bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual Dysfunction and Psychotropic Medications
Authors: Stimmel Glen L. , Gutierrez Mary A. 
Published: August 2016

AbstractPsychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in ≥50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.
Social Influences on the Concept of Fibromyalgia
Authors: Merskey Harold 
Published: August 2016

AbstractDespite relevant evidence of physical illness promoting fibromyalgia syndrome (FMS), some authors claim that it is a psychological illness, or due to “psychological amplification.” Good evi-dence for such views is lacking. Selection processes lead to increased rates of psychological illness in general practice and in specialist practice. The phys-ical distress of FMS can increase both anxiety and depression. Questionable research supported by the insurance industry has tended to provide nega-tive and disparaging views of pain. Current imag-ing studies support the view that central effects connected with FMS relate to the processing of noxious stimulation more than affective disorder.
Mechanisms of Fibromyalgia Pain
Authors: Staud Roland 
Published: August 2016

Chronic musculoskeletal pain is highly prevalent in the United States and includes inflammatory and non-inflammatory syndromes, such as low back pain (reported by 59 million Americans in the past 3 months), neck pain (reported by 30.1 million Americans in the past 3 months), clinical osteoarthritis (reported by 27 million Americans in the past 3 months), and fibromyalgia (FM). FM affects between 2% to 4% of the US population or 12 million people. Inflammatory pain conditions commonly reported by patients include rheumatoid arthritis (2.5 million) and gout (3 million), among others. This article will focus primarily on FM, which is a chronic pain condition that predominately affects women.The current diagnostic criteria for FM include chronic widespread pain for at least 3 months and the presence of widespread mechanical tenderness. A patient with suspected FM must report pain in all four body quadrants and have at least 11 of 18 tender points for a positive diagnosis to be made. Tender points are areas of the body where pressure is applied until pain threshold is achieved. In addition to pain and tenderness, FM patients very frequently describe widespread stiffness and fatigue, disrupted or poor sleep, dyscognition, and mild soft tissue swelling. Patients often also report symptoms of anxiety and depression.
Emotional Regulation: Implications for the Psychobiology of Psychotherapy
Authors: Stein Dan J. 
Published: August 2016

ABSTRACTA range of studies have contributed to understanding the psychobiology of emotional regulation. Functional imaging studies have demonstrated that cortico-limbic circuitry plays an important role in mediating processes such as reappraisal and suppression. Dorsolateral prefrontal cortex may be important in conscious reframing, while ventromedial prefrontal cortex and orbitofrontal cortex may be particularly important in emotion evaluation. Gene variants and early environments impact underlying emotional regulation and its neurobiology. It may be hypothesized that during interventions such as psychotherapy there are improvements in emotional regulation, together with the normalization of related psycho-biological mechanisms.
Characteristics and Symptomatology of Patients Diagnosed with Unipolar Depression at Risk for Undiagnosed Bipolar Disorder: A Bipolar Survey
Authors: Bolge Susan C. , Thompson Thomas , Bourne Eric , Nanry Kevin 
Published: August 2016

ABSTRACTObjective: To identify characteristics of patients diagnosed with unipolar depression who may have undiagnosed bipolar disorder.Methods: Patients diagnosed with unipolar depression by a healthcare provider were identified through the Consumer Health Sciences National Health and Wellness Survey. Manic symptoms, comorbid conditions, psychiatric symptomatology, use of healthcare resources, and patient demographics were identified through Internet-based questionnaires. A self-report adapted version of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria identified symptoms consistent with a manic episode. Psychological well-being was measured by the Psychological General Well-Being Index.Results: Of the 1,602 respondents who met inclusion criteria, 219 (14% or ~1 out of 7) reported symptoms consistent with a manic episode and were considered at risk for undiagnosed bipolar disorder. These respondents were younger and had a lower socioeconomic status. At-risk patients rated their depression as more severe and experienced greater impairment of psychological well-being. More than 70% of those at risk reported speaking with a healthcare provider about their mania symptoms. Comorbid mental disorders, especially anxiety-related conditions, were common in these patients.Conclusion: These findings underscore the importance of evaluating unipolar patients for bipolar disorder and may help clinicians identify symptoms and comorbidities associated with patients with unipolar depression at risk for undiagnosed bipolar disorder.
Bipolar Disorder: A National Health Concern
Authors: McIntyre Roger S. , Konarski Jakub Z. 
Published: August 2016

AbstractBipolar disorders are prevalent, disabling, and costly diseases that often pursue an inexorable course. Underdetection, misdiagnosis, and diagnostic delay frequently and unnecessarily interfere with appropriate treatment of the disorder. Mortality studies in bipolar disorder underscore the relevance of both unnatural and natural causes of death, inviting the need for improved preventative and primary health care for bipolar patients. The treatment framework for bipolar disorder must recognize and anticipate the multidirnensionality and comorbidity of this illness. Pharmacotherapy is necessary, with multiple concomitant medications required for most patients, In addition, adjunctive psychosocial interventions offer enhanced compliance and may beneficially influence psychopathological and functional outcomes. This article emphasizes the public health concern of bipolr disorder, and provides tactics to enhance detection of cryptic bipolar states, underscore the clinical and pathophysiological relevance of comorbidity in bipolar disorder, and provide a framework for multimodality therapy for this condition.
Emerging Treatment Options in Treatment-Resistant Depression and Anxiety Disorders
Authors: IsHak Waguih William , Rapaport Mark H. , Gotto Jennifer G. 
Published: August 2016

ABSTRACTManagement strategies for treatment-resistant depression and anxiety disorders have evolved over the last decade. Our understanding of the factors that impair recovery from an episode of major depression has increased, leading to the development of more precise diagnostic methodology that highlight the presence of comorbid conditions. New medications, creative uses of existing medications, increased empirical data about augmentation strategies, and the development of innovative nonpharmacologic interventions are responsible for a marked expansion in treatment options. Traditionally, augmentations with lithium, thyroid hormones, or electroconvulsive therapy have demonstrated effectiveness in some patients with treatment-resistant mood disorders. Among the promising treatments in both depression and anxiety is augmentation using low-dose antipsychotics medications, combining antidepressants of different classes, and the addition of psychotherapy. Nonpharmacologic interventions that may have potential include transcranial magnetic stimulation, deep-brain stimulation, and vagus-nerve stimulation. This article provides a brief review of the available data summarizing existing and new treatment strategies in depression and anxiety disorders.
The use of patient-level outcomes to inform treatment
Authors: Slade Mike 
Published: August 2016

SummaryObjective – The assessment of outcome for any purpose is not undertaken routinely in European mental health services. This paper discusses the merits of using outcome data to inform the planning of mental health care for individual patients, and provides practical advice to support the implementation of this new approach to working. Method – The use of outcomes in North America and Europe is briefly reviewed. A conceptual basis is proposed for routine outcome assessment – the ongoing measurement and use of outcome data to inform decisions about whether to continue, change or curtail treatment. A cognitive psychology model is developed which indicates that the routine use of outcomes will improve mental health care. Perceived problems with routine outcome assessment are discussed, and principles for implementation are identified. Results – Outcomes are used mainly for generating local-level (rather than patient-level) data in North America, and rarely used in Europe. The use of outcome data routinely may facilitate reflective clinical practice, a model of decision-making which leads to a higher quality of clinical care than automated problem-solving. One issue relates to the use of standardised assessments designed for research purposes in clinical settings, and this is being addressed through the development of a new generation of outcome measures which are explicitly designed for clinical use. However, most clinicians remain unconvinced of the benefits of routine outcome assessment, and relevant research is currently underway across Europe which will address this concern. Scientific principles to maximise quality and pragmatic principles to maximise the chances of successful implementation are identified. Conclusions – The routine use of outcomes will become increasingly prominent in European mental health services. This provides clinicians with an opportunity to improve the quality of clinical care offered to patients.
A systematic review of the European Agency for the Evaluation of Medicinal Products (EMEA) recommendations on the conduct of clinical trials in psychiatry
Authors: Guaiana Giuseppe , Barbui Corrado 
Published: August 2016

SummaryObjective – This article critically reviews the European Agency for the Evaluation of Medicinal Products (EMEA) recommendations on the conduct of clinical trials in psychiatry. The EMEA is a regulatory body which provides the institutions of the European Community with the best possible scientific advice on the quality, safety, and efficacy of medicinal products. Method – Systematic review of recommendations, guide-lines and official documents available in the EMEA web site. Results – Out of nearly 400 documents, we identified 4 documents on the conduct of clinical trials in specific psychiatric disorders and 5 on the use of placebo or active comparator in evaluating a new drug's efficacy and on methodological issues in establishing difference and equivalence of effect. The EMEA recommends clinical trials to detect a difference between the compound under investigation and placebo, and to assess at least non-inferiority against an active comparator. A placebo arm is intended to validate the study. The EMEA supports the use of placebo only when there is no serious risk for the patient. In schizophrenia, depression and bipolar disorder the Agency suggests that a three-arm study is the design of choice, to demonstrate superiority against placebo and a similar balance against an active comparator. Conclusions – Despite the many effective therapeutic options available for the pharmacological management of psychiatric disorders, the EMEA regulatory process still relies on the demonstration of efficacy in absolute terms, against a placebo. We discuss this position and put at issue the possibility of developing a new generation of trials to demonstrate superiority of effect of new compounds over reference ones.
Does Apolipoprotein e4 Status Moderate the Association of Family Environment with Long-Term Child Functioning following Early Moderate to Severe Traumatic Brain Injury? A Preliminary Study
Authors: Treble-Barna Amery , Zang Huaiyu , Zhang Nanhua , Martin Lisa J. , Yeates Keith Owen , Taylor H. Gerry , Wade Shari L. , Kurowski Brad G. 
Published: August 2016

AbstractObjectives:To examine whether apolipoprotein e4 (APOE) status moderates the association of family environment with child functioning following early traumatic brain injury (TBI).Methods:Sixty-five children with moderate to severe TBI and 70 children with orthopedic injury (OI) completed assessments 6, 12, 18 months, and 3.5 and 6.8 years post injury. DNA was extracted from saliva samples and genotyped for APOE e4 status. Linear mixed models examined moderating effects of APOE e4 status on associations between two family environment factors (parenting style, home environment) and three child outcomes (executive functioning, behavioral adjustment, adaptive functioning).Results:Children with TBI who were carriers of the e4 allele showed poorer adaptive functioning relative to non-carriers with TBI and children with OI in the context of low authoritarianism. At high levels of authoritarianism, non-carriers with TBI showed the poorest adaptive functioning among groups. There were no main effects or interactions involving APOE and executive functioning or behavioral adjustment.Conclusions:The APOE e4 allele was detrimental for long-term adaptive functioning in the context of positive parenting, whereas in less optimal parenting contexts, being a non-carrier was detrimental. We provide preliminary evidence for an interaction of APOE e4 status and parenting style in predicting long-term outcomes following early TBI. (JINS, 2016,22, 859–864)
Spatial clustering of tuning in mouse primary visual cortex
Authors: Ringach Dario L. , Mineault Patrick J. , Tring Elaine , Olivas Nicholas D. , Garcia-Junco-Clemente Pablo , Trachtenberg Joshua T. 
Published: August 2016

AbstractThe primary visual cortex of higher mammals is organized into two-dimensional maps, where the preference of cells for stimulus parameters is arranged regularly on the cortical surface. In contrast, the preference of neurons in the rodent appears to be arranged randomly, in what is termed a salt-and-pepper map. Here we revisited the spatial organization of receptive fields in mouse primary visual cortex by measuring the tuning of pyramidal neurons in the joint orientation and spatial frequency domain. We found that the similarity of tuning decreases as a function of cortical distance, revealing a weak but statistically significant spatial clustering. Clustering was also observed across different cortical depths, consistent with a columnar organization. Thus, the mouse visual cortex is not strictly a salt-and-pepper map. At least on a local scale, it resembles a degraded version of the organization seen in higher mammals, hinting at a possible common origin.
Selective directed self-assembly of coexisting morphologies using block copolymer blends
Authors: Stein A. , Wright G. , Yager K. G. , Doerk G. S. , Black C. T. 
Published: August 2016

AbstractDirected self-assembly (DSA) of block copolymers is an emergent technique for nano-lithography, but is limited in the range of structures possible in a single fabrication step. Here we expand on traditional DSA chemical patterning. A blend of lamellar- and cylinder-forming block copolymers assembles on specially designed surface chemical line gratings, leading to the simultaneous formation of coexisting ordered morphologies in separate areas of the substrate. The competing energetics of polymer chain distortions and chemical mismatch with the substrate grating bias the system towards either line/space or dot array patterns, depending on the pitch and linewidth of the prepattern. This is in contrast to the typical DSA, wherein assembly of a single-component block copolymer on chemical templates generates patterns of either lines/spaces (lamellar) or hexagonal dot arrays (cylinders). In our approach, the chemical template encodes desired local spatial arrangements of coexisting design motifs, self-assembled from a single, sophisticated resist.
PTH/SDF-1α cotherapy induces CD90+CD34− stromal cells migration and promotes tissue regeneration in a rat periodontal defect model
Authors: Wang Fang , Du Lingqian , Ge Shaohua 
Published: August 2016

AbstractStromal cell-derived factor-1α (SDF-1α) is a key stem cell homing factor that is crucial for recruitment of stem cells to many diseased organs. However, the therapeutic activity of SDF-1α is potentially limited by N-terminal cleavage at position-2 proline by a cell surface protein CD26/dipeptidyl peptidase-IV (DPP-IV). Parathyroid hormone (PTH) is a DPP-IV inhibitor and has been suggested as a promising agent for periodontal tissue repair. The purpose of this study was to explore the effects of a cell-free system comprising SDF-1α and scaffold plus PTH systemic application on periodontal tissue regeneration in vivo. The results showed that PTH/SDF-1α cotherapy improved the quantity of regenerated bone and resulted in better organization of ligament interface. We further investigated the possible mechanisms and found that PTH/SDF-1α cotherapy enhanced CD90+CD34− stromal cells migration in vivo, increased the number of CXCR4 + cells in periodontal defects, induced early bone osteoclastogenesis and enhanced the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and collagen I (Col I) in newly formed bone tissue. In conclusion, this cell-free tissue engineering system with local administration of SDF-1α and systemic application of PTH could be employed to induce CD90+CD34− stromal cells recruitment and promote periodontal tissue regeneration.
Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function
Authors: Fujii Momo , Sunagawa Genshiro A. , Kondo Mineo , Takahashi Masayo , Mandai Michiko 
Published: August 2016

AbstractFull-field electroretinograms (ERGs) are used to objectively assess the mass function of the retina, whereas focal ERGs are used to evaluate the focal retinal function. The purpose of this study was to determine the usefulness of a multiple electrode array (MEA) system for recording ex vivo micro ERGs (mERGs) together with multiunit spike responses of the retinal ganglion cells (RGCs) to assess focal retinal function in isolated mouse retinas. The a- and b-waves of the full-field ERGs were present in the mERG. The b-wave was blocked by L-AP4, an inhibitor of the mGluR6 receptor and the OFF-component was blocked by exposure to PDA, an antagonist of ionotropic glutamate receptors, with a corresponding RGC responses. mERGs were also recorded from mice with progressive retinal degeneration, the C57BL/6J-Pde6brd1-2J/J (rd1) mice, from which conventional full-field ERGs are non-recordable. A blockade of the glutamate receptors indicated that the negative wave of rd1 mice do not originate from the photoreceptors but from the second or third order neurons. This technique of recording mERGs will be useful in assessing the focal properties of the retinas obtained from eyes with pathology and also to follow the recovery of the physiology of the retina in regenerative studies.
A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein
Authors: Seo Joonbae , Singh Natalia N. , Ottesen Eric W. , Lee Brian M. , Singh Ravindra N. 
Published: August 2016

AbstractSpinal muscular atrophy (SMA), a leading genetic disease of children and infants, is caused by mutations or deletions of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to skipping of exon 7. SMN2 predominantly produces SMNΔ7, an unstable protein. Here we report exon 6B, a novel exon, generated by exonization of an intronic Alu-like sequence of SMN. We validate the expression of exon 6B-containing transcripts SMN6B and SMN6BΔ7 in human tissues and cell lines. We confirm generation of SMN6B transcripts from both SMN1 and SMN2. We detect expression of SMN6B protein using antibodies raised against a unique polypeptide encoded by exon 6B. We analyze RNA-Seq data to show that hnRNP C is a potential regulator of SMN6B expression and demonstrate that SMN6B is a substrate of nonsense-mediated decay. We show interaction of SMN6B with Gemin2, a critical SMN-interacting protein. We demonstrate that SMN6B is more stable than SMNΔ7 and localizes to both the nucleus and the cytoplasm. Our finding expands the diversity of transcripts generated from human SMN genes and reveals a novel protein isoform predicted to be stably expressed during conditions of stress.
Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension
Authors: Liu Xin , Hu Cheng , Bao Minghui , Li Jing , Liu Xiaoyan , Tan Xuerui , Zhou Yong , Chen Yequn , Wu Shouling , Chen Shuohua , Zhang Rong , Jiang Feng , Jia Weiping , Wang Xingyu , Yang Xinchun , Cai Jun 
Published: August 2016

AbstractHypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10−9; LOC729251 and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-β binding protein 1 (LTBP1) and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention.