bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current State of Immunotherapy for Alzheimer’s Disease
Authors: Relkin Norman R. 
Published: August 2016

There are currently over two dozen agents targeting β-amyloid (Aβ) in human clinical trials. More than a dozen of these are forms of anti-amyloid immunotherapy. Although other anti-amyloid interventions are further along in the development process, thus far only immunotherapy has provided post-mortem evidence that it can alter elements of the underlying pathology of Alzheimer’s disease (AD) in actual patients.In the past 30 years, there have been many attempts to develop treatments for AD. Early therapies were developed based on a limited understanding of the disease (Slide 1). Prior to the 1980s, a clear pathophysiologic mechanism for AD was not known; instead, symptomatic therapies targeted associated symptoms, such as agitation, insomnia, and psychosis. In the 1970s, several preclinical studies pointed toward synaptic transmission abnormalities, particularly neurochemical abnormalities, as the root cause of AD, and treatments with cholinesterase inhibitors grew out of that theory. Today, the cholinergic hypothesis has been largely discredited in the primary pathogenesis of AD. Another theory based on neurotransmitter abnormalities, the glutaminergic hypothesis, has also gone out of favor as a causal explanation for AD. This did not stop medications based on these mechanisms from finding a meaningful place in the clinical pharmacopeia for treatment of AD.In the 1990s, many clinical trials followed up on epidemiologic studies suggesting systemic causes of AD. These clinical trials focused on anti-inflammatories, hormone replacement, and antioxidants. The trials performed have largely failed, with the possible exception of the trials of vitamin E, an antioxidant. None of these agents have proven useful as disease-modifying therapies for symptomatic AD.
Food and Drug Administration Regulation
Authors: Katz Russell 
Published: August 2016

As disease-modifying therapies near realization, there are concerns about the criteria by which these therapies will be judged. It is not yet clear what kind of evidence (clinical, biomarker, or otherwise) will be required to support a disease-modifying claim. When such a drug is approved, regulators must be certain that the claims in the label are factual and unambiguous, yet a definition for “disease modification” remains to be established. One strong potential definition is: “a therapy that affects the underlying pathology and structure of the disease”. However, this is only one possibility, and a consensus definition must be codified before criteria to evaluate it can be determined.There is room for informed speculation, however. Criteria to evaluate disease-modifying effects have been proposed, and typically involve one of two approaches (neither of which has yet been endorsed by regulators). The first is a clinical approach, in which clinical designs are employed that would ideally force a conclusion that a drug has a disease-modifying effect. In one proposed design, patients would be randomized to drug or placebo for an appropriate duration. At the end of that period, and if a difference in outcome between drug and placebo on an appropriate clinical measure or measures has been achieved, patients originally randomized to drug would then be treated with placebo, while patients originally treated with placebo would remain on placebo.
Pharmacologic Treatments for Anxiety
Authors: Pollack Mark H. 
Published: August 2016

While the public health perspective prioritizes large populations of affected individuals, our job as clinicians is to help one patient at a time. Over the last 10–20 years, there has been marked improvement in pharmacologic and psychosocial interventions available for patients with anxiety disorders (Slide 8).The use of antidepressants, particularly the serotonergic and serotonergic noradrenergic agents, have received increased attention as first-line treatment for most of the anxiety disorders, including panic disorder, social phobia, posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Antidepressants are often used as first-line therapy for anxiety disorders because of their broad spectrum of efficacy against common comorbidities, especially depression, and because of concern about benzodiazepine-associated dependence, abuse liability, and lack of efficacy for depression and other comorbidities (Slide 9).These newer antidepressants have advantages over the older antidepressants, particularly the tricyclics and the monoamine oxidase inhibitors, in that they are generally better tolerated and more appropriate for use in potentially suicidal patients because they are less lethal in overdose. However, there are some side effects that may limit their use in some patients. In the case of the serotonergic antidepressants, many patients are hesitant to initiate or maintain treatment due to concerns about sexual dysfunction.
Improving the Recognition of Anxiety Disorders in Depressed Patients
Authors: Chelminski Iwona 
Published: August 2016

