Inflammation Without Astrogliosis in Response to High Sucrose Intake Is Modulated by Neonatal Nutrition in Male Rats
Authors: Fuente-Martín Esther , García-Cáceres Cristina , Díaz Francisca , Argente-Arizón Pilar , Granado Miram , Barrios Vicente , Argente Jesús , Chowen Julie A.
Published: May 2013

Hypothalamic inflammation and gliosis are proposed to participate in the pathogenesis of high-fat diet-induced obesity. Because other factors and nutrients also induce weight gain and adiposity, we analyzed the inflammatory and glial responses to a sucrose (S)-enriched diet. Neonatal overnutrition (NON) exacerbates weight gain in response to metabolic challenges; thus, we compared the inflammatory response of male Wistar rats with NON (4 pups/litter) and controls (12 pups/litter) to increased S intake. At weaning rats received water or a 33% sucrose solution and normal chow ad libitum for 2 months. Sucrose increased serum IL-1β and -6 and hypothalamic IL-6 mRNA levels in NON and TNFα mRNA levels in control and NON rats, whereas NON alone had no effect. The astrocyte marker glial fibrillary acidic protein was increased by NON but decreased by S. This was associated with hypothalamic nuclei specific changes in glial fibrillary acidic protein-positive cell number and morphology. Sucrose increased the number of microglia and phosphorylation of inhibitor of -κB and c-Jun N-terminal kinase in control but not NON rats, with no effect on microglia activation markers. Proteins highly expressed in astrocytes (glutamate, glucose, and lactate transporters) were increased by NON but not S, with no increase in vimentin expression in astrocytes, further suggesting that S-induced adiposity is not associated with hypothalamic astrogliosis. Hence, activation of hypothalamic inflammatory processes and gliosis depend not only on weight gain but also on the diet inducing this weight gain and the early nutritional status. These diverse inflammatory processes could indicate a differential disposition to obesity-induced pathologies.
The Impact of Ventral Noradrenergic Bundle Lesions on Increased IL-1 in the PVN and Hormonal Responses to Stress in Male Sprague Dawley Rats
Authors: Blandino Peter , Hueston Cara M. , Barnum Christopher J. , Bishop Christopher , Deak Terrence
Published: May 2013

The impact of acute stress on inflammatory signaling within the central nervous system is of interest because these factors influence neuroendocrine function both directly and indirectly. Exposure to certain stressors increases expression of the proinflammatory cytokine, Il-1β in the hypothalamus. Increased IL-1 is reciprocally regulated by norepinephrine (stimulatory) and corticosterone (inhibitory), yet neural pathways underlying increased IL-1 have not been clarified. These experiments explored the impact of bilateral lesions of the ventral noradrenergic bundle (VNAB) on IL-1 expression in the paraventricular nucleus of the hypothalamus (PVN) after foot shock. Adult male Sprague Dawley rats received bilateral 6-hydroxydopamine lesions of the VNAB (VNABx) and were exposed to intermittent foot shock. VNABx depleted approximately 64% of norepinephrine in the PVN and attenuated the IL-1 response produced by foot shock. However, characterization of the hypothalamic-pituitary-adrenal response, a crucial prerequisite for interpreting the effect of VNABx on IL-1 expression, revealed a profound dissociation between ACTH and corticosterone. Specifically, VNABx blocked the intronic CRH response in the PVN and the increase in plasma ACTH, whereas corticosterone was unaffected at all time points examined. Additionally, foot shock led to a rapid and profound increase in cyclooxygenase-2 and IL-1 expression within the adrenal glands, whereas more subtle effects were observed in the pituitary gland. Together the findings were the 1) demonstration that exposure to acute stress increased expression of inflammatory factors more broadly throughout the hypothalamic-pituitary-adrenal axis; 2) implication of a modest role for norepinephrine-containing fibers of the VNAB as an upstream regulator of PVN IL-1; and 3) suggestion of an ACTH-independent mechanism controlling the release of corticosterone in VNABx rats.
Redefining the Initiation and Maintenance of Zebrafish Interrenal Steroidogenesis by Characterizing the Key Enzyme Cyp11a2
Authors: Parajes Silvia , Griffin Aliesha , Taylor Angela E. , Rose Ian T. , Miguel-Escalada Irene , Hadzhiev Yavor , Arlt Wiebke , Shackleton Cedric , Müller Ferenc , Krone Nils
Published: May 2013

Zebrafish are emerging as a model to study steroid hormone action and associated disease. However, steroidogenesis in zebrafish is not well characterized. Mammalian P450 side-chain cleavage enzyme (CYP11A1) catalyzes the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Previous studies describe an essential role for zebrafish Cyp11a1 during early development. Cyp11a1 has been suggested to be the functional equivalent of mammalian CYP11A1 in the zebrafish interrenal gland (equivalent to the mammalian adrenal), gonad, and brain. However, reported cyp11a1 expression is inconsistent in zebrafish larvae, after active cortisol synthesis commences. Recently a duplicated cyp11a gene, cyp11a2, has been described, which shares an 85% identity with cyp11a1. We aimed to elucidate the specific role of the two cyp11a paralogs. cyp11a1 was expressed from 0 to 48 hours post-fertilization (hpf), whereas cyp11a2 expression started after the development of the interrenal primordium (32 hpf) and was the only paralog in larvae. cyp11a2 is expressed in adult steroidogenic tissues, such as the interrenal, gonads, and brain. In contrast, cyp11a1 was mainly restricted to the gonads. Antisense morpholino knockdown studies confirmed abnormal gastrulation in cyp11a1 morphants. cyp11a2 morphants showed impaired steroidogenesis and a phenotype indicative of metabolic abnormalities. The phenotype was rescued by pregnenolone replacement in cyp11a2 morphants. Thus, we conclude that cyp11a1 is required for early development, whereas cyp11a2 is essential for the initiation and maintenance of zebrafish interrenal steroidogenesis. Importantly, this study highlights the need for a comprehensive characterization of steroidogenesis in zebrafish prior to its implementation as a model organism in translational research of adrenal disease.