bluuebunny/crossref_metadata_2025 huggingface dataset:
GLP‐1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c‐JNK
Authors: Zhang Lili , Yang Mengliu , Ren Hong , Hu Huaidong , Boden Guenther , Li Ling , Yang Gangyi
Published: January 2013

Background & Aims

Liraglutide, a Glucagon‐like peptide‐1(GLP‐1) analogue with 97% sequence identity to human GLP‐1, increases insulin secretion and insulin sensitivity. Its effect on non‐alcoholic fatty liver disease (NAFLD) remains poorly understood. In this study, we examined whether liraglutide can protect against inflammatory stress by inhibiting activation of c‐Jun N‐terminal protein kinase (JNK).

Methods

ApoE KO and adiponectin (Acrp30) knockdown mice fed a high‐fat diet (HFD) were treated with liraglutide (1 mg/kg, twice daily) for 8 weeks. Liver tissue was procured for histological examination, real‐time RT‐PCR and Western blot analysis.

Results

The results showed that the combination of HFD, Acrp30 knockdown and ApoE deficiency had additive effects on the development of insulin resistance (IR) and NAFLD. Administration of liraglutide prevented the development of HFD and hypoadiponectinaemia–induced IR and NAFLD in this model. Liraglutide also attenuated the expression of proinflammatory cytokines or transcription factor, including TNF‐α and NF‐κB65, and the expression of two lipogenesis‐related genes, Acetyl‐CoA Carboxylase (ACC) and fatty acid synthase (FAS). These changes were accompanied by elevated plasma of Acrp30, increased Acrp30 mRNA, AMP Kinase phosphorylation, and decreased mitogen‐activated protein kinase 4 (MKK4) mRNA expression and JNK phosphorylation.

Conclusions

Our study also showed potent inhibitory effects of liraglutide on MKK4/JNK signalling which may be a mechanism for the observed improved insulin sensitivity and inflammatory stress induced by HFD and hypoadiponectinaemia.
Panel of real‐time PCRs for the multiplexed detection of two tomato‐infecting begomoviruses and their cognate whitefly vector species
Authors: van Brunschot S. L. , Gambley C. F. , De Barro P. J. , Grams R. , Thomas J. E. , Henderson J. , Drenth A. , Geering A. D. W.
Published: January 2013

A new approach for the simultaneous identification of the viruses and vectors responsible for tomato yellow leaf curl disease (TYLCD) epidemics is presented. A panel of quantitative multiplexed real‐time PCR assays was developed for the sensitive and reliable detection of Tomato yellow leaf curl virus‐Israel (TYLCV‐IL), Tomato leaf curl virus (ToLCV), Bemisia tabaci Middle East Asia Minor 1 species (MEAM1, B biotype) and B. tabaci Mediterranean species (MED, Q biotype) from either plant or whitefly samples. For quality‐assurance purposes, two internal control assays were included in the assay panel for the co‐amplification of solanaceous plant DNA or B. tabaci DNA. All assays were shown to be specific and reproducible. The multiplexed assays were able to reliably detect as few as 10 plasmid copies of TYLCV‐IL, 100 plasmid copies of ToLCV, 500 fg B. tabaci MEAM1 and 300 fg B. tabaci MED DNA. Evaluated methods for routine testing of field‐collected whiteflies are presented, including protocols for processing B. tabaci captured on yellow sticky traps and for bulking of multiple B. tabaci individuals prior to DNA extraction. This work assembles all of the essential features of a validated and quality‐assured diagnostic method for the identification and discrimination of tomato‐infecting begomovirus and B. tabaci vector species in Australia. This flexible panel of assays will facilitate improved quarantine, biosecurity and disease‐management programmes both in Australia and worldwide.
Preferential responses to extinguished face stimuli are preserved in frontal and occipito‐temporal cortex at initial but not later stages of processing
Authors: Steinberg Christian , Bröckelmann Ann‐Kathrin , Dobel Christian , Elling Ludger , Zwanzger Peter , Pantev Christo , Junghöfer Markus
Published: January 2013

Magnetoencephalographic correlates of rapid emotional responses (50–80 ms) in frontal and occipito‐temporal regions have recently been reported using a novel MultiCS Conditioning paradigm with odor‐conditioned faces. As those short‐latency responses were supposed to partially reflect initial access to nonextinguished emotional memories, it could be predicted that they outlast the extinction phase. To test this hypothesis, appetitively and aversively odor‐conditioned faces were frequently presented during extinction while event‐related magnetic fields were recorded. Affect‐specific responses in frontal and occipito‐temporal areas were found in the early (50–80 ms) but not in the later (130–190 ms) time interval following extinction learning. These results suggest that previously acquired emotional memories can be accessed at initial processing stages but become ineffective in modulating processing at later stages as extinction proceeds.
Sensory suppression effects to self‐initiated sounds reflect the attenuation of the unspecific N1 component of the auditory ERP
Authors: Sanmiguel Iria , Todd Juanita , Schröger Erich
Published: January 2013

The suppression of the auditory N1 event‐related potential (ERP) to self‐initiated sounds became a popular tool to tap into sensory‐specific forward modeling. It is assumed that processing in the auditory cortex is attenuated due to a match between sensory stimulation and a specific sensory prediction afforded by a forward model of the motor command. The present study shows that N1 suppression was dramatically increased with long (∼3 s) stimulus onset asynchronies (SOA), whereas P2 suppression was equal in all SOA conditions (0.8, 1.6, 3.2 s). Thus, the P2 was found to be more sensitive to self‐initiation effects than the N1 with short SOAs. Moreover, only the unspecific but not the sensory‐specific N1 components were suppressed for self‐initiated sounds suggesting that N1‐suppression effects mainly reflect an attenuated orienting response. We argue that the N1‐suppression effect is a rather indirect measure of sensory‐specific forward models.
Draft Genome Sequence of the First Isolate of Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia
Authors: Ng Kee Peng , Yew Su Mei , Chan Chai Ling , Chong Jennifer , Tang Soo Nee , Soo-Hoo Tuck Soon , Na Shiang Ling , Hassan Hamimah , Ngeow Yun Fong , Hoh Chee Choong , Lee Kok Wei , Yee Wai Yan
Published: January 2013

The emergence of the global threat of extensively drug-resistant (XDR)
Mycobacterium tuberculosis
reveals weaknesses in tuberculosis management and diagnostic services. We report the draft genome sequence of the first extensively drug-resistant
Mycobacterium tuberculosis
strain isolated in Malaysia. The sequence was also compared against a reference strain to elucidate the polymorphism that is related to their extensive resistance.
Harnessing the cloud of patient experience: using social media to detect poor quality healthcare
Authors: Greaves Felix , Ramirez-Cano Daniel , Millett Christopher , Darzi Ara , Donaldson Liam
Published: January 2013

Recent years have seen increasing interest in patient-centred care and calls to focus on improving the patient experience. At the same time, a growing number of patients are using the internet to describe their experiences of healthcare. We believe the increasing availability of patients’ accounts of their care on blogs, social networks, Twitter and hospital review sites presents an intriguing opportunity to advance the patient-centred care agenda and provide novel quality of care data. We describe this concept as a ‘cloud of patient experience’. In this commentary, we outline the ways in which the collection and aggregation of patients’ descriptions of their experiences on the internet could be used to detect poor clinical care. Over time, such an approach could also identify excellence and allow it to be built on. We suggest using the techniques of natural language processing and sentiment analysis to transform unstructured descriptions of patient experience on the internet into usable measures of healthcare performance. We consider the various sources of information that could be used, the limitations of the approach and discuss whether these new techniques could detect poor performance before conventional measures of healthcare quality.
ru2hot?: A public health education campaign for men who have sex with men to increase awareness of symptoms of acute HIV infection
Authors: Stekler Joanne D , Baldwin Heather D , Louella Michael W , Katz David A , Golden Matthew R
Published: January 2013

Objectives

Teach HIV-negative men who have sex with men (MSM) symptoms of acute HIV infection (AHI) and direct them to nucleic acid amplification testing (NAAT) though Public Health—Seattle & King County (PHSKC).

Design

Cross-sectional surveys, retrospective database analysis and chart review.

Methods

Beginning in June 2009, the ru2hot? campaign described AHI symptoms and NAAT. Two preintervention and two postintervention surveys assessed campaign visibility, symptom knowledge, and healthcare-seeking behaviour. Regression analyses evaluated secular trends in case-finding.

Results

366 MSM completed surveys. In survey 4, 23% of 100 men reported seeing the campaign, and 25% knew ‘ru2hot?’ referred to AHI. From survey 1 to survey 4, the proportion of subjects who knew ≥2 symptoms or that AHI was a ‘flu-like’ illness was unchanged (61% vs 57%, p=0.6). However, in survey 4, 13 (72%) of 18 subjects who saw the campaign named fever as a symptom of AHI compared with 19 (35%) of 55 subjects who had not seen the campaign (p=0.005). From 9/2003 to 12/2010, 622 (2.2%) of 27 661 MSM tested HIV-positive, and 111 (18%) were identified by the Public Health—Seattle & King County NAAT programme. In terms of the impact of the campaign on case-finding, diagnosis of EIA-negative/NAAT-positive and OraQuick-negative/EIA-positive cases increased from six in 2004 to 20 in 2010 (p=0.01), but postcampaign numbers were unchanged. 23 (51%) of 45 cases identified before and 8 (44%) of 18 cases identified after the campaign reported symptoms at initial testing (p=0.6).

Conclusions

Although a quarter of MSM surveyed saw the campaign and knowledge of fever (the symptom of emphasis) was high, case-finding was unchanged. Increasing campaign visibility could have had greater impact.
The effects of strength training and endurance training order on running economy and performance
Authors: Doma Kenji , Deakin Glen Bede
Published: January 2013

