bluuebunny/crossref_metadata_2025 huggingface dataset:
A one‐port pneumovesicum method in en bloc laparoscopic nephroureterectomy with bladder cuff resection is feasible and safe for upper tract transitional cell carcinoma
Authors: Zou Xiaofeng , Zhang Guoxi , Wang Xiaoning , Yuan Yuanhu , Xiao Rihai , Wu Gengqing , Long Dazhi , Xu Hui , Wu Yuting , Liu Folin
Published: April 2011

Study Type – Therapy (case series)

Level of Evidence 4

OBJECTIVE

• To introduce a modified method for managing the distal ureter in laparoscopic nephroureterectomy (LNU) for upper tract transitional cell carcinoma (TCC) and to evaluate the feasibility and safety of this method.

PATIENTS AND METHODS

• Six consecutive patients underwent LNU using a one‐port pneumovesicum method for pathologically confirmed upper tract TCC.

• Each patient was placed on the operating table in the lithotomy position and the pneumovesicum method was applied with CO2 insufflation. Dissection was performed circumferentially through the entire detrusor muscle to disconnect the ureter from the bladder wall. A 10‐mm trocar was placed into the bladder above the pubic bone. The distal ureter was occluded using a Hem‐o‐lok clip and pushed out of the bladder. Laparoscopic nephroureterectomy was then performed with the patient in the lateral position.

• After surgery, all six patients received systemic chemotherapy and follow‐up.

RESULTS

• All procedures were performed successfully.

• The median (range) operating time for the complete procedure was 105 (85–140) min, and the median (range) estimated blood loss was 125 (60–230) mL.

• Seven days after surgery, each patient underwent cystography, which confirmed no extravasation of urine.

• None of the patients developed bladder tumour recurrence or metastatic disease during follow‐up.

CONCLUSIONS

• The one‐port pneumovesicum method in LNU, which is applied to manage the distal ureter and bladder cuff, is technically feasible and safe.

• The method simplifies management of the distal ureter, reduces the invasiveness of the procedure and improves cosmesis.
Vibrotactile sense in patients with diabetes and carpal tunnel syndrome
Authors: Thomsen N. O. B. , Cederlund R. , Speidel T. , Dahlin L. B.
Published: April 2011

Diabet. Med. 28, 1401–1406 (2011)

Aim  To evaluate vibration perception thresholds of patients with and without diabetes, before and after surgical carpal tunnel release.

Methods  In a prospective study, 35 consecutive patients with diabetes and carpal tunnel syndrome were age and gender matched with 31 patients without diabetes having idiopathic carpal tunnel syndrome. Preoperatively, 6, 12 and 52 weeks after surgery, the vibration perception threshold of the index and little finger (median and ulnar nerve, respectively) was measured at seven different frequencies (8, 16, 32, 64, 125, 250 and 500 Hz).

Results  At several frequencies, patients with diabetes and carpal tunnel syndrome demonstrated significantly impaired vibration perception thresholds of both the index and the little finger, before as well as after carpal tunnel release, compared with patients without diabetes with idiopathic carpal tunnel syndrome. After surgery, the overall sensibility index improved for the index finger [patients with diabetes and carpal tunnel syndrome (0.79 to 0.91, P < 0.001), patients without diabetes with idiopathic carpal tunnel syndrome (0.91 to 0.96, P > 0.05)] as well as for the little finger [patients with diabetes and carpal tunnel syndrome (0.82 to 0.90, P < 0.008), patients without diabetes with idiopathic carpal tunnel syndrome (0.95 to 0.99, P < 0.05)]. For the index finger, the sensibility index improved to a significantly higher degree for patients with diabetes and carpal tunnel syndrome not having signs of peripheral neuropathy (0.83 to 0.95, P < 0.001) compared with those with neuropathy (0.74 to 0.84, P < 0.02). Vibration perception threshold correlates with age of both patients with diabetes and carpal tunnel syndrome and patients without diabetes with idiopathic carpal tunnel syndrome, while no relationship was found based on duration of diabetes.

Conclusions  Vibrotactile sense is significantly impaired in patients with diabetes before and after carpal tunnel release compared with patients without diabetes. However, patients with diabetes obtained significant recovery of vibration perception threshold, particularly those without peripheral neuropathy.
Behind the scenes: the changing roles of parents in the transition from child to adult diabetes service
Authors: Allen D. , Channon S. , Lowes L. , Atwell C. , Lane C.
Published: April 2011

Diabet. Med. 28, 994–1000 (2011)

Aims  To explore the experiences of young people and their carers during the transition from child to adult diabetes services.

Methods  Longitudinal qualitative case studies of young people and carers undergoing transition in five different diabetes services in the UK.

Results  When young people make the transition from child to adult diabetes services, it is assumed that they will also undergo a parallel transition away from dependence on parents to independent diabetes management. However, the lives of young people are characterized by interdependencies, which are facilitative of their diabetes management and which are not always reflected in healthcare policy and practice. This can lead to discontinuities of information and undermine mothers’ ability to continue to support their child into young adulthood. Mothers also lose contact with the service at a time when they are undergoing developmental challenges of their own and need support in adjusting to a new existence.

