bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Incidence of Bleeding‐Related Morbidity With Left Ventricular Assist Device Implantation in the Current Era
Authors: Krishan Kewal , Nair Ajith , Pinney Sean , Adams David , Anyanwu Anelechi C.
Published: May 2012

Left ventricular assist device (LVAD) implantation is historically associated with high incidence of bleeding‐related complications, very high reexploration rates, and frequently massive blood transfusion. Bleeding predisposes to mortality, sepsis, allosensitization, and right ventricular failure. We present results of an integrated approach to reduce bleeding complications. Analysis of 51 implantable LVADs implanted in 50 patients (mean age 52 years; male, 45; Intragency Registry for Mechanically Assisted Circulatory Support [INTERMACS] 1 or 2, 25) in our center in 2008 and 2009, including 15 reoperations. Preoperative coagulopathy was evident in 10 patients. Our strategy included: early LVAD implantation, preoperative nutritional support and hemodynamic optimization, preferential use of continuous flow LVADs, meticulous surgical hemostasis, liberal application of tricuspid annuloplasty, and blood product utilization based on point‐of‐care testing. Two patients (4%) were reexplored for bleeding. Median transfusion rates intraoperatively were: blood: 2 units (interquartile range [IQR] 0–4); plasma: 0 units (0–2.75); platelets: 0 pools (0–1.75), while postoperative transfusion rates for first 48 h were blood: 1 unit (0–2); plasma: 0 units (0–0.75); and platelets: 0 pools (0,1). Right ventricular assist device was utilized in six patients (11%). Median chest tube drainage in first 24 h was 1230 mL (IQR 862–1687). Median time on ventilator was 2 days, intensive care unit was 6 days, and hospitalization was 18 days. Hospital mortality was 20%. Using an integrated approach, we have experienced bleeding and transfusion rates similar to that seen in non‐LVAD complex cardiac operations. The potential to reduce bleeding reduces invasiveness of LVAD surgery, reduces allosensitization, may improve outcomes, and may increase mainstream acceptability of LVADs as definitive therapy for heart failure.
Fine structure of hippocampal mossy fiber synapses following rapid high‐pressure freezing
Authors: Zhao Shanting , Studer Daniel , Graber Werner , Nestel Sigrun , Frotscher Michael
Published: May 2012

Synapses of hippocampal neurons play important roles in learning and memory processes and are involved in aberrant hippocampal function in temporal lobe epilepsy. Major neuronal types in the hippocampus as well as their input and output synapses are well known, but it has remained an open question to what extent conventional electron microscopy (EM) has provided us with the real appearance of synaptic fine structure under in vivo conditions. There is reason to assume that conventional aldehyde fixation and dehydration lead to protein denaturation and tissue shrinkage, likely associated with the occurrence of artifacts. However, realistic fine‐structural data of synapses are required for our understanding of the transmission process and for its simulation. Here, we used high‐pressure freezing and cryosubstitution of hippocampal tissue that was not subjected to aldehyde fixation and dehydration in ethanol to monitor the fine structure of an identified synapse in the hippocampal CA3 region, that is, the synapse between granule cell axons, the mossy fibers, and the proximal dendrites of CA3 pyramidal neurons. Our results showed that high‐pressure freezing nicely preserved ultrastructural detail of this particular synapse and allowed us to study rapid structural changes associated with synaptic plasticity.
Mossy cell dendritic structure quantified and compared with other hippocampal neurons labeled in rats in vivo
Authors: Buckmaster Paul S.
Published: May 2012

Mossy cells are likely to contribute to normal hippocampal function and to the pathogenesis of neurologic disorders that involve the hippocampus, including epilepsy. Mossy cells are the least well‐characterized excitatory neurons in the hippocampus. Their somatic and dendritic morphology has been described qualitatively but not quantitatively. In the present study rat mossy cells were labeled intracellularly with biocytin in vivo. Somatic and dendritic structure was reconstructed three‐dimensionally. For comparison, granule cells, CA3 pyramidal cells, and CA1 pyramidal cells were labeled and analyzed using the same approach. Among the four types of hippocampal neurons, granule cells had the smallest somata, fewest primary dendrites and dendritic branches, and shortest total dendritic length. CA1 pyramidal cells had the most dendritic branches and longest total dendritic length. Mossy cells and CA3 pyramidal cells both had large somata and similar total dendritic lengths. However, mossy cell dendrites branched less than CA3 pyramidal cells, especially close to the soma. These findings suggest that mossy cells have dendritic features that are not identical to any other type of hippocampal neuron. Therefore, electrotonic properties that depend on soma‐dendritic structure are likely to be distinct in mossy cells compared to other neurons.
Optical imaging of visual cortex epileptic foci and propagation pathways
Authors: Haglund Michael M.
Published: May 2012

Precise localization of neocortical epileptic foci is a complex problem that usually requires ictal video–electroencephalography (EEG) recordings; high‐resolution magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) studies; and/or invasive monitoring with implanted grid array electrodes. The exact ictal‐onset site must be identified and removed to obtain the best opportunity for a seizure‐free outcome. The goal of this study was to determine if high‐resolution optical imaging could precisely identify neocortical epileptic foci and what role underlying neuroanatomic pathways played in the seizure propagation. Small acute epileptic foci (0.5 × 0.5 mm2) were created in the primate visual neocortex and single‐unit and surface EEG recordings were combined with optical imaging of voltage‐sensitive dye changes. Brief visual stimulation was used to evoke interictal bursts. In addition, different visually evoked epileptiform bursts were analyzed to determine the location of the epileptic focus. Spike‐triggered averaging of the optical images associated with the surface EEG interictal bursts were analyzed to determine the exact location of the epileptic focus. Specific orientations of brief visual stimulation evoked different intensity optical changes and precisely localized the epileptic focus. Optical imaging identified individual epileptic foci that were <3 mm apart. The development of individual epileptic focus was monitored with optical imaging, which demonstrated excitatory activity at the focus with a surrounding zone of inhibitory‐like activity. Propagation pathways outside of the inhibitory‐like surround demonstrated alternating bands of excitation and inhibition with a pattern orthogonal to the ocular dominance columns. This experimental study demonstrates that optical imaging can precisely localize an epileptic focus, and provides excellent spatial resolution of the changes that occur in and around the site of the epileptic focus.
Impact of seizures on developing dendrites: Implications for intellectual developmental disabilities
Authors: Casanova Jose R. , Nishimura Masataka , Owens James W. , Swann John W.
Published: May 2012

Childhood epilepsy can be severe and even catastrophic. In these instances, cognition can be impaired—leading to long‐term intellectual disabilities. One factor that could potentially cause cognitive deficits is the frequent seizures that characterize intractable epilepsy. However, it has been difficult to separate the effects seizures may have from those of preexisting neuropathologies and/or the effects of ongoing anticonvulsant therapies. Therefore, important questions are: Do early life seizures produce the learning deficits? And if they do, how do they do it? Results from recent animal models studies reviewed here show that recurrent seizures in infancy stop the growth of CA1 hippocampal dendrites. We speculate that the molecular mechanisms responsible for seizure‐induced growth suppression are homeostatic/neuroprotective, used by the developing nervous system in an attempt to limit neuronal and network excitability and prevent the continued generation of seizures. However, by preventing the normal growth of dendrites, there is a reduction in CA1 glutamatergic synapses that supports long‐lasting forms of synaptic plasticity thought to be the cellular basis of learning and memory. Therefore, dendrite growth suppression would reduce the neuroanatomic substrates for learning and memory, and in so doing could contribute in important ways to spatial learning and memory deficits that may be relevant to the cognitive deficits associated with childhood epilepsy.
Acute, but reversible, kainic acid–induced DNA damage in hippocampal CA1 pyramidal cells of p53‐deficient mice
Authors: Kinoshita Yoshito , Jürgen Wenzel H. , Kinoshita Chizuru , Schwartzkroin Philip A. , Morrison Richard S.
Published: May 2012

p53 plays an essential role in mediating apoptotic responses to cellular stress, especially DNA damage. In a kainic acid (KA)–induced seizure model in mice, hippocampal CA1 pyramidal cells undergo delayed neuronal death at day 3–4 following systemic KA administration. We previously demonstrated that CA1 neurons in p53−/− animals are protected from such apoptotic neuronal loss. However, extensive morphological damage associated with DNA strand breaks in CA1 neurons was found in a fraction of p53−/− animals at earlier time points (8 h to 2 days). No comparable acute damage was observed in wild‐type animals. Stereological counting confirmed that there was no significant loss of CA1 pyramidal cells in p53−/− animals at 7 days post‐KA injection. These results suggest that seizure‐induced DNA strand breaks are accumulated to a greater extent but do not lead to apoptosis in the absence of p53. In wild‐type animals, therefore, p53 appears to stimulate DNA repair and also mediate apoptosis in CA1 neurons in this excitotoxicity model. These results also reflect remarkable plasticity of neurons in recovery from injury.
Quantitative trait locus on distal chromosome 1 regulates the occurrence of spontaneous spike‐wave discharges in DBA/2 mice
Authors: Bessaïh Thomas , de Yebenes Esther Garcia , Kirkland Kyle , Higley Michael J. , Buono Russell J. , Ferraro Thomas N. , Contreras Diego
Published: May 2012

Purpose:  Most common forms of human epilepsy result from a complex combination of polygenetic and environmental factors. Quantitative trait locus (QTL) mapping is a first step toward the nonbiased discovery of epilepsy‐related candidate genes. QTL studies of susceptibility to induced seizures in mouse strains have consistently converged on a distal region of chromosome 1 as a major phenotypic determinant; however, its influence on spontaneous epilepsy remains unclear. In the present study we characterized the influence of allelic variations within this QTL, termed Szs1, on the occurrence of spontaneous spike‐wave discharges (SWDs) characteristic of absence seizures in DBA/2 (D2) mice.

Methods:  We analyzed SWD occurrence and patterns in freely behaving D2, C57BL/6 (B6) and the congenic strains D2.B6‐Szs1 and B6.D2‐Szs1.

Key Findings:  We showed that congenic manipulation of the Szs1 locus drastically reduced the number and the duration of SWDs in D2.B6‐Szs1 mice, which are homozygous for Szs1 from B6 strain on a D2 strain background. However, it failed to induce the full expression of SWDs in the reverse congenic animals B6.D2‐Szs1.

Significance:  Our results demonstrate that the occurrence of SWDs in D2 animals is under polygenic control and, therefore, the D2 and B6 strains might be a useful model to dissect the genetic determinants of polygenic SWDs characteristic of typical absence seizures. Furthermore, we point to the existence of epistatic interactions between at least one modifier gene within Szs1 and genes within unlinked QTLs in regulating the occurrence of spontaneous nonconvulsive forms of epilepsies.
Music and epilepsy: A critical review
Authors: Maguire Melissa Jane
Published: May 2012

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl’s gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native‐born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe.
BEFORE OCEAN ACIDIFICATION: CALCIFIER CHEMISTRY LESSONS1
Authors: Roleda Michael Y. , Boyd Philip W. , Hurd Catriona L.
Published: May 2012

Ocean Acidification (OA) has been an important research topic for a decade. Scientists have focused on how the predicted 56% decline in the seawater carbonate ion () concentration will dramatically impair the ability of calcifiers, ranging from coccolithophores to shellfish, to form calcium carbonate (CaCO3) structures, and the implications of the reduced carbonate saturation state (Ω) for increased dissolution of such structures. However, many published OA studies have overlooked a fundamental issue: most calcifying organisms do not rely on carbonate from seawater to calcify; they use either bicarbonate () or metabolically‐produced CO2. The ability of important primary (corals, coralline seaweeds, and coccolithophores) and secondary (mollusks) producers to modify their local carbonate chemistry suggests that the primary threat to them from OA is by dissolution rather than impaired calcification. Here, we draw on calcification research from an era before OA and combine it with recent studies that question the source of the carbonate ion, to provide new insights into how OA might affect calcifying organisms. Organismal modification of local carbonate chemistry may enable some calcifiers to successfully form calcareous structures despite OA.
Listening for Stories in All the Right Places: Narrative and Racial Formation Theory
Authors: Lawrence Charles
Published: May 2012

“I will tell you something about stories, … they are all we have … to fight off illness and death.”
Looking and Seeing, Meanwhile
Authors: Greenhouse Carol J.
Published: May 2012

Laura Gómez's meditation on race invites us to think again about where we have been and where we are headed—as a professional association, as an intellectual community, and as individual scholars. Reading these pages brings back the exhilaration of the event: the sense of hearing said something that needed saying, that was possible to say without misunderstanding. The implicit “now” in that understanding reminds us how short the history of that possibility is. The personal and analytical generosity of President Gómez's address is integral to the force of its rendering visible a constitutive “we”—inclusive and yet still partially concealed to itself by virtue of the unintended consequences of standard disciplinary practices.
Ignorance in Bliss: Modeling Knowledge of Rights in Marriage and Cohabitation
Authors: Pleasence Pascoe , Balmer Nigel J.
Published: May 2012

We live our lives against an extensive backdrop of legal rights and responsibilities, yet a growing number of studies indicates low levels of public legal literacy. In the context of opposite-sex cohabitation and marriage law, this study employs new survey data from the United Kingdom to explore, in detail, how many and which people are ignorant of the law, and what are the nature and origins of erroneous beliefs. We find that people's beliefs about both cohabitation and marriage law are frequently wrong. They are also strikingly similar, and reflect the divergence of social attitudes from the law. Our findings are consistent with the notion that legal literacy links to salience of issue. They are also consistent with recent public legal education initiatives that affected public understanding of cohabitation law, but we argue that social attitudes and the intransigence of erroneous beliefs generally present significant challenges to such initiatives.
Corporate Governance and Capital Structure Dynamics
Authors: MORELLEC ERWAN , NIKOLOV BORIS , SCHÜRHOFF NORMAN
Published: May 2012

We develop a dynamic tradeoff model to examine the importance of manager–shareholder conflicts in capital structure choice. In the model, firms face taxation, refinancing costs, and liquidation costs. Managers own a fraction of the firms’ equity, capture part of the free cash flow to equity as private benefits, and have control over financing decisions. Using data on leverage choices and the model's predictions for different statistical moments of leverage, we find that agency costs of 1.5% of equity value on average are sufficient to resolve the low‐leverage puzzle and to explain the dynamics of leverage ratios. Our estimates also reveal that agency costs vary significantly across firms and correlate with commonly used proxies for corporate governance.
The Real Effects of Financial Markets: The Impact of Prices on Takeovers
Authors: EDMANS ALEX , GOLDSTEIN ITAY , JIANG WEI
Published: May 2012

