bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational flexibility of the agonist binding jaw of the human P2X3 receptor is a prerequisite for channel opening
Authors: Kowalski M , Hausmann R , Dopychai A , Grohmann M , Franke H , Nieber K , Schmalzing G , Illes P , Riedel T
Published: July 2014

Background and Purpose

It is assumed that ATP induces closure of the binding jaw of ligand‐gated P2X receptors, which eventually results in the opening of the membrane channel and the flux of cations. Immobilization by cysteine mutagenesis of the binding jaw inhibited ATP‐induced current responses, but did not allow discrimination between disturbances of binding, gating, subunit assembly or trafficking to the plasma membrane.

Experimental Approach

A molecular model of the pain‐relevant human (h)P2X3 receptor was used to identify amino acid pairs, which were located at the lips of the binding jaw and did not participate in agonist binding but strongly approached each other even in the absence of ATP.

Key Results

A series of cysteine double mutant hP2X3 receptors, expressed in HEK293 cells or Xenopus laevis oocytes, exhibited depressed current responses to α,β‐methylene ATP (α,β‐meATP) due to the formation of spontaneous inter‐subunit disulfide bonds. Reducing these bonds with dithiothreitol reversed the blockade of the α,β‐meATP transmembrane current. Amino‐reactive fluorescence labelling of the His‐tagged hP2X3 receptor and its mutants expressed in HEK293 or X. laevis oocytes demonstrated the formation of inter‐subunit cross links in cysteine double mutants and, in addition, confirmed their correct trimeric assembly and cell surface expression.

Conclusions and Implications

In conclusion, spontaneous tightening of the binding jaw of the hP2X3 receptor by inter‐subunit cross‐linking of cysteine residues substituted at positions not directly involved in agonist binding inhibited agonist‐evoked currents without interfering with binding, subunit assembly or trafficking.
Synthesis and Biological Evaluation of 5‐Nitropyrimidine‐2,4‐dione Analogues as Inhibitors of Nitric Oxide and iNOS Activity
Authors: Ma Liang , He Linhong , Lei Lei , Liang Xiaolin , Lei Kai , Zhang Ronghong , Yang Zhuang , Chen Lijuan
Published: July 2014

Fifty two compounds based on 5‐nitropyrimidine‐2,4‐dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50: 8.6 μm) on lipopolysaccharide‐induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50: 6.2 μm), as well as exerted no potential cytotoxicity (IC50 > 80.0 μm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan‐induced paw edema of male ICR mice.
Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer
Authors: Mantere T. , Haanpää M. , Hanenberg H. , Schleutker J. , Kallioniemi A. , Kähkönen M. , Parto K. , Avela K. , Aittomäki K. , von Koskull H. , Hartikainen J.M. , Kosma V.‐M. , Laasanen S.‐L. , Mannermaa A. , Pylkäs K. , Winqvist R.
Published: July 2014

Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA‐A (n = 3), FA‐G (n = 1) and FA‐I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland.
A founder mutation in the TCIRG1 gene causes osteopetrosis in the Ashkenazi Jewish population
Authors: Anderson S.L. , Jalas C. , Fedick A. , Reid K.F. , Carpenter T.O. , Chirnomas D. , Treff N.R. , Ekstein J. , Rubin B.Y.
Published: July 2014

Osteopetrosis is a rare and heterogeneous genetic disorder characterized by dense bone mass that is a consequence of defective osteoclast function and/or development. Autosomal recessive osteopetrosis (ARO) is the most severe form and is often fatal within the first years of life; early hematopoietic stem cell transplant (HSCT) remains the only curative treatment for ARO. The majority of the ARO‐causing mutations are located in the TCIRG1 gene. We report here the identification and characterization of an A to T transversion in the fourth base of the intron 2 donor splice site (c.117+4A→T) in TCIRG1, a mutation not previously seen in the Ashkenazi Jewish (AJ) population. Analysis of a random sample of individuals of AJ descent revealed a carrier frequency of approximately 1 in 350. Genotyping of five loci adjacent to the c.117+4A→T‐containing TCIRG1 allele revealed that the presence of this mutation in the AJ population is due to a single founder. The identification of this mutation will enable population carrier testing and will facilitate the identification and treatment of individuals homozygous for this mutation.
A review of mismatch repair gene transcripts: issues for interpretation of mRNA splicing assays
Authors: Thompson B.A. , Martins A. , Spurdle A.B.
Published: July 2014

