bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute liver failure in Sweden: etiology and outcome
Authors: Wei G. , Bergquist A. , Broomé U. , Lindgren S. , Wallerstedt S. , Almer S. , Sangfelt P. , Danielsson Å. , Sandberg‐Gertzén H. , Lööf L. , Prytz H. , Björnsson E.
Published: June 2007

Objective.  To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994–2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end‐stage liver disease (MELD) score with transplant‐free deaths as a positive outcome.

Research design and methods.  Adult patients in Sweden with international normalized ratio (INR) of ≥1.5 due to severe liver injury with and without encephalopathy at admission between 1994–2003 were included.

Results.  A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive‐predictive value (PPV) of 67%, negative‐predictive value (NPV) of 84% in the acetaminophen group. Positive‐predictive value and negative‐predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive‐predictive value of 21%, negative‐predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively.

Conclusions.  Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation.
Endothelial dysfunction in insulin resistance and type 2 diabetes
Authors: Jansson P.‐A.
Published: June 2007

Macrovascular disease is the number one killer in type 2 diabetes patients. The cluster of risk factors in the insulin resistance syndrome (IRS) partly explains this notion. Insulin action in muscle, liver or adipose tissue has been thoroughly described in the literature, whilst this has been less described for the endothelium. Insulin stimulates nitric oxide (NO) production in the endothelium and reduced bioavailability of NO is usually defined as endothelial dysfunction. This impairment might be related to defective insulin signalling in the endothelial cell. Therefore, insulin resistance mechanisms in the endothelial cell will be emphasized in this review.

Imbalance between the vasodilating agent NO and the vasoconstrictor endothelin‐1 (ET‐1) contributes to endothelial dysfunction. Different methods and circulating markers to assess endothelial function will be outlined. Circulating markers of an activated endothelium appear long before type 2 diabetes develops suggesting a unique role of the endothelium in the pathophysiology of the disease.

Hampered blood flow in nutritive capillaries due to endothelial dysfunction is coupled with decreased glucose uptake and hyperglycemia. The forearm model combined with muscle microdialysis enables us to measure interstitial glucose and an index for capillary recruitment, the permeability surface area (PS). Available data from this method suggest that capillary recruitment in response of insulin is impaired in insulin resistant human subjects.
Hyperglycaemia and cardiovascular disease
Authors: Bartnik M. , Norhammar A. , Rydén L.
Published: June 2007

Coronary artery disease and type 2 diabetes are chronic diseases of substantial and growing prevalence. Their coincidence is common, markedly enhancing mortality and morbidity. The risk for cardiovascular disease increases along a spectrum of blood glucose concentrations already apparent at levels regarded as normal. Accordingly, strategies for the early detection of glucometabolic disturbances are needed to find ways to prevent the occurrence of cardiovascular complications or to treat them already at an early stage. More specifically, abnormal glucose tolerance is almost twice as common amongst patients with a myocardial infarction as in population‐based controls and a normal glucose regulation is indeed less common than abnormal glucose metabolism also amongst patients with stable coronary artery disease. Already an abnormal glucose tolerance is a strong risk factor for future cardiovascular events after an acute myocardial infarction. An oral glucose tolerance test should, therefore, be a part of the evaluation of total risk in all patients with coronary artery disease. As glucose disturbances are common and easy to detect, they may be suitable targets for novel secondary preventive efforts.
Regulatory T cells in health and disease
Authors: Rouse B. T.
Published: June 2007

The healthy host does not normally develop tissue destructive autoimmunity in part because of the presence of natural regulatory T cells. These cells are best identified by their expression of a unique transcription factor forkhead box transcription factor (Foxp3) that controls their regulatory function. Several other types of regulatory T cells also occur most of which are induced in response to antigen stimulation. Some of these express the Foxp3 transcription factor but many do not. The role of natural T‐regulatory cells as well as induceable regulatory cells in autoimmunity, cancer, allergy and infectious disease is described. The current status of therapeutic approaches that modulate regulatory T‐cell responses on the outcome of experimental animal and human disease is also discussed.
Coalescence methods reveal the impact of vicariance on the spatial genetic structure of Elephantulus edwardii (Afrotheria, Macroscelidea)
Authors: SMIT H. A. , ROBINSON T. J. , VAN VUUREN B. J.
Published: June 2007

Within the Macroscelidea 15 species of elephant‐shrews are recognized, of which nine occur in the southern African subregion. The Cape rock elephant‐shrew (Elephantulus edwardii) is the only strictly endemic South African elephant‐shrew species. Recent distribution data suggest that E. edwardii is continuously distributed from Namaqualand in the Western Cape Province to Port Elizabeth in the Eastern Cape Province. Molecular sequences from the mitochondrial cytochrome b gene and variable control region indicate significant substructure within the Cape rock elephant‐shrew across its distribution. Our data unequivocally showed the presence of a northern Namaqua and central Fynbos clade with four evolutionary lineages identified within the latter. The geographical delimitation of the northern and central clades corresponds closely with patterns reported for other rock‐dwelling vertebrate species, indicating a shared biogeographical history for these taxa in South Africa. A coalescent method revealed the effects of ancestral polymorphism in shaping the Namaqua and Fynbos populations since their divergence ~1.7 million years ago. Furthermore, our analyses uncovered a distinct Karoo lineage(s) that does not correspond to any of the previously described and/or currently recognized species, and we therefore argue for the possible recognition of a new sister taxon to E. edwardii. The taxonomic affinities of this clade were examined by sequencing corresponding regions from the type specimens of species described in the past, but which presently are synonimized within E. edwardii. Our results reveal the morphological misidentification of one of these types, accentuating the problems of field identification.
Effects of population succession on demographic and genetic processes: predictions and tests in the daylily Hemerocallis thunbergii (Liliaceae)
Authors: CHUNG MI YOON , NASON JOHN D. , CHUNG MYONG GI
Published: June 2007