Using mutual fund redemptions as an instrument for price changes, we identify a strong effect of market prices on takeover activity (the “trigger effect”). An interquartile decrease in valuation leads to a seven percentage point increase in acquisition likelihood, relative to a 6% unconditional takeover probability. Instrumentation addresses the fact that prices are endogenous and increase in anticipation of a takeover (the “anticipation effect”). Our results overturn prior literature that finds a weak relation between prices and takeovers without instrumentation. These findings imply that financial markets have real effects: They impose discipline on managers by triggering takeover threats.
Determinants of Cross‐Border Mergers and Acquisitions
Authors: EREL ISIL , LIAO ROSE C. , WEISBACH MICHAEL S.
Published: May 2012

The vast majority of cross‐border mergers involve private firms outside of the United States. We analyze a sample of 56,978 cross‐border mergers between 1990 and 2007. We find that geography, the quality of accounting disclosure, and bilateral trade increase the likelihood of mergers between two countries. Valuation appears to play a role in motivating mergers: firms in countries whose stock market has increased in value, whose currency has recently appreciated, and that have a relatively high market‐to‐book value tend to be purchasers, while firms from weaker‐performing economies tend to be targets.
Threshold Events and Identification: A Study of Cash Shortfalls
Authors: BAKKE TOR‐ERIK , WHITED TONI M.
Published: May 2012

Threshold events are discrete events triggered when an observable continuous variable passes a known threshold. We demonstrate how to use threshold events as identification strategies by revisiting the evidence in Rauh (2006, Investment and financing constraints: Evidence from the funding of corporate pension plans, Journal of Finance 61, 33–71) that mandatory pension contributions cause investment declines. Rauh's result stems from heavily underfunded firms that constitute a small fraction of the sample and that differ sharply from the rest of the sample. To alleviate this issue, we use observations near funding thresholds and find causal effects of mandatory contributions on receivables, R&D, and hiring, but not on investment. We also provide useful suggestions and diagnostics for analyzing threshold events.
Investment, Idiosyncratic Risk, and Ownership
Authors: PANOUSI VASIA , PAPANIKOLAOU DIMITRIS
Published: May 2012

High‐powered incentives may induce higher managerial effort, but they also expose managers to idiosyncratic risk. If managers are risk averse, they might underinvest when firm‐specific uncertainty increases, leading to suboptimal investment decisions from the perspective of well‐diversified shareholders. We empirically document that, when idiosyncratic risk rises, firm investment falls, and more so when managers own a larger fraction of the firm. This negative effect of managerial risk aversion on investment is mitigated if executives are compensated with options rather than with shares or if institutional investors form a large part of the shareholder base.
CEO Compensation and Board Structure Revisited
Authors: GUTHRIE KATHERINE , SOKOLOWSKY JAN , WAN KAM‐MING
Published: May 2012

Chhaochharia and Grinstein estimate that CEO pay decreases 17% more in firms that were not compliant with the recent NYSE/Nasdaq board independence requirement than in firms that were compliant. We document that 74% of this magnitude is attributable to two outliers of 865 sample firms. In addition, we find that the compensation committee independence requirement increases CEO total pay, particularly in the presence of effective shareholder monitoring. Our evidence casts doubt on the effectiveness of independent directors in constraining CEO pay as suggested by the managerial power hypothesis.
Easy Now, Desirable Later: The Moderating Role of Temporal Distance in Opportunity Evaluation and Exploitation
Authors: Tumasjan Andranik , Welpe Isabell , Spörrle Matthias
Published: May 2012

How does the temporal distance between the phases of evaluation and exploitation alter entrepreneurs’ opportunity evaluation? Building on construal level theory, we argue that the impact of an opportunity's desirability and feasibility on evaluation and exploitation intentions varies systematically with temporal distance. We experimentally demonstrate stronger influences of desirability on evaluation when the exploitation phase is temporally distant rather than near, whereas feasibility more strongly affects evaluation when exploitation is near rather than distant. Using construal level theory, we explain empirical inconsistencies in previous research and demonstrate the usefulness of integrating the concept of temporal distance in entrepreneurship research and education.
Impact of the Type of Corporate Spin–Off on Growth
Authors: Bruneel Johan , Van de Velde Els , Clarysse Bart
Published: May 2012

Although previous research shows that corporate spin–offs contribute to economic growth, few studies link growth to the type of corporate spin–off. We distinguish between three types of corporate spin–offs: incumbent–backed, opportunity, and necessity spin–offs. Using empirical data on 46 corporate spin–offs in Flanders, we find that opportunity spin–offs outperform the other two types. By identifying the type of corporate spin–offs, this study aims to add to our knowledge on the relationship between spin–off type and firm growth.
Low Proliferative Potential and Impaired Angiogenesis of Cultured Rat Kidney Endothelial Cells
Authors: BASILE DAVID P. , ZENG PINGYU , FRIEDRICH JESSICA L. , LEONARD ELLEN C. , YODER MERVIN C.
Published: May 2012

Please cite this paper as: Basile DP, Zeng P, Friedrich JL, Leonard EC, Yoder MC. Low proliferative potential and impaired angiogenesis of cultured rat kidney endothelial cells. Microcirculation 19: 598–609, 2012.

Objective:  CKD is histologically characterized by interstitial fibrosis, which may be driven by peritubular capillary dropout and hypoxia. Surprisingly, peritubular capillaries have little repair capacity. We sought to establish long‐term cultures of rat kidney endothelial cells to investigate their growth regulatory properties.

Methods:  AKEC or YKEC were isolated using CD31‐based isolation techniques and sustained in long‐term cultures.

Results:  Although YKEC grew slightly better than AKEC, both performed poorly compared with endothelial cells of the rat adult PMVEC, PAEC, or HUVEC cells. PMVEC and PAEC contained a large percentage of cells with high colony‐forming potential. In contrast, KECs were incapable of forming large colonies and most remained as single nondividing cells. KEC expressed high levels of mRNA for VEGF receptors, but were surprisingly insensitive to VEGF stimulation. KEC did not form branching structures on Matrigel when cultured alone, but in mixed cultures, KEC incorporated into branching structures with PMVEC.

Conclusions:  These data suggest that the intrinsic growth of rat kidney endothelial cells is limited by unknown mechanisms. The low growth rate may be related to the minimal intrinsic regenerative capacity of renal capillaries.
A Concept of Thrombolysis as a Corrosion–Erosion Process Verified by Optical Microscopy
Authors: BAJD FRANCI , SERŠA IGOR
Published: May 2012

Please cite this paper as: Bajd F, Serša I. A concept of thrombolysis as a corrosion–erosion process verified by optical microscopy. Microcirculation 19: 632–641, 2012.

Objective:  Outcome of the thrombolytic treatment is dependent on biochemical reactions of the fibrinolytic system as well as on hemodynamic conditions. However, understanding of the interaction between these two processes is still deficient.

Methods:  Model blood clot thrombolysis in an artificial perfusion system was studied by stroboscopic optical microscopy. The obtained images were analyzed by particle‐tracking software for clot size distributions of removed clot fragments, and for non‐lysed blood clot areas as function of time. Based on the experimental results, a probabilistic phenomenological model of blood clot dissolution was developed, in which mechanical forces of streaming plasma are in balance with binding forces of blood cells to the remaining clot.

Results:  The clot dissolution rate and maximum size of removed clot fragments were increased with greater flow rate. A 3.3‐fold flow rate increase resulted in a two‐fold clot dissolution rate increase, while sizes of the removed fragments were in the range of single blood cells, up to thousand‐cell clusters. Our phenomenological microscale model of clot dissolution suggests that thrombolysis is a corrosion–erosion‐like process.

Conclusions:  The findings of this study provide a possible explanation for the origin of clot fragment formation in the blood clot dissolution process.
Glycogen Accumulation and Degradation by the Trichomonads Trichomonas vaginalis and Trichomonas tenax
Authors: Nielsen Tyler J. , Pradhan Prajakta , Brittingham Andrew , Wilson Wayne A.
Published: May 2012

Several species of trichomonad have been shown to accumulate significant quantities of glycogen during growth, suggesting an important role for this compound in cell physiology. We provide the first analysis of the changes in glycogen content and glycogen phosphorylase activity that occur during in vitro growth of two trichomonad species: Trichomonas vaginalis and Trichomonas tenax. Both species accumulated glycogen following inoculation into fresh medium and utilized this compound during logarithmic growth. Glycogen phosphorylase activity also varied during growth in a species‐specific manner. The expression of phosphorylase genes in T. vaginalis remained constant during growth and thus transcriptional control did not explain the observed fluctuations in phosphorylase activity. After cloning, expression, and purification, two recombinant glycogen phosphorylases from T. vaginalis and one recombinant glycogen phosphorylase from T. tenax had robust activity and, in contrast to many other eukaryotic glycogen phosphorylases, did not appear to be regulated by reversible protein phosphorylation. Furthermore, allosteric regulation, if present, was not mediated by compounds known to impact the activity of better characterized phosphorylases.
Local activation of cardiac stem cells for post‐myocardial infarction cardiac repair
Authors: Wen Zhuzhi , Mai Zun , Zhang Haifeng , Chen Yangxin , Geng Dengfeng , Zhou Shuxian , Wang Jingfeng
Published: May 2012

The prognosis of patients with myocardial infarction (MI) and resultant chronic heart failure remains extremely poor despite continuous advancements in optimal medical therapy and interventional procedures. Animal experiments and clinical trials using adult stem cell therapy following MI have shown a global improvement of myocardial function. The emergence of stem cell transplantation approaches has recently represented promising alternatives to stimulate myocardial regeneration. Regarding their tissue‐specific properties, cardiac stem cells (CSCs) residing within the heart have advantages over other stem cell types to be the best cell source for cell transplantation. However, time‐consuming and costly procedures to expanse cells prior to cell transplantation and the reliability of cell culture and expansion may both be major obstacles in the clinical application of CSC‐based transplantation therapy after MI. The recognition that the adult heart possesses endogenous CSCs that can regenerate cardiomyocytes and vascular cells has raised the unique therapeutic strategy to reconstitute dead myocardium via activating these cells post‐MI. Several strategies, such as growth factors, mircoRNAs and drugs, may be implemented to potentiate endogenous CSCs to repair infarcted heart without cell transplantation. Most molecular and cellular mechanism involved in the process of CSC‐based endogenous regeneration after MI is far from understanding. This article reviews current knowledge opening up the possibilities of cardiac repair through CSCs activation in situ in the setting of MI.
Rumination, gender, and depressive symptoms associated with caregiving strain in bipolar disorder
Authors: Perlick D. A. , Gonzalez J. , Michael L. , Huth M. , Culver J. , Kaczynski R. , Calabrese J. , Miklowitz D. J.
Published: May 2012

Perlick DA, Gonzalez J, Michael L, Huth M, Culver J, Kaczynski R. Calabrese J. Miklowitz DJ. Rumination, gender, and depressive symptoms associated with caregiving strain in bipolar disorder.

Objective:  To evaluate the associations between indices of caregiving strain, ruminative style, depressive symptoms, and gender among family members of patients with bipolar disorder.

Method:  One hundred and fifty primary caregivers of patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) participated in a cross‐sectional study to evaluate the role of ruminative style in maintaining depressive symptoms associated with caregiving strain. Patient lifetime diagnosis and current episode status were evaluated by the Affective Disorder Evaluation and the Clinical Monitoring Form. Caregivers were evaluated within 30 days of the patient on measures of family strain, depressive symptoms, and ruminative style.

Results:  Men and women did not differ on depression, caregiver strain, or ruminative style scores. Scores suggest an overall mild level of depression and moderate caregiver strain for the sample. Greater caregiver strain was significantly associated (P < 0.05) with rumination and level of depressive symptoms, controlling for patient clinical status and demographic variables. Rumination reduced the apparent association between strain and depression by nearly half. Gender was not significantly associated with depression or rumination.

Conclusion:  Rumination helps explain depressive symptoms experienced by both male and female caregivers of patients with bipolar disorder. Interventions for caregivers targeted at decreasing rumination should be considered.
Illness perception and quality of life in patients with contact dermatitis
Authors: Benyamini Yael , Goner‐Shilo Daphna , Lazarov Aneta
Published: May 2012

Background. People's subjective perceptions of illness are important determinants of their ways of coping with health threats and the ensuing physical and mental outcomes, including quality of life (QoL), which has been consistently reported to be impaired by contact dermatitis.

Objectives. To investigate the relationships of subjective illness perceptions and dermatological QoL in atopic, contact and occupational dermatitis patients and a comparison group of patients with other dermatological diseases.

Patients and methods. Three hundred and three patients of four diagnostic groups filled in the Brief Illness Perception Questionnaire and the Skindex‐16 (+ occupational impact items) Dermatological QoL questionnaire before clinical examination and patch testing.

Results. Perceptions of serious consequences, greater symptom burden and more uncertainty and worry were associated with lower QoL (rs > 0.50). Overall, patients reported low personal control over their condition and low understanding of the disease (3.5 and 4.8, respectively, on a 0–10 scale). QoL was most impaired among occupational dermatitis patients (mean = 46) and least impaired among patients who were later diagnosed as suffering from conditions other than contact dermatitis (mean = 62).

Conclusions. Identifying critical components of illness perceptions in patients with atopic, contact and occupational dermatitis may enable the design of consultations and interventions to fit patients' perceptions, which could affect their QoL.
Animal models of wound repair: Are they cutting it?
Authors: Ansell David M. , Holden Kirsty A. , Hardman Matthew J.
Published: May 2012

Current understanding of the complex process of wound repair is based on decades of study. Integral to this understanding has been the use of in vitro and in vivo models to uncover the key molecular players. Now that major wound processes are more fully understood, therapeutic strategies can be developed to manipulate wound repair. Particularly important areas for future research include developing therapies to aid treatment of healing pathologies such as chronic wounds, and manipulating the normal healing processes to drive a more regenerative phenotype in adults. Here, we discuss the benefits and limitations of current animal‐based models and highlight the urgent need for improved predictive preclinical models for wound healing research. We conclude by suggesting directions where more robust models of chronic wound pathologies may arise, expediting the development of novel therapies.
The effect of Q Factor on gross mechanical efficiency and muscular activation in cycling
Authors: Disley B. X. , Li F.‐X.
Published: May 2012

Unexplored in scientific literature, Q Factor describes the horizontal width between bicycle pedals and determines where the foot is laterally positioned throughout the pedal stroke. The aim of the study was to determine whether changing Q Factor has a beneficial effect upon cycling efficiency and muscular activation. A total of 24 trained cyclists (11 men, 13 women; VO2max 57.5 ml·kg/min ± 6.1) pedaled at 60% of peak power output for 5 min at 90 rpm using Q Factors of 90, 120, 150, and 180 mm. Power output and gas were collected and muscular activity of the gastrocnemius medialis (GM), tibialis anterior (TA), vastus medialis (VM), and vastus lateralis (VL) measured using surface electromyography. There was a significant increase (P < 0.006) in gross mechanical efficiency (GME) for 90 and 120 mm (both 19.38%) compared with 150 and 180 mm (19.09% and 19.05%), representing an increase in external mechanical work performed of approximately 4–5 W (1.5–2.0%) at submaximal power outputs. There was no significant difference in the level of activity or timing of activation of the GM, TA, VM, and VL between Q Factors. Other muscles used in cycling, and possibly an improved application of force during the pedal stroke may play a role in the observed increase in GME with narrower Q Factors.
Factors associated with missing teeth in the Brazilian elderly institutionalised population
Authors: Piuvezam Grasiela , de Lima Kenio Costa
Published: May 2012

doi:10.1111/j.1741‐2358.2012.00655.x

Factors associated with missing teeth in the Brazilian elderly institutionalised population

Objective:  Identify factors associated with missing teeth in the elderly institutionalised population in Brazil.

Methodology:  Cross‐sectional study of elderly institutionalised Brazilians with 1192 subjects. A questionnaire was applied as well as an epidemiological survey of oral health conditions in accordance with WHO. Factorial analysis was carried out with variables related to missing teeth, as well as the Fisher’s exact test, chi‐squared test and multiple logistic regression.

Results:  Mean age was 76.3 (±9.8), 53.5% (638) of subjects were women and 717 (60.2) were dependent. Mean of Decayed Missing and Filled Teeth Index (DMFT index) was 29.4 (±4.9). The subjects that did not use upper and lower dentures were 61.5% (732) and 79.2% (944), respectively. Median number of missing teeth per person was 27.88 (±6.8) with a mean of 4 (±6.6) teeth present and 2.4 (±4.5) caries‐free teeth. Factors associated with missing teeth following multivariate analysis were: age, sex, self‐assessment of oral health, access to health services, type of institution and area of the country.

Conclusions:  High level of tooth loss and low level of rehabilitation demonstrate precarious oral health. It is therefore necessary to improve institutional access mechanisms to public health facilities for the institutionalised elderly.
Identification of a potential tumor differentiation factor receptor candidate in prostate cancer cells
Authors: Sokolowska Izabela , Woods Alisa G. , Gawinowicz Mary Ann , Roy Urmi , Darie Costel C.
Published: May 2012

Tumor differentiation factor (TDF) is a pituitary protein that is secreted into the bloodstream and has an endocrine function. TDF and TDF‐P1, a 20‐residue peptide selected from the ORF of TDF, induce differentiation in human breast and prostate cancer cells, but not in other cells. TDF has no known mechanism of action. In our recent study, we identified heat shock 70 kDa proteins (HSP70s) as TDF receptors (TDF‐Rs) in breast cancer cells. Therefore, we sought to investigate whether TDF‐R candidates from prostate cancer cells are the same as those identified in breast cancer cells. Here, we used TDF‐P1 to purify the potential TDF‐R candidates by affinity purification chromatography from DU145 and PC3 steroid‐resistant prostate cancer cells, LNCaP steroid‐responsive prostate cancer cells, and nonprostate NG108 neuroblastoma and BLK CL.4 fibroblast‐like cells. We identified the purified proteins by MS, and validated them by western blotting, immunofluorescence microscopy, immunoaffinity purification chromatography, and structural biology. We identified seven candidate proteins, of which three were from the HSP70 family. These three proteins were validated as potential TDF‐R candidates in LNCaP steroid‐responsive and in DU145 and PC3 steroid‐resistant prostate cancer cells, but not in NG108 neuroblastoma and BLK CL.4 fibroblast‐like cells. Our previous study and the current study suggest that GRP78, and perhaps HSP70s, are strong TDF‐R candidates, and further suggest that TDF interacts with its receptors exclusively in breast and prostate cells, inducing cell differentiation through a novel, steroid‐independent pathway.

Structured digital abstract

 TDF‐P1 physicallyinteracts with GRP78and HSP70 by pulldown (Viewinteraction)

 GRP78 binds to TDF‐P1 by antibaitcoimmunoprecipitation (Viewinteraction)

 TDF‐P1 physicallyinteracts with GRP78, HSP8, HSP70, HSP90‐beta, Sequestosome1 and valosin‐containing‐protein by pulldown (Viewinteraction)
Increased Risk of Sexual Dysfunction in Male Patients with Psoriasis: A Nationwide Population-Based Follow-Up Study
Authors: Chen Yi-Ju , Chen Chih-Chiang , Lin Ming-Wei , Chen Tzeng-Ji , Li Cheng-Yuan , Hwang Chian-Yaw , Chu Szu-Ying , Lee Ding-Dar , Chang Yun-Ting , Wang Wen-Jen , Liu Han-Nan
Published: May 2012

Introduction

An association between psoriasis and sexual dysfunction (SD) has been explored. However, the risk of SD after the diagnosis of psoriasis relative to the age-matched general population remains unknown.

Aim

To clarify the risk of developing SD in male patients with psoriasis.

Methods

From 2000 to 2001, we identified 12,300 male patients with newly diagnosed psoriasis and 61,500 matching controls from National Health Insurance Database in Taiwan.

Main Outcome Measures

The two cohorts were followed up until 2008, and we observed the occurrence of SD by registry of SD diagnosis in the database. Stratified Cox proportional hazard regressions were used to calculate the 7-year SD risk for these two groups.

Results

Of the 73,800 sampled patients, 1,812 patients (2.46%) experienced SD during the 7-year follow-up period, including 373 (3.03% of patients with psoriasis) in the study group and 1,439 (2.34% of patients without psoriasis) in the comparison group. The hazard ratio (HR) for SD for patients with psoriasis was 1.27 times (95% confidence interval [CI], 1.11–1.46; P = 0.001) as high as that for patients without psoriasis after adjusting for age, monthly income, number of health-care visits, systemic treatment, and other comorbidities. Stratified analysis showed that the risk of SD was higher in patients older than 60 years old (HR: 1.42, 95% CI: 1.12–1.81) and patients with psoriatic arthritis (HR: 1.78, 95% CI: 1.08–2.91). However, the risk of SD was not significantly elevated in patients receiving systemic treatment, including retinoid, methotrexate, and cyclosporine.

Conclusions

Male patients with psoriasis are at increased risk of developing SD. Physicians should pay attention to the impact of psoriasis on psychosocial and sexual health, especially in old-aged patients.
Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction
Authors: Ertemi Hani , Lau David H.W. , Mikhailidis Dimitri P. , Mumtaz Faiz H. , Thompson Cecil S.
Published: May 2012

Introduction

We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells.

Aim

To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO.

Methods

Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide).

Main Outcome Measure

Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function.

Results

Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan.

Conclusions

These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.
5-HT2A Receptor -1438 G/A Polymorphism and Serotonergic Antidepressant-Induced Sexual Dysfunction in Male Patients with Major Depressive Disorder: A Prospective Exploratory Study
Authors: Liang Chih-Sung , Ho Pei-Shen , Chiang Kuo-Tung , Su Hsuan-Chi
Published: May 2012

Introduction

To date, few studies have specifically investigated the genetic determinants of antidepressant-induced sexual dysfunction (SD).

Aim

The aim of this prospective study was to examine whether the 5-HT2A receptor -1438 G/A polymorphism has functional consequences on sexual well-being in young adult men presenting with their first episode of major depressive disorder (MDD) after serotonergic antidepressant treatment.

Methods

Between May 2010 and June 2011, a total of 56 drug-naïve patients presenting with their first episode of MDD were recruited from a psychiatric hospital and received either a selective serotonin reuptake inhibitor or venlafaxine monotherapy; the patients were then genotyped. Over the course of antidepressant treatment, the population was divided into a SD group (N = 16) and a non-SD group (N = 29) based on the Arizona Sexual Experience Scale (ASEX). Participants who did not achieve a significant improvement, as assessed by the Hamilton Depression Rating Scale (HAMD-17), were excluded from the final data analysis.

Main Outcome Measures

The primary outcome measures were the differences in the genotype distribution and allele frequencies between groups.

Results

In the SD group, the AA genotype was significantly overrepresented (P = 0.004), and the mean baseline HAMD-17 score, the mean baseline ASEX score, and the mean end-point ASEX score were significantly higher than those in the non-SD group (P = 0.026, P = 0.004, and P < 0.001, respectively). The mean end-point HAMD-17 score (P = 0.115) did not differ significantly between the two groups.

Conclusion

These results suggest that the AA genotype may be a genetic trait offering an opportunity to strengthen early detection of serotonergic antidepressant-induced SD in young adult male patients with MDD, whereas the G allele is protective against SD in this population.
PDEI-5 for Erectile Dysfunction: A Potential Role in Seizure Susceptibility
Authors: Matos Gabriela , Scorza Fulvio A. , Cavalheiro Esper A. , Tufik Sergio , Andersen Monica L.
Published: May 2012

Introduction

There is a high prevalence of erectile dysfunction (ED) in men with epilepsy; however, few studies have been conducted concerning the treatment of ED in this neurological group.

Aim

The main purpose of this review is to highlight the influence of phosphodiesterase type 5 inhibitor (PDEI-5) for ED on seizure susceptibility.

Methods

All available online articles with information pertaining to PDEI-5 and seizure susceptibility were included in this review.

Main Outcome Measures

The main outcome assessed demonstrated the intriguing role of PDEI-5 and its metabolites on seizure susceptibility.

Results

Case reports in men without epilepsy described seizure occurrence and electrophysiological changes following sildenafil, tadalafil, or vardenafil treatment. Consistent with these findings, preclinical studies suggested a proconvulsant effect of PDEI-5 on models of seizure induction.

Conclusions

Evidence suggests an influence of PDEI-5 on seizure susceptibility in humans. In addition, preclinical studies have demonstrated the role of nitric oxide metabolites in the facilitation of paroxysmal phenomenon. Although there are many causes of seizures, medical professionals should be aware of the possible influence of PDEI-5 on seizure susceptibility. Further investigation by physicians and scientists is required to improve our understanding of this important topic.