bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Disorganization and Gang Homicides in Chicago
Authors: Mares Dennis
Published: August 2009

This study examines gang-motivated homicides in Chicago neighborhoods between 1985 and 1995. Qualitative studies have illustrated that gang-motivated homicides may have different characteristics than other types of homicides. Particularly at the neighborhood level, gang homicides have not yet been fully studied, and thus little is known about the interaction between gang violence and the neighborhoods they operate in. By examining the effects of social disorganization on both gang-related homicides and other types of homicides—such as intimate killings and homicides committed during street robberies—this study explores the relative uniqueness of gang homicides. Results indicate that social disorganization theory helps explain various types of homicides, including gang homicides. Nonetheless, gang homicides are also different from other types of homicides, justifying more research that looks at these homicides as a unique type of violence.
Evaluation of Tooth-Click Triggering and Speech Recognition in Assistive Technology for Computer Access
Authors: Simpson Tyler , Gauthier Michel , Prochazka Arthur
Published: August 2009

Background. Computer access can play an important role in employment and leisure activities following spinal cord injury. The authors’ prior work has shown that a tooth-click detecting device, when paired with an optical head mouse, may be used by people with tetraplegia for controlling cursor movement and mouse button clicks. Objective. To compare the efficacy of tooth clicks to speech recognition and that of an optical head mouse to a gyrometer head mouse for cursor and mouse button control of a computer. Methods. Six able-bodied and 3 tetraplegic subjects used the devices listed above to produce cursor movements and mouse clicks in response to a series of prompts displayed on a computer. The time taken to move to and click on each target was recorded. Results. The use of tooth clicks in combination with either an optical head mouse or a gyrometer head mouse can provide hands-free cursor movement and mouse button control at a speed of up to 22% of that of a standard mouse. Tooth clicks were significantly faster at generating mouse button clicks than speech recognition when paired with either type of head mouse device. Conclusions. Tooth-click detection performed better than speech recognition when paired with both the optical head mouse and the gyrometer head mouse. Such a system may improve computer access for people with tetraplegia.
Consumer-Driven Health Care: The Changing Nature of Health Insurance
Authors: Herrick Devon M.
Published: August 2009

Consumer-driven health care (CDHC) plans are a new health insurance paradigm that lets consumers control some of their own health care dollars. It also provides financial incentives to manage medical spending wisely while affording consumers greater choice and control over the types of medical services received. The premise of CDHC is coupling a tax-preferred, personal health account, used to fund day-to-day medical expenses, with a high-deductible health plan to fund care of a catastrophic nature. When individuals enter the medical marketplace, they will spend first from their health savings accounts, health reimbursement arrangements, or flexible spending accounts. Once they reach their deductible, insurance pays all remaining costs. CDHC plans are relatively new to the market, and the market share is still quite small compared to traditional forms of health insurance. CDHC is not for everyone—and not everyone wants to take greater control of health care spending. However, early evidence is encouraging. Virtually all the studies have found that people treat their own money with more care than funds belonging to someone else. Many individuals will appreciate the flexibility in benefits and the added convenience that controlling health care dollars allows.
Impact of Aerobic and Resistance Exercise on the Health of HIV-Infected Persons
Authors: Hand Gregory A. , Lyerly G. William , Jaggers Jason R. , Dudgeon Wesley D.
Published: August 2009

Individuals infected with HIV experience numerous comorbidities caused by the disease progression and medications, lack of (or inability to perform) physical activity, malnutrition, or a combination of these causes. Common symptoms include loss of muscle mass, fatigue, lypodystrophy, lypoatrophy, and decreases in strength, functional capacity, and overall quality of life. Studies have shown that exercise is a potential treatment of many of these symptoms. Research suggests that exercise may produce beneficial physiological changes in the HIV-infected population such as improved body composition and increases in both strength and endurance. In addition, psychological conditions such as depression and anxiety have been shown to be positively affected by exercise. The purpose of this review is to examine the literature regarding effects of aerobic, resistance, and combined aerobic and resistance exercise training on HIV-infected individuals.
Phosphate-silicate composite coating formed on AM60 magnesium alloy
Authors: Song X. M. , Yu G. , Yi H. B. , Ye L. Y. , Hu B. N.
Published: August 2009

A phosphate–silicate composite coating was investigated for AM60 magnesium alloy. The coating was achieved in a phosphate–permanganate solution which involved sealing in sodium silicate solution. The morphology, composition and corrosion resistance on the coatings were analysed. The phosphate–permanganate conversion coating was shown to exhibit network feature and plenty of cracks. The coating containing increased Mn element was produced using acetic acid to adjust the pH of the phosphating bath. The corrosion resistance of the coating was improved. The phosphate–silicate composite coating became more compact. The cracks on the phosphate–permanganate conversion coating were filled in by silica gel through sealing. The main elemental compositions of the phosphate–silicate composite coating were Mg, O, K, P, Mn and Si. The electrochemical polarisation curves demonstrated that the phosphate–silicate composite coating provided more effective protection against corrosion than that of phosphate–permanganate conversion coating and traditional chromate conversion coating.
Effect of laser scanning speed on nitrided layers fabricated on titanium alloy
Authors: Tian Y S , Zhang Q Y , Qin C P , Wang D Y
Published: August 2009

Laser nitriding of Ti–6Al–4V alloy was performed at different laser scanning speed. The results show that higher nitride concentration and microhardness are formed in the coatings laser nitrided with lower scanning speed. Nevertheless, higher nitride concentration results in higher residual stress which induces cracks occurring in the coatings.
Preparation and performance of lubrication composite coating based on poly(4-oxybenzoyl) (I)
Authors: Wang J , Ding Y-H , Zhao W-Z , Yu S-H , Ji Z-P
Published: August 2009

Poly(4-oxybenzoyl) (POB) based composite films were sintered on test blocks, while POB was synthesised in situ by melt polycondensation. The XRD analysis corroborates a high degree of crystallinity of the obtained POB. However, the obtained POB exhibited a lower decomposition temperature Td and a lower crystal transition temperature Tc than the commercial POB. Sand blasting of the substrates’ surfaces led to a substantial increase in the bonding strength between the prepared composite coatings and the substrates. Nevertheless, increasing the coating's thickness, increasing the MoS2 mass content in a coating or elevating the sintering temperatures resulted in a decrease in bonding. The fracture modes of the coatings during the peel tests were depicted as a combination of the separation of the coatings from the substrates and the breaking of the coatings themselves when the coatings’ thicknesses ranged from 50 to 200 μm.
Leukotriene D4activates β2-integrin adhesion in human polymorphonuclear leukocytes
Authors: Meliton A. Y. , Muñoz N. M. , Osan C. M. , Meliton L. N. , Leff A. R.
Published: August 2009

We examined the functional role and mechanisms by which activation of cysteinyl leukotriene-1 receptor (cysLT1R) regulates β2-integrin adhesion to intercellular adhesion molecule (ICAM)-1 in human polymorphonuclear leukocytes (PMNs)in vitro.

Human peripheral blood PMNs and eosinophils were isolated separately from the same mildly atopic donors. Surface expression of cysLT1R was identified both in PMNs and in eosinophils by immunofluorescence analysis. Total cysLT1R protein was substantially greater in eosinophils than in PMNs as determined by Western blot analysis. However, leukotriene D4(LTD4) upregulated β2-integrin adhesion of PMNs to ICAM-1 with high efficacy in a time- and concentration-dependent manner. Upregulated β2-integrin adhesion of PMNs was related temporally and quantitatively to phosphorylation of 85-kDa cytosolic group IVa phospholipase A2 (gIVaPLA2). Augmented LTD4-induced adhesion was blocked significantly by montelukast, a cysLT1R antagonist. Trifluoromethylketone (a gIVaPLA2 inhibitor) blocked β2-integrin adhesion caused by LTD4activation, as did anti-CD18 monoclonal antibody directed against β2-integrin on the PMN surface.

Our data demonstrate that LTD4causes phosphorylation of gIVaPLA2 and upregulation of β2-integrin adhesion to ICAM-1 or ICAM-1 surrogate through cysLT1R activation. Activation of gIVaPLA2 is a critical step through which β2-integrin adhesion is upregulated by the cysLT1R expressed on the surface membrane of human PMN.
CARD15/NOD2polymorphisms are associated with severe pulmonary sarcoidosis
Authors: Sato H. , Williams H. R. T. , Spagnolo P. , Abdallah A. , Ahmad T. , Orchard T. R. , Copley S. J. , Desai S. R. , Wells A. U. , du Bois R. M. , Welsh K. I.
Published: August 2009

Sarcoidosis and Crohn’s disease are heterogeneous systemic diseases characterised by granulomatous inflammation.Caspase recruitment domain(CARD)15is a major susceptibility gene for Crohn’s disease, and specifically for ileal and fibrostenotic subtypes. TheC-C chemokine receptor(CCR)5gene has been associated with both parenchymal pulmonary sarcoidosis and perianal Crohn’s disease.