Spatial genetic structure within plant populations is influenced by variation in demographic processes through space and time, including a population's successional status. To determine how demographic structure and fine‐scale genetic structure (FSGS) change with stages in a population's successional history, we studied Hemerocallis thunbergii (Liliaceae), a nocturnal flowering and hawkmoth‐pollinated herbaceous perennial with rapid population turnover dynamics. We examined nine populations assigned to three successive stages of population succession: expansion, maturation, and senescence. We developed stage‐specific expectations for within‐population demographic and genetic structure, and then for each population quantified the spatial aggregation of individuals and genotypes using spatial autocorrelation methods (nonaccumulative O‐ring and kinship statistics, respectively), and at the landscape level measured inbreeding and genetic structure using Wright's F‐statistics. Analyses using the O‐ring statistic revealed significant aggregation of individuals at short spatial scales in expanding and senescing populations, in particular, which may reflect restricted seed dispersal around maternal individuals combined with relatively low local population densities at these stages. Significant FSGS was found for three of four expanding, no mature, and only one senescing population, a pattern generally consistent with expectations of successional processes. Although allozyme genetic diversity was high within populations (mean %P = 78.9 and HE = 0.281), landscape‐level differentiation among sites was also high (FST = 0.166) and all populations exhibited a significant deficit of heterozygotes relative to Hardy–Weinberg expectations (range F = 0.201–0.424, mean FIS = 0.321). Within populations, F was not correlated with the degree of FSGS, thus suggesting inbreeding due primarily to selfing as opposed to mating among close relatives in spatially structured populations. Our results demonstrate considerable variation in the spatial distribution of individuals and patterns and magnitude of FSGS in H. thunbergii populations across the landscape. This variation is generally consistent with succession‐stage‐specific differences in ecological processes operating within these populations.
Impact of Plio‐Pleistocene arid cycling on the population history of a southwestern Australian frog
Authors: EDWARDS DANIELLE L. , ROBERTS J. DALE , KEOGH J. SCOTT
Published: June 2007

Southwestern Australia is regarded as a global biodiversity hotspot. The region contains a high number of endemic species, ranging from Gondwanan relicts to much more recently evolved plant and animal species. Myobatrachid frogs are diverse in southwestern Australia, and while we know they have speciatedin situin the southwest, we know little about the temporal and geographical patterning of speciation events.Crinia georgianais an ideal subject to test hypotheses concerning the effect of climatic history on southwestern Australian anurans, as it is an old lineage with a broad distribution covering the entire region. We compiled an extensive phylogeographical data set based on 1085 bp of the mitochondrial gene ND2 for 68 individuals from 18 sites across the species’ range. Two major genetic clades were identified which were largely confined to the high rainfall and southeast coastal biogeographical zones, respectively. The clades appear to have diverged around the Plio‐Pleistocene border (1.26–1.72 million years ago), concordant with increasing intensity and frequency of arid climate cycles. Subsequent phylogeographical structure appears to have developed primarily during the Pleistocene climatic fluctuations that also have been integral in generating species diversity in the endemic southwestern Australian flora. Phylogeographical analyses identified several dispersal routes, possible refugial areas within the range of the species and also regions of secondary contact. Dispersal routes identified may now be closed to the species because of habitat destruction and salinity problems in inland regions, posing concerns about the evolutionary potential of the species in light of predicted climate change.
Rapid mixing between old and new C pools in the canopy of mature forest trees
Authors: KEEL SONJA G. , SIEGWOLF ROLF T.W. , JÄGGI MAYA , KÖRNER CHRISTIAN
Published: June 2007

Stable C isotope signals in plant tissues became a key tool in explaining growth responses to the environment. The technique is based on the fundamental assumption that the isotopic composition of a given unit of tissue (e.g. a tree ring) reflects the specific C uptake conditions in the leaf at a given time. Beyond the methodological implications of any deviation from this assumption, it is of physiological interest whether new C is transferred directly from sources (a photosynthesizing leaf) to structural sinks (e.g. adjacent stem tissue), or inherently passes through existing (mobile) C pools, which may be of variable (older) age. Here, we explore the fate of 13C‐labelled photosynthates in the crowns of a 30–35 m tall, mixed forest using a canopy crane. In all nine study species labelled C reached woody tissue within 2–9 h after labelling. Four months later, very small signals were left in branch wood of Tilia suggesting that low mixing of new, labelled C with old C had taken place. In contrast, signals in Fagus and Quercus had increased, indicating more intense mixing. This species‐specific mixing of new with old C pools is likely to mask year‐ or season‐specific linkages between tree ring formation and climate and has considerable implications for climate reconstruction using stable isotopes as proxies for past climatic conditions.
Does cystic fibrosis neonatal screening detect atypical CF forms? Extended genetic characterization and 4‐year clinical follow‐up
Authors: Narzi L , Ferraguti G , Stamato A , Narzi F , Valentini SB , Lelli A , Delaroche I , Lucarelli M , Strom R , Quattrucci S
Published: June 2007

The neonatal screening protocol for cystic fibrosis (CF) is based on a first determination of blood immunoreactive trypsin (IRT1), followed by a first level genetic test that includes the 31 worldwide most common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (DNA31), and a second determination of blood immunoreactive trypsin (IRT2). This approach identifies, in addition to affected subjects, a high proportion of newborns with hypertrypsinaemia at birth, in whom only one mutation is identified and who have a negative or borderline sweat test and pancreatic sufficiency. Although it has been suggested that hypertrypsinaemia may be caused by a single CFTR mutation, whether such neonates should be merely considered as healthy carriers remains a matter of debate as hypertrypsinaemia at birth may be a biochemical marker of a CFTR malfunction because of a second mild mutation. We analyzed, by means of an extended sequencing protocol, 32 newborns who tested positive at an IRT1/DNA31/IRT2 screening protocol and in whom only one CFTR mutation was found. The results obtained demonstrate that 62.5% of these newborns were also carrying a second mild CFTR mutation. The high proportion of compound heterozygous subjects, combined with the results of a 4‐year follow‐up in nine of these subjects all of whom displaying initial CF clinical symptoms, suggest that it may be possible to use the IRT1/DNA31/IRT2 protocol of neonatal screening to identify newborns with atypical forms of CF. In view of these findings, an extended genetic search for subjects with compound heterozygosity and a periodic clinical assessment should be considered.
Clinical application prospects of gastric pacing for treating postoperative gastric motility disorders
Authors: Li Fu‐Yu , Jiang Li‐Sheng , Cheng Jing‐Qiu , Mao Hui , Li Ning , Cheng Nan‐Sheng
Published: June 2007

Similar to the heartbeat, gastric peristalsis is regulated by an electrical rhythm generated by a pacemaker. Thus, electrical dysrhythmia of gastric slow waves will inevitably affect gastric peristalsis and emptying. The recurrence of postoperative gastroparesis is thereby closely related to the abnormalities of electrical dysrhythmia and ectopic pacemakers, resulting in postoperatively persistent gastric motility disorders in some severe cases, despite the use of prokinetic and antiemetic drugs. Recent studies have demonstrated that gastric pacing, analogous to pacing the human heart, is an attractive and promising therapy that is both feasible and safe. Gastric pacing has been shown to be strikingly effective in normalizing gastric dysrhythmia, increasing the activity of the gastric slow wave and thereby prompting gastric dynamia and emptying. Furthermore, the long‐term utilization of gastric pacing can (i) relieve patients from clinical symptoms, such as nausea and vomiting; (ii) release patients with severe postoperative gastroparesis from relying on prokinetic drugs and the jejunal feeding tube; (iii) return patients to normal oral nutritional intake and provide a more satisfactory nutritional status and most importantly; and (iv) give patients a better quality of life. Overall, research focused on gastric pacing has demonstrated excellent prospects for clinical application in the treatment of postoperative gastroparesis disorders, especially for those unresponsive to prokinetic drugs.
Polymorphisms in NFKBIA and ICAM‐1 genes in New Zealand Caucasian Crohn's disease patients
Authors: Hong Jiwon , Leung Euphemia , Fraser Alan G , Merriman Tony R , Vishnu Prakash , Krissansen Geoffrey W
Published: June 2007

Background and Aim:  Crohn's disease (CD) is a complex polygenetic inflammatory disease of the bowel. NFKBIA (IκBα) is a downstream regulator of NF‐κB, which is an effector of the major Crohn's susceptibility gene CARD15/NOD2. ICAM‐1 is an integrin ligand and vascular addressin, which contributes to the trafficking of pathogenic leukocytes into the inflamed bowel. Here we examined whether the NFKBIA 2758G/A and ICAM‐1 K469E variants, recently shown to be CD susceptibility genes in Caucasian populations in Germany and the United Kingdom, are associated with CD in Caucasian patients in New Zealand.

Methods:  PCR‐RFLP analysis was used to examine the frequency of gene polymorphisms in 182 CD patients and 188 ethnically matched controls.

Results:  There was no significant evidence of a difference in the allele frequency of either the 2758G/A polymorphism in NFKBIA (0.38 vs 0.35, P = 0.47) or the K469E polymorphism in ICAM‐1 (0.43 vs 0.37, P = 0.10) between CD patients and controls. Nevertheless, the ICAM‐1 469E allele significantly (P = 0.016, Pc = 0.047) influenced the age of diagnosis of CD. Meta‐analysis with five other studies confirmed a lack of association of the K469E polymorphism with Crohn's disease (P = 0.33; OR = 0.93; 95% CI, 0.82–1.07).

Conclusion:  The NFKBIA 2758G/A and ICAM‐1 K469E polymorphisms are not significant risk factors for CD in New Zealand; however, there is evidence that the latter polymorphism influences the age of diagnosis.
A high‐threshold heat‐activated channel in cultured rat dorsal root ganglion neurons resembles TRPV2 and is blocked by gadolinium
Authors: Leffler Andreas , Linte Ramona Madalina , Nau Carla , Reeh Peter , Babes Alexandru
Published: June 2007

Heat‐activated ion channels from the vanilloid‐type TRP group (TRPV1–4) seem to be central for heat‐sensitivity of nociceptive sensory neurons. Displaying a high‐threshold (> 52 °C) for activation, TRPV2 was proposed to act as a sensor for intense noxious heat in mammalian sensory neurons. However, although TRPV2 is expressed in a distinct population of thinly myelinated primary afferents, a widespread expression in a variety of neuronal and non‐neuronal tissues suggests a more diverse physiological role of TRPV2. In its role as a heat‐sensor, TRPV2 has not been thoroughly characterized in terms of biophysical and pharmacological properties. In the present study, we demonstrate that the features of heterologously expressed rat TRPV2 closely resemble those of high‐threshold heat‐evoked currents in medium‐ and large‐sized capsaicin‐insensitive rat dorsal root ganglion (DRG) neurons. Both in TRPV2‐expressing human embryonic kidney (HEK)293t cells and in DRGs, high‐threshold heat‐currents were sensitized by repeated activation and by the TRPV1–3 agonist, 2‐aminoethoxydiphenyl borate (2‐APB). In addition to a previously described block by ruthenium red, we identified the trivalent cations, lanthanum (La3+) and gadolinium (Gd3+) as potent blockers of TRPV2. Thus, we present a new pharmacological tool to distinguish between heat responses of TRPV2 and the closely related capsaicin‐receptor, TRPV1, which is strongly sensitized by trivalent cations. We demonstrate that self‐sensitization of heat‐evoked currents through TRPV2 does not require extracellular calcium and that TRPV2 can be activated in cell‐free membrane patches in the outside‐out configuration. Taken together our results provide new evidence for a role of TRPV2 in mediating high‐threshold heat responses in a subpopulation of mammalian sensory neurons.
Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei
Authors: Grassi Silvarosa , Frondaroli Adele , Dieni Cristina , Dutia Mayank B. , Pettorossi Vito E.
Published: June 2007

In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with γ‐aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABAA (bicuculline), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/ kainate [2,3‐dioxo‐6‐nitro‐1,2,3,4‐tetrahydrobenzo(f)quinoxaline‐7‐sulphonamide disodium salt (NBQX)], N‐methyl‐d‐aspartate (NMDA) [d‐(–)‐2‐amino‐5‐phosphonopentanoic acid (AP‐5)] and group I metabotropic glutamate receptors (mGlu‐I) [(R,S)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long‐lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABAA receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABAA inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABAA receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABAA and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal conditions and during the stress response that accompanies many forms of vestibular dysfunction.
Identification of genes differentially expressed in SH‐SY5Y neuroblastoma cells exposed to the prion peptide 106–126
Authors: Martínez Tamara , Pascual Angel
Published: June 2007

Prion diseases are a group of neurodegenerative disorders characterized by astrocytosis and progressive neuronal degeneration. As a causative agent, prions have been intensely investigated in different experimental models. However, the mechanisms and pathways involved in the prion‐induced neurological dysfunction are poorly understood. In this work we have investigated the influence of prion infection on the gene expression profile in a human neuroblastoma cell line. Using a DNA microarray and quantitative reverse transcriptase‐polymerase chain reaction methods, we have analysed in SH‐SY5Y cells the effects of a synthetic peptide corresponding to the 106–126 neurotoxic region of the cellular human prion protein. Our results show that addition of this peptide to the neuronal culture specifically changes the expression of a relative high number of genes, and causes a progressive neuronal death even in the absence of microglia.
Effects of pilocarpine on the cortical and hippocampal theta rhythm in different vigilance states in rats
Authors: Tejada S. , Rial R. V. , Coenen A. M. L. , Gamundi A. , Esteban S.
Published: June 2007

It has been suggested that theta rhythm gates the flow of information between the hippocampus and cortex during memory processes. The cholinergic system plays an important role in regulating vigilance states and in generating theta rhythm. This study aims to analyse the effects of the muscarinic agonist pilocarpine (120 and 360 µg, i.c.v.) on hippocampal and frontal cortical theta rhythm during several vigilance states in rats. Pilocarpine injection increased the duration and number of episodes with theta activity, particularly when theta rhythm appeared during waking states in the cortex and hippocampus simultaneously. It seems that the effects of pilocarpine are related to the appearance of cortical theta activity in waking states, and suggest that pilocarpine could modify the transference rate of information from the hippocampus to cortex in rats during wakefulness states, in relation to the postulated effect of cholinergic system modulating memory consolidation.
Trophic effects of keratinocytes on the axonal development of sensory neurons in a coculture model
Authors: Ulmann Lauriane , Rodeau Jean‐Luc , Danoux Louis , Contet‐Audonneau Jean‐Luc , Pauly Gilles , Schlichter Rémy
Published: June 2007

