bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dysfunction in Patients with Epilepsy: Communication Strategies and Assessment Tools
Authors: Fishman Olga , Ettinger Alan B.
Published: August 2016

Sexual dysfunction is common among patients with epilepsy, but many clinicians do not include inquiries about this aspect of the patient's health in their routine evaluations. This article presents approaches for taking a sexual history and for discussing sexual problems. The utility of standardized sexual dysfunction questionnaires is reviewed and the important elements of appropriate and effective counseling are highlighted.
Psychophysical and Neurochemical Abnormalities of Pain Processing in Fibromyalgia
Authors: Staud Roland , Spaeth Michael
Published: August 2016

Fibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.
Fibromyalgia Syndrome: Approach to Management
Authors: Russell I. Jon
Published: August 2016

The management of fibromyalgia syndrome (FMS) has traditionally been multimodal and multidisciplinary, including education, physical modalities, and medication. In this article, an acronym is offered to help the clinician remember the important components of management. An improved understanding of the pathogenesis of FMS has allowed substantial refinements in its treatment. This is particularly true for medications that target specific symptom domains, allowing individualization of therapy. Since all FMS patients experience pain, there has been emphasis on that domain although medications are now available to address two or more domains with monotherapy. In addition, a logical basis is provided to help the clinician design strategic polypharmacy.
Obsessive-Compulsive Disorder Spectrum as a Scientific “Metaphor”
Authors: Pallanti Stefano , Hollander Eric
Published: August 2016

As a result of clinical, epidemiological, neuroimaging, and therapy studies that took place in the late 1980s, obsessive-compulsive disorder (OCD) has been well-characterized in the field of anxiety disorders. Other disorders attracted attention for their similarities to OCD, and were located in the orbit of the disorder. OCD has become known as the “primary domain” of a scientific “metaphor” comprising the putative cluster of OCD-related disorders (OCRDs). It is a “paradigm” with which to explore basal ganglia dysfunction. The OCRDs share common phenomenology, comorbidities, lifetime course, demographics, possible genetics, and frontostriatal dysfunction (particularly caudate hyperactivity.) The adoption of this metaphor analogy has proven useful. However, 15 years since its emergence, the spectrum of obsessive-compulsive disorders remains controversial. Questions under debate include whether OCD is a unitary or split condition, whether it is an anxiety disorder, and whether there exists only one spectrum or several possible spectrums. Further work is needed to clarify obsessive-compulsive symptoms, subtypes, and endophenotypes. There is need to integrate existing databases, better define associated symptom domains, and create a more comprehensive endophenotyping protocol for OCRDs. There is also a need to integrate biological and psychological perspectives, concepts, and data to drive this evolution. By increasing research in this field, the OCD spectrum may evolve from a fragmented level of conceptualization as a “metaphor” to one that is more comprehensive and structured.
Psychobiology of Anxiety Disorders and Obsessive-Compulsive Spectrum Disorders
Authors: Stein Dan J.
Published: August 2016

Obsessive-compulsive disorder is currently classified as an anxiety disorder. However, there is growing interest in the concept of an obsessive-compulsive spectrum of disorders (OCSDs). The relationship between anxiety disorders and OCSDs has been questioned. The psychobiology of anxiety disorders and OCSDs is briefly reviewed in this article. While there appear to be several distinct contrasts in the underlying psychobiology of these conditions, there is also evidence of overlapping mechanisms. In addition, there are crucial gaps in our current database, confounding nosological decision-making. Conceptualizing various anxiety disorders and putative OCSDs as lying within a broader spectrum of emotional disorders may be useful. However, clinicians must also recognize that individual anxiety and obsessive-compulsive spectrum conditions, including disorders characterized by body-focused repetitive behaviors, have distinct psychobiological underpinnings and require different treatment approaches.
Subclinical Obsessive-Compulsive Disorder in Children and Adolescents: Additional Results From a “High-Risk” Study
Authors: Black Donald W. , Gaffney Gary R.
Published: August 2016

Introduction: The concept of subclinical obsessive-compulsive disorder is explored using data from a “high-risk” study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment.

Methods: Adults with OCD and their offspring 7–18 years of age were recruited through a tertiary care center psychiatric outpatient clinic, while controls (and their children) were recruited via advertisement. Parents and offspring were assessed using structured interviews and validated questionnaires at baseline and follow-up interviews.

Results: Offspring from both proband groups were pooled to create three subject groups: group 1, offspring with neither condition (n=43); group 2, offspring with subclinical OCD (n=24); and group 3, offspring with full OCD (n=11). Offspring with subclinical OCD held the middle ground for most comparisons. They were more symptomatic than offspring without either condition (group 1), but less symptomatic than subjects with OCD (group 3). Across the board, comparisons of diagnoses, Child Behavior Checklist (CBCL) results; Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey results; and Leyton Obsessional Inventory (LOI) results were associated with subject group at baseline and follow-up. In post-hoc comparisons, subjects with subclinical OCD had fewer comorbid anxiety disorders and lower CBCL internalizing scale scores at follow-up. Parents of children with OCD had higher LOI symptom and severity scores than parents in those of groups 1 or 2.

Conclusion: The findings suggest that subclinical OCD holds the middle ground between full-blown OCD and having neither condition in terms of obsessive-compulsive symptoms and severity, tics, associated mood/anxiety disorders, and general functioning. At least in persons at risk for OCD, the presence of subclinical OCD may herald the onset of OCD, though in others may be an independent condition that does not lead to full OCD.
Computerized Neuropsychological Assessments
Authors: Woo Ellen
Published: August 2016

Computer-based measures to evaluate cognition have been used with growing frequency in recent years. These batteries are shown to be useful for identifying mild cognitive impairment (MCI) and dementia. There are few requirements to administer these tests. All that is typically needed is a computer, a response pad for patients to input their answers, and an examiner. In many cases, the examiner does not need to be a trained neuropsychologist. These computer-based assessments should yield a score report detailing the patient’s cognitive profile.

An important advantage of computerized assessments over standard paper-and-pencil testing is that they can provide precise measurement at the millisecond level. This can be a more sensitive measure of cognitive impairment, especially in high-functioning older adults and in patients with milder levels of cognitive deficit. Computer tests also have a shorter assessment time. Many batteries take <1 hour to administer, whereas many standard neuropsychological batteries require >4 hours to complete. The presentation of items in some batteries can be adapted to patients’ performance levels to avoid floor effects (the test restricts how low a patients’ scores can be) and ceiling effects (the test restricts how high scores can be). Computer tests have increased standardization; they are administered the same way every time. Scoring is automatic, meaning the results are available immediately and human scoring error is reduced. Examiner effects are reduced, which is an important advantage because clinicians may differ in how they administer standard tests, which may impact patients’ responses. In addition, the batteries are easily transported, and multiple tasks can be made available on a single computer.
Cerebrospinal Fluid: When Is It Worthwhile to Do a Lumbar Puncture?
Authors: Peskind Elaine R.
Published: August 2016

Clinicians should have an understanding of a lumbar puncture is indicated in the differential diagnosis of dementia and delirium. In most cases, this procedure is not commonly performed in outpatient practice for the differential diagnosis of dementia. However, in patients who have acute or subacute onset or a very rapid decline—such as in suspected Creutzfeldt-Jakob disease (CJD)—cerebrospinal fluid (CSF) 14-3-3, and tau proteins can be diagnostic for at least sporadic CJD. Practice parameters from the American Academy of Neurology (AAN) suggest performing a spinal tap on patients ≤55 years of age. However, that recommendation may not always be beneficial, particularly in a patient who has a prominent family history of either Alzheimer’s disease (AD) or frontotemporal dementia. Per the AAN practice parameter, lumbar puncture for CSF analysis is indicated in the diagnosis of central nervous system (CNS) infection, carcinomatous meningitis, or CNS vasculitis.

Beyond the clinically indicated lumbar puncture, there is utility of CSF biomarkers, including CSF Aβ42, total tau, and phospho-tau, which are the best studied. These biomarkers may be useful for cases involving atypical presentations of dementia, eg, when it is difficult to determine if the patient has AD versus frontotemporal dementia. They may be most useful for cases in which there is an atypical presentation of the fluorodeoxyglucose PET image or PET image features of both AD and frontotemporal dementia.
Beyond Standard Anti-Dementia Therapies: Diet, Exercise, Socialization, and Supplements
Authors: Small Gary W.
Published: August 2016

Several lines of evidence point to lifestyle choices that may improve brain health. Genetic factors are important to the process of aging, especially as it relates to vulnerability to Alzheimer’s disease (AD), but non-genetic factors clearly have a role as well. This paper highlights studies suggesting that diet, exercise, socialization, and supplements may protect the brain from age-related decline.

Observational evidence has indicated that several dietary practices can help maintain the health of one’s brain. The first such practice is to moderate one’s caloric intake. Illnesses related to obesity, such as diabetes, hypertension, and high cholesterol, are associated with poorer brain health. The second is to increase one’s intake of antioxidant foods, such as fresh fruits, and vegetables. The third is to increase intake of foods rich in omega-3 fatty acids, such as fish and olive oil. These fats in the diet may be associated with lower risk of dementia. Finally, consuming low glycemic-index carbohydrates instead of high glycemic-index carbohydrates, which spike blood sugar levels and are associated with higher risk of type 2 diabetes, may benefit the brain.