There is considerable symptom overlap and high levels of comorbidity between anxiety disorders and depression. The recognition of this comorbidity has both academic interest and clinical significance. Epidemiological studies have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from the depression. These individuals also tend to have a more chronic course of depression, as observed in psychiatric patients, primary care patients, and epidemiological samples. Van Valkenberg and colleagues reported that depressed patients with anxiety had poorer outcome and greater psychosocial impairment than those without an anxiety disorder. In the National Institute of Mental Health Collaborative Depression Study, the presence of panic attacks predicted a lower rate of recovery during the first 2 years of the follow-up interval. Similarly, Grunhaus found poorer outcome in depressed patients with comorbid panic disorder than in depressed patients without panic. In an 8-month follow-up study, depressed primary care patients with a history of generalized anxiety disorder (GAD) or panic disorder were less likely to have recovered from their depressive episode.Gaynes and colleagues prospectively followed primary care patients with major depressive disorder (MDD) every 3 months for 1 year after their initial diagnostic evaluation. At baseline, half of the original 85 patients had a coexisting anxiety disorder, the most frequent being social phobia (n=38). Twelve months after intake, 68 of the patients were available for the final interview. Those with a comorbid anxiety disorder were significantly more likely to still be in an episode of depression (82% vs 57%; risk ratio=1.44; 95% CI 1.02-2.04), and they experienced more disability days during the course of the 12 months than the depressed patients without an anxiety disorder (67.1 days vs 27.5 days).
Cooling Core Body Temperature May Slow Down Neurodegeneration
Authors: Salerian Alen J. , Saleri Nansen G. 
Published: August 2016

ABSTRACTReduction of core body temperature has been proposed to contribute to the increased lifespan and the anti-aging effects conferred by caloric restriction in mice and higher primates. Cooler biologically compatible core body temperatures have also been hypothesized to combat neurodegenerative disorders. Yet, validation of these hypotheses has been difficult until recently, when it demonstrated that transgenic mice engineered to have chronic low core body temperature have longer lifespan independent of alteration in diet or caloric restriction. This article reviews the literature and highlights the potential influence of core body temperature's governing role on aging and in the pathophysiology of neurodegenerative disorders in humans. What makes recent findings more significant for humans is the existence of several methods to lower and maintain low core body temperatures in human subjects. The therapeutic potential of “cooler people” may also raise the possibility that this could reverse the adverse-health consequences of elevations in core body temperature.
Gender-related Differences in Individuals Seeking Treatment for Kleptomania
Authors: Grant Jon E. , Potenza Marc N. 
Published: August 2016

ABSTRACTObjective: Understanding variations in disease presentation in men and women is clinically important as differences may reflect biological and sociocultural factors and have implications for prevention and treatment strategies. Few empirical investigations have been performed in kleptomania, particularly with respect to gender-related influences.Methods: From 2001–2007, 95 adult subjects (n = 27 [28.4%] males) withDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined kleptomania were assessed on sociodemographics and clinical characteristics, including symptom severity, comorbidity, and functional impairment, to identify gender-related differences.Results: Men and women showed substantial symptom severity and functional impairment. Compared with affected men, women with kleptomania were more likely to be married (47.1% vs 25.9%;P= .039), have a later age at shoplifting onset (20.9 vs 14 years of age;P= .001), steal household items (P<.001), hoard stolen items (P=.020), and have an eating disorder (P= .017) and less likely to steal electronic goods (P< .001) and have another impulse-control disorder (P= .018).Conclusion: Kleptomania is similarly associated with significant impairment in women and men. Gender-related differences in clinical features and co-occurring disorders suggest that prevention and treatment strategies incorporate gender considerations.
Single-Isomer Science: The Phenomenon and Its Terminology
Authors: Gal Joseph 
Published: August 2016

ABSTRACTSingle-isomer drugs are of great importance in modern therapeutics. In this article, the basics of the underlying phenomenon are explained. Some molecules are chiral, ie, their mirror image is not superposable on the original. The most common element producing molecular chirality is a chiral center, typically a carbon atom carrying four different groups. The mirror-image molecules are termed enantiomers, but the less specific terms stereoisomers and isomers are also used. A substance consisting of only one of the two enantiomers is a single enantiomer or single isomer, and the 1:1 mixture of the enantiomers is the racemic mixture or racemate. A graphical convention that conveys the three-dimensional aspects of chiral molecules drawn in two dimensions, as well as two nongraphical conventions, based on optical rotation and configuration, are used to identify enantiomers. Optical rotation is a physical property of single enantiomers and involves rotation of the plane of plane-polarized light, each pure enantiomer rotating with equal magnitude but in the opposite direction (dextro and levo). Configuration is the actual arrangement in space of the atoms of chiral molecules. Two systems of indicating configuration are in use. One employs D and L to denote the respective enantiomers, and is applicable only to α-amino acids and carbohydrates. The other is a universal system using R and S as descriptors for the two possible arrangements, respectively, of the atoms around the chiral center. Interest in chiral drugs stems from the frequently observed biological differences between enantiomers. Such enantioselectivity is the result of different interactions of the drug enantiomers with target receptors that are themselves chiral and single-enantiomeric.
Factors that Enhance Treatment Outcome of Cognitive-Behavioral Therapy for Anxiety Disorders
Authors: Foa Edna B. , Cahill Shawn P. , Pontoski Kristin 
Published: August 2016

ABSTRACTEffective cognitive-behavioral therapy (CBT) programs have been developed for aU of the anxiety disorders. Common elements ofCBTfor these disorders include exposure to feared objects, situations, activities, thoughts, memories, and sensations; cognitive restructuring of dysfunctional beliefs; and training in anxiety management skills, such as controlled breathing and relaxation. This article describesCBTprocedures for anxiety disorders and summarizes the research documenting its efficacy. Next, the article discusses the factors that influence the efficacy of these treatment program. Finally, emotional-processing theory is discussed to explain the efficacy of CBT for anxiety and how this theory can assist in selecting optimal treatment brocedures.
Valutazione del carico familiare in un campione di parenti di pazienti con diagnosi di schizofrenia paranoide: risultati preliminari
Authors: Veltro Franco , Magliano Lorenza , Lobrace Silvana , Morosini Pierluigi , Maj Mario 
Published: August 2016

SummaryObjective - assessment of the burden perceived by a sample of key-relatives of schizophrenic patients. Design - Observational study of key-relatives of patients with a PSE-CATEGO diagnosis of active paranoid schizophrenia. Assessment of possible correlations between the family burden, the patients' symptoms and disabilities, as well as the relatives attitude of overinvolvement and criticism. Setting - Inpatient and outpatient psychiatric units of the Department of Psychiatry of the First Medical School, University of Naples. Subjects - 25 patients, with a diagnosis of active paranoid schizophrenia, according to ICD-9 diagnostic criteria, minimun illness history 1 year, at least one previous admission, living with at least one adult relative. Main outcome measures - Standardized assessment of patients clinical status and social disability and of relatives clinical status attitude and perceived burden. Results - The burden, both objective and subjective, was found to be present to a marked or very marked degree in more than 50% of the inteviewed relatives. A marked effect of the patients illness was observed especially on relatives social contacts and leisure activities. Also the attitudes of criticism and overinvolvement were detected in the great majority of the relatives. 52% of the relatives, when assessed by the PSE-9, received a psychiatric diagnosis. The objective burden was found to be associated with some «negative» symptoms and deficits of social functioning in the patients. Finally, significant correlations were observed between the objective and subjective dimensions of the burden and the relatives attitudes of hypercriticism toward the patients. Conclusions - The present study seems to be relevant both from the epidemiological point of view and for psychiatric care planning.
Il progetto dell'Istituto ≪Mario Negri≫: salute mentale in America Latina
Authors: Saraceno Benedetto 
Published: August 2016

SummaryObjective - To describe the cooperation in mental health that, since ten years, the Institute for Pharmacological Research ≪Mario Negri≫, Milan, is carrying out in Latin America. The project has developed along three main lines: the training of the mental health services personnel, the promotion of an epidemiological approach to the mental health care, and the assistance to the local health authorities in the field of mental health policy. Results - The most relevant goals of the project have been the Caracas Conference on the Latin American psychiatric hospitals and the constitution of an European Consortium for the technical cooperation with Latin America in mental health. Most of the activities have been done in cooperation with WHO regional office (Organización Panamericana de la Salud). Furthemore the paper outlines the main results of two epidemiologic studies carried out in Central America. Conclusions - The psychiatric hospitals phasing out, the setting up of mental health community-based services and the close cooperation between psychiatric services and primary health care services are the main objectives of a project of cooperation in mental health; training and epidemiological research must be the methodological tools of this type of cooperation.
La mortalità e le cause di morte fra i pazienti psichiatrici
Authors: Aguglia Eugenio , Pagnanelli Roberto , Clocchiatti Marco , de Vanna Maurizio 
Published: August 2016

SummaryObjective - Gathering, comparing and, if possible, commenting on datas and experimental evidences which have emerged in the principal literary works about mortality and psychiatric patients' causes of death. Particularly finding an answer (and a possible explanation) to some of the most important questions about these matters: does a psychiatric patient die easier than a healthy man? Does a correlation exist between nosographic diagnosis and causes of death? Finally do factors of risk, which are connected with death, exist? Method - The principal bibliographies which exist in national and international literature, from the middle of the last century until present days, have been consulted. Results - Essential agreement among existing dates in literature have emerged. Psychiatric patients dies easier than healthy man: rates of mortality have fallen from 6-7 (SMR), value of the middle of 1800 to 1,5-3 which is the value of present days. Respiratory, cardiovascular and, still, infectious diseases are the most important causes of death. There is not agreement about deaths caused by cancer. Some researchers affirm the protective action of psychiatric disease against the rising and diffusion of cancer. Non natural deaths (in primis suicide and accidental deaths) are rapresented too. All diagnostic categories (from alcholism to homosexuality, from organic brain disorders to schizophrenia) have a high risk of death while affective disorders have to be studied further. Young people have the highest risk. Conclusions - The frequency of physical beside psychic disease suggests to pay more attention to patient's general conditions even by some diagnostic ascertainments (TAC, RMN, etc) which are able to identify the most disabling conditions for the prognosis (diabetes, arterial hypertension, organic cerebral syndromes, etc).
Causes and psychosocial consequences of schizophrenia: the opinions of Mental Health services' staff
Authors: Magliano Lorenza , de Rosa Corrado , Guarneri Manuela , Cozzolino Pasquale , Malangone Claudio , Marasco Cecilia , Fiorillo Andrea , Maj Mario ,   Gruppo di Lavoro
Published: August 2016

SummaryObjective– Description of the opinions about causes and psychosocial consequences of schizophrenia in a sample of psychiatric professionals, recruited in 29 Italian Mental Health Centres (MHC).Design– Each professional was asked to read a case-vignette describing a patient who met the ICD-10 criteria for schizophrenia. Referring to case-vignette, he/she was asked to fill the Questionnaire on the Opinions about Mental Illness – Professionals' version (QO-P). Professionals' opinions were explored in relation to: a) their socio-demographic variables and professional background; b) geographic location of the MHC.Setting– 29 MHC stratified by geographic area (Northern, Central, Southern Italy) and population density of their catchment areas (> 100000 inhabitants; between 100000 and 25000 inhabitants; < 25000 inhabitants) and randomly selected.Results– Data on 465 professionals were collected. 75% of the sample identified in the vignette a case of schizophrenia, 22% of depression/anxiety disorder. Factors most frequently mentioned as causes of the detected disorder were heredity (68%), stress (61%), family difficulties (46%). More pessimistic opinions about psychosocial consequences of schizophrenia were found among nurses and among professionals of Southern Italy, among those with lower educational level, older age and among those working longer in psychiatry. No statistical difference in the opinions about psychosocial consequences of schizophrenia was found among staff who referred the case-vignette to schizophrenia and those who did not.Conclusions– The results of this study outline the need to: a) include issues such as disability and psychosocial consequences of mental disorders in the basic training of professionals; b) increase the number of professionals trained in evidence-based psychosocial interventions.
Disability in schizophrenia. Intrinsic factors and prediction of psychosocial outcome. An analysis of literature
Authors: Carpiniello Bernardo , Carta Mauro G. 
Published: August 2016

SummaryObjective– Many different factors, both related to the individual and illness (“intrinsic” factors) and to the environment (“extrinsic” factors), contribute in different ways to the development of disability. Basing on data of literature, this review focuses the main “intrinsic” factors predicting disability in schizophrenia.Method– A systematic search on Mediline of all papers published during the period 1965-2001 was performed, using “schizophrenia”, “outcome”, “psychosocial outcome”, “social disability” and “social adjustment” as key words. Only papers reporting specifically data about predictive factors and psychosocial outcome variables were considered; prospective follow-up studies were considered, but retrospective and cross-sectional studies were also taken into account when data deriving from prospective studies were inconsistent.Results– Male sex predicts a higher disability among demographic factors; lower social and occupational adjustment are premorbid personality factors associated with higher disability; among factors related to illness, younger age at onset of illess, “nuclear”, “non paranoid” and in particular “deficit” forms of schizophrenia seem to predict more disability. The latter seems to be predicted also by higher levels of negative symptoms and neuropsychological deficits ; the role of depressive symptoms seems to be less supported by follow-up data; a continuous course of the illness predicts more disability, although some evidences show a progressive reduction of disability, at least in the long term.Conclusions– Disability shows a largely autonomous course respect to symptoms and has to be considered an independent parameter of outcome. Few intrinsic factors show a predictive role also in the long term.