bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid S-Nitrosylation of Actin by NO-Generating Donors and in Inflammatory Pain Model Mice
Authors: Lu Jingshan , Katano Tayo , Uta Daisuke , Furue Hidemasa , Ito Seiji 
Published: December 2011

Background: S-Nitrosylation, the reversible post-translational modification of reactive cysteine residues in proteins, has emerged as an important mechanism by which NO acts as a signaling molecule. We recently demonstrated that actin is a major S-nitrosylated protein in the spinal cord and suggested that NO directly attenuates dopamine release from PC12 cells by causing the breakdown of F-actin. However, the occurrence of S-nitrosylation of actin remained unclarified in animal pain model. Kinetic analysis of S-nitrosylation of actin in the present study was made by using NO-generating donors. The biotin-switch assay and purification on streptavidin-agarose were employed for identification of S-nitrosylated actin. Results: Dopamine release from PC12 cells was markedly attenuated by NOR1 ( t1/2 = 1.8 min) and much less by NOR3 ( t1/2 = 30 min), but not by S-nitroso-glutathione, an endogenous NO donor. A membrane-permeable cGMP analogue could not substitute for NOR1 as a suppressor nor could inhibitors of soluble guanylate cyclase and cGMP-dependent protein kinase attenuate the suppression. S-Nitrosylated actin was detected by the biotin-switch assay at 5 min after the addition of NOR1. Consistent with the kinetic analysis, actin in the spinal cord was rapidly and maximally S-nitrosylated in an inflammatory pain model at 5 min after the injection of 2% formalin into the hind paws. In vivo patch-clamp recordings of the spinal dorsal horn, NOR3 showed an inhibitory action on inhibitory synaptic transmission in interneurons of the substantia gelatinosa. Conclusions: The present study demonstrates that rapid S-nitrosylation of actin occurred in vitro in the presence of exogenous NO-generating donors and in vivo in inflammatory pain model mice. Our data suggest that, in addition to the well-known cGMP-dependent protein kinase pathway, S-nitrosylation is involved in pain transmission via disinhibition of inhibitory neurons.
Bush animal attacks: management of complex injuries in a resource-limited setting
Authors: Mitchell Katrina B , Kotecha Vihar R , Chandika Alphonce 
Published: December 2011

Abstract

Introduction
Though animal-related injuries and fatalities have been documented throughout the world, the variety of attacks by wild animals native to rural East Africa are less commonly described. Given the proximity of our northwestern Tanzania hospital to Lake Victoria, Lake Tanganyika, and the Serengeti National Park, and presentation of several patients attacked by bush animals and suffering a variety of complex injuries, we sought to report the pattern of attacks and surgical management in a resource-limited setting.

Materials and methods
Four patients who were admitted to the northwestern Tanzania tertiary referral hospital, Bugando Medical Centre (BMC), in 2010-2011 suffered attacks by different bush animals: hyena, elephant, crocodile, and vervet monkey. These patients were triaged as trauma patients in the Casualty Ward, then admitted for inpatient monitoring and treatment. Their outcomes were followed to discharge.

Results
The age and gender of the patients attacked was variable, though all but the pediatric patient were participating in food gathering or guarding activities in rural locations at the time of the attacks. All patients required surgical management of their injuries, which included debridement and closure of wounds, chest tube insertion, amputation, and external fixation of an extremity fracture. All patients survived and were discharged home.

Discussion
Though human injuries secondary to encounters with undomesticated animals such as cows, moose, and camel are reported, they often are indirect traumas resulting from road traffic collisions. Snake attacks are well documented and common. However, this series of unique bush animal attacks describes the initial and surgical management of human injuries in the resource-limited setting of the developing world.

Conclusion
Animal attacks are common throughout the world, but their pattern may vary in Africa throughout jungle and bush environmental settings. It is important to understand the management of these attacks in resource-limited health care environment. Further, the growing population and human encroachment on previously wild habitats such as the northwestern Tanzania bush argues for increased community awareness to assist in prevention of human injuries by animals.
A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections
Authors: Chang Stewart T , Tchitchek Nicolas , Ghosh Debashis , Benecke Arndt , Katze Michael G 
Published: December 2011

Abstract

Background
During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections.

Results
From a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS coronavirus, we used meta-analysis to derive multiple gene expression signatures. We compared these signatures by their capacity to segregate biological conditions by pathogenicity and predict pathogenicity in a test data set. The highest-performing signature was expressed as a continuum in low-, medium-, and high-pathogenicity samples, suggesting a direct, analog relationship between expression and pathogenicity. This signature comprised 57 genes including a subnetwork of chemokines, implicating dysregulated cell recruitment in injury.

Conclusions
Highly pathogenic viruses elicit expression of many of the same key genes as lower pathogenic viruses but to a higher degree. This increased degree of expression may result in the uncontrolled co-localization of inflammatory cell types and lead to irreversible host damage.
Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model
Authors: Xu Dan , O Teresa M , Shartava Archil , Fowles Taylor C , Yang Jianchang , Fink Louis M , Ward David C , Mihm Martin C , Waner Milton , Ma Yupo 
Published: December 2011

Abstract

Background
Infantile hemangiomas (IH) are the most common benign tumors of infancy. The typical clinical course consists of rapid growth during the first year of life, followed by natural and gradual involution over a multi-year time span through unknown cellular mechanisms. Some tumors respond to medical treatment with corticosteroids or beta-blockers, however, when this therapy fails or is incomplete, surgical extirpation may be necessary. Noninvasive therapies to debulk or eliminate these tumors would be an important advance. The development of an in vitro cell culture system and an animal model would allow new insights into the biological processes involved in the development and pathogenesis of IH.

Results
We observed that proliferative stage IH specimens contain significantly more SALL4+ and CD133+ cells than involuting tumors, suggesting a possible stem cell origin. A tumor sphere formation assay was adapted to culture IH cells in vitro. Cells in IH tumor spheres express GLUT1, indicative of an IH cell of origin, elevated levels of VEGF, and various stem/progenitor cell markers such as SALL4, KDR, Oct4, Nanog and CD133. These cells were able to self-renew and differentiate to endothelial lineages, both hallmarks of tumor stem cells. Treatment with Rapamycin, a potent mTOR/VEGF inhibitor, dramatically suppressed IH cell growth in vitro. Subcutaneous injection of cells from IH tumor spheres into immunodeficient NOD-SCID mice produced GLUT1 and CD31 positive tumors with the same cellular proliferation, differentiation and involution patterns as human hemangiomas.

Conclusions
The ability to propagate large numbers of IH stem cells in vitro and the generation of an in vivo mouse model provides novel avenues for testing IH therapeutic agents in the future.
Accuracy of a Novel Non-Invasive technology based EZSCAN system for the diagnosis of diabetes mellitus in Chinese
Authors: Sheng Chang-Sheng , Zeng Wei-Fang , Huang Qi-Fang , Deslypere Jean-Paul , Li Yan , Wang Ji-Guang 
Published: December 2011

Abstract

Background
A new simple technique based on iontophoresis technology (EZSCAN, Impeto Medical, Paris, France) has recently been developed for the screening of diabetes. In the present study, we investigated the accuracy of this system for the diagnosis of diabetes mellitus in Chinese.

Methods
We performed the EZSCAN test in diabetic and non-diabetic subjects. EZSCAN measures electrochemical conductance (EC) at forehead, hands and feet, and derives a diabetes index with a value ranging from 0 to 100. Diabetes mellitus was defined as a plasma glucose concentration of at least 7 mmol/l at fasting or 11.1 mmol/l at 2 hours after glucose load, or as the use of antidiabetic drugs.

Results
The 195 study participants (51% men, mean age 52 years) included 75 diabetic patients (use of antidiabetic drugs 81%) and 120 non-diabetic subjects. EC (micro Siemens, μSi) was significantly (P < 0.001) lower in diabetic patients at the hands (44 vs. 61) and feet (51 vs. 69) locations, but not at the forehead (15 vs. 17, P = 0.39). When a diabetes index of 40 (suggested by the manufacturer) was used as the threshold, the sensitivity and specificity for the diagnosis of diabetes mellitus was 85% and 64%, respectively. In 80 patients who underwent an oral glucose tolerance test, EC at hands and feet and the diabetes index were significantly (P < 0.001) associated with both 2-hour post-load plasma glucose and serum glycosylated haemoglobin.

Conclusions
EZSCAN might be useful in screening diabetes mellitus with reasonable sensitivity and specificity.
Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles
Authors: Jacot William , Lopez-Crapez Evelyne , Thezenas Simon , Senal Romain , Fina Frédéric , Bibeau Frédéric , Romieu Gilles , Lamy Pierre-Jean 
Published: December 2011

Abstract
Introduction
Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC.

Methods
We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples.

Results
HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified.

Conclusions
This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population.
Characterisation of adiponectin multimers and the IGF axis in humans with a heterozygote mutation in the tyrosine kinase domain of the insulin receptor gene
Authors: Højlund Kurt , Beck-Nielsen Henning , Flyvbjerg Allan , Frystyk Jan 
Published: December 2011

ObjectiveLow levels of adiponectin, IGF-binding protein 1 (IGFBP1) and IGFBP2 and high levels of leptin correlate with several indices of insulin resistance and risk of type 2 diabetes. However, in insulin receptoropathies, plasma adiponectin is paradoxically increased despite severe insulin resistance, whereas the IGF axis is sparsely described. Here, we aimed to characterise the multimeric distribution of adiponectin and the IGF axis in humans with a heterozygous INSR mutation (Arg1174Gln).MethodsBlood samples obtained from six Arg1174Gln carriers and ten lean, healthy controls before and after a euglycaemic–hyperinsulinaemic clamp were examined for plasma adiponectin multimers, leptin, total IGF1, IGF2, free IGF1, IGFBP1 and IGFBP2.ResultsDespite tenfold elevated fasting insulin and marked insulin resistance in Arg1174Gln carriers, the levels of total adiponectin, leptin, IGFBP1 and IGFBP2 were similar to those observed in controls, while total IGF1, IGF2 and free IGF1 levels were increased. The relative fraction of high-molecular weight adiponectin was increased, whereas both the absolute concentration and the fraction of low-molecular weight adiponectin were decreased in Arg1174Gln carriers. Interestingly, exogenous insulin failed to suppress total adiponectin in Arg1174Gln carriers, but reduced IGFBP1 and increased IGFBP2 as in controls.ConclusionThe normal levels of adiponectin, IGFBP1 and IGFBP2 in the face of highly elevated insulin levels suggest an impaired ability of insulin to suppress markers of common insulin resistance in carriers of a dominant-negative INSR mutation. However, together with the adaptive increases in IGF1 and IGF2 and a potentially improved distribution of adiponectin multimers, these changes may contribute to rescue insulin action in insulin receptor-deficient individuals.
The use of “High Dose” Dexmedetomidine in a Patient with Critical
Tracheal Stenosis and Anterior Mediastinal Mass
Authors: Voscopoulos C. , Kirk F.L. , Lovrincevic M. , Lema M. 
Published: December 2011

The anterior medial mass patient continues to offer great challenges for the anesthesiologist. As such, newer
and safer methods of providing anesthetic care are continually being sought. To this end, there is a growing body of
evidence that may suggest that higher than Food and Drug Administration approved dosages of dexmedetomidine may
offer another option in the arsenal of the anesthesiologist in this patient population.
We recently cared for a middle aged male who presented with a large mediastinal mass, extrinsic compression critical
tracheal stenosis, superior vena cava syndrome, and massive supraclavicular lymphadenopathy, scheduled for tracheal
stent placement, biopsy, and diagnostic evaluation of the esophagus. After reviewing anesthetic options, we deemed the
safest technique available to us to be the use of a high dose dexmedetomidine based technique with continuous infusion
rate of 2mcg/kg/hr. Spontaneous respirations were maintained throughout the case, with a stable heart rate and blood
pressure, and our patient tolerated the procedure without complications.
Putting People at the Center of Climate Change Adaptation Plans: A Vulnerability Approach
Authors: Rumbach Andrew J. , Kudva Neema 
Published: December 2011

AbstractThe majority of research and writing on climate change and planning focuses on mitigation, reducing emissions and climate change impacts over long time cycles. However, the realization that human settlements will see immediate and near‐term impacts, regardless of emissions reductions, has given urgency to questions about how communities will adapt. We are interested in municipal level adaptation plans: “incipient plans” where implementation has either just begun or not even started, and evaluation and rethinking belong to the future. Our intention is to inform this process. We reviewed more than a dozen municipal and regional climate change and adaptation planning processes, and selected six to examine further. Our case selection includes plans from coastal and inland cities, both large and small, and all but one are from counties amongst the most vulnerable in the U.S. We found that while mitigation of green house gases (GHGs), which is important and necessary, was central to all plans, adaptation strategies were not considered to the same extent or left out completely. We argue that an adaptation strategy that uses a vulnerability approach can be the most effective way to assess climate risk because it puts people and communities at the center of the analysis; helps planners and policy makers to design adaptation strategies that will reduce suffering in local areas while making effective use of scarce resources; and enables better coordination among different elements of planning. To be efficient and effective, adaptation plans must be generated at different scales and must downscale climate information to a local level. Most importantly, the first step in adaptation planning must be to understand vulnerability and the full range of variables that contribute to it. We conclude by suggesting that cities must integrate climate action strategies into their long‐range Comprehensive Plans to take full advantage of the targeting and coordination possibilities that a vulnerability approach offers.
Perceiving Need for Lifestyle Counseling
Authors: Salmela Sanna M. , Vähäsarja Kati A. , Villberg Jari J. , Vanhala Mauno J. , Saaristo Timo E. , Lindström Jaana , Oksa Heikki H. , Korpi-Hyövälti Eeva A.-L. , Moilanen Leena , Keinänen-Kiukaanniemi Sirkka , Poskiparta Marita E. 
Published: December 2011

OBJECTIVE
To investigate the proportion of individuals at high risk of type 2 diabetes who perceive the need for lifestyle counseling, factors associated with this perception, and whether the perceived need is associated with subsequent attendance in lifestyle intervention.

RESEARCH DESIGN AND METHODS
Baseline and intervention data were obtained from 10,149 participants in a Finnish National Diabetes Prevention Project.

RESULTS
In total, 36% of men and 52% of women perceived the need for counseling. Most of the risk factors did not increase the perceived need for counseling. Those agreeing to attend supervised lifestyle intervention were more likely to report a perceived need than those who agreed on a self-initiated lifestyle change or those who refused to attend lifestyle intervention. The perceived need was associated with actual attendance in the lifestyle intervention only among women.

CONCLUSIONS
It will be vital to find additional means to support lifestyle change.
Glucose Metabolism in 105 Children and Adolescents After Pancreatectomy for Congenital Hyperinsulinism
Authors: Beltrand Jacques , Caquard Marylène , Arnoux Jean-Baptiste , Laborde Kathleen , Velho Gilberto , Verkarre Virginie , Rahier Jacques , Brunelle Francis , Nihoul-Fékété Claire , Saudubray Jean-Marie , Robert Jean-Jacques , de Lonlay Pascale 
Published: December 2011

OBJECTIVE
To describe the long-term metabolic outcome of children with congenital hyperinsulinism after near-total or partial elective pancreatectomy.

