bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifetime Risk of Depression
Authors: Wittchen Hans-Ulrich , Knäuper Bärbel , Kessler Ronald C.
Published: August 2018

Over the past decade, major epidemiological studies have been conducted to determine the prevalence of depressive syndromes, primarily major depression or dysthymia. The highest prevalences occur in younger cohorts (18–29 years); considerably lower prevalences are found in older individuals (45 years and above), with the lowest in those aged 65 and older. Several studies have confirmed an increase in the cumulative lifetime estimates of major depression in successively younger birth cohorts during this century. At the same time, questions have been raised about the low prevalence of depression in the elderly, including the role of confounding factors (e.g. differential morbidity and response-biased memory). Standardised diagnostic assessment procedures may be insufficiently adapted for use in the elderly. It has also been recognised that a substantial number of elderly individuals suffer from clinically relevant symptoms of depression but do not meet the criteria for major depression. Future research will be required to elucidate fully the apparently changing rates of depression.
The Social Costs of Anxiety Disorders
Authors: Leon Andrew C. , Portera Laura , Weissman Myrna M.
Published: August 2018

Background. The social costs of anxiety disorders, which afflict a substantial proportion of the general population in the United States, are considered.

Method. Data from the National Institute of Mental Health (NIMH) Epidemiological Catchment Area Program were analysed.

Results. Over 6% of men and 13% of women in the sample of 18 571 had suffered from a DSM–III anxiety disorder in the past six months. Nearly 30% of those with panic disorder had used the general medical system for emotional, alcohol or drug-related problems in the six months prior to the interview. Those with anxiety disorders were also more likely to seek help from emergency rooms and from the specialised mental health system. Men with panic disorder, phobias or obsessive–compulsive disorder in the previous six months are more likely to be chronically unemployed and to receive disability or welfare.

Discussion. Once correctly diagnosed there are safe and effective psychopharmacologic and behavioural treatments for the anxiety disorders. Nevertheless the burden of anxiety disorders extends beyond the direct costs of treatment to the indirect costs of impaired social functioning.
Costs and Offset Effect in Panic Disorders
Authors: Salvador-Carulla L. , Seguí J. , Fernández-Cano P. , Canet J.
Published: August 2018

Background. The study is aimed at assessing the costs before and after the diagnosis and the provision of effective treatment for panic disorder (PD), and the offset effect related to the psychiatric encounter.

Method. A 24-month prepost design was used to collect data on clinical status and health care services utilisation in a natural environment. The 61 PD patients' assessment included the SCID-UP, ratings on general functioning, improvement, severity of symptoms and level of disability. All health care services used and lost workdays were recorded.

Results. Both sociodemographic characteristics and the outcome show that this was a standard group of PD patients, who received effective treatment for their condition. The total direct costs of health care use during the previous year and the year after the diagnosis were, respectively, US$ 29 1 58 and US$ 46 256. The indirect costs of lost productivity were US$ 65 643 in period I and US$ 13 883 in period II.

Conclusions. A strong offset effect (94%) has been found in this study, significantly greater than the one described for psychiatric disorders as a whole. The costs of nondiagnosis are usually overlooked when estimating the global costs of PD. Methods for improving early detection of PD may substantially reduce the costs incurred before diagnosis.
Prevalence of anxiety disorders and their comorbidity with mood and addictive disorders
Authors: Regier D. A. , Rae D. S. , Narrow W. E. , Kaelber C. T. , Schatzberg A. F.
Published: August 2018

Background The co-occurrence of anxiety disorders with other mental, addictive, and physical disorders has important implications for treatment and for prediction of clinical course and associated morbidity.

Method Cross-sectional and prospective data on 20 291 individuals from the Epidemiologic Catchment Area (ECA) study were analysed to determine one-month, current disorders, one-year incidence, and one-year and lifetime prevalence of anxiety, mood, and addictive disorders, and to identify the onset and offset of disorders within the one-year prospective period.

Results Nearly half (47.2%) of those meeting lifetime criteria for major depression also have met criteria for a comorbid anxiety disorder. The average age of onset of any lifetime anxiety disorder (16.4 years) and social phobia (11.6 years) among those with major depression was much younger than the onset age for major depression (23.2 years) and panic disorder.

Conclusions Anxiety disorders, especially social and simple phobias, appear to have an early onset in adolescence with potentially severe consequences, predisposing those affected to greater vulnerability to major depression and addictive disorders.
Methodological Issues in Psychiatric Classification
Authors: Jablensky A.
Published: August 2018

Against the background of impressive advances in the neurosciences, which are opening new perspectives on the mechanisms of mind, and the development of increasingly powerful instruments and methods with a potential to revolutionise clinical research in psychiatry, clinicians continue to disagree on the definition and taxonomy of the elementary units of observation in their universe of discourse: the individual mental disorders.
The Platelet α2-Adrenoceptor as a Potential Biological Marker in Depression
Authors: García-Sevilla Jesús A.
Published: August 2018

Insights into the cellular and molecular mechanisms of action of anti-depressant drugs have led to the study of possible dysfunctions of monoamine neurotransmitter receptors in endogenous depression. Presynaptic receptors play an important role in the regulation of transmitter release from neurons. The major mechanism that regulates the release of noradrenaline appears to be feedback inhibition by the neurotransmitter located in the synaptic cleft. This inhibition is mediated by stimulation of a presynaptic autoreceptor, the inhibitory α2-adrenoceptor. When this is stimulated, further release of noradrenaline is inhibited; therefore, increased autoreceptor sensitivity could result in insufficient neuronal release of noradrenaline, and lead to depression.
Suiting Therapeutic Intervention to the Scientific Models of Aetiology
Authors: Zubin Joseph
Published: August 2018

Since descriptive psychiatry offers only the surface exploration of psychopathology we must turn to aetiology for the deeper understanding of our problems. It has become quite clear during the last few decades that the factors in the aetiology of schizophrenia are less established than those in the efficacy of therapeutic intervention. The former are still highly theoretical scientific models whose tenability is often difficult to establish, while the latter can be tested more objectively through clinical trials. In this manner, the efficacy of neuroleptic therapy and of the various behavioural and psychosocial therapeutic interventions has been examined and some found to be wanting (e.g. renal dialysis). Nevertheless, the therapeutic clinical trials probably arose as a result of some aetiological considerations and for new therapeutic approaches we need to turn again to our aetiological models. However, the connection between aetiological models and therapeutic intervention has never been examined. As a result we have elaborate aetiology on the one hand and specific therapies on the other but the two pass each other by. The purpose of this paper is to weave the threads of practice into the web of theory.
The Logical and Psychometric Prerequisites for Cognitive Therapy of Schizophrenia
Authors: Spaulding Will , Garbin Calvin P. , Crinean W. Jeff
Published: August 2018

This discussion follows from a key premise that there is potential clinical value in identifying and directly treating the cognitive abnormalities which for over a century have been seen as the hallmarks of schizophrenia. This is both an old and a relatively new idea. It is old, in that the psychodynamic approaches to psychotherapy, especially ego psychology, have long sought to modify cognition in schizophrenia, if unsystematically and indirectly. It is new, in that only in the last decade have both the contemporary technologies of the information processing laboratory and of cognitive-behaviour modification been applied to the problem of treatment. The failures of psychodynamic treatment approaches with schizophrenic patients have perhaps discouraged widespread experimentation with cognitive models in clinical assessment and treatment. This is unfortunate, as contemporary clinical procedures and laboratory technologies are hardly comparable to psychodynamic methods. In the past decade findings have accumulated, in the form of case reports, single-subject experiments and treatment trials, which support the potential usefulness of assessing and directly treating schizophrenic patients' cognitive abnormalities (reviewed by Spaulding et al, 1986).
Treating Prodromal Episodes to Prevent Relapse in Schizophrenia
Authors: Herz Marvin I. , Glazer William , Mirza Mahmud , Mostert Marcelle , Hafez Hisham
Published: August 2018

Our current study compares intermittent medication with maintenance medication in the treatment of stable schizophrenic out-patients. According to the intermittent approach, known active medication is given only when the patient develops prodromal signs of relapse and until the patient restabilises. After restabilisation, medication is discontinued. The impetus for this work came as the result of our interest in finding ways to diminish the incidence of tardive dyskinesia. Many investigators believe that tardive dyskinesia is generally related to the amount of neuroleptic medication a patient has taken during his lifetime. Since it is routine for many aftercare clinics to maintain these patients indefinitely on antipsychotic medication, ways must be found to reduce the amount of medication taken by chronic schizophrenic patients. This paper will present the background ideas and preliminary studies which led to the present study and preliminary results of the present study.
III. Clinical Findings. Abnormalities of the Mental State and Movement Disorder and their Correlates
Authors: Johnstone Eve C. , Owens D. G. C. , Frith C. D. , Leary J.
Published: August 2018

Persisting positive symptoms largely unresponsive to treatment (Tuma & May, 1979; Macmillan et al, 1986; May et al, 1989) occur in about 7% of patients with schizophrenia but lesser degrees of treatment resistance are common (Hogarty, 1988; Johnstone, 1990) and problems of recurrence of positive symptoms and deterioration of negative symptoms are well known (Johnstone, 1990). Schizophrenic patients have also been found to have persisting non-psychotic symptoms, particularly depression (Cheadle et al, 1978). Disorders of movement in relation to schizophrenia and their treatment have been found to be disabling in a few patients and to cause lesser problems for many (Kane et al, 1985). The assessment of the mental state and of clinical evidence of movement disorder in the patients who form the subjects of the Harrow study was therefore clearly of interest, as it is rarely possible to examine these issues in a large, unselected sample.
Factors Involved in Delusion Formation
Authors: Brockington Ian
Published: August 2018

I write as one who has grappled with improving the classification of the psychoses, but I believe that the strategy of developing a set of descriptive concepts, and using such preliminary groupings to search for the primary causes of the ‘diseases‘ defined (genes, brain damage, social and psychological stressors, etc.) is insufficiently ambitious. Psychiatry has been too reductionist in its attitude to both the causes and the treatment of symptoms (such as delusions), placing the entire emphasis on investigating and treating the ‘underlying disease‘, not the delusional process itself. Internal medicine has often been able to unfold the whole disease process from primary causes and preconditions through disordered physiology to symptoms. In psychiatry it is also important to understand the pathogenesis of symptoms, that is, to specify the stages in the transposition of stress and cerebral pathology into the phenomena of mental illness.
Depression as a Consequence of Inadequate Neurochemical Adaptation in Response to Stressors
Authors: Anisman Hymie , Zacharko Robert M.
Published: August 2018

Stressors induce behavioural disturbances and neurochemical changes in animals, some of which are reminiscent of the symptoms and presumed neurochemical concomitants of depression in humans. Just as in humans, where considerable inter-individual variability is evident in the symptom profile of depression, there is marked inter-individual and inter-strain variability in the behavioural effects of stressors in animals. It is proposed that stressors induce adaptive neurochemical changes, failure of which may engender behavioural disturbances. Variability in the symptoms of depression and in the efficacy of its pharmacological treatment may reflect the biochemical heterogeneity of the illness. Inter-individual differences in vulnerability to stressor-provoked neurochemical changes may contribute to the behavioural profiles observed.
Neurochemical and Pharmacological Properties of Tianeptine, A Novel Antidepressant
Authors: Labrid C. , Mocaër E. , Kamoun A.
Published: August 2018

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.
Fluoxetine Efficacy vs Comparative Drugs: An Overview
Authors: Lader Malcolm
Published: August 2018

The tricyclic antidepressants (TCAs) were discovered accidentally by pharmaceutical chemists seeking first, better antihistamines and then antipsychotic agents. Careful clinical assessment revealed the antidepressant properties and suggested that the closer the patient resembled the classical textbook description of ‘endogenous’ depression, the more likely was an adequate clinical response to occur (Kuhn, 1958). However, it was quickly realised that the TCAs possess a plethora of side-effects, particularly sedation and symptoms related to their anticholinergic effects.

Despite much research over the past 25 years, it is unclear how TCAs effect clinical improvement. The two main neurotransmitters involved in some way are noradrenaline (Schildkraut, 1965) and 5-hydroxytryptamine (5-HT; serotonin; Van Praag, 1977). It was proposed that TCAs acted by blocking the reuptake of one or other or both of these neurotransmitters, thereby increasing their concentration in the synaptic cleft. However, as well as these acute effects, chronic effects, such as a decrease in the number of central beta-adrenoceptors (‘down-regulation’) occur, and these are probably more relevant to the clinical action.
Fluoxetine: Efficacy Against Placebo and by Dose-An Overview
Authors: Hall John
Published: August 2018

The most unequivocal demonstration of efficacy with putative or reference antidepressants is normally obtained from placebo-controlled studies; heavy reliance is therefore placed on such investigations, particularly in the early stages of development of any new therapeutic agent. However, many clinicians are understandably reluctant to allow some patients to be treated with placebo, which may lead to a sampling bias. It is equally understandable that doctors taking part in such studies are anxious about clinical deterioration or lack of response, and this in turn may result in a higher drop-out rate than would be seen in studies using reference antidepressants without a placebo treatment group. However, in spite of these and other drawbacks, it is still generally accepted that the efficacy of potential antidepressants is established in a more scientific and unequivocal way using placebo-controlled methodology. Fluoxetine has been the subject of a number of such investigations (Table I); their findings are reviewed in this paper.
The Genetics of Depression: Current Approaches
Authors: McGuffin P. , Katz R.
Published: August 2018

It is widely accepted that depression shows a tendency to run in families. This is partly due to genetic influences — and the subject has been covered in recent reviews. This article, therefore, does not aim to recapitulate the genetic evidence but rather aims to elucidate the mode of transmission, to achieve an understanding of relevant gene-environment co-actions and interactions, and to describe attempts to identify and localise major genes.
Suicide and Antidepressant Overdosage in General Practice
Authors: Beaumont G.
Published: August 2018

Depression is a very common condition, and most depressed patients in many countries are treated by their General Practitioners. It is a frequent cause of suicide – one of the major causes of death in young adults – and is the disorder most commonly associated with deliberate self-poisoning, a large percentage of suicides being due to poisoning with drugs that are only available on prescription. Self-poisoning with older tricyclic antidepressants (TCAs) poses major clinical management problems, since the majority of patients who overdose with these agents do not reach hospital alive. Though there is no convincing evidence that any one antidepressant is more effective than others or more rapid in onset of therapeutic action, antidepressants do differ substantially in their side-effect profiles and in their toxicity in overdosage, those introduced before 1970 being relatively more toxic. Since suicide rates have been reduced by limiting the availability of toxic substances such as barbiturates and harmful domestic gas, restricting the use of older antidepressants in favour of newer, safer compounds for depressed patients being treated in general practice would also seem to be advisable.
A Double-blind Comparative Trial of Moclobemide v. Imipramine and Placebo in Major Depressive Episodes
Authors: Versiani M. , Oggero U. , Alterwain P. , Capponi R. , Dajas F. , Heinze-Martin G. , Marquez C.A. , Poleo M.A. , Rivero-Almanzor L.E. , Rossel L. , Schmid-Burgk W. , Ucha-Udabe R.
Published: August 2018