This study examined the acute effect of strength and endurance training sequence on running economy (RE) at 70% and 90% ventilatory threshold (VT) and on running time to exhaustion (TTE) at 110% VT the following day. Fourteen trained and moderately trained male runners performed strength training prior to running sessions (SR) and running prior to strength training sessions (RS) with each mode of training session separated by 6 h. RE tests were conducted at baseline (Base-RE) and the day following each sequence to examine cost of running (CR), TTE, and lower extremity kinematics. Maximal isometric knee extensor torque was measured prior to and following each training session and the RE tests. Results showed that CR at 70% and 90% VT for SR-RE (0.76 ± 0.10 and 0.77 ± 0.07 mL·kg–0.75·m–1) was significantly greater than Base-RE (0.72 ± 0.10 and 0.70 ± 0.11 mL·kg–0.75·m–1) and RS-RE (0.73 ± 0.09 and 0.72 ± 0.09 mL·kg–0.75·m–1) (P < 0.05). TTE was significantly less for SR-RE (237.8 ± 67.4 s) and RS-RE (275.3 ± 68.0 s) compared with Base-RE (335.4 ± 92.1 s) (P < 0.01). The torque during the SR sequence was significantly reduced for every time point following the strength training session (P < 0.05). However, no significant differences were found in torque following the running session (P > 0.05), although it was significantly reduced following the strength training session (P < 0.05) during the RS sequence. These findings show that running performance is impaired to a greater degree the day following the SR sequence compared with the RS sequence.
Asthmatic Response to Milk Ingestion Challenge in Adults: A Comparison of the Open and Double-Blind Challenges
Authors: Pelikan Zdenek
Published: January 2013

Background: Cow’s milk allergy can participate in pathophysiological mechanisms underlying bronchial asthma in some adult patients. This role should ultimately be confirmed by means of a milk ingestion challenge. In this study, the diagnostic value of the open food ingestion challenge (OFICH) and the double-blind placebo-controlled food challenge (DBPCFC) techniques with milk were compared in adult patients suffering from bronchial asthma with suspected milk allergy. Methods: In 87 asthmatics with a suspected history and positive skin tests for milk, the 87 OFICHs and DBPCFCs were performed in combination with spirometry and followed up to 72 h after the challenge. Results: Of 87 patients, 74 (85%) developed a positive asthmatic response (AR) (20 immediate, 33 late, 6 dual late and 15 delayed; p < 0.01) and 13 (15%) developed a negative AR (p > 0.1) to OFICH. Seventy-five (86%) developed a positive AR (17 immediate, 35 late, 8 dual late and 15 delayed; p < 0.01) and 12 (14%) developed a negative AR (p > 0.05) to DBPCFC. The correlation between the OFICH and DBPCFC was statistically significant (p < 0.01). All placebo control challenges were negative (p > 0.2). Conclusions: In some adults with bronchial asthma, involvement of an allergy to cow’s milk results in the appearance of various AR types (immediate, late, dual late or delayed). The milk allergy can be confirmed by open or double-blind techniques, combined with spirometry. No significant differences were found between the OFICH and DBPCFC results. OFICH with natural milk combined with spirometry seems, therefore, to be an adequate technique for the detection of milk allergy in asthmatics. The DBPCFC can be performed as an additional check, if necessary.
Active Eosinophilic Esophagitis Is Associated with Impaired Elimination of Budesonide by Cytochrome P450 3A Enzymes
Authors: Dilger Karin , Lopez-Lazaro Luis , Marx Claudia , Bussmann Christian , Straumann Alex
Published: January 2013

Background/Aims: Topically administered glucocorticoids such as budesonide have the potential of being established as first-line medical treatment of eosinophilic esophagitis (EoE). Safety of budesonide is based on high elimination by cytochrome P450 3A (CYP3A) enzymes. We aimed to investigate systemic absorption and elimination of a new budesonide formulation in patients with active EoE in comparison with healthy controls. Methods: After single and multiple doses of orodispersible budesonide (4 mg/day) the parent drug, its CYP3A-dependent metabolites, and endogenous cortisol were determined in 12 adult patients with active EoE and 12 healthy controls. An approved ileal-release formulation of budesonide was taken for reference. Molar ratios of metabolite formation in plasma were used as indices of CYP3A metabolic function. Results: CYP3A-dependent metabolite formation was significantly reduced in patients with active EoE as compared to healthy controls. Impaired biotransformation was reflected by a significantly higher extent of budesonide absorption and elongated elimination half-life in EoE patients. Comparison of morning serum cortisol levels at baseline with those after 1 week of treatment with budesonide revealed a significant decrease in EoE patients but not in healthy subjects. Conclusion: Active EoE is associated with reduced elimination of budesonide via CYP3A, the major subfamily of drug-metabolizing enzymes in humans.
The Revolution Is Dissent
Authors: Baker Gideon
Published: January 2013

Underlying Giorgio Agamben’s and Alain Badiou’s disagreement over the apostle Paul we find common cause: following Paul’s deactivation of law, both Agamben and Badiou see the fixed identities necessary to the naturalised nomos of State politics as transfigured by a politics of grace. This transfiguration is differently rendered as either the emergence of a universal subject (Badiou) or the opening up of existing subjectivities (Agamben), but both the messianic vocation in Agamben and the universal subject in Badiou allow subjective possibility to that which is not in the present objectified order. Developing this theme of a basic emancipatory affinity, two moments of the political which exist in a difficult but necessary tension are identified: revolution and dissent. While revolution signals subjective possibility itself by determining that the truth of the event is for all, dissidence keeps that possibility alive by pointing to the human subject’s fundamental indeterminacy.
The Influence of Mental Health Disorders on Severity of Reoffending in Juveniles
Authors: Hoeve Machteld , McReynolds Larkin S. , Wasserman Gail A. , McMillan Cary
Published: January 2013

The authors conducted secondary data analyses on mental health assessment and offense history data for 700 juveniles referred to juvenile justice agencies in Alabama (probation and detention). Multiple regression analysis was applied to predict subsequent offense severity by disorder profile, adjusting for prior offense severity and background variables. Juveniles with a substance use disorder with or without co-occurring disorders were at greater risk for escalations in offense seriousness over time. Early in juvenile justice system contact, juveniles should get effective treatment for substance use to prevent offending escalation.
Biofilm Formations in Nasopharyngeal Tissues of Patients with Nasopharyngeal Osteoradionecrosis
Authors: Tsai Yih‐Jeng , Lin Yu‐Chi , Wu Wen‐Bin , Chiu Po‐Han , Lin Brian J. , Hao Sheng‐Po
Published: January 2013

Objective

Determine the presence of nasopharynx biofilms in patients with nasopharyngeal cancer (NPC) and osteoradionecrosis (ORN) and patients with NPC but no ORN.

Study Design

Cross‐sectional study.

Setting

Tertiary referral medical center.

Subjects and Methods

We enrolled 27 patients with NPC from our outpatient clinic during January 2010 to June 2012. These patients were diagnosed with NPC between 1980 and 2012, and all had received radiotherapy. Of these 27 patients, 15 presented with ORN, and 12 did not. The nasopharynx biopsied specimens were processed and analyzed within 2 hours of collection with the FilmTracer LIVE_DEAD Biofilm Viability Kit (Molecular Probes, Invitrogen, Carlsbad, California). A blinded investigator determined the formation of biofilms by fluorescence microscopy. Bacterial cultures were collected.

Results

Eleven of 15 (73%) ORN patients had biofilm formations in nasopharynx biopsy specimens. Five of these samples (45%) yielded positive cultures, and 4 of these cultures indicated the presence of methicillin‐resistant Staphylococcus aureus (MRSA). Only 1 of 12 NPC patients without ORN had nasopharynx biofilm formation, and all culture results were negative.

Conclusion

Biofilm formations were common in nasopharynx samples of NPC patients with ORN but rare in samples of NPC patients without ORN. The presence of biofilms, especially MRSA, may have a role in the disease progression of ORN or may contribute to the chronicity and resistance to antibiotic treatment.
Prevention of postoperative recurrence of Crohn’s disease: Tripterygium wilfordii polyglycoside versus mesalazine
Authors: Ren Jianan , Wu Xiuwen , Liao Nansheng , Wang Gefei , Fan Chaogang , Liu Song , Ren Huajian , Zhao Yunzhao , Li Jieshou
Published: January 2013

Objectives

To explore effectiveness and safety of polyglycosides of Tripterygium wilfordii (GTW) and mesalazine (5-aminosalicylic acid [5-ASA]) in preventing postoperative clinical and endoscopic recurrence of Crohn’s disease.

Methods

In this prospective, single-centre, single-blind study, postoperative Crohn’s disease patients in remission were randomized to receive 1 mg/kg GTW daily, orally, or 4 g 5-ASA daily, orally, for 52 weeks. Patients underwent physical examinations, ileocolonoscopies and biochemical analyses at baseline and weeks 13, 26 and 52, or when clinical recurrence was suspected. Outcome measures were proportion of patients showing clinical or endoscopic recurrence at week 52, and changes in Rutgeerts’ and Crohn’s Disease Activity Index (CDAI) scores.

Results

Twenty-one patients were assigned to receive GTW and 18 to 5-ASA; two patients on GTW and one on 5-ASA were withdrawn. Clinical and endoscopic recurrences were less common in the GTW group ( n = 4) versus the 5-ASA group ( n = 9). There were improvements in Rutgeerts’ scores for those taking GTW. Mean between-group CDAI scores were similar. No serious adverse events were reported.

Conclusion

These findings indicate that GTW appears to be an effective, well-tolerated prophylactic regimen, superior to oral 5-ASA, for preventing clinical and endoscopic recurrence in postsurgical Crohn’s disease.
Attitude Toward Euthanasia Scale
Authors: Aghababaei Naser , Wasserman Jason Adam
Published: January 2013

End-of-life decisions (ELDs) represent a controversial subject, with ethical dilemmas and empirical ambiguities that stand at the intersection of ethics and medicine. In a non-Western population, we examined individual differences in perceiving ELDs that end the life of a patient as acceptable and found that an attitude toward euthanasia (ATE) scale consists of 2 factors representing voluntary and nonvoluntary euthanasia. Also, acceptance of ELDs that end the life of a patient negatively correlated with life satisfaction, honesty–humility, conscientiousness, and intrinsic and extrinsic personal motivation toward religion. These findings provided additional construct validity of the ATE scale.
Cribriform-Morular Variant of Papillary Thyroid Carcinoma Displaying Poorly Differentiated Features
Authors: Nakazawa Tadao , Celestino Ricardo , Machado José Carlos , Cameselle-Teijeiro José Manuel , Vinagre João , Eloy Catarina , Benserai Fátima , Lameche Samia , Soares Paula , Sobrinho-Simões Manuel
Published: January 2013

Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) usually occurs in the setting of familial adenomatous polyposis (FAP) although it can rarely arise sporadically. Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived neoplasm with more aggressive behavior than well-differentiated carcinomas such as CMVPTC. We report the case of a 35-year-old woman without FAP history who presented a left neck mass and complained of back pain. Imagiological examinations revealed a nodule in the left lobe of thyroid and multiple nodular lesions in the bone and lungs suggestive of metastases. The patient was submitted to total thyroidectomy and radioactive iodine. The tumor was composed of CMVPTC and PDTC components that shared the same somatic APC gene mutation (p.Cys520Tyr_fsX534). Besides this mutation, no CTNNB1, BRAF, N- RAS, and H- RAS gene mutations were detected in any of the 2 components. To the best of our knowledge, this is the first report of a sporadic CMVPTC with transformation into PDTC. Although the majority of CMVPTCs carry an indolent clinical outcome, the coexistence of poorly differentiated areas may justify the aggressiveness of the CMVPTC reported here.
Evaluation of the clinical use of tepoxalin and meloxicam in cats
Authors: Charlton Anna N , Benito Javier , Simpson Wendy , Freire Mila , Lascelles B Duncan X
Published: January 2013

Medical records where tepoxalin (Zubrin) or meloxicam (Metacam) were prescribed in cats were reviewed and data extracted. Comparisons were performed for exploring changes between pre- and post-non-steroidal anti-inflammatory drug course laboratory tests. Seventy-nine medical records fit the inclusion criteria (n = 57 and n = 22, tepoxalin and meloxicam, respectively). The median dosages administered were 13 and 0.029 mg/kg/day (tepoxalin and meloxicam, respectively). Median prescription durations were 11 (2–919) and 93 (4–1814) days for tepoxalin and meloxicam, respectively. Suspected adverse events were reported for tepoxalin (9%, 5/57 cats) and meloxicam (18%, 4/22 cats) a median of 774 and 448 days, respectively, after the prescription started. For cats prescribed meloxicam, there were several statistically significant changes for serum biochemistry and hematology parameters, but median values were within normal limits. These valuable clinical data suggest that tepoxalin and meloxicam are well tolerated in the clinical setting at the doses prescribed in this study.
Drinking contexts and the legitimacy of alcohol use: Findings from a focus group study on alcohol use in Denmark
Authors: Grønkjær Mette , Curtis Tine , de Crespigny Charlotte , Delmar Charlotte
Published: January 2013

Aim: To examine the perceptions and meanings of alcohol use in Denmark with specific focus on drinking contexts. Methods: A qualitative study using focus group interviews. The sample consisted of five focus groups of adults with one group for each of the following age groups: 16–20; 21–34; 35–44; 45–64; and 65–82 years. The groups consisted of both men and women with five to six participants in each group (27 in total). Results: Alcohol use is perceived as legitimate in many social contexts with few being defined as inappropriate. Drinking alone is mostly associated with having alcohol-related problems, but considered legitimate if it is characterized by activity. Drinking socially plays an important role in people’s considerations of legitimate use and seems to overrule the actual alcohol amount consumed. Different contexts influence different meanings of drinking with context and purpose changing with age and life stages. Conclusions: The social drinking context is pivotal in people’s perception of the legitimacy of their alcohol use, leaving the alcohol amount less important. This calls for the need to focus on and incorporate the drinking context within public health initiatives aimed at reducing high risk drinking, just as the focus on the actual amount of alcohol people consume or their frequency of use.
(Re)performing emotions in diary-interviews
Authors: Spowart Lucy , Nairn Karen
Published: January 2013

Research with mothers who snowboard generated emotionally rich data. In this article, we make the case for combining diaries and interviews in research concerned with understanding the fluid and complex nature of emotions and subjectivities. The diary-interview method can also enable participants to exert greater influence over the interview agenda than they might if they simply engaged in a one-off interview. In the first part of the article, we provide an overview of the literature about the use of diaries in research before discussing the combination of diary and interview. In the second part of the article, we draw on the data produced by one participant, to illustrate how the diary-interview method can facilitate the sharing and collection of emotional data, and provide a glimpse of the constitution of subjectivity. While we found that the diary-interview method proved insightful, we add a note of caution about the potential for intrusion and/or harm.
Lawn Mower Injuries to the Lower Extremity
Authors: Greenhagen Robert M. , Raspovic Katherine M. , Crim Brandon E. , Ryan Michael T. , Gruen Gary G.
Published: January 2013

Introduction. Lawn mower injuries occur frequently in the United States and oftentimes result in extensive trauma to the lower extremities. These injuries can be quite devastating and cause there to be loss of function and amputation. The purpose of this study was to determine if there are specific factors that would help determine the best treatment protocol, patient outcomes, and prognosis after lawn mower injury to the foot and ankle. Material and Methods. A retrospective review of medical records was performed on all patients treated at a university level 1 trauma center from 2000 to 2010. Only subjects 18 years or older who sustained an injury below the level of the knee were included for review. Results. Seventy-three patients were included in this review. The results revealed that patients who developed a complication were significantly older than the group of patients without complications ( P = .03). Digits were found to be injured most often but the odds of developing a complication were much higher if these injuries involved the plantar foot, dorsal foot, or ankle. Interestingly, patients on prolonged antibiotic therapy had a significantly higher risk of developing complications. The presence of comorbidities significantly increased the risk of complication ( P = .008); the greatest risk factors were cardiovascular disease ( P = .001) and diabetes ( P = .06). Discussion. The authors present the largest cohort of lawn mower injuries in the medical literature, which demonstrates that factors such as age, location of injury, and the presence of comorbidities influence the outcome and increase the risk of injury to the foot and ankle. These results may be useful in determining the best treatment plan possible for patients with these severe injuries.

Levels of Evidence: Therapeutic, Level IV, Retrospective case series
Three-dimensional culture model to distinguish normal from malignant human bronchial epithelial cells
Authors: Fessart Delphine , Begueret Hugues , Delom Frederic
Published: January 2013

In the present study, we have developed anin vitrothree-dimensional model to differentiate normal lung cells from lung cancer cells in order to study the mechanisms resulting in lung cancer.

Using a reconstituted laminin-rich basement membrane (Matrigel), we were able to culture normal human bronchial epithelial cells and a subset of malignant cells. The two cell types can be readily distinguished by the ability of normal cells to express a structurally and functionally differentiated phenotype within Matrigel. Human bronchial epithelial cells embedded in Matrigel as single cells were able to form multi-cellular spherical colonies with a final size close to that of true aciniin situ. Sections of mature spheres revealed a central lumen surrounded by polarised epithelial cells. In contrast, none of malignant cells tested, cell lines and lung biopsies responded to basement membrane by lumen formation.

These results demonstrated that thisin vitroglandular tumour model can be useful for studies of bronchial oncogene. Indeed, these findings may provide the basis for a rapid assay to discriminate normal human bronchial epithelial cells from their malignant counterparts.

In conclusion, the three-dimensional tumour bronchial epithelial acinar-like sphere represents a novelin vitromodel to further investigate pathophysiological functions resulting in lung cancer.
Airway and systemic inflammation in obese children with asthma
Authors: Jensen Megan E. , Gibson Peter G. , Collins Clare E. , Wood Lisa G.
Published: January 2013

Obese asthma presentsviaaltered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls.

In a cross-sectional study, children aged 8–17 years were assigned to one of four groups: obese asthma (OA, n=74); nonobese asthma (NOA, n=249); obese control (OC, n=9); nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured.

Non-eosinophilic asthma was more prevalent among OA females (60.0%)versusOA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA,versusNOA and NOC, while adiponectin was reduced in OAversusNOC only. Expiratory reserve volume was reduced in OA,versusNOC. Residual volume (RV) and RV/total lung capacity were reduced in OCversusOA, and OCversusOA and NOA, respectively.

Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.
Early patterns of wheezing in asthmatic and nonasthmatic children
Authors: Cano Garcinuño Alfredo , Mora Gandarillas Isabel ,   the SLAM Study Group
Published: January 2013

The aim of this study was to describe the time patterns of wheezing in both asthmatic and nonasthmatic children during the first 36 months of life, and to determine whether there are asthma-related breakpoints in the incidence of wheezing.

Data from a historical cohort of children followed from birth to 6 years (SLAM cohort) were used. Wheezing episodes until 36 months and asthma at 6 years were both recorded by a doctor. Monthly mean incidence rate of wheezing and rate ratio were calculated. Joinpoint regression models were built to identify breakpoints in the risk of wheeze.

Complete information was available for 3739 children. Wheezing in the first 36 months was more frequent in asthmatic than in nonasthmatic children (rate ratio 2.62, 95% CI 1.81–3.78). Differences were appreciable within the first months and increased steadily thereafter because of a persistently high rate in asthmatic children. No breakpoint in the rate ratio could be identified. Asthmatic children exhibited a one-phase curve of incidence and nonasthmatic children exhibited a two-phase curve. However, children with allergic asthma also displayed a two-phase curve.

There is no identifiable breakpoint during the first 36 months of life at which the incidence of wheezing in asthmatic children begins to stand out.
Brazilin isolated from Caesalpinia sappan L. acts as a novel collagen receptor agonist in human platelets
Authors: Chang Yi , Huang Steven Kuan-Hua , Lu Wan-Jung , Chung Chi-Li , Chen Wei-Lin , Lu Shun-Hua , Lin Kuan-Hung , Sheu Joen-Rong
Published: January 2013

Background

Brazilin, isolated from the heartwood of Caesalpinia sappan L., has been shown to possess multiple pharmacological properties.

Methods

In this study, platelet aggregation, flow cytometry, immunoblotting analysis, and electron spin resonance (ESR) spectrometry were used to investigate the effects of brazilin on platelet activation ex vivo. Moreover, fluorescein sodium-induced platelet thrombi of mesenteric microvessels was also used in in vivo study.

Results

We demonstrated that relatively low concentrations of brazilin (1 to 10 μM) potentiated platelet aggregation induced by collagen (0.1 μg/ml) in washed human platelets. Higher concentrations of brazilin (20 to 50 μM) directly triggered platelet aggregation. Brazilin-mediated platelet aggregation was slightly inhibited by ATP (an antagonist of ADP). It was not inhibited by yohimbine (an antagonist of epinephrine), by SCH79797 (an antagonist of thrombin protease-activated receptor [PAR] 1), or by tcY-NH2 (an antagonist of PAR 4). Brazilin did not significantly affect FITC-triflavin binding to the integrin αIIbβ3 in platelet suspensions. Pretreatment of the platelets with caffeic acid phenethyl ester (an antagonist of collagen receptors) or JAQ1 and Sam.G4 monoclonal antibodies raised against collagen receptor glycoprotein VI and integrin α2β1, respectively, abolished platelet aggregation stimulated by collagen or brazilin. The immunoblotting analysis showed that brazilin stimulated the phosphorylation of phospholipase C (PLC)γ2 and Lyn, which were significantly attenuated in the presence of JAQ1 and Sam.G4. In addition, brazilin did not significantly trigger hydroxyl radical formation in ESR analysis. An in vivo mouse study showed that brazilin treatment (2 and 4 mg/kg) significantly shortened the occlusion time for platelet plug formation in mesenteric venules.

Conclusion

To the best of our knowledge, this study provides the first evidence that brazilin acts a novel collagen receptor agonist. Brazilin is a plant-based natural product, may offer therapeutic potential as intended anti-thrombotic agents for targeting of collagen receptors or to be used a useful tool for the study of detailed mechanisms in collagen receptors-mediated platelet activation.
Molecular and functional characterization of hemocyanin of the giant African millipede,Archispirostreptus gigas
Authors: Damsgaard Christian , Fago Angela , Hagner-Holler Silke , Malte Hans , Burmester Thorsten , Weber Roy E.
Published: January 2013

In contrast to other terrestrial arthropods where gaseous O2 that fuels aerobic metabolism diffuses to the tissues in tracheal tubes, and most other metazoans where O2 is transported to tissues by circulating respiratory proteins, the myriapods (millipedes and centipedes) strikingly have tracheal systems as well as circulating hemocyanin (Hc). In order to elucidate the evolutionary origin and biological significance of millipede Hc we report the molecular structure (subunit composition and amino acid sequence) of multimeric (36-mer) Hc from the forest-floor dwelling giant African millipede Archispirostreptus gigas and its allosteric oxygen binding properties under various physico-chemical conditions. A. gigas Hc consists of only a single subunit type with differential glycosylation. Phylogenic analysis reveals that millipede Hc is a sister group to centipede HcA, which supports an early divergence of distinct Hc subunits in myriapods and an ancient origin of multimeric Hcs. A. gigas Hc binds O2 with a high affinity and shows a strong normal Bohr effect. O2 binding is moreover modulated by Ca2+ ions, which increase the O2 affinity of the Hc in the T (tense; deoxygenated) as well as the R (relaxed; oxygenated) states, and by (L)-lactate, which modulates Hc-O2 affinity by changing the allosteric equilibrium constant, L. Cooperativity in O2-binding at half O2-saturation (n50) is pH-dependent and maximal at pH ~7.4 and the number of interacting O2 binding sites (q) is markedly increased by binding Ca2+. The data is discussed in the light of the role of mutually supplementary roles of Hc and the tracheal system for tissue O2 supply.
Snapshots in ants? New interpretations of paradigmatic experiments
Authors: Wystrach Antoine , Mangan Michael , Philippides Andrew , Graham Paul
Published: January 2013

Ants can use visual information to guide long idiosyncratic routes and accurately pinpoint locations in complex natural environments. It has often been assumed that the world knowledge of these foragers consists of multiple discrete views that are retrieved sequentially for breaking routes into sections controlling approaches to a goal. Here we challenge this idea by using a model of visual navigation that does not store and use discrete views to replicate the results from paradigmatic experiments which have been taken as evidence that ants navigate using such discrete snapshots. Instead of sequentially retrieving views, the proposed architecture gathers information from all experienced views into a single memory network, and uses this network to determine the most familiar heading at a given location. This algorithm is consistent with the navigation of ants in both laboratory and natural environments, and provides a parsimonious solution to deal with visual information from multiple locations.
Differentially expressed genes and pathways induced by organophosphates in human neuroblastoma cells
Authors: Li Tianwei , Zhao Hongtao , Hung Guo-Chiuan , Han Jing , Tsai Shien , Li Bingjie , Zhang Jing , Puri Raj K , Lo Shyh-Ching
Published: January 2013

Organophosphates (OPs) are toxic chemicals commonly used as pesticides and herbicides. Some OPs are highly toxic to humans and have been used in warfare and terrorist attacks. In order to elucidate the molecular mechanisms of injury caused by OPs, the differentially expressed genes were analyzed in human SK-N-SH neuroblastoma cells induced by three OPs. The SK-N-SH cells were treated with one of the three OPs, chlorpyrifos, dichlorvos or methamidophos at LC20 (high-dose), the concentration causing 20% cell death, as well as 1/20 of LC20 (low-dose), a sub-lethal concentration with no detectable cell death, for 24 h. The genome-wide gene changes were identified by Agilent Microarray System, and analyzed by microarray analysis tools. The analysis revealed neuroblastoma cells treated with the high doses of all three OPs markedly activated cell apoptosis and inhibited cell growth and proliferation genes, which would most likely lead to the process of cell death. Interestingly, the analysis also revealed significant decrease in expressions of many genes in a specific spliceosome pathway in cells treated with the low doses of all three different OPs. The change of spliceosome pathway may represent an important mechanism of injury in neuronal cells exposed to low doses of various OPs. In addition to unraveling a potentially different form of OP pathogenesis, this finding could provide a new diagnostic marker in assessing OP-associated injury in cells or tissues. In addition, these results could also contribute to the development of new prevention and/or therapeutic regimens against OP toxicity.
Dreistufiger Kolbenkompressor mit vorgeschaltetem Drehkolbenkompressor: Teil 2, Regelung
Authors: Glück Tobias , Kemmetmüller Wolfgang , Zanolin Patrick , Kugi Andreas
Published: January 2013

