bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Sequence of Pseudomonas aeruginosa PA45, a Highly Virulent Strain Isolated from a Patient with Bloodstream Infection
Authors: Segata Nicola , Ballarini Annalisa , Jousson Olivier
Published: May 2013

Pseudomonas aeruginosa
is a ubiquitous opportunistic pathogen causing a broad range of infections in humans. We provide the draft genome sequence of the recently identified and highly virulent
P. aeruginosa
PA45 strain. Its 6.6-Mb genome contains 6,822 genes, including an unparalleled number of virulence genes, which might explain its aggressive phenotype.
Cellular schwannoma masquerading as malignant peripheral nerve sheath tumour: a diagnostic dilemma
Authors: Alam Kiran , Jain Anshu , Misra Aroonima , khan A H
Published: May 2013

We present a case of a 15-year-old girl with a pulsatile, rapidly enlarging mass at the root of the nose suspected to be malignant. Excisional biopsy showed worrisome histological features; however, a final diagnosis of cellular schwannoma was reached excluding the possibility of malignant peripheral nerve sheath tumour by histological and immunohistochemical attributes. Cellular schwannoma, a pseudosarcomatous entity, is a rare benign neoplasm that may cause bone erosion and may be mistaken for a malignancy, clinically and histologically. Diagnosis of cellular schwannoma is essential to prevent mismanagement as it never metastasises and responds to local excision as opposed to aggressive treatment required by a malignant neoplasm.
Tandem symptomatic internal carotid artery and persistent hypoglossal artery stenosis treated by endovascular stenting and flow reversal
Authors: Eller Jorge L , Jahshan Shady , Dumont Travis M , Kan Peter , Siddiqui Adnan H
Published: May 2013

Persistence of the hypoglossal artery into adulthood is a rare vascular anomaly and, when present, provides the predominant vascular supply to the posterior circulation. We describe a case of vertebrobasilar insufficiency associated with severe high-grade stenosis of the persistent hypoglossal artery and tandem stenosis of the proximal ipsilateral internal carotid artery, treated by an endovascular approach. The unique anatomical and technical challenges associated with this case are reviewed in detail.
Isolated diffuse type B-cell lymphoma of the palate: an unusual entity
Authors: Roche Phoebe , O'Neill Paul , Kavanagh Eoin , Rowley Helena
Published: May 2013

Lymphomas frequently occur as extranodal lesions in the head and neck, but are rarely seen in the palate. We present a case of isolated diffuse type B-cell lymphoma of the palate, which occurred in a 28-year-old man. The patient had no history of immune compromise, and he presented to the emergency department with a 7-month history of a painful, non-healing ulcerative mass in the hard and soft palate. Positron emission tomography facilitated pretreatment assessment of the extent and activity of the lesion. Histopathological and immunohistochemical analyses of biopsied tissue confirmed a diagnosis of diffuse type B-cell lymphoma. The clinical findings and therapeutic challenges in this heterogeneous group of malignancies are discussed.
Multiple solitary plasmacytoma with multifocal bone involvement. First clinical case report in a uraemic patient
Authors: Dattolo Pietro , Allinovi Marco , Michelassi Stefano , Pizzarelli Francesco
Published: May 2013

Multiple solitary plasmacytoma (MSP) is a rare plasma cell dyscrasia, characterised by multiple lesions of neoplastic monoclonal plasma cells. It differs from multiple myeloma by the lack of hypercalcaemia, renal insufficiency, anaemia and pathological monoclonal plasmocytosis on a random bone biopsy. We present the case of an MSP described for the first time in a patient on peritoneal dialysis. There are only few cases of MSP described in literature, and we performed a review of these cases trying to systematise the topic. The increasing clinical use of CT, MRI and positron emission tomography will enhance in the future the correct diagnosis of MSP.
Hypoparathyroidism presenting as cognitive dysfunction
Authors: Kumar Gunjan , Kaur Darshpreet , Aggarwal Puneet , Khurana Tilak
Published: May 2013

Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education.
‘Legal high’ associated Wallenberg syndrome
Authors: Arora Alok , Kumar Anil , Raza Muhammad Naeem
Published: May 2013

‘Legal highs’ are substances of synthetic or natural origin having psychotropic properties. ‘Legal highs’ are often new and, in many cases, the actual chemical ingredients in a branded product can be changed without notifications and the risks are unpredictable. Acute recreational drug toxicity is a common reason for presentation to both hospital and prehospital medical services. It appears that, generally, the pattern of toxicity associated with ‘legal highs’ is broadly similar to that seen with classical stimulant recreational drugs such as cocaine, MDMA (3,4 methylenedioxy-N-methyl amphetamine) and amphetamine. Lack of clear literature pertaining to their chemical properties, pharmacology and toxicology makes an evaluation of their effects difficult. We describe a unique case in which consumption of such a substance led to hospital admission and a diagnosis of ‘lateral medullary stroke’ or ‘Wallenberg syndrome’. We believe that this is the first described case of a ‘legal high’ intake linked to a posterior circulation stroke.
Co-infusion of adipose tissue derived mesenchymal stem cell-differentiated insulin-making cells and haematopoietic cells with renal transplantation: a novel therapy for type 1 diabetes mellitus with end-stage renal disease
Authors: Dave Shruti D , Vanikar Aruna V , Trivedi Hargovind L
Published: May 2013

Type 1 diabetes mellitus (T1DM) is a common cause of end-stage renal disease (ESRD). Various factors contribute to wide fluctuations in blood glucose levels and exogenous insulin requirement in such patients even after renal transplantation (RT). Simultaneous pancreas–kidney transplantation is one of the therapies for these patients. Stem cell (SC) therapy for T1DM and for minimisation of immunosuppression after RT has shown encouraging results. We report a 30-year-old-man with T1DM since 15 years and ESRD since 2 years, who underwent living donor RT  and co-infusion of in vitro generated insulin-making cells differentiated from donor adipose tissue derived mesenchymal stem cells  and bone marrow -derived haematopoietic SC  into subcutaneous tissue, portal and thymic circulation under non-myeloablative conditioning. Over follow-up of 13 months he has stable graft function with serum creatinine, 1.2 mg/dl, zero rejection and glycosylated haemoglobin level of 6.1% on calcineurin-inhibitor based therapy.
The Housestaff Incentive Program: improving the timeliness and quality of discharge summaries by engaging residents in quality improvement
Authors: Bischoff Kara , Goel Aparna , Hollander Harry , Ranji Sumant R , Mourad Michelle
Published: May 2013

Background

Quality improvement has become increasingly important in the practice of medicine; however, engaging residents in meaningful projects within the demanding training environment remains challenging.

Methods

We conducted a year-long quality improvement project involving internal medicine residents at an academic medical centre. Resident champions designed and implemented a discharge summary improvement bundle, which employed an educational curriculum, an electronic discharge summary template, regular data feedback and a financial incentive. The timeliness and quality of discharge summaries were measured before and after the intervention. Residents and faculty were surveyed about their perceptions of the project; primary care providers were surveyed about their satisfaction with hospital provider communication.

Results

With implementation of the bundle, the average time from patient discharge to completion of the discharge summary fell from 3.5 to 0.61 days (p<0.001). The percentage of summaries completed on the day of discharge rose from 38% to 83% (p<0.001) and this improvement was sustained for 6 months following the end of the project. The percentage of summaries that included all recommended elements increased from 5% to 88% (p<0.001). Primary care providers reported a lower likelihood of discharge summaries being unavailable at the time of outpatient follow-up (38% to 4%, p<0.001). Residents reported that the systems changes, more than the financial incentive, accounted for their behaviour change.

Conclusions

Our discharge summary improvement project provides an instructive example of how residents can lead clinically meaningful quality improvement projects.
The pursuit of better diagnostic performance: a human factors perspective
Authors: Henriksen Kerm , Brady Jeff
Published: May 2013

Despite the relatively slow start in treating diagnostic error as an amenable research topic at the beginning of the patient safety movement, interest has steadily increased over the past few years in the form of solicitations for research, regularly scheduled conferences, an expanding literature and even a new professional society. Yet improving diagnostic performance increasingly is recognised as a multifaceted challenge. With the aid of a human factors perspective, this paper addresses a few of these challenges, including questions that focus on who owns the problem, treating cognitive and system shortcomings as separate issues, why knowledge in the head is not enough, and what we are learning from health information technology (IT) and the use of checklists. To encourage empirical testing of interventions that aim to improve diagnostic performance, a systems engineering approach making use of rapid-cycle prototyping and simulation is proposed. To gain a fuller understanding of the complexity of the sociotechnical space where diagnostic work is performed, a final note calls for the formation of substantive partnerships with those in disciplines beyond the clinical domain.
Cervical spine clearance in the elderly: do elderly patients get a bad deal?
Authors: Edwards M A , Verwey J , Herbert S , Horne S , Smith J E
Published: May 2013

Objective

To investigate whether elderly patients, presenting following trauma and requiring immobilisation and imaging of the cervical spine, require increased use of CT and spend longer immobilised when compared to the younger population.

Methods

A retrospective chart review was undertaken of 35 adults aged 18–65 years, and 32 adults over 65 years, requiring cervical spine imaging following trauma.

Results

1 of the 35 younger patients, and 16 of the 32 elderly patients, underwent CT. Elderly patients spent 1:05 h longer immobilised (p<0.005).

Conclusions

Half of the elderly patients underwent CT, and they were immobilised for significantly longer than younger patients. Measures should be adopted to facilitate early diagnosis and mitigate complications of prolonged immobilisation in elderly patients with neck trauma.
Impact of stops for road traffic accidents on the inter-hospital transport of critically ill children
Authors: Raman Sainath , Ramnarayan Padmanabhan
Published: May 2013

Transport of critically ill children has become necessary following centralisation of paediatric specialist services. Children's Acute Transport Service (CATS) retrieves critically ill children in the Greater London area. Our teams have had to stop during these journeys to assist in road traffic accidents or ill passers-by. We undertook a review of our practice over a 3.5-year period. Our teams had to stop on 12 occasions over this period amounting to an incidence rate of 1 per 959 ambulance journeys. Although this is an infrequent occurrence, the impact on the retrieved patient and service delivery could be significant. We would like to direct the attention of transport services to this problem.
The relationship between hyperlactatemia and microcirculation in the thenar eminence as measured using near-infrared spectroscopy in patients with sepsis
Authors: Soga Taketomo , Sakatani Kaoru , Yagi Tsukasa , Kawamorita Tsuyoshi , Yoshino Atsuo
Published: May 2013

Objective

Near-infrared spectroscopy (NIRS)-derived variables during a vascular occlusion test (VOT) have recently been used to evaluate peripheral circulatory insufficiency in patients with sepsis. We investigated the relationship between NIRS-derived variables and the lactate concentration during sepsis.

Methods

This was a prospective observational study. Forty-one patients with sepsis were divided into two groups according to their blood lactate concentration: a high lactate group (≥2.0 mmol/l; n=15) and a normal lactate group (<2.0 mmol/l; n=26). NIRS was used to evaluate the tissue oxygen index (TOI) at the thenar eminence before and after a VOT. VOT was performed by sphygmomanometer cuff inflation around upper arm for 3 min. The TOI value before VOT was defined as the TOI baseline, the TOI value immediately after VOT was defined as the minimum TOI and the TOI value after releasing the muscle from the VOT was defined as the TOI after VOT. The ΔTOI was defined as the difference between the TOI after VOT and minimum TOI.

Results

NIRS-derived variables had significant differences between the normal lactate group and the high lactate group with respect to the TOI baseline (median: 65% vs 55%, p=0.01), TOI after VOT (median: 65% vs 46%, p<0.001) and ΔTOI (median: 19% vs 6%, p<0.001). The lactate concentration was significantly correlated with the TOI after VOT (R=0.594, p<0.001), TOI baseline (R=0.513, p<0.001), ΔTOI (R=0.488, p=0.001) and minimum TOI (R=0.377, p=0.02).

Conclusions

We revealed a significant correlation between NIRS-derived variables and the lactate concentration during sepsis.
Accuracy of visual assessments of proliferation indices in gastroenteropancreatic neuroendocrine tumours
Authors: Young Helen T M , Carr Norman J , Green Bryan , Tilley Charles , Bhargava Vidhi , Pearce Neil
Published: May 2013

Aims

To compare the accuracy of eyeball estimates of the Ki-67 proliferation index (PI) with formal counting of 2000 cells as recommend by the Royal College of Pathologists.

Methods

Sections from gastroenteropancreatic neuroendocrine tumours were immunostained for Ki-67. PI was calculated using three methods: (1) a manual tally count of 2000 cells from the area of highest nuclear labelling using a microscope eyepiece graticule; (2) eyeball estimates made by four pathologists within the same area of highest nuclear labelling; and (3) image analysis of microscope photographs taken from this area using the ImageJ ‘cell counter’ tool. ImageJ analysis was considered the gold standard for comparison.

Results

Levels of agreement between methods were evaluated using Bland–Altman plots. Agreement between the manual tally and ImageJ assessments was very high at low PIs. Agreement between eyeball assessments and ImageJ analysis varied between pathologists. Where data for low PIs alone were analysed, there was a moderate level of agreement between pathologists’ estimates and the gold standard, but when all data were included, agreement was poor.

Conclusions

Manual tally counts of 2000 cells exhibited similar levels of accuracy to the gold standard, especially at low PIs. Eyeball estimates were significantly less accurate than the gold standard. This suggests that tumour grades may be misclassified by eyeballing and that formal tally counting of positive cells produces more reliable results. Further studies are needed to identify accurate clinically appropriate ways of calculating.
T-cell clonality is detected in a high frequency among patients with incidental lymphocytosis by PCR assays forTCRgene rearrangements
Authors: Cao Fenglin , Wang Shuye , Zhao Hui , Zhou Jin , Yang Guisheng , Wang Chen
Published: May 2013

Aims

Clonal expansion of lymphocytes may account for asymptomatic lymphocytosis. Unlike monoclonal B lymphocytosis, the detection of T-cell clones is difficult using immunophenotype-based assays. This study aimed to evaluate PCR-based clonality assays for the identification of T-cell clones among patients with unexplained lymphocytosis.

Methods

We incorporated the BIOMED-2 multiplex PCR into the investigation of peripheral lymphocytosis. Clonality analysis was performed with three reactions forTCRβand two reactions forTCRγgene rearrangements. The analysis was performed with blood specimens from a total of 150 adult patients who presented with incidental lymphocytosis.

Results

PCR assays were validated using confirmed T-cell malignancies and the detection sensitivity was determined at a level of 2%. Using theTCRβandTCRγcombination, 25 (16.6%) of 150 patients were found to have clonalTCRarrangement. Patients who harboured clonal T cells presented with a mild to moderate absolute lymphocytosis, with a median lymphocyte count of 4.5 × 109/l (range 3.7–9.8 × 109) and the absence of other haematological abnormalities. Immunophenotyping confirmed T-cell lymphocytosis with an increase in CD8 T cells in the majority of patients.

Conclusions

This study demonstrated the use of PCR assays for the effective detection of clonal T lymphocytosis. Our data indicate a high prevalence of silent T-cell clones among patients with peripheral lymphocytosis.
Usual interstitial pneumonia-patternfibrosis in surgical lung biopsies. Clinical, radiological and histopathological clues to aetiology
Authors: Smith Maxwell , Dalurzo Mercedes , Panse Prasad , Parish James , Leslie Kevin
Published: May 2013

Pulmonary fibrosis in surgical lung biopsies is said to have a ‘usual interstitial pneumonia-pattern’ (UIP-pattern) of disease when scarring of the parenchyma is present in a patchy, ‘temporally heterogeneous’ distribution. These biopsies are one of the more common non-neoplastic specimens surgical pathologists encounter and often pose a number of challenges. UIP is the expected histopathological pattern in patients with clinical idiopathic pulmonary fibrosis (IPF), but the UIP-patterncan be seen in other conditions on occasion. Most important among these are the rheumatic interstitial lung diseases (RILD) and chronic hypersensitivity pneumonitis (CHrHP). Because theses entities have different mechanisms of injury, approach to therapy, and expected clinical progression, it is imperative for the surgical pathologist to correctly classify them. Taken in isolation, the UIP-patternseen in patients with IPF may appear to overlap with that of RILD and CHrHP, at least when using the broadest definition of this term (patchy fibrosis). However, important distinguishing features are nearly always present in our experience, and the addition of a multidisciplinary approach will often resolve the critical differences between these diseases. In this manuscript, we review the distinguishing clinical, radiologic and histopathological features of UIP of IPF, RILD and CHrHP, based, in part, on the existing literature, but also lessons learned from a busy lung biopsy consultation practice.
Understanding perceptions of genital herpes disclosure through analysis of an online video contest
Authors: Catallozzi Marina , Ebel Sophia C , Chávez Noé R , Shearer Lee S , Mindel Adrian , Rosenthal Susan L
Published: May 2013

Objective

The aims of this study were to examine pre-existing videos in order to explore the motivation for, possible approaches to, and timing and context of disclosure of genital herpes infection as described by the lay public.

Methods

A thematic content analysis was performed on 63 videos submitted to an Australian online contest sponsored by the Australian Herpes Management Forum and Novartis Pharmaceuticals designed to promote disclosure of genital herpes.

Results

Videos either provided a motivation for disclosure of genital herpes or directed disclosure without an explicit rationale. Motivations included manageability of the disease or consistency with important values. Evaluation of strategies and logistics of disclosure revealed a variety of communication styles including direct and indirect. Disclosure settings included those that were private, semiprivate and public. Disclosure was portrayed in a variety of relationship types, and at different times within those relationships, with many videos demonstrating disclosure in connection with a romantic setting.

Conclusions

Individuals with genital herpes are expected to disclose to susceptible partners. This analysis suggests that understanding lay perspectives on herpes disclosure to a partner may help healthcare providers develop counselling messages that decrease anxiety and foster disclosure to prevent transmission.
Genetic diversity inTrichomonas vaginalis
Authors: Meade John C , Carlton Jane M
Published: May 2013

Recent advances in genetic characterisation ofTrichomonas vaginalisisolates show that the extensive clinical variability in trichomoniasis and its disease sequelae are matched by significant genetic diversity in the organism itself, suggesting a connection between the genetic identity of isolates and their clinical manifestations. Indeed, a high degree of genetic heterogeneity inT vaginalisisolates has been observed using multiple genotyping techniques. A unique two-type population structure that is both local and global in distribution has been identified, and there is evidence of recombination within each group, although sexual recombination between the groups appears to be constrained. There is conflicting evidence in these studies for correlations betweenT vaginalisgenetic identity and clinical presentation, metronidazole susceptibility, and the presence ofT vaginalisvirus, underscoring the need for adoption of a common standard for genotyping the parasite. Moving forward, microsatellite genotyping and multilocus sequence typing are the most robust techniques for future investigations ofT vaginalisgenotype-phenotype associations.
Diagnostic imaging: reflecting on the past and looking to the future
Authors: Johnson Victoria
Published: May 2013

Victoria Johnson traces the development of veterinary diagnostic imaging from its earliest stages to the present day and considers the challenges and changes ahead.
Self-Organization and the Self-Assembling Process in Tissue Engineering
Authors: Athanasiou Kyriacos A. , Eswaramoorthy Rajalakshmanan , Hadidi Pasha , Hu Jerry C.
Published: May 2013

In recent years, the tissue engineering paradigm has shifted to include a new and growing subfield of scaffoldless techniques that generate self-organizing and self-assembling tissues. This review aims to cogently describe this relatively new research area, with special focus on applications toward clinical use and research models. Particular emphasis is placed on providing clear definitions of self-organization and the self-assembling process, as delineated from other scaffoldless techniques in tissue engineering and regenerative medicine. Significantly, during formation, self-organizing and self-assembling tissues display biological processes similar to those that occur in vivo. These processes help lead to the recapitulation of native tissue morphological structure and organization. Notably, functional properties of these engineered tissues, some of which are already in clinical trials, also approach native tissue values. This review endeavors to provide a cohesive summary of work in this field and to highlight the potential of self-organization and the self-assembling process for providing cogent solutions to currently intractable problems in tissue engineering.
Genome Engineering at the Dawn of the Golden Age
Authors: Segal David J. , Meckler Joshua F.
Published: May 2013

Genome engineering—the ability to precisely alter the DNA information in living cells—is beginning to transform human genetics and genomics. Advances in tools and methods have enabled genetic modifications ranging from the “scarless” correction of a single base pair to the deletion of entire chromosomes. Targetable nucleases are leading the advances in this field, providing the tools to modify any gene in seemingly any organism with high efficiency. Targeted gene alterations have now been reported in more than 30 diverse species, ending the reign of mice as the exclusive model of mammalian genetics, and targetable nucleases have been used to modify more than 150 human genes and loci. A nuclease has also already entered clinical trials, signaling the beginning of genome engineering as therapy. The recent dramatic increase in the number of investigators using these techniques signifies a transition away from methods development toward a new age of exciting applications.
Racial Formation in Perspective: Connecting Individuals, Institutions, and Power Relations
Authors: Saperstein Aliya , Penner Andrew M. , Light Ryan
Published: May 2013

Over the past 25 years, since the publication of Omi & Winant's Racial Formation in the United States, the statement that race is socially constructed has become a truism in sociological circles. Yet many struggle to describe exactly what the claim means. This review brings together empirical literature on the social construction of race from different levels of analysis to highlight the variety of approaches to studying racial formation processes. For example, macro-level scholarship often focuses on the creation of racial categories, micro-level studies examine who comes to occupy these categories, and meso-level research captures the effects of institutional and social context. Each of these levels of analysis has yielded important contributions to our understanding of the social construction of race, yet there is little conversation across boundaries. Scholarship that bridges methodological and disciplinary divides is needed to continue to advance the racial formation perspective and demonstrate its broader relevance.
Sociology of Fashion: Order and Change
Authors: Aspers Patrik , Godart Frédéric
Published: May 2013

In this article, we synthesize and analyze sociological understanding of fashion, with the main part of the review devoted to classical and recent sociological work. To further the development of this largely interdisciplinary field, we also highlight the key points of research in other disciplines. We define fashion as an unplanned process of recurrent change against a backdrop of order in the public realm. We clarify this definition after tracing fashion's origins and history. As a social phenomenon, fashion has been culturally and economically significant since the dawn of Modernity and has increased in importance with the emergence of mass markets, in terms of both production and consumption. Most research on this topic is concerned with dress, but we argue that there are no domain restrictions that should constrain fashion theories. We identify venues around which sociologists could develop further research in this field.
Activation of muscarinic M3 receptors inhibits large-conductance voltage- and Ca2+-activated K+ channels in rat urinary bladder smooth muscle cells
Authors: Parajuli Shankar P. , Petkov Georgi V.
Published: May 2013

Large conductance voltage- and Ca2+-activated K+ (BK) channels are key regulators of detrusor smooth muscle (DSM) contraction and relaxation during urine voiding and storage. Here, we explored whether BK channels are regulated by muscarinic receptors (M-Rs) in native freshly isolated rat DSM cells under physiological conditions using the perforated whole cell patch-clamp technique and pharmacological inhibitors. M-R activation with carbachol (1 μM) initially evoked large transient outward BK currents, followed by inhibition of the spontaneous transient outward BK currents (STBKCs) in DSM cells. Carbachol (1 μM) also inhibited the amplitude and frequency of spontaneous transient hyperpolarizations (STHs) and depolarized the DSM cell membrane potential. Selective inhibition of the muscarinic M3 receptors (M3-Rs) with 4-diphenylacetoxy- N-methylpiperidine (4-DAMP; 0.1 μM), but not muscarinic M2 receptors with methoctramine (1 μM), blocked the carbachol inhibitory effects on STBKCs. Furthermore, blocking the inositol 1,4,5-triphosphate (IP3) receptors with xestospongin-C (1 μM) inhibited the carbachol-induced large transient outward BK currents without affecting carbachol inhibitory effects on STBKCs. Upon pharmacological inhibition of all known cellular sources of Ca2+ for BK channel activation, carbachol (1 μM) did not affect the voltage-step-induced steady-state BK currents, suggesting that the muscarinic effects in DSM cells are mediated by mobilization of intracellular Ca2+. In conclusion, our findings provide strong evidence that activation of M3-Rs leads to inhibition of the STBKCs, STHs, and depolarization of DSM cells. Collectively, the data suggest the existence of functional interactions between BK channels and M3-Rs at a cellular level in DSM.
Identification of a high-mannose ICAM-1 glycoform: effects of ICAM-1 hypoglycosylation on monocyte adhesion and outside in signaling
Authors: Scott David W. , Dunn Taylor S. , Ballestas Mary E. , Litovsky Silvio H. , Patel Rakesh P.
Published: May 2013

Endothelial adhesion molecules are critical effectors of inflammation ensuring coordinated interactions that allow leukocytes to home to sites of injury. These adhesion molecules are often extensively modified posttranslationaly by the addition of N-glycans, but if, or how, these modifications contribute to the protein function remains poorly understood. Herein we show that activated endothelial cells express two distinct N-glycoforms of intercellular adhesion molecule 1 (ICAM-1) that comprise a complex N-glycoform with α-2,6 sialic acid present at relatively high levels and a second, less abundant and previously undescribed high-mannose glycoform (HM-ICAM-1). This novel HM-ICAM-1 glycoform was also detected in human coronary artery specimens and moreover appeared to be the dominant glycoform in vivo. Production of exclusively HM-ICAM-1 in cells by α-mannosidase inhibition increased monocyte rolling and adhesion compared with mature ICAM-1 consistent with high-mannose epitopes providing leukocyte ligands. Cross-linking of ICAM-1 transmits outside-in signals that affect endothelial permeability and survival. Interestingly, cell signaling (assessed using ERK, VE-cadherin, and Akt phosphorylation) was maintained after cross-linking of HM-ICAM-1 compared with mature ICAM-1; however, interactions with the actin cytoskeleton were lost with HM-ICAM-1. These findings suggest that specific ICAM-1 N-glycoforms modulate distinct aspects of the inflammatory response and identify HM-ICAM-1 as a new therapeutic target for controlling leukocyte trafficking and endothelial inflammation.
PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells
Authors: Zachos Nicholas C. , Lee Luke J. , Kovbasnjuk Olga , Li Xuhang , Donowitz Mark
Published: May 2013

Elevated levels of intracellular Ca2+ ([Ca2+]i) inhibit Na+/H+ exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca2+]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca2+ signaling proteins necessary for regulation of NHE3 activity. [Ca2+]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca2+]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y416 phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca2+]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca2+]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca2+]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.
Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation
Authors: Nayebosadri Arman , Ji Julie Y.
Published: May 2013

The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an anti-inflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm2) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-κB inhibitor alpha (NF-κBIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction.
Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response
Authors: Singh Kshipra , Coburn Lori A. , Barry Daniel P. , Asim Mohammad , Scull Brooks P. , Allaman Margaret M. , Lewis Nuruddeen D. , Washington M. Kay , Rosen Michael J. , Williams Christopher S. , Chaturvedi Rupesh , Wilson Keith T.
Published: May 2013

l-Arginine (l-Arg) is a semiessential amino acid that has altered availability in human ulcerative colitis (UC), a form of inflammatory bowel disease, and is beneficial in murine colitis induced by dextran sulfate sodium (DSS), a model with similarity to UC. We assessed the role of cationic amino acid transporter 2 (CAT2), the inducible transporter of l-Arg, in DSS colitis. Expression of CAT2 was upregulated in tissues from colitic mice and localized predominantly to colonic macrophages. CAT2-deficient (CAT2−/−) mice exposed to DSS exhibited worsening of survival, body weight loss, colon weight, and histological injury. These effects were associated with increased serum l-Arg and decreased tissue l-Arg uptake and inducible nitric oxide synthase protein expression. Clinical benefits of l-Arg supplementation in wild-type mice were lost in CAT2−/−mice. There was increased infiltration of macrophages, dendritic cells, granulocytes, and T cells in colitic CAT2−/−compared with wild-type mice. Cytokine profiling revealed increases in proinflammatory granulocyte colony-stimulating factor, macrophage inflammatory protein-1α, IL-15, and regulated and normal T cell-expressed and -secreted and a shift from an IFN-γ- to an IL-17-predominant T cell response, as well as an increase in IL-13, in tissues from colitic CAT2−/−mice. However, there were no increases in other T helper cell type 2 cytokines, nor was there a global increase in macrophage-derived proinflammatory cytokines. The increase in IL-17 derived from both CD4 and γδ T cells and was associated with colonic IL-6 expression. Thus CAT2 plays an important role in controlling inflammation and IL-17 activation in an injury model of colitis, and impaired l-Arg availability may contribute to UC pathogenesis.
Translational aspects of rectal evoked potentials: a comparative study in rats and humans
Authors: Nissen Thomas Dahl , Brock Christina , Graversen Carina , Coen Steven J. , Hultin Leif , Aziz Qasim , Lykkesfeldt Jens , Drewes Asbjørn Mohr
Published: May 2013

Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21–56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain.
Time course of regional vascular adaptations to low load resistance training with blood flow restriction
Authors: Hunt Julie E. A. , Galea Dermot , Tufft Graham , Bunce Danny , Ferguson Richard A.
Published: May 2013

Distortion to hemodynamic and ischemic stimuli during blood flow restriction (BFR) exercise may influence regional vascular adaptation. We examined changes at the conduit, resistance, and capillary level in response to low load resistance exercise with BFR. Eleven males (22 ± 3 yr, 178 ± 4 cm, 78 ± 9 kg) completed 6 wk (3 days/wk) unilateral plantar flexion training with BFR at 30% 1 repetition maximum (1-RM). The contralateral leg acted as a nonexercised control (CON). Popliteal artery function [flow-mediated dilation, FMD%] and structure [maximal diameter] and resistance vessel structure [peak reactive hyperemia] were assessed using Doppler ultrasound before and at 2-wk intervals. Calf filtration capacity was assessed using venous occlusion plethysmography before and after training. BFR training elicited an early increase in peak reactive hyperemia (1,400 ± 278 vs. 1,716 ± 362 ml/min at 0 vs. 2 wk; t-test: P = 0.047), a transient improvement in popliteal FMD% (5.0 ± 2.1, 7.6 ± 2.9, 6.6 ± 2.1, 5.7 ± 1.6% at 0, 2, 4 and 6 wk, respectively; ANOVA: P = 0.002), and an increase in maximum diameter (6.06 ± 0.44 vs. 6.26 ± 0.39 mm at 0 vs. 6 wk; Bonferroni t-test: P = 0.048). Capillary filtration increased after 6 wk BFR training ( P = 0.043). No changes in the CON leg were observed. Adaptation occurred at all levels of the vascular tree in response to low load resistance exercise with BFR. Enhanced peak reactive hyperemia and transient improvement in popliteal artery function occurred before changes in artery structural capacity.
Chronic phase advance alters circadian physiological rhythms and peripheral molecular clocks
Authors: Wolff Gretchen , Duncan Marilyn J. , Esser Karyn A.
Published: May 2013