Patients (n = 490) suffering from a major depressive episode according to DSM-III criteria were randomly allocated to groups receiving either moclobemide, imipramine, or placebo treatment. Subjects were treated as out-patients for 6 weeks. On overall assessment of efficacy and on results of the Hamilton Rating Scale for Depression, both moclobemide and imipramine were superior to placebo, but the differences between moclobemide and imipramine were not significant. Premature termination due to insufficient efficacy was more frequent with placebo than with moclobemide or with imipramine, these differences being significant. The overall assessment of tolerance clearly favoured placebo and moclobemide over imipramine. This was also reflected in the frequency of premature terminations due to poor tolerance, as well as in the frequency of adverse events, which were highest in the imipramine group. The only cardiovascular finding was an increase of the mean heart rate with imipramine, maximum at the end of week 1, while placebo and moclobemide displayed no relevant changes. There were no other important drug-related changes.
Home-oriented management programme for people with early psychosis
Authors: Fitzgerald Paul , Kulkarni Jayashri
Published: August 2018

Background The HOMES (Home-Oriented Management of Early Psychosis) programme is a new home-based management programme for people presenting for the firsttime with psychotic illnesses. The present paper aims to present preliminary data as to the efficacy of this programme and factors identified as being associated with successful prevention of hospital admission.

Method The programme applied to all the people presenting to the Dandenong Hospital Department of Psychiatry with first-episode psychosis who are considered suitable at first assessment for home-based management. A programme description is included in the paper. Prospective evaluation data on the first 31 people managed within the programme is presented.

Results Twenty-two out of 31 people were managed without the necessity for hospital admission. Illness severity was not related to the ability to manage this group of people outside of hospital. The level of social support and duration of untreated psychosis prior to treatment, may be most closely related to home-based treatment success.

Conclusions Home-based management of people with first-episode psychosis is feasible and offers a viable alternative to admission for this group. Home-based treatment is dependent on the degree of social support but is independent of the degree of illness severity.
Behavioural pharmacology of the new generation of antipsychotic agents
Authors: Moore N. A.
Published: August 2018

Antipsychotic agents have been the mainstay in the management of schizophrenia for a number of years. Their therapeutic efficacy is primarily attributed to dopamine receptor antagonism (Creese et al, 1976), leading to a reduction in the positive symptoms of schizophrenia such as paranoia and hallucinations. Unfortunately, they have little effect on the negative symptoms (such as flattened affect, poverty of speech, anhedonia and social withdrawal) or cognitive deficits. The blockade of central dopamine receptors by classical antipsychotic agents also leads to the development of both acute and chronic motor disturbances (extrapyramidal side-effects) (EPS) (Meltzer, 1992).
Cognitive effects of conventional and atypical antipsychotics in schizophrenia
Authors: Sharma Tonmoy
Published: August 2018

“Mental efficiency is always diminished to a considerable extent. The patients are distracted, inattentive, tired, dull, do not take pleasure in work, their mind wanders, they lose the connection, they ‘cannot keep the thought in mind‘…” (Kraepelin, 1898)

Cognitive dysfunction has long been recognised as a cardinal feature of schizophrenia, dating back to Kraepelin's description of dementia praecox (1919). Cognitive dysfunction in schizophrenia is seen early in the illness and is initially mild, increasing in severity in some chronic patients. It is recognised as a primary and pervasive deficit that is independent of positive symptoms in that it persists after resolution of acute symptoms. It is not restricted to a subgroup and is seen to a greater or lesser extent in almost all patients suffering from schizophrenia (Goldberg et al, 1990).
Positron Emission Tomography of in-vivo Binding Characteristics of Atypical Antipsychotic Drugs
Authors: Nyberg Svante , Nakashima Yoshifumi , Nordström Anna-Lena , Halldin Christer , Farde Lars
Published: August 2018

Several types of neuroreceptors are of interest with respect to antipsychotic activity, in particular the D2, D1, and 5-HT2 receptors. Among currently prescribed antipsychotic drugs, some have an affinity for a broad range of neuroreceptors, while others are more selective for the D2 receptor (Hytell et al, 1985). The most widely accepted hypothesis of neuroleptic drug action is that antipsychotic effects are mediated by a blockade of the dopamine receptors (Carlsson & Lindqvist, 1963; van Rossum, 1966; Creese et al, 1976; Seeman et al, 1976; Peroutka & Snyder, 1980). This hypothesis has been supported by consistent findings of high D2 receptor occupancy in positron emission tomography (PET) studies of patients treated with antipsychotic drugs (Farde et al, 1986; Smith et al, 1988; Baron et al, 1989). At the same time, the risk of extrapyramidal side-effects (EPS) seems particularly high in patients with occupancy above 80% (Farde et al, 1992) (Fig. 1).
Depression Comorbid with Anxiety: Results from the WHO Study on Psychological Disorders in Primary Health Care
Authors: Sartorius Nornam , Üstün T. Bedirhan , Lecrubier Yves , Wittchen Hans-Ulrich
Published: August 2018

The World Health Organization collaborative study on “Psychological Problems in General Health Care” investigated the form, frequency, course and outcome of common psychological problems in primary care settings at 15 international sites. The research employed a two-stage case-finding procedure. GHQ–12 was administered to 25 916 adults who consulted health-care services. The second-stage assessment (n=5438) consisted of the Composite International Diagnostic Interview (GDI), the Social Disability Schedule, and questionnaires. Possible cases or borderline cases of mental disorder, and a sample of known cases, were followed up at three months and one year. Using standard diagnostic algorithms (ICD–10), prevalence rates were calculated for current disorder (one-month) and lifetime experience disorder. Well-defined psychological problems are frequent in all the general health-care settings examined (median 24.0%). Among the most common were depression, anxiety, alcohol misuse, somatoform disorders, and neurasthenia. Nine per cent of patients suffered from a “subthreshold condition” that did not meet diagnostic criteria but had clinically significant symptoms and functional impairment. The most common co-occurrence was depression and anxiety. Comorbidity increases the likelihood of recognition of mental disorders in general health care, and the likelihood of receiving treatment.
Biological Determinants of Difficult to Treat Patients with Schizophrenia
Authors: Sharma Tonmoy , Kerwin Robert
Published: August 2018

Numerous studies have attempted to relate brain morphology to treatment outcome in schizophrenia in an attempt to define subtypes of schizophrenia that may respond well to antipsychotic treatment (Brown & Herz, 1989). This has potential clinical significance since, if we can predict outcome based on brain structure, it would then influence treatment.
The epidemiology of crime, violence and schizophrenia
Authors: Wessely Simon
Published: August 2018

The infamous Hungerford Massacre, the multiple murders committed by Michael Ryan in the Berkshire town of Hungerford on 19 August 1987, remain firmly in the public's imagination. It would have been difficult for anyone reviewing the newspapers of that and subsequent days not to conclude that Michael Ryan was mentally ill – headlines ranged from “Day of the Maniac” to “Matricide Points to Schizophrenia”. Because Ryan killed himself and thus there was no possibility of a court case, psychiatrists were free to comment about his mental state and psychiatric diagnosis.
Practical aspects of clinical risk assessment and management
Authors: Snowden Peter
Published: August 2018

It is debatable whether the notion of dangerousness now has any utilitarian value for psychiatry. The presence or absence of dangerousness is very much in the eye of the beholder. It is an all or nothing term – you either have it or you do not! While there is usually little disagreement about the few very violent individuals “who, for 24 hours a day, and in any situation, are likely to cause harm to others” (Chiswick, 1995), most patients are not in this category and “little bit dangerous” is unlikely to be of much comfort to clinical staff. It is unhelpful to deny that dangerousness is any more than an adjective which has been elevated into a pseudoscientific construct whose definitions (Scott, 1977; Walker, 1978; Home Office & DHSS, 1975) amount to little more than “past harm predicts future behaviour”.
Characterization of diabetic neuropathy progression in a mouse model of type 2 diabetes mellitus
Authors: De Gregorio Cristian , Contador David , Campero Mario , Ezquer Marcelo , Ezquer Fernando
Published: August 2018

Diabetes mellitus (DM) is one of most frequent chronic diseases with an increasing incidence in most countries. Diabetic neuropathy (DN) is one of the earliest and main complications of diabetic patients, which is characterized by progressive, distal-to-proximal degeneration of peripheral nerves. The cellular and molecular mechanisms that trigger DN are highly complex, heterogeneous and not completely known. Animal models have constituted a valuable tool for understanding diabetes pathophysiology; however, the temporal course of DN progression in animal models of type 2 diabetes (T2DM) is not completely understood.

In this work, we characterized the onset and progression of DN in BKS db/db mice, including the main functional and histological features observed in the human disease. We demonstrated that diabetic animals display a progressive sensory loss and electrophysiological impairments in early-to-mid phases of disease. Furthermore, we detected an early decrease in intraepidermal nerve fibers (IENF) density in 18-week-old diabetic mice, which is highly associated with sensory loss and constitutes a reliable marker of DN. Other common histological parameters of DN, like Schwann cells apoptosis and infiltration of CD3+ cells in the sciatic nerve, were altered in mid-to-late phases of disease.

Our results support the general consensus that DN evolves from initial functional to late structural changes. This work aimed to characterize the progression of DN in a reliable animal model sharing the main human disease features, which is necessary to assess new therapies for this complex disease. Finally, we also aimed to identify an effective temporal window where these potential treatments could be successfully applied.
Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition
Authors: Hu Bo , Gao Yuanyuan , Davies Lauren , Woo Stephanie , Topczewski Jacek , Jessen Jason R. , Lin Fang
Published: August 2018

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia. An endoderm transplantation assay showed that Gpc4 regulates endoderm migration in a non-cell-autonomous fashion. Further analyses revealed that the impaired endoderm migration in gpc4 mutants results from increases in the expression and assembly of fibronectin and laminin, major components of the extracellular matrix (ECM). Notably, we found that matrix metalloproteinase 14 (Mmp14a/b) is required for the control of ECM expression during endoderm migration, with Gpc4 acting through Mmp14a/b to limit ECM expression. Our results suggest that Gpc4 is crucial for generating the environment required for efficient migration of endodermal cells, uncovering a novel function of Gpc4 during development.
Arginine and the metabolic regulation of nitric oxide synthesis in cancer
Authors: Keshet Rom , Erez Ayelet
Published: August 2018