The epidermis, the outermost structure of the skin, fulfils important roles as a physical barrier between the organism and its environment and as a neuroendocrine, immune and sensory organ. It is innervated by unmyelinated sensory fibres conveying nociceptive and thermoceptive information. Little is known concerning the functional interactions between these sensory fibres and the keratinocytes, which constitute 95% of the epidermal cells. We have developed a coculture model of primary rat sensory neurons and keratinocytes, as well as of equivalent cell‐lines: ND7‐23 neurons and A431 keratinocytes. We show that primary dorsal root ganglion neurons survive well in a standard keratinocyte reference medium containing a low concentration of calcium, but fail to extend axons. However, when neurons are cocultured with keratinocytes, axonal outgrowth is strongly stimulated. The use of a Transwell culture system indicated that the stimulation of axonal growth depends on a soluble factor secreted by keratinocytes. Axon outgrowth was also induced by nerve growth factor or brain‐derived neurotrophic factor, but not by neurotrophin 3 or glial cell‐derived neurotrophic factor. Neurons cocultured with keratinocytes did not change their responses to ATP, capsaicin or high potassium solution, as measured by calcium imaging. The trophic effect of keratinocytes concerned essentially a population of medium‐sized (17–25 µm) neurons, some of which expressed substance P‐like immunoreactivity and responded to capsaicin. Our preparation, in which cells are maintained at low external calcium concentration, could represent a useful in vitro model for characterizing the effect of skin‐derived guidance and trophic factors.
Insulin glulisine: a faster onset of action compared with insulin lispro
Authors: Heise T. , Nosek L. , Spitzer H. , Heinemann L. , Niemöller E. , Frick A. D. , Becker R. H. A.
Published: June 2007

Aim:  This randomized, single‐centre, double‐blind, crossover study compared the pharmacodynamic and pharmacokinetic properties of two different doses of insulin glulisine (glulisine) and insulin lispro (lispro) in lean to obese subjects.

Methods:  Eighty subjects without diabetes, stratified into four body mass index (BMI) classes (<25, ≥25 to <30, ≥30 to <35 and ≥35 kg/m2), were randomized to receive single injections of glulisine and lispro (0.2 and 0.4 U/kg) on four study days under glucose clamp conditions. Glucose infusion rates (GIR) and insulin (INS) concentrations were assessed for 10 h postdose.

Results:  Glulisine showed a greater early metabolic action than lispro [GIR‐area under the curve (GIR‐AUC) between 0 and 1 h (0.2 U/kg: 102.3 ± 75.1 vs. 83.1 ± 72.8 mg/kg, p < 0.05; 0.4 U/kg: 158.0 ± 100.0 vs. 112.3 ± 70.8 mg/kg, p < 0.001)], with an earlier time to 10% of total GIR‐AUC (0.2 U/kg: 1.4 ± 0.4 vs. 1.5 ± 0.4 h; 0.4 U/kg: 1.4 ± 0.3 vs. 1.5 ± 0.3 h, p < 0.05). The total metabolic effect was not different between the two insulins. In accordance with these findings, the time to 10% of total INS‐AUC was faster with glulisine compared with lispro at either dose (0.2 U/kg: 0.7 ± 0.2 vs. 0.8 ± 0.2 h; 0.4 U/kg: 0.8 ± 0.2 vs. 0.9 ± 0.2 h, p < 0.001). The faster rise in insulin concentrations and the earlier onset of activity of glulisine vs. lispro was consistently observed in each individual BMI class.

Conclusions:  Glulisine shows a faster onset of action than lispro, independent of BMI and dose.
Overnight CSII as supplement to oral antidiabetic drugs in Type 2 diabetes
Authors: Parkner T. , Møller M. K. , Chen J. W. , Laursen T. , Jørgensen C. , Smedegaard J. S. , Lauritzen T. , Christiansen J. S.
Published: June 2007

Aim:  To evaluate the potential advantages of a constant overnight subcutaneous delivery of insulin in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetics.

Methods:  Ten type 2 diabetic patients treated with oral antidiabetic drugs without gaining sufficient glycaemic control were included in this three‐period study. All patients received continuous subcutaneous insulin infusion (CSII) with a short‐acting insulin analogue, 2 IU/h, for 8 h during three consecutive nights (period A). Based upon the results from period A, two additional dose regimens of three nights (period B and C) were studied in random order. Serum insulin aspart, human insulin and plasma glucose (PG) profiles were recorded.

Results:  In period A, fasting plasma glucose (FPG) was reduced from a mean ± s.d. (mmol/l) value of 11.6 ± 2.9 to 5.5 ± 1.6 (p < 0.0001) during the first night. No additional lowering of FPG was seen the two succeeding nights. FPG narrowed as the range before the infusion was 7.3–15.2 mmol/l compared with 3.6–6.1 mmol/l on the last morning after infusion. The variability in PG profile during the first and the last night of CSII was small and not significantly different. The rising insulin aspart was mirrored by a decrease in human insulin. In period B and C, similar tendencies as for period A were seen. In period A, two patients each experienced one mild hypoglycaemic episode.

Conclusions:  CSII with an insulin analogue overnight effectively reduced FPG without occurrence of major hypoglycaemia in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetic treatment.
Pioglitazone attenuates fatty acid–induced oxidative stress and apoptosis in pancreatic β‐cells
Authors: Saitoh Y. , Chun‐ping C. , Noma K. , Ueno H. , Mizuta M. , Nakazato M.
Published: June 2007

Aims:  Thiazolidinediones (TZDs), ligands for peroxisome proliferator–activated receptor γ, are antidiabetic agents that improve hyperglycemia by decreasing insulin resistance in obese diabetic animal models and patients with type 2 diabetes. We have studied whether pioglitazone, a TZD, can exert a direct effect against pancreatic β‐cell lipoapoptosis.

