bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dalradian rocks of Shetland and their implications for the plate tectonics of the northern Iapetus
Authors: Flinn Derek
Published: January 2010

Synopsis

The Dalradian succession in Shetland is shown to have experienced an extensional tectonic and metamorphic episode prior to the Caledonian orogeny. Sedimentary deposition ended with a major basic and ultrabasic volcanic episode following a long period of extensional basin deposition involving both basic volcanics and turbidites. The ending of deposition was marked by the emplacement of a spinifex-textured komatiite indicating instantaneous rifting of the crust and the underlying Laurentian plate, and the formation of a Laurentian passive continental margin, probably during the opening of Iapetus. The entire contents of the Dalradian depositional basin were rotated bodily 90° to face the rift and to form a 12 km wide vertical belt in the middle of Shetland. A continued rotation in the same sense formed a 25 km wide recumbent inverted limb to form a mega-monocline. The formation of this monocline is considered to have occurred during the extensional phase accompanying rifting because the absence of subsidiary buckle folds of any and every size precludes compressional folding. The metamorphism of the rocks shows a gradual increase from bottom to top of the stratigraphic succession, predating the formation of the monocline, and probably owes its existence to crustal thinning and heating from below the deposition basin during extension. Much of the tectonic and metamorphic history shown by the Dalradian of Shetland may have been overprinted and masked in Scotland by the Caledonian orogeny. In the Dalradian of Shetland the Caledonian orogeny is represented only by the emplacement of the Shetland Ophiolite.
Palaeotemperatures and palaeoenvironments during the Younger Dryas: arthropod evidence from Croftamie at the type area of the Loch Lomond Readvance, and significance for the timing of glacier expansion during the Lateglacial period in Scotland
Authors: Coope G. Russell , Rose James
Published: January 2010

Synopsis

This paper reports the results of a study of arthropod remains from an organic deposit located between tills of the Last Glacial Maximum and the Younger Dryas glaciations, at Croftamie in the type area of the Loch Lomond Readvance in western central Scotland. The arthropod fauna shows that the organic deposit was laid down in a shallow freshwater pool surrounded by moss and leaf debris. Quantified palaeotemperature estimates made using the Mutual Climatic Range method on the coleopteran assemblage show that the climate was severe with mean annual temperatures of about −5°C, and by reference to a previously derived radiocarbon date, this temperature is ascribed to the period around 10 560 ± 160
14
C years
bp
. The results from Croftamie are compared with other sites from Britain and Ireland and it is demonstrated that the Loch Lomond glacier reached its limit at about the middle of the Younger Dryas cold period. The age estimates derived by calibration of the radiocarbon ages may suggest earlier glacier expansion and that the lower boundary of the Younger Dryas in Britain may have been misplaced in the radiocarbon timescale.
Marie Stopes and the Jurassic floras of Brora, NE Scotland
Authors: Falcon-Lang Howard J.
Published: January 2010

Synopsis

Marie Stopes (1880–1958) is best known as a birth control pioneer, but she was also a world-renowned coal geologist and palaeobotanist. This paper provides a historical account of her fieldwork on the Jurassic coast of Brora, NE Scotland. Accompanied by her undergraduate assistant, David Meredith Seares Watson (who was later a well-known vertebrate palaeontologist), Stopes visited this remote region amid a freak heatwave in March 1907. The aim of the trip was to locate Mesozoic permineralized peat deposits (coal balls) similar to those found in the Carboniferous rocks of northern England. Stopes controversially believed that if one understood the mode of origin of a geological phenomenon, it was possible to predict exactly where it would occur. It was this kind of ‘geoprophesy’ (as she called it) that had led her to explore Brora for coal balls. However, in this case, Stopes’s prophetic powers seem to have failed her and no coal balls were located. Nevertheless, it is a tribute to her flexibility and determination that she went on to find an important Middle Jurassic flora, which improved correlation between the Brora succession and the classic reference sections of the Yorkshire coast. In the course of this research, Stopes corresponded with several highly influential geologists. Of these, John Wesley Judd and Albert Charles Seward proved particularly useful, helping her to secure her first major grant from the Royal Society (both men were on the review board). That grant was to fund an 18-month expedition to Japan, and its purpose was also to search for Mesozoic coal balls.
The Upper Morar Psammite of the Moine Supergroup, Ardnamurchan Peninsula, Scotland: depositional setting, tectonic implications
Authors: Bonsor H. C. , Prave A. R.
Published: January 2010

Synopsis

The Upper Morar Psammite of the Moine Supergroup is well developed along the Ardnamurchan Peninsula where it is
c.
2.5 km thick and consists of fine to pebbly arkosic psammite to feldspathic quartzite. Five lithofacies (LF) are recognized. LF1 and LF5 typify the lowermost units and consist of amalgamated and multistorey nested sets of decimetre-scale trough cross-bedding filling channel forms. LF2 and LF3 are distinguished by smaller-scale sets and co-sets of trough and planar cross-bedded units and, in LF3, ripple cross-laminated and planar laminated units. Soft-sediment deformation structures (mostly convolute lamination) are present in both LF2 and LF3. LF4 consists of planar laminated very fine-grained psammite and pelite. There is a progressive decrease in the scale of sedimentary structures upsection concomitant with a greater compositional maturity and textural fining. Palaeo-current data are broadly unimodal but change upward from NNE to NNW directed. No 180° flow reversals are observed nor any other features indicating shallow-marine settings. These observations are used to interpret the Upper Morar Psammite as a retrogradational alluvial braidplain and call into question the commonly held view that the Morar rocks were deposited in a shallow-marine rift basin.
The altitude of the last ice sheet in Caithness and east Sutherland, northern Scotland
Authors: Ballantyne Colin K. , Hall Adrian M.
Published: January 2010