Many mismatch repair (MMR) gene disease‐causing mutations identified in cancer patients result in aberrant messenger RNA (mRNA) splicing. However, mRNA assay interpretation can be complicated by the existence of naturally occurring alternative mRNA transcripts, most of which have not been formally described or fully characterized. Here, we provide a comprehensive catalogue of all MMR transcripts described to date, and a review of MMR nucleotide variants associated with an apparent upregulation of alternatively spliced transcripts. This work sets reference starting points for designing and interpreting MMR RNA analyses. Our database and literature searches retrieved 30 MLH1, 22 MSH2, 4 MSH6 and 9 PMS2 alternative transcripts, many predicted to introduce premature termination codons. Furthermore, we collected information on 66 MLH1, 24 MSH2 and 6 PMS2 nucleotide variants reported to be associated with altered expression of at least one of these alternative transcripts, and in many instances reported as splicing mutations. This review shows that there are many alternatively spliced MMR transcripts, which have potential to confound interpretation of splicing assays. These findings highlight the need to perform RNA analysis of patients systematically in parallel with control individuals, and call for the implementation of quantitative assessment of transcript levels for informed interpretation of mRNA assays.
Phylogeny of fossil and extant glypheid and litogastrid lobsters (Crustacea, Decapoda) as revealed by morphological characters
Authors: Charbonnier Sylvain , Audo Denis , Barriel Véronique , Garassino Alessandro , Schweigert Günter , Simpson Martin
Published: July 2014

A phylogenetic analysis of a total of 31 species: 27 fossil species from seven families (Glypheidae, Litogastridae, Mecochiridae, Pemphicidae, Erymidae, Clytiopsidae, Chimaerastacidae), and four extant species from three families (Glypheidae, Nephropidae, Stenopodidae) is proposed. Most of the genera considered are coded exclusively based upon their type species and, as much as possible, based upon the type specimens. The cladistic analysis demonstrates that the glypheidean lobsters (infraorder Glypheidea) form a monophyletic group including two superfamilies: Glypheoidea and Pemphicoidea new status. Glypheoidea includes three families: Glypheidae, Mecochiridae and Litogastridae. Litogastridae is the sister group of the clade Glypheidae + Mecochiridae. Pemphicoidea includes a single family: Pemphicidae. A new classification of Glypheidea is proposed and currently known genera are rearranged based upon the phylogenetic analysis.
The prognostic impact of the log odds of positive lymph nodes in colon cancer
Authors: Arslan N. C. , Sokmen S. , Canda A. E. , Terzi C. , Sarioglu S.
Published: July 2014

Aim

This study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer.

Method

Four hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed.

Results

The 5‐year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node‐negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node‐negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor.

Conclusion

Conventional TNM staging for nodes (pN) and LNR status cannot reliably classify node‐negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN.
Does rectal cancer height influence the oncological outcome?
Authors: Bhangu A. , Rasheed S. , Brown G. , Tait D. , Cunningham D. , Tekkis P.
Published: July 2014

Aim

The influence of the height of rectal cancer from the anal verge on the oncological outcome is controversial. This study aimed to determine the influence of the height of the tumour on the survival of patients treated in a specialized rectal cancer unit.

Method

Patients undergoing surgery for primary rectal cancer from 2006 to 2013 were identified from a prospectively maintained rectal cancer database. Those requiring total or multicompartmental pelvic exenteration were excluded. Low cancer was defined as tumour < 5 cm from the anal verge, as assessed by endoscopy and/or digital rectal examination. The primary outcome was 3‐year disease‐free survival (DFS).

Results

Of 340 patients, 203 (59.7%) had low cancer. There were 302 (89%) restorative and 38 (11%) nonrestorative procedures. The rate of positive circumferential resection margin was similar for low compared with high cancer (3.4% vs 2.9%, P = 1.0) and for restorative compared with nonrestorative procedures in low cancer only (3.0% and 5.3%, P = 0.619). Low compared with high anterior resection was associated with increased anastomotic leakage (8.5% vs 2.2%, P = 0.023). Three‐year DFS was similar for low and high resection (82% vs 86%, P = 0.305) and between restorative vs nonrestorative procedures in low cancer only (88% vs 77%, P = 0.215). In an adjusted model, low height did not lead to worse survival outcome (3‐year DFS hazard ratio 0.54, 95% CI 0.24–1.24, P = 0.147).

Conclusion

With careful planning and a multidisciplinary approach, equivalent oncological outcome can be achieved for patients with rectal cancer who undergo curative surgery regardless of differences in tumour characteristics, location and operation performed.
Reversion of developmental mode in insects: evolution from long germband to short germband in the polyembrionic wasp Macrocentrus cingulum Brischke
Authors: Sucena Élio , Vanderberghe Koen , Zhurov Vladimir , Grbić Miodrag
Published: July 2014

Germband size in insects has played a central role in our understanding of insect patterning mechanisms and their evolution. The polarity of evolutionary change in insect patterning has been viewed so far as the unidirectional shift from the ancestral short germband patterning of basal hemimetabolous insects to the long germband patterning observed in most modern Holometabola. However, some orders of holometabolic insects display both short and long germband development, though the absence of a clear phylogenetic context does not permit definite conclusions on the polarity of change. Derived hymenoptera, that is, bees and wasps, represent a classical textbook example of long germband development. Yet, in some wasps putative short germband development has been described correlating with lifestyle changes, namely with evolution of endoparasitism and polyembryony. To address the potential reversion from long to short germband, we focused on the family Braconidae, which displays ancestral long germband development, and examined the derived polyembryonic braconid Macrocentrus cingulum. Using SEM analysis of M. cingulum embryogenesis coupled with analyses of embryonic patterning markers, we show that this wasp evolved short germband embryogenesis secondarily, in a way that is reminiscent of embryogenesis in the beetle Tribolium castaneum. This work shows that the evolution of germband size in insects is a reversible process that may correlate with other life‐history traits and suggests broader implications on the mechanisms and evolvability of insect development.
Back to Basics: The Great Recession and the Narrowing of IMF Policy Advice
Authors: Broome André
Published: July 2014

This article contributes to the literature on the dynamics of change and continuity in the International Monetary Fund's (IMF's) policy paradigm. The IMF embarked on a process of “streamlining conditionality” during the 2000s, but many observers have argued that the IMF's policy paradigm from the 1990s remains intact. This article examines whether the scope of the IMF's policy advice to borrowers during the Great Recession narrowed in comparison to its advice to borrowers during the heyday of the Washington consensus in the 1980s and 1990s. The article uses qualitative content analysis to establish the frequency of a series of policy dialogue indicators in four sample sets of countries requesting IMF stand‐by arrangements over three decades. The evidence suggests that contemporary IMF policy advice to borrowers continues to stress the importance of fiscal consolidation, with reduced emphasis on promoting the structural economic reforms associated with the Washington consensus era.
Operational Diagnostic Criteria for Chronic Migraine: Expert Opinion
Authors: Silberstein Stephen D. , Lipton Richard B. , Dodick David W.
Published: July 2014

Objective

The prevalence, disability, progression, and treatment needs associated with chronic migraine (CM) mandate epidemiological, clinical, and basic research to better understand the clinical course of this disorder and to facilitate development of more effective therapies. Such efforts have been significantly impeded by lack of agreement within the headache specialist community of the most appropriate diagnostic criteria for CM.

Methods

This paper reviews the pertinent nosological literature and extensive field testing already performed.

Results

We recommend that the International Classification of Headache Disorders‐3β criteria for CM be modified. We would remove the need for 5 prior migraine attacks and would replace “Headache considered by patient to be onset migraine and relieved by a triptan or an ergotamine derivative” with “criteria A and B for 1.5 probable migraine.”

Conclusions

The proposed criteria are guided by the aims of accurately characterizing patients with migraine who develop primary chronic daily headache, reflecting the large numbers of patients with CM in clinical practice, and facilitating research into a disorder that is an academic and clinical priority.
Medication Overuse Headache
Authors: Munksgaard Signe B. , Jensen Rigmor H.
Published: July 2014

Background

Medication overuse headache (MOH) affects between 1% and 2% of the general population but is present in up to 50% of patients seen in headache centers. There are currently no internationally accepted guidelines for treatment ofMOH.

Methods

A review of the current literature on MOH treatment and pathophysiology.

Results

We conclude that headache frequency can be reduced to episodic headache in more than 50% of the patients by simple detoxification and information. Approximately half the patients will not have need for prophylactic medication after withdrawal. Pain perception is altered in patients withMOHbut can be restored to a baseline pattern, indicating a reversible mechanism in the central sensitization leading to chronic pain. The great comorbidity with depression and anxiety could be a consequence of the altered serotonin metabolism indicating a reversible and potentially treatable condition.

Conclusion

Increased focus onMOHis extremely important, asMOHboth can and should be treated and prevented.MOHis thus a diagnosis that should be considered in all chronic headache patients as the very first step in their management strategy. In the general population, prevention campaigns againstMOHare essential to minimize chronic pain disability.
Impact of the ‘Healthy Dads, Healthy Kids’ lifestyle programme on the activity‐ and diet‐related parenting practices of fathers and mothers
Authors: Lloyd A. B. , Lubans D. R. , Plotnikoff R. C. , Morgan P. J.
Published: July 2014

Objectives

The aim was to evaluate the impact of the ‘Healthy Dads, Healthy Kids’ programme on fathers' and mothers' activity‐ and diet‐related parenting practices.

Methods

Overweight/obese fathers (n = 87) and their primary school‐aged children (56% boys) were randomized to either (i) 7‐week programme (n = 45) or (ii) control group (n = 42). The programme involved four sessions for fathers only and three for fathers/children. Mothers were not directly involved. Parenting practices of both fathers and mothers were measured using the parenting strategies for eating and activity scale at baseline and 14‐week follow‐up.

Results

Intention‐to‐treat analysis using linear mixed models revealed significant group‐by‐time effects for fathers' limit setting (P = 0.048, d = 0.36) and reinforcement for multiple lifestyle behaviours (P = 0.001, d = 0.79). No significant intervention effects were found for fathers' control, monitoring, discipline or mothers' parenting practices (P > 0.05).