Methods:  MIN6 cells were cultured in medium containing either 5.6 (low glucose) or 25 mM glucose (high glucose) in the presence or absence of 0.5 mM palmitate for 48 h. We examined the effect of 10 μM pioglitazone on MIN6 cells on glucose‐stimulated insulin secretion, cellular ATP, uncoupling protein‐2 (UCP‐2) mRNA expression, intracellular triglyceride content, reactive oxygen species production, the number of apoptotic cells and nuclear factor‐κB (NF‐κB) activity.

Results:  Pioglitazone recovered partly impaired glucose‐stimulated insulin secretion and cellular ATP in MIN6 cell exposed to high glucose with 0.5 mM palmitate. Pioglitazone suppressed intracellular triglyceride accumulation in cells exposed to high glucose with 0.5 mM palmitate. Palmitate‐induced upregulation of UCP‐2 mRNA levels was suppressed by pioglitazone in a dose‐dependent manner. Pioglitazone decreased palmitate‐induced reactive oxygen species production in MIN6 cells by 24% and in mouse islet cells by 53%. Pioglitazone also decreased palmitate‐induced NF‐κB activity by 40% and protected β‐cells from palmitate‐induced apoptosis by 22% in MIN6 cell.

Conclusions:  Pioglitazone attenuated fatty acid–induced oxidative stress and apoptosis in pancreatic β‐cells. TZDs might be used as a mean for maintaining β‐cell survival and preserving capacity of insulin secretion in patients with diabetes mellitus.
In Search of the “Third Dimension” of Burnout: Efficacy or Inefficacy?
Authors: Bresó Edgar , Salanova Marisa , Schaufeli Wilmar B.
Published: June 2007

This article contributes to the ongoing debate about whether or not lack of efficacy constitutes the “third dimension” of burnout. This debate is obscured by the fact that lack of efficacy is measured by positively framed efficacy items that are reversed in order to be indicative of burnout. Instead, this study includes aninefficacy scale that consists of negatively worded items that arenotreversed. In two samples of university students from Spain (n= 193) and The Netherlands (n= 235), the factor structure of the traditional Maslach Burnout Inventory‐Student Survey (MBI‐SS), that includes an “efficacy” scale, is assessed and compared with that of academic burnout that includes an “inefficacy” scale instead. Confirmatory factor analyses in both samples showed a slightly better fit of the latter. Furthermore, results were remarkably similar across samples, which illustrates the robustness of our findings. It is concluded that in future research, instead of efficacy, an inefficacy scale should be used to assess burnout.

Cet article contribue à savoir si le manque d’efficacité est ou n’est pas la troisième dimension constitutive du burnout. Au lieu de mesurer le manque d’efficacité au moyen d’items efficacité construits positivement et qui sont inversés pour être des indicateurs du burnout, cette étude introduit une échelle d’inefficacité composée d’items formulés négativement et qui n’ont donc pas àêtre inversés. Deux échantillons d’étudiants espagnols (n= 193) et néerlandais (n= 235) ont répondu au traditionnel Maslach Burnout Inventory‐Student Survey (MBI‐SS) qui comprend une échelle d’efficacité. La structure factorielle qui s’en dégage a été comparée à celle qui inclut une échelle d’inefficacité. Comme attendu, les analyses factorielles sur les deux échantillons montrent une légère supériorité de la seconde. En outre, les résultats des deux échantillons sont particulièrement proches ce qui illustre la robustesse de nos résultats. En conclusion, on peut dire que dans les recherches futures, plutôt qu’une échelle d’efficacité pour mesurer le burnout, on pourrait lui préférer une échelle d’inefficacité.
Refining our Understanding of Traumatic Growth in the Face of Terrorism: Moving from Meaning Cognitions to Doing what is Meaningful
Authors: Hobfoll Stevan E. , Hall Brian J. , Canetti‐Nisim Daphna , Galea Sandro , Johnson Robert J. , Palmieri Patrick A.
Published: June 2007

Recent studies related to global terrorism have suggested the potential of posttraumatic growth (PTG) following experiences of terror exposure. However, investigations of whether psychological distress is reduced or increased by PTG in other trauma contexts have been inconsistent. Results from our studies conducted in New York following the attacks of 11 September 2001 and in Israel during recent tumultuous periods of violence and terrorism, the Al Aqsa Intifada, have found posttraumatic growth to be related to greater psychological distress, more right‐wing political attitudes, and support for retaliatory violence. Only when individuals were deeply involved in translating growth cognitions to growth actions in our research on the forced disengagement of settlers from Gaza did we find positive benefit in posttraumatic growth. Findings are considered within the framework of a new formulation of action‐focused growth.