Synopsis

On the mountains of southern Caithness and east Sutherland, geomorphological evidence for the upper limit of glacial erosion implies that, at the last glacial maximum (LGM), warm-based erosive ice extended up to altitudes of 410–600 m. Above the upper limit of glacial erosion is a cover of frost-weathered detritus, with tors on conglomerate bedrock. Kaolinite and gibbsite in soils on such terrain imply that it escaped significant glacial erosion at the LGM. This is confirmed by cosmogenic
10
Be exposure ages of (>) 146.6±15.1 ka and (>) 178.2 ± 18.1 ka obtained for summit tors; sites below the upper limit of glacial erosion yielded deglacial ages of 16.6 ±2.1 to 18.5 ± 2.4 ka. It is unlikely that glacially unmodified summits represent LGM nunataks, as the implied ice thickness is inconsistent with an ice sheet that extended across high ground on Orkney onto the Atlantic shelf; under conservative assumptions at least 70 m of ice must have covered the highest ground in southern Caithness at the LGM. We infer that the absence of evidence for glacial erosion on some summits and plateaux reflects cover by cold-based ice, frozen to the underlying substrate, that preserved the underlying tors and blockfields. This inference calls into question the use of similar evidence in NW Scotland to identify the maximum altitude of the last ice sheet.
Increased Responsiveness of Human Coronary Artery Endothelial Cells in Inflammation and Coagulation
Authors: Lakota Katja , Mrak-Poljsak Katjusa , Rozman Blaz , Sodin-Semrl Snezna
Published: January 2010

The effects of anti-inflammatory plant extracts, such as black tea extract (BTE) and resveratrol (RSV) could modulate cell activation leading to atherosclerosis, however there is little comparative information about how different endothelial cell types are affected by these compounds. In order to compare human endothelial cells derived from different origins (umbilical vein or HUVEC, coronary artery or HCAEC, microvascular or HMVEC) and their interleukin-1β(IL-1β) responsiveness, IL-6 ELISA, RT-PCR, tissue factor assay, and prostacyclin responses using 6-ketoPGF1αELISA were determined. The IL-1β-induced IL-6 levels were dose-dependent with highest responses seen in HCAEC. Significant inhibition of IL-1βresponses was achieved with BTE and RSV, with the largest decrease of IL-6 and TF seen in HCAEC. Prostacyclin levels were highest in HUVEC and were inhibited by RSV in all cell types. The differences between the endothelial cell types could account for greater susceptibility of coronary arteries to inflammation and atherogenesis.
Simpler Evaluation of Predictions and Signature Stability for Gene Expression Data
Authors: Pittelkow Yvonne E. , Wilson Susan R.
Published: January 2010

Scientific advances are raising expectations that patient‐tailored treatment will soon be available. The development of resulting clinical approaches needs to be based on well‐designed experimental and observational procedures that provide data to which proper biostatistical analyses are applied. Gene expression microarray and related technology are rapidly evolving. It is providing extremely large gene expression profiles containing many thousands of measurements. Choosing a subset from these gene expression measurements to include in a gene expression signature is one of the many challenges needing to be met. Choice of this signature depends on many factors, including the selection of patients in the training set. So the reliability and reproducibility of the resultant prognostic gene signature needs to be evaluated, in such a way as to be relevant to the clinical setting. A relatively straightforward approach is based on cross validation, with separate selection of genes at each iteration to avoid selection bias. Within this approach we developed two different methods, one based on forward selection, the other on genes that were statistically significant in all training blocks of data. We demonstrate our approach to gene signature evaluation with a well‐known breast cancer data set.
Genotypic and Phenotypic Assessment of Hyaluronidase among Type Strains of a Select Group of Staphylococcal Species
Authors: Hart Mark E. , Hart Morgan J. , Roop Anna J.
Published: January 2010

Hyaluronidases degrade hyaluronic acid, a major polysaccharide of the extracellular matrix of tissues, and are considered important for virulence in a number of Gram-positive and -negative bacteria. The purpose of the present study was to determine the prevalence of hyaluronidase among clinical strains ofStaphylococcus aureusand among otherStaphylococcusspecies. Spent media and chromosomal DNA were assessed for hyaluronidase activity and the absence or presence of a hyaluronidase gene (hysA) by Southern analysis, respectively. AllS. aureusstrains examined exhibited at least one hybridizing band (half of the strains exhibited two or more hybridizing bands) when probed forhysAand all but three of these strains produced hyaluronidase. In contrast, none of the type strains of 19 other species exhibited either hyaluronidase activity or hybridizing bands when probed forhysA. These data support the hypothesis that among members of theStaphylococcusgenus only strains ofS. aureuspossess the enzyme hyaluronidase. This would suggest that hyaluronidase represents yet another potential virulence factor employed byS. aureusto cause disease and may represent a diagnostically important characteristic for distinguishingS. aureusfrom other members of this genus.
The Influence of Age and Skull Conductivity on Surface and Subdermal Bipolar EEG Leads
Authors: Wendel Katrina , Väisänen Juho , Seemann Gunnar , Hyttinen Jari , Malmivuo Jaakko
Published: January 2010

Bioelectric source measurements are influenced by the measurement location as well as the conductive properties of the tissues. Volume conductor effects such as the poorly conducting bones or the moderately conducting skin are known to affect the measurement precision and accuracy of the surface electroencephalography (EEG) measurements. This paper investigates the influence of age via skull conductivity upon surface and subdermal bipolar EEG measurement sensitivity conducted on two realistic head models from the Visible Human Project. Subdermal electrodes (a.k.a. subcutaneous electrodes) are implanted on the skull beneath the skin, fat, and muscles. We studied the effect of age upon these two electrode types according to the scalp-to-skull conductivity ratios of 5, 8, 15, and 30 : 1. The effects on the measurement sensitivity were studied by means of the half-sensitivity volume (HSV) and the region of interest sensitivity ratio (ROISR). The results indicate that the subdermal implantation notably enhances the precision and accuracy of EEG measurements by a factor of eight compared to the scalp surface measurements. In summary, the evidence indicates that both surface and subdermal EEG measurements benefit better recordings in terms of precision and accuracy on younger patients.
Bone Age Assessment in the Workup of Children with Endocrine Disorders
Authors: Spadoni Gian Luigi , Cianfarani Stefano
Published: January 2010

Bone age is a measure of developmental age, or physiological maturity, which represents more truthfully than chronological age, how far an individual has progressed towards full maturity. It is particularly helpful in the clinical workup of children with growth and/or puberty disorders as well as in treating decisions, such as whether to start replacement therapy in a patient with hypogonadism. Skeletal maturity assessment plays a pivotal role in confirming the diagnosis of normal variants of growth such as familial short stature and constitutional delay of growth, in interpreting hormone tests during puberty, and in the diagnosis of precocious puberty and hyperandrogenism. On the other hand, it is important to recognize that overemphasizing bone age evaluation can be misleading if not used in the proper settings. Adult height prediction is based on skeletal maturity assessment and can be used to predict with acceptable accuracy which adult height will be achieved by a ‘normal’ child. However, the predictions do not apply to children with endocrine or bone pathologies affecting growth.
Clinical Characterization and Analysis of the SRD5A2 Gene in Six Korean Patients with 5α-Reductase Type 2 Deficiency
Authors: Ko Jung Min , Cheon Chong-Kun , Kim Gu-Hwan , Kim Sung Hoon , Kim Kun Suk , Yoo Han-Wook
Published: January 2010

Aims: The aim of this study was to perform a 5α-reductase type 2 gene (SRD5A2) analysis in 6 Korean patients with external genitalia ranging from predominantly female to male in whom 5α-reductase type 2 deficiency was suspected. Patients: Six patients from five unrelated families participated, and all of their parents were non-consanguineous. Three patients presented with ambiguous genitalia at birth, and 2 were referred owing to delayed puberty. The other patient was presented incidentally during an operation for inguinal hernia. Basal and post-human chorionic gonadotropin-stimulated serum testosterone and dihydrotestosterone levels were determined, but neither the levels nor ratio yielded enough information for differential diagnosis. Confirmative diagnosis was achieved by SRD5A2 gene analysis. Results: Four different pathologic mutations were identified. All have already been reported, and are located in exon 1 (p.Q6X), exon 4 (p.G203S and c.655delT), and exon 5 (p.R246Q). p.R246Q was the most frequently identified mutation in our study, and c.655delT has been detected only in Korean patients to date. Conclusion: The molecular analysis is the most reliable method for a correct diagnosis of 5α-reductase type 2 deficiency. Identification of mutations also enables genetic counseling for families at risk.
Treatment with Thyroxine Reduces Thyroid Volume in Euthyroid Children and Adolescents with Chronic Autoimmune Thyroiditis
Authors: Scarpa V. , Kousta E. , Tertipi A. , Vakaki M. , Fotinou A. , Petrou V. , Hadjiathanasiou C. , Papathanasiou A.
Published: January 2010

Background/Aims: Treatment with thyroxine in children with chronic autoimmune thyroiditis (AT) is controversial. The aim of this study is to investigate, by using thyroid ultrasonography, whether thyroxine influences thyroid volume in non-goitrous euthyroid children with AT. Methods: We studied 50 euthyroid non-goitrous children and adolescents with AT for 2 years by thyroid function tests and ultrasonography; 25 were randomized to receive thyroxine and 25 did not receive treatment. Median (IQR) age was 12.1 (11.1–13.2) years. Results: At baseline there was no difference in thyroid volume SDS between the two groups (treatment group 1.1 (0.7–1.5) and controls 0.9 (0.4–1.4), respectively). After 2 years the treatment group had lower thyroid volume SDS compared to the controls (0.6 (0.3–1.0) vs. 2.0 (1.1–2.3), p = 0.001). One child of the treatment group and 12 of the control group developed goiter. Two control children developed subclinical hypothyroidism. Within the treatment group, thyroid volume SDS was lower after 2 years of treatment (p = 0.002). Within the control group, thyroid volume SDS and TSH levels increased after 2 years of follow-up (p = 0.016, 1.9 (1.5–2.8) vs. 3.2 (2.4–4.4) mIU/ml, p = 0.006, respectively). Conclusions: Treatment with thyroxine reduces thyroid volume in non-goitrous euthyroid children with AT and may prevent goiter development.
Eight-Year Follow-Up of a Child with a GH/Prolactin-Secreting Adenoma: Efficacy of Pegvisomant Therapy
Authors: Bergamaschi S. , Ronchi C.L. , Giavoli C. , Ferrante E. , Verrua E. , Ferrari D.I. , Lania A. , Rusconi R. , Spada A. , Beck-Peccoz P.
Published: January 2010

A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40–190), prolactin (PRL) (98.0 ng/ml, nv 1.7–24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.
Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke
Authors: Miedema I. , Uyttenboogaart M. , Koopman K. , De Keyser J. , Luijckx G.J.
Published: January 2010

Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional outcome than statin-naïve patients. Methods: In a prospective observational cohort study of 476 acute ischaemic stroke patients treated with tPA we investigated the relationship between prior statin use and functional outcome at 3 months, the occurrence of symptomatic intracerebral haemorrhage (SICH) and early in-hospital mortality. Ischaemic stroke subtypes were defined according to the TOAST classification. Favourable outcome was defined as a modified Rankin Scale score ≤2. Results: Of the 476 patients included, 98 (20.6%) used a statin at stroke presentation. In the entire cohort, 45.6% of patients had a favourable outcome with no difference between patients with or without statin therapy (45.9 vs. 45.5%, p = 0.94). In the multivariable analysis, statin use was not associated with favourable outcome (OR = 1.1, 95% CI = 0.6–1.9, p = 0.87). In none of the different stroke subtype groups was statin use associated with favourable outcome. Finally, statin use was not an independent risk factor of SICH or of early in-hospital mortality. Conclusion: Prior statin therapy in patients with acute ischaemic stroke treated with tPA is not associated with a more favourable outcome, and this is independent of stroke subtype.
Atheromatous Plaques at the Origin of the Left Subclavian Artery in Patients with Ischemic Stroke
Authors: Kuwashiro Takahiro , Toyoda Kazunori , Yoshimura Sohei , Koga Masatoshi , Naganuma Masaki , Otsubo Ryoichi , Konaka Kuni , Uehara Toshiyuki , Naritomi Hiroaki , Minematsu Kazuo
Published: January 2010

Background: Atheromatous plaques of the aortic arch that extend to the origin of its branches may cause stroke. The frequency and clinical implications of plaque at the origin of the left subclavian artery (LSCA) in patients with recent ischemic stroke were investigated. Methods: We studied 347 consecutive patients (223 men, 69 ± 12 years) who developed symptomatic ischemic stroke and underwent transesophageal echocardiography (TEE). Results: The origin of the LSCA was identified in 303 of 347 patients (87.3%). Plaque ≧1.0 mm was detected in 108 of the 303 patients (35.6%), ranging between 1.0 and 6.1 mm (median, 2.5 mm). Patients having thicker plaque (≧2.5 mm) were older (p = 0.012) and more commonly took antiplatelets prior to stroke (p = 0.038) than patients with no plaque and those with thinner plaque (<2.5 mm). Of the aortic arch findings detected on TEE, maximum intima-media thickness (IMT) was the highest (p < 0.001) in patients with thicker plaque, and large plaque (≧4.0 mm) (p = 0.017), ulcerative plaques (p < 0.001), and spontaneous echo contrasts (p = 0.001) were identified most commonly in patients with thicker plaque. The frequency of infarcts involving the posterior circulation was similar among the three groups. After multivariate adjustment, maximum IMT of the aortic arch was independently related to thicker plaque at the LSCA origin (OR = 1.24, 95% CI = 1.03–1.51, p = 0.024, per 1-mm increase). Conclusions: Atheromatous plaque at the origin of the LSCA was present in approximately one third of patients with a recent ischemic stroke. High IMT at the aortic arch was independently related to the presence of thick plaque at the LSCA origin. The present study does not support the concept that plaque at the LSCA origin may be associated with posterior circulation infarction.
Casein Phosphopeptide-Amorphous Calcium Phosphate Incorporated into Sugar Confections Inhibits the Progression of Enamel Subsurface Lesions in situ
Authors: Walker G.D. , Cai F. , Shen P. , Adams G.G. , Reynolds C. , Reynolds E.C.
Published: January 2010

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has been demonstrated to exhibit anticariogenic activity in randomized, controlled clinical trials of sugar-free gum and a tooth cream. Two randomized, double-blind, crossover studies were conducted to investigate the potential of CPP-ACP added to hard candy confections to slow the progression of enamel subsurface lesions in an in situ model. The confections studied were: (1) control sugar (65% sucrose + 33% glucose syrup); (2) control sugar-free; (3) sugar + 0.5% (w/w) CPP-ACP; (4) sugar + 1.0% (w/w) CPP-ACP; (5) sugar-free + 0.5% (w/w) CPP-ACP. Participants (10 and 14 in study 1 and 2) wore a removable palatal appliance containing enamel half-slabs with subsurface lesions, except for meals and oral hygiene procedures, and consumed 1 confection 6 times a day for 10 days. The enamel half-slabs were inset to allow the development of plaque on the enamel surface. Participants rested for 1 week before crossing over to another confection. The appliances were stored in a humid container at 37°C when not in the mouth. After each treatment period, the enamel half-slabs were removed, paired with their demineralized control half-slabs, embedded, sectioned and then analysed using transverse microradiography. In both studies consumption of the control sugar confection resulted in significant demineralization (progression) of the enamel subsurface lesions. However, consumption of the sugar confections containing CPP-ACP did not result in lesion progression, but in fact in significant remineralization (regression) of the lesions. Remineralization by consumption of the sugar + 1.0% CPP-ACP confection was significantly greater than that obtained with the sugar-free confection.
Leukocyte Toll-Like Receptor Expression in End-Stage Kidney Disease
Authors: Gollapudi P. , Yoon J.-W. , Gollapudi S. , Pahl M.V. , Vaziri N.D.
Published: January 2010

Background: End-stage renal disease (ESRD) is simultaneously associated with inflammation, impaired immunity and increased susceptibility to microbial infections. Innate immune cells, monocytes and polymorphonuclear leukocytes (PMN) recognize pathogens via toll-like receptors (TLR) triggering phagocytosis, cellular activation and secretion of inflammatory cytokines. Data on expression and function of TLRs in ESRD are limited. Methods: Blood samples from 21 stable ESRD patients and 21 normal controls were processed for TLR2, TLR4, TLR7 and TLR 9 expression on monocytes and PMN by flow cytometry. TLR activity was examined by determining the response to TLR4 and TLR2 ligands. Results: The ESRD group exhibited significant upregulation of TLR2 and TLR4 (but not TLR7 or TLR 9) expressions on monocytes and of TLR4 on PMN. This was coupled with heightened cytokine production in response to TLR4 activation with lipopolysaccharide. However, the response to TLR2 stimulation with peptidoglycan was unchanged in the ESRD group. Conclusions: Monocyte TLR2 and TLR4 and neutrophil TLR4 expressions and TLR4 activity are increased hemodialysis patients, representing another dimension of ESRD-associated inflammation.
Regional Systems of Care for Out-of-Hospital Cardiac Arrest
Authors: Nichol Graham , Aufderheide Tom P. , Eigel Brian , Neumar Robert W. , Lurie Keith G. , Bufalino Vincent J. , Callaway Clifton W. , Menon Venugopal , Bass Robert R. , Abella Benjamin S. , Sayre Michael , Dougherty Cynthia M. , Racht Edward M. , Kleinman Monica E. , O'Connor Robert E. , Reilly John P. , Ossmann Eric W. , Peterson Eric ,   Council on Arteriosclerosis, Thrombosis, and Vascular Biology,   Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation,   Council on Cardiovascular Nursing,   Council on Clinical Cardiology,   Advocacy Committee,   Council on Quality of Care and Outcomes Research
Published: January 2010

Out-of-hospital cardiac arrest continues to be an important public health problem, with large and important regional variations in outcomes. Survival rates vary widely among patients treated with out-of-hospital cardiac arrest by emergency medical services and among patients transported to the hospital after return of spontaneous circulation. Most regions lack a well-coordinated approach to post–cardiac arrest care. Effective hospital-based interventions for out-of-hospital cardiac arrest exist but are used infrequently. Barriers to implementation of these interventions include lack of knowledge, experience, personnel, resources, and infrastructure. A well-defined relationship between an increased volume of patients or procedures and better outcomes among individual providers and hospitals has been observed for several other clinical disorders. Regional systems of care have improved provider experience and patient outcomes for those with ST-elevation myocardial infarction and life-threatening traumatic injury. This statement describes the rationale for regional systems of care for patients resuscitated from cardiac arrest and the preliminary recommended elements of such systems. Many more people could potentially survive out-of-hospital cardiac arrest if regional systems of cardiac resuscitation were established. A national process is necessary to develop and implement evidence-based guidelines for such systems that must include standards for the categorization, verification, and designation of components of such systems. The time to do so is now.
DPP-4 Inhibition by Sitagliptin Improves the Myocardial Response to Dobutamine Stress and Mitigates Stunning in a Pilot Study of Patients With Coronary Artery Disease
Authors: Read Philip A. , Khan Fakhar Z. , Heck Patrick M. , Hoole Stephen P. , Dutka David P.
Published: January 2010

Background—

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted postprandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography in patients with coronary artery disease.

Methods and Results—

Fourteen patients with coronary artery disease and preserved LV function awaiting revascularization were studied. After either a single dose of 100 mg sitagliptin or placebo, 75 g of glucose was given orally to promote GLP-1 secretion and dobutamine stress echocardiography was conducted with tissue Doppler imaging at rest, peak stress, and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5�10.7 versus 9.7�8.7 pg/mL;
P
=0.003) and in recovery (12.4�5.5 versus 9.0�5.5 pg/mL;
P
=0.01), and the LV response to stress was enhanced (ejection fraction, 72.6�7.2 versus 63.9�7.9%,
P
=0.0001; mitral annular systolic velocity, 12.54�3.18 versus 11.49�2.52 cm/s;
P
=0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired nonapical segments assessed by peak systolic tissue Doppler (velocity, 10.56�4.49 versus 9.81�4.26 cm/s,
P
=0.002; strain, −15.9�6.3 versus −14.6�6.6%,
P
=0.01; strain rate, −2.04�1.04 versus −1.75�0.98 s
−1
,
P
=0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments, 9.77�4.18 versus 8.74�3.87,
P
=0.007; velocity in nonischemic segments, 11.51�4.70 versus 11.14�4.38,
P
=0.14). In recovery, sitagliptin attenuated the postischemic stunning seen after the control study.

Conclusions—

The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates postischemic stunning in humans with coronary artery disease.

Clinical Trial Registration—

URL: http://www.isrctn.org. Unique identifier: ISRCTN78649100.
Peroxisome Proliferator-Activated Receptor δ Is an Essential Transcriptional Regulator for Mitochondrial Protection and Biogenesis in Adult Heart
Authors: Wang Peiyong , Liu Jian , Li Yuquan , Wu Sijie , Luo Jinwen , Yang Huan , Subbiah Ramasamy , Chatham John , Zhelyabovska Olga , Yang Qinglin
Published: January 2010

Rationale:

Peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ/β) are nuclear hormone receptors and ligand-activated transcription factors that serve as key determinants of myocardial fatty acid metabolism. Long-term cardiomyocyte-restricted PPARδ deficiency in mice leads to depressed myocardial fatty acid oxidation, bioenergetics, and premature death with lipotoxic cardiomyopathy.

Objective:

To explore the essential role of PPARδ in the adult heart.

Methods and Results:

We investigated the consequences of inducible short-term PPARδ knockout in the adult mouse heart. In addition to a substantial transcriptional downregulation of lipid metabolic proteins, short-term PPARδ knockout in the adult mouse heart attenuated cardiac expression of both Cu/Zn superoxide dismutase and manganese superoxide dismutase, leading to increased oxidative damage to the heart. Moreover, expression of key mitochondrial biogenesis determinants such as PPARγ coactivator-1 were substantially decreased in the short-term PPARδ deficient heart, concomitant with a decreased mitochondrial DNA copy number. Rates of palmitate and glucose oxidation were markedly depressed in cardiomyocytes of PPARδ knockout hearts. Consequently, PPARδ deficiency in the adult heart led to depressed cardiac performance and cardiac hypertrophy.

Conclusions:

PPARδ is an essential regulator of cardiac mitochondrial protection and biogenesis and PPARδ activation can be a potential therapeutic target for cardiac disorders.
Coffee Consumption Enhances High-Density Lipoprotein-Mediated Cholesterol Efflux in Macrophages
Authors: Uto-Kondo Harumi , Ayaori Makoto , Ogura Masatsune , Nakaya Kazuhiro , Ito Mai , Suzuki Atsushi , Takiguchi Shun-ichi , Yakushiji Emi , Terao Yoshio , Ozasa Hideki , Hisada Tetsuya , Sasaki Makoto , Ohsuzu Fumitaka , Ikewaki Katsunori
Published: January 2010

Rationale
:

Association of habitual coffee consumption with coronary heart disease morbidity and mortality has not been established. We hypothesized that coffee may enhance reverse cholesterol transport (RCT) as the antiatherogenic properties of high-density lipoprotein (HDL).

Objective
:

This study was to investigate whether the phenolic acids of coffee and coffee regulates RCT from macrophages in vitro, ex vivo and in vivo.

Methods and Results
:

Caffeic acid and ferulic acid, the major phenolic acids of coffee, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, but not apoA-I. Furthermore, these phenolic acids increased both the mRNA and protein levels of ATP-binding cassette transporter (ABC)G1 and scavenger receptor class B type I (SR-BI), but not ABCA1. Eight healthy volunteers were recruited for the ex vivo study, and blood samples were taken before and 30 minutes after consumption of coffee or water in a crossover study. The mRNA as well as protein levels of ABCG1, SR-BI, and cholesterol efflux by HDL were increased in the macrophages differentiated under autologous sera obtained after coffee consumption compared to baseline sera. Finally, effects of coffee and phenolic acid on in vivo RCT were assessed by intraperitoneally injecting [
3
H]cholesterol-labeled acetyl low-density lipoprotein-loaded RAW264.7 cells into mice, then monitoring appearance of
3
H tracer in plasma, liver, and feces. Supporting in vitro and ex vivo data, ferulic acid was found to significantly increase the levels of
3
H tracer in feces.

Conclusions
:

Coffee intake might have an antiatherogenic property by increasing ABCG1 and SR-BI expression and enhancing HDL-mediated cholesterol efflux from the macrophages via its plasma phenolic acids.
TRPM7-Mediated Ca
2+
Signals Confer Fibrogenesis in Human Atrial Fibrillation
Authors: Du Jianyang , Xie Jia , Zhang Zheng , Tsujikawa Hiroto , Fusco Daniel , Silverman David , Liang Bruce , Yue Lixia
Published: January 2010

Rationale:

Cardiac fibrosis contributes to pathogenesis of atrial fibrillation (AF), which is the most commonly sustained arrhythmia and a major cause of morbidity and mortality. Although it has been suggested that Ca
2+
signals are involved in fibrosis promotion, the molecular basis of Ca
2+
signaling mechanisms and how Ca
2+
signals contribute to fibrogenesis remain unknown.

