bluuebunny/crossref_metadata_2025 huggingface dataset:
Antenatal corticosteroid exposure at term increases adult adiposity: an experimental study in sheep
Authors: Berry Mary J. , Jaquiery Anne L. , Oliver Mark H. , Harding Jane E. , Bloomfield Frank H.
Published: April 2013

Clinical practice guidelines for elective cesarean section at early‐term gestation (37–38 weeks) recommend antenatal corticosteroids to reduce neonatal respiratory morbidity. However, the long‐term health implications for offspring exposed to corticosteroids at term are unknown and may differ from the effects of preterm corticosteroid exposure. We therefore randomized singleton‐bearing ewes (n = 64) to receive a clinically relevant dose of corticosteroids at term or no treatment. Body composition was assessed in adult offspring using dual‐energy X‐ray absorptiometry. Relative to skeletal size female, but not male, offspring of steroid‐treated ewes had increased weight and a greater fat mass than controls (relative weight: 49.1 ± 1.1 vs. 52.9 ± 1.2 kg/m2, p = 0.02; relative fat mass: 5.4 ± 0.7 vs. 3.4 ± 0.7 kg/m2, p = 0.04). Whether corticosteroid exposure at early‐term gestation increases adult adiposity in humans is unknown and needs further investigation.
Eye motion increases temporal visual field extent
Authors: Denion Eric , Dugué Audrey‐E. , Coffin‐Pichonnet Sophie , Augy Sylvain , Mouriaux Frédéric
Published: April 2013

Purpose:  To study the impact of eye motion on visual field extent.

Methods:  Visual fields were tested in 15 healthy volunteers with the Goldmann perimeter using a V4 test object, from seen to unseen, first in primary position of gaze, then allowing eye motion. Temporal points falling out of the cupola were tested again after a controlled nasal head rotation using a headband prototype fitted with a line‐laser level having two orthogonal vial levels. Visual field surface areas (cm2) were calculated as projections on a 30‐cm virtual Goldmann cupola, whose extent would have been large enough to include all points. Reproducibility error of the method assessed by calculation of the relative difference between surface areas of 12 visual field tests and 12 visual field retests was estimated at 14%. Hertel exophthalmometry was recorded to study the influence of globe position on visual field extent.

Results:  Binocular visual field surface area increased by 37% with eye motion (p‐value = 1.20·10−9). This increase was highest (46%; p‐value = 1.2·10−24) in the temporal quadrant. Median maximal visual field temporal eccentricity with eye motion was 128.3° (minimum: 109.5°; maximum: 137.7°) and more than 135° in four eyes of three subjects. Hertel exophthalmometry was positively linked to visual field temporal surface area with eye motion (p‐value = 0.013).

Conclusions:  Eye motion greatly expands the temporal visual field. This peculiarity is likely an adaptation to terrestrial life with upright bipedal locomotion and may save head movements through horizontal eyeball scanning.
The diameter of the inferior vena cava provides a noninvasive way of calculating central venous pressure in neonates
Authors: Sato Yoshiaki , Kawataki Motoyoshi , Hirakawa Akihiro , Toyoshima Katsuaki , Kato Taichi , Itani Yasufumi , Hayakawa Masahiro
Published: April 2013

Aim

To explore a less invasive way of assessing preload in neonates than fitting catheters to measure central venous pressure (CVP). This study evaluated the relationship between inferior vena cava (IVC) measurements and gestational age (GA) or body weight (BW) in term and premature infants and the correlation between those measurements and CVP in sick infants under mechanical ventilation.

Methods

We studied 57 clinically stable infants, together with14 sick infants fitted with central venous catheters to measure CVP. Subcostal transverse views were recorded at the level of the left branch of portal vein, and the minimum (DS) and maximum (DL) diameters of the IVC were measured. We evaluated the values of DS and DL and the S/L ratio (DS divided by DL) in the clinically stable infants and the correlation between S/L and CVP in the sick infants with central catheters.

Results

DS and DL correlated positively and strongly with both GA and BW, whereas S/L was almost independent of both GA and BW and correlated strongly with CVP.

Conclusion

At the subcostal transverse views, S/L is much less affected by either GA or BW than DS or DL and correlates strongly with CVP in mechanically ventilated infants.
Pathophysiology of hypertension in pre‐eclampsia: a lesson in integrative physiology
Authors: Palei A. C. , Spradley F. T. , Warrington J. P. , George E. M. , Granger J. P.
Published: April 2013

Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of pre‐eclampsia have yet to be fully elucidated. However, it is evident that this is a complex disorder involving multiple organ systems, and by using integrative approaches, enormous progress has been made towards understanding the pathophysiology of pre‐eclampsia. Growing evidence supports the concept that the placenta plays a central role in the pathogenesis of pre‐eclampsia and that reduced uteroplacental perfusion, which develops as a result of abnormal cytotrophoblast invasion of spiral arterioles, triggers the cascade of events leading to the maternal disorder. Placental ischaemia leads to release of soluble placental factors, many of which are classified as anti‐angiogenic or pro‐inflammatory. Once these ischaemic placental factors reach the maternal circulation, they cause widespread activation and dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin‐1 and superoxide, increased vascular sensitivity to angiotensin II and decreased formation of vasodilators such as nitric oxide. This review highlights these links between placental ischaemia, maternal endothelial activation and renal dysfunction in the pathogenesis of hypertension in pre‐eclampsia.
Community resilience, social memory and the post‐2010 Christchurch (New Zealand) earthquakes
Authors: Wilson Geoff A
Published: April 2013