Conclusions

The Healthy Dads, Healthy Kids programme had a positive impact on some parenting practices for fathers but not mothers.
iPad use at the bedside: a tool for engaging patients in care processes during ward rounds?
Authors: Baysari M. T. , Adams K. , Lehnbom E. C. , Westbrook J. I. , Day R. O.
Published: July 2014

Background

Previous work has examined the impact of technology on information sharing and communication between doctors and patients in general practice consultations, but very few studies have explored this in hospital settings.

Aims

To assess if, and how, senior clinicians use an iPad to share information (e.g. patient test results) with patients during ward rounds and to explore patients' and doctors' experiences of information sharing events.

Methods

Ten senior doctors were shadowed on ward rounds on general wards during interactions with 525 patients over 77.3 h, seven senior doctors were interviewed and 180 patients completed a short survey.

Results

Doctors reported that information sharing with patients is critical to the delivery of high‐quality healthcare, but were not seen to use the iPad to share information with patients on ward rounds. Patients did not think the iPad had impacted on their engagement with doctors on rounds. Ward rounds were observed to follow set routines and patient interactions were brief.

Conclusions

Although the iPad potentially creates new opportunities for information sharing and patient engagement, the ward round may not present the most appropriate context for this to be done.
Assessment of renal involvement in patients with familial Mediterranean fever: a clinical study from Ardabil, Iran
Authors: Bashardoust B. , Maleki N.
Published: July 2014

Background and Aim

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent episodes of painful inflammation in the abdomen, chest or joints. The association between FMF and non‐amyloid glomerulopathies are unusual. In this study, we describe our experiences and observations about renal involvement in patients with FMF.

Methods

A total of 108 patients with FMF was enrolled in the study. Twelve patients with FMF were referred to the Nephrology Service, for evaluation and assessment of the degree of renal involvement. All the 12 patients underwent percutaneous ultrasound‐guided renal biopsies and genetic analysis.

Results

On microscopic examination of the kidney specimens, six patients were found to have amyloidosis, five focal segmental glomerulosclerosis and one patient membranoproliferative glomerulonephritis. It seems that in patients with FMF and renal amyloidosis, the response to treatment with colchicine is excellent, but in patients with FMF and focal segmental glomerulosclerosis, the response to treatment with colchicine is poor. We present an evidence‐based algorithm, constructed based on literature review, to aid decision making in management of renal involvement in patients with FMF.

Conclusion

The results of our study suggest that in patients with FMF and renal involvement, non‐amyloid renal lesions should be considered in the differential diagnosis in addition to amyloidosis.
Simulator for Demonstration of Some Bioelectric Properties of Biological Transducers
Authors: ÖBerg P. Å. , Sjöstrand U.
Published: July 2014

An electronic simulator demonstrating some of the properties of biological transducers is described. It is possible to simulate the “nerve activity” and its relation to “generator potential” and the “adaptation phenomenon” for some different kinds of biological receptors.
Differences in the Subcellular Localization of Choline, Acetylcholine and Atropine Taken up by Mouse Brain Slices in vitro
Authors: Schuberth J. , Sundwall A.
Published: July 2014

Mouse brain cortex slices have been incubated with tritium labelled acetylcholine, choline and atropine. The subcellular distribution of radioactivity has then been studied by homogenization of the slices in sucrose and separation of the subcellular particles on a continuous exponential sucrose gradient. It was found that about 30 per cent of the radioactivity in the slices were localized in the fraction containing nerve‐endings and mitochondria. Using differential centrifugation and gradient centrifugation of the crude mitochondrial fraction obtained, it was found that acetylcholine is specifically bound to the nerve‐ending particles. Choline had a subcellular distribution similar to acetylcholine, while atropine was not specifically bound to the nerve‐endings.
Demonstration of a Receptor Reserve for Acetylcholine in the Human Fetus
Authors: Boréus Lars O.
Published: July 2014

The development of the acetylcholine (ACh) receptor function in man was studied by means of determination of dose‐effect curves for ACh action upon fetal smooth muscle tension in vitro. Segments of ileum from human fetuses of various gestational ages (6.5–20.5 cm head‐rump length) were used. Phenoxybenzamine (POB) blocked irreversibly the spasmogenic action of ACh. Exposure of the tissue to low concentrations of POB for a short period led to a shift of the subsequent dose‐effect curve for ACh along the dose‐axis. By varying the length of the POB exposure period (4–10 min) different degrees of shift, i.e. different degrees of antagonism, could be produced. It was found that the shift could amount to as much as about one logarithmic unit with preserved maximum of the dose‐effect curves. This means that activation of only a fraction of ACh receptors is enough for maximal response. Thus, the phenomenon of “receptor reserve” to ACh was demonstrated. Furthermore, the extent of this “reserve” was not significantly changing during the fetal age period studied. It is concluded that the characteristics of ACh receptor function in man are fully developed in early fetal life.
Nervous Control of Urinary Bladder in Cats
Authors: Edvardsen Per
Published: July 2014