De récentes recherches en rapport avec le terrorisme international ont souligné le potentiel du développement post‐traumatique (PTG) découlant de la confrontation à la terreur. Toutefois, les travaux cherchant à savoir si la détresse psychologique était atténuée ou accentuée par le PTG dans d’autres contextes traumatiques se sont révélés contradictoires. Nos investigations à New York après l’attentat du 11 septembre 2001 et en Israël durant des périodes récentes de violence et de terrorisme, la seconde Intifada, ont montré que le développement post‐traumatique était plutôt liéà une grande détresse psychologique, à des opinions politiques de droite et à une attente de représailles. On a observé lors du déménagement obligatoire des colons de Gaza que ce n’est que lorsque les individus étaient profondément impliqués dans la transformation des cognitions de développement en actions de développement que le développement post‐traumatique avait des retombées positives. Ces résultats sont appréhendés dans le cadre d’une nouvelle approche du développement centré sur l’action.
Traumatic Growth in the Face of Terrorism: Threshold Effects and Action‐Based Growth
Authors: Stasko Emily C. , Ickovics Jeannette R.
Published: June 2007

Although posttraumatic growth is generally thought of as a protective factor for posttraumatic stress disorder, Hobfoll and colleagues (this issue) suggest that the benefits derived from posttraumatic growth are dependent upon the translation from cognition to action, an occurrence they term action‐based growth. In their latest examination of traumatic growth in the face of terrorism, Hobfoll et al. reviewed five studies and found that posttraumatic growth was positively associated with posttraumatic stress disorder. This commentary addresses the strengths and limitations of the studies’ methodology and the theoretical and clinical implications of action‐based growth. We speculate that the severity and chronicity of terrorism result in psychosocial vulnerability, such that PTG cannot ameliorate risk of adverse consequences. It is expected that psychosocial vulnerability may be related to all traumas falling above a certain threshold of severity. However, when cognition and action are linked—as they are in one of the studies of the Gaza disengagement—posttraumatic growth may be protective, even in the face of persistent terrorism.

Bien que le développement post‐traumatique soit généralement considéré comme protégeant des troubles dus au stress post‐traumatique, Hobfoll et ses collègues écrivent dans leur article que les bénéfices provenant du développement post‐traumatique dépendent du transfert de la cognition vers l’action, une opération qu’ils dénomment développement basé sur l’action. Dans leur récente étude du développement traumatique devant le terrorisme, Hobfoll et al. passent en revue cinq recherches et concluent que le développement post‐traumatique entretient un lien positif avec les troubles dus au stress post‐traumatique. Ce commentaire porte sur les forces et les faiblesses de la méthodologie des études et sur les implications théoriques et cliniques du développement basé sur l’action. Nous pensons que la violence et la récurrence du terrorisme provoquent une vulnérabilité psychologique dont le PTG est incapable de réduire les risques de conséquences néfastes. On s’attend à ce que la vulnérabilité psychosociale soit provoquée par tout traumatisme dépassant un certain seuil de gravité. Toutefois, quand cognition et action se rejoignent (comme c’est le cas dans l’une des recherches sur l’évacuation de Gaza), le développement post‐traumatique peut être protecteur, même confrontéà un terrorisme permanent.
Innocent or Not‐so‐innocent Bystanders: Evidence from the Gravity Model of International Trade About the Effects of UN Sanctions on Neighbour Countries
Authors: Slavov Slavi T.
Published: June 2007

This paper examines two hypotheses about the effects of UN sanctions on trade flows between land neighbours of the target country and the rest of the world. First, there have been claims that sanctions hurt neighbour countries by cutting off trading routes, increasing transportation costs and disrupting established trading ties. We would expect that a neighbour's trade with the rest of the world would fall, as a result. Second, there is extensive evidence that neighbours have been involved in smuggling. Consequently, neighbours should trade more with the rest of the world during UN trade embargoes, because now they also trade on behalf of the target. I employ the gravity model of international trade to show that, overall, a neighbour's trade with the rest of the world tends to fall during UN sanctions episodes. This confirms the first hypothesis above: on a net basis, land neighbours have been ‘innocent bystanders’ hit by UN sanctions.
What difference do different settings in residential care make for young people? A comparison of family‐style homes and institutions in Sweden
Authors: Johansson Jan , Andersson Bengt , Hwang C. Philip
Published: June 2007

Residential care in Sweden has undergone great change in recent decades. With new small family‐style institutions, the boundaries between residential care and foster care have been blurred. Almost all residential care used to be run by the public sector. Today about 80 per cent is privately run. This study compares three different settings in residential care: institutions run by the public sector, privately run institutions and family‐style homes. Among other things, it is found that the institutions run by the public sector have better educated staff and a higher staff–resident ratio than privately run institutions. Despite this, they are more restrictive in their intake and they have youths with fewer problems, especially delinquency and other antisocial behaviour. The results are discussed in relation to developments in the residential care sector in Sweden and in relation to the balance between care and treatment.
Sperm contamination in archived and contemporary herring samples
Authors: MITCHELL DANIELLE , McALLISTER PATRICK , STICK KURT , HAUSER LORENZ
Published: June 2007

Studies using archived scales and otoliths to examine ancient fish populations have become increasingly common, despite many methodological challenges in ancient DNA research. Here, we describe a case of DNA contamination in both modern and historical samples of Pacific herring (Clupea pallasii), where the source of the contamination is likely from milt spillage during collection. We describe a series of experiments to remove contamination using pre‐extraction wash treatments. Though contamination was easily removed from contemporary fin clippings, no method was successful at removing contamination from historical scales. We discuss the implications of our findings to the genetic analysis of archived samples.
Polymorphic microsatellite markers for studies of the conservation and reproductive genetics of imperilled sand tiger sharks (Carcharias taurus)
Authors: FELDHEIM KEVIN A. , STOW ADAM J. , AHONEN HEIDI , CHAPMAN DEMIAN D. , SHIVJI MAHMOOD , PEDDEMORS VIC , WINTNER SABINE
Published: June 2007