Objective:

To determine the molecular mechanisms of Ca
2+
-permeable channel(s) in human atrial fibroblasts, and to investigate how Ca
2+
signals contribute to fibrogenesis in human AF.

Methods and Results:

We demonstrate that the transient receptor potential (TRP) melastatin related 7 (TRPM7) is the molecular basis of the major Ca
2+
-permeable channel in human atrial fibroblasts. Endogenous TRPM7 currents in atrial fibroblasts resemble the biophysical and pharmacological properties of heterologous expressed TRPM7. Knocking down TRPM7 by small hairpin RNA largely eliminates TRPM7 current and Ca
2+
influx in atrial fibroblasts. More importantly, atrial fibroblasts from AF patients show a striking upregulation of both TRPM7 currents and Ca
2+
influx and are more prone to myofibroblast differentiation, presumably attributable to the enhanced expression of TRPM7. TRPM7 small hairpin RNA markedly reduced basal AF fibroblast differentiation. Transforming growth factor (TGF)-β1, the major stimulator of atrial fibrosis, requires TRPM7-mediated Ca
2+
signal for its effect on fibroblast proliferation and differentiation. Furthermore, TGF-β1–induced differentiation of cultured human atrial fibroblasts is well correlated with an increase of TRPM7 expression induced by TGF-β1.

Conclusions:

Our results establish that TRPM7 is the major Ca
2+
-permeable channel in human atrial fibroblasts and likely plays an essential role in TGF-β1–elicited fibrogenesis in human AF.
Targeted Deletion of the Extracellular Signal-Regulated Protein Kinase 5 Attenuates Hypertrophic Response and Promotes Pressure Overload–Induced Apoptosis in the Heart
Authors: Kimura Tomomi E. , Jin Jiawei , Zi Min , Prehar Sukhpal , Liu Wei , Oceandy Delvac , Abe Jun-ichi , Neyses Ludwig , Weston Arthur H. , Cartwright Elizabeth J. , Wang Xin
Published: January 2010

Rationale:

Mitogen-activated protein kinase (MAPK) pathways provide a critical connection between extrinsic and intrinsic signals to cardiac hypertrophy. Extracellular signal-regulated protein kinase (ERK)5, an atypical MAPK is activated in the heart by pressure overload. However, the role of ERK5 plays in regulating hypertrophic growth and hypertrophy-induced apoptosis is not completely understood.

Objective:

Herein, we investigate the in vivo role and signaling mechanism whereby ERK5 regulates cardiac hypertrophy and hypertrophy-induced apoptosis.

Methods and Results:

We generated and examined the phenotypes of mice with cardiomyocyte-specific deletion of the
erk5
gene (ERK5
cko
). In response to hypertrophic stress, ERK5
cko
mice developed less hypertrophic growth and fibrosis than controls. However, increased apoptosis together with upregulated expression levels of p53 and Bad were observed in the mutant hearts. Consistently, we found that silencing ERK5 expression or specific inhibition of its kinase activity using BIX02189 in neonatal rat cardiomyocytes (NRCMs) reduced myocyte enhancer factor (MEF)2 transcriptional activity and blunted hypertrophic responses. Furthermore, the inhibition of MEF2 activity in NRCMs using a non-DNA binding mutant form of MEF2 was found to attenuate the ERK5-regulated hypertrophic response.

Conclusions:

These results reveal an important function of ERK5 in cardiac hypertrophic remodeling and cardiomyocyte survival. The role of ERK5 in hypertrophic remodeling is likely to be mediated via the regulation of MEF2 activity.
In-Hospital Complication Rates After Stent Treatment of 388 Symptomatic Intracranial Stenoses
Authors: Kurre Wiebke , Berkefeld Joachim , Brassel Friedhelm , Brüning Roland , Eckert Bernd , Kamek Seniye , Klein Guenther E. , Knauth Michael , Liebig Thomas , Maskova Jana , Mucha Dirk , Neumann-Haefelin Tobias , Pilgram-Pastor Sara , Sitzer Matthias , Sonnberger Michael , Tietke Mark , Trenkler Johannes , Turowski Bernd
Published: January 2010

Background and Purpose—

Stenting is increasingly used as an adjunct to medical therapy in symptomatic intracranial stenoses. High periprocedural adverse event rates are one of the limitations of endovascular treatment. Data from the INTRASTENT multicentric registry should demonstrate in-hospital complications at the current stage of clinical development of the stent procedure.

Methods—

Participating centers entered the records of all their consecutive intracranial stent procedures into the database. To determine the clinical outcome in the acute phase, we distinguished transient ischemic attack/nondisabling stroke (modified Rankin Scale <2), disabling stroke, death, and intracranial hemorrhage as clinical complications and analyzed whether they were associated with patient- or stenosis-related risk factors.