This article explores the importance of social memory for community resilience pathways in the city of Christchurch (New Zealand) in the wake of the post‐2010 earthquakes. Specific emphasis is placed on understanding how past earthquake history in Christchurch has influenced knowledge about, and responses to, the recent series of earthquakes. Building on previous work about possible impacts of social memory on community resilience, the paper argues that Christchurch residents were ill prepared for the sudden onset of on‐going earthquakes, and that the continuing threat, and associated uncertainty, posed by these tremors is gradually eroding residents’ ability to cope and plan for the future.
Understanding the dose–response relationship of allopurinol: predicting the optimal dosage
Authors: Graham Garry G. , Kannangara Diluk R. W. , Stocker Sophie L. , Portek Ian , Pile Kevin D. , Indraratna Praveen L. , Datta Indira , Williams Kenneth M. , Day Richard O.
Published: April 2013

Aims

The aim of the study was to identify and quantify factors that control the plasma concentrations of urate during allopurinol treatment and to predict optimal doses of allopurinol.

Methods

Plasma concentrations of urate and creatinine (112 samples, 46 patients) before and during treatment with various doses of allopurinol (50–600 mg daily) were monitored. Non‐linear and multiple linear regression equations were used to examine the relationships between allopurinol dose (D), creatinine clearance (CLcr) and plasma concentrations of urate before (UP) and during treatment with allopurinol (UT).

Results

Plasma concentrations of urate achieved during allopurinol therapy were dependent on the daily dose of allopurinol and the plasma concentration of urate pre‐treatment. The non‐linear equation: UT = (1 – D/(ID50 + D)) × (UP – UR) + UR, fitted the data well (r2 = 0.74, P < 0.0001). The parameters and their best fit values were: daily dose of allopurinol reducing the inhibitable plasma urate by 50% (ID50 = 226 mg, 95% CI 167, 303 mg), apparent resistant plasma urate (UR = 0.20 mmol l−1, 95 % CI 0.14, 0.25 mmol l−1). Incorporation of CLcr did not significantly improve the fit (P = 0.09).

Conclusions

A high baseline plasma urate concentration requires a high dose of allopurinol to reduce plasma urate below recommended concentrations. This dose is dependent on only the pre‐treatment plasma urate concentration and is not influenced by CLcr.
Stimulation of Suicidal Erythrocyte Death by Fumagillin
Authors: Zbidah Mohanad , Lupescu Adrian , Jilani Kashif , Lang Florian
Published: April 2013

Fumagillin, a cyclohexane isolated from fungus Aspergillus fumigatus, has anti‐infective and anti‐cancer potency. Fumagillin is at least partially effective by inducing suicidal death or apoptosis. In analogy to apoptosis of nucleated cells, eryptosis is the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Stimulators of eryptosis include increase of cytosolic Ca2+‐activity ([Ca2+]i) and ceramide. The present study explored whether fumagillin (5–100 μM) could stimulate eryptosis. To this end, [Ca2+]i was estimated from Fluo3 fluorescence, ceramide by utilizing specific antibodies, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding and haemolysis from haemoglobin release. As a result, a 48‐hr exposure to fumagillin significantly increased [Ca2+]i (≥10 μM), enhanced ceramide abundance (100 μM), triggered annexin V binding (≥10 μM) and decreased forward scatter (≥10 μM). Fumagillin exposure was followed by slight but significant increase of haemolysis. Removal of extracellular Ca2+ significantly blunted but did not abolish the effect of fumagillin (100 μM) on annexin V binding. The present observations disclose a novel effect of fumagillin, that is, stimulation of eryptosis, paralleled by Ca2+ entry, ceramide formation, phosphatidylserine exposure and decrease of cell volume.
The Contractile Effect of Anandamide in the Guinea‐Pig Small Intestine is Mediated by Prostanoids but not TRPV1 Receptors or Capsaicin‐Sensitive Nerves
Authors: Dékány András , Benko Rita , Szombati Veronika , Bartho Lorand
Published: April 2013

Although exogenous and endogenous cannabinoid receptor agonists have well‐documented inhibitory effects on gastrointestinal motility, a TRPV1 receptor‐mediated excitatory action of anandamide (arachidonoyl ethanolamide, AEA) in the guinea‐pig ileum strip has also been described. We used in vitro capsaicin desensitization for assessing the possible participation of sensory neurons in the contractile effect of anandamide on the guinea‐pig whole ileum, as well as autonomic drugs and a cyclooxygenase inhibitor for characterizing this response. Isolated organ experiments were used with isotonic recording. Contractions induced by anandamide (1 or 10 μM) were strongly inhibited by tetrodotoxin, indomethacin or atropine plus a tachykinin NK1 receptor antagonist, but weakly to moderately reduced by atropine alone and partly diminished by the fatty acid amide hydrolase inhibitor URB 597. Neither capsaicin pre‐treatment nor the TRPV1 receptor antagonist BCTC, the ganglionic blocking drug hexamethonium or cannabinoid (CB1 or CB2) receptor antagonists, influenced the effect of anandamide. It is concluded that the capsaicin‐insensitive, neuronal excitatory effect of anandamide in the intestine is most probably mediated by cyclooxygenase products. Such a mechanism may also play a role at other sites in the mammalian body.
Stigmatization and Denormalization as Public Health Policies: Some Kantian Thoughts
Authors: Dean Richard
Published: April 2013

The stigmatization of some groups of people, whether for some characteristic they possess or some behavior they engage in, will initially strike most of us as wrong. For many years, academic work in public health, which focused mainly on the stigmatization of HIV‐positive individuals, reinforced this natural reaction to stigmatization, by pointing out the negative health effects of stigmatization. But more recently, the apparent success of anti‐smoking campaigns which employ stigmatization of smokers has raised questions about whether stigmatization may sometimes be justified, because of its positive effects on public health. Discussion of the issue so far has focused on consequences, and on some Kantian considerations regarding the status of the stigmatized. In this article, I argue that further Kantian considerations regarding the treatment of the general public (the potential stigmatizers) also count against any public health policy involving stigmatization. Attempts to encourage stigmatization are likely to fail to appeal to the rational decision‐making abilities of the general public, and the creation of stigmatized groups (even if they are stigmatized for their voluntary behavior) is an obstacle to the self‐improvement of members of the general public.
Absolute Biological Needs
Authors: McLeod Stephen
Published: April 2013

Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb ‘need’ has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind‐dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of ‘normative’ are distinguished. On two of these, to describe a phenomenon or claim as ‘normative’ is to describe it as value‐dependent. A description of a phenomenon or claim as ‘normative’ in the third sense does not entail such value‐dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses.
Prion Disease: A Tale of Folds and Strains
Authors: Kretzschmar Hans , Tatzelt Jörg
Published: April 2013

Research on prions, the infectious agents of devastating neurological diseases in humans and animals, has been in the forefront of developing the concept of protein aggregation diseases. Prion diseases are distinguished from other neurodegenerative diseases by three peculiarities. First, prion diseases, in addition to being sporadic or genetic like all other neurodegenerative diseases, are infectious diseases. Animal models were developed early on (a long time before the advent of transgenic technology), and this has made possible the discovery of the prion protein as the infectious agent. Second, human prion diseases have true equivalents in animals, such as scrapie, which has been the subject of experimental research for many years. Variant Creutzfeldt–Jakob disease (vCJD) is a zoonosis caused by bovine spongiform encephalopathy (BSE) prions. Third, they show a wide variety of phenotypes in humans and animals, much wider than the variants of any other sporadic or genetic neurodegenerative disease. It has now become firmly established that particular PrPSc isoforms are closely related to specific human prion strains. The variety of human prion diseases, still an enigma in its own right, is a focus of this article. Recently, a series of experiments has shown that the concept of aberrant protein folding and templating, first developed for prions, may apply to a variety of neurodegenerative diseases. In the wake of these discoveries, the term prion has come to be used for Aβ, α‐synuclein, tau and possibly others. The self‐propagation of alternative conformations seems to be the common denominator of these “prions,” which in future, in order to avoid confusion, may have to be specified either as “neurodegenerative prions” or “infectious prions.”
Cell injury and Premature Neurodegeneration in Focal Malformations of Cortical Development
Authors: Iyer Anand , Prabowo Avanita , Anink Jasper , Spliet Wim G. M. , van Rijen Peter C. , Aronica Eleonora
Published: April 2013

Several lines of evidence suggest that cell injury may occur in malformations of cortical development associated with epilepsy. Moreover, recent studies support the link between neurodevelopmental and neurodegenerative mechanisms. We evaluated a series of focal cortical dysplasia (FCD,n = 26; typeIandII) and tuberous sclerosis complex (TSC,n = 6) cases. Sections were processed for terminal deoxynucleotidyl transferase‐mediated 2′‐deoxyuridine 5′‐triphosphate nick‐end labeling (TUNEL) labeling and immunohistochemistry using markers for the evaluation of apoptosis signaling pathways and neurodegeneration‐related proteins/pathways. In bothFCD IIandTSCspecimens, we observed significant increases in bothTUNEL‐positive and caspase–3‐positive cells compared with controls andFCD I. Expression ofβ‐amyloid precursor protein was observed in neuronal soma and processes inFCD IIandTSC. In these specimens, we also observed an abnormal expression of death receptor‐6. Immunoreactivity for phosphorylated tau was only found in older patients withFCD IIandTSC. In these cases, prominent nuclear/cytoplasmic p62 immunoreactivity was detected in both dysmorphic neurons and balloon/giant cells. Our data provide evidence of complex, but similar, mechanisms of cell injury in focal malformations of cortical development associated with mammalian target of rapamycin pathway hyperactivation, with prominent induction of apoptosis‐signaling pathways and premature activation of mechanisms of neurodegeneration.
Smooth muscle relaxation and activation of the large conductance Ca++ – activated K+ (BKCa) channel by novel oestrogens
Authors: Maher J , Hunter A C , Mabley J G , Lippiat J , Allen M C
Published: April 2013

Background and Purpose

Oestrogens can interact directly with membrane receptors and channels and can activate vascular BKCa channels. We hypothesized that novel oestrogen derivatives could relax smooth muscle by an extracllular effect on the α and β1 subunits of the BKCa channel, rather than at an intracellular site.

Experimental Approach

We studied the effects of novel oestrogens on the tension of pre‐contracted isolated rat aortic rings, and on the electrophysiological properties of HEK 293 cells expressing the hSloα or hSloα+β1 subunits. Two of the derivatives incorporated a quaternary ammonium side‐chain making them membrane impermeable.

Key Results

Oestrone, oestrone oxime and Quat DME‐oestradiol relaxed pre‐contracted rat aorta, but only Quat DME‐oestradiol‐induced relaxation was iberiotoxin sensitive. However, only potassium currents recorded in HEK 293 cells over‐expressing both hSloα and hSloβ1 were activated by oestrone, oestrone oxime and Quat DME‐oestradiol.

Conclusion and Implications

The novel oestrogens were able to relax smooth muscle, but through different mechanisms. In particular, oestrone oxime required the presence of the endothelium to exert much of its effect, whilst Quat DME‐oestradiol depended both on NO and BKCa channel activation. The activation of BKCa currents in HEK 293 cells expressing hSloα+β1 by Quat DME‐oestradiol is consistent with an extracellular binding site between the two subunits. The binding site resides between the extracellular N terminal of the α subunit and the extracellular loop between TM1 and 2 of the β1 subunit. Membrane‐impermeant Quat DME‐oestradiol lacks an exchangeable hydrogen on the A ring obviating antioxidant activity.
No difference in phenotype of the main Dutch SDHD founder mutations
Authors: van Hulsteijn L. T. , den Dulk A. C. , Hes F. J. , Bayley J. P. , Jansen J. C. , Corssmit E. P. M.
Published: April 2013

Objective

SDHD mutations predispose carriers to hereditary paraganglioma syndrome. The objective of this study was to assess the genotype–phenotype correlation of a large Dutch cohort of SDHD mutation carriers and evaluate potential differences in clinical phenotypes due to specific SDHD gene mutations.

Design

Retrospective, descriptive single‐centre study.

Patients

All consecutive SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center were included.

Measurements

Subjects were investigated according to structured protocols used for standard care, including repetitive biochemical and radiological screening for paragangliomas.

Results

Two hundred and one SDHD mutation carriers with a mean age at presentation of 42·6 ± 14·4 years and a mean follow‐up of 5·8 ± 5·4 years were evaluated. Eighty‐one percent carried the SDHD c.274G>T (p.Asp92Tyr) mutation and 13% the SDHD c.416T>C (p.Leu139Pro) mutation. No differences in clinical phenotype between these two specific SDHD mutations were found. Ninety‐one percent developed one or multiple paragangliomas in the head and neck region (HNPGLs), of which the carotid body tumour was the most prevalent (85%). Eighteen carriers developed pheochromocytomas, fifteen sympathetic paragangliomas and nine carriers (4%) suffered from malignant paraganglioma. By end of follow‐up, sixteen SDHD mutation carriers (8%) displayed no biochemical or radiological evidence of manifest disease.

Conclusions

The two main Dutch SDHD founder mutations do not differ in clinical expression. SDHD mutations are associated with the development of multiple HNPGLs and predominantly benign disease.
Perceptions of genetic counseling services in direct‐to‐consumer personal genomic testing
Authors: Darst BF , Madlensky L , Schork NJ , Topol EJ , Bloss CS
Published: April 2013

To describe consumers' perceptions of genetic counseling services in the context of direct‐to‐consumer personal genomic testing is the purpose of this research. Utilizing data from the Scripps Genomic Health Initiative, we assessed direct‐to‐consumer genomic test consumers' utilization and perceptions of genetic counseling services. At long‐term follow‐up, approximately 14 months post‐testing, participants were asked to respond to several items gauging their interactions, if any, with a Navigenics genetic counselor, and their perceptions of those interactions. Out of 1325 individuals who completed long‐term follow‐up, 187 (14.1%) indicated that they had spoken with a genetic counselor. The most commonly given reason for not utilizing the counseling service was a lack of need due to the perception of already understanding one's results (55.6%). The most common reasons for utilizing the service included wanting to take advantage of a free service (43.9%) and wanting more information on risk calculations (42.2%). Among those who utilized the service, a large fraction reported that counseling improved their understanding of their results (54.5%) and genetics in general (43.9%). A relatively small proportion of participants utilized genetic counseling after direct‐to‐consumer personal genomic testing. Among those individuals who did utilize the service, however, a large fraction perceived it to be informative, and thus presumably beneficial.
Dimethylfumarate: potency prediction and clinical experience
Authors: Basketter David A. , White Ian R. , Burleson Florence G. , Burleson Gary R. , Kimber Ian
Published: April 2013

Background. Dimethylfumarate (DMF) was the cause of a major outbreak of allergic contact dermatitis as a consequence of its use as an antifungal agent in leather products, particularly in furniture, with what became known as ‘toxic sofa dermatitis'.

Objectives. To determine whether the frequency and severity of reactions to DMF arose as a function of its intrinsic potency and/or the nature and extent of exposure.

Methods. The intrinsic potency of DMF was measured with the standard local lymph node assay (LLNA), with determination of an EC3 value, which is the threshold in the LLNA and serves as an indicator of relative skin‐sensitizing potency in humans.

Results. The EC3 value for DMF was 0.35% when tested in dimethylformamide as a vehicle, indicating that DMF is a strong, but not an extreme, skin sensitizer in this mouse model.

Conclusions. DMF appears to have a sensitizing potency in the mouse that is very similar to that of formaldehyde, which is also a strong human skin sensitizer. However, the frequency and intensity of allergic contact dermatitis reactions to DMF suggest that it was the prolonged, repeated and occlusive exposure to this chemical over large skin areas, combined with the strong sensitizing potency, that generated the ‘perfect storm’ conditions that caused the DMF epidemic.
The role of faecal diversion in low rectal cancer: a review of 1791 patients having rectal resection with anastomosis for cancer, with and without a proximal stoma
Authors: Nurkin S. , Kakarla V. R. , Ruiz D. E. , Cance W. G. , Tiszenkel H. I.
Published: April 2013

Aim

The morbidity of anastomotic dehiscence may be mitigated by a defunctioning stoma, but it is unclear if it is required for most low rectal anastomoses. Preoperative risk factors leading to anastomotic complications and the indications for faecal diversion have yet to be clearly defined.

Method

Using the American College of Surgeons‐National Surgical Quality Improvement Project (ACS‐NSQIP) participant‐use file, patients were identified who underwent low anterior resection with anastomosis for cancer at the 211 participating hospitals in 2005–08.

Results

A total of 1791 patients underwent low anterior resection. Patients were subdivided into two groups based on the level of the anastomosis. Of these 1266 patients had a low pelvic anastomosis (LPA) and 525 a coloanal anastomosis (CAA). In the LPA group, 606 patients had a stoma and 660 had no stoma. There were no differences in wound complications, sepsis or septic shock. Patients who had a stoma were more likely to have postoperative acute renal failure (1.7 vs 0.5%, P = 0.0485, OR 3.674). In the CAA group, 352 had a stoma and 173 had no stoma. In patients without faecal diversion, there was a significantly greater incidence of sepsis (8.7 vs 3.7%, P = 0.022, OR 2.47), septic shock (3.5 vs 0.57%, P = 0.018, OR 6.29) and need for reoperation (11 vs 1.7%, P = 0.0001, OR 7.11). Hospital length of stay was significantly longer with CAA and no stoma. On multivariate analysis, not having a stoma with a CAA was a risk factor for serious postoperative morbidity.

Conclusion

While a defunctioning stoma with a coloanal anastomosis seems to protect from postoperative sepsis, septic shock and need for reoperation, it is likely that it is overused in rectal cancer surgery.
Non‐symbolic halving in an Amazonian indigene group
Authors: McCrink Koleen , Spelke Elizabeth S. , Dehaene Stanislas , Pica Pierre
Published: April 2013

Much research supports the existence of an Approximate Number System (ANS) that is recruited by infants, children, adults, and non‐human animals to generate coarse, non‐symbolic representations of number. This system supports simple arithmetic operations such as addition, subtraction, and ordering of amounts. The current study tests whether an intuition of a more complex calculation, division, exists in an indigene group in the Amazon, the Mundurucu, whose language includes no words for large numbers. Mundurucu children were presented with a video event depicting a division transformation of halving, in which pairs of objects turned into single objects, reducing the array's numerical magnitude. Then they were tested on their ability to calculate the outcome of this division transformation with other large‐number arrays. The Mundurucu children effected this transformation even when non‐numerical variables were controlled, performed above chance levels on the very first set of test trials, and exhibited performance similar to urban children who had access to precise number words and a surrounding symbolic culture. We conclude that a halving calculation is part of the suite of intuitive operations supported by the ANS.
In‐treatment HDL cholesterol levels and development of new diabetes mellitus in hypertensive patients: The LIFE Study
Authors: Okin P. M. , Hille D. A. , Wiik B. P. , Kjeldsen S. E. , Lindholm L. H. , Dahlöf B. , Devereux R. B.
Published: April 2013

Aims

Although hypertensive patients with low baseline HDL cholesterol levels have a higher incidence of diabetes mellitus, whether changing levels of HDL over time are more strongly related to the risk of new diabetes in hypertensive patients has not been examined.

Methods

Incident diabetes mellitus was examined in relation to baseline and in‐treatment HDL levels in 7485 hypertensive patients with no history of diabetes randomly assigned to losartan‐ or atenolol‐based treatment.

Results

During 4.7 ± 1.2 years follow‐up, 520 patients (6.9%) developed new diabetes. In univariate Cox analyses, compared with the highest quartile of HDL levels (> 1.78 mmol/l), baseline and in‐treatment HDL in the lowest quartile (< 1.21 mmol/l) identified patients with > 5‐fold and > 9 fold higher risks of new diabetes, respectively; patients with baseline or in‐treatment HDL in the 2nd and 3rd quartiles had intermediate risk of diabetes. In multivariable Cox analyses, adjusting for randomized treatment, age, sex, race, prior anti‐hypertensive therapy, baseline uric acid, serum creatinine and glucose entered as standard covariates, and in‐treatment non‐HDL cholesterol, Cornell product left ventricular hypertrophy, diastolic and systolic pressure, BMI, hydrochlorothiazide and statin use as time‐varying covariates, the lowest quartile of in‐treatment HDL remained associated with a nearly 9‐fold increased risk of new diabetes (hazard ratio 8.7, 95% CI 5.0–15.2), whereas the risk of new diabetes was significantly attenuated for baseline HDL < 1.21 mmol/l (hazard ratio 3.9, 95% CI 2.8–5.4).

Conclusions

Lower in‐treatment HDL is more strongly associated with increased risk of new diabetes than baseline HDL level.
Trends in selection and timing of first‐line pharmacotherapy in older patients with Type 2 diabetes diagnosed between 1994 and 2006
Authors: Foster P. D. , Mamdani M. M. , Juurlink D. N. , Shah B. R. , Paterson J. M. , Gomes T.
Published: April 2013

Aims

To characterize temporal trends in the selection and timing of first‐line pharmacotherapy among older patients with Type 2 diabetes.