The bladder response to electrical stimulation of the parasympathetic and sympathetic nerves was recorded in anesthetized cats. Stimulation of the pelvic nerves caused a sustained bladder contraction. This response was not changed significantly by blockade with atropine at 5 cps stimulation, while at 30 cps only an initial contraction was obtained. It was abolished with hexamethonium, whereas it remained unchanged after guanethidine, propranolol and dibenzyline. There was no evidence to suggest the presence of inhibitory fibres. Stimulation of the hypogastric nerves gave rise to an initial contraction followed by relaxation. On continuous stimulation the slope of the pressure/volume curve was flattened in proportion to the strength of stimulation. However, during the relaxation phase of the detrusor muscle, the bladder outlet responded by contraction. The sympathetic response was blocked by guanethidine, but this, in small doses, augmented the contraction phase. Propranolol increased the contraction phase, and in addition converted the relaxation to contraction. The contraction response could be blocked selectively by administration of dibenzyline. It is suggested that adrenergic alpha‐receptors are present both at the bladder outlet, and in the detrusor muscle as well, but that in the latter case their presence is masked by the inhibitory beta‐receptors.
On the Components of the Kr85 Wash‐Out Curves from the Small Intestine of the Cat
Authors: Kampp Mogens , Lundgren Ove , Sjöstrand Johan
Published: July 2014

The wash‐out of intra‐arterially injected Kr85 from denervated small intestinal segments (mainly jejunum) of the cat was recorded by means of a scintillation detector at various levels of vascular tone. The elimination curve could be resolved into four components (I‐IV) at all blood flow levels. Four independent methods were used in an attempt to localize the different components, namely, registration of the elimination of β‐activity, local injections into different parts of the intestinal segment, autoradiography and comparisons of weights of the compartments. The following localization of the four components was made probable. The first component reflected predominantly a countercurrent exchange of krypton between the ascending and descending limbs of the vascular loops in the mucosa at “resting” flow levels. During vasodilatation, this component mirrored mainly the wash‐out of the tracer from a well‐perfused region in the mucosa‐submucosa. The second and third components mainly reflected the disappearance of Kr85 from the mucosa and the muscularis, respectively. The slowest component (IV) probably mirrored an elimination of Kr85 from the perivascular fat of the mesentery and an absorption of the tracer from the intestinal lumen.
The Inhibitory Effect of Various Phenols upon ATP‐induced Vasoconstriction in Isolated Perfused Rabbit Lungs
Authors: Lunde P. K. M. , Waaler B. A. , Walløe L.
Published: July 2014

A spontaneously developing vasoconstriction in isolated perfused lungs and the vasoconstriction caused by arterially injected ATP (50 μg) were both inhibited by the addition to the perfusate of various phenols. The inhibitory effect upon ATP‐induced vasoconstriction of phenol, the 3 isomers of cresol (mono‐methyl‐phenol) and the 6 isomers of xylenol (di‐methyl‐phenol) was compared on a rank scale. There was a definite pattern in the results. Methyl groups in either o‐ or p‐position in relation to the hydroxy group increased the inhibitory effect of the phenol, whereas a methyl group in m‐position resulted in little inhibitory effect.
The Effect of Barbiturate Anesthesia and Hypothermia on the Edema Formation Caused by Subcutaneous Injection of 5‐Hydroxytryptamine in Mice
Authors: Svanes Knut
Published: July 2014

Local edema formation caused by subcutaneous injection of 5‐hydroxytryptamine (5‐HT) was studied in unanesthetized, anesthetized normothermic and hypothermic mice. The edema was estimated quantitatively by a method involving the assay of extravasated trypan blue. Pentobarbital was used for anesthesia. The hypothermic mice were kept at a rectal temperature of 21–22° C. In unanesthetized and anesthetized normothermic mice the edema formation increased with increasing doses of 5‐HT. At normal temperature light anesthesia greatly reduced the edema caused by 100 μg/ml 5‐HT, but did not modify the edema caused by 10 or 1 μg/ml 5‐HT. A lowering of the body temperature led to reduced edema formation, and the edema caused by 100 μg/ml 5‐HT was relatively more reduced than that caused by 10 μg/ml 5‐HT. The reduced edema formation under anesthesia and hypothermia might in part be due to increased constriction of the local arteries and arterioles under these conditions.
Symptoms dermatologists should look for in daily practice to improve detection of psoriatic arthritis in psoriasis patients: an expert group consensus
Authors: Villani A.P. , Rouzaud M. , Sevrain M. , Barnetche T. , Paul C. , Richard M.‐A. , Beylot‐Barry M. , Misery L. , Joly P. , Aractingi S. , Aubin F. , Le Maître M. , Cantagrel A. , Ortonne J.‐P. , Jullien D.
Published: July 2014

Background

Up to 29% of patients with psoriasis seen by dermatologists have undiagnosed psoriatic arthritis (PsA). As early detection of PsA may be associated with improved joint and skin outcomes, it is essential for dermatologists to improve their ability to diagnose PsA. Skin and nail features of psoriasis associated with PsA are well known to dermatologists but they may feel less confortable assessing other symptoms and they rarely use PsA screening questionnaires.