Dieser Beitrag beschäftigt sich mit der Regelung eines dreistufigen Kolbenkompressors mit vorgeschaltetem Drehkolbenkompressor. Ausgehend von dem im ersten Teil dieses Beitrags vorgestellten vollständigen Modell wird in diesem zweiten Teil ein vereinfachtes Entwurfsmodell für den Reglerentwurf abgeleitet, das die Periodizität der Systemgrößen des Kolbenkompressors gezielt nutzt. Zur Regelung des Drucks sowie zum Ausgleich der thermischen Belastung des Kolbenkompressors wird eine nichtlineare Regelungsstrategie vorgeschlagen. Simulationsstudien zeigen die Güte der entworfenen Regelungsstrategie.
First Application of Progressing Cavity Pumps for Appraisal Well Testing in the Ugandan Albertine Graben Basin
Authors: Sathyamoorthy S.. , Steyn A.. , McGilvray J.. , Fuchs H.. , Ainebyona B.. , Kyomugisha P.. , Vijapurapu S.. , Kagga N.. , Rindfuss R.. , Basiima D..
Published: January 2013

Over 28 production well tests and two interference tests have been conducted in the Albertine Graben basin in Uganda since the first oil discovery in 2006. The Uganda crude is moderately viscous, and low-gas/oil ratio (GOR), and later discoveries were mostly in shallow lower-energy systems. In addition, Uganda crude has relatively high pour points and wax appearance temperatures (WATs), which result in flow-assurance challenges during production testing operations. Production challenges brought about by the low energy scenario are offset by high formation permeability (mostly in the multi-Darcy range).

Field X was discovered in 2008 by Well X-1, and subsequently appraised by several wells. Zone 1 of Well X-1 was production tested under natural flow without a rig. Although hydrocarbons were brought to surface successfully during the testing operation, the maximum flow rate achieved was approximately 262 BOPD, and a stable flow rate could not be sustained. Fluid-segregation effects distorted the early-time data. In addition, flow-assurance challenges prevented acquisition of late-time response from the pressure buildup (PBU). Therefore, important dynamic information, particularly in regard to flow barriers, was not obtained.

A change in completion philosophy was proposed after detailed analysis of the test results. Well X-1 was retested with a new completion design incorporating real-time surface-readout (SRO) pressure and temperature monitoring capability, a hydraulically controlled inflow control valve (ICV), a progressing cavity pump (PCP), and a surface-controlled electrical heat trace system. High-quality well-test data was acquired, and the real-time data was used extensively throughout operations to optimize flow and buildup periods and well operating envelopes. Several challenges were faced during the first completion run, leading to the use of the contingent insert PCP system to retest Zone 1.

This paper highlights the first application of a PCP completion in Uganda and describes the challenges faced during the completion and well-testing operation. The experience from Well X-1 has demonstrated that high-quality exploration and appraisal well-test data can be acquired using a PCP completion. Similar well-completion designs will be used in Uganda for appraisal of other discoveries.
Impaired Local Production of Proresolving Lipid Mediators in Obesity and 17-HDHA as a Potential Treatment for Obesity-Associated Inflammation
Authors: Neuhofer Angelika , Zeyda Maximilian , Mascher Daniel , Itariu Bianca K. , Murano Incoronata , Leitner Lukas , Hochbrugger Eva E. , Fraisl Peter , Cinti Saverio , Serhan Charles N. , Stulnig Thomas M.
Published: January 2013

Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration, including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation and could result from a lack of local specialized proresolving lipid mediators (SPMs), such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3–derived SPMs in adipose tissue and the effects of dietary EPA/DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated the effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 (PD1) levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3–derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression, and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors, including 17-HDHA and PD1, contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications.
Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance
Authors: Ahlqvist Emma , Osmark Peter , Kuulasmaa Tiina , Pilgaard Kasper , Omar Bilal , Brøns Charlotte , Kotova Olga , Zetterqvist Anna V. , Stančáková Alena , Jonsson Anna , Hansson Ola , Kuusisto Johanna , Kieffer Timothy J. , Tuomi Tiinamaija , Isomaa Bo , Madsbad Sten , Gomez Maria F. , Poulsen Pernille , Laakso Markku , Degerman Eva , Pihlajamäki Jussi , Wierup Nils , Vaag Allan , Groop Leif , Lyssenko Valeriya
Published: January 2013

Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13 ± 0.04 vs. 0.04 ± 0.01, P < 0.05) and correlated inversely with measures of insulin sensitivity (r = −0.24, P = 0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with a lower amount of the exon 9–containing isoform required for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of the GIPR rs10423928 A allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.