Design and methods

We studied five population‐based cohorts every 3 years, from 1994 to 2006. In each of those years, we identified all subjects aged 66 years or older newly diagnosed with diabetes and determined the initial glucose‐lowering drug and the time between diagnosis and drug initiation. We calculated the proportion of patients prescribed each agent and estimated time from diagnosis to initiation using Kaplan–Meier survival analysis.

Results

We identified a total of 64 368 eligible people who initiated drug therapy during the study period. From 1994 to 2006, first‐line metformin use increased from 20.1 to 79.0%. Glyburide (glibenclamide) decreased from 71.1% of all first‐line therapies in 1994 to 9.8% in 2006, while first‐line use of insulin or combination therapy have changed little at approximately 5% each. No other medication exceeded 2% of first‐line therapies. The median time from diagnosis to initiation of pharmacotherapy increased dramatically during the study period, from 1.8 years in 1994 to 4.6 years in 2006.

Conclusions

Metformin has become the most commonly used initial medication for the treatment of diabetes. Although guidelines have evolved to recommend more aggressive initiation and intensification of pharmacotherapy, our results suggest that the time from diagnosis to initiation has increased substantially.
Workplace Friendships among Bank Employees in Eastern Libya
Authors: Bader Hind A. M. , Hashim Intan H. M. , Zaharim Norzarina Mohd
Published: April 2013

The purpose of this study was to examine workplace friendships among 536 employees of Wahda Bank in four cities in Eastern Libya. In this study, a Workplace Friendship Scale (WFS) was used to assess opportunities for and the presence of friendships. Participants in this study reported mainly positive friendships at the workplace. Participants of different gender, ages, education levels, cities, and durations of work in different departments reported various opportunities for workplace friendships. However, marital status and type of occupation were not significantly related to friendships at the workplace. Findings suggest both similar and unique patterns of friendships compared to those studied outside Libya.
Antioxidants restore protoporphyrinogen oxidase in variegate porphyria patients
Authors: Ferrer Miguel D. , Tauler Pedro , Sureda Antoni , Palacín Clara , Tur Josep A. , Pons Antoni
Published: April 2013

Background

Variegate porphyria (VP) is the result of decreased protoporphyrinogen oxidase (PPOX) activity and results in the accumulation of porphyrins and porphyrin precursors. Our aims were to analyse the basal antioxidant defences and oxidative damage markers and the effects of a diet supplementation with vitamins E and C on the oxidant/antioxidant status and PPOX gene expression in lymphocytes of variegate porphyria (VP) patients.

Materials and methods

Twelve women affected by VP and 12 control women participated in a randomized and double‐blind crossover study. Each participant took either 50 mg/day vitamin E and 150 mg/day vitamin C or a placebo for 6 months.

Results

Lymphocyte PPOX gene expression, together with catalase and glutathione peroxidase activities, was reduced in VP women. No differences were observed in the levels of malondialdehyde and protein carbonyl derivatives. Stimulated lymphocyte H2O2 production was higher in porphyric women. Supplementation with antioxidant vitamins increased PPOX expression in VP patients. Glutathione reductase (GRd) and superoxide dismutase (SOD) activities were higher in the treatment groups.

Conclusions

Lymphocytes from VP patients show reduced PPOX expression and present a greater susceptibility to producing H2O2 and impaired H2O2 detoxifying mechanisms. Supplementation with vitamins E and C restores PPOX expression in VP patients and enhances GRd and SOD activity, suggesting the potential benefits of a diet rich in vitamins E and C in these patients.
Preserved thrombin‐inducible platelet activation in thienopyridine‐treated patients
Authors: Gremmel Thomas , Kopp Christoph W. , Seidinger Daniela , Koppensteiner Renate , Steiner Sabine , Panzer Simon
Published: April 2013

Background

Abundant thrombin generation may be a major reason for subsequent thromboembolic events in patients with cardiovascular disease receiving dual antiplatelet therapy. We therefore investigated the susceptibility of thienopyridine responders and nonresponders to thrombin receptor–activating peptide (TRAP)‐6‐ and adenosine diphosphate (ADP)‐inducible platelet activation.

Materials and methods

Response to clopidogrel or prasugrel was determined by the vasodilator‐stimulated phosphoprotein (VASP) phosphorylation assay and multiple electrode aggregometry (MEA) in 317 patients undergoing angioplasty and stenting for cardiovascular disease. Baseline, TRAP‐6‐, and ADP‐inducible P‐selectin expression, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and monocyte–platelet aggregate (MPA) formation were measured as sensitive parameters of platelet activation.

Results

In patients with high on‐treatment residual ADP‐inducible platelet reactivity (HRPR), baseline P‐selectin expression, GPIIb/IIIa and MPA formation were similar to those in patients without HRPR (all P > 0·05). After platelet activation with TRAP‐6 or ADP, patients with HRPR by both assays exhibited significantly higher levels of P‐selectin expression, GPIIb/IIIa and MPA formation than patients with an adequate thienopyridine‐mediated platelet inhibition (all P ≤ 0·02). However, high levels of TRAP‐6‐inducible P‐selectin, GPIIb/IIIa and MPA formation also occurred in 20·4%, 19·1% and 20·1% of the good responders by the VASP assay, and in 19·6%, 16·6% and 20·6% of the good responders by MEA, respectively.