RESEARCH DESIGN AND METHODS
Patients (n = 105: 58 diffuse and 47 focal congenital hyperinsulinism) received operations between 1984 and 2006. Follow-up consisted of periodic measurements of pre- and postprandial plasma glucose over 24 h, OGTT, and IVGTT. Cumulative incidence of hypo- or hyperglycemia/insulin treatment was estimated by Kaplan-Meier analysis.

RESULTS
After near-total pancreatectomy, 59% of children with diffuse congenital hyperinsulinism still presented mild or asymptomatic hypoglycemia that responded to medical treatments and disappeared within 5 years. One-third of the patients had both preprandial hypoglycemia and postprandial hyperglycemia. Hyperglycemia was found in 53% of the patients immediately after surgery; its incidence increased regularly to 100% at 13 years. The cumulative incidence of insulin-treated patients was 42% at 8 years and reached 91% at 14 years, but the progression to insulin dependence was very variable among the patients. Plasma insulin responses to IVGTT and OGTT correlated well with glycemic alterations. In focal congenital hyperinsulinism, hypoglycemia or hyperglycemia were rare, mild, and transient.

CONCLUSIONS
Patients with focal congenital hyperinsulinism are cured of hypoglycemia after limited surgery, while the outcome of diffuse congenital hyperinsulinism is very variable after near-total pancreatectomy. The incidence of insulin-dependent diabetes is very high in early adolescence.
A Single Nucleotide Polymorphism Associates With the Response of Muscle ATP Synthesis to Long-Term Exercise Training in Relatives of Type 2 Diabetic Humans
Authors: Kacerovsky-Bielesz Gertrud , Kacerovsky Michaela , Chmelik Marek , Farukuoye Michaela , Ling Charlotte , Pokan Rochus , Tschan Harald , Szendroedi Julia , Schmid Albrecht Ingo , Gruber Stephan , Herder Christian , Wolzt Michael , Moser Ewald , Pacini Giovanni , Smekal Gerhard , Groop Leif , Roden Michael 
Published: December 2011

OBJECTIVE
Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort.

RESEARCH DESIGN AND METHODS
A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (Vo2) during incremental tests and from maximal torque of knee flexors (MaxTflex) and extensors (MaxText) using isokinetic dynamometry. fATP and ectopic lipids were measured with 1H/31P magnetic resonance spectroscopy.

RESULTS
Endurance training increased power output and Vo2 by 44 and 30%, respectively (both P &lt; 0.001), whereas resistance training increased MaxText and MaxTflex by 23 and 40%, respectively (both P &lt; 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL ⋅ min−1 ⋅ m−2) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 μmol ⋅ mL−1 ⋅ m−1 (P &lt; 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I.

CONCLUSIONS
Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.
Drogues et conflits : éléments pour une modélisation
Authors: Labrousse Alain 
Published: December 2011

Résumé Les relations entre drogues et conflits ont leur racine dans l’histoire. Mais c’est durant la guerre froide qu’elles prennent une acuité particulière. Après la chute du mur de Berlin, elles se démocratisent et se retrouvent dans la plupart des conflits locaux, ce qui permet de les modéliser. La spécificité de ces relations repose sur des modalités propres au trafic de drogue, en particulier « l’escalade des profits » qui permet aux groupes armés de se greffer au niveau d’articulation des différentes étapes de la production, de la transformation des drogues ainsi qu’à celui du franchissements des différents obstacles sur les routes qui mènent des zones de production aux marchés de consommation. Les exemples de la guérilla colombienne et des talibans afghans ou d’autres suggèrent que lorsque des groupes qui se battent dans les zones de production utilisent l’alibi de la défense des producteurs pour s’insérer dans le système des drogues, ils interviennent en général au niveau du trafic au risque de se criminaliser. Risque auquel n’échappent pas non plus les forces de répression.