bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of state estimation explains improvements in sensorimotor performance across childhood
Authors: King Bradley R. , Oliveira Marcio A. , Contreras-Vidal Jose L. , Clark Jane E.
Published: March 2012

Previous developmental research examining sensorimotor control of the arm in school-age children has demonstrated age-related improvements in movement kinematics. However, the mechanisms that underlie these age-related improvements are still unclear. This study hypothesized that changes in sensorimotor performance across childhood can be attributed, in part, to the development of state estimation, defined as estimates computed by the central nervous system, which specify both current and future hand positions and velocities (i.e., hand “state”). Two behavioral experiments were conducted, in which 6- to 12-year-old children and young adults executed goal-directed arm movements. Results from Experiment 1 revealed that young children (i.e., ∼6–8 years) have less precise proprioceptive feedback for static (i.e., stationary) hand state estimation compared with older children (i.e., ∼10–12 years), resulting in increased variability of target-directed reaching movements. Experiment 2 demonstrated that young children rely on delayed and unreliable state estimates during the execution of goal-directed hand movements (i.e., dynamic state estimation), resulting in both increased movement errors and directional variability. Collectively, these results suggest that improvements in sensorimotor behavior across childhood can be attributed, at least partially, to the development of both static and dynamic state estimation.
Preferential Replication of Systemically Delivered Oncolytic Vaccinia Virus in Focally Irradiated Glioma Xenografts
Authors: Advani Sunil J. , Buckel Lisa , Chen Nanhai G. , Scanderbeg Daniel J. , Geissinger Ulrike , Zhang Qian , Yu Yong A. , Aguilar Richard J. , Mundt Arno J. , Szalay Aladar A.
Published: March 2012

Purpose: Radiotherapy is part of the standard of care in high-grade gliomas but its outcomes remain poor. Integrating oncolytic viruses with standard anticancer therapies is an area of active investigation. The aim of this study was to determine how tumor-targeted ionizing radiation (IR) could be combined with systemically delivered oncolytic vaccinia virus.

Experimental Design: U-87 glioma xenografts were grown subcutaneously or orthotopically. Oncolytic vaccinia viruses GLV-1h68 and LIVP 1.1.1 were injected systemically and IR was given focally to glioma xenografts. In a bilateral tumor model, glioma xenografts were grown in both flanks, oncolytic vaccinia was injected systemically and radiation was delivered specifically to the right flank tumor, whereas the left flank tumor was shielded. Viral replication and tumor regression, after systemic injection, was analyzed and compared in irradiated and nonirradiated glioma xenografts.

Results: Systemically administered oncolytic vaccinia virus replicated to higher titers in preirradiated U-87 xenografts than in nonirradiated glioma xenografts. This increased oncolytic viral replication correlated with increased tumor xenograft regression and mouse survival in subcutaneous and orthotopic U-87 glioma models compared with monotherapies. The ability of focal IR to mediate selective replication of oncolytic vaccinia was shown in a bilateral glioma model in which systemically administered oncolytic vaccinia replicated preferentially in the irradiated tumor compared with the nonirradiated tumor in the same mouse.

Conclusion: These findings show a potential clinical role of focal IR in sensitizing irradiated tumor sites for preferential vaccinia virus–mediated oncolysis. Clin Cancer Res; 18(9); 2579–90. ©2012 AACR.
Feasibility Study on Biweekly Paclitaxel Treatment as Maintenance Chemotherapy in Advanced Müllerian Carcinoma
Authors: Minagawa Yukihisa , Shimada Muneaki , Itamochi Hiroaki , Sato Shinya , Sato Seiya , Okada Makoto , Kitada Fuminori , Kigawa Junzo
Published: March 2012

Aim: To evaluate the feasibility of biweekly paclitaxel treatment as maintenance chemotherapy for patients with advanced müllerian carcinoma. Methods: Thirty patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who underwent primary optimal surgery and standard 6 cycles of carboplatin/taxane-based chemotherapy and exhibited a complete clinical response were entered in this study. Paclitaxel 80 mg/m2 was administered biweekly for 12 cycles. Patients were evaluated monthly for treatment-related toxicity. Results: Four patients, including 3 disease progressions and 1 bone marrow suppression, came off the protocol therapy. Twenty-six (86.7%) patients received complete treatment. Although the major toxicity was neutropenia, most of those patients (27/30, 90.0%) did not experience grade 3 or 4 neutropenia. Twenty-four (80.0%) patients showed persistent grade 1 neuropathy and the remaining 6 (20.0%) did not as a result of prior therapy. However, none experienced neuropathy progression during or after the protocol therapy. Most (17/22, 77.3%) of the completely treated patients experienced a regression of symptoms during and after therapy. Conclusion: Biweekly paclitaxel therapy is well tolerated by patients with advanced müllerian carcinoma and is therefore acceptable as a candidate for maintenance chemotherapy in these patients.
Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA2LEN – ARIA Position Paper
Authors:   In collaboration with the WHO Collaborating Center for Asthma and Rhinitis
Published: March 2012

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
Structured Coculture of Mesenchymal Stem Cells and Disc Cells Enhances Differentiation and Proliferation
Authors: Allon Aliza A. , Butcher Kristin , Schneider Richard A. , Lotz Jeffrey C.
Published: March 2012

Purpose: During in vivo stem cell differentiation, mature cells often induce the differentiation of nearby stem cells. Accordingly, prior studies indicate that a randomly mixed coculture can help transform mesenchymal stem cells (MSC) into nucleus pulposus cells (NPC). However, because in vivo signaling typically occurs heterotopically between adjacent cell layers, we hypothesized that a structurally organized coculture between MSC and NPC will result in greater cell differentiation and proliferation over single cell-type controls and cocultures with random organization. Methods: We developed a novel bilaminar cell pellet (BCP) system where a sphere of MSC is enclosed in a shell of NPC by successive centrifugation. Controls were made using single cell-type pellets and coculture pellets with random organization. The pellets were evaluated for DNA content, gene expression, and histology. Results: A bilaminar 3D organization enhanced cell proliferation and differentiation. BCP showed significantly more cell proliferation than pellets with one cell type and those with random organization. Enhanced differentiation of MSC within the BCP pellet relative to single cell-type pellets was demonstrated by quantitative RT-PCR, histology, and in situ hybridization. Conclusions: The BCP culture system increases MSC proliferation and differentiation as compared to single cell type or randomly mixed coculture controls.
Short- and Long-Term Major Adverse Cardiac Events in Patients Undergoing Percutaneous Coronary Intervention with Stenting for Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Marcolino Milena Soriano , Simsek Cihan , de Boer Sanneke P.M. , van Domburg Ron T. , van Geuns Robert-Jan , de Jaegere Peter , Akkerhuis K. Martijn , Daemen Joost , Serruys Patrick W. , Boersma Eric
Published: March 2012

Objectives: To determine the risk of short- and long-term mortality and major adverse cardiac events (MACE) in acute myocardial infarction (AMI) patients complicated by cardiogenic shock (CS) in the contemporary practice of primary percutaneous coronary intervention with stenting. Methods: Of the 1,755 consecutive AMI patients undergoing percutaneous coronary intervention with stenting enrolled, 103 had CS at admission. Primary endpoints were early mortality (within 30 days after the index event) and late mortality (from day 31 up to 4 years). Secondary endpoints included MACE [all-cause death, myocardial infarction or target vessel revascularization (TVR)], myocardial infarction, TVR and stent thrombosis. Results: Thirty-day mortality was higher among CS patients, and CS was a strong independent predictor of a higher risk of early death (adjusted HR 3.64, 95% CI 2.44–5.44). The late mortality rate was significantly higher in CS patients, and CS was also a predictor of higher risk of death at a 4-year follow-up (adjusted HR 1.95, 95% CI 1.11–3.45). Recurrent AMI, TVR and stent thrombosis rates were similar among patients with and without CS. Conclusion: CS complicating AMI is still a severe clinical event, mainly with regard to a significant higher risk of early mortality, but also associated with a worse prognosis in 30-day survivors.
Middle Lobe Syndrome: A Review of Clinicopathological Features, Diagnosis and Treatment
Authors: Gudbjartsson Tomas , Gudmundsson Gunnar
Published: March 2012

Middle lobe syndrome (MLS) is a rare but important clinical entity that has been poorly defined in the literature. It is characterized by recurrent or chronic collapse of the middle lobe of the right lung but can also involve the lingula of the left lung. Pathophysiologically, there are two forms of MLS, namely obstructive and nonobstructive. Obstructive MLS is usually caused by endobronchial lesions or extrinsic compression of the middle lobe bronchus such as from hilar lymphadenopathy or tumors of neoplastic origin, resulting in postobstructive atelectasis and pneumonitis. In the nonobstructive type, no obstruction of the middle lobe bronchus is evident during bronchoscopy or with computerized tomography of the chest. The etiology of the nonobstructive form is not completely understood. Inefficient collateral ventilation, infection and inflammation in the middle lobe or lingula are thought to play a role, and bronchiectasis is the most common histological finding. Patients with proven endobronchial lesions or malignancy are usually offered surgical resection directly. This contrasts with nonobstructive MLS, where most patients respond to medical treatment consisting of bronchodilators, mucolytics and broad-spectrum antibiotics. However, some patients do not respond to conservative treatment and may suffer irreversible damage of the middle lobe or lingula, in addition to having recurrent symptoms of infection or inflammation. These selected patients can be offered surgical resection of the middle lobe or lingula, which is associated with a low mortality rate and favorable outcome.
Chromosome Analysis of 82 Species of Scarabaeoidea (Coleoptera), with Special Focus on NOR Localization
Authors: Dutrillaux A.-M. , Dutrillaux B.
Published: March 2012

The aim of this study was the identification of the ancestral location of the nucleolus organizer region (NOR) in the Scarabaeoidea superfamily, and its evolutive trends in the karyotypes. For this purpose, the mitotic and meiotic chromosomes at pachynema of 82 species belonging to 4 families and 8 subfamilies, including 49 species without any published data, were examined after Giemsa staining, C-banding and NOR staining. It could be perceived that most karyotypes are composed of 18 nonacrocentric autosomes, an acrocentric X and a punctiform Y. NORs are frequently located on the X independent of its morphology. In contrast, autosomal NORs are frequently on the rare acrocentric short arms. Thus, it could be shown that the ancestral karyotype was very probably composed of 18 metacentric/submetacentric autosomes, an NOR carrier acrocentric X and a punctiform Y. The NOR translocation on autosomes parallels the passage to their acrocentric morphology. It is proposed that the frequent location of the NOR on the X of beetles, and possibly other insects, is made possible by their mode of dosage compensation of the X chromosome, consisting in the overexpression of the unique X of the males.
Perioperative Antibiotic in Adenoidectomy with Partial Tonsillectomy: A Randomized Trial
Authors: Zagólski Olaf , Kulisiewicz Jan
Published: March 2012

Objectives: To examine potential benefits of perioperative antibiotic therapy in children undergoing adenotonsillotomy. Methods: Adenoidectomy with tonsillotomy was performed in 124 children with obstructive symptoms, aged 5–7 years. Of these, 120 completed the study. Intraoperative intravenous and postoperative oral clindamycin, or placebo for 7 days, were administered. Results: There were significant differences between the groups regarding pain intensity (p < 0.001) and duration (p < 0.05), day of return to normal physical activity (p < 0.05), occurrence and duration of oral malodor (p < 0.001), number of doses of additional analgesic (p < 0.001), healing grading (p < 0.05) and parents’/caregivers’ satisfaction scores on the 4th postoperative day. There were indications for antibiotic in 2 individuals in the placebo group. Conclusions: There are significant differences in the course of convalescence related to perioperative antibiotic in children after adenotonsillotomy, but strict indications for antibiotics in these patients are rare.
The Heart in Friedreich Ataxia
Authors: Weidemann Frank , Rummey Christian , Bijnens Bart , Störk Stefan , Jasaityte Ruta , Dhooge Jan , Baltabaeva Aigul , Sutherland George , Schulz Jörg B. , Meier Thomas
Published: March 2012

Background—

This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM).

Methods and Results—

A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and exercise stress testing, was performed in 205 FA patients. To assess myocardial hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness (IVSTd) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging–determined left ventricular mass. With the use of this parameter, 4 groups of patients with FA-CM could be defined. Patients with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM (40%) if IVSTd exceeded the normal value by <18% or as having intermediate FA-CM (16.1%) if IVSTd exceeded the normal value by ≥18%. Patients with ejection fraction <50% were classified as having severe FA-CM (12.2%). In addition to increased myocardial mass, severe FA-CM was further characterized by dilatation of the left ventricle, reduced systolic strain rate of the posterior wall, and ECG abnormalities. Regional myocardial function correlated negatively with FA-CM groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no clear correlation was found between FA-CM groups and neurological function.

Conclusions—

We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data. Because no distinct interrelations between FA-CM and neurological status could be determined, regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice.

Clinical Trial Registration—

https://www.clinicaltrials.gov
. Unique identifier: NCT00905268.
Critical care resources in the Solomon Islands: a cross-sectional survey
Authors: Westcott Mia , Martiniuk Alexandra LC , Fowler Robert A , Adhikari Neill KJ , Dalipanda Tenneth
Published: March 2012

Background

There are minimal data available on critical care case-mix, care processes and outcomes in lower and middle income countries (LMICs). The objectives of this paper were to gather data in the Solomon Islands in order to gain a better understanding of common presentations of critical illness, available hospital resources, and what resources would be helpful in improving the care of these patients in the future.

Methods

This study used a mixed methods approach, including a cross sectional survey of respondents' opinions regarding critical care needs, ethnographic information and qualitative data.

Results

The four most common conditions leading to critical illness in the Solomon Islands are malaria, diseases of the respiratory system including pneumonia and influenza, diabetes mellitus and tuberculosis. Complications of surgery and trauma less frequently result in critical illness. Respondents emphasised the need for basic critical care resources in LMICs, including equipment such as oximeters and oxygen concentrators; greater access to medications and blood products; laboratory services; staff education; and the need for at least one national critical care facility.

Conclusions

A large degree of critical illness in LMICs is likely due to inadequate resources for primary prevention and healthcare; however, for patients who fall through the net of prevention, there may be simple therapies and context-appropriate resources to mitigate the high burden of morbidity and mortality. Emphasis should be on the development and acquisition of simple and inexpensive tools rather than complicated equipment, to prevent critical care from unduly diverting resources away from other important parts of the health system.
Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism
Authors: Jackson Lauren R , Farin Char E , Whisnant Scott
Published: March 2012

Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα) are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P < 0.01) compared with controls (30.5 ± 2.4%) or embryos developed in TNFα plus indomethacin (25.8 ± 2.8%). There was no difference between control embryos and embryos developed in TNFα plus indomethacin. These results indicate that TNFα is inhibitory to the in vitro development of bovine embryos and that this inhibition may be mediated by prostaglandins because it can be blocked by indomethacin.
Effects of the standardized ileal digestible lysine to metabolizable energy ratio on performance and carcass characteristics of growing-finishing pigs
Authors: Li Pengfei , Zeng Zhikai , Wang Ding , Xue Lingfeng , Zhang Rongfei , Piao Xiangshu
Published: March 2012

A total of 2,121 growing-finishing pigs (Duroc × Landrace × Large White) were utilized in six experiments conducted to determine the effects of different ratios of standardized ileal digestible lysine (SID-Lys) to metabolizable energy (ME) on the performance and carcass characteristics of growing-finishing pigs. Exps. 1 (30 to 50 kg), 2 (52 to 70 kg) and 3 (81 to 104 kg) were conducted to find an optimum ME level and then this level was used in Exps. 4 (29 to 47 kg), 5 (54 to 76 kg) and 6 (84 to 109 kg) to test the response of pigs to different ratios of SID-Lys:ME. In Exps.1 to 3, four treatments were used consisting of diets with a formulated ME content of 3.1, 3.2, 3.3 or 3.4 in Exps. 1 and 2 while Exp. 3 used 3.05, 3.15, 3.25 or 3.35 Mcal/kg. A constant SID-Lys:ME ratio of 2.6, 2.3 or 2.0 g/Mcal was used in Exps. 1, 2 and 3, respectively. Weight gain was significantly increased with increasing energy level in Exp.1 while weight gain was unaltered in Exps. 2 and 3. For all three experiments, feed intake was decreased (P < 0.05) and feed efficiency was improved (P < 0.05) with increasing energy level. Tenth rib back fat thickness linearly increased (P < 0.05) with increasing energy level. In Exps. 4 to 6, five treatments were used consisting of diets with a SID-Lys:ME ratio of 2.4, 2.6, 2.8, 3.0 or 3.2 in Exp. 1, 2.1, 2.3, 2.5, 2.7, 2.9 or 3.2 in Exp. 2 and 1.8, 2.0, 2.2, 2.4, or 2.6 in Exp. 3. A constant ME level 3.2, 3.2 and 3.05 Mcal/kg was used in Exps. 1, 2 and 3, respectively (selected based on the results of weight gain). For all three experiments, weight gain increased (P < 0.05) and feed efficiency improved linearly (P < 0.05) as the SID-Lys:ME ratio increased. Tenth rib back fat thickness linearly decreased (P < 0.05) as the SID-Lys:ME ratio increased. Based on a straight broken-line model, the estimated SID-Lys:ME ratio to maximize weight gain was 3.0, 2.43 and 2.2 for 29 to 47, 54 to76 and 84 to 109 kg of pigs, respectively.
Effects of pulmonary acid aspiration on the lungs and extra-pulmonary organs: a randomized study in pigs
Authors: Heuer Jan Florian , Sauter Philip , Pelosi Paolo , Herrmann Peter , Brück Wolfgang , Perske Christina , Schöndube Fritz , Crozier Thomas A , Bleckmann Annalen , Beißbarth Tim , Quintel Michael
Published: March 2012

Introduction

There is mounting evidence that injury to one organ causes indirect damage to other organ systems with increased morbidity and mortality. The aim of this study was to determine the effects of acid aspiration pneumonitis (AAP) on extrapulmonary organs and to test the hypothesis that these could be due to circulatory depression or hypoxemia.