Conclusions

Thienopyridine nonresponders are more susceptible to thrombin‐ and ADP‐inducible platelet activation than patients with good platelet inhibition. However, even patients with adequate thienopyridine‐mediated platelet inhibition often show a preserved responsiveness to thrombin. These patients may benefit from additional thrombin receptor blockage or inhibition of thrombin generation.
The LPS‐induced increase in circulating microparticles is not affected by vitamin C in humans
Authors: Weisshaar Stefan , Gouya Ghazaleh , Nguyen Daniel , Kapiotis Stylianos , Wolzt Michael
Published: April 2013

Objective

Microparticles (MP) are considered to promote coagulation. This study aimed to characterize the time course of MP levels and the effect of high‐dose vitamin C on MP formation during inflammation in an in vivo Escherichia coli endotoxin (LPS) model.

Methods

Microparticle formation was studied in 14 male subjects in a cross‐over trial who received either intravenous vitamin C at 320 mg/kg body weight (BW) or 480 mg/kg BW or saline solution in a random order on alternate trial days 3 h after intravenous exposure to LPS (2 ng/kg BW). Venous blood samples were taken before, 3 and 6 h after LPS. D‐dimer, leucocyte count, C‐reactive protein, plasma vitamin C and body temperature were assessed as inflammatory parameters. MP were detected using flow cytometric analysis and expressed in 10³ MP/mL plasma.

Results

Microparticles levels were decreased from baseline 848 units [range 431–1705] by 21% to 671 units [253–1586] at 3 h and increased by 32% to 1119 units [288–4443] at 6 h after LPS. This pattern was not influenced by administration of vitamin C, with a change from 730 units [399–1396] at baseline by an increase to 832 units [215–2168] at 3 h to 1055 units [350–4858] at 6 h. MP subpopulations followed similar dynamics. Alterations in inflammatory parameters were independent from vitamin C administration during endotoxemia.

Conclusion

Microparticles are increased in acute systemic inflammation with inconsistent changes in MP subgroups in healthy subjects. Systemic vitamin C administration does not mitigate MP formation and D‐dimer levels during acute systemic inflammation, suggesting that MP‐induced coagulation activity is not affected by vitamin C.
Prognostic impact of pretransplant iron overload measured with magnetic resonance imaging on severe infections in allogeneic stem cell transplantation
Authors: Virtanen Johanna M. , Itälä‐Remes Maija A. , Remes Kari J. , Vahlberg Tero , Saunavaara Jani P. , Sinisalo Marjatta , Parkkola Riitta K.
Published: April 2013

Objective

Infections and graft‐versus‐host disease (GVHD) are the main causes of transplant‐related mortality (TRM) of patients undergoing allo‐SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non‐specific surrogate markers of iron, suggest that IO predicts poor outcome after allo‐SCT.

Methods

In this prospective study, we quantified pretransplant IO with MRI‐based hepatic iron concentration (HIC) measurement; the degree of IO was used to predict infections, GVHD, and mortality after allo‐SCT. Logistic univariate, multivariate, and Cox's regression analyses were performed.

Results

Iron overload was present in 78% of the patients (HIC>36 μmol/g). The median HIC was 98 μmol/g (range 5–348). There were no cases of cardiac iron excess. IO was significantly associated with severe infections during the early post‐transplant period (for every 10 μmol/g increase OR: 1.15, 95% CI 1.05–1.26, P = 0.003). The odds for severe infections increased 6.5‐ (>125 μmol/g OR: 6.5, P = 0.013) to 14‐fold (>269 μmol/g OR: 14.1, P = 0.040) with increasing HIC. IO was found to be associated with reduced risk of acute and chronic GVHD. Although TRM was due to infection‐related deaths, IO was not associated with TRM or OS.

Conclusion

Pretransplant IO, measured with a direct MRI‐based measurement, predicts severe infections in the early post‐transplant period.
Decreased expression of GLT‐1 in the R6/2 model of Huntington's disease does not worsen disease progression
Authors: Petr Geraldine T. , Schultheis Laurel A. , Hussey Kayla C. , Sun Yan , Dubinsky Janet M. , Aoki Chiye , Rosenberg Paul A.
Published: April 2013

Excitotoxicity is thought to be important in the pathogenesis of Huntington's disease (HD). Glutamate is the predominant excitatory neurotransmitter in the brain, and excess activation of glutamate receptors can cause neuronal dysfunction and death. Glutamate transporters regulate the extracellular concentration of glutamate. GLT‐1 is the most abundant glutamate transporter, and accounts for most of the glutamate transport in the brain. Administration of ceftriaxone, an antibiotic that increases the functional expression of GLT‐1, can improve the behavioral phenotype of the R6/2 mouse model of HD. To test the hypothesis that GLT‐1 expression critically affects the HD disease process, we generated a novel mouse model that is heterozygous for the null allele of GLT‐1 and carries the R6/2 transgene (double mutation). We demonstrated that the protein expression of total GLT‐1, as well as two of its isoforms, is decreased within the cortex and striatum of 12‐week‐old R6/2 mice, and that the expression of EAAC1 was decreased in the striatum. Protein expression of GLT‐1 was further decreased in the cortex and striatum of the double mutation mice compared with the R6/2 mice at 11 weeks. However, the effects of the R6/2 transgene on weight loss, accelerating rotarod, climbing and paw‐clasping were not exacerbated in these double mutants. Na+‐dependent glutamate uptake into synapatosomes isolated from the striatum and cortex of 11‐week‐old R6/2 mice was unchanged compared with controls. These results suggest that changes in GLT‐1 expression or function per se are unlikely to potentiate or ameliorate the progression of HD.
The Evolving and Multilayered EU–India Investment Relations—Regulatory Issues and Policy Conjectures
Authors: Chaisse Julien , Chakraborty Debashis
Published: April 2013