Many studies have been conducted on the connection between a lower risk for AD and healthy diet. While there are not much data from randomized-controlled trials, epidemiologic studies support the theory that diet can have an impact on vulnerability to AD.
Non-Amyloid Approaches to Neuroprotection
Authors: Sano Mary
Published: August 2016

The introduction of the amyloid hypothesis, which identifies amyloid as the primary target for treating Alzheimer’s disease (AD), was a watershed in the field of AD research. Treatment approaches have since focused on how amyloid might be manipulated. In fact, there are challenges to amyloid manipulation. First, removal of amyloid has shown minimal clinical effects. Second, some data indicate that secretase modulation shows hints of stimulating feedback systems, which cause concern over how to effectively manipulate amyloid. Third, side-effect profiles of the direct manipulation of amyloid are not currently optimal. Finally, evidence suggests that cell and synapse loss may be better markers of dementia and its severity. Alternative approaches to direct manipulation of amyloid include antioxidant mechanisms for prevention, anti-inflammatory mechanisms for neuroprotection, manipulation of metabolic risks, modification of tau accumulation, and neuroregeneration.

These alternative mechanisms of action provide support for a wide range of potential agents for clinical trials. The exact connection between mechanism of action and clinical outcomes is not well defined, but typically trial designs using these mechanisms attempt to measure affects on disease progression, often with longer studies that include established clinical outcomes accompanied by putative biomarkers of disease. One trend that has provided much information has been to examine the effects of these drugs in subjects at risk for AD, thereby expanding the intervention to prevention of disease. These studies include both secondary prevention studies, for example deferring onset in those with prodromal disease such as mild cognitive impairment (MCI), and primary prevention directed at those with no specific signs or symptoms.
Resilience and Anxiety
Authors: Davidson Jonathan R. T.
Published: August 2016

While resilience has been overlooked in the therapeutics area, it has been well-documented in the literature. Since at least the 1970s, there has been an extensive literature published on child resilience including the longitudinal follow up studies of children from the Hawaiian island of Kawaii.

The Anxiety and Traumatic Stress Program at Duke University Medical Center in Durham, North Carolina, became interested in resiliency as a slightly serendipitous observation during the course of a trial studying fluoxetine and placebo in people with PTSD. A measure evaluating how upset a person had been in the last week by life stresses, showed that fluoxetine was very effective in helping people cope with daily stresses (Slide 13).

The simple definition of resilience is the ability to bounce back from adversity. However, the literature cites a number of other aspects to resilience (Slide 14). Kobasa, a psychologist who has worked extensively in the area of resilience, tends to see it as similar to hardiness, in which there are certain components that are very salient. The first component is the view of stress, or difficulty, as a challenge. Second, is to have a sustained commitment to overcome whatever is necessary. Third, is the ability to possess internal control while being able to accept things one does not have complete control over.

The importance of having support from other people has been emphasized by Rutter. He theorized that one has the capacity to have close and secure attachments and a good sense of self-efficacy. He also notes the strengthening effects of stress. In children who cope well with difficulties, it is useful to tap into previous successes in order to harness some confidence from prior success. An action-oriented approach to problems, called active coping, can be useful.
Integrating Neurobiology and Psychopathology into Evidence-Based Treatment of Social Anxiety Disorder
Authors: Liebowitz Michael R. , Ninan Philip T. , Schneier Franklin R. , Blanco Carlos , Ginsberg David L. , Hollander Eric
Published: August 2016

Social anxiety disorder (SAD) is a common, chronic psychiatric disorder characterized by a persistent fear of social or performance situations in which embarrassment can occur. This disorder typically appears during the mid-adolescent years and is unremitting throughout life if not properly treated. SAD presents as two subtypes: the more common and debilitating generalized form, and the nongeneralized form, which consists predominantly of performance anxiety. The majority of patients with SAD have comorbid mental disorders, including mood, anxiety, and substance abuse. No single development theory has been proposed to account for the origins of SAD, although current understanding of the etiology of SAD posits an interaction between psychological and biological factors. Risk factors include environmental and parenting influences and dysfunctional cognitive and conditioning events in early childhood. The neurobiology of SAD appears to involve neurochemical dysfunction, as evidenced by studies of neuroreceptor imaging, neuroendocrine function, and profiles of response to specific medications. Clinical trials have demonstrated that benzodiazepines and antidepressants are effective in the treatment of SAD. The selective serotonin reuptake inhibitors are emerging as the first-line treatment for SAD, based on their proven safety, tolerability, and efficacy. Goals for ongoing future research include development of approaches to achieve remission, to convert nonresponders and partial responders to full responders, and to prevent relapse and maintain long-term efficacy.

This monograph explores the epidemiology, clinical presentation, and differential diagnosis of SAD, with a focus on neural circuitry of social relationships and neurochemical dysfunction. The prevalence, rates of recognition and treatment, patterns of comorbidity, quality-of-life issues, and natural history of SAD are discussed as well as pharmacologic and psychosocial treatment strategies for SAD.
Recognition and Treatment of Depression With or Without Comorbid Anxiety Disorders
Authors: Zimmerman Mark , Chelminski Iwona , Zisook Sidney , Ginsberg David L.
Published: August 2016

Anxiety disorders are common in depressed patients. Several studies of the full range of Diagnostic and Statistical Manual of Mental

Disorders-defined anxiety disorders in depressed psychiatric outpatients each found that when diagnoses are based on semi-structured diagnostic interviews >40% of the patients had a comorbid anxiety disorder. The recognition of comorbidity is not simply of academic interest, but it has important clinical significance. Epidemiological studies, such as the National Comorbidity Study, 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. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients, primary care patients, and epidemiological samples. Recent research has suggested that clinicians underrecognize anxiety disorder comorbidity in depressed patients. The clinical significance of this underrecognition is highlighted by the finding that patients often want treatment to address their anxiety disorder comorbidity. When anxiety disorders are detected they often influence clinicians' selection of antidepressant medication, though some of clinicians' prescribing biases are not supported by empirical data.

In this monograph, Iwona Chelminski, PhD, reviews the significance of anxiety in patients with depression as well as diagnostic instruments for recognizing this comorbidity. Next, Mark Zimmerman, MD, addresses the factors that affect the clinician's choice of antidepressant, focusing on the influence of comorbid anxiety. Finally, Sidney Zisook, MD, discusses the differential efficacy of antidepressants as well as the role of psychotherapy in patients with comorbid anxiety and depression.
Treating Depression with SNRIs: Who Will Benefit Most?
Authors: Isaac Michael T.
Published: August 2016

There is evidence that the serotonin norepinephrine reuptake inhibitors (SNRIs) venlafaxine, milnacipran, and duloxetine, have probable superior antidepressant activity to most selective serotonin reuptake inhibitors (SSRIs), especially in more severe depression. Some patients, however, respond better than others to SNRIs. Several factors influencing response to milnacipran have been recently studied. The presence of certain polymorphisms related to noradrenergic neurotransmission has been shown to be related to different degrees or rapidity of response to milnacipran. In addition, patients with low pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol have a better response to milnacipran. These recent genomic and neurochemical data confirm that milnacipran, in contrast to SSRIs and venlafaxine, has an impact on the noradrenergic system. Differences in metabolism determined by genetic variables in cytochrome P450 (CYP) 2D6 activity are a major determinant of venlafaxine levels to such an extent that genetically determined decreases in CYP 2D6 activity have been associated increased adverse effects. Milnacipran, which is not metabolized by the enzymes of the CYP system is not influenced by polymorphism of these enzymes. These preliminary data suggest that a patient's biochemical and pharmacogenetic characteristics may be useful in the future to help clinicians chose the most  effective antidepressant medication.
Tolerability of Serotonin Norepinephrine Reuptake Inhibitor Antidepressants
Authors: Montgomery Stuart A.
Published: August 2016

All three serotonin norepinephrine reuptake inhibitors (SNRIs) inhibit the reuptake of both serotonin and norepinephrine but they do so with differing affinity ratios. Venlafaxine has a 30-fold higher affinity for serotonin than for norepinephrine while duloxetine has a 10-fold selectivity for serotonin. Milnacipran has a balanced (1:1) ratio of potency for inhibition of reuptake of the two neurotransmitters. The most frequent adverse event with SNRIs is nausea. Not unexpectedly, adverse effects related to a noradrenergic stimulation, such as dry mouth, sweating, and constipation, are found more frequently with SNRIs than with selective serotonin reuptake inhibitors. At true SNRI doses, venlafaxine is associated with dose-dependent cardiovascular phenomena (principally increased blood pressure), an effect which is less frequent with duloxetine and rare with milnacipran. Serious and potentially fatal hepatotoxity has been reported with duloxetine. This problem appears to be unique to duloxetine and not a characteristic of the SNRI class. There are differences in overdose toxicity between venlafaxine and the other SNRIs, possibly related to its increased cardiotoxicity.
Escitalopram: A Second-Generation SSRI
Authors: Owens Michael J. , Rosenbaum Jerrold F.
Published: August 2016

Serotonin (5-hydroxytryptamine, 5-HT) has long been suspected to play a role in the etiology of depression, and modern neurochemical techniques have confirmed this suspicion. Furthermore, all drugs known to be selective (a relative term) serotonin transporter (SERT) inhibitors are effective antidepressants. Of the selective serotonin reuptake inhibitors (SSRIs) approved in a number of countries for use in depression, panic disorder, and obsessive-compulsive disorder, citalopram is the most selective. Citalopram has been used worldwide to treat an estimated 35 million patients, with an excellent safety record. Citalopram is a racemic drug, and its effects on serotonin transport are thought to reside in the S-enantiomer, known as (S)-citalopram or escitalopram. Escitalopram is the most selective SSRI yet developed. Its receptor binding properties and activity in preclinical animal models of depression predict that escitalopram would be effective in the treatment of depression, with approximately twice the potency of the racemate. The pivotal clinical trials of escitalopram not only support this conclusion, but also suggest escitalopram possesses advantages over citalopram in terms of both efficacy and safety. In conclusion, escitalopram is a promising candidate for use as a first-line antidepressant.
New Single-Isomer Compounds on the Horizon
Authors: Gal Joseph
Published: August 2016

In 1992, the Food and Drug Administration (FDA) issued new guidelines governing stereoisomerism in new-drug development. The guidelines strongly encourage the development of single isomers and discourage stereoisomeric (eg, racemic) mixtures. As a result, most new chiral drugs are being developed as single enantiomers (ie, single isomers). There are three mechanisms for the identification and development of new single-isomer drugs: chiral switches (CS), chiral metashifts (CM), and new single-isomer chemical entities (NSICEs). In a CS, one of the two enantiomers of an established racemate is developed as a new drug, with the expectation that the single-isomer form has advantages over the racemic parent in terms of efficacy and/or adverse effects. Many new CS drugs are in development, eg, (S)-oxybutynin for urinary incontinence and escitalopram for depression. In a CM, a chiral metabolite of a drug is developed, in single-isomer form, as an agent with advantages over the parent. Among the current CM drugs in development are (+)-norcisapride (safer GI prokinetic agent than the racemic parent cisapride) and (S)-desmethylzopiclone (antianxiety agent, metabolite of the sedative-hypnotic zopi-clone). Many NSICEs are in development, eg, rosuvastatin as an antihypercholesterolemic, posaconazole as an antifungal, sitafloxacin as a fluoroquinolone antibacterial, pregabalin as an anticonvulsant, abarelix as an antineoplastic, etc. As in the development of any new drug, not every single-isomer candidate will reach the clinic, but there is no doubt that the move to single-isomer agents is an important step forward in the search for better and safer drugs.
Treatment-Resistant Bipolar Disorder: A Comparison of Rapid Cyclers and Nonrapid Cyclers
Authors: Vo Dong , Dunner David L.
Published: August 2016

Background: We investigated clinical factors to determine their relationship to treatment resistance among bipolar patients who had a consultation at a tertiary care facility.

Methods: Patients were separated into two categories: rapid-cycling disorders and nonrapid-cycling disorders. We hypothesized that there would be less usage of lithium carbonate among nonrapid-cycling treatment-resistant patients than among rapid cyclers and also that there would be higher rates of comorbidity seen among nonrapid-cycling than rapid-cycling patients in order to account for these particular patients being treatment resistant.

Findings: Continued recyling and persistent depression characterized rapid cyclers, whereas persistent depression characterized nonrapid cyclers. Less than 30% of patients had adequate lithium treatment and there was no significant difference comparing rapid cyclers with non-rapid cyclers. Rates of comorbidity were also not significantly different between these groups. We also assessed a number of other factors.

Conclusion: Some of these factors were significant, but when a Bonferonni correction was applied, these significant differences were not maintained. The study of treatment resistance among nonrapid-cycling bipolar patients merits further research.
The Role and Impact of Psychotherapy in the Management of Bipolar Disorder
Authors: Otto Michael W. , Miklowitz David J.
Published: August 2016

A growing body of evidence documents the value of structured psychotherapeutic interventions for the co-management of bipolar disorder in the context of ongoing medication treatment. This article reviews the rationale, elements, and outcomes for those psychosocial treatments for bipolar disorder that have been emmined in randomized trials. The available evidence suggests that interventions delivered in individual, group, or family settings, can provide significant benefit to patients undergoing pharmaco-theraby for bibolar disorder.
Introduction—Treatment Resistance: Concepts and Management in Mood and Anxiety Disorders
Authors: Rapaport Mark H.
Published: August 2016

This supplement to CNS Spectrums focuses on exciting emerging data on therapeutic approaches that can help the clinician with difficult-to-treat patients. Over the last decade, there have been tremendous advances in our conceptualization of difficult-to-treat patients, including diagnostic, psychotherapeutic, pharmacotherapeutic, and somatic approaches. A series of articles addressing these advances in the field are presented in this supplement.

Edna B. Foa, PhD, has been a leading expert in cognitive-behavioral therapy (CBT) for anxiety disorders for many years. Foa and colleagues provide a thoughtful analysis of the particular components of CBT that may be responsible for its efficacy in anxiety disorders. This article goes beyond simple trials looking at the efficacy of CBT or combined treatment with pharmacotherapy and CBT. Foa and colleagues identify individual treatment and patient factors as well as the interaction between the two, that may influence treatment response. Treatment of posttraumatic stress disorder is used as a model for helping us understand this exciting work.

Next, Waguih William IsHak, MD, presents important data about the use of practical and pragmatic treatment paradigms in patients with mood and anxiety disorders. Dr. IsHak emphasizes the importance of standardized structured approaches to facilitate understanding of the breadth of psychopathology present in the patient. The model Dr. IsHak proposes for the evaluation and conceptualization of the patient facilitates the integration of biological factors, psychological factors, and psychosocial variables. His algorithms go beyond merely a technique for assessment and present a rational approach to therapy for patients. These algorithms are limited by existing data, but the steps elaborated within the algorithm are powerful and useful for the clinician. This article serves as a useful guide for both trainees and clinicians with many years in practice.
Clinical Pathways for Mood and Anxiety Disorders
Authors: IsHak Waguih William
Published: August 2016

Clinical pathways generally recommend potential steps in the diagnosis and treatment of a condition or procedure for individual patients. Their usefulness in guiding clinicians through the steps of nonresponse or partial response to interventions has been documented. They are predominantly management tools based on clinical information developed from evidence-based psychiatry, practice guidelines, or expert consensus statements. Pathways may not be appropriate for use in all circumstances, nor are they a substitute for the practitioner's experience and judgment. Their applicability must be assessed by the responsible practitioner in light of relevant circumstances presented by individual patients in order to optimize treatment.
La revisione da parte dei referee degli articoli inviati ad EPS. Alcune riflessioni sul fenomeno della «pressione a pubblicare» e sulla «ambiguous authorship»
Authors: Tansella Michele
Published: August 2016

In una recente intervista (Pincus & Ferris, 1993), Nancy C. Andreasen, nuovo editor dell' American Journal of Psychiatry (AJP), ha ricordato come la proposta di adottare il metodo della blind review, cioè della revisione degli articoli inviati per la pubblicazione da parte di referee ai quali non viene reso noto il nome degli autori, venga riproposta ad ogni riunione del Comitato Direttivo dell'AJP. Finora, dice Andreasen, il Comitato si è sempre espresso in senso contrario, sostanzialmente per due motivi: il primo è che alcune Unità di Ricerca ed alcuni gruppi sono noti per essere più rigorosi di altri e questa «autorevolezza» è utile al referee per prendere una decisione; il secondo dipende dalla difficoltà di fare una review veramente blind, in quanto lo stile, la bibliografia e altri elementi spesso rendono possibile o addirittura facile l'identificazione degli autori del lavoro. Ciò non è giusto per quelli che invece non vengono identificati.

Il problema di assicurare una valutazione equilibrata e non distorta degli articoli inviati potrebbe più semplicemente essere risolto: a) facendo in modo che la revisione «in aperto» da parte dei referee sia fatta da persone non solo competenti, ma anche disinteressate, attendibili e note per la loro correttezza; b) garantendo ampia possibilità di accesso alla pubblicazione anche ai gruppi «minori» o agli autori che lavorano fuori dalle istituzioni più note, purché ovviamente i loro articoli soddisfino gli standard di qualità della rivista in questione. Il punto cruciale, dunque, è la scelta dei referee, scelta che spetta quasi sempre al direttore della rivista.
La valutazione dei costi del trattamento farmacologico nella depressione. Una revisione critica della letteratura
Authors: Bellantuono Cesario , Balestrieri Matteo
Published: August 2016

Aims-. To review the factors which are relevant for a correct evaluation of the costs of antidepressant drug treatment and to report the results of the studies on the efficacy, tollerability and costs of the most utilized antidepressants (tricyclics and SSRI).Methods- We reviewed the international literature concerning both with comparative studies on efficacy, tollerability and safety of tricyclics and SSRI and with studies of pharmacoeconomics that have focused on the costs of depression and of different antidepressant treatments.Results- Depression involves high costs, especially if indirect costs are considered. Comparative studies indicate a substantial equivalence of efficacy between tricyclics and SSRI, but a better tolerability of the latters. The few studies of pharmacoeconomics that have evaluated different antidepressant drugs indicate that a treatment with SSRI involves lower costs as compared with tricyclics. These results are due to the higher indirect costs (compliance, drop-out for side-effects, work loss, etc.) of tricyclics.Conclusions- A correct economic evaluation of an antidepressant drug treatment should consider both direct and indirect costs. Available studies indicate that SSRI involves lower costs as compared with tricyclics; however in order to confirm these results more studies of pharmacoeconomics are needed with experimental designes (longitudinal studies) taking into account the outcome of patients treated in routine clinical practice.
An exploratory study into the health beliefs and behaviours of British Indians with type II diabetes
Authors: Patel Vishal , Iliffe Steve
Published: August 2016

Aim

To explore the influence of health beliefs and behaviours on diabetes management in British Indians, as successful management of diabetes is dependent on underlying cultural beliefs and behaviours.

Background

British South Asians are six times more likely to suffer from type II diabetes than those in the general population. Yet, little research has been carried out into beliefs about diabetes among the British Indian population.

Method

The study used semi-structured interviews, a structured vignette and a pile-sorting exercise. In all, 10 British Indians were interviewed at a General Practice in North West London.

Findings

Those interviewed were informed about their diabetes but had difficulties in adapting their diet. Themes identified included causal beliefs of diabetes, use of alternative therapies, moderation of food, adaption of exercise regimes and sources of information. All were aware of avoiding certain foods yet some still continued to consume these items. Participants expressed the need for culturally sensitive forums to help manage their diabetes.
Outer space and cyber space: meeting ET in the cloud
Authors: Peters Ted
Published: August 2016

What justifies the astrobiologist's search for post-biological or machine-intelligence in outer space? Four assumptions borrowed from transhumanism (H+) seem to be at work: (1) it is reasonable to speculate that life on Earth will evolve in the direction of post-biological intelligence; (2) if extraterrestrials have evolved longer than we on Earth, then they will be more scientifically and technologically advanced; (3) superintelligence, computer uploads of brains, and dis-embodied mind belong together; and (4) evolutionary progress is guided by the drive toward increased intelligence. When subjected to critical review, these assumptions prove to be weak. Most importantly, evolutionary biologists do not support the idea that evolution is internally directed toward increased intelligence. Without this assumption, justifying the search for ET more intelligent than earthlings is anaemic. Nevertheless, one can still hope that in the near future we will be communicating with new neighbours in the Milky Way. Can sheer hope inspire science?
Impact of long-term high-fat diet intake gestational protein-restricted offspring on kidney morphology and function
Authors: Rizzi V. H. G. , Sene L. d. B. , Fernandez C. D. B. , Gontijo J. A. R. , Boer P. A.
Published: August 2016

Emerging evidence highlights the far-reaching consequences of high-fat diet (HFD) and obesity on kidney morphological and functional disorders. In the present study, we aim to evaluate the effects of early HFD intake on renal function and morphology in maternal protein-restricted offspring (LP). LP and normal protein-intake offspring (NP) were fed HFD (LPH and NPH, respectively) or standard rodent (LPN and NPN) diet from the 8th to 13th week of age. Blood pressure, kidney function, immunohistochemistry and scanning electron microscopy were analyzed. Increased total cholesterol and low-density lipoprotein serum levels were observed in LPH offspring. The adiposity index was reduced in the (LPN) group and, conversely, increased in the NPH and LPH groups. Blood pressure was higher beyond the 10th week of age in the LPH group compared with the other groups. Decreased urinary sodium excretion was observed in LP offspring, whereas the HFD-treated groups presented a decreased urine pH in a time-dependent fashion. The LPN, NPH and LPH groups showed increased expression of type 1 angiotensin II (AngII) receptor (AT1R), TGF-β1, collagen and fibronectin in the kidneys. Moreover, the adult fetal-programmed offspring showed pronounced effacement of the podocyte foot process associated with the rupture of cell membranes and striking urinary protein excretion, exacerbated by HFD treatment. To the best of our knowledge, this is the first study demonstrating that young fetal-programmed offspring submitted to long-term HFD intake have increased susceptibility to renal structural and functional disorders associated with an accentuated stage of fibrosis and tubular dysfunction.
Entwicklung und Validierung eines Kurzfragebogens zur Erfassung computerbezogener Anreizfaktoren bei Erwachsenen
Authors: Senkbeil Martin , Ihme Jan Marten
Published: August 2016

Zusammenfassung. Im vorliegenden Beitrag wird die Konstruktion und erste Validierung eines Kurzfragebogens vorgestellt, der auf der Grundlage der sozial-kognitiven Theorie der Internetnutzung computerbezogene Anreizfaktoren bei Erwachsenen erfasst. Der Fragebogen ist für den Einsatz in Large-Scale-Untersuchungen als Outcome-Variable sowie zur Vorhersage der Computernutzung und computerbezogener Fertigkeiten konzipiert. Die Ergebnisse einer Studie im Rahmen des Nationalen Bildungspanels (N = 462) zeigen, dass das vorgeschlagene Modell zur Erfassung computerbezogener Anreizfaktoren empirisch gestützt werden kann und der Fragebogen gute psychometrische Eigenschaften besitzt. Überdies konnte partielle Messinvarianz über Geschlecht und Alter belegt werden. Aspekte der Konstruktvalidität wurden über Zusammenhänge mit computerbezogenen Personenmerkmalen (z. B. Fertigkeiten) und Persönlichkeitsmerkmalen (z. B. Need for Cognition) überprüft.
Bacteria Preserve Record of Earth's Magnetic Fields
Authors: Deatrick Elizabeth
Published: August 2016

Tiny yet stable magnetized particles created by microbes long ago could help scientists better determine the strength and orientation of ancient magnetic fields.
Regulation of B-cell development and tolerance by different members of the miR-17∼92 family microRNAs
Authors: Lai Maoyi , Gonzalez-Martin Alicia , Cooper Anthony B. , Oda Hiroyo , Jin Hyun Yong , Shepherd Jovan , He Linling , Zhu Jiang , Nemazee David , Xiao Changchun
Published: August 2016

The molecular mechanisms that regulate B-cell development and tolerance remain incompletely understood. In this study, we identify a critical role for the miR-17∼92 microRNA cluster in regulating B-cell central tolerance and demonstrate that these miRNAs control early B-cell development in a cell-intrinsic manner. While the cluster member miR-19 suppresses the expression of Pten and plays a key role in regulating B-cell tolerance, miR-17 controls early B-cell development through other molecular pathways. These findings demonstrate differential control of two closely linked B-cell developmental stages by different members of a single microRNA cluster through distinct molecular pathways.
Distinct Differentiation Programs Triggered by IL-6 and LPS in Teleost IgM+ B Cells in The Absence of Germinal Centers
Authors: Abós Beatriz , Wang Tiehui , Castro Rosario , Granja Aitor G. , Leal Esther , Havixbeck Jeffrey , Luque Alfonso , Barreda Daniel R. , Secombes Chris J. , Tafalla Carolina
Published: August 2016

Although originally identified as a B cell differentiation factor, it is now known that mammalian interleukin-6 (IL-6) only regulates B cells committed to plasma cells in response to T-dependent (TD) antigens within germinal centers (GCs). Even though adaptive immunity is present in teleost fish, these species lack lymph nodes and GCs. Thus, the aim of the present study was to establish the role of trout IL-6 on B cells, comparing its effects to those induced by bacterial lipopolysaccharide (LPS). We demonstrate that the effects of teleost IL-6 on naïve spleen B cells include proliferation, activation of NF-κB, increased IgM secretion, up-regulation of Blimp1 transcription and decreased MHC-II surface expression that point to trout IL-6 as a differentiation factor for IgM antibody-secreting cells (ASCs). However, LPS induced the secretion of IgM without up-regulating Blimp1, driving the cells towards an intermediate activation state in which antigen presenting mechanisms are elicited together with antibody secretion and expression of pro-inflammatory genes. Our results reveal that, in trout, IL-6 is a differentiation factor for B cells, stimulating IgM responses in the absence of follicular structures and suggest that it was after follicular structures appeared that this cytokine evolved to modulate TD responses within the GC.
Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives
Authors: Shao Jingwei , Zhou Suxia , Jiang Zhou , Chi Ting , Ma Ji , Kuo Minliang , Lee Alan Yueh-Luen , Jia Lee
Published: August 2016

We recently defined cancer metastatic chemoprevention as utilizing safe and effective molecules to comprehensively prevent the spark of activation-adhesion-extravasation-proliferation metastatic cascade caused by circulating tumor cells (CTCs). The strategy focuses on preventing the most important starting point of the cascade. We identified an extract from a well-known medical plant Murraya paniculata, which inhibited both embryonic implantation to human endometrium as traditionally-used for abortion and CTC adhesion to human endothelium. Here, we separated and characterized five coumarin-containing components (Z1–Z5) from the botanic extract. Flow cytometry revealed that within 1–100 μg/mL, Z3 and Z5 down-regulated EpCAM expression in human colon HCT116, whereas, Z1 and Z2 did oppositely. Warfarin and Z1-Z5 component mixture (CM) also down-regulated EpCAM expression. The down-regulation of EpCAM by Z3, Z5, CM and warfarin was confirmed by western blotting and caused inhibition on adhesion of cancer cells to human endothelial cells. Rat coagulation study showed that warfarin prolonged prothrombin time, whereas, Z3 did not. The present studies revealed that, for the first time, warfarin and coumarin-like components Z3, Z5 and CM from Murraya paniculata could directly inhibit EpCAM-mediated cell-cell adhesion.
Strain and rate-dependent neuronal injury in a 3D in vitro compression model of traumatic brain injury
Authors: Bar-Kochba Eyal , Scimone Mark T. , Estrada Jonathan B. , Franck Christian
Published: August 2016

In the United States over 1.7 million cases of traumatic brain injury are reported yearly, but predictive correlation of cellular injury to impact tissue strain is still lacking, particularly for neuronal injury resulting from compression. Given the prevalence of compressive deformations in most blunt head trauma, this information is critically important for the development of future mitigation and diagnosis strategies. Using a 3D in vitro neuronal compression model, we investigated the role of impact strain and strain rate on neuronal lifetime, viability, and pathomorphology. We find that strain magnitude and rate have profound, yet distinctively different effects on the injury pathology. While strain magnitude affects the time of neuronal death, strain rate influences the pathomorphology and extent of population injury. Cellular injury is not initiated through localized deformation of the cytoskeleton but rather driven by excess strain on the entire cell. Furthermore we find that, mechanoporation, one of the key pathological trigger mechanisms in stretch and shear neuronal injuries, was not observed under compression.
Role of the Gut Microbiome in Modulating Arthritis Progression in Mice
Authors: Liu Xiaofei , Zeng Benhua , Zhang Juan , Li Wenxia , Mou Fangxiang , Wang Heng , Zou Qinghua , Zhong Bing , Wu Like , Wei Hong , Fang Yongfei
Published: August 2016

Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset. With disease development, the abundance of OTUs affiliated with the families Bacteroidaceae, Lachnospiraceae, and S24-7 increased significantly in CIA-susceptible mice. Notably, germ-free mice conventionalized with the microbiota from CIA-susceptible mice showed a higher frequency of arthritis induction than those conventionalized with the microbiota from CIA-resistant mice. Consistently, the concentration of the cytokine interleukin-17 in serum and the proportions of CD8+T cells and Th17 lymphocytes in the spleen were significantly higher in the former group, whereas the abundances of dendritic cells, B cells, and Treg cells in the spleen were significantly lower. Our results suggest that the gut microbiome influences arthritis susceptibility.