Objective

To develop a limited list of clinical signs and symptoms that a dermatologist should be looking for in a psoriasis patient in addition to specific skin features and nail involvement, to improve PsA detection.

Methods

A systematic search was performed in Pubmed, Cochrane and Embase databases to identify clinical key symptoms associated with PsA. It yielded 27 studies in which we extracted a list of clinical signs and symptoms observed in PsA and submitted it to a panel of dermatology experts through a DELPHI selection process. The experts had to determine which minimal set of signs and symptoms dermatologists should look for in daily practice to improve detection of PsA in patients with psoriasis.

Results

The four items that received a score higher than 90% in the DELPHI process were finally selected. Those items were as follows: peripheral inflammatory pain (100%), axial inflammatory pain (95.3%), dactylitis (93%), buttock and sciatic pain (90.7%). The remaining items: distal interphalangeal joints (DIPs) involvement (83.7%), Talalgia (79.1%), swollen Achille's tendon (41.9%), costo‐chondral involvement (32.6%), uveitis (7%), mouth ulcerations (2.3%), were not retained.

Conclusion

We propose a set of four items to screen psoriasis patients for psoriatic arthritis for routine clinical use by dermatologists.
Treatment (biotherapy excluded) of psoriatic arthritis: an appraisal of methodological quality of international guidelines
Authors: Sevrain M. , Villani A.P. , Rouzaud M. , Barnetche T. , Paul C. , Richard M.‐A. , Beylot‐Barry M. , Jullien D. , Aractingi S. , Aubin F. , Joly P. , Le Maitre M. , Cantagrel A. , Ortonne J.‐P. , Misery L.
Published: July 2014

Background

Some international guidelines have been published to provide the best care for patients with psoriatic arthritis (PsA) but little is known about their quality.

Objective

The primary aim of this study was to examine the quality of guidelines that concern treatment (biotherapy exluded) of PsA. The secondary aim was to review studies published since the publication of the most recent guideline.

Methods

A systematic literature search was carried out from 2007 to February 2013, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including ‘Arthritis, Psoriatic/therapy’ NOT ‘Biological Therapy’ OR ‘Antibodies, Monoclonal’ OR ‘Recombinant Fusion Proteins’ OR ‘tumour necrosis factor‐alpha’. The AGREE instrument (Appraisal of Guidelines Research and Evaluation) was used by four reviewers to evaluate the quality of selected guidelines according to the proposed methodology.

Results

Of the 518 identified references, six guidelines and two studies were selected. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well‐addressed domains were ‘applicability’, ‘stakeholder involvement’, ‘scope and purpose’ and ‘quality of development’, whereas ‘editorial independence’ and ‘clarity and presentation’ were less problematic.

Conclusion

Although guidelines development was of good quality, many of the studies that they included are of poorer quality. This work indicates that the current guidelines can be improved, particularly the stakeholder domain and the applicability domain. The prospective use of the AGREE instrument should improve the guideline quality. More controlled trials should be required but are unlikely to be conducted, given the lack of interest in studying old drugs.
The association of metabolic syndrome and psoriasis: a population‐ and hospital‐based cross‐sectional study
Authors: Miller I.M. , Ellervik C. , Zarchi K. , Ibler K.S. , Vinding G.R. , Knudsen K.M. , Jemec G.B.
Published: July 2014

Background

Psoriasis (PS) has been suggested to be associated with the metabolic syndrome (MetS) in numerous studies with conflicting results. The vast majority of previous data were based on PS subjects from hospitals, and when based on data from the general population the PS subjects were often identified in insurance health databases. Furthermore, many studies used a single method approach, e.g. self‐reported diagnosis.

Objective

We have therefore investigated a possible association between PS and MetS on PS subjects from the hospital as well as the general population using combined methods, i.e. self‐reported diagnosis, physical examinations and blood samples.

Methods

A population‐ and hospital‐based cross‐sectional study of the possible association between PS and MetS.

Results

Thirty‐six hospital PS subjects, 860 population PS subjects and 14 016 non‐PS subjects were identified. The odds ratios (ORs) for hospital PS subjects and population PS subjects vs. population non‐PS subjects, respectively, were 5.14 (2.47–10.69) and 1.29 (1.09–1.53) for MetS, 4.55 (1.91–10.85) and 1.16 (0.85–1.59) for diabetes, 1.92 (0.87–4.22) and 1.00 (0.86–1.17) for hypertension, 4.34 (1.86–10.10) and 1.15 (1.00–1.34) for hypertriglyceridaemia, 3.88 (1.96–7.69) and 1.19 (1.01–1.42) for hypoHDL, 5.77 (2.89–11.52) and 1.19 (1.00–1.41) for general obesity and 2.92 (1.45–5.88) and 1.34 (1.16–1.55) for abdominal obesity. Obesity acted as a possible confounder. A uniform pattern of higher ORs for hospital PS subjects when compared to population PS subjects was observed. The severity and duration of PS did not seem to affect the results. As this is a cross‐sectional study we cannot demonstrate causality.