India and several EU member countries share a rich history of investment collaborations. The collaboration has been cemented with several formal agreements with individual EU members, and the recent negotiations with the trade bloc since June 2007 on a broad‐based Bilateral Trade and Investment Agreement (BTIA) can be considered as a culmination of this process while ongoing WTO negotiations on Mode 3 commitments remain essential in terms of market opening. The present article analyzes the multi‐layered regulation of foreign investment against the backdrop of the evolving EU‐India economic relations. The 2009 Treaty of Lisbon gave a new competence to the EU which will impact ongoing negotiations with India whose global standing has been significantly changing in recent years. The economic vibrancy, coupled with large market size, has earned India greater relevance in several international forums, thereby making the future EU—India investment treaty one of the most promising investment agreements.
Longitudinal study of regional cerebral blood flow in elderly patients with idiopathic rapid eye movement sleep behavior disorder
Authors: Sakurai Hirofumi , Hanyu Haruo , Inoue Yuichi , Kanetaka Hidekazu , Nakamura Masaki , Miyamoto Tomoyuki , Sasai Taeko , Iwamoto Toshihiko
Published: April 2013

Aim

Single photon emission computed tomography (SPECT) studies showed that regional cerebral blood flow (rCBF) abnormalities in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are similar to those seen in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The aim of the present study was to assess the longitudinal rCBF changes in patients with iRBD using repeated SPECT.

Methods

Nine patients with iRBD (7 men and 2 women; mean age 71.1 ± 3.2 years) underwent baseline and follow‐up SPECT studies (a mean interval of 22.8 ± 9.2 months).

Results

A decrease in rCBF was found in bilateral parietotemporal and occipital areas at the first and second SPECT. Compared with the first SPECT, the second SPECT showed a decreased rCBF in the medial portions of the parietooccipital lobe with a significant decrease in rCBF of the right posterior cingulate. None of the patients showed any neurological deficits, including extrapyramidal and cerebellar signs, visual hallucinations, and neuropsychological impairments during the study.

Conclusion

These findings suggest that longitudinal measurements of rCBF can show the presence of progressing neurodegenerative process in iRBD. Longitudinal SPECT study can be used to monitor the progression of degenerative process in patients with iRBD, even though there were no evolving neurological and neuropsychiatric impairments. Geriatr Gerontol Int 2014; 14: 115–120.
Nodal reactive and neoplastic proliferation of monocytoid and marginal zone B cells: an immunoarchitectural and molecular study highlighting the relevance of IRTA1 and T‐bet as positive markers
Authors: Bob Roshanak , Falini Brunangelo , Marafioti Teresa , Paterson Jennifer C , Pileri Stefano , Stein Harald
Published: April 2013

Aims

Marginal zone B cells (MZCs) and monocytoid B cells (MBCs) appear to be related lymphoid cells that take part in reactive and neoplastic marginal zone proliferations. These lesions are not yet well characterized, and the aim of this study was to find better diagnostic criteria for them.

Methods and results

We analysed 60 nodal lesions with MBC and/or MZC proliferation for their morphological, immunophenotypic, molecular genetic and IG gene rearrangement features. On the basis of the results of the rearrangement assay and immunoglobulin light chain restriction, the lesions were divided into reactive and neoplastic groups. Among the neoplastic lesions, polymorphic and monomorphic subgroups emerged. All reactive lesions had morphological features of the polymorphic subgroup. By immunohistochemistry, IRTA1 and/or T‐bet expression was found in all reactive lesions and in 90% of neoplastic lesions.

Conclusions

IRTA1 and T‐bet are positive markers for the identification of MZC/MBC proliferations, and thus for the diagnosis of nodal marginal zone lymphoma (NMZL). Polymorphic and monomorphic subgroups of NMZL could be distinguished. Most morphological and immunophenotypic patterns in reactive and neoplastic nodal expansions of MZCs and MBCs overlapped. Therefore, PCR clonality assay of the immunoglobulin heavy and light chain gene loci is the most reliable method for their differentiation.
Study of the Glass Transition Temperature of As‐S Glasses for the Fabrication of Chalcogenide Optical Fibers
Authors: Skripachev Igor V. , El‐Amraoui Mohamed , Messaddeq Younes , Santagneli Silvia H.
Published: April 2013

Values of glass transition temperature (Tg) and of linear expansion coefficient (α) for Asx S100−x glasses were measured in the range of concentrations 35 × 42. Because of the importance of the glass formation region 35 × 42 for the optical fibers elaboration, special attention was made on high‐pure Asx S100−x glasses. For the glass in the range of 35 × 38, we measure Tg with the interval of x equal to 1 at.% of arsenic. We also measured the Tg values with the interval of x equal to 0.5 at.% of As. We obtained nonlinear behavior of Tg, reflecting the change in molecular composition of As‐S glass in the glass composition range studied. The control of such parameters is important to produce optical fibers with specific numerical aperture.