bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effect of Indian hedgehog and bone morphogenetic protein-2 gene transfer to increase the osteogenic potential of human mesenchymal stem cells
Authors: Reichert Johannes C , Schmalzl Jonas , Prager Patrick , Gilbert Fabian , Quent Verena MC , Steinert Andre F , Rudert Maximilian , Nöth Ulrich 
Published: September 2013

Abstract
Introduction
To stimulate healing of large bone defects research has concentrated on the application of mesenchymal stem cells (MSCs).

Methods
In the present study, we induced the overexpression of the growth factors bone morphogenetic protein 2 (BMP-2) and/or Indian hedgehog (IHH) in human MSCs by adenoviral transduction to increase their osteogenic potential. GFP and nontransduced MSCs served as controls. The influence of the respective genetic modification on cell metabolic activity, proliferation, alkaline phosphatase (ALP) activity, mineralization in cell culture, and osteogenic marker gene expression was investigated.

Results
Transduction had no negative influence on cell metabolic activity or proliferation. ALP activity showed a typical rise-and-fall pattern with a maximal activity at day 14 and 21 after osteogenic induction. Enzyme activity was significantly higher in groups cultured with osteogenic media. The overexpression of BMP-2 and especially IHH + BMP-2 resulted in a significantly higher mineralization after 28 days. This was in line with obtained quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analyses, which showed a significant increase in osteopontin and osteocalcin expression for osteogenically induced BMP-2 and IHH + BMP-2 transduced cells when compared with the other groups. Moreover, an increase in runx2 expression was observed in all osteogenic groups toward day 21. It was again more pronounced for BMP-2 and IHH + BMP-2 transduced cells cultured in osteogenic media.

Conclusions
In summary, viral transduction did not negatively influence cell metabolic activity and proliferation. The overexpression of BMP-2 in combination with or without IHH resulted in an increased deposition of mineralized extracellular matrix, and expression of osteogenic marker genes. Viral transduction therefore represents a promising means to increase the osteogenic potential of MSCs and the combination of different transgenes may result in synergistic effects.
Portfolio-based learning in medical education
Authors: Ingrassia Antonina 
Published: September 2013

SummaryThe use of portfolios has rapidly expanded in recent years and is now relevant to a number of different aspects of professional practice in medicine in general and psychiatry in particular, including training, appraisal and revalidation as well as continuing professional development. In this article I will examine the background of important changes and new trends in medical education on which the increasing use of portfolios is based, their potential value as learning and assessment tools, and some of the challenges and dilemmas associated with their use.
Talking about madness and melancholy: Boswell'sLife of Samuel Johnson
Authors: Beveridge Allan 
Published: September 2013

SummaryThis article examines James Boswell'sLife of Samuel Johnson, his celebrated biography of his friend, the great 18th-century literary figure, Samuel Johnson. The book records their many conversations, much of which was concerned with madness and melancholy. This is not surprising as both men experienced recurrent bouts of low spirits. They also lived in an era which has been called ‘The Age of Nerves’. This article will consider how they conceived of ‘nervous disease’ and how they tried to remedy it. It will also look at Johnson's role as a therapeutic mentor to Boswell.
Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy
Authors: Choi Kee-Hong , Wykes Til , Kurtz Matthew M. 
Published: September 2013

BackgroundA growing number of studies have investigated the efficacy of novel, adjunctive pharmacotherapies for treatment of cognitive deficits in schizophrenia with conflicting results.AimsTo investigate the comparative efficacy of these agents on cognition and symptoms in schizophrenia, and to identify promising cognitive domains and candidate medications that can be incorporated in treatment trials combined with cognitive remediation to maximise treatment effects.MethodA total of 26 double-blind, placebo-controlled studies investigating medications targeted at cholinergic, glutamatergic or serotonergic receptor classes and with participants with schizophrenia or schizoaffective disorder were identified.ResultsMedications targeted at the cholinergic receptor class produced marginal improvements in verbal learning and memory (d= 0.23,P= 0.06), and donepezil, a specific type of cholinergic agonist, produced a moderate effect (d= 0.58) on spatial learning and memory. Cholinergic and glutamatergic agents produced moderate effect-size improvements on negative symptoms (d= 0.54 andd= 0.62 respectively), and small effect-size improvements on general symptoms (d= 0.46 andd= 0.41 respectively). Serotonergic agents produced small effect-size improvements in positive symptoms (d= 0.33).ConclusionsCholinergic medications produced marginal improvement in verbal learning and memory and moderate improvements on spatial learning and memory, although there was no evidence to support the use of glutamatergic or serotonergic medications as a stand-alone treatment for improving cognitive function. Cholinergic and glutamatergic agents improved negative and general symptoms, whereas serotenergic medications improved positive symptoms.
Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials
Authors: Koesters Markus , Guaiana Giuseppe , Cipriani Andrea , Becker Thomas , Barbui Corrado 
Published: September 2013