We report on the isolation of eight microsatellites from the sand tiger shark, Carcharias taurus, using an enrichment protocol. All loci, with the exception of Cta45–183, were in Hardy–Weinberg equilibrium. Loci exhibited three to 15 alleles, and observed and expected heterozygosities of 0.095–1.000 and 0.284–0.924, respectively. An additional marker (Iox‐12) developed from a shortfin mako library was variable in sand tigers. These markers will be used to examine population genetics and mating patterns of this imperilled species.
Key concepts in urban studies By M Gottdiener and Leslie Budd
Authors: Woods Michael
Published: June 2007

Statement The Editors do not necessarily agree with the statements contained in the book reviews, and neither they nor the RGS‐IBG assume responsibility for the reviewers’ assessments of the books that they evaluate.
Multicolor real‐time polymerase chain reaction genotyping of six human platelet antigens using displacing probes
Authors: Ruan Li , Pei Bin , Li Qingge
Published: June 2007

BACKGROUND: Several genotyping methods for six clinically relevant human platelet antigens (HPAs) have been reported. A four‐color real‐time polymerase chain reaction (PCR) method using displacing probes for genotyping of the six HPAs is described.

STUDY DESIGN AND METHODS: Primers and four differently fluorophor‐labeled displacing probes were designed and synthesized to detect single‐nucleotide polymorphisms responsible for each of the HPA‐1, ‐2, ‐3, ‐4, ‐5, and ‐15 genotypes. Two HPA systems were analyzed in a single PCR procedure. After validation with samples of known genotypes, a total of 150 blood samples from healthy donors were genotyped. The results were compared with PCR with sequence‐specific primers (SSP), PCR‐restriction fragment length polymorphism (RFLP), and/or direct DNA sequencing. The frequencies of each HPA allele were calculated.

RESULTS: Unequivocal real‐time PCR genotyping results were obtained with minimal manual manipulation and carryover contamination. All 150 blood samples were correctly genotyped as confirmed by PCR‐SSP, PCR‐RFLP, and/or direct DNA sequencing. The allelic frequencies of HPA‐1 through ‐5 and ‐15 among the Chinese population in Xiamen were comparable with those previously reported with Chinese living in other territories. For each specimen, genotyping of all six HPA biallelic systems was achieved in three tubes of PCR within 90 minutes and with material cost of no more than $1.

CONCLUSION: Genotyping of HPA with real‐time PCR using displacing probes is more rapid and reliable compared with PCR‐SSP and PCR‐RFLP methods and is more affordable than existing real‐time PCR–based HPA genotyping assays. Thus, our approach is more suitable for routine HPA analysis and ideal for both urgent clinical testing and high‐throughput screening.
Prevalence and quantitation of parvovirus B19 DNA levels in blood donors with a sensitive polymerase chain reaction screening assay
Authors: Kleinman Steven H. , Glynn Simone A. , Lee Tzong‐Hae , Tobler Leslie , Montalvo Leilani , Todd Deborah , Kiss Joseph E. , Shyamala Venkatakrishna , Busch Michael P. ,   National Heart, Lung, Blood Institute Retrovirus Epidemiology Donor Study (REDS‐II)
Published: June 2007

BACKGROUND: Blood donor parvovirus B19 DNA prevalence with sensitive nucleic acid test assays has recently been demonstrated to be higher than that found with assays designed to detect high viral titers in the plasma manufacturing sector.

STUDY DESIGN AND METHODS: Stored plasma aliquots from 5020 donations collected between 2000 and 2003 at seven US blood centers were tested. Testing was performed with a real‐time B19 DNA polymerase chain reaction (PCR; TaqMan, Applied Biosystems) assay with a 50 percent limit of detection (LOD) of 1.6 IU per mL (95% confidence interval [CI], 1.2‐2.1 IU/mL) and a 95 percent LOD of 16.5 IU per mL (95% CI, 10.6‐33.9 IU/mL). Confirmation and quantitation of B19 DNA was accomplished by retesting of two additional subaliquots. Confirmed‐positive specimens were tested for the presence of anti‐B19 immunoglobulin M (IgM) and IgG with FDA‐licensed assays.

RESULTS: B19 DNA prevalence was 0.88 percent (95% CI, 0.64%‐1.2%). Among the 23 donations with B19 DNA titers of at least 20 IU per mL, the median DNA concentration was 105 IU per mL with an interquartile range of 42 to 481 IU per mL; the highest value was 1869 IU per mL. All B19 DNA–positive donations were positive for the presence of IgG and 10 (23%) were also positive for the presence of IgM; IgM seropositivity was associated with increasing DNA levels (p = 0.0013).

CONCLUSION: Low‐level B19 DNA was detected in nearly 1 percent of donations. The 23 percent of DNA‐positive donations with both IgM and IgG B19 antibody most likely represent acute resolving infection, whereas those with IgG but no IgM are most consistent with a more chronic and possibly persistent phase of B19 infection.