bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Resistance to Weight Gain, Lack of Stored Triglycerides in Adipose Tissue, Hypoglycaemia, and Increased Energy Expenditure: A Novel Disorder of Energy Homeostasis
Authors: Padidela Raja , Bennett Kate , Nessa Azizun , Wells Jonathan , Aufieri Roberto , James Chela , Smith Virpi V. , Brain Caroline , Eaton Simon , Hussain Khalid
Published: May 2012

Background: Growth during childhood is a consequence of the equilibrium of energy balance. Obesity results from a shift of the equilibrium towards increased energy intake over expenditure. A clinical description of extreme leanness and failure to thrive secondary to a shift of the equilibrium towards increased energy expenditure over energy intake has not been previously described in the medical literature. Subjects and Methods: We report the case of a female child born premature with a birth weight of 1.1 kg who presented with extreme failure to thrive, persistent hypoglycaemia, paucity of fat in the adipose tissue with increased brown fat and increased resting energy expenditure. Results: Complete cessation of weight and height was noted between 3 months to 3.5 years of age. Hypoglycaemia was secondary to depleted energy stores and increased insulin sensitivity. Increased resting energy expenditure was demonstrated on indirect calorimetric assessment. Biopsy of adipose tissue demonstrated paucity of stored fat with increase in brown fat. No gain in weight and height was demonstrated despite high calorie intake of enteral and parenteral feeds. Conclusion: We describe a unique case of extreme failure to thrive with increased energy expenditure and severe hypoglycaemia. Unravelling the molecular basis of this novel disorder has the potential to provide insights into the prevention of obesity.
Patient Satisfaction after Pulmonary Resection for Lung Cancer: A Multicenter Comparative Analysis
Authors: Pompili Cecilia , Brunelli Alessandro , Rocco Gaetano , Salvi Rosario , Xiumé Francesco , La Rocca Antonello , Sabbatini Armando , Martucci Nicola
Published: May 2012

Background: Patient satisfaction reflects the perception of the customer about the level of quality of care received during the episode of hospitalization. Objective: To compare the levels of satisfaction of patients submitted to lung resection in two different thoracic surgical units. Methods: Prospective analysis of 280 consecutive patients submitted to pulmonary resection for neoplastic disease in two centers (center A: 139 patients; center B: 141 patients; 2009–2010). Patients’ satisfaction was assessed at discharge through the EORTC-InPatSat32 module, a 32-item, multi-scale self-administered anonymous questionnaire. Each scale (ranging from 0 to 100 in score) was compared between the two units. Multivariable regression and bootstrap were used to verify factors associated with the patients’ general satisfaction (dependent variable). Results: Patients from unit B reported a higher general satisfaction (91.5 vs. 88.3, p = 0.04), mainly due to a significantly higher satisfaction in the doctor-related scales (doctors’ technical skill: p = 0.001; doctors’ interpersonal skill: p = 0.008; doctors’ availability: p = 0.005, and doctors information provision: p = 0.0006). Multivariable regression analysis and bootstrap confirmed that level of care in unit B (p = 0.006, bootstrap frequency 60%) along with lower level of education of the patient population (p = 0.02, bootstrap frequency 62%) were independent factors associated with a higher general patient satisfaction. Conclusion: We were able to show a different level of patient satisfaction in patients operated on in two different thoracic surgery units. A reduced level of patient satisfaction may trigger changes in the management policy of individual units in order to meet patients’ expectations and improve organizational efficiency.
Myeloschisis Repair in a Premature Neonate with a Birth Weight of 599 g
Authors: Oi Shizuo , Miwa Tomoru , Kobayashi Masahisa , Ida Hiroyuki
Published: May 2012

This report describes the case of a neonate with myeloschisis weighing 599 g that underwent an operation for spinal cord reconstruction resulting in substantial neuronal functional recovery. At 28 weeks of gestation, oligohydramnios was detected and the female fetus was diagnosed with intrauterine growth retardation. At birth by emergency caesarean section, she showed lumbosacral myeloschisis and complete paralysis of the lower extremities. Surgical repair and spinal cord reconstruction was performed 2 days after birth by closing the neural placode. Total blood loss was only 2 ml. Within 3 months of the operation, lower extremity neurologic function gradually improved down to the level of the knee joint. To our knowledge, this case is the lowest recorded body weight for a neonate with myeloschisis repair at birth, and this further suggests the possibility of improvement of lower extremity neurologic function after birth and surgical reconstruction.
Alpha-Tocopherol and BAY 11-7082 Reduce Vascular Cell Adhesion Molecule in Human Aortic Endothelial Cells
Authors: Catalán Úrsula , Fernández-Castillejo Sara , Pons Laia , Heras Mercedes , Aragonés Gemma , Anglès Neus , Morelló Jose-Ramon , Solà Rosa
Published: May 2012

Background: In endothelial dysfunction, vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression (collectively termed cell adhesion molecules; CAMs) increase at sites of atherosclerosis and are stimulated by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α). Methods: We evaluated the effect of alpha-tocopherol (AT; 10–150 µM) and BAY 11-7082 (BAY; 0.1 or 1 µM) on CAMs mRNA expression as well as their protein in soluble release form (sCAMs) in human aortic endothelial cells (HAECs) activated by TNF-α (1 or 10 ng/ml). Also, we determined the extent of lymphocyte adhesion to activated HAECs. Results: BAY reduced VCAM-1, E-selectin and ICAM-1 mRNA expression by 30, 30 and 10%, respectively. Furthermore, protein reduction of sVCAM-1 by 70%, sE-selectin by 51% and sICAM-1 by 25% compared to HAECs stimulated by TNF-α was observed (p < 0.05). AT (50, 75 and 150 µM) decreased VCAM-1 mRNA expression by 30% and sVCAM-1 protein by 33% compared to HAECs stimulated by TNF-α (p < 0.05). TNF-α-activated HAEC adhesion to human Jurkat T lymphocytes was higher compared to nonactivated HAECs (p < 0.05). BAY (2 and 5 µM) reduced this lymphocyte adhesion (p < 0.05). Conclusion: BAY reduces all the CAMs studied as well as cell adhesion, while AT selectively inhibits VCAM-1; both induce endothelial dysfunction improvement.
Chronic Reduction of Nitric Oxide Level in Adult Spontaneously Hypertensive Rats Induces Aortic Stiffness Similar to Old Spontaneously Hypertensive Rats
Authors: Isabelle Marc , Simonet Serge , Ragonnet Christophe , Sansilvestri-Morel Patricia , Clavreul Nicolas , Vayssettes-Courchay Christine , Verbeuren Tony J.
Published: May 2012

Introduction: Age and hypertension are two major determinants of arterial stiffness, as well as endothelial dysfunction. The present study was designed to test whether a chronic reduction of endogenous nitric oxide (NO) produces arterial stiffening close to that observed in old spontaneously hypertensive rats (SHR), and also to study the effect of an acute or a chronic decrease in blood pressure (BP) on aortic distensibility. Methods: BP, aortic stiffness, endothelial dysfunction and remodelling were measured in male adult (20-week-old) SHR, in adult SHR treated with a nonspecific NO synthase inhibitor L-NAME (SHR/L-NAME) for 2 weeks, in adult SHR/L-NAME cotreated with perindopril (1 mg/kg/day) and in old SHR (55-week-old). Age-matched WKY were used as a normotensive group. Results: Aortic endothelial dysfunction, remodelling and stiffening appeared in old SHR. Reduction of NO production in adult SHR caused similar alterations. Acute decreases in BP in SHR/L-NAME did not improve isobaric aortic distensibility but a chronic reduction of BP prevented endothelial dysfunction, aortic remodelling and aortic wall stiffening. Conclusion: NO reduction in adult SHR induces aortic alterations similar to those observed during aging, which supports the major role of NO in the development of arterial stiffening. These aortic alterations can be prevented by angiotensin-converting enzyme inhibitor treatment.
Societal Value of Stem Cell Therapy in Stroke – A Modeling Study
Authors: Svensson Johanna , Ghatnekar Ola , Lindgren Arne , Lindvall Olle , Norrving Bo , Persson Ulf , Kokaia Zaal
Published: May 2012

Background: Stroke is one of the major causes of disability in the adult population and represents a heavy social and economic burden. Currently available therapeutic tools to support the recovery of impaired brain functions are quite limited. Animal studies have demonstrated that neuronal replacement and partial reconstruction of neural circuitry or modulation of the recovery process is possible with cell transplantation in the damaged adult brain. Stem cell therapy (SCT) may promote functional recovery also in stroke patients, thereby improving quality of life and reducing costs. Our aim was to estimate the potential societal value of SCT in stroke patients. Methods: We created a decision-analytic model in Microsoft Excel 2010 to assess life-long costs and quality-adjusted life years (QALYs) of SCT versus standard care for stroke patients from a societal perspective. The model structure consisted of 7 health states in accordance with the modified Rankin Scale (mRS). We modeled for age (55, 65, and 75 years), functional status at discharge (mRS 2, 3, and 4), effectiveness of SCT (50 and 25% increase in the probability to improve 1 mRS grade), mode of stem cell administration, risk of recurrent stroke, complications of intervention, and use of immunosuppressive drugs. The difference between an assumed societal willingness to pay for a QALY gain in Sweden (110,400 USD) and the cost per QALY gain resulting from the model was interpreted as the value of SCT. Results: Increased survival (1.06 life years) and improved functional status gave rise to an estimated gain of 1.34 QALY in a cohort of patients aged 55 with mRS 2 at hospital discharge. Although the SCT intervention increased costs by 64,014 USD (excluding cost of stem cells), the costs of intervention were offset mainly by decreased productivity losses. In total, the intervention saved 19,055 USD, i.e., at a price of 19,055 USD for stem cells, the SCT would be cost neutral. The societal value of SCT was 166,500 USD. Conclusions: The application of the health-economic model to Sweden shows that in younger stroke patients with moderate disability, the societal value of SCT given a zero price of stem cells is 166,500 USD. Although the transplantation itself is more costly, SCT offers potential for cost offset and cost savings in a long-term perspective by reducing the disability after stroke. The therapy appeared cost effective under a wide range of assumptions. Hence, further research and development in stem cells suitable for stroke therapy could potentially produce great value to society.
Cosecretion of Glycosylated Prolactin and Non-Glycosylated Prolactin from Childhood to the End of Puberty
Authors: Fideleff H.L. , Sequera A.M. , Ruibal G.F. , Boquete H.R. , Suárez M.G. , Colombani M. , Azaretzky M. , Brunetto O. , Scaglia H.E.
Published: May 2012

Background: Glycosylated prolactin (G-PRL) is considered as the major post-translational modification of prolactin (PRL) showing reduced lactotropic and mitogenic activities compared to non-glycosylated prolactin (NG-PRL). Aim: To evaluate the evolution of G-PRL in normoprolactinemic children and adolescents and to analyze possible variations in glycosylated/total prolactin (T-PRL) ratios. Methods: T-PRL, G-PRL and NG-PRL were evaluated in 111 healthy female and male children and adolescents (4.1–18 years), classified as group 1 (Tanner I), group 2 (Tanner II–III) and group 3 (Tanner IV–V). G-PRL and NG-PRL were identified by chromatography on concanavalin-A-Sepharose. Results: G-PRL/T-PRL (median-range): females, group 1: 0.59 (0.17–0.77), group 2: 0.56 (0.31–0.78), group 3: 0.60 (0.38–0.79); males, group 1: 0.64 (0.39–0.80), group 2: 0.61 (0.24–0.79), group 3: 0.62 (0.35–0.90); the p value is not significant among the different groups in both genders. G-PRL/T-PRL ratios do not change when comparing low (first quartile) versus high (third quartile) T-PRL levels in the different groups. Conclusion: Our study would appear to support cosecretion of G-PRL and NG-PRL from childhood to the end of puberty. Such cosecretion would not be dependent on sex steroid levels. It is important to point out that puberty does not change the proportions of G-PRL and NG-PRL.
Short-Term Changes in Intraocular Pressure after Phacoemulsification in Glaucoma Patients
Authors: Fogagnolo Paolo , Centofanti Marco , Figus Michele , Frezzotti Paolo , Fea Antonio , Ligorio Paolo , Lembo Andrea , Digiuni Maurizio , Lorenzi Umberto , Rossetti Luca
Published: May 2012

Purpose: To evaluate short-term intraocular pressure (IOP) changes after phacoemulsification in glaucoma and normal patients and the effect of oral acetazolamide (Diamox) to control IOP in these patients. Methods: 120 patients undergoing cataract surgery were included in this prospective multicenter study involving 6 University Eye Clinics: 60 patients with well-controlled primary open-angle glaucoma (POAG) and 60 controls. Half of the study participants received oral acetazolamide, 250 mg, 1 and 6 h after surgery. The treated and untreated groups were matched for age and density of cataract. All patients underwent a standard phacoemulsification procedure and were checked for IOP with Goldmann tonometry in the morning before surgery and then at 3, 6, 21 and 24 h postoperatively by a masked evaluator. Results: The group with POAG showed a significant postsurgical increase in IOP (p < 0.001) at all time points. Six of thirty (20%) untreated POAG patients showed at least 1 IOP reading above 30 mm Hg whereas acetazolamide significantly reduced postoperative IOP at all time points (p < 0.01) and in no case was IOP >30 mm Hg. The control group had high IOP during the first 6 h (p < 0.01), but normal values thereafter. Conclusion: A significant short-term IOP increase may be found after phacoemulsification both in POAG and normal patients; this is not dangerous in normal subjects, but can be potentially dangerous in POAG patients. The use of systemic acetazolamide provided significant control of IOP and could be considered a ‘possible standard’ management of cataract surgery in POAG patients.
Professor Bernhard Pollack (1865–1928) of Friedrich Wilhelm University, Berlin: Neurohistologist, Ophthalmologist, Pianist
Authors: Triarhou Lazaros C.
Published: May 2012

This article highlights the life and work of Bernhard Pollack (1865–1928), a pioneer neurohistologist, ophthalmologist, and world-class pianist. In 1897, Pollack published the first standard manual on staining methods for the nervous system. Born into a Prussian-Jewish family, he received his piano education from the composer Moritz Moszkowski and his pathology education from Carl Weigert. Pollack worked in the Institutes of Wilhelm Waldeyer (anatomy), Emanuel Mendel (neuropsychiatry), the later Nobel laureate Robert Koch (infectious diseases), and the Eye Policlinic of Paul Silex (ophthalmology), becoming a Professor of Ophthalmology at Berlin’s Friedrich-Wilhelms-Universität in 1919. The study also chronicles the founding by Pollack of the Berlin Doctors’ Orchestra in 1911.
Virtualizing the Assessment: A Novel Pragmatic Paradigm to Evaluate Lower Extremity Joint Perception in Diabetes
Authors: Grewal Gurtej , Sayeed Rashad , Yeschek Steve , Menzies Robert Alexander , Talal Talal K. , Lavery Lawrence A. , Armstrong David G. , Najafi Bijan
Published: May 2012

Background: Individuals with diabetes have a higher risk of falls and fall-related injuries. People with diabetes often develop peripheral neuropathy (DPN) as well as nerve damage throughout the body. In particular, reduced lower extremity proprioception due to DPN may cause a misjudgment of foot position and thus increase the risk of fall. Objective: An innovative virtual obstacle-crossing paradigm using wearable sensors was developed in an attempt to assess lower extremity position perception damage due to DPN. Methods: 67 participants (age 55.4 ± 8.9, BMI 28.1 ± 5.8) including diabetics with and without DPN as well as aged-matched healthy controls were recruited. Severity of neuropathy was quantified using a vibratory perception threshold (VPT) test. The ability of perception of lower extremity was quantified by measuring obstacle-crossing success rate (OCSR), toe-obstacle clearance (TOC), and reaction time (TR) while crossing a series of virtual obstacles with heights at 10% and 20% of the subject’s leg length. Results: No significant difference was found between groups for age and BMI. The data revealed that DPN subjects had a significantly lower OCSR compared to diabetics with no neuropathy and controls at an obstacle size of 10% of leg length (p < 0.05). DPN subjects also demonstrated longer TR compared to other groups and for both obstacle sizes. In addition, TOC was reduced in neuropathy groups. Interestingly, a significant correlation between TR and VPT (r = 0.5, p < 10–3) was observed indicating a delay in reaction with increasing neuropathy severity. The delay becomes more pronounced by increasing the size of the obstacle. Using a regression model suggests that the change in TR between obstacle sizes of 10% and 20% of leg length is the most sensitive predictor for neuropathy severity with an odds ratio of 2.70 (p = 0.02). Conclusion: The findings demonstrate proof of a concept of virtual-reality application as a promising method for objective assessment of neuropathy severity, however a further study is warranted to establish a stronger relationship between the measured parameters and neuropathy.
IGF1, IGF1R and SHOX Mutation Analysis in Short Children Born Small for Gestational Age and Short Children with Normal Birth Size (Idiopathic Short Stature)
Authors: Caliebe Janina , Broekman Sander , Boogaard Merel , Bosch Cathy A.J. , Ruivenkamp Claudia A.L. , Oostdijk Wilma , Kant S.G. , Binder Gerhard , Ranke Michael B. , Wit Jan M. , Losekoot Monique
Published: May 2012

Background/Aims: Because the criteria for genetic screening of short children are unknown, we performed genetic analysis of 199 short children born small for gestational age (SGA) or with normal birth size (idiopathic short stature, ISS). Methods: After selection with a modified scoring system for SHOX and a novel score for IGF1 and IGF1R defects, direct sequencing and multiplex ligation-dependent probe amplification (MLPA) was performed for SHOX and IGF1R in selected patients, and confirmed by SNP array analysis. Results: In 6 children, gene variants were identified in SHOX, its adjacent pseudoautosomal region (PAR) and IGF1R: a SHOX mutation, terminal 15q deletion, a SHOX and IGF1R defect, a deletion of the Xp22.3 PAR region, and two patients with duplications in the Xp22.3 PAR region. In a seventh patient, steroid sulfatase deficiency was detected because a probe for STS was used as control; this syndrome has not been associated with short stature before. Conclusion: A selection process using clinical scores for SHOX, IGF1 and IGF1R defects followed by genetic testing with MLPA and direct sequencing led to the detection of a SHOX or IGF1R genetic variant in 6% of short children.
The Glucocorticoid-Induced Leucine Zipper (GILZ) Is Essential for Spermatogonial Survival and Spermatogenesis
Authors: Romero Y. , Vuandaba M. , Suarez P. , Grey C. , Calvel P. , Conne B. , Pearce D. , de Massy B. , Hummler E. , Nef S.
Published: May 2012

Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of the glucocorticoid-induced leucine zipper protein (GILZ) encoded by the X-linked Tsc22d3 (Gilz) gene. We found that GILZ is specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes. While Gilz mutant female mice were fully fertile, constitutive or male germ cell-specific ablation of Gilz led to sterility due to a complete absence of post-meiotic germ cells and mature spermatozoa. Alterations were observed as early as postnatal day 5 during the first spermatogenic wave and included extensive apoptosis at the spermatogonial level and meiotic arrest in the mid-late zygotene stage. Overall, these data emphasize the essential role played by GILZ in mediating spermatogonial survival and spermatogenesis.
Relationship of Urine Dopamine with Phosphorus Homeostasis in Humans: The Heart and Soul Study
Authors: Bansal Nisha , Hsu Chi-yuan , Whooley Mary , Berg Anders H. , Ix Joachim H.
Published: May 2012

Background: Urine dopamine (DA) is produced in the proximal tubule and has been found to increase in response to dietary phosphorus intake, and to contribute to greater urinary phosphorus excretion in animal models. Whether urine DA is associated with phosphorus homeostasis in humans is uncertain. Methods: This was a cross-sectional study of 884 outpatients. DA was measured from 24-hour urine collections. We examined cross-sectional associations between urine DA and serum phosphorus, 24-hour urine phosphorus (as an indicator of dietary phosphorus absorption), fractional excretion of phosphorus (FEphos), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). Models were adjusted for age, sex, race, eGFR, albuminuria, hypertension, heart failure, tobacco use, body mass index, and diuretic use. Results: Mean age was 66.6 ± 11 years and mean eGFR was 71 ± 21.3 ml/min/1.73 m2. The mean urine DA was 193 ± 86 µg/day, mean serum phosphorus was 3.6 ± 0.6 mg/dl, mean daily urine phosphorus excretion was 671 ± 312 mg/day, and mean FEphos was 17 ± 9%. In adjusted models, each standard deviation higher DA was associated with 78.4 mg/day higher urine phosphorus and 0.9% lower FEphos (p < 0.05 for both). There was no statistically significant association between urine DA, serum phosphorus, FGF-23 or PTH in adjusted models. Conclusions: Higher dietary phosphorus absorption is associated with higher urine DA in humans, consistent with animal models. However, higher urine DA is not associated with FGF-23 or PTH, suggesting that known mechanisms of renal tubular handling of phosphorus may not be involved in the renal dopamine-phosphorus regulatory pathway in humans.
Outcomes of Children Following a First Hospitalization for Dilated Cardiomyopathy
Authors: Hollander Seth A. , Bernstein Daniel , Yeh Justin , Dao Duy , Sun Heather Y. , Rosenthal David
Published: May 2012

Background—

We hypothesized that children with dilated cardiomyopathy who require hospital admission are at increased risk for death or transplantation during their first hospitalization and in the first year that follows. We also assessed the value of routine data collected during that time to predict death or the need for transplantation prior to discharge and within 1 year of admission.

Methods and Results—

We conducted a retrospective review of 83 pediatric patients with dilated cardiomyopathy whose initial hospitalization fell between 2004 and 2009. The mean age at hospitalization was 7 years. The majority of patients demonstrated moderate or severe left ventricular dysfunction on initial echocardiogram (80%) and/or the need for intravenous inotropes within 7 days of hospital admission (69%). Five patients (6%) died, and 15 (18%) were transplanted in the initial hospitalization. At 1 year, 11/71 (15%) had died, and 27/71 (38%) were transplanted. The overall freedom from death, transplantation, or rehospitalization at 1 year following admission was 21%. Fractional shortening, left ventricular ejection fraction, serum cholesterol, uric acid, mixed venous saturation, and atrial filling pressures were all predictive of death or transplantation during the initial hospitalization. Left ventricular ejection fraction was predictive of death or transplantation at 1 year.

Conclusions—

The first hospitalization for dilated cardiomyopathy marks a period of high risk for clinical decline, end stage heart failure, and the need for cardiac transplantation. Echocardiographic function and hemodynamic and serum measurements may aid in predicting outcomes. Despite medical management, most patients will be rehospitalized and/or require cardiac transplantation within 1 year of admission.
Shock and Patient Preimplantation Type D Personality Are Associated With Poor Health Status in Patients With Implantable Cardioverter-Defibrillator
Authors: Pedersen Susanne S. , Tekle Fetene B. , Hoogwegt Madelein T. , Jordaens Luc , Theuns Dominic A.M.J.
Published: May 2012

Background—

Implantable cardioverter-defibrillator (ICD) shock is a critical event to patients associated with well-being after implantation, although other factors may play an equally important role. We compared the association of shock and the patient's preimplantation personality with health status, using a prospective study design.

Methods and Results—

Consecutively implanted ICD patients (n=383; 79% men) completed the Type D Scale at baseline and the Short-Form Health Survey 36 (SF-36) at baseline and 3, 6, and 12 months. Of all patients, 23.5% had a Type D personality and 13.8% received a shock during follow-up. Shocked patients reported significantly poorer health status, as did Type D patients. Health status patterns were poorest in patients with combined Type D personality and shock during follow-up. Shock during follow-up was a significant independent associate of poorer health status for 4 of 8 subscales of the SF-36 and the Mental Component Summary (all
P
<.05), with shocked patients scoring between 2.60 to 13.30 points lower than nonshocked patients. Type D personality was an independent associate of poor postimplantation health status for 6 of 8 of the SF-36 subscales and the Mental Component Summary, with Type D patients scoring between 2.12 to 8.02 points lower, adjusting for demographic and clinical characteristics.

Conclusions—

ICD shock and the patient's preimplantation personality disposition were equally important associates of health status 12 months after implantation. Identification of the patient's personality profile before ICD implantation may help identify subsets of patients who may need additional care, for example, with a psychosocial component.
Clopidogrel Use and Hospital Quality in Medically Managed Patients With Non–ST-Segment–Elevation Myocardial Infarction
Authors: Maddox Thomas M. , Ho P. Michael , Tsai Thomas T. , Wang Tracy Y. , Li Shuang , Peng S. Andrew , Wiviott Stephen D. , Masoudi Fredrick A. , Rumsfeld John S.
Published: May 2012

Background—

Clopidogrel prescription is a class I guideline recommendation for medically managed patients with non–ST-segment–elevation myocardial infarction (NSTEMI). However, clopidogrel has historically been underused in this population. We evaluated contemporary rates of its use and evaluated associated factors, with a particular focus on hospital quality of myocardial infarction (MI) care.

Methods and Results—

We examined clopidogrel prescription rates among 23 186 patients with NSTEMI discharged from 382 US hospitals between October 2009 and March 2011. Associations between clopidogrel prescription and various patient and hospital factors, including hospital quality of MI care, were determined with regression modeling. Of the sample, 54.9% of eligible patients with NSTEMI received clopidogrel prescription at hospital discharge. Variation in rate by hospital was large, ranging from 22% to 97%. A variety of patient and hospital factors were associated with clopidogrel prescription. Hospital quality of MI care demonstrated modest association with clopidogrel prescription (odds ratio, 0.68; 95% CI, 0.54–0.85) between the lowest and highest hospital quality quartile) and accounted for 5.7% of the variation in prescription rates.

Conclusions—

Clopidogrel prescription is significantly underused in the medically managed NSTEMI population and demonstrates wide variability by hospital. Although hospital quality of MI care is associated with its use, the findings suggest that it only has a modest effect. Therefore, efforts to improve clopidogrel use likely will require measures beyond improving the overall hospital quality of MI care.
Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell–Derived Cardiac Myocyte Monolayers
Authors: Lee Peter , Klos Matt , Bollensdorff Christian , Hou Luqia , Ewart Paul , Kamp Timothy J. , Zhang Jianhua , Bizy Alexandra , Guerrero-Serna Guadalupe , Kohl Peter , Jalife José , Herron Todd J.
Published: May 2012

Rationale:

Human induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) offer a powerful in vitro tool to investigate disease mechanisms and to perform patient-specific drug screening. To date, electrophysiological analysis of iPSC-CMs has been limited to single-cell recordings or low-resolution microelectrode array mapping of small cardiomyocyte aggregates. New methods of generating and optically mapping impulse propagation of large human iPSC-CM cardiac monolayers are needed.

Objective:

Our first aim was to develop an imaging platform with versatility for multiparameter electrophysiological mapping of cardiac preparations, including human iPSC-CM monolayers. Our second aim was to create large electrically coupled human iPSC-CM monolayers for simultaneous action potential and calcium wave propagation measurements.

Methods and Results:

A fluorescence imaging platform based on electronically controlled light-emitting diode illumination, a multiband emission filter, and single camera sensor was developed and utilized to monitor simultaneously action potential and intracellular calcium wave propagation in cardiac preparations. Multiple, large-diameter (≥1 cm), electrically coupled human cardiac monolayers were then generated that propagated action potentials and calcium waves at velocities similar to those commonly observed in rodent cardiac monolayers.

Conclusions:

The multiparametric imaging system presented here offers a scalable enabling technology to measure simultaneously action potential and intracellular calcium wave amplitude and dynamics of cardiac monolayers. The advent of large-scale production of human iPSC-CMs makes it possible to now generate sufficient numbers of uniform cardiac monolayers that can be utilized for the study of arrhythmia mechanisms and offers advantages over commonly used rodent models.
Targeted Deletion of MicroRNA-22 Promotes Stress-Induced Cardiac Dilation and Contractile Dysfunction
Authors: Gurha Priyatansh , Abreu-Goodger Cei , Wang Tiannan , Ramirez Maricela O. , Drumond Ana L. , van Dongen Stijn , Chen Yuqing , Bartonicek Nenad , Enright Anton J. , Lee Brendan , Kelm Robert J. , Reddy Anilkumar K. , Taffet George E. , Bradley Allan , Wehrens Xander H. , Entman Mark L. , Rodriguez Antony
Published: May 2012

Background—

Delineating the role of microRNAs (miRNAs) in the posttranscriptional gene regulation offers new insights into how the heart adapts to pathological stress. We developed a knockout of
miR-22
in mice and investigated its function in the heart.

Methods and Results—

Here, we show that
miR-22
–deficient mice are impaired in inotropic and lusitropic response to acute stress by dobutamine. Furthermore, the absence of
miR-22
sensitized mice to cardiac decompensation and left ventricular dilation after long-term stimulation by pressure overload. Calcium transient analysis revealed reduced sarcoplasmic reticulum Ca
2+
load in association with repressed sarcoplasmic reticulum Ca
2+
ATPase activity in mutant myocytes. Genetic ablation of
miR-22
also led to a decrease in cardiac expression levels for
Serca2a
and muscle-restricted genes encoding proteins in the vicinity of the cardiac Z disk/titin cytoskeleton. These phenotypes were attributed in part to inappropriate repression of serum response factor activity in stressed hearts. Global analysis revealed increased expression of the transcriptional/translational repressor purine-rich element binding protein B, a highly conserved
miR-22
target implicated in the negative control of muscle expression.

Conclusion—

These data indicate that
miR-22
functions as an integrator of Ca
2+
homeostasis and myofibrillar protein content during stress in the heart and shed light on the mechanisms that enhance propensity toward heart failure.
T2′ Imaging Within Perfusion-Restricted Tissue in High-Grade Occlusive Carotid Disease
Authors: Seiler Alexander , Jurcoane Alina , Magerkurth Jörg , Wagner Marlies , Hattingen Elke , Deichmann Ralf , Neumann-Haefelin Tobias , Singer Oliver C.
Published: May 2012

Background and Purpose—

Quantitative T2′ imaging presumably detects regional changes in the relation of oxygenated and deoxygenated hemoglobin. Regional differences in hemoglobin oxygenation might reflect areas with increased oxygen extraction for compensation of reduced perfusion pressure. We investigated quantitative T2′ imaging in patients with high-grade stenoses of brain-supplying arteries and hypothesized that T2′ values are lower in perfusion-restricted areas as compared with normally perfused tissue.

Methods—

Eighteen patients (15 men; mean age±SD, 54±12.8 years) with unilateral symptomatic or asymptomatic high-grade extracranial or intracranial internal carotid artery or proximal middle cerebral artery stenosis/occlusion were included. MR examination included perfusion-weighted imaging and quantitative, motion-corrected mapping of T2′ time. Time-to-peak and mean transit time maps were thresholded for different degrees of perfusion delays (eg, >0 seconds, ≥2 seconds) compared with the contralateral hemisphere. Mean T2′ values in areas of impaired perfusion were compared with T2′ values in corresponding contralateral or ipsilateral, normoperfused areas.

Results—

Mean size of perfusion-impaired areas in time-to-peak maps (time-to-peak delay >0 seconds) was 10.8 mL (±6.3) and 11.5 mL (±6.4) in mean transit time maps (mean transit time delay >0 seconds). T2′ values were significantly (
P
<0.01) lower in all perfusion-restricted compared with corresponding contralateral brain areas (ipsilateral versus contralateral). For time-to-peak delay >0 seconds, T2′ values were 115 ms (±9) versus 125 ms (±12). For mean transit time delay >0 seconds, T2′ values were 115 ms (±9) versus 128 ms (±10). Differences in T2′ values increased with the severity of the perfusion delay. Ipsilateral T2′ values outside the perfusion-disturbed areas did not differ from contralateral T2′ values.

Conclusions—

Motion-corrected T2′ imaging presumably detects areas with increased oxygen extraction within perfusion-restricted tissue in patients with high-grade occlusive vessel disease.
Intracranial Carotid Artery Atherosclerosis
Authors: Bos Daniel , van der Rijk Maggee J.M. , Geeraedts Tychon E.A. , Hofman Albert , Krestin Gabriel P. , Witteman Jacqueline C.M. , van der Lugt Aad , Ikram M. Arfan , Vernooij Meike W.
Published: May 2012

Background and Purpose—

Intracranial atherosclerosis is worldwide one of the leading causes of stroke. However, surprisingly little is known about its prevalence and risk factors in a community-dwelling population of white descent. In this study, we determined the prevalence and investigated risk factors of intracranial internal carotid artery calcification (ICAC) as a marker of intracranial atherosclerosis.

Methods—

To quantify the volume of ICAC, 2495 participants (mean age, 69.6 years) from the population-based Rotterdam Study underwent a nonenhanced computed tomography of the intracranial internal carotid arteries. We calculated the prevalence of ICAC. Next, we defined sex-specific quartiles and defined the upper quartile as severe ICAC. Risk factors of ICAC were investigated by linear and logistic multivariate modeling and were stratified by sex.

Results—

The overall prevalence of ICAC was 82.2%. The median volume of ICAC was 44 mm
3
and was larger in men. Age was independently associated with ICAC in both men and women. In men, excessive alcohol intake and smoking (OR, 1.74 [95% CI, 1.28–2.37] and 1.72 [95% CI, 1.10–2.70]) were strong risk factors of ICAC, whereas diabetes and hypertension were in women (OR, 2.02 [95% CI, 1.29–3.17] and 1.79 [95% CI, 1.20–2.68]). A low high-density-lipoprotein concentration was not associated with ICAC.

Conclusions—

ICAC is highly prevalent and occurs in over 80% of older, white persons. Conventional cardiovascular risk factors are associated with ICAC, but risk factor profiles differ between men and women.
White Matter Structure Changes as Adults Learn a Second Language
Authors: Schlegel Alexander A. , Rudelson Justin J. , Tse Peter U.
Published: May 2012

Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878–3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670–11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370–1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311–312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes occurred in frontal lobe tracts crossing the genu of the corpus callosum—a region not generally included in current neural models of language processing. These results indicate that plasticity of white matter plays an important role in adult language learning and additionally demonstrate the potential of longitudinal diffusion tensor imaging as a new tool to yield insights into cognitive processes.
The Phenomenology of Error Processing: The Dorsal ACC Response to Stop-signal Errors Tracks Reports of Negative Affect
Authors: Spunt Robert P. , Lieberman Matthew D. , Cohen Jessica R. , Eisenberger Naomi I.
Published: May 2012

A reliable observation in neuroimaging studies of cognitive control is the response of dorsal ACC (dACC) to events that demand increased cognitive control (e.g., response conflicts and performance errors). This observation is apparently at odds with a comparably reliable association of the dACC with the subjective experience of negative affective states such as pain, fear, and anxiety. Whereas “affective” associates of the dACC are based on studies that explicitly manipulate and/or measure the subjective experience of negative affect, the “cognitive” associates of dACC are based on studies using tasks designed to manipulate the demand for cognitive control, such as the Stroop, flanker, and stop-signal tasks. Critically, extant neuroimaging research has not systematically considered the extent to which these cognitive tasks induce negative affective experiences and, if so, to what extent negative affect can account for any variance in the dACC response during task performance. While undergoing fMRI, participants in this study performed a stop-signal task while regularly reporting their experience of performance on several dimensions. We observed that within-subject variability in the dACC response to stop-signal errors tracked changes in subjective frustration throughout task performance. This association remained when controlling for within-subject variability in subjective reports of cognitive engagement and several performance-related variables indexing task difficulty. These results fit with existing models characterizing the dACC as a hub for monitoring ongoing behavior and motivating adjustments when necessary and further emphasize that such a function may be linked to the subjective experience of negative affect.
Analysis of the Model Climate Sensitivity Spread Forced by Mean Sea Surface Temperature Biases
Authors: Dommenget Dietmar
Published: May 2012