Conclusion

The data suggested an association between PS and MetS as well as its individual parameters on a hospital‐based level, with the exception of hypertension. On a population‐based level the associations were only significant for MetS, hypoHDL and abdominal obesity.
“Quiero ir y no quiero ir” (I Want to Go and I Don't Want to Go): Nicaraguan Children's Ambivalent Experiences of Transnational Family Life
Authors: Yarris Kristin Elizabeth
Published: July 2014

Este artículo explora las experiencias de los niños nicaragüenses cuyas madres han migrado. Utilizo la idea del “imaginario del migrante” (Jackson ) como marco teórico para capturar la manera en que las experiencias subjetivas que los niños tienen de la migración, son estructuradas por procesos sociales, culturales, políticos y económicos. Demuestro que los niños son actores centrales en procesos mundiales de migración (Coe et al. ). Conscientes de los factores (principalmente económicos) que empujan a sus madres a emigrar, los niños participan del proceso como receptores de las remesas en niveles materiales y afectivos, forman vínculos relacionales con sus abuelas y otras cuidadoras ante la ausencia de sus madres, y responden con incertidumbre a la posibilidad de reunificación con sus madres migrantes en países de destino. El deseo ambivalente de los niños de estar tanto “aquí” como “allá” (Hondagneu‐Sotelo y Avila ) ‐tanto en Nicaragua con sus familias extendidas como con sus madres viviendo afuera – es central en el imaginario que los niños tienen de la migración y en su experiencia real de formar parte de una familia transnacional.
Spontaneous glomerular mesangial lesions in common marmoset monkeys (Callithrix jacchus): a benign non‐progressive glomerulopathy
Authors: Collins Michael G. , Rogers Natasha M. , Jesudason Shilpanjali , Kireta Svjetlana , Brealey John , Coates Patrick Toby
Published: July 2014

Background

Common marmosets are known to develop an IgM glomerulopathy, which has been linked with ‘wasting marmoset’ syndrome. This study investigated renal pathology in a colony of marmosets, with and without weight loss.

Methods

Renal histology, immunofluorescence, and electron microscopy were performed on marmosets euthanized for research or for weight loss. Serum and urine biochemistry were measured during life and at euthanasia.

Results

Histology from 25 adult marmosets (19 research and 6 weight loss) showed mesangial expansion in the majority of glomeruli. Mesangial changes correlated with electron‐dense deposits and IgM deposition by immunofluorescence; negligible other pathology was seen. Glomerular basement membrane thickness appeared increased compared to reported human measurements. Low‐grade proteinuria was present in all animals, but did not progress. Renal function was normal in all animals.

Conclusions

Marmosets develop a glomerulopathy characterized by mesangial expansion, IgM deposition, and proteinuria. This is a benign occurrence and not specifically associated with weight loss.
A Mixed‐Methods Study on Factors Influencing Prenatal Weight Gain in Ethnic‐Minority Women
Authors: Hackley Barbara , Kennedy Holly Powell , Berry Diane C. , Melkus Gail D'Eramo
Published: July 2014

Introduction

Gaining too much weight in pregnancy is associated with perinatal complications and increases the risks of future obesity for both women and their infants. Unfortunately, women enrolled in intervention trials have seen little improvement in adherence to prenatal weight gain recommendations compared to women receiving standard prenatal care. Therefore, the purpose of this descriptive mixed‐methods study was to explore factors related to excessive weight gain in pregnancy.

Methods

Nonpregnant nulliparous women, currently pregnant women, and postpartum women (N = 43) were recruited from a health center serving an inner‐city minority community. Women completed questionnaires on knowledge, self‐efficacy, and behaviors related to nutrition, exercise, and prenatal weight gain. Fifteen of these women participated in focus groups. Focus group data were analyzed using ATLAS.ti (Scientific Software Development GmbH, Berlin, Germany). Codes were created, themes were identified, and consensus was reached through multiple iterations of the analysis by study personnel.

Results

Excessive weight gain was common. Nutritional knowledge was poor and significantly lower among nonpregnant nulliparous women. Women felt sure that they could engage in healthy behaviors, but few did so. Participants in focus groups identified multiple barriers to healthy behaviors in pregnancy and made suggestions on how to help women more readily make improvements in these behaviors.

