bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial Deletion of Proximal 8q Including Part of the Centromere from Unbalanced Segregation of a Paternal Deletion/Marker Karyotype with Neocentromere Formation at 8p22
Authors: Burnside R.D. , Ibrahim J. , Flora C. , Schwartz S. , Tepperberg J.H. , Papenhausen P.R. , Warburton P.E.
Published: February 2011

Background/Aims: The ‘McClintock mechanism’ of chromosome breakage and centromere misdivision, in which a deleted chromosome with its concomitant excised marker or ring chromosome is formed, has been described in approximately one dozen reports. We report a case of a girl with short stature, developmental delay, and dysmorphic features. Methods: Analysis was performed on the proband and father using cytogenetic chromosome analysis and the Affymetrix 6.0 SNP microarray. Fluorescence in situ hybridization (FISH) using a chromosome 8 alpha-satellite probe and immunofluorescence with antibodies to CENP-C were used to examine the centromere positions in these chromosomes. Results: An abnormal chromosome 8 with a cytogenetically visible deletion was further defined by SNP array as a 10.6-Mb deletion from 8q11.1→q12.1. FISH with a chromosome 8 alpha-satellite probe demonstrated that the deletion removed a significant portion of the pericentromeric alpha-satellite repeat sequences and proximal q arm. The deleted chromosome 8 appeared to have a constriction at 8p22, suggesting the formation of a neocentromere, even though alpha-satellite sequences still appeared at the normal location. Chromosome analysis of the phenotypically normal father revealed the same deleted chromosome 8, as well as an apparently balancing mosaic marker chromosome 8. FISH studies revealed that the majority of the chromosome 8 alpha-satellite DNA resided in the marker chromosome. Immunofluorescence studies with antibodies to CENP-C, a kinetochore protein, proved the presence of a neocentromere at 8p22. The excision of the marker from the deleted chromosome 8 likely necessitated the formation of a new kinetochore at the 8p22 neocentromere to stabilize the chromosome during mitosis. Conclusion: This case clearly illustrates the utilization of classic cytogenetics, FISH, and array technologies to better characterize chromosomal abnormalities and provide information on recurrence risks. It also represents a rare case where a neocentromere can form even in the presence of existing alpha-satellite DNA.
Karyotype Reorganisation in the subtilis Group of Birch Mice (Rodentia, Dipodidae, Sicista): Unexpected Taxonomic Diversity within a Limited Distribution
Authors: Kovalskaya Y.M. , Aniskin V.M. , Bogomolov P.L. , Surov A.V. , Tikhonov I.A. , Tikhonova G.N. , Robinson T.J. , Volobouev V.T.
Published: February 2011

Conventional cytogenetic studies of Sicista subtilis and S. severtzovi (Dipodidae, Sicistinae), both attributable to the subtilis group of birch mice, revealed extensive karyotype diversity with 2n = 16–26 and NFa values of 26–46 indicating the overwhelming non-Robertsonian nature of chromosomal reorganization in these species. The numerical and structural chromosome variability was principally found in specimens located within a confined region of the East European (Russian) Plain. The approximately 135,000-km2 area occurs in the vicinity of the Don River bend between 49°13’N/43°46’E and 51°32’N/36°16’E. The detection of cytotypes sharing similar 2n and NF values, but having morphologically distinct chromosomes, suggests that these may result from polymorphisms present both within recognized species and in cryptic taxa not hitherto described. We conducted a comprehensive, comparative chromosome banding analysis of 52 birch mice (21 localities) referable to the subtilis group and report the presence of 5 distinct karyotypes, each characterized by a combination of stable, variable, and partly overlapping 2n/NFa values. These karyotypes differed from each other by 10–29 structural chromosomal rearrangements (18.1 ± 6.3) that comprised Rb fusions/fissions (42.2%), pericentric inversions (31.1%), and tandem translocations (22.2%). The composition, and the high numbers of these chromosomal changes, is likely to provide an effective means of post-mating isolation, suggesting that taxonomic diversity within the subtilis group is larger than currently accepted. Additionally, we report the frequent fixation of tandem translocations in sample populations, one of which was found in a polymorphic state representing, as far as we are aware, the first case of an in statu nascendi tandem fusion in wild populations. Moreover, our data revealed that bi-armed chromosomes were involved in fusions detected in some of the subtilis taxa. In each instance, however, fusions were preceded by pericentric inversions that transform one or both bi-armed chromosomes into acrocentrics resulting in either centromere-telomere or Robertsonian translocations. Finally, a phylogenetic scenario inferred from a cladistic analysis of the chromosomal data suggests that the extensive karyotypic diversification within the subtilis group in the south-east region of the Russian Plain most likely results from fragmentation of a continuously distributed, ancestral population. It is thought that this occurred at the last glacial maximum (18,000–14,000 years B.P.), and that the process of isolation has been exacerbated by increasing human activity in the region in modern times.
Novel Variant Ph Translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in Chronic Myeloid Leukemia Involving a One-Step Mechanism
Authors: Belli C. , Alú M.F. , Alfonso G. , Bianchini M. , Larripa I.
Published: February 2011

Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of ABL1.
Nissen versus Dor Fundoplication for Treatment of Gastroesophageal Reflux Disease: A Blinded Randomized Clinical Trial
Authors: Raue W. , Ordemann J. , Jacobi C.A. , Menenakos C. , Buchholz A. , Hartmann J.
Published: February 2011

Introduction: Fundoplication techniques for treatment of gastroesophageal reflux are discussed concerning impairments and success. This randomized trial was conducted to compare Nissen’s wrap and the anterior partial technique (Dor) concerning patients’ quality of life (QoL) and functional data after a mid-term follow-up. Methods: In a 24-month period, 64 patients were equally randomized into group A (Nissen’s fundoplication) and group B (180° anterior partial fundoplication). After a mean follow-up of 18 months, all patients were examined and interviewed using standardized QoL questionnaires (Gastrointestinal Quality of Life Index), Visick score, 24-hour pH-metry and esophageal manometry. Data of 57 patients (group A: 27, group B: 30) could be analyzed. Results: After partial fundoplication, 9 patients (30%) stated the operative results were worse than perfect. Only 2 patients (7%) evaluated the outcome after Nissen’s fundoplication as unsuccessful (p = 0.04). However, postoperative Gastrointestinal Quality of Life Index showed no differences between groups (p = 0.5). Additionally, functional data were not different (DeMeester 10 vs. 12, p = 0.17, and lower esophageal sphincter pressure 13 vs. 12 mm Hg, p = 0.5). Conclusion: The anterior partial fundoplication technique did not lead to disadvantages in postoperative QoL, physiological function and reflux control when compared to Nissen’s approach in a mid-term follow-up.
Effects of an N-Type Calcium Antagonist on Angiotensin II-Renin Feedback
Authors: Aritomi Shizuka , Niinuma Kazumi , Ogawa Tetsuya , Konda Tomoyuki , Nitta Kosaku
Published: February 2011

Background: Interrupting the renin-angiotensin system (RAS) with an angiotensin II receptor blocker (ARB) has been found to induce RAS overactivation. In this study, we investigated the effect of 2 calcium channel blockers (CCBs), cilnidipine (L-/N-type CCB) and amlodipine (L-type CCB), on the RAS activation induced by an ARB in a strain of spontaneously hypertensive rats (SHR/Izm, 10 weeks of age). Methods: Rats intravenously catheterized for blood collection were randomly divided into groups that were administered the vehicle, the ARB valsartan or valsartan combined with one of the 2 CCBs. Their blood and kidneys were collected 270 min after administration. Results: Valsartan increased the plasma angiotensin II (Ang II) level in a dose-dependent manner. Cilnidipine suppressed the increase in plasma renin activity and plasma Ang II levels induced by valsartan, but amlodipine did not. Combined administration of cilnidipine, but not amlodipine, and valsartan significantly reduced the noradrenaline content in the renal cortex. Conclusions: The results of this study suggest that the suppressive effect of cilnidipine on the valsartan-induced increase in RAS activity can be partly explained by its sympatholytic action mediated by N-type calcium channel blockade, and that combined administration of cilnidipine and valsartan might provide a synergistic therapeutic effect.
Racial and Ethnic Differences in Mortality of Hemodialysis Patients: Role of Dietary and Nutritional Status and Inflammation
Authors: Noori Nazanin , Kovesdy Csaba P. , Dukkipati Ramanath , Feroze Usama , Molnar Miklos Z. , Bross Rachelle , Nissenson Allen R. , Kopple Joel D. , Norris Keith C. , Kalantar-Zadeh Kamyar
Published: February 2011

Background: Racial/ethnic disparities prevail among hemodialysis patients. We hypothesized that significant differences exist between Black and non-Hispanic and Hispanic White hemodialysis patients in nutritional status, dietary intake and inflammation, and that they account for racial survival disparities. Methods: In a 6-year (2001–2007) cohort of 799 hemodialysis patients, we compared diet and surrogates of nutritional-inflammatory status and their mortality-predictabilities between 279 Blacks and 520 Whites using matched and regression analyses and Cox with cubic splines. Results: In age-, gender- and diabetes-matched analyses, Blacks had higher lean body mass and serum prealbumin, creatinine and homocysteine levels than Whites. In case-mix-adjusted analyses, dietary intakes in Blacks versus Whites were higher in energy (+293 ± 119 cal/day) and fat (+18 ± 5 g/day), but lower in fiber (–2.9 ± 1.3 g/day) than Whites. In both races, higher serum albumin, prealbumin and creatinine were associated with greater survival, whereas CRP and IL-6, but not TNF-α, were associated with increased mortality. The highest (vs. lowest) quartile of IL-6 was associated with a 2.4-fold (95% CI: 1.3–3.8) and 4.1-fold (2.2–7.2) higher death risk in Blacks and Whites, respectively. Conclusions: Significant racial disparities exist in dietary, nutritional and inflammatory measures, which may contribute to hemodialysis outcome disparities. Testing race-specific dietary and/or anti-inflammatory interventions is indicated.
Beta-Cell Dysfunction and Insulin Resistance after Subarachnoid Haemorrhage
Authors: Kruyt N.D. , Musters A. , Biessels G.J. , DeVries J.H. , Coert B.A. , Vergouwen M.D.I. , Horn J. , Roos Y.B.
Published: February 2011

Background: Hyperglycaemia is a common finding and an independent risk factor for increased morbidity and mortality in aneurysmal subarachnoid haemorrhage (SAH). Although in these patients hyperglycaemia is commonly ascribed to insulin resistance, there is little understanding of underlying mechanisms. Aims: To prospectively study temporal disturbances of glucose metabolism after aneurysmal SAH in patients without known abnormalities of glucose metabolism and to explore possible correlations with markers of stress. Methods: In consecutive aneurysmal SAH patients not subjected to insulin therapy, in-hospital and follow-up oral glucose tolerance tests (OGTTs) and assessments of insulin resistance, pancreatic β-cell function, free fatty acids (FFA) and cortisol were performed and compared with reference values. Results: We included 13 patients. In the first 2 weeks of admission, median fasting glucose and FFA levels were elevated while insulin levels were not. OGTTs were indicative of glucose intolerance in all patients at days 3 and 7, while on follow-up 1 patient had glucose intolerance and all patients had normal fasting glucose levels. Pancreatic β-cell function was impaired throughout the first week and insulin resistance from day 4 to 10. Levels of cortisol correlated with higher fasting glucose and increased FFA. FFA in turn correlated with pancreatic β-cell dysfunction. Conclusions: Aneurysmal SAH patients have transient abnormalities of glucose metabolism. During the first week, it appears to result predominantly from transient pancreatic β-cell dysfunction, in combination with insulin resistance.
Short Stature due to SHOX Deficiency: Genotype, Phenotype, and Therapy
Authors: Binder Gerhard
Published: February 2011

SHOX deficiency is a frequent cause of short stature. The short stature homeobox-containing gene resides in the telomeric PAR1 region on the short arm of both sex chromosomes and escapes X inactivation. For this review, abstracts of 207 publications presented by PubMed for the search term ‘SHOX’ were screened. Heterozygote SHOX mutations (80% deletions) were detected in 2–15% of individuals with formerly idiopathic short stature, in 50–90% of individuals with Leri-Weill dyschondrosteosis, and in almost 100% of girls with Turner syndrome. Mutational analysis is primarily performed by MLPA analysis followed by gene sequencing if necessary. SHOX is a nuclear protein that binds to DNA and acts as a transcriptional activator. Orthologs are present in many vertebrates but not in rodents. Gene expression starting as early as 33 days postconception in humans is predominant in the mid portion of the buds and in the first and second pharyngeal arches. In the growth plate, hypertrophic chondrocytes express SHOX where it seems to have antiproliferative potency. The penetrance of SHOX deficiency is high, but its clinical expression is very variable becoming more pronounced with age and being more severe in females. Growth failure starts early during the first years of life and the height deficit present at preschool age seems not to deteriorate further. The mean adult height is –2.2 SDS. Auxological analysis of the body proportions (mesomelia), the presence of minor abnormalities, and the search for subtle radiographic signs are important keys to the diagnosis which has to be confirmed by genetic analysis. The growth-promoting effect of GH therapy approved for individuals with SHOX mutations seems to be equal to the effect seen in Turner syndrome.
Tissue Factor Pathway Inhibitor
Authors: Regnault Veronique , Perret-Guillaume Christine , Kearney-Schwartz Anna , Max Jean-Pierre , Labat Carlos , Louis Huguette , Wahl Denis , Pannier Bruno , Lecompte Thomas , Weryha Georges , Challande Pascal , Safar Michel E. , Benetos Athanase , Lacolley Patrick
Published: February 2011

Objective—

To investigate in women older than 60 whether aortic stiffness or pulse pressure (PP) is associated with selected procoagulant or anticoagulant factors and to examine whether pulsatile stretch influences these factors in human vascular smooth muscle cells (VSMCs) in vitro.

Methods and Results—

Aortic pulse wave velocity (PWV) and carotid PP were studied in 123 apparently healthy postmenopausal women. PWV, PP, von Willebrand factor, and free tissue factor pathway inhibitor (TFPI), but not mean arterial pressure, increased with age. Free TFPI and PWV were positively correlated, even after adjustment for age and PP and other confounding parameters. In vitro, 5% or 10% pulsatile stretch (at 1 Hz) enhanced TFPI synthesis and secretion by VSMCs in a time-independent manner (1 to 48 hours) without changes in protein level of smooth muscle myosin heavy chain. Application of 5% static stretch had no effect.

Conclusion—

In postmenopausal women, free TFPI increases as vascular wall function deteriorates and PP increases. These findings are supported by the increase in TFPI synthesized by VSMCs in response to cyclic stress in vitro. They suggest that VSMCs require pulsatility to interfere with the coagulation process and highlight the relevance of plasma free TFPI levels to cardiovascular diseases.
Tissue Kallikrein Inhibits Retinal Neovascularization via the Cleavage of Vascular Endothelial Growth Factor-165
Authors: Nakamura Shinsuke , Morimoto Nobutaka , Tsuruma Kazuhiro , Izuta Hiroshi , Yasuda Yoshika , Kato Noriaki , Ikeda Tsunehiko , Shimazawa Masamitsu , Hara Hideaki
Published: February 2011

Objective—

Tissue kallikrein, a widely used vasodilator for the treatment of hypertension and peripheral circulatory disorder, acts by releasing kinin, a potent vasodilator peptide. To identify the role of tissue kallikrein in retinal neovascularization, we investigated the antiangiogenic effect by using an in vitro and in vivo angiogenesis model.

Methods and Results—

Tissue kallikrein in vitreous fluid was markedly elevated in proliferative diabetic retinopathy patients compared with that in control patients with macular hole and epiretinal membrane. Tissue kallikrein inhibited vascular endothelial growth factor-165 (VEGF
165
)–induced tube formation, proliferation, and migration in vitro angiogenesis model via suppression of the VEGF
165
-induced phosphorylation of VEGF receptor-2. Furthermore, tissue kallikrein cleavage of VEGF
165
was on the C-terminal side, which was analyzed by Western blotting and mass spectrometry. When administered subcutaneously, tissue kallikrein reduced the pathological vascular changes in retinal neovascularization induced in neonatal mice by returning the retina to normoxia after exposure to hyperoxia.

Conclusion—

These findings indicate that tissue kallikrein is partly involved in pathogenesis of proliferative diabetic retinopathy and may be a promising therapeutic agent that could cleave VEGF
165
itself when administered by a peripheral route.
The Effect of Survival Bias on Case-Control Genetic Association Studies of Highly Lethal Diseases
Authors: Anderson Christopher D. , Nalls Michael A. , Biffi Alessandro , Rost Natalia S. , Greenberg Steven M. , Singleton Andrew B. , Meschia James F. , Rosand Jonathan
Published: February 2011

Background—

Survival bias is the phenomenon by which individuals are excluded from analysis of a trait because of mortality related to the expression of that trait. In genetic association studies, variants increasing risk for disease onset as well as risk of disease-related mortality (lethality) could be difficult to detect in genetic association case-control designs, possibly leading to underestimation of a variant's effect on disease risk.

Methods and Results—

We modeled cohorts for 3 diseases of high lethality (intracerebral hemorrhage, ischemic stroke, and myocardial infarction) using existing longitudinal data. Based on these models, we simulated case-control genetic association studies for genetic risk factors of varying effect sizes, lethality, and minor allele frequencies. For each disease, erosion of detected effect size was larger for case-control studies of individuals of advanced age (age >75 years) and/or variants with very high event-associated lethality (genotype relative risk for event-related death >2.0). We found that survival bias results in no more than 20% effect size erosion for cohorts with mean age <75 years, even for variants that double lethality risk. Furthermore, we found that increasing effect size erosion was accompanied by depletion of minor allele frequencies in the case population, yielding a “signature” of the presence of survival bias.

Conclusions—

Our simulation provides formulas to allow estimation of effect size erosion given a variant's odds ratio of disease, odds ratio of lethality, and minor allele frequencies. These formulas will add precision to power calculation and replication efforts for case-control genetic studies. Our approach requires validation using prospective data.
Human Resistin Stimulates Hepatic Overproduction of Atherogenic ApoB-Containing Lipoprotein Particles by Enhancing ApoB Stability and Impairing Intracellular Insulin Signaling
Authors: Costandi Justina , Melone Michelle , Zhao Alex , Rashid Shirya
Published: February 2011

Rationale:

Obese individuals are at high risk for developing atherosclerosis primarily attributable to elevated plasma concentrations of apolipoprotein (apo)B-containing particles, including very-low-density lipoprotein (VLDL). Plasma levels of the adipose tissue adipokine resistin are increased in human obesity, and resistin expression is positively correlated with coronary atherosclerosis and VLDL levels.

Objective:

We sought to determine for the first time whether resistin directly stimulates human hepatocyte production of apoB-containing particles and to elucidate the mechanisms responsible.

Methods and Results:

Treatment of human hepatocytes with resistin at levels observed in human obesity stimulated apoB secretion up to 10-fold, because of increased microsomal triglyceride transfer protein (MTP) activity and decreased expression/phosphorylation of proteins in the insulin signaling pathways (insulin receptor substrate-2, Akt, and extracellular signal-regulated kinase). Resistin also increased hepatocyte lipid content by stimulating de novo lipogenesis via the
SREBP1
and
SREBP2
pathways. Furthermore, obese serum with elevated resistin levels induced greater hepatocyte stimulation of apoB secretion than lean human serum, an effect that was ameliorated by antibody immunoprecipitation removal of serum resistin.

Conclusions:

Resistin has a direct deleterious impact on human hepatic lipid and lipoprotein regulation. Resistin greatly increased hepatocyte VLDL apoB and lipid secretion because of MTP activation and induction of hepatocyte insulin resistance. Conversely, antibody removal of serum resistin ameliorated human serum stimulation of apoB secretion. Increased hepatic cellular lipids mediated by resistin reflects the fatty liver/steatosis observed with elevated resistin in humans. Thus, human resistin is a novel therapeutic target for mitigating common hepatic pathophysiological processes associated with human obesity, dyslipidemia and atherosclerosis.
Effect of the oxLDL Binding Protein Fc-CD68 on Plaque Extension and Vulnerability in Atherosclerosis
Authors: Zeibig Stephan , Li Zhongmin , Wagner Silvia , Holthoff Hans-Peter , Ungerer Martin , Bültmann Andreas , Uhland Kerstin , Vogelmann Jasmin , Simmet Thomas , Gawaz Meinrad , Münch Götz
Published: February 2011

Rationale:

There is strong evidence that oxidative modification of low-density lipoprotein (oxLDL) plays a critical role in atherogenesis and that oxLDL may profoundly influence the mechanical stability of atherosclerotic plaques.

Objective:

To block oxLDL, we designed, expressed, and tested Fc-CD68, a soluble oxLDL binding protein consisting of human Fc and the extracellular domain of the human oxLDL-binding receptor CD68.

Methods and Results:

Fc-CD68 bound with high specific affinity to oxLDL and strongly bound and colocalized with oxLDL in plaques. To study the effects of repeated administrations of Fc-CD68 on the progression of atherosclerosis and plaque vulnerability, 12- and 16-week old cholesterol-fed ApoE
−/−
mice received either Fc-CD68 (n=6) or Fc control protein (n=6 to 8) thrice weekly for 4 weeks. Macroscopic and histological analysis of Sudan red lipid staining showed strong and significant reduction of plaque extension in the aorta and in the aortic root, respectively. Histological analysis of pentachrome- and Sirius-stained sections of the brachiocephalic arteries of 20 week-old ApoE
−/−
mice revealed that Fc-CD68 significantly reduced the occurrence of spontaneous ruptures of established plaques by ≈20%, compared with Fc and drastically increased the collagen content of plaques. Furthermore, in immunostained sections of the brachiocephalic artery and the aortic root, Fc-CD68 reduced the infiltration of plaques with T lymphocytes, and macrophages by ≈50% and 30%, respectively.

Conclusions:

The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.
The Hidden Mismatch
Authors: Ma Henry K. , Zavala Jorge A. , Churilov Leonid , Ly John , Wright Perter M. , Phan Thanh G. , Arakawa Shuji , Davis Stephen M. , Donnan Geoffrey A.
Published: February 2011

Background and Purpose—

In ischemic stroke, MR perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) mismatch represents tissue at risk for infarction. Infarct growth should only take place in the presence of mismatch, although there have been reports of this occurring. We hypothesized that this observation may be attributable to the presence of undetected “hidden mismatch,” which may become obvious when coregistration techniques are used.

Methods—

MR PWI/DWI was performed within 48 hours of stroke onset and a final T2-weighted image at ≈3 months. Volumetric-subtraction mismatch volume was defined as PWI minus DWI volume and infarct growth was defined as T2 minus DWI volume. Coregistration mismatch volume was PWI not overlapped by DWI. Mismatch salvage was the proportion of coregistered mismatch tissue that had not progressed to infarction.

Results—

Thirty-four patients were studied with MR at a median of 4.9 hours (interquartile range, 2.9–21.1 hours). With the volumetric-subtraction technique, 5 patients (14.7%; 95% CI, 0.05%–0.31%) had infarct growth exceeding mismatch volume, 11 patients (32.0%) had no mismatch and, among these, 3 (27.3%) had infarct growth (median volume, 2.2 mL; interquartile range, 1.0–6.5 mL). All patients had mismatch volume identified by coregistration method that was greater than infarct growth volume. The proportion of this volume salvaged was 77.7% (interquartile range, 63.0%–98.9%).

Conclusions—

The illogical finding of infarct growth volume being greater than the presence of mismatch volume can be explained by the presence of “hidden mismatch,” which may be detected by coregistration methods.
Intracortical Infarcts in Small Vessel Disease
Authors: Jouvent Eric , Poupon Cyril , Gray Françoise , Paquet Claire , Mangin Jean-François , Le Bihan Denis , Chabriat Hugues
Published: February 2011

Background and Purpose—

The purpose of this study was to report the detection of infarcts of the cerebral cortex in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using high-resolution postmortem 7-T MRI in association with pathological examination.

Methods—

Whole brain high-resolution MRI data were obtained postmortem at 7 T in a 53-year-old patient with CADASIL. These MRI data were used to guide the neuropathological examination of the cortex.

Results—

Combined with neuropathology, MRI allowed the delineation of intracortical infarcts confirmed by histological examination in this case. These lesions were not visible on the last in vivo MRI obtained at 1.5 T and were difficult to detect on neuropathological examination only.

Conclusions—

Postmortem high-resolution MRI may help to detect intracortical infarcts in CADASIL and possibly in other small vessel diseases of the brain.
NCX1 Is a Novel Target Gene for Hypoxia-Inducible Factor-1 in Ischemic Brain Preconditioning
Authors: Valsecchi Valeria , Pignataro Giuseppe , Del Prete Annalisa , Sirabella Rossana , Matrone Carmela , Boscia Francesca , Scorziello Antonella , Sisalli Maria Josè , Esposito Elga , Zambrano Nicola , Di Renzo Gianfranco , Annunziato Lucio
Published: February 2011

Background and Purpose—

The sodium–calcium exchanger-1 (NCX1) represents a key mediator for maintaining [Na
+
]
i
and [Ca
2+
]
i
homeostasis. Although changes in NCX1 protein and transcript expression have been detected during stroke, its transcriptional regulation is still unknown. Thus far, however, there is evidence that hypoxia-inducible factor-1 (HIF-1) is a nuclear factor required for transcriptional activation of several genes implicated in stroke. The main objective of this study was to investigate whether NCX1 gene might be a novel target of HIF-1 in the brain.

Methods and Results—

Here we report that: (1) in neuronal cells, NCX1 increased expression after oxygen and glucose deprivation or cobalt-induced HIF-1 activation was prevented by silencing HIF-1; (2) the brain NCX1 promoter cloned upstream of the firefly-luciferase gene contained 2 regions of HIF-1 target genes called hypoxia-responsive elements that are sensitive to oxygen and glucose deprivation or cobalt chloride; (3) HIF-1 specifically bound hypoxia-responsive elements on brain NCX1, as demonstrated by band-shift and chromatin immunoprecipitation assays; (4) HIF-1α silencing prevented NCX1 upregulation and neuroprotection induced by ischemic preconditioning; and (5) NCX1 silencing partially reverted the preconditioning-induced neuroprotection in rats.

Conclusions—

NCX1 gene is a novel HIF-1 target, and HIF-1 exerts its prosurvival role through NCX1 upregulation during brain preconditioning.
A Mixed Exponential Distribution Model for Retrieving Ground Flash Fraction from Satellite Lightning Imager Data
Authors: Koshak W. J.
Published: February 2011

A Bayesian inversion method is introduced for retrieving the fraction of ground flashes in a set of flashes observed from a (low earth orbiting or geostationary) satellite lightning imager. The method employs a constrained mixed exponential distribution model to describe the lightning optical measurements. Because the method also retrieves certain population statistics of ground and cloud flash optical properties, the method can be applied to an arbitrary geographical region, including those regions where the lightning optical statistics either are not known or are difficult to obtain. The approach is tested by performing simulated retrievals, and retrieval error statistics are provided. A first-attempt retrieval of the global geographical distribution of ground flash fraction is obtained using the 5-yr Optical Transient Detector (OTD) dataset; the spatially averaged ground flash fraction over the global-scale domain studied was 0.151 with a standard deviation of 0.081. The ability to retrieve ground flash fraction has important benefits to the atmospheric chemistry community. For example, using the method to partition the existing OTD/Lightning Imaging Sensor (LIS) satellite global lightning climatology into separate ground and cloud flash climatologies would improve estimates of regional and global lightning nitrogen oxides (NOx) production; this, in turn, would improve both regional air quality and global chemistry/climate model predictions.
The Influence of the Quasi-Biennial Oscillation on the Troposphere in Winter in a Hierarchy of Models. Part I: Simplified Dry GCMs
Authors: Garfinkel Chaim I. , Hartmann Dennis L.
Published: February 2011

A dry primitive equation model is used to explain how the quasi-biennial oscillation (QBO) of the tropical stratosphere can influence the troposphere, even in the absence of tropical convection anomalies and a variable stratospheric polar vortex. QBO momentum anomalies induce a meridional circulation to maintain thermal wind balance. This circulation includes zonal wind anomalies that extend from the equatorial stratosphere into the subtropical troposphere. In the presence of extratropical eddies, the zonal wind anomalies are intensified and extend downward to the surface. The tropospheric response differs qualitatively between integrations in which the subtropical jet is strong and integrations in which the subtropical jet is weak. While fluctuation–dissipation theory provides a guide to predicting the response in some cases, significant nonlinearity in others, particularly those designed to model the midwinter subtropical jet of the North Pacific, prevents its universal application. When the extratropical circulation is made zonally asymmetric, the response to the QBO is greatest in the exit region of the subtropical jet. The dry model is able to simulate much of the Northern Hemisphere wintertime tropospheric response to the QBO observed in reanalysis datasets and in long time integrations of the Whole Atmosphere Community Climate Model (WACCM).
Cell Therapy for Salivary Gland Regeneration
Authors: Lin C.-Y. , Chang F.-H. , Chen C.-Y. , Huang C.-Y. , Hu F.-C. , Huang W.-K. , Ju S.-S. , Chen M.-H.
Published: February 2011

There are still no effective therapies for hyposalivation caused by irradiation. In our previous study, bone marrow stem cells can be transdifferentiated into acinar-like cells in vitro. Therefore, we hypothesized that transplantation with bone marrow stem cells or acinar-like cells may help functional regeneration of salivary glands. Bone marrow stem cells were labeled with nanoparticles and directly co-cultured with acinar cells to obtain labeled acinar-like cells. In total, 140 severely combined immune-deficiency mice were divided into 4 groups for cell therapy experiments: (1) normal mice, (2) mice receiving irradiation around their head-and-neck areas; (3) mice receiving irradiation and intra-gland transplantation with labeled stem cells; and (4) mice receiving irradiation and intra-gland transplantation with labeled acinar-like cells. Our results showed that salivary glands damaged due to irradiation can be rescued by cell therapy with either bone marrow stem cells or acinar-like cells for recovery of saliva production, body weight, and gland weight. Transdifferentiation of bone marrow stem cells into acinar-like cells in vivo was also noted. This study demonstrated that cell therapy with bone marrow stem cells or acinar-like cells can help functional regeneration of salivary glands, and that acinar-like cells showed better therapeutic potentials than those of bone marrow stem cells.
Genetic Diversity of Plaque Mutans Streptococci with rep-PCR
Authors: Cheon K. , Moser S.A. , Whiddon J. , Osgood R.C. , Momeni S. , Ruby J.D. , Cutter G.R. , Allison D.B. , Childers N.K.
Published: February 2011