Uncertainties in the numerical realization of the physical climate system in coarse-resolution climate models in the Coupled Model Intercomparison Project phase 3 (CMIP3) cause large spread in the global mean and regional response amplitude to a given anthropogenic forcing scenario, and they cause the climate models to have mean state climates different from the observed and different from each other. In a series of sensitivity simulations with an atmospheric general circulation model coupled to a Slab Ocean Model, the role of differences in the control mean sea surface temperature (SST) in simulating the global mean and regional response amplitude is explored. The model simulations are forced into the control mean state SST of 24 CMIP3 climate models, and 2xCO2 forcing experiments are started from the different control states. The differences in the SST mean state cause large differences in other climate variables, but they do not reproduce most of the large spread in the mean state climate over land and ice-covered regions found in the CMIP3 model simulations. The spread in the mean SST climatology leads to a spread in the global mean and regional response amplitude of about 10%, which is about half as much as the spread in the response of the CMIP3 climate models and is therefore of considerable size. Since the SST climatology biases are only a small part of the models’ mean state climate biases, it is likely that the climate model’s mean state climate biases are accounting for a large part of the model’s climate sensitivity spread.
Marine Boundary Layer Cloud Observations in the Azores
Authors: Rémillard Jasmine , Kollias Pavlos , Luke Edward , Wood Robert
Published: May 2012

The recent deployment of the Atmospheric Radiation Measurement Program (ARM) Mobile Facility at Graciosa Island, Azores, in the context of the Clouds, Aerosol and Precipitation in the Marine Boundary Layer (CAP-MBL) field campaign added the most extensive (19 months) and comprehensive dataset of marine boundary layer (MBL) clouds to date. Cloud occurrence is high (60%–80%), with a summertime minimum. Liquid precipitation is frequently present (30%–40%), mainly in the form of virga. Boundary layer clouds are the most frequently observed cloud type (40%–50%) with a maximum of occurrence during the summer and fall months under the presence of anticyclonic conditions. Cumulus clouds are the most frequently occurring MBL cloud type (20%) with cumulus under stratocumulus layers (10%–30%) and single-layer stratocumulus (0%–10%) following in frequency of occurrence. A stable transition layer in the subcloud layer is commonly observed (92% of the soundings). Cumulus cloud bases and stratocumulus cloud tops correlate very well with the top of the transition layer and the inversion base, respectively. Drizzling stratocumulus layers are thicker (350–400 m) and have higher liquid water path (75–150 g m−2) than their nondrizzling counterparts (100–250 m and 30–75 g m−2, respectively). The variance of the vertical air motion is maximum near the cloud base and is higher at night. The updraft mass flux is around 0.17 kg m−2 s−1 with 40%–60% explained by coherent updraft structures. Despite a high frequency of stratocumulus clouds in the Azores, the MBL is almost never well mixed and is often cumulus coupled.
A Test for Nonlinearity in Temperature Proxy Records
Authors: Støve Bård , Ljungqvist Fredrik Charpentier , Thejll Peter
Published: May 2012

Are temperature proxy records linear recorders of past temperature conditions? A statistical test for linearity is applied to 15 millennial-long proxy records with an annual resolution that was shown to significantly respond to Northern Hemisphere annual mean temperature selected from a collection of 30 proxies. The test, based on generalized additive modeling, shows that most of the proxies can indeed be shown to be linear functions of annual mean temperature, but two proxy records do not appear to have a linear relationship with temperature—this supports the assumption of linearity in most climate reconstruction work. The method tests for nonlinearity in a proxy relative to the group of proxies with which it is being used together. The robustness of the results is tested, and it was found that the results are stable to the choice of proxies. The linearity-testing method is quite general and could in the future be used for larger and more extensive sets of proxies.
The Vasa Vasorum and Associated Endothelial Nitric Oxide Synthase is More Important for Saphenous Vein Than Arterial Bypass Grafts
Authors: Dreifaldt Mats , Souza Domingos , Bodin Lennart , Shi-Wen Xu , Dooley Audrey , Muddle John , Loesch Andrzej , Dashwood Michael R.
Published: May 2012

No-touch (NT) saphenous vein (SV) grafts are superior to SVs harvested by the conventional technique (CT), with a patency comparable with the internal thoracic artery (ITA). Preservation of the vasa vasorum is implicated in the success of NT harvesting. We compared the vasa vasorum and endothelial nitric oxide synthase (eNOS) in NT SV with ITA and radial artery (RA) grafts. Skeletonized SV (SSV) was also analyzed. The NT SV had a higher number and larger vasa vasorum compared with ITA ( P = .0001) and RA ( P = .0004) that correlated with eNOS protein. Activity of eNOS in SSV grafts was significantly lower than NT SV grafts ( P = 004). Since a high proportion of the vasa vasorum are removed in SSV using the CT, we suggest that preservation of the vasa vasorum and eNOS-derived NO contributes to the high patency for NT as compared with SSV grafts.