Methods

Mechanically ventilated anesthetized pigs were randomized to receive intrabronchial instillation of hydrochloric acid (n = 7) or no treatment (n = 7). Hydrochloric acid (0.1 N, pH 1.1, 2.5 ml/kg BW) was instilled into the lungs during the inspiratory phase of ventilation. Hemodynamics, respiratory function and computer tomography (CT) scans of lung and brain were followed over a four-hour period. Tissue samples of lung, heart, liver, kidney and hippocampus were collected at the end of the experiment.

Results

Acid instillation caused pulmonary edema, measured as increased extravascular lung water index (ELWI), impaired gas exchange and increased mean pulmonary artery pressure. Gas exchange tended to improve during the course of the study, despite increasing ELWI. In AAP animals compared to controls we found: a) cardiac leukocyte infiltration and necrosis in the conduction system and myocardium; b) lymphocyte infiltration in the liver, spreading from the periportal zone with prominent areas of necrosis; c) renal inflammation with lymphocyte infiltration, edema and necrosis in the proximal and distal tubules; and d) a tendency towards more severe hippocampal damage (P > 0.05).

Conclusions

Acid aspiration pneumonitis induces extrapulmonary organ injury. Circulatory depression and hypoxemia are unlikely causative factors. ELWI is a sensitive bedside parameter of early lung damage.
Assessing and managing mild to moderate emotion dysregulation
Authors: Raju Rajiv , Corrigan Frank M. , Davidson Alan J. W. , Johnson David
Published: March 2012

This article reviews the putative role of emotion dysregulation in diverse clinical presentations and considers some of its aetiological factors, such as insecure attachments in early life and traumatic experiences in later life. The neurobiology of emotional processes is described in relation to the ‘window of tolerance’ model of arousal levels optimal for information processing. Treatment options are considered and ways to regulate distress, derived from different approaches, are summarised in a ‘toolbox’. Fictitious case vignettes illustrate clinical applications.
Couple relationship problems and sexual dysfunctions: therapeutic guidelines
Authors: Crowe Michael
Published: March 2012

Sex is central to most intimate relationships, and there is inevitably a two-way interaction between sex and intimacy. Sex is a physical, a psychological and an interpersonal event, and treatment of sexual problems should take account of all three aspects. Couple relationship problems that can affect sexual interaction include pervasive hostility, poor communication, lack of trust and disparate levels of sexual desire. Therapists should be able to manage therapy sessions with both partners present, without taking sides, and treating the relationship, rather than either individual, as the ‘client’. They should be able to balance the physical approach to problems with managing relationship issues and the partners' individual psychological problems. Techniques are recommended for understanding and modifying the couple relationship during therapy, as well as for dealing with specific sexual problems using a behavioural systems approach.
Working with guilt and shame
Authors: Clark Andrew
Published: March 2012

This article describes the psychological experiences of guilt and shame. Although these affects have an important role in holding our communities together, they can also become extremely distressing and debilitating for individuals. As such, they are transdiagnostic problems which are frequently encountered in mental healthcare. The origin of these affects is considered from religious, cultural and psychological perspectives. The article then explores the clinical manifestations of guilt and shame. Finally, consideration is given to therapeutic options, including general approaches as well as specific psychological therapies.
Anxiety: a hidden element in dementia
Authors: Badrakalimuthu Vellingiri Raja , Tarbuck Andrew F.
Published: March 2012

Anxiety has reported prevalence rates between 38 and 72% among people with dementia. It has a negative impact on cognitive impairment and is associated with agitation and poor quality of life. The presence of excessive anxiety can be difficult to establish in people with dementia, especially when expressive or receptive speech is impaired. Unfortunately, there is a lack of research on the treatment of anxiety in dementia, and also on the wider issue of the management of anxiety disorders in old age. We explore the prevalence, presentation and diagnosis of anxiety in dementia and discuss the therapeutic options available.
Personality disorder in adolescence
Authors: Adshead Gwen , Brodrick Paul , Preston Jackie , Deshpande Mayura
Published: March 2012

There is considerable debate about the diagnosis of personality disorder in adolescence. It is argued that, because personality is still developing in the teenage years, it is impossible to state with certainty that a young person's personality is disordered. Alternatively, some researchers and clinicians argue that it is possible to diagnose emerging personality disorder on the basis of trait theories of personality. We review the evidence for both sides of the debate.
Patients' experience of dangerous and severe personality disorder services: qualitative interview study
Authors: Sinclair Julia , Willmott Lucy , Fitzpatrick Ray , Burns Tom , Yiend Jenny ,   the IDEA Group
Published: March 2012

As part of an evaluation of the Dangerous and Severe Personality Disorder (DSPD) Programme, we conducted in-depth interviews with 60 participants purposely sampled across four pilot DSPD units. This report is limited to the finding with potential ‘conceptual generalisability’: namely the unanticipated finding of negative and hostile attitudes of participants being managed in hospital units compared with the prison system. The recent UK government policy decision to concentrate this programme in prisons may, in part, reflect the significance of these findings.
Assessing fitness to drive in dementia and other psychiatric conditions: a higher training learning opportunity at a driving assessment centre
Authors: Sheridan Matthew P.
Published: March 2012

With an ageing population and expected rise in cases of dementia, driving safety will become increasingly important. Doctors have a professional obligation to identify patients who are unsafe to drive and in cases of dementia this decision is often complex. As a result, many centres in the UK offer driving assessments for people with medical conditions that may affect their on-road performance. I aim to identify a valuable learning opportunity for psychiatrists in training, particularly those working with older adults, to improve their knowledge of driving assessment. I also provide an overview of the Scottish Driving Assessment Service and reflect on my visit there.
Going the extra mile
Authors: Fear Chris , Scheepers Mark , Ansell Martin , Richards Rosemary , Winterbottom Paul
Published: March 2012

Stephen Tyrer's commentary on Fair Horizons was generally supportive of the principles underpinning the model, while offering a number of questions and caveats. In this response, we provide responses to the points made and offer further insights into the practicalities of the Fair Horizons model.
The American Empire’s Terrorist Network
Authors: Gerassi John
Published: March 2012

U.S. militarism provides an emotional compensation for Americans who are being screwed over by the corporate rich.
The Chemistry of Friendship: My Lunches With Norman
Authors: Pinsky Mark I.
Published: March 2012

A portrait of an amazing and well-lived life.
Ingestion or Aspiration of Foreign Objects or Toxic Substances ISMP Issues Statement on Use of Metric Measurements Oral Potassium Chloride Overdose Fatal
Authors: Cohen Michael R. , Smetzer Judy L.
Published: March 2012

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Bevacizumab-Induced Laryngeal Necrosis Olanzapine-Related Hyperosmolar Hyperglycemic Syndrome Dangerous Fruit Juice Drug-Induced Hypertension Drug-Induced Pancreatitis Anticoagulation-Associated Adverse Drug Events Severe Cutaneous Adverse Reactions to Antiepileptic Drugs in Asians
Authors: Shuster Joel
Published: March 2012

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.
Rifaximin in Combination with Metronidazole and Oral Vancomycin for the Treatment of an Initial Episode of Clostridium difficile–Associated Diarrhea: Case Report and Literature Review
Authors: Cribb Jennifer L. , O'Brien Karly , DeRemer Christina E.
Published: March 2012

Purpose

Example of successful use of rifaximin in the treatment of an apparent Clostridium difficile infection refractory to vancomycin and metronidazole with literature review.

Case Summary

A 69-year-old Caucasian female developed C. difficile infectious diarrhea, confirmed by enzyme immunoassay (EIA) test. Following diagnosis, the patient was initiated on a treatment regimen of intravenous (IV) metronidazole and oral vancomycin. The patient sought additional medical treatment 3 days after initiating this treatment regimen. She presented with continued symptoms of diarrhea, bloating, anorexia, weakness, and leukocytosis nonresponsive to metronidazole and vancomycin. After a total of 7 days of treatment with metronidazole and vancomycin, the patient remained symptomatic with loose stools occurring approximately every 2 hours. Oral rifaximin 400 mg 3 times a day was added to the regimen, after which the patient's symptoms improved rapidly.

Conclusion

A patient with presumed C. difficile–associated diarrhea refractory to metronidazole and vancomycin was successfully treated after the addition of oral rifaximin 400 mg 3 times a day. Based on current literature and this case, rifaximin should not replace metronidazole or vancomycin as primary therapy for presumed or diagnosed C. difficile but should be retained as a useful alternative, especially in light of limited alternatives.
Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Authors: Baker Danial E.
Published: March 2012

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at bakerdan@wsu.edu .
The Role of the Pharmacy Informatics Position in Practice Model Development
Authors: Bonkowski Joseph , Seki David , Prier Beth , Weber Robert
Published: March 2012

The Director's Forum series is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. Health care information systems are becoming more integrated and interoperable and are able to connect with a variety of software and systems. A key position that helps to connect the pharmacy to the organization's information system needs is the Informatics Pharmacist (IP). This position's distinct expertise in systems capabilities and pharmacy operations can support innovations in practice and strong communication throughout the organization. The director of pharmacy can leverage the talents of the IP to enhance the patient-centered services of the pharmacy. Given that most pharmacy departments are small and may not have resources to hire a full-time IP, this article provides the pharmacy director with information about the IP position, which can be used to justify additional resources to focus on pharmacy informatics.
Fetuin-A Is Inversely Associated with Coronary Artery Calcification in Community-Living Persons: The Multi-Ethnic Study of Atherosclerosis
Authors: Ix Joachim H , Katz Ronit , de Boer Ian H , Kestenbaum Bryan R , Peralta Carmen A , Jenny Nancy S , Budoff Matthew , Allison Matthew A , Criqui Michael H , Siscovick David , Shlipak Michael G
Published: March 2012

BACKGROUND

Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain.

METHODS

Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC incidence and progression.

RESULTS

The mean age was 62 (SD 10) years, and the mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline, there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence. In models adjusted for demographics, traditional cardiovascular disease (CVD) risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%–13%; P = 0.04) greater CAC prevalence compared with quartiles 2–4. Similar associations were observed with CAC severity at baseline, but the association was more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI 3%–21%; P = 0.01) greater CAC severity in adjusted models. There was no significant association of fetuin-A with CAC incidence or progression.

CONCLUSIONS

Fetuin-A is inversely associated with CAC severity among community-living individuals without CVD. Whether fetuin-A concentrations are associated with incident CVD event in the general population requires future study.
5-HT7R/G12Signaling Regulates Neuronal Morphology and Function in an Age-Dependent Manner
Authors: Kobe Fritz , Guseva Daria , Jensen Thomas P. , Wirth Alexander , Renner Ute , Hess Dietmar , Müller Michael , Medrihan Lucian , Zhang Weiqi , Zhang Mingyue , Braun Katharina , Westerholz Sören , Herzog Andreas , Radyushkin Konstantin , El-Kordi Ahmed , Ehrenreich Hannelore , Richter Diethelm W. , Rusakov Dmitri A. , Ponimaskin Evgeni
Published: March 2012

The common neurotransmitter serotonin controls different aspects of early neuronal differentiation, although the underlying mechanisms are poorly understood. Here we report that activation of the serotonin 5-HT7receptor promotes synaptogenesis and enhances synaptic activity in hippocampal neurons at early postnatal stages. An analysis of Gα12-deficient mice reveals a critical role of G12-protein for 5-HT7receptor-mediated effects in neurons. In organotypic preparations from the hippocampus of juvenile mice, stimulation of 5-HT7R/G12signaling potentiates formation of dendritic spines, increases neuronal excitability, and modulates synaptic plasticity. In contrast, in older neuronal preparations, morphogenetic and synaptogenic effects of 5-HT7/G12signaling are abolished. Moreover, inhibition of 5-HT7receptor had no effect on synaptic plasticity in hippocampus of adult animals. Expression analysis reveals that the production of 5-HT7and Gα12-proteins in the hippocampus undergoes strong regulation with a pronounced transient increase during early postnatal stages. Thus, regulated expression of 5-HT7receptor and Gα12-protein may represent a molecular mechanism by which serotonin specifically modulates formation of initial neuronal networks during early postnatal development.
Adaptation of Granule Cell to Purkinje Cell Synapses to High-Frequency Transmission
Authors: Valera Antoine M. , Doussau Frédéric , Poulain Bernard , Barbour Boris , Isope Philippe
Published: March 2012

The mossy fiber (MF)–granule cell (GC) pathway conveys multiple modalities of information to the cerebellar cortex, converging on Purkinje cells (PC), the sole output of the cerebellar cortex. Recentin vivoexperiments have shown that activity in GCs varies from tonic firing at a few hertz to phasic bursts >500 Hz. However, the responses of parallel fiber (PF)–PC synapses to this wide range of input frequencies are unknown, and there is controversy regarding several frequency-related parameters of transmission at this synapse. We performed recordings of unitary synapses and combined variance–mean analysis with a carefully adapted extracellular stimulation method in young and adult rats. We show that, although the probability of release at individual sites is low at physiological calcium concentration, PF–PC synapses release one or more vesicles with a probability of 0.44 at 1.5 mm[Ca2+]e. Paired-pulse facilitation was observed over a wide range of frequencies; it renders burst inputs particularly effective and reproducible. These properties are primarily independent of synaptic weight and age. Furthermore, we show that the PF–PC synapse is able to sustain transmission at very high frequencies for tens of stimuli, as a result of accelerated vesicle replenishment and an apparent recruitment of release site vesicles, which appears to be a central mechanism of paired-pulse facilitation at this synapse. These properties ensure that PF–PC synapses possess a dynamic range enabling the temporal code of MF inputs to be transmitted reliably to the PC.
A Cre-Dependent GCaMP3 Reporter Mouse for Neuronal ImagingIn Vivo
Authors: Zariwala Hatim A. , Borghuis Bart G. , Hoogland Tycho M. , Madisen Linda , Tian Lin , De Zeeuw Chris I. , Zeng Hongkui , Looger Loren L. , Svoboda Karel , Chen Tsai-Wen
Published: March 2012