Mutans streptococci (MS) are key organisms associated with the etiology of dental caries. Using probabilities that were tested by oversampling, we designed this study to determine the minimal number of MS isolates from an individual required to evaluate diversity of genotypes. MS isolates were genotyped by repetitive extragenic palindromic-polymerase chain-reaction (rep-PCR). Analysis of 20 isolates from individuals resulted in a mean of 1.6 and 2.4 genotypes in children (N = 12) and adults (N = 10), respectively. In a follow-up study, reducing the number of isolates to 7-10 resulted in a theoretical probability of up to 78% for detecting up to 4 genotypes. A mean of 1.5 genotypes was found in 35 children and 10 adults. These findings provide evidence for the design of studies of MS genotyping that can serve as a model for the analysis of genotypes within individuals.
rEnolase Maternal Immunization Confers Caries Protection on Offspring
Authors: Dinis M. , Trigo G. , Chaves N. , Fonseca A.J.M.M. , Ribeiro A. , Tavares D. , Cabrita A.M.S. , Ferreira P.
Published: February 2011

Therapeutic vaccination with Streptococcus sobrinus recombinant enolase (rEnolase) protects rats from dental caries. Here, we investigated the effect that maternal rEnolase vaccination before pregnancy had on the offspring’s immune response to S. sobrinus oral infection and dental caries progression. Female Wistar rats were immunized by intranasal and subcutaneous routes with rEnolase adsorbed onto aluminum hydroxide as adjuvant or similarly treated with the adjuvant alone (sham-immunized). Ten days after the last administration, the immunized females were paired with a male rat. The oral immune responses to S. sobrinus infection and dental caries in the offspring were evaluated. The results showed that pups born from rEnolase-immunized mothers had higher levels of rEnolase-specific salivary IgA and IgG antibodies (indicating a placental antibody transfer) and lower sulcal and proximal enamel caries scores than rats born from sham-immunized mothers. In conclusion, rEnolase maternal immunization before pregnancy provides offspring with protection against S. sobrinus-induced dental caries.
Finding Prosperity as a Lottery Winner: Presentations of Self after Acquisition of Sudden Wealth
Authors: Hedenus Anna
Published: February 2011

The narrative about the squandering lottery winner ending up alone and in debt has been shown to affect other lottery winners’ thinking about how to manage their money. Based on a narrative analysis of interviews with 14 Swedish lottery winners, this article considers the ways in which lottery winners present themselves and their post-winning life in counter-position to this story about the squandering winner. By spending their prize money responsibly in order to project moderate, non-luxury consumption, the winners are ‘rewarded’ by feelings of fortune, security, and happiness. Finally, the article discusses how this narrative about ‘the prospering winner’ might be understood in relation to norms about consumption and identity.
Drug Burden Index and Beers Criteria: Impact on Functional Outcomes in Older People Living in Self‐Care Retirement Villages
Authors: Gnjidic Danijela , Couteur David G. Le , Abernethy Darrell R. , Hilmer Sarah N.
Published: February 2011

The objectives of this study were to determine whether Drug Burden Index (DBI), a measure of individuals' exposure to anticholinergic and sedative drugs, and Beers criteria, an explicit measure of potentially inappropriate drug use, are associated with function in older adults living in low‐level care facilities; and to compare DBI with Beers criteria as a predictor of function in older people. The study population consisted of 115 residents living in low‐level care facilities in Sydney, Australia. Data on demographics, drugs, and comorbidities were collected. Outcomes included objective measures of physical function Short Performance Physical Battery (SPPB) and grip strength. In total, 50 (44%) participants were exposed to DBI drugs, 51 (44%) participants received at least 1 Beers criteria drug, and 30 (26%) were exposed to both. After adjusting for confounders, for every unit increase in DBI, the SPPB score decreased by 1.3 (P = .04). DBI was not associated with weaker grip strength. Beers criteria were not associated with any of the outcomes. In older adults living in self‐care retirement villages, DBI was associated with impairments in physical functioning. Exposure to Beers criteria drugs was common; however, Beers criteria did not predict functional outcomes in this population of older adults.
Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology
Authors: Barnes Thomas RE ,   the Schizophrenia Consensus Group of the British Association for Psychopharmacology
Published: February 2011

These guidelines from the British Association for Psychopharmacology address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting, involving experts in schizophrenia and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from the participants and interested parties, and cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. The practice recommendations presented are based on the available evidence to date, and seek to clarify which interventions are of proven benefit. It is hoped that the recommendations will help to inform clinical decision making for practitioners, and perhaps also serve as a source of information for patients and carers. They are accompanied by a more detailed qualitative review of the available evidence. The strength of supporting evidence for each recommendation is rated.
Expert Psychological Testimony
Authors: Cutler Brian L. , Kovera Margaret Bull
Published: February 2011

Psychologists serve as expert witnesses in criminal and civil cases and testify about a wide range of clinical, cognitive, developmental, industrial-organizational, biological, and social psychological topics. We review the topics about which psychologists offer testimony, the rules governing the admissibility of expert testimony, and contemporary research on expert testimony. With respect to the latter, we review research concerning the need for, appropriateness of, and effect of expert testimony. We discuss research pertaining to admissibility issues, including the effect of changes in admissibility criteria on admissibility decisions and judge and juror sensitivity to the quality of scientific psychological research. Because judges and jurors lack sensitivity to variations in expert evidence quality and common safeguards do not appear to increase sensitivity to research flaws, additional research is needed to identify methods of assisting fact finders who must evaluate expert testimony.
Forensic Interviewing Aids: Do Props Help Children Answer Questions About Touching?
Authors: Poole Debra Ann , Bruck Maggie , Pipe Margaret-Ellen
Published: February 2011

The belief that props help children report abuse has fostered the widespread use of anatomical dolls and body diagrams in forensic interviews. Yet studies involving alleged abuse victims, children who have experienced medical examinations, and children who have participated in staged events have failed to find consistent evidence that props improve young children’s ability to report key information related to bodily contact. Because props elevate the risk of erroneous touch reports, interviewers need to reconsider the belief that props are developmentally appropriate in forensic interviews, and researchers need to explore new approaches for eliciting disclosures of inappropriate touching.
Eyewitness Identification
Authors: Brewer Neil , Wells Gary L.
Published: February 2011

Eyewitness identifications play an important role in many police investigations and courtroom decisions. Identification decision accuracy is shaped not only by the quality of a witness's memory but also by social-influence variables. Some variables can be categorized as general impairments, whereas others produce biases against a specific suspect. We review some of the key variables in each category and consider postidentification indicators of identification accuracy. Finally, we highlight what we think are some of the major directions for future research. These include addressing some of the significant limitations of past research, examining variables that are not directly related to memory or social influence, and developing some radical new directions for identification tests.
Current Issues and Advances in Misinformation Research
Authors: Frenda Steven J. , Nichols Rebecca M. , Loftus Elizabeth F.
Published: February 2011

Eyewitnesses are often called upon to report information about what they have seen. A wealth of research from the past century has demonstrated, however, that eyewitness memory is malleable and vulnerable to distorting influences, including the effects of misinformation. In this article, we review recent developments in research related to the misinformation effect, including individual differences in susceptibility, neuroimaging approaches, and protective interview procedures that may better elicit accurate event details. We conclude with a section on related false memory research.
Future Directions in the Restoration of Competency to Stand Trial
Authors: Zapf Patricia A. , Roesch Ronald
Published: February 2011

While a vast amount of research has focused on the evaluation of competency to stand trial, there is a relative dearth of research on competency restoration. Only recently have systematic research efforts begun to focus on the issue of restoration. Two primary areas of inquiry regarding restoration have emerged: the prediction of restorability (and the examination of variables related to successful and unsuccessful restoration attempts) and the investigation of various treatment programs for competency restoration. This article will briefly summarize the recent research with respect to these two areas and will highlight deficiencies in our current knowledge with the hope of providing an impetus for future research on competency restoration and related issues.
Suspect Interviews and False Confessions
Authors: Gudjonsson Gisli H. , Pearse John
Published: February 2011

In this article, we review two influential methods of police interviewing practice and their associations with false confessions. These are the Reid technique, which is commonly used by police forces in the United States, and the PEACE model, which is routinely used in the United Kingdom. Several authors have recently expressed concerns about the guilt-presumptive and confrontational aspects of the Reid technique and its association with false confessions and recommend that it be replaced by the PEACE model. Anecdotal case studies and DNA exonerations have shown that false confessions are more common than previously thought and are typically associated with two main causes: manipulative/coercive interrogation techniques and suspects' vulnerabilities in interviews. The main challenge for the future is to develop interview techniques that maximize the number of noncoerced true confessions while minimizing the rate of false confessions. In the meantime, the electronic recording of police interviews, which provides invaluable transparency and accountability, is the single best protection against police-induced false confessions.
Interviewing Cooperative Witnesses
Authors: Fisher Ronald P. , Milne Rebecca , Bull Ray
Published: February 2011

Police interviews of witnesses are critical for solving crimes, yet police are poorly trained and often make mistakes when interviewing witnesses who are cooperative. To overcome this limitation, researchers have developed the cognitive interview (CI), which incorporates principles of cognitive and social psychology in a face-to-face interview format. Laboratory and field research show that the CI elicits considerably more information than conventional interviews in criminal and noncriminal investigations. We explore the real-world applications of the CI.
Current Directions in Violence Risk Assessment
Authors: Skeem Jennifer L. , Monahan John
Published: February 2011

Over recent years, a variety of instruments that improve clinicians' ability to forecast the likelihood that an individual will behave violently have been published. Increasingly, these instruments are being applied in response to laws that require specialized risk assessments. In this article, we present a framework that goes beyond the “clinical” and “actuarial” dichotomy to describe a continuum of structured approaches to risk assessment. Despite differences among validated instruments, there is little evidence that one predicts violence better than another. We believe that these group-based instruments are useful for assessing an individual’s risk and that an instrument should be chosen based on an evaluation’s purpose (i.e., risk assessment vs. risk reduction). The time is ripe to shift attention from predicting violence to understanding its causes and preventing its (re)occurrence.