This study explored associations betweenCARD15polymorphisms,CCR5haplotype and distinct pulmonary sarcoidosis subtypes. 185 Caucasian sarcoidosis patients were genotyped forCARD15andCCR5polymorphisms. The genetic data were compared with 347 healthy controls and were examined for associations with serial pulmonary function tests and chest radiographs. CARD15genotypes did not differ between the unselected sarcoidosis cohort and controls. However, patients carrying the functional2104T(702W) polymorphism were more likely to have radiographic stage IV disease at 4-yr follow-up. All patients possessing bothCARD15 2104TandCCR5HHChaplotype had stage IV disease at presentation. Carriage of2104Twas associated with worse forced expiratory volume in 1 s, whereas carriage of theCARD15 1761G (587R)polymorphism was associated with better lung function.

For the first time, an association between twoCARD15polymorphisms and specific sarcoidosis phenotypes has been demonstrated, as well as an additive effect of possessingCARD15 2104TandCCR5HHChaplotype.
β2-Agonists block tussive responses in guinea pigsviaan atypical cAMP-dependent pathway
Authors: Freund-Michel V. C. , Birrell M. A. , Giembycz M. A. , Hele D. J. , Haj-Yahia S. , Belvisi M. G.
Published: August 2009

β2-Adrenoceptor agonists are the most effective bronchodilators currently available, and are used for symptom management in asthmatics. However, whether β2-agonists are also antitussive is controversial. Identifying an antitussive role for β2-agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not β2-agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved.

Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model.

A β2-agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another β2-agonist, fenoterol, blocked sensory nerve activationin vitro. Using these mechanistic models, it was established that β2-agonists suppress the tussive responseviaa nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of large-conductance calcium-activated potassium channels.

In conclusion, β2-adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.
Acute inflammatory response secondary to intrapleural administration of two types of talc
Authors: Rossi V. F. , Vargas F. S. , Marchi E. , Acencio M. M. P. , Genofre E. H. , Capelozzi V. L. , Antonangelo L.
Published: August 2009

Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT).

100 rabbits received intrapleural talc, 50 with ST (median 6.41 μm) and 50 with MT (median 21.15 μm); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h.

Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group.

In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.
Carbon monoxide pollution is associated with decreased lung function in asthmatic adults
Authors: Canova C. , Torresan S. , Simonato L. , Scapellato M. L. , Tessari R. , Visentin A. , Lotti M. , Maestrelli P.
Published: August 2009

The aim of the present study was to test the effects of exposure to air pollutants on lung function.

A panel of 19 adult asthmatics living in Padua (Italy) was followed for five 30-day periods during 2 yrs consecutively (1,492 morning and 1,434 evening measures analysed). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were measured using a pocket electronic meter. Daily levels of air pollutants and meteorological variables were collected at outdoor city monitoring sites.

Significant inverse associations were observed between morning and evening PEF and carbon monoxide level (p = 0.01–0.03), without clear differences between lags (0–3 days). An increment of 1 mg·m−3CO was associated with a PEF variation ranging -2.6– -2.8%. All effect estimates on PEF for CO remained significant and even increased after controlling for particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10), nitrogen dioxide and sulphur dioxide in single and multi-pollutant models. A similar trend was observed for FEV1, but the associations were nonsignificant. A nonsignificant inverse relationship between evening PEF and SO2was also detected. PEF and FEV1were not related to PM10and NO2concentrations.

The present results indicate that, in this panel of adult asthmatics, the worsening of lung function is associated with exposure to gaseous pollutants and occurs at levels of CO and SO2lower than current European standards.
Lung function predicts lung cancer risk in smokers: a tool for targeting screening programmes
Authors: Calabrò E. , Randi G. , La Vecchia C. , Sverzellati N. , Marchianò A. , Villani M. , Zompatori M. , Cassandro R. , Harari S. , Pastorino U.
Published: August 2009

The relationship between smoking, lung cancer and airflow obstruction is recognised but it is unclear whether the presence of minimal lung function damage constitutes an independent risk factor for the development of lung cancer.

In order to identify those individuals at higher risk of lung cancer on the basis of functional impairment, we evaluated baseline pulmonary function tests of 3,806 heavy smokers undergoing annual chest computed tomography screening, and compared the forced expiratory volume in 1 s (FEV1) % predicted of 57 lung cancer cases and that of 3,749 subjects without cancer.

We obtained odds ratios (ORs) of lung cancer and the corresponding 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for age, sex, study and smoking variables. Compared with subjects with FEV1≥90% pred, the OR of lung cancer was 2.45 (95% CI 1.39–4.33) for subjects with FEV1<90% pred and 2.90 (95% CI 1.34–6.27) for subjects with FEV1<70% pred.

These data show that even a relatively small reduction in FEV1% pred is a significant predictor of increased lung cancer risk. Test screening for lung cancer using airflow obstruction with FEV1<90% is a strategy worth future consideration.
Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1)
Authors: Raghu G. , King T. E. , Behr J. , Brown K. K. , du Bois R. M. , Leconte I. , Roux S. , Swigris J.
Published: August 2009

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial.

In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George’s Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index.

Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36.

HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.
SNAD: sequence name annotation-based designer
Authors: Sidorov Igor A , Reshetov Denis A , Gorbalenya Alexander E
Published: August 2009

Background

A growing diversity of biological data is tagged with unique identifiers (UIDs) associated with polynucleotides and proteins to ensure efficient computer-mediated data storage, maintenance, and processing. These identifiers, which are not informative for most people, are often substituted by biologically meaningful names in various presentations to facilitate utilization and dissemination of sequence-based knowledge. This substitution is commonly done manually that may be a tedious exercise prone to mistakes and omissions.

Results

Here we introduce SNAD (Sequence Name Annotation-based Designer) that mediates automatic conversion of sequence UIDs (associated with multiple alignment or phylogenetic tree, or supplied as plain text list) into biologically meaningful names and acronyms. This conversion is directed by precompiled or user-defined templates that exploit wealth of annotation available in cognate entries of external databases. Using examples, we demonstrate how this tool can be used to generate names for practical purposes, particularly in virology.

Conclusion

A tool for controllable annotation-based conversion of sequence UIDs into biologically meaningful names and acronyms has been developed and placed into service, fostering links between quality of sequence annotation, and efficiency of communication and knowledge dissemination among researchers.
Evolution and functional divergence of NLRPgenes in mammalian reproductive systems
Authors: Tian Xin , Pascal Géraldine , Monget Philippe
Published: August 2009

Background

NLRPs (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins) are members of NLR (Nod-like receptors) protein family. Recent researches have shown that NLRP genes play important roles in both mammalian innate immune system and reproductive system. Several of NLRP genes were shown to be specifically expressed in the oocyte in mammals. The aim of the present work was to study how these genes evolved and diverged after their duplication, as well as whether natural selection played a role during their evolution.

Results

By using in silico methods, we have evaluated the evolution and functional divergence of NLRP genes, in particular of mouse reproduction-related Nlrp genes. We found that (1) major NLRP genes have been duplicated before the divergence of mammals, with certain lineage-specific duplications in primates (NLRP7 and 11) and in rodents (Nlrp1, 4 and 9 duplicates); (2) tandem duplication events gave rise to a mammalian reproduction-related NLRP cluster including NLRP2, 4, 5, 7, 8, 9, 11, 13 and 14 genes; (3) the function of mammalian oocyte-specific NLRP genes (NLRP4, 5, 9 and 14) might have diverged during gene evolution; (4) recent segmental duplications concerning Nlrp4 copies and vomeronasal 1 receptor encoding genes (V1r) have been undertaken in the mouse; and (5) duplicates of Nlrp4 and 9 in the mouse might have been subjected to adaptive evolution.

Conclusion

In conclusion, this study brings us novel information on the evolution of mammalian reproduction-related NLRPs. On the one hand, NLRP genes duplicated and functionally diversified in mammalian reproductive systems (such as NLRP4, 5, 9 and 14). On the other hand, during evolution, different lineages adapted to develop their own NLRP genes, particularly in reproductive function (such as the specific expansion of Nlrp4 and Nlrp9 in the mouse).
Identification and expression of differentially expressed genes in the hard clam, Mercenaria mercenaria, in response to quahog parasite unknown (QPX)
Authors: Perrigault Mickael , Tanguy Arnaud , Allam Bassem
Published: August 2009

Background

The hard clam, Mercenaria mercenaria, has been affected by severe mortality episodes associated with the protistan parasite QPX (Quahog Parasite Unknown) for several years. Despite the commercial importance of hard clams in the United States, molecular bases of defense mechanisms in M. mercenaria, especially during QPX infection, remain unknown.

Results

Our study used suppression subtractive hybridization (SSH), as well as the construction of cDNA libraries from hemocytes to identify genes related to the defense of the hard clam against its parasite. Hard clams were experimentally infected with QPX and SSH was performed on mRNA samples extracted from mantle and gill tissues at different times post-challenge. A total of 298 clones from SSH libraries and 1352 clones from cDNA libraries were sequenced. Among these sequences, homologies with genes involved in different physiological processes related to signal transduction, stress response, immunity and protein synthesis were identified. Quantitative PCR revealed significant changes in the expression of several of these genes in response to QPX challenge and demonstrated significant correlations in terms of levels of gene expression between intermediates of signalling pathways and humoral defense factors, such as big defensin and lysozyme.

Conclusion

Results of this study allowed the detection of modifications caused by QPX at the transcriptional level providing insight into clam immune response to the infection. These investigations permitted the identification of candidate genes and pathways for further analyses of biological bases of clam resistance to QPX allowing for a better understanding of bivalve immunity in general.
Rapid detection of ERG11 gene mutations in clinical Candida albicans isolates with reduced susceptibility to fluconazole by rolling circle amplification and DNA sequencing
Authors: Wang Huiping , Kong Fanrong , Sorrell Tania C , Wang Bin , McNicholas Paul , Pantarat Namfon , Ellis David , Xiao Meng , Widmer Fred , Chen Sharon CA
Published: August 2009

Background

Amino acid substitutions in the target enzyme Erg11p of azole antifungals contribute to clinically-relevant azole resistance in Candida albicans. A simple molecular method for rapid detection of ERG11 gene mutations would be an advantage as a screening tool to identify potentially-resistant strains and to track their movement. To complement DNA sequencing, we developed a padlock probe and rolling circle amplification (RCA)-based method to detect a series of mutations in the C. albicans ERG11 gene using "reference" azole-resistant isolates with known mutations. The method was then used to estimate the frequency of ERG11 mutations and their type in 25 Australian clinical C. albicans isolates with reduced susceptibility to fluconazole and in 23 fluconazole-susceptible isolates. RCA results were compared DNA sequencing.

Results

The RCA assay correctly identified all ERG11 mutations in eight "reference" C. albicans isolates. When applied to 48 test strains, the RCA method showed 100% agreement with DNA sequencing where an ERG11 mutation-specific probe was used. Of 20 different missense mutations detected by sequencing in 24 of 25 (96%) isolates with reduced fluconazole susceptibility, 16 were detected by RCA. Five missense mutations were detected by both methods in 18 of 23 (78%) fluconazole-susceptible strains. DNA sequencing revealed that mutations in non-susceptible isolates were all due to homozygous nucleotide changes. With the exception of the mutations leading to amino acid substitution E266D, those in fluconazole-susceptible strains were heterozygous. Amino acid substitutions common to both sets of isolates were D116E, E266D, K128T, V437I and V488I. Substitutions unique to isolates with reduced fluconazole susceptibility were G464 S (n = 4 isolates), G448E (n = 3), G307S (n = 3), K143R (n = 3) and Y123H, S405F and R467K (each n = 1). DNA sequencing revealed a novel substitution, G450V, in one isolate.

Conclusion

The sensitive RCA assay described here is a simple, robust and rapid (2 h) method for the detection of ERG11 polymorphisms. It showed excellent concordance with ERG11 sequencing and is a potentially valuable tool to track the emergence and spread of azole-resistant C. albicans and to study the epidemiology of ERG11 mutations. The RCA method is applicable to the study of azole resistance in other fungi.
Common polymorphisms within the NR4A3 locus, encoding the orphan nuclear receptor Nor-1, are associated with enhanced β-cell function in non-diabetic subjects
Authors: Weyrich Peter , Staiger Harald , Stančáková Alena , Schäfer Silke A , Kirchhoff Kerstin , Ullrich Susanne , Ranta Felicia , Gallwitz Baptist , Stefan Norbert , Machicao Fausto , Kuusisto Johanna , Laakso Markku , Fritsche Andreas , Häring Hans-Ulrich
Published: August 2009

Background

Neuron-derived orphan receptor (Nor) 1, nuclear receptor (Nur) 77, and nuclear receptor-related protein (Nurr) 1 constitute the NR4A family of orphan nuclear receptors which were recently found to modulate hepatic glucose production, insulin signalling in adipocytes, and oxidative metabolism in skeletal muscle. In this study, we assessed whether common genetic variation within the NR4A3 locus, encoding Nor-1, contributes to the development of prediabetic phenotypes, such as glucose intolerance, insulin resistance, or β-cell dysfunction.

Methods

We genotyped 1495 non-diabetic subjects from Southern Germany for the five tagging single nucleotide polymorphisms (SNPs) rs7047636, rs1526267, rs2416879, rs12686676, and rs10819699 (minor allele frequencies ≥ 0.05) covering 100% of genetic variation within the NR4A3 locus (with D' = 1.0, r2 ≥ 0.9) and assessed their association with metabolic data derived from the fasting state, an oral glucose tolerance test (OGTT), and a hyperinsulinemic-euglycemic clamp (subgroup, N = 506). SNPs that revealed consistent associations with prediabetic phenotypes were subsequently genotyped in a second cohort (METSIM Study; Finland; N = 5265) for replication.

Results

All five SNPs were in Hardy-Weinberg equilibrium (p ≥ 0.7, all). The minor alleles of three SNPs, i.e., rs1526267, rs12686676, and rs10819699, consistently tended to associate with higher insulin release as derived from plasma insulin at 30 min(OGTT), AUCC-peptide-to-AUCGluc ratio and the AUCIns30-to-AUCGluc30 ratio with rs12686676 reaching the level of significance (p ≤ 0.03, all; additive model). The association of the SNP rs12686676 with insulin secretion was replicated in the METSIM cohort (p ≤ 0.03, additive model). There was no consistent association with glucose tolerance or insulin resistance in both study cohorts.

Conclusion

We conclude that common genetic variation within the NR4A3 locus determines insulin secretion. Thus, NR4A3 represents a novel candidate gene for β-cell function which was not covered by the SNP arrays of recent genome-wide association studies for type 2 diabetes mellitus.
Aerobic exercise and intraocular pressure in normotensive and glaucoma patients
Authors: Natsis Konstantinos , Asouhidou Irene , Nousios George , Chatzibalis Theodosios , Vlasis Konstantinos , Karabatakis Vasilios
Published: August 2009

Background

With the increasing number of people participating in physical aerobic exercise, jogging in particular, we considered that it would be worth knowing if there are should be limits to the exercise with regard to the intraocular pressure (IOP) of the eyes. The purpose of this study is to check IOP in healthy and primary glaucoma patients after aerobic exercise.

Methods

145 individuals were subdivided into seven groups: normotensives who exercised regularly (Group A); normotensives in whose right eye (RE) timolol maleate 0.5% (Group B), latanoprost 0.005% (Group C), or brimonidine tartrate 0.2% (Group D) was instilled; and primary glaucoma patients under monotherapy with β-blockers (Group E), prostaglandin analogues (Group F) or combined antiglaucoma treatment (Group G) instilled in both eyes. The IOP of both eyes was measured before and after exercise.

Results

A statistically significant decrease was found in IOP during jogging. The aerobic exercise reduces the IOP in those eyes where a b-blocker, a prostaglandin analogue or an α-agonist was previously instilled. The IOP is also decreased in glaucoma patients who are already under antiglaucoma treatment.

Conclusion

There is no ocular restriction for simple glaucoma patients in performing aerobic physical activity.
Influence of gender, sexual orientation, and need on treatment utilization for substance use and mental disorders: Findings from the California Quality of Life Survey
Authors: Grella Christine E , Greenwell Lisa , Mays Vickie M , Cochran Susan D
Published: August 2009

Background

Prior research has shown a higher prevalence of substance use and mental disorders among sexual minorities, however, the influence of sexual orientation on treatment seeking has not been widely studied. We use a model of help-seeking for vulnerable populations to investigate factors related to treatment for alcohol or drug use disorders and mental health disorders, focusing on the contributions of gender, sexual orientation, and need.

Methods

Survey data were obtained from a population-based probability sample of California residents that oversampled for sexual minorities. Logistic regression was used to model the enabling, predisposing, and need-related factors associated with past-year mental health or substance abuse treatment utilization among adults aged 18–64 (N = 2,074).

Results

Compared with individuals without a diagnosed disorder, those with any disorder were more likely to receive treatment. After controlling for both presence of disorder and other factors, lesbians and bisexual women were most likely to receive treatment and heterosexual men were the least likely. Moreover, a considerable proportion of sexual orientation minorities without any diagnosable disorder, particularly lesbians and bisexual women, also reported receiving treatment.

Conclusion

The study highlights the need to better understand the factors beyond meeting diagnostic criteria that underlie treatment utilization among sexual minorities. Future research should also aim to ascertain the effects of treatment provided to sexual minorities with and without diagnosable disorders, including the possibility that the provision of such treatment may reduce the likelihood of their progression to greater severity of distress, disorders, or impairments in functioning.
Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study
Authors: Oben Julius , Enonchong Ebangha , Kothari Shil , Chambliss Walter , Garrison Robert , Dolnick Deanne
Published: August 2009

Background

The objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis.

Methods

An 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo were given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]).

Results

Eighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 ± 2.3 vs 11.8 ± 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 ± 1.4 vs 9.9 ± 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 ± 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups.

Conclusion

In this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contributing factor to the other benefits.
Combined therapy with cyclophosphamide and DNA preparation inhibits the tumor growth in mice
Authors: Alyamkina Ekaterina A , Dolgova Evgenia V , Likhacheva Anastasia S , Rogachev Vladimir A , Sebeleva Tamara E , Nikolin Valeriy P , Popova Nelly A , Orishchenko Konstantin E , Strunkin Dmitriy N , Chernykh Elena R , Zagrebelniy Stanislav N , Bogachev Sergei S , Shurdov Mikhail A
Published: August 2009

Background

When cyclophosphamide and preparations of fragmented exogenous genomic double stranded DNA were administered in sequence, the regressive effect on the tumor was synergic: this combined treatment had a more pronounced effect than cyclophosphamide alone. Our further studies demonstrated that exogenous DNA stimulated the maturation and specific activities of dendritic cells. This suggests that cyclophosphamide, combined with DNA, leads to an immune response to the tumors that were grafted into the subjects post treatment.

Methods

Three-month old CBA/Lac mice were used in the experiments. The mice were injected with cyclosphamide (200 mkg per 1 kg body weight) and genomic DNA (of human, mouse or salmon sperm origin). The DNA was administered intraperitoneally or subcutaneously. After 23 to 60 days, one million tumor cells were intramuscularly grafted into the mice. In the final experiment, the mice were pre-immunized by subcutaneous injections of 20 million repeatedly thawed and frozen tumor cells. Changes in tumor growth were determined by multiplying the three perpendicular diameters (measured by caliper). Students' t-tests were used to determine the difference between tumor growth and average survival rate between the mouse groups and the controls.

Results

An analysis of varying treatments with cyclophosphamide and exogenous DNA, followed by tumor grafting, provided evidence that this combined treatment had an immunizing effect. This inhibitory effect in mice was analyzed in an experiment with the classical immunization of a tumor homogenate. The strongest inhibitory action on a transplanted graft was created through the following steps: cyclophosphamide at 200 mg/kg of body weight administered as a pretreatment; 6 mg fragmented exogenous DNA administered over the course of 3 days; tumor homogenate grafted 10 days following the final DNA injection.

Conclusion

Fragmented exogenous DNA injected with cyclophosphamide inhibits the growth of tumors that are grafted to mice after this combined treatment.
Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice
Authors: Chao Pei-chun , Hsu Cheng-chin , Yin Mei-chin
Published: August 2009

Background

Caffeic acid (CA) and ellagic acid (EA) are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined.

Methods

Diabetic mice were divided into three groups (15 mice per group): diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured.

Results

The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p < 0.05). These treatments also significantly enhanced plasma antithrombin-III and protein C activities (p < 0.05); and decreased triglyceride content in cardiac tissue and plasma (p < 0.05), in which the hypolipidemic effects of EA were significantly greater than that of CA (p < 0.05). CA or EA significantly lowered cardiac levels of malondialdehyde, reactive oxygen species, interleukin (IL)-beta, IL-6, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 (p < 0.05); and retained cardiac activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (p < 0.05). These compounds also significantly up-regulated cardiac mRNA expression of GPX1, SOD and catalase; and down-regulated IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA expression in diabetic mice (p < 0.05).

Conclusion

These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.
Endoscopic T-tube placement in the management of lye-induced esophageal perforation: Case report of a safe treatment strategy
Authors: McMahon Mary Aisling , O'Kelly Fardod , Lim Kheng Tian , Ravi Narayanasamy , Reynolds John Vincent
Published: August 2009

Esophageal perforation is associated with a significant risk of morbidity and mortality. We report herein a case of lye-induced esophageal perforation managed successfully by employing endoscopic T-tube placement with a successful outcome.
Fat head: an analysis of head and neck insulation in the leatherback turtle (Dermochelys coriacea)
Authors: Davenport John , Fraher John , Fitzgerald Edward , McLaughlin Patrick , Doyle Tom , Harman Luke , Cuffe Tracy
Published: August 2009

Adult leatherback turtles are gigantothermic/endothermic when foraging in cool temperate waters, maintaining a core body temperature within the main body cavity of ca. 25°C despite encountering surface temperatures of ca. 15°C and temperatures as low as 0.4°C during dives. Leatherbacks also eat very large quantities of cold, gelatinous prey (medusae and pyrosomas). We hypothesised that the head and neck of the leatherback would have structural features to minimise cephalic heat loss and limit cooling of the head and neck during food ingestion. By gross dissection and analytical computed tomography (validated by ground truthing dissection) of an embalmed specimen we confirmed this prediction. 21% of the head and neck was occupied by adipose tissue. This occurred as intracranial blubber,encapsulating the salt glands, medial portions of the eyeballs, plus the neurocranium and brain. The dorsal and lateral surfaces of the neck featured thick blubber pads whereas the carotid arteries and jugular veins were deeply buried in the neck and protected laterally by blubber. The oesophagus was surrounded by a thick sheath of adipose tissue whereas the oropharyngeal cavity had an adipose layer between it and the bony proportion of the palate,providing further ventral insulation for salt glands and neurocranium.
Are stress hormone levels a good proxy of foraging success? An experiment with King Penguins,Aptenodytes patagonicus
Authors: Angelier Frédéric , Giraudeau Mathieu , Bost Charles-André , Le Bouard Fabrice , Chastel Olivier
Published: August 2009

In seabirds, variations in stress hormone (corticosterone; henceforth CORT)levels have been shown to reflect changing marine conditions and, especially,changes in food availability. However, it remains unclear how CORT levels can be mechanistically affected by these changes at the individual level. Specifically, the influence of food acquisition and foraging success on CORT secretion is poorly understood. In this study, we tested whether food acquisition can reduce baseline CORT levels (`the food intake hypothesis') by experimentally reducing foraging success of King Penguins (Aptenodytes patagonicus). Although CORT levels overall decreased during a foraging trip, CORT levels did not differ between experimental birds and controls. These results demonstrate that mass gain at sea is not involved in changes in baseline CORT levels in this species. The overall decrease in CORT levels during a foraging trip could result from CORT-mediated energy regulation (`the energy utilisation hypothesis'). Along with other evidence, we suggest that the influence of foraging success and food intake on CORT levels is complex and that the ecological meaning of baseline CORT levels can definitely vary between species and ecological contexts. Therefore, further studies are needed to better understand (1) how baseline CORT levels are functionally regulated according to energetic status and energetic demands and (2) to what extent CORT can be used to aid in the conservation of seabird populations.
Cyclomorphosis in Tardigrada: adaptation to environmental constraints
Authors: Halberg Kenneth Agerlin , Persson Dennis , Ramløv Hans , Westh Peter , Kristensen Reinhardt Møbjerg , Møbjerg Nadja
Published: August 2009

Tardigrades exhibit a remarkable resilience against environmental extremes. In the present study, we investigate mechanisms of survival and physiological adaptations associated with sub-zero temperatures and severe osmotic stress in two commonly found cyclomorphic stages of the marine eutardigrade Halobiotus crispae. Our results show that only animals in the so-called pseudosimplex 1 stage are freeze tolerant. In pseudosimplex 1, as well as active-stage animals kept at a salinity of 20 ppt, ice formation proceeds rapidly at a crystallization temperature of around –20°C,revealing extensive supercooling in both stages, while excluding the presence of physiologically relevant ice-nucleating agents. Experiments on osmotic stress tolerance show that the active stage tolerates the largest range of salinities. Changes in body volume and hemolymph osmolality of active-stage specimens (350–500 μm) were measured following salinity transfers from 20 ppt. Hemolymph osmolality at 20 ppt was approximately 950 mOsm kg–1. Exposure to hypo-osmotic stress in 2 and 10 ppt caused(1) rapid swelling followed by a regulatory volume decrease, with body volume reaching control levels after 48 h and (2) decrease in hemolymph osmolality followed by a stabilization at significantly lower osmolalities. Exposure to hyperosmotic stress in 40 ppt caused (1) rapid volume reduction, followed by a regulatory increase, but with a new steady-state after 24 h below control values and (2) significant increase in hemolymph osmolality. At any investigated external salinity, active-stage H. crispaehyper-regulate, indicating a high water turnover and excretion of dilute urine. This is likely a general feature of eutardigrades.
Metabolic correlates of selection on aerobic capacity in laboratory mice:a test of the model for the evolution of endothermy
Authors: Gębczyński Andrzej K. , Konarzewski Marek
Published: August 2009

According to the aerobic capacity model of the evolution of endothermy,high levels of basal/resting metabolic rate (BMR/RMR) underlying endothermy have evolved as a correlated response to selection for high rates of aerobic metabolism (VO2max). To test the model we studied metabolic, behavioural and morphological correlates of replicated selection on maximum body mass-corrected metabolism elicited by swimming(VO2swim) in male laboratory mice. While 10 generations of selection did not change body mass, it resulted in a 12%difference in VO2swim between mice of selected and control line types and significant, correlated responses in maximum metabolic rates elicited by exposure to cold in a helium–oxygen atmosphere (VO2He), and during forced running on a motorized treadmill (VO2run). Selected and control lines also significantly differed with respect to duration of running(a measure of stamina, trun), and the distance run to exhaustion (de). However, the selection protocol did not result in elevated BMR and voluntary activity. Higher VO2max in selected animals was positively correlated with higher masses of gastrocnemius muscles and heart but not of other visceral organs (intestine, stomach, liver and kidneys). These findings provide a mechanistic explanation for the lack of correlation between basal and maximal metabolic rates in selected mice. Overall, our study does not support the assumptions of the aerobic capacity model for the evolution of endothermy.