Fluorescent calcium indicator proteins, such as GCaMP3, allow imaging of activity in genetically defined neuronal populations. GCaMP3 can be expressed using various gene delivery methods, such as viral infection or electroporation. However, these methods are invasive and provide inhomogeneous and nonstationary expression. Here, we developed a genetic reporter mouse, Ai38, which expresses GCaMP3 in a Cre-dependent manner from theROSA26locus, driven by a strongCAGpromoter. Crossing Ai38 with appropriate Cre mice produced robust GCaMP3 expression in defined cell populations in the retina, cortex, and cerebellum. In the primary visual cortex, visually evoked GCaMP3 signals showed normal orientation and direction selectivity. GCaMP3 signals were rapid, compared with virally expressed GCaMP3 and synthetic calcium indicators. In the retina, Ai38 allowed imaging spontaneous calcium waves in starburst amacrine cells during development, and light-evoked responses in ganglion cells in adult tissue. Our results show that the Ai38 reporter mouse provides a flexible method for targeted expression of GCaMP3.
Role of HCN Channels in Neuronal Hyperexcitability after Subarachnoid Hemorrhage in Rats
Authors: Li Bo , Luo Chunxia , Tang Weihua , Chen Zhi , Li Qiang , Hu Bo , Lin Jiangkai , Zhu Gang , Zhang John H. , Feng Hua
Published: March 2012

Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from whole-cell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, whilel-nitroarginine (l-NNA), an inhibitor of nitric oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on HCN currents was reversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely,l-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavenged the production of nitric oxide and decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model, the expression of HCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH.
Neurons with Stereotyped and Rapid Responses Provide a Reference Frame for Relative Temporal Coding in Primate Auditory Cortex
Authors: Brasselet Romain , Panzeri Stefano , Logothetis Nikos K. , Kayser Christoph
Published: March 2012

The precise timing of spikes of cortical neurons relative to stimulus onset carries substantial sensory information. To access this information the sensory systems would need to maintain an internal temporal reference that reflects the precise stimulus timing. Whether and how sensory systems implement such reference frames to decode time-dependent responses, however, remains debated. Studying the encoding of naturalistic sounds in primate (Macaca mulatta) auditory cortex we here investigate potential intrinsic references for decoding temporally precise information. Within the population of recorded neurons, we found one subset responding with stereotyped fast latencies that varied little across trials or stimuli, while the remaining neurons had stimulus-modulated responses with longer and variable latencies. Computational analysis demonstrated that the neurons with stereotyped short latencies constitute an effective temporal reference for relative coding. Using the response onset of a simultaneously recorded stereotyped neuron allowed decoding most of the stimulus information carried by onset latencies and the full spike train of stimulus-modulated neurons. Computational modeling showed that few tens of such stereotyped reference neurons suffice to recover nearly all information that would be available when decoding the same responses relative to the actual stimulus onset. These findings reveal an explicit neural signature of an intrinsic reference for decoding temporal response patterns in the auditory cortex of alert animals. Furthermore, they highlight a role for apparently unselective neurons as an early saliency signal that provides a temporal reference for extracting stimulus information from other neurons.
A Mouse Model forMeCP2Duplication Syndrome: MeCP2 Overexpression Impairs Learning and Memory and Synaptic Transmission
Authors: Na Elisa S. , Nelson Erika D. , Adachi Megumi , Autry Anita E. , Mahgoub Melissa A. , Kavalali Ege T. , Monteggia Lisa M.
Published: March 2012

Rett syndrome andMECP2duplication syndrome are neurodevelopmental disorders that arise from loss-of-function and gain-of-function alterations in methyl-CpG binding protein 2 (MeCP2) expression, respectively. Although there have been studies examining MeCP2 loss of function in animal models, there is limited information on MeCP2 overexpression in animal models. Here, we characterize a mouse line with MeCP2 overexpression restricted to neurons (Tau–Mecp2). This MeCP2 overexpression line shows motor coordination deficits, heightened anxiety, and impairments in learning and memory that are accompanied by deficits in long-term potentiation and short-term synaptic plasticity. Whole-cell voltage-clamp recordings of cultured hippocampal neurons fromTau–Mecp2mice reveal augmented frequency of miniature EPSCs with no change in miniature IPSCs, indicating that overexpression of MeCP2 selectively impacts excitatory synapse function. Moreover, we show that alterations in transcriptional repression mechanisms underlie the synaptic phenotypes in hippocampal neurons from theTau–Mecp2mice. These results demonstrate that theTau–Mecp2mouse line recapitulates many key phenotypes ofMECP2duplication syndrome and support the use of these mice to further study this devastating disorder.