Nitric oxide (NO) is a signaling molecule that plays important roles in diverse biological processes and thus its dysregulation is involved in the pathogenesis of various disorders. In cancer, NO has broad and sometimes dichotomous roles; it is involved in cancer initiation and progression, but also restricts cancer proliferation and invasion, and contributes to the anti-tumor immune response. The importance of NO in a range of cellular processes is exemplified by its tight spatial and dosage control at multiple levels, including via its transcriptional, post-translational and metabolic regulation. In this Review, we focus on the regulation of NO via the synthesis and availability of its precursor, arginine, and discuss the implications of this metabolic regulation for cancer biology and therapy. Despite the established contribution of NO to cancer pathogenesis, the implementation of NO-related cancer therapeutics remains limited, likely due to the challenge of targeting and inducing its protective functions in a cell- and dosage-specific manner. A better understanding of how arginine regulates the production of NO in cancer might thus support the development of anti-cancer drugs that target this key metabolic pathway, and other metabolic pathways involved in NO production.
In vitro drusen model – three-dimensional spheroid culture of retinal pigment epithelial cells
Authors: Usui Hideaki , Nishiwaki Akiko , Landiev Lanors , Kacza Johannes , Eichler Wolfram , Wako Rina , Kato Aki , Takase Noriaki , Kuwayama Soichiro , Ohashi Kazuki , Yafai Yousef , Bringmann Andreas , Kubota Ayae , Ogura Yuichiro , Seeger Johannes , Wiedemann Peter , Yasukawa Tsutomu
Published: August 2018

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids of human RPE cells constructed a well-differentiated monolayer of RPE with a Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between the RPE and Bruch's membrane with expression of many drusen-associated proteins, such as amyloid β and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases, such as AMD.
Cleptocracia brasileira
Authors: Silva Marcos Fernandes Gonçalves da
Published: August 2018

A liberalização democrática brasileira não coincidiu com a eliminação da corrupção crônica. A proliferação de escândalos demonstra que a sociedade não é ainda capaz de controlar o fenômeno. Sob um regime democrático, a corrupção é inaceitável, porque os cidadãos elegem seus pares para representá-los, e não para trabalhar contra eles. Tornar a corrupção objeto de análise econômica pode contribuir para a compreensão e o combate ao fenômeno.
Razão insuficiente
Authors: Halfeld Mauro , Torres Fábio de Freitas Leitão
Published: August 2018

Desde o surgimento da psicanálise, sabe-se que o comportamento humano é largamente influenciado por emoções inconscientes. Por que então os adeptos da Teoria do Mercado Eficiente (TME) continuam a defender que o investidor é um ser perfeitamente racional? Há evidências da realidade do mercado de que essa hipótese é uma simplificação exagerada? Com a palavra, os estudiosos das Finanças Comportamentais.
Indigestão antropofágica
Authors: Caldas Miguel Pinto , Wood Junior Thomaz
Published: August 2018

A importação e o uso indiscriminado de tecnologia gerencial vinda de países desenvolvidos podem provocar efeitos colaterais indesejáveis, como a perda da visão estratégica ou a incontinência verbal. A solução é retomar os antigos rituais antropofágicos e mandar para o caldeirão as dezenas de gurus e curandeiros que invadiram a Terra Brasilis. Os que provarem seu valor poderão ser adotados.
Processo, que processo?
Authors: Gonçalves José Ernesto Lima
Published: August 2018

Muitas empresas querem organizar-se por processo, mas não têm uma noção clara dos passos a seguir. Há, ainda, aquelas que não têm certeza se a sua forma atual de organização é adequada para a gestão por processos. Todas precisam de mais esclarecimentos e informações sobre o assunto, para que possam analisar as vantagens da aplicação desta alternativa de arquitetura organizacional.
Mais evolução, menos revolução
Authors: Albertin Alberto Luiz , Moura Rosa Maria de
Published: August 2018

O comércio eletrônico, tanto no Brasil como no mundo, passou pela fase de euforia e, em seguida, pela fase de ceticismo exagerado. Atualmente, encontra-se em um momento de consolidação por meio do desenvolvimento dos processos que já eram realizados anteriormente em um ambiente com menor apoio da infra-estrutura de tecnologia de informação e comunicação pública.
A bolha e a tormenta
Authors: Fachada Pedro
Published: August 2018

O milênio começou com recessão, atentados terroristas espetaculares e escândalos corporativos, como as fraudes contábeis da Enron e da Worldcom. Nos EUA, a década de 1990 fora marcada pela escalada exagerada do preço das ações. A valorização do índice Nasdaq entre 1991 e 1999 alcançou quase 1000%. Desde o início de 2000 até setembro de 2002, porém, o mesmo índice amargou uma perda de mais de 71%. Com o estouro da bolha especulativa, o valor de mercado das empresas norte-americanas já encolheu US$ 7,6 trilhões. Qual é o impacto dessa reação aos excessos dos anos 1990?
Rota inexplorada
Authors: Cyrino Álvaro Bruno , Oliveira Junior Moacir de Miranda
Published: August 2018

A maior parte das grandes empresas brasileiras engatinha nos mercados globais. Mais de um quarto delas atua apenas no mercado interno; mais da metade compete em outros países apenas com exportações – fase que envolve menor comprometimento de recursos e está sujeita a menores riscos. O “custo Brasil” e o tamanho do mercado interno são apontados como as principais barreiras à internacionalização. Esses dados constam de uma pesquisa realizada com apoio da Fundação Dom Cabral, de Minas Gerais. A seguir, discutimos os resultados – por vezes surpreendentes – dessa investigação.
O conhecimento em ação
Authors: Salim Jean Jacques
Published: August 2018

A gestão do conhecimento é um campo em rápida evolução. Conceitos e teorias foram criados por autores identificados com várias especializações e já há notícias de vários projetos implementados com sucesso, no exterior e no Brasil. De fato, muitas empresas realizam uma infindável lista de atividades relacionadas à gestão do conhecimento. Suas iniciativas, porém, padecem de três defeitos: baixa sintonia entre as ações, pouca ou nenhuma vinculação com os objetivos estratégicos e ausência de controle de resultados. Falta-lhes um modelo geral para a gestão do conhecimento. É essa lacuna que procuramos preencher neste artigo.
Na areia movediça
Authors: Tonelli Maria José , Lacombe Beatriz Maria Braga
Published: August 2018

Muitos profissionais de Recursos Humanos podem estar fundamentando suas práticas em princípios pouco consistentes, porém repetidos à exaustão e passados adiante como verdades inquestionáveis. O resultado pode ser danoso para as empresas e seus profissionais. Uma maior aproximação entre o mundo empresarial e a academia pode proporcionar as reflexões necessárias para garantir abordagens mais confiáveis.
Educação permanente [entrevistado por Thomaz Wood Júnior]
Authors: Fleury Maria Tereza Leme , Mazzucca Francisco Sylvio de Oliveira
Published: August 2018

Maria Tereza Leme Fleury, diretora da Faculdade de Economia, Administração e Contabilidade, da Universidade de São Paulo (FEA-USP), e Francisco Sylvio de Oliveira Mazzucca, diretor da Escola de Administração de Empresas de São Paulo, da Fundação Getúlio Vargas (FGV-EAESP), estão à frente de duas das mais tradicionais e importantes escolas de negócios do Brasil. Nesta entrevista à RAE-executivo, falam sobre desafios, contradições e perspectivas do ensino de Administração para executivos.
Marketing etnográfico
Authors: Barbosa Lívia
Published: August 2018

A etnografia pode oferecer ao marketing um rico instrumental para o mapeamento do universo simbólico e das práticas de consumo. Sua eficiência será maior se utilizada segundo os pressupostos teóricos e metodológicos definidos pela antropologia, bastante diversos daqueles da pesquisa tradicional. Conduzida por pesquisadores sem formação adequada, a pesquisa de campo é desperdício de tempo, de dinheiro e de expectativas.
Evitando o colapso organizacional
Authors: Rego Arménio , Cunha Miguel Pina e
Published: August 2018

Assistimos, dia após dia, ao desaparecimento de empresas. O fato é corriqueiro, mas uma pergunta permanece, despertando nossa preocupação ou curiosidade: que fatores conduzem as empresas ao colapso? Entre as diversas razões, muitas podem ser tratadas, e algumas delas com medidas relativamente simples. Este artigo mostra ao leitor algumas dessas razões e propõe medidas de prevenção contra o declínio e o colapso.
Fábio Barbosa [entrevistado por Adriana Wilner]
Authors: Barbosa Fábio
Published: August 2018

O presidente do banco REAL ABN-AMRO, Fábio Barbosa, é uma figura de destaque no cenário empresarial brasileiro por suas posições abertas e arejadas. Com experiência em grandes empresas multinacionais, como Nestlé e Citibank, Fábio esteve à frente de grandes processos de mudança organizacional, como a aquisição e fusão do Banco Real. Nesta entrevista concedida à RAE-executivo, ele fala sobre produtividade, fusão de empresas e responsabilidade social.
Errar é humano
Authors: Barbosa Allan Claudius Queiroz
Published: August 2018

Nesta obra, Christian Morel – executivo de uma grande empresa automobilística francesa – dedica-se à compreensão do intrincado processo que leva à tomada de decisões absurdas: os erros radicais e persistentes cometidos pelas pessoas contra os objetivos que fixaram para si mesmas.
Corporações na vitrine
Authors: Reis Dayr , Peña Leticia , Betton John
Published: August 2018

Por muito tempo as empresas agiram como se não tivessem nenhuma outra responsabilidade além da produção de bens e serviços. Essa realidade mudou. Mais expostas ao ambiente, as empresas hoje interagem com diversos grupos sociais de interesse. Seu sucesso, e sua perenidade, agora depende da capacidade de entender as demandas explícitas e latentes desses grupos e prover respostas adequadas e alinhadas com sua própria estratégia.
Camargo Corrêa
Authors: Terzian Françoise
Published: August 2018

A gestão de projetos tornou-se um tema de extrema importância no mundo empresarial. Para fazer frente à crescente complexidade do mercado, aoaumento do nível de competição e à sofisticação dos clientes, a Camargo Corrêa desenvolveu um sistema próprio de gestão de empreendimentos,baseado no estado-da-arte do conhecimento sobre o tema. Entre os resultados colhidos, destacam-se a otimização e a uniformização dos processos de trabalho.
Cinco décadas de finanças [entrevistado por Pedro F. Bendassolli]
Authors: Eid Junior William , Tedeschi Piero
Published: August 2018

A área de Finanças experimentou, no Brasil, desenvolvimento importante. A partir de simples apêndice da Contabilidade, evoluiu com modelos próprios, os quais se caracterizam pelo rigor analítico e pelo suporte à tomada de decisão. Para falar desse processo, convidamos os professores William Eid Jr. e Piero Tedeschi, ambos da FGV-EAESP. Na entrevista, tratam ainda de como os profissionais financeiros podem contribuir para a geração de valor nas empresas em um momento de grande ênfase nos mercados de capitais.
Gestão à brasileira
Authors: Bertero Carlos Osmar
Published: August 2018

O Brasil possui uma maneira própria de administrar? Será a forma como conduzimos nossas organizações distinta daquela praticada em outros países? Este ensaio trata dessas questões e mostra que, apesar de termos alguns traços particulares, ainda não conseguimos desenvolver um modelo de gestão forte o bastante para nos diferenciar e levar nossas empresas a algum tipo de vantagem comparativa.
Como avaliar ação social
Authors: Rodrigues Maria Cecília Prates , Fleury Sonia
Published: August 2018

O tema da ação social corporativa passou a ocupar lugar de destaque no contexto da gestão de empresas. A ação social das empresas deixou de ser uma atividade isolada, baseada em interesses assistencias, para assumir uma posição de importância entre as demais questões estratégicas da organização. O desafio agora é avaliar o resultado que essas ações trazem tanto para o público atendido quanto para a própria organização.
Economia em comunidades
Authors: Diniz Eduardo Henrique , Wilner Adriana , Chistopoulos Tania P.
Published: August 2018

As comunidades de prática virtuais, grupos organizados que se comunicam a distância pela Internet com o objetivo de trocar informações, partilhar conhecimento e realizar tarefa comum, apresentam-se hoje como uma nova proposta de produção econômica. Nela, estruturas tradicionais, baseadas no modelo da empresa ou do mercado, são substituídas por um estilo de trabalho voluntário, flexível e pautado pela especialização por habilidades e competências. O artigo analisa a emergência desse novo modelo e discute suas principais vantagens.
Responsabilidade ampliada
Authors: Oliveira José Antonio Puppim de
Published: August 2018

Mudanças nos cenários político, econômico e social vêm ampliando o leque de responsabilidades das empresas. Hoje, cobra-se delas transparência em suas atividades e um comportamento exemplar com todos que com elas interagem, como funcionários, clientes, acionistas e comunidade. O artigo analisa o conceito de responsabilidade social empresarial, discutindo suas origens e sua evolução como tema de crescente interesse.
Ciclos e estratégia
Authors: Bertero Carlos Osmar
Published: August 2018

Ciclos econômicos são períodos caracterizados por crescimento ou recesso da economia de um país ao longo de um determinado período do tempo. Representam, para as empresas, oportunidades ou grandes ameaças. Por esse motivo, os empreendedores e gestores devem considerá-los no momento preciso em que forem elaborar ou revisar suas análises estratégicas. O artigo apresenta as influências desses ciclos sobre as diversas áreas estratégicas da empresa e destaca como esta pode lidar com a inflexibilidade das condições macroeconômicas por eles representadas.
Varejo multicanal
Authors: Porto Roseli Morena
Published: August 2018

Cresce o número de empresas brasileiras que disponibilizam vários canais para a comercialização de seus produtos e serviços. No varejo, apesar de a prática não ser recente, o uso do comércio eletrônico via Internet vem se apresentando como estratégia para as empresas ampliarem sua inserção no mercado. O artigo discute os desafios da gestão do varejo multicanal e aponta que, se de um lado, ele traz vantagens competitivas, de outro, representa um desafio para as empresas que o adotam.
Poder e gênero no século 21
Authors: Azevedo Márcia Carvalho de
Published: August 2018

Obra analisa mudanças etnográficas globais na família ao longo do século passado e ao redor do mundo. Em particular, acompanha criticamente as revoluções pelas quais passaram o patriarcado, o casamento e a fecundidade. Em perspectiva, analisa o novo papel social das mulheres.
Bancos federais
Authors: Mettenheim Kurt Eberhart , Lins Maria Antonieta Del Tedesco
Published: August 2018

Contrariamente à visão comum de que há uma mudança global em andamento para substituir a alocação governamental de recursos em favor dos mercados, a experiência brasileira sugere que os bancos públicos federais ainda desempenham um papel essencial no crescimento sustentável do país e no desafio de inclusão social. O artigo analisa as transformações pelas quais passaram esses bancos após a liberalização financeira do governo FHC e as reestruturasções recentes do setor financeiro.