Results—

Data from 372 patients with 388 stenoses proved 4.8% disabling strokes and 2.2% deaths. Transient or minor events were detected in 5.4% of the cases. Hemorrhagic events (3.5%) occurred more frequently after treatment of middle cerebral artery stenoses (
P
=0.004) and were associated with significantly higher morbidity and mortality rates. Ischemic strokes by compromise of perforating branches were detected mainly in the posterior circulation. However, the overall rate of severe adverse events was not dependent from location, degree, and morphology of the stenosis or from patient’s age, gender, vascular risk factors, or type of qualifying event.

Conclusion—

The complication rates within the registry are within the limits of previously published data. Severe adverse events were equally distributed between potential risk groups with similar rates but different types of main complications in the anterior and posterior circulation.
Caregiving Strain and Estimated Risk for Stroke and Coronary Heart Disease Among Spouse Caregivers
Authors: Haley William E. , Roth David L. , Howard George , Safford Monika M.
Published: January 2010

Background and Purpose—

Psychosocial stress has been widely studied as a risk factor for stroke and coronary heart disease (CHD) but little is known about the differential effects of stress on stroke and CHD risk by race and sex. Caregiving for a disabled spouse has been associated with increased mortality and CHD risk, but the association of caregiving strain with stroke and CHD risk across race and sex is unknown.

Methods—

Participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study who were providing in-home caregiving to a disabled spouse reported on caregiving strain (high, some, or none), depressive symptoms, social network, education, and age. Caregiving strain groups were compared on the Framingham Stroke Risk Score (N=716) and Framingham CHD Risk Score (N=607), which estimate the projected 10-year risk of incident stroke and ischemic heart disease, respectively.

Results—

High caregiving strain was associated with a 23% higher covariate-adjusted estimated stroke risk (11.06% for caregivers with no strain versus 13.62% risk for high-strain caregivers). This association was stronger in men, particularly African American men with high caregiving strain (26.95% estimated 10-year stroke risk). Caregiving strain was not associated with CHD risk scores.

Conclusions—

Caregiving strain is significantly associated with higher estimated stroke risk with greatest effects for men, particularly African American men, providing caregiving to their wives. Male spouse caregivers may need special caregiving support. Prospective longitudinal studies should examine how sex and race may moderate the impact of stress on stroke and CHD risk.
Infectious Burden and Carotid Plaque Thickness
Authors: Elkind Mitchell S.V. , Luna Jorge M. , Moon Yeseon Park , Boden-Albala Bernadette , Liu Khin M. , Spitalnik Steven , Rundek Tanja , Sacco Ralph L. , Paik Myunghee C.
Published: January 2010

Background and Purpose—

The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multiethnic cohort.

Methods—

Antibody titers to 5 common infectious microorganisms (ie,
Chlamydia pneumoniae, Helicobacter pylori
, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants and a weighted index of infectious burden was calculated based on Cox models previously derived for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness. Weighted least squares regression was used to measure the association between infectious burden and maximum carotid plaque thickness after adjusting for other risk factors.

Results—

Serological results for all 5 infectious organisms were available in 861 participants with maximum carotid plaque thickness measurements available (mean age, 67.2±9.6 years). Each individual infection was associated with stroke risk after adjusting for other risk factors. The infectious burden index (n=861) had a mean of 1.00±0.35 SD and a median of 1.08. Plaque was present in 52% of participants (mean, 0.90±1.04 mm). Infectious burden was associated with maximum carotid plaque thickness (adjusted increase in maximum carotid plaque thickness 0.09 mm; 95% CI, 0.03 to 0.15 mm per SD increase of infectious burden).

Conclusion—

A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multiethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.
Roman Catholic/Pentecostal Dialogue: A Contribution to Christian Unity
Authors: Sandidge Jerry L.
Published: January 2010

There is roughly a 60-year period between the formation of the first Pentecostal denominations and the beginning of international dialogue between the Vatican Secretariat for Promoting Christian Unity and some members of the Pentecostal churches. It is obvious that something significant had to occur on both sides before there could even be the suggestion of some kind of discussion at the dialogue table. This article is an attempt to trace the origins of the Dialogue and to summarize the ten-year history of this unique theological exchange. Consideration will also be given to the way the dialogue process works and to a discussion of theological issues. A few remarks will be given about the ecumenical significance of the Dialogue, and in conclusion, some comments will be made on the future of the Dialogue.
Updated Parental Viewpoints on Male Neonatal Circumcision in the United States
Authors: Wang Marvin L. , Macklin Eric A. , Tracy Erin , Nadel Hiyam , Catlin Elizabeth A.
Published: January 2010

Through a questionnaire, the authors sought to elicit information about initial attitudes concerning circumcision after reading a summary of the American Academy of Pediatrics (AAP) Policy Statement and, again, after reading a description of recent HIV/HPV studies. Predictors of increased support for circumcision included having a prior circumcised boy and being US born. Predictors of decreased support included being of Hispanic ethnicity and believing that the uncircumcised penis was more culturally normal. After reading the AAP statement, 86% of respondents remained favorable of elective circumcision, whereas 13% viewed it less favorably. After reading the passage about the HIV/HPV studies, the majority maintained their initial level of support. Certain characteristics were associated with an individual’s desire to perform circumcision on his/her infant. Despite a slight decrease in support to perform circumcision after reading the AAP policy summary, respondents’ initial attitudes toward circumcision were unchanged after subsequent review of recent HIV/HPV research.