Shifting the onset of light, acutely or chronically, can profoundly affect responses to infection, tumor progression, development of metabolic disease, and mortality in mammals. To date, the majority of phase-shifting studies have focused on acute exposure to a shift in the timing of the light cycle, whereas the consequences of chronic phase shifts alone on molecular rhythms in peripheral tissues such as skeletal muscle have not been studied. In this study, we tested the effect of chronic phase advance on the molecular clock mechanism in two phenotypically different skeletal muscles. The phase advance protocol (CPA) involved 6-h phase advances (earlier light onset) every 4 days for 8 wk. Analysis of the molecular clock, via bioluminescence recording, in the soleus and flexor digitorum brevis (FDB) muscles and lung demonstrated that CPA advanced the phase of the rhythm when studied immediately after CPA. However, if the mice were placed into free-running conditions (DD) for 2 wk after CPA, the molecular clock was not phase shifted in the two muscles but was still shifted in the lung. Wheel running behavior remained rhythmic in CPA mice; however, the endogenous period length of the free-running rhythm was significantly shorter than that of control mice. Core body temperature, cage activity, and heart rate remained rhythmic throughout the experiment, although the onset of the rhythms was significantly delayed with CPA. These results provide clues that lifestyles associated with chronic environmental desynchrony, such as shift work, can have disruptive effects on the molecular clock mechanism in peripheral tissues, including both types of skeletal muscle. Whether this can contribute, long term, to increased incidence of insulin resistance/metabolic disease requires further study.
Uniformly Asymptotic Stability of Positive Almost Periodic Solutions for a Discrete Competitive System
Authors: Wang Qinglong , Liu Zhijun
Published: May 2013

This paper is devoted to the study of almost periodic solutions of a discrete two-species competitive system. With the help of the methods of the Lyapunov function, some analysis techniques, and preliminary lemmas, we establish a criterion for the existence, uniqueness, and uniformly asymptotic stability of positive almost periodic solution of the system. Numerical simulations are presented to illustrate the analytical results.
New Trends in Secure Routing Protocols for Wireless Sensor Networks
Authors: El-Semary Aly Mohamed , Abdel-Azim Mohamed Mostafa
Published: May 2013

Recently, Wireless Sensor Networks (WSNs) have been deployed into a variety of applications including homeland security, military systems, and health care. Sensor nodes deployed in such networks are subject to several attacks such as sinkhole and select forwarding, wormhole, Hello flood, and replication attacks. Therefore, developing secure and energy-efficient routing protocols to protect WSNs against these attacks while efficiently utilizing the energy of the deployed nodes has become imperative. Several routing protocols have been proposed in the literature for WSNs. Most of these protocols assume static nodes and sinks to collect data from network fields. However, they may be highly movable, and recent advances show that mobile sensors in WSNs have a promising performance. Therefore, this paper surveys the state of the art on routing protocols related to WSNs and presents the security issues or problems associated with the current protocols as well as discusses the future trends and open research issues on secure routing protocols of WSNs.
The Effects of Decision-Making Processes and Population Turnover on the Formation of Social Networks
Authors: Xu Zhijing , Zu Zhenghu , Zheng Tao , Zhang Wendou , Xu Qing
Published: May 2013

The researchs on the structure and formation mechanism of social networks lead to several models with differences in the attachment patterns of new links (edges). In fact, the driving factor behind the addition of new links is just as important as the attachment patterns, while very little attention has been devoted so far to this exploration. We present an agent-based model which could successfully reproduce large-scale social networks. We find that the structure of social networks is a consequence of continuous individuals’ decision-making processes based on self-evaluations and the turnover of the population. The individuals’ self-evaluation processes are key motivating factors for the addition of new links, while the attachment patterns and the turnover of the population should be responsible for the topology of social networks. The resulting networks of our model display dynamics between order and randomness, which is greatly consistent with current observations and research achievements of social networks. We also find that some plausible properties of empirical data are actually artifacts due to the boundedness of sampling. Our research has revealed the driving factors behind the evolution of social networks as well as the underlying evolving patterns. These findings will lead to a better understanding of social structures.
A New Celestial Navigation Method for Spacecraft on a Gravity Assist Trajectory
Authors: Xiaolin Ning , Panpan Huang , Jiancheng Fang
Published: May 2013

A practical and reliable capability for autonomous navigation needs to reduce operation cost, to improve operational efficiency, and to increase mission safety. Celestial navigation is a very attractive autonomous navigation solution for deep space spacecraft. There are mainly two kinds of celestial navigation methods: the direct calculation method and the filter method. The accuracy of the direct calculation method is low and very sensitive to the measurement noise. The filter method can provide a better navigation performance if a high accuracy dynamical model is available. However, the main practical problem existing in the autonomous celestial navigation of spacecraft on a gravity assist trajectory is that the accuracy of trajectory model is not enough to be used in the real navigation sometimes, which may introduce large estimation error and even cause filter divergence. To solve this problem, a new celestial navigation method is proposed in this paper, which effectively combines the direct calculation method and the filter method using an interacting multiple model unscented Kalman filter (IMMUKF). The ground experimental results demonstrate that this method can provide better navigation performance and higher reliability than the traditional direct calculation method and filter method.