BackgroundAgomelatine is a novel antidepressant drug with narrative, non-systematic reviews making claims of efficacy.AimsThe present study systematically reviewed published and unpublished evidence of the acute and long-term efficacy and acceptability of agomelatine compared with placebo in the treatment of major depression.MethodRandomised controlled trials comparing agomelatine with placebo in the treatment of unipolar major depression were systematically reviewed. Primary outcomes were (a) Hamilton Rating Scale for Depression (HRSD) score at the end of treatment (short-term studies) and (b) number of relapses (long-term studies).ResultsMeta-analyses included 10 acute-phase and 3 relapse prevention studies. Seven of the included studies were unpublished. Acute treatment with agomelatine was associated with a statistically significant superiority over placebo of −1.51 HRSD points (99% Cl −2.29 to −0.73, nine studies). Data extracted from three relapse prevention studies failed to show significant effects of agomelatine over placebo (relative risk 0.78, 99% Cl 0.41−1.48). Secondary efficacy analyses showed a significant advantage of agomelatine over placebo in terms of response (with no effect for remission). None of the negative trials were published and conflicting results between published and unpublished studies were observed.ConclusionsWe found evidence suggesting that a clinically important difference between agomelatine and placebo in patients with unipolar major depression is unlikely. There was evidence of substantial publication bias.
Differing perspectives on what is important in media reporting of suicide
Authors: Pirkis Jane , Machlin Anna 
Published: September 2013

SummaryThere is a substantial literature which demonstrates that irresponsible reporting of suicide can lead to copycat acts and, as a result, many countries have developed guidelines for media professionals. Some of the recommendations in these guidelines draw directly on the evidence and describe how reporting can be done in a measured fashion that minimises any likely negative influence. Other recommendations relate more to good journalistic practice and are about showing respect for the bereaved in their time of grieving. The study by Chapple et al, in this issue, indicates that there may sometimes be tensions between what media guidelines recommend and what those bereaved by suicide believe is important. We would argue that in such cases common ground can be reached.
A human right to be detained? Mental healthcare after ‘Savage’ and ‘Rabone'
Authors: Rahman Mohammad Shaiyan , Wolferstan Nadya 
Published: September 2013

SummaryThe UK courts have recently considered the management of suicidal patients in the cases of Savage and Rabone. As a result of these judgments, the case law has extended significantly the responsibilities of mental healthcare providers. In this article we discuss the repercussions of these landmark decisions which are likely to have significant consequences for mental health service providers in the UK.
Impact of the European Working Time Directive on trainees and trainers 3 years post-implementation
Authors: Shaddel Farshad , Banerjee Subimal 
Published: September 2013

Aims and methodTo assess the views of trainees and trainers of the impact of the European Working Time Directive (EWTD). The study was conducted in two stages. First, a qualitative survey of trainees and trainers in the Oxford Deanery was carried out on the positive and negative aspects of the EWTD to identify key areas. Second, a self-completed questionnaire was developed separately for trainees and trainers and the results collated. Twenty trainers and nineteen trainees took part in the study.ResultsAbout 70% of trainees and trainers were aware of the EWTD objectives. Ninety per cent of trainers and 30% of trainees believed that the introduction of the EWTD was a negative development. Compared with 42% of trainees, 80% of trainers believed that the EWTD had not improved the quality of care and instead had a negative effect on doctor–patient alliance and continuity of care. Although 53% of trainees believed that the quality of training was not compromised by the introduction of the EWTD, 84% of trainers thought otherwise. Less hands-on experience and some doctors' roles being given to other professionals were the most stated negative impacts of the EWTD on the quality of doctors' training. Positive effects of the EWTD from both trainees' and trainers' points of view were a better work-life balance and less burnout for junior doctors.Clinical implicationsThe EWTD may not have been successful in achieving all of its intended objectives. Further studies on different sample groups would help clarify the wider impact of the EWTD.
Jinn and mental health: looking at jinn possession in modern psychiatric practice
Authors: Dein Simon , Illaiee Abdool Samad 
Published: September 2013

SummaryThis article focuses on jinn possession and mental illness in Islam. After discussing spirit possession generally and its classification in DSM-5, we present an overview of several studies examining the role of jinn in mental distress in Muslims in the UK. A case study which exemplifies jinn possession is presented and the clinical implications of the findings are discussed. We argue for collaborative working relationships between Islamic religious professionals and mental health professionals. Finally, we discuss potential areas for future research.
‘Rabone’ and four unresolved problems in mental health law
Authors: Szmukler George , Richardson Genevra , Owen Gareth 
Published: September 2013

SummaryIn a landmark decision, the Supreme Court of the UK ruled that the state has a special operational duty to protect the right to life in informal psychiatric in-patients (‘Rabone case'), in sharp distinction to general medical or surgical patients. We will argue that the significance of this case is general, not just local, and that it exposes four important unresolved problems in mental health law: the place of decision-making capacity; the meaning of ‘informal’ admission; parity between mental and physical health; and the accuracy of risk assessment.
Cabozantinib in Progressive Medullary Thyroid Cancer
Authors: Elisei Rossella , Schlumberger Martin J. , Müller Stefan P. , Schöffski Patrick , Brose Marcia S. , Shah Manisha H. , Licitra Lisa , Jarzab Barbara , Medvedev Viktor , Kreissl Michael C. , Niederle Bruno , Cohen Ezra E.W. , Wirth Lori J. , Ali Haythem , Hessel Colin , Yaron Yifah , Ball Douglas , Nelkin Barry , Sherman Steven I. 
Published: September 2013

Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. Conclusion Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity.
Single-Agent Lenalidomide in Patients With Mantle-Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib: Phase II MCL-001 (EMERGE) Study
Authors: Goy Andre , Sinha Rajni , Williams Michael E. , Kalayoglu Besisik Sevgi , Drach Johannes , Ramchandren Radhakrishnan , Zhang Lei , Cicero Sherri , Fu Tommy , Witzig Thomas E. 
Published: September 2013

PurposeAlthough dose-intensive strategies or high-dose therapy induction followed by autologous stem-cell transplantation have improved the outcome for patients with mantle-cell lymphoma (MCL), most eventually relapse and subsequently respond poorly to additional therapy. Bortezomib (in the United States) and temsirolimus (in Europe) are currently the only two treatments approved for relapsed disease. Lenalidomide is an immunomodulatory agent with proven tumoricidal and antiproliferative activity in MCL. The MCL-001 (EMERGE) trial is a global, multicenter phase II study examining the safety and efficacy of lenalidomide in patients who had relapsed or were refractory to bortezomib.Patients and MethodsLenalidomide 25 mg orally was administered on days 1 through 21 every 28 days until disease progression or intolerance. Primary end points were overall response rate (ORR) and duration of response (DOR); secondary end points included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety.ResultsIn all, 134 patients were enrolled with a median age of 67 years and a median of four prior therapies (range, two to 10 prior therapies). The ORR was 28% (7.5% CR/CR unconfirmed) with rapid time to response (median, 2.2 months) and a median DOR of 16.6 months (95% CI, 7.7 to 26.7 months). Median PFS was 4.0 months (95% CI, 3.6 to 5.6 months), and median OS was 19.0 months (95% CI, 12.5 to 23.9 months). The most common grade 3 to 4 adverse events were neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%).ConclusionThe MCL-001 study demonstrated durable efficacy of lenalidomide with a predictable safety profile in heavily pretreated patients with MCL who had all relapsed or progressed after or were refractory to bortezomib.
Rates of Bone Loss Among Women Initiating Antidepressant Medication Use in Midlife
Authors: Diem Susan J. , Ruppert Kristine , Cauley Jane A. , Lian YinJuan , Bromberger Joyce T. , Finkelstein Joel S. , Greendale Gail A. , Solomon Daniel H. 
Published: September 2013

Context:
Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss.

Objective:
The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications.

Design and Setting:
We conducted a prospective cohort study at five clinical centers in the United States.

Participants:
The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN).

Exposure:
The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication.

Main Outcome Measures:
BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits.

Results:
BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (&lt;16 vs ≥16).

Conclusions:
In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased rate of bone loss at the spine, total hip, or femoral neck.
Predictors of Subsequent Overdrainage and Clinical Outcomes After Ventriculoperitoneal Shunting for Idiopathic Normal Pressure Hydrocephalus
Authors: Meier Ullrich , Stengel Dirk , Müller Cornelia , Fritsch Michael J. , Kehler Uwe , Langer Niels , Kiefer Michael , Eymann Regina , Schuhmann Martin U. , Speil Andreas , Weber Friedrich , Remenez Victor , Rohde Veit , Ludwig Hans-Christoph , Lemcke Johannes 
Published: September 2013

Abstract

BACKGROUND:
Little is known about variables associated with overdrainage complications and neurofunctional and health-related quality of life outcomes in idiopathic normal-pressure hydrocephalus (iNPH) patients after shunt surgery.

OBJECTIVE:
To identify candidate demographic and disease-specific predictors of overdrainage and patient-related outcomes, allowing for more personalized care of patients with iNPH.

METHODS:
This was a secondary analysis of the dataset of the SVASONA study, a multicenter randomized trial comparing gravitational and conventional gravitational valves for treating iNPH. We evaluated the association between baseline items and the incidence of overdrainage, using different endpoint definitions.

RESULTS:
We identified only a few variables associated with a possible increased risk of overdrainage. Apart from using conventional rather than gravitational valves, longer duration of surgery and female sex were associated with a higher risk of clinical signs and symptoms suggestive of overdrainage (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04 and 1.84, 95% confidence interval: 0.81-4.16). The occurrence of clinical symptoms of overdrainage, and the need for exchanging a programmable by a gravitational valve may adversely affect disease-specific outcomes like the Kiefer score.

CONCLUSION:
Few, if any, baseline and treatment characteristics may be helpful in estimating the individual risk of complications and clinical outcomes after shunt surgery for iNPH. Patients should be informed that longer surgery for any reason may increase the risk of later overdrainage. Also, women should be counseled about a sex-associated increased risk of the development of clinical symptoms of overdrainage, although the latter cannot be distinguished from a generally higher prevalence of headaches in the female population.
The eel heart: multilevel insights into functional organ plasticity
Authors: Imbrogno Sandra 
Published: September 2013

SummaryThe remarkable functional homogeneity of the heart as an organ requires a well-coordinated myocardial heterogeneity. An example is represented by the selective sensitivity of the different cardiac cells to physical (i.e. shear stress and/or stretch) or chemical stimuli (e.g. catecholamines, angiotensin II, natriuretic peptides, etc.), and the cell-specific synthesis and release of these substances. The biological significance of the cardiac heterogeneity has recently received great attention in attempts to dissect the complexity of the mechanisms that control the cardiac form and function. A useful approach in this regard is to identify natural models of cardiac plasticity. Among fishes, eels (genus Anguilla), for their adaptive and acclimatory abilities, represent a group of animals so far largely used to explore the structural and ultrastructural myoarchitecture organization, as well as the complex molecular networks involved in the modulation of the heart function, such as those converting environmental signals into physiological responses. However, an overview on the existing current knowledge of eel cardiac form and function is not yet available. In this context, this review will illustrate major features of eel cardiac organization and pumping performance. Aspects of autocrine–paracrine modulation and the influence of factors such as body growth, exercise, hypoxia and temperature will highlight the power of the eel heart as an experimental model useful to decipher how the cardiac morpho-functional heterogeneities may support the uniformity of the whole-organ mechanics.
Synthesis and Characterization of Fluorohydrogenate Ionic Liquids Based on Azoniaspiro-type Cations
Authors: Taniki Ryosuke , Matsumoto Kazuhiko , Hagiwara Rika 
Published: September 2013

Abstract
New fluorohydrogenate salts based on azoniaspiro-type cations (AS[x.y]+, x and y denote the number of methylene carbon atoms in each cyclic group) have been synthesized and characterized. Effects of the number of rings and carbon number on physical and structural properties are discussed. Introduction of oxygen atoms in the ring structure is also conducted.
Microwave-assisted Synthesis and Sensing Properties of CuO Microspheres
Authors: Wang Jing , Xu Hongbo , Yang Shilei , Wang Bingbing , Wang Jian 
Published: September 2013

Abstract
A facile microwave-assisted synthetic route has been successfully developed to prepare CuO microspheres in the presence of poly(vinylpyrrolidone) (PVP). The products were characterized by X-ray diffraction and scanning electron microscopy. The effects of microwave irradiation time and surfactant on the morphologies of the resulting products were investigated. Gas-sensing tests demonstrated that the sensors based on the CuO microspheres show higher responses to ethanol and methanol.