Conclusions  There is a clear need to develop service structures that recognize the continuing role played by mothers in the diabetes care of young adults.
Orwell and the Oligarchs: George Orwell Memorial Lecture, 26 November 2010
Authors: MOUNT FERDINAND
Published: April 2011

The unique quality of George Orwell's political journalism is to force us to examine not just the utterances of our opponents, but what we say ourselves, in particular how we deceive ourselves as well as deceiving others. What would Orwell diagnose as our major self‐deception if he were alive today? Orwell was much taken with James Burnham's 1941 bestseller The Managerial Society. He agreed with Burnham that the predominant drift in modern society was towards oligarchy, and not towards democracy as we like to flatter ourselves. Whether in business or politics, decisions today rest in fewer hands. Power is concentrated, not dispersed. As in Russia, the emerging system enables oligarchs to collar a disproportionate share of the rewards. Management becomes a self‐remunerating elite. Inequality of income increases sharply as a result. Oligarchy is a perversion of liberal capitalism and not a natural development of it. It can be reversed. The Coalition government has set out in a liberal and localist direction. It remains to be seen whether these promising signs will develop into a sustained and effective programme.
THE MAP OF MULTILATERAL TREATY‐MAKING 1600–2000: A CONTRIBUTION TO THE HISTORICAL GEOGRAPHY OF DIPLOMACY
Authors: VAN DER WUSTEN HERMAN , DENEMARK ROBERT A. , HOFFMANN MATTHEW , YONTEN HASAN
Published: April 2011

The paper describes and analyses the successive geographical distributions of places where multilateral treaties have been signed over the life course of the state system. A large proportion of all negotiations occurred in just a few places and the collection of most frequently selected places shows considerable continuity over time. Treaty‐making emerges as more of a secular trend than a cyclical pulse, being insignificantly impacted by economic cycles, and inconsistently impacted by hegemonic cycles. The work presents a measure of specialisation that helps to identify types of central venues in the multilateral treaty‐making system. The actual selection of specific venues suggests functional and political considerations to have been most important. The sustained preference for national political centres expresses the importance of such considerations, while the actual choice of a venue in a specific case can be highly contingent.
Estrogen destabilizes microtubules through an ion‐conductivity‐independent TRPV1 pathway
Authors: Goswami Chandan , Kuhn Julia , Dina Olayinka A. , Fernández‐Ballester Gregorio , Levine Jon D. , Ferrer‐Montiel Antonio , Hucho Tim
Published: April 2011

J. Neurochem. (2011) 117, 995–1008.

Recently, we described estrogen and agonists of the G‐protein coupled estrogen receptor GPR30 to induce protein kinase C (PKC)ε‐dependent pain sensitization. PKCε phosphorylates the ion channel transient receptor potential, vanilloid subclass I (TRPV1) close to a novel microtubule‐TRPV1 binding site. We now modeled the binding of tubulin to the TRPV1 C‐terminus. The model suggests PKCε phosphorylation of TRPV1‐S800 to abolish the tubulin‐TRPV1 interaction. Indeed, in vitro PKCε phosphorylation of TRPV1 hindered tubulin‐binding to TRPV1. In vivo, treatment of sensory neurons and F‐11 cells with estrogen and the GPR30 agonist, G‐1, resulted in microtubule destabilization and retraction of microtubules from filopodial structures. We found estrogen and G‐1 to regulate the stability of the microtubular network via PKC phosphorylation of the PKCε‐phosphorylation site TRPV1‐S800. Microtubule disassembly was not, however, dependent on TRPV1 ion conductivity. TRPV1 knock‐down in rats inverted the effect of the microtubule‐modulating drugs, Taxol and Nocodazole, on estrogen‐induced and PKCε‐dependent mechanical pain sensitization. Thus, we suggest the C‐terminus of TRPV1 to be a signaling intermediate downstream of estrogen and PKCε, regulating microtubule‐stability and microtubule‐dependent pain sensitization.
Angiotensin IV displays only low affinity for native insulin‐regulated aminopeptidase (IRAP)
Authors: Demaegdt Heidi , De Backer Jean‐Paul , Lukaszuk Aneta , Tóth Géza , Szemenyei Erzsébet , Tourwé Dirk , Vauquelin Georges
Published: April 2011

Radioligand binding studies revealed that Ang IV binds to insulin‐regulated aminopeptidase (IRAP)/’AT4 receptors’ with high affinity. Yet, as these experiments were routinely carried out in the presence of chelators, only the catalytic zinc‐depleted apo‐form of IRAP was labelled. While the chelators remove the catalytic zinc from IRAP and protect Ang IV from proteolytic degradation, the aminopeptidase N selective inhibitor ‘7B’ only exerts the latter effect. By using 7B along with the new stable Ang IV‐analog [3H]AL‐11, we here show that the native enzyme is only a low‐affinity target for Ang IV.
Attachment styles in dating couples: Predicting relationship functioning over time
Authors: HOLLAND ASHLEY S. , FRALEY R. CHRIS , ROISMAN GLENN I.
Published: April 2011

This study examined the associations between self‐reported attachment style dimensions and romantic relationship functioning over 1 year in a sample of heterosexual dating couples between the ages of 18 and 25 (115 dyads at T1, 57 dyads at T2; 74% Caucasian). Relationship functioning was assessed at multiple levels of analysis via self‐reports of interpersonal functioning, observers' ratings of dyadic interactions, and measures of autonomic responding during the interactions. No significant cross‐sectional associations were found between attachment style dimensions and interpersonal functioning. However, individuals who reported greater attachment‐related anxiety at T1 described their relationships as being of lower quality, were rated by observers as interacting less positively, and exhibited greater electrodermal reactivity during interactions 1 year later.
Spillover between mothers' postdivorce relationships: The mediating role of parenting stress
Authors: HAKVOORT ESTHER M. , BOS HENNY M. W. , VAN BALEN FRANK , HERMANNS JO M. A.
Published: April 2011

This study examined the differences and associations between divorced mothers' relationships with their ex‐partners and with their children, and investigated whether this association is mediated by mothers' experience of parenting stress. A questionnaire was completed by 117 divorced single mothers and 64 remarried mothers. Results show that the single mothers and the remarried mothers did not differ on postdivorce family relationship quality or on their experience of parenting stress. Furthermore, divorced mothers' relationship with their ex‐partners was found to be associated with the quality of the mother–child relationship, but not when controlling for mothers' experience of parenting stress. The results show that maternal parenting stress mediates the association between conflicts between ex‐partners and the quality of the mother–child relationship.
Anthropology as a Sustainability Science
Authors: Singer Merrill
Published: April 2011

[sustainability, climate change, environment, applied anthropology, NCARE, Center for Environmental Science, sustainable development]
Sense and Sustainability: Teaching Sustainability in Global Health
Authors: Closser Svea
Published: April 2011

[sustainability, teaching strategies, global health, organic garden, anthropology education, Middlebury College]
Dearth and Deluge: Sustaining Lives and Livelihoods under Threat
Authors: McMahan Ben , Seibert David
Published: April 2011

[sustainability, risk environment, landscape, rural anthropology, Altar Valley, Southern Louisiana, identity]
Sustainable Ecologies and Unsustainable Politics: Chinampa Farming in Ancient Central Mexico
Authors: Morehart Christopher T
Published: April 2011

[sustainability, archaeology, chinampa, xaltocan, farmscape, agriculture, agrarian system]
Cultivating Sustainability through Anthropology: University of Idaho's Campus Trash Project
Authors: Camp Stacey Lynn , Allen Josh , Bayly Elaine , Capawana Jamie , Galbraith Sara , Henry Shea , Jones Meaghan , Parker‐McGlynn Kyle , Petrich‐Guy Mary , Sargent Heather , Stokeld Rachel
Published: April 2011

[sustainability, archaeology, archeological method, anthropology of trash, education]
Anthropology as Key to Sustainability Science: An Interview with Charles Redman
Authors: Guyot Jodi
Published: April 2011

[sustainability, charles redman, School of Human Evolution and Social Change, education, sustainability science, curriculum development]
Citizenship and Sustainability: Toward Global‐Reach Curricula
Authors: Davis‐Salazar Karla , Wells E Christian
Published: April 2011

[sustainability, curriculum development, global citizenship, global sustainability, education, University of South Florida]
Soldiers, War and Sacrifice: How Ethnography Contributes to the Casualty Debate
Authors: Rough Jill A
Published: April 2011

[public affairs, research on policy, ethnography, military mobilization, military anthropology]

Janine Wedel is the contributing editor of Research on Policy, the AN column of the AAA Interest Group for the Anthropology of Public Policy.
Human Rights Advocacy: Tip of Compassion or the Sword of Discretion?
Authors: Reyes Julie A
Published: April 2011

[public affairs, human rights forum, intrapersonal violence]

Gretchen E Schafft is the contributing editor of Human Rights Forum, the AN column of the AAA Committee for Human Rights.
Anthropology's Value: Legacies, Tidemarks, Surprises and Measures
Authors: Dominguez Virginia R
Published: April 2011

[president, anthropology profession, anthropology major]
Maternal malnutrition, environmental exposure during pregnancy and the risk of non‐syndromic orofacial clefts
Authors: Jia Z‐L , Shi B , Chen C‐H , Shi J‐Y , Wu J , Xu X
Published: April 2011

Oral Diseases (2011) 17, 584–589

Objective:  To explore the risk factors of non‐syndromic orofacial clefts.

Subjects and Methods:  A case–control study was conducted in China, 537 infants born with non‐syndromic cleft lip with/without cleft palate, 176 infants born with cleft palate (CP), and 221 normal controls were recruited to participate in a questionnaire based study to identify risk factors related to maternal nutrition.

Results:  Single‐factor Chi‐square analysis identified 12 factors as significantly related to non‐syndromic orofacial clefts (P < 0.05). Multiple logistic regression showed five of these factors were associated with non‐syndromic orofacial clefts, male gender and maternal passive smoking during early pregnancy were risk factors for non‐syndromic orofacial clefts (OR = 1.86 and 11.42; 95%CI: 2.28–2.69 and 6.87–19.00, respectively), whereas maternal weight gain during pregnancy and folic acid supplementation during early pregnancy were protective (OR = 0.15 and 0.67; 95%CI: 0.034–0.63 and 0.44–1.00, respectively).

Conclusions:  Our data may provide references for cleft lip and CP prevention programs, and counseling programs in China.
Inflammatory bowel disease
Authors: Boirivant M , Cossu A
Published: April 2011

Oral Diseases (2011) 18, 1–15

This review focuses on the prominent etiological and pathogenetic aspects of inflammatory bowel disease (IBD), with particular attention being paid to the mucosal immune response to commensal micro‐organisms in health and disease. Pathogenetic implications for target therapy will also be discussed. The clinical presentation, diagnostic aspects, and currently recommended therapeutic options for the two main types of IBD are also taken into consideration, including manifestations of these conditions in the oral cavity.
Harry Potter and “the landscape of consciousness”: repeat home viewers’ understandings about character
Authors: Finch Brian
Published: April 2011

Many children view favourite feature films repeatedly at home and develop understandings of them. This article discusses findings from a study which focused on the understandings that 9‐ and 10‐year‐old children showed about character in Harry Potter and the Chamber of Secrets. These findings are reported in terms of a framework appropriate for responses to character in literature or in film. The children's home‐based engagement with characters provides evidence for teachers who are planning to extend understandings about character in their classrooms. The article shows that children's interpretative and structural engagement can build significant understandings and informed appreciation which are similar to those that teachers aim for.
Increased flexibility and liposome‐binding capacity of CD1e at endosomal pH
Authors: Bushmarina Natalia , Tourne Sylvie , Giacometti Gaëlle , Signorino‐Gelo François , Garcia‐Alles Luis F. , Cazenave Jean‐Pierre , Hanau Daniel , de la Salle Henri
Published: April 2011

The plasma membrane proteins CD1a, CD1b and CD1c are expressed by human dendritic cells, the professional antigen‐presenting cells of the immune system, and present lipid antigens to T lymphocytes. CD1e belongs to the same family of molecules, but accumulates as a membrane‐associated form in the Golgi compartments of immature dendritic cells and as a soluble cleaved form in the lysosomes of mature dendritic cells. In lysosomes, the N‐terminal propeptide of CD1e is also cleaved, but the functional consequences of this step are unknown. Here, we investigated how the pH changes encountered during transport to lysosomes affect the structure of CD1e and its ligand‐binding properties. Circular dichroism studies demonstrated that the secondary and tertiary structures of recombinant CD1e were barely altered by pH changes. Nevertheless, at acidic pH, guanidium chloride‐induced unfolding of CD1e molecules required lower concentrations of denaturing agent. The nonfunctional L194P allelic variant was found to be structurally less stable at acidic pH than the functional forms, providing an explanation for the lack of its detection in lysosomes. The number of water‐exposed hydrophobic patches that bind 8‐anilinonaphthalene‐1‐sulfonate was higher in acidic conditions, especially for the L194P variant. CD1e molecules interacted with lipid surfaces enriched in anionic lipids, such as bis(monoacylglycero)phosphate, a late endosomal/lysosomal lipid, especially at acidic pH, or when the propeptide was present. Altogether, these data indicate that, in the late endosomes/lysosomes of DCs, the acid pH promotes the binding of lipid antigens to CD1e through increased hydrophobic and ionic interactions.
MicroRNA‐373, a new regulator of protein phosphatase 6, functions as an oncogene in hepatocellular carcinoma
Authors: Wu Nannan , Liu Xuyuan , Xu Xuemei , Fan Xingxing , Liu Min , Li Xin , Zhong Qiping , Tang Hua
Published: April 2011

MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post‐transcriptional level. Recently, microRNA‐373 (miR‐373) has been found to function as an oncogene in testicular germ cell tumors. In our study, we found that miR‐373 is upregulated in human hepatocellular carcinoma (HCC) tissues as compared with adjacent normal tissues, and promotes the proliferation of the HCC cell lines HepG2 and QGY‐7703 by regulating the transition between G1‐phaseand S‐phase. The gene encoding the protein phosphatase 6 catalytic subunit (PPP6C ), a negative cell cycle regulator, was identified as a direct target gene of miR‐373 by use of a fluorescent reporter assay. The mRNA and protein levels of PPP6C were both inversely correlated with the miR‐373 expression level. Overexpression of PPP6C abolished the regulation of cell cycle and cell growth exercised by miR‐373 in HepG2 cells. These results indicate that miR‐373 plays an important role in the pathogenesis of HCC, and may be a new biomarker in HCC. Our results demonstrate that miR‐373 can regulate cell cycle progression by targeting PPP6C transcripts and promotes the growth activity of HCC cells in vitro. The downregulation of PPP6C by miR‐373 may explain why the expression of miR‐373 can promote HCC cell proliferation.
Auto‐methylation of the mouse DNA‐(cytosine C5)‐methyltransferase Dnmt3a at its active site cysteine residue
Authors: Siddique Abu Nasar , Jurkowska Renata Z. , Jurkowski Tomasz P. , Jeltsch Albert
Published: April 2011

The Dnmt3a DNA methyltransferase is responsible for establishing DNA methylation patterns during mammalian development. We show here that the mouse Dnmt3a DNA methyltransferase is able to transfer the methyl group from S‐adenosyl‐l‐methionine (AdoMet) to a cysteine residue in its catalytic center. This reaction is irreversible and relatively slow. The yield of auto‐methylation is increased by addition of Dnmt3L, which functions as a stimulator of Dnmt3a and enhances its AdoMet binding. Auto‐methylation was observed in binary Dnmt3a AdoMet complexes. In the presence of CpG containing dsDNA, which is the natural substrate for Dnmt3a, the transfer of the methyl group from AdoMet to the flipped target base was preferred and auto‐methylation was not detected. Therefore, this reaction might constitute a regulatory mechanism which could inactivate unused DNA methyltransferases in the cell, or it could simply be an aberrant side reaction caused by the high methyl group transfer potential of AdoMet.

Enzymes

Dnmt3a is a DNA‐(cytosine C5)‐methyltransferase, EC 2.1.1.37.

Structured digital abstract

 Dnmt3amethylatesDnmt3a by methyltransferase assay(View interaction)

 Dnmt3a and DNMT3LmethylateDnmt3a by methyltransferase assay(View interaction)
Expression analysis of the nucleocytoplasmic lectin ‘Orysata’ from rice in Pichia pastoris
Authors: Al Atalah Bassam , Fouquaert Elke , Vanderschaeghe Dieter , Proost Paul , Balzarini Jan , Smith David F. , Rougé Pierre , Lasanajak Yi , Callewaert Nico , Van Damme Els J. M.
Published: April 2011

The Oryza sativa lectin, abbreviated Orysata, is a mannose‐specific, jacalin‐related lectin expressed in rice plants after exposure to certain stress conditions. Expression of a fusion construct containing the rice lectin sequence linked to enhanced green fluorescent protein in Bright Yellow 2 tobacco cells revealed that Orysata is located in the nucleus and the cytoplasm of the plant cell, indicating that it belongs to the class of nucleocytoplasmic jacalin‐related lectins. Since the expression level of Orysata in rice tissues is very low the lectin was expressed in the methylotrophic yeast Pichia pastoris with the Saccharomycesα‐factor sequence to direct the recombinant protein into the secretory pathway and express the protein into the medium. Approximately 12 mg of recombinant lectin was purified per liter medium. SDS/PAGE and western blot analysis showed that the recombinant lectin exists in two molecular forms. Far western blot analysis revealed that the 23 kDa lectin polypeptide contains an N‐glycan which is absent in the 18.5 kDa polypeptide. Characterization of the glycans present in the recombinant Orysata revealed high‐mannose structures, Man9–11 glycans being the most abundant. Glycan array analysis showed that Orysata interacts with high‐mannose as well as with more complex N‐glycan structures. Orysata has potent anti‐human immunodeficiency virus and anti‐respiratory syncytial virus activity in cell culture compared with other jacalin‐related lectins.
Medical student/student doctor access to patients in an emergency department
Authors: Celenza Antonio , Li Jesse , Teng Justin
Published: April 2011

Objectives: To determine the proportion of patients in a teaching hospital ED who are available to medical students; identify barriers to student access to patients; and determine whether patients are more likely to be accessible if the term student doctor is used rather than medical student.

Methods: Repeated cross‐sectional study of the ED of a tertiary teaching hospital. Interviews were attempted with all patients in the ED during six 4 h periods. Outcome measures included: number of patients present and accessible to students; present but inaccessible, absent or unfit to be seen for clinical reasons; number of patients consenting to history, physical examination and certain procedures; and difference in patient consent between the terms ‘medical student’ and ‘student doctor’.

Results: Overall, 180 of 450 (40.0%) patients completed the interview, 72 (16.0%) were able to be observed only, and 198 (44.0%) were not suitable for interview or observation. The common reasons for patient unsuitability were: physically not available (60%), being assessed by a health professional or undergoing a procedure (13.0%) altered mental status (7.4%), unstable or terminally ill (5.2%); refusal to participate in the study (4.8%), or dangerous or under arrest (4.1%). No significant differences were found in patient willingness to undergo clinical skills from ‘student doctors’ compared with ‘medical students’.

Conclusion: A minimum 40% of patients in a tertiary ED are accessible for student learning, with high proportions of patients accepting of students practising supervised history‐taking, physical examination, and most less‐invasive procedural skills.
Selective targeting of G‐protein‐coupled receptor subtypes with venom peptides
Authors: Näreoja K. , Näsman J.
Published: April 2011

The G‐protein‐coupled receptor (GPCR) family is one of the largest gene superfamilies with approx. 370 members responding to endogenous ligands in humans and a roughly equal amount of receptors sensitive to external stimuli from the surrounding. A number of receptors from this superfamily are well recognized targets for medical treatment of various disease conditions, whereas for many others the potential medical benefit of interference is still obscure. A general problem associated with GPCR research and therapeutics is the insufficient specificity of available ligands to differentiate between closely homologous receptor subtypes. In this context, venom peptides could make a significant contribution to the development of more specific drugs.

Venoms from certain animals specialized in biochemical hunting contain a mixture of molecules that are directed towards a variety of membrane proteins. Peptide toxins isolated from these mixtures usually exhibit high specificity for their targets. Muscarinic toxins found from mamba snakes attracted much attention during the 1990s. These are 65–66 amino acid long peptides with a structural three‐finger folding similar to the α‐neurotoxins and they target the muscarinic acetylcholine receptors in a subtype‐selective manner. Recently, several members of the three‐finger toxins from mamba snakes as well as conotoxins from marine cone snails have been shown to selectively interact with subtypes of adrenergic receptors.

In this review, we will discuss the GPCR‐directed peptide toxins found from different venoms and how some of these can be useful in exploring specific roles of receptor subtypes.
Post‐translational modifications regulate signalling by Ror1
Authors: Kaucká M. , Krejčí P. , Plevová K. , Pavlová Š. , Procházková J. , Janovská P. , Valnohová J. , Kozubík A. , Pospíšilová Š. , Bryja V.
Published: April 2011

Aim:  In this study, we analysed the post‐translational modification of receptor tyrosine kinase‐like orphan receptor (Ror1). Ror1 is highly upregulated in B cells of patients with chronic lymphocytic leukaemia (CLL). Molecularly, Ror1 acts as the Wnt receptor in the non‐canonical Wnt pathway.

Methods:  The level of Ror1 glycosylation in HEK293 cells and in primary human CLL cells was analysed by treatment of inhibitors interfering with different steps of glycosylation process and by direct treatment of cell lysates with N‐glycosidase. Ror1 ubiquitination was determined by ubiquitination assay. Functional consequences of post‐translational modifications were analysed by immunohistochemistry and by analysis of cell surface proteins. Differences in Ror1 glycosylation were confirmed by analysis of 14 samples of B cells from CLL patients.

Results:  We demonstrate that Ror1 is extensively modified by N‐linked glycosylation. Glycosylation produces several variants of Ror1 with electrophoretic migration of approx. 100, 115 and 130 kDa. Inhibition of glycosylation interferes with cell surface localization of the 130‐kDa variant of Ror1 and prevents Ror1‐induced formation of filopodia. Moreover, we show that 130‐kDa Ror1 is mono‐ubiquitinated. Furthermore, individual CLL patients show striking differences in the electrophoretic migration of Ror1, which correspond to the level of glycosylation.

Conclusion:  Our data show that Ror1 undergoes complex post‐translational modifications by glycosylation and mono‐ubiquitination. These modifications regulate Ror1 localization and signalling, and are highly variable among individual CLL patients. These may suggest that Ror1 signals only in a subset of CLL patients despite Ror1 levels are ubiquitously high in all CLL patients.
Counter‐regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin: a double‐blinded randomized cross‐over study
Authors: Brock Jacobsen I. , Vind B. F. , Korsholm L. , Flyvbjerg A. , Frystyk J. , Holst J. J. , Beck‐Nielsen H. , Henriksen J. E.
Published: April 2011

Aims:  To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter‐regulatory responses to spontaneous hypoglycaemia.

Methods:  Glycaemic control, hypoglycaemic frequency, p‐insulin concentrations, insulin dosages and patients’ satisfaction were examined in a randomized, double‐blinded cross‐over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed by hospitalization where episodes of spontaneous hypoglycaemia and counter‐regulatory hormone responses were evaluated from frequently obtained blood samples.

Results:  No difference between soluble insulin and insulin Aspart was found regarding HbA1c (7.0 ± 0.2 vs. 7.0 ± 0.2%, ns), hypoglycaemic frequency (1.1 ± 0.2 vs. 0.9 ± 0.1 events per patient per week, ns), nocturnal hypoglycaemia, severe hypoglycaemic events, dosages of bolus insulin (31.8 ± 0.4 vs. 30.0 ± 0.6 IU day−1, ns), or NPH insulin (26.7 ± 1.8 vs. 26.0 ± 1.7 IU day−1, ns) or in patients satisfaction (ns). Modest differences existed in the counter‐regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin‐like growth factor (IGF)‐I, IGF‐II and IGF‐binding proteins 1 and 2. Treatment with insulin Aspart resulted in well‐defined peaks in serum insulin concentrations as compared with more blunted insulin peaks using human soluble insulin.

Conclusion:  Although insulin Aspart treatment was associated with clear postprandial insulin peaks, no improvement in glycaemic control was obtained and no difference in the hypoglycaemic frequency was observed. However, insulin Aspart elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin.
Taste receptor signalling – from tongues to lungs
Authors: Kinnamon S. C.
Published: April 2011

Taste buds are the transducing endorgans of gustation. Each taste bud comprises 50–100 elongated cells, which extend from the basal lamina to the surface of the tongue, where their apical microvilli encounter taste stimuli in the oral cavity. Salts and acids utilize apically located ion channels for transduction, while bitter, sweet and umami (glutamate) stimuli utilize G‐protein‐coupled receptors (GPCRs) and second‐messenger signalling mechanisms. This review will focus on GPCR signalling mechanisms. Two classes of taste GPCRs have been identified, the T1Rs for sweet and umami (glutamate) stimuli and the T2Rs for bitter stimuli. These low affinity GPCRs all couple to the same downstream signalling effectors that include Gβγ activation of phospholipase Cβ2, 1,4,5‐inositol trisphosphate mediated release of Ca2+ from intracellular stores and Ca2+‐dependent activation of the monovalent selective cation channel, TrpM5. These events lead to membrane depolarization, action potentials and release of ATP as a transmitter to activate gustatory afferents. The Gα subunit, α‐gustducin, activates a phosphodiesterase to decrease intracellular cAMP levels, although the precise targets of cAMP have not been identified. With the molecular identification of the taste GPCRs, it has become clear that taste signalling is not limited to taste buds, but occurs in many cell types of the airways. These include solitary chemosensory cells, ciliated epithelial cells and smooth muscle cells. Bitter receptors are most abundantly expressed in the airways, where they respond to irritating chemicals and promote protective airway reflexes, utilizing the same downstream signalling effectors as taste cells.
Towards better patient safety: WHO Surgical Safety Checklist in otorhinolaryngology
Authors: Helmiö P. , Blomgren K. , Takala A. , Pauniaho S.‐L. , Takala R.S.K. , Ikonen T.S.
Published: April 2011

Clin. Otolaryngol. 2011, 36, 242–247

Objectives:  The World Health Organisation has developed a Surgical Safety Checklist to improve patient safety during surgery. This checklist has reduced postoperative morbidity and mortality. Prior to checklist implementation, we wanted to evaluate how it would fit into the process of otorhinolaryngology‐head and neck surgery and whether it would have an impact on the awareness of safety‐related issues.

Design:  A structured questionnaire was addressed to the operating room team after consecutive operations during a 1‐month period before and after checklist implementation.

Setting and participants:  This study was conducted at the Department of Otorhinolaryngology at the Helsinki University Central Hospital as a part of a multicentre study. Responses were received regarding 288 operations before and 412 after checklist implementation.

Main outcome measures:  The questions concerned patient‐related safety checks, teamwork and communication.

Results:  The checklist improved verification of the patient’s identity (P < 0.001). Awareness of the patient’s medical history, medication and allergies increased (P < 0.001). Knowledge of the names and roles among the team members improved. The otolaryngologists and anaesthesiologists discussed possible critical events more often (P < 0.001), and postoperative instructions were better recorded after use of the checklist. In addition, the checklist enhanced communication between operation team members.

Conclusions:  Our study confirms that the Surgical Safety Checklist fits well into the surgical working process in otorhinolaryngology‐head and neck surgery improving the sharing of patient‐related medical information between team members. Development of a specific checklist for otolaryngology calls for further study.
Using the global functioning social and role scales in a first‐episode sample
Authors: Piskulic Danijela , Addington Jean , Auther Andrea , Cornblatt Barbara A.
Published: April 2011

Aims: Dysfunction in social and role functioning is a hallmark of schizophrenia, which is present in both the prodromal phase and at the first episode of the illness. Two new measures, Global Functioning: Social and Global Functioning: Role, were developed to address functioning in the prodromal phase of the illness. The purpose of this study was to determine if these measures would be useful in a first episode population.

Methods: Forty‐eight stable outpatients were assessed using the new social and role scales. A subsample of 33 subjects was assessed at 6 and 12 months. All subjects were additionally assessed using standardized measures of psychotic symptoms, social functioning, self‐esteem and beliefs about illness.

Results: Average ratings on the Global Functioning: Social and Role scales were 6 (standard deviation (SD) = 1.60) and 5.5 (SD = 2.2), respectively. Both social and role scales were significantly correlated with relevant subscales on the Social Functioning Scale. Good social but not role functioning was related to low levels of both positive and negative symptoms and to high self‐esteem. Role but not social functioning was related to personal beliefs about the illness, such as having control over illness and feeling less stigmatized. Repeated measures analyses demonstrated no change over time for either social or role functioning.

Conclusion: The Global Functioning: Social and Role scales appear to be useful and valid measures of functioning in first‐episode patients. These ratings are similar to those reported in prodromal studies supporting the idea that poor functioning may be a stable long‐standing deficit.
A public-health approach to site-specific formulary management: addressing deficient drug supplies in Malawi†
Authors: Lauffenburger Julie C , Jonkman Lauren J , Lange C Elliott , Connor Sharon E , Sibale Chakunja
Published: April 2011

Objectives

Maintaining a well-stocked dispensary at a private non-profit clinic in a developing country can often be challenging due to limited financial and human resources. Organizations face frequent drug shortages, excesses of unnecessary medications and potentially inappropriate international donations. To promote adherence to international recommendations and enable targeted requests for international drug donations, this paper describes a process using a public-health approach to create a site-specific pharmacy formulary in a resource-poor setting using the World Health Organization's (WHO) Model List of Essential Medicines (‘Model List’).

Methods

The study site was a Malawian-run non-profit private clinic serving over 3000 people annually. The organization focuses on providing community support for orphans from the HIV/AIDS crisis in sub-Saharan Africa. While using the Model List as a backbone, we incorporated the clinic's drug inventory, patient needs, clinician prescribing patterns, and the country's national drug list into the final formulary. After analyzing site-specific factors, we determined which WHO Model List therapeutic classes were necessary for the clinic to address in the final formulary.

Key findings

Of the drug products currently available in the inventory, 65.6% were expired, 29.8% of which were international donations. After removing expired medications from the inventory, seven Model List priority categories remained unaddressed by the clinic's initial inventory. Based on the results of a structured needs assessment, 54 products were selected for the final simplified formulary.

Conclusions

Conscious selection of pharmaceuticals, resulting in a systematic formulary for drug distribution management, is critical so that a clinic can focus on procuring and prescribing the most needed medications. This selection process using the WHO Model List and a public-health approach to drug management could serve as a private clinic model for pharmaceutical optimization and targeted international drug donations in sub-Saharan Africa and other resource limited settings.
Severity and probability of harm of medication errors intercepted by an emergency department pharmacist
Authors: Patanwala Asad E , Hays Daniel P , Sanders Arthur B , Erstad Brian L
Published: April 2011

Objectives

The objective of this study was to evaluate the severity and probability of harm of medication errors (MEs) intercepted by an emergency department pharmacist. The phases of the medication-use process where MEs were most likely to be intercepted were determined.

Methods

The emergency department was staffed with a full-time pharmacist during the 7-month study period. The MEs that were intercepted by the pharmacist were recorded in a database. Each ME in the database was independently scored for severity and probability of harm by two pharmacists and one physician investigator who were not involved in the data collection process.

Key findings

There were 237 ME interceptions by the pharmacist during the study period. The final classification of MEs by severity was as follows: minor (n = 42; 18%), significant (n = 160; 67%) and serious (n = 35; 15%). The final classification of MEs by probability of harm was as follows: none (n = 13; 6%), very low (n = 96; 41%), low (n = 84; 35%), medium (n = 41; 17%) and high (n = 3; 1%). Inter-rater reliability for classification was as follows: error severity (agreement = 75.5%, kappa = 0.35) and probability of harm (agreement = 76.8%, kappa = 0.42). The MEs were most likely to be intercepted during the prescribing phase of the medication-use process (n = 236; 90.1%).

Conclusions

A high proportion of MEs intercepted by the emergency department pharmacist are considered to be significant or serious. However, a smaller percentage of these errors are likely to result in patient harm.
Core Protection Calculator System: Past, Present, and Future
Authors: Hung Peter L.
Published: April 2011

The Core Protection Calculator System (CPCS) was the first implementation of digital computers in a nuclear power plant safety protection system. The system was based on first principles to calculate the specified acceptable fuel design limit (SAFDL) online. This approach provides the theoretical optimum safety margin. The first-of-its-kind system was installed in the United States at Arkansas Nuclear One Unit 2 (ANO-2) in 1980. Extensive efforts were made by Combustion Engineering and U.S. Nuclear Regulatory Commission (NRC) staff to gain licensing approval of the CPCS. Based on accumulated operating experience, numerous improvements were made to enhance the performance of the CPCS. The CPCS software provided the flexibility to readily accommodate these design changes. Currently, CPCS is implemented in 21 nuclear power plants in operation or under construction in the U.S.A. and Asia. The next generation CPCS will focus on optimizing the plant protection by improving the SAFDL calculation. By taking advantage of the advances in digital computer technology, the comprehensive safety analysis code will be used online. A more detailed core power map using the incore detector signals will be used as the basis of the departure from nucleate boiling ratio (DNBR) and local power density (LPD) calculation. A quick power reduction will provide adequate margin for most of the design basis events. For these events, CPCS will initiate a reactor power cutback as opposed to a reactor trip, which will maintain the plant at a safe condition with a reduced power level.
Visualization Study of Cavity Tone in Closed Tandem Side-Branches Using a High Time-Resolved PIV Technique
Authors: Li Yanrong , Someya Satoshi , Okamoto Koji
Published: April 2011

Flow-induced acoustic resonance in a piping system containing closed tandem side-branches was investigated experimentally in this study. Velocity perturbation was induced at the mouth of the cavity using two pumps and a block. An uncommon acoustic mode change, from a higher mode to a lower mode, was observed when the flow rate in the main pipe increased. This phenomenon was examined by high-time-resolved Particle Image Velocimetry (PIV). The instantaneous velocity field in a cross section was visualized two-dimensionally using PIV technique, simultaneously with the pressure measurement at multi-points around the cavity by microphones. The fluid flows at different points in the cavity interact, with some phase differences between them, and the relation between the fluid flows was clarified. The phase difference of the acoustic pressure fluctuation at different points around the cavity was also obtained. Consequently, phase delays of oscillation at different points were obtained two-dimensionally. 2-D phase map was helpful to discuss the feedback mechanism of the self-induced vibration. This is the first research which can obtain this kind contour map using the time sequential instantaneous velocity fields for closed tandem side-branches system which has long side-branches (L/D ≫1) and high inflow velocity at high resonant frequency.
Study on Technical Improvements for Human System Interface in the Main Control Room of LingAo 3 and 4
Authors: Ji Shi , Xu Xiaomei , Zhang Jianbo , Wang Zhifang
Published: April 2011

This paper focuses on the technical improvements for Human System Interface (HSI) implemented to be designed to manage normal and accidental situation of the Nuclear Power Plants (NPPs) on the LING AO 3&4 nuclear plants project under construction in the South of China. Regarding the operation principles of the NPPs, two major improvements on the LAO 3&4 NPPs are introduced: Implementation of a Digital Control System (DCS) combined with a computerized Human System Interface and backed-up with a conventional control mean Back-up panel (BUP). Some technical improvements for HSIs such as State Oriented Procedures (SOP), Large Display Panel (LDP), Computerized-base procedures, Advanced alarm system, Safety Parameter Display system (SPDS) are detailed in this paper. Finally, in the scope of these studies, the human factors considerations are considered in order to reduce the likelihood of human errors, to gain maximum benefit of the implemented technology and to increase the performance.
Optimizing Gamma-Ray Shielding Material by Using Genetic Algorithm and MCNP Code
Authors: Ashayer Sahar , Asgari Mansur , Afarideh Hossein
Published: April 2011

Radiation shielding material investigations is an important subject which relates to human safety, for those engaging in medical radiation, radiology, and facilities related with nuclear radiation, manned spacecraft and so on. Therefore necessity of finding effective shielding materials which have low weight, and cost, and have stability against radiation, with high temperature resistant, and no biological damage,… is obvious. On the other hand, because of the multi-variability of the problem, it is experimentally difficult to determine the optimum values of the concerned variables. For this reason, simulation for discovering optimized shielding material is important. Parameters such as attenuation, thickness, and cost of gamma radiation shielding materials were optimized by using genetic algorithm combined with MCNP code. Multi objective genetic algorithm (GA) is one of the scientific solutions for this problem.