Blood-cerebrospinal fluid barrier permeability in Alzheimer's disease.

PubMed

Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Andreasen, Niels; Grundke-Iqbal, Inge; Iqbal, Khalid

2011-01-01

The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer's disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-β1-42 (Aβ1-42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, Aβ1-42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both Aβ and tau pathologies in a restricted subgroup of AD patients.

Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic β Cell Dysfunction*

PubMed Central

Kuo, Taiyi; Kim-Muller, Ja Young; McGraw, Timothy E.; Accili, Domenico

2016-01-01

Insulin resistance and β cell dysfunction contribute to the pathogenesis of type 2 diabetes. Unlike insulin resistance, β cell dysfunction remains difficult to predict and monitor, because of the inaccessibility of the endocrine pancreas, the integrated relationship with insulin sensitivity, and the paracrine effects of incretins. The goal of our study was to survey the plasma response to a metabolic challenge in order to identify factors predictive of β cell dysfunction. To this end, we combined (i) the power of unbiased iTRAQ (isobaric tag for relative and absolute quantification) mass spectrometry with (ii) direct sampling of the portal vein following an intravenous glucose/arginine challenge (IVGATT) in (iii) mice with a genetic β cell defect. By so doing, we excluded the effects of peripheral insulin sensitivity as well as those of incretins on β cells, and focused on the first phase of insulin secretion to capture the early pathophysiology of β cell dysfunction. We compared plasma protein profiles with ex vivo islet secretome and transcriptome analyses. We detected changes to 418 plasma proteins in vivo, and detected changes to 262 proteins ex vivo. The impairment of insulin secretion was associated with greater overall changes in the plasma response to IVGATT, possibly reflecting metabolic instability. Reduced levels of proteins regulating redox state and neuronal stress markers, as well as increased levels of coagulation factors, antedated the loss of insulin secretion in diabetic mice. These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future β cell failure. PMID:26917725

A Motion-Sensing Game-Based Therapy to Foster the Learning of Children with Sensory Integration Dysfunction

ERIC Educational Resources Information Center

Chuang, Tsung-Yen; Kuo, Ming-Shiou

2016-01-01

Children with Sensory Integration Dysfunction (SID, also known as Sensory Processing Disorder, SPD) are also learners with disabilities with regard to responding adequately to the demands made by a learning environment. With problems of organizing and processing the sensation information coming from body modalities, children with SID (CwSID)…

Metacognition moderates the relationship between dysfunctional self-appraisal and social functioning in prolonged schizophrenia independent of psychopathology.

PubMed

James, Alison V; Hasson-Ohayon, Ilanit; Vohs, Jenifer; Minor, Kyle S; Leonhardt, Bethany L; Buck, Kelly D; George, Sunita; Lysaker, Paul H

2016-08-01

Both dysfunctional self-appraisal and metacognitive deficits, or impairments in the ability to form complex and integrated ideas about oneself and others, may contribute to social deficits in schizophrenia. Little is known, however, about how they interact with each other. In this study, we examined the hypothesis that both higher metacognition and more positive self-appraisal are necessary for increased social functioning. Concurrent assessments of self-appraisal, metacognition, and social functioning were gathered from 66 adults with schizophrenia in a non-acute phase of disorder. Three forms of self-appraisal were used: self-esteem, hope and self-efficacy. Metacognition was assessed using the Metacognitive Assessment Scale-Abbreviated, and social functioning with the Quality of Life Scale. Measures of psychopathology, neurocognition and social cognition were also gathered for use as potential covariates. A single index of self-appraisal was generated from subjecting the assessments of self-appraisal to a principal components analysis. Linear regression analyses revealed that after controlling for severity of psychopathology, metacognition moderated the effect of the self-appraisal factor score upon social functioning. A median split of metacognition and the self-appraisal index yielded four groups. ANCOVA analyses revealed that participants with higher levels of metacognition and more positive self-appraisal had greater capacities for social relatedness than all other participants, regardless of levels of positive and negative symptoms. Correlational analyses revealed that metacognition but not self-appraisal was related to the frequencies of social contact independent of the effects of psychopathology. Assessments of social cognition and neurocognition were not significantly linked with social dysfunction. Greater social functioning is made possible by a combination of both more positive self-appraisals and greater metacognitive capacity. Individuals with schizophrenia who struggle to relate to others may benefit from interventions which address both their beliefs about themselves and their capacity for metacognition. Published by Elsevier Inc.

Preservice Teacher Education about Drug or Alcohol-Impaired Dysfunctional Families.

ERIC Educational Resources Information Center

Burke, Robert W.

2003-01-01

This article provides an overview of family systems theory, with a particular focus on the roles adapted by children in dysfunctional families. In addition, analyses of narratives about dysfunctional families, written by 125 preservice teachers, provide implications for new directions in teacher education. (Contains references.) (Author/CR)

Early Stages of Musical Development: Relationships between Sensory Integration Dysfunction, Parental Influence, and Musical Disposition of a Three-Year-Old "Maestro"

ERIC Educational Resources Information Center

Hendricks, Karin S.; McPherson, Gary E.