Discussion

Strategies identified in this study such as providing focused education directed at nonpregnant nulliparous women, stressing portion control, helping women better manage their cravings, and providing more pragmatic support and resources need to be explored in future research.
Elevation of striatal urate in experimental models of Parkinson's disease: a compensatory mechanism triggered by dopaminergic nigrostriatal degeneration?
Authors: De Luca Maria Antonietta , Cauli Omar , Morelli Micaela , Simola Nicola
Published: July 2014

Epidemiological studies have indicated an inverse association between high uricemia and incidence of Parkinson's disease (PD). To investigate the link between endogenous urate and neurotoxic changes involving the dopaminergic nigrostriatal system, this study evaluated the modifications in the striatal urate levels in two models of PD. To this end, a partial dopaminergic degeneration was induced by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in mice, while a severe dopaminergic degeneration was elicited by unilateral medial forebrain bundle infusion of 6‐hydroxydopamine (6‐OHDA) in rats. Urate levels were measured by in vivo microdialysis at 7 or 14 days from toxin exposure. The results obtained demonstrated higher urate levels in the dopamine‐denervated striatum of 6‐OHDA‐lesioned rats compared with the intact striatum. Moreover, an inverse correlation between urate and dopamine levels was observed in the same area. In contrast, only a trend to significant increase in striatal urate was observed in MPTP‐treated mice. These results demonstrate that a damage to the dopaminergic nigrostriatal system elevates the striatal levels of urate, and suggest that this could be an endogenous compensatory mechanism to attenuate dopaminergic neurodegeneration. This finding may be important in light of the epidemiological and preclinical evidences that indicate a link between urate and development of PD.

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This study evaluated the in vivo modifications in the striatal urate levels in the mouse MPTP and the rat 6‐OHDA models of Parkinson's disease‐like dopaminergic nigrostriatal toxicity. The results obtained demonstrated that dopaminergic neurotoxicity is associated with higher urate levels in the striatum, which would strengthen the idea of a link between endogenous urate and Parkinson's disease.
Glutamate synthesis has to be matched by its degradation – where do all the carbons go?
Authors: Sonnewald Ursula
Published: July 2014

The central process in energy production is the oxidation of acetyl‐CoA to CO2 by the tricarboxylic acid (TCA, Krebs, citric acid) cycle. However, this cycle functions also as a biosynthetic pathway from which intermediates leave to be converted primarily to glutamate, GABA, glutamine and aspartate and to a smaller extent to glucose derivatives and fatty acids in the brain. When TCA cycle ketoacids are removed, they must be replaced to permit the continued function of this essential pathway, by a process termed anaplerosis. Since the TCA cycle cannot act as a carbon sink, anaplerosis must be coupled with cataplerosis; the exit of intermediates from the TCA cycle. The role of anaplerotic reactions for cellular metabolism in the brain has been studied extensively. However, the coupling of this process with cataplerosis and the roles that both pathways play in the regulation of amino acid, glucose, and fatty acid homeostasis have not been emphasized. The concept of a linkage between anaplerosis and cataplerosis should be underscored, because the balance between these two processes is essential. The hypothesis that cataplerosis in the brain is achieved by exporting the lactate generated from the TCA cycle intermediates into the blood and perivascular area is presented. This shifts the generally accepted paradigm of lactate generation as simply derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.

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Intermediates leave the tricarboxylic acid cycle and must be replaced by a process termed anaplerosis that must be coupled to cataplerosis. We hypothesize that cataplerosis is achieved by exporting the lactate generated from the cycle into the blood and perivascular area. This shifts the paradigm of lactate generation as solely derived from glycolysis to that of oxidation and might present an alternative explanation for aerobic glycolysis.
Corporate Governance and Cash Holdings: Evidence From the U.S. Property–Liability Insurance Industry
Authors: Hsu Wen‐Yen , Huang Yenyu (Rebecca) , Lai Gene
Published: July 2014

This article examines the impact of board and finance committee characteristics on insurers' cash holdings using a sample of 1,454 U.S. stock property–liability insurer‐year observations. We focus on the roles of independent board members and independent finance committee members. Our results suggest that independent board members allow managers to hold excess cash holdings to avoid underinvestment and play a monitoring role in managers' cash spending behavior in a regulated industry. The overall findings are consistent with the independent director responsibility hypothesis, which suggests that independent directors play a monitoring role in managers' cash spending behavior and avoiding underinvestment problems.
Optimal Social Insurance for Heterogeneous Agents With Private Insurance
Authors: Lehr Brandon
Published: July 2014

This article analytically characterizes optimal social insurance in an economy with bothex anteheterogeneity andex postrisk, decomposing the benefits of social insurance into a redistributive and insurance benefit. Agents exert effort to increase the likelihood of high outcome events and are additionally supplied actuarially fair private insurance for this earnings risk. This article is novel in its joint consideration of two sources of heterogeneity, two potential sources of insurance, and an endogenousex postdistribution of outcomes. The introduction of optimal private insurance eliminates the insurance benefit of social insurance, but leaves the redistributive benefit intact. An income effect induced by the crowding out of private insurance generates an additional benefit to social insurance when it takes the form of a linear income tax. Finally, numerical simulations illustrate how the relative contributions ofex anteandex postrisk differentially impact the welfare loss associated with setting optimal social insurance without recognizing the presence of private insurance.