2010-01-01

Current literature offers only scant information on very young children who display high attention and engagement in music, but who are not drawn from normal populations. This study of three-year-old Danny, who possesses the neurological disorder Sensory Integration Dysfunction, provides a case study of the types of parent-child interactions that…

Bem Sex Role Inventory Undifferentiated Score: A Comparison of Sexual Dysfunction Patients with Sexual Offenders.

ERIC Educational Resources Information Center

Dwyer, Margretta; And Others

1988-01-01

Examined Bem Sex Role undifferentiated scores on 93 male sex offenders as compared with 50 male sexually dysfunctional patients. Chi-square analyses revealed significant difference: offenders obtained undifferentiated scores more often than did sexual dysfunctional population. Concluded that Bem Sex Role Inventory is useful in identifying sexual…

The Development and Application of the Explanatory Model of School Dysfunctions

ERIC Educational Resources Information Center

Bergman, Manfred Max; Bergman, Zinette; Gravett, Sarah

2011-01-01

This article develops the Explanatory Model of School Dysfunctions based on 80 essays of school principals and their representatives in Gauteng. It reveals the degree and kinds of school dysfunctions, as well as their interconnectedness with actors, networks, and domains. The model provides a basis for theory-based analyses of specific…

Erectile dysfunction and coronary atherothrombosis in diabetic patients: pathophysiology, clinical features and treatment.

PubMed

Gazzaruso, Carmine

2006-03-01

The current review reports recent data available in the literature on the prevalence of erectile dysfunction and the association of erectile dysfunction with overt and silent coronary artery disease in patients with diabetes mellitus. The mechanisms by which erectile dysfunction is associated with coronary artery disease and potential clinical implications of this association have been extensively analysed. In particular, the role of endothelial dysfunction in the pathophysiology of erectile dysfunction and the potential clinical usefulness of erectile dysfunction to identify diabetic patients with silent coronary artery disease have been outlined. Finally, recent guidelines on the treatment of erectile dysfunction with phosphodiesterase-5 inhibitors in diabetic patients with and without coronary artery disease have been reported and discussed.

Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

PubMed Central

Blaber, Elizabeth A.; Pecaut, Michael J.

2017-01-01

Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-‘omic analyses of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a downregulation in nuclear factor (erythroid-derived 2)-like 2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment. PMID:28953266

Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver.

PubMed

Blaber, Elizabeth A; Pecaut, Michael J; Jonscher, Karen R

2017-09-27

Increased oxidative stress is an unavoidable consequence of exposure to the space environment. Our previous studies showed that mice exposed to space for 13.5 days had decreased glutathione levels, suggesting impairments in oxidative defense. Here we performed unbiased, unsupervised and integrated multi-'omic analyses of metabolomic and transcriptomic datasets from mice flown aboard the Space Shuttle Atlantis. Enrichment analyses of metabolite and gene sets showed significant changes in osmolyte concentrations and pathways related to glycerophospholipid and sphingolipid metabolism, likely consequences of relative dehydration of the spaceflight mice. However, we also found increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways, concomitant with enrichment of genes associated with autophagy and the ubiquitin-proteasome. When taken together with a downregulation in nuclear factor (erythroid-derived 2)-like 2-mediated signaling, our analyses suggest that decreased hepatic oxidative defense may lead to aberrant tRNA post-translational processing, induction of degradation programs and senescence-associated mitochondrial dysfunction in response to the spaceflight environment.

Accuracy of integrated total pelvic floor ultrasound compared to defaecatory MRI in females with pelvic floor defaecatory dysfunction

PubMed Central

Pilkington, Sophie A; Grierson, Catherine; Rutherford, Elizabeth; Schizas, Alexis M P; Nugent, Karen P; Williams, Andrew B

2016-01-01

Objective: Defaecatory MRI allows multicompartmental assessment of defaecatory dysfunction but is often inaccessible. Integrated total pelvic floor ultrasound (transperineal, transvaginal, endoanal) may provide a cheap, portable alternative. The accuracy of total pelvic floor ultrasound for anatomical abnormalities when compared with defaecatory MRI was assessed. Methods: The dynamic images from 68 females who had undergone integrated total pelvic floor ultrasound and defaecatory MRI between 2009 and 2015 were blindly reviewed. The following were recorded: rectocoele, enterocoele, intussusception and cystocoele. Results: There were 26 rectocoeles on MRI (49 rectocoeles on ultrasound), 24 rectocoeles with intussusception on MRI (19 rectocoeles on ultrasound), 23 enterocoeles on MRI (24 enterocoeles on ultrasound) and 49 cystocoeles on MRI (35 cystocoeles on ultrasound). Sensitivity and specificity of total pelvic floor ultrasound were 81% and 33% for rectocoele, 60% and 91% for intussusception, 65% and 80% for enterocoele and 65% and 84% for cystocoele when compared with defaecatory MRI. This gave a negative-predictive value and positive-predictive value of 74% and 43% for rectocoele, 80% and 79% for intussusception, 82% and 63% for enterocoele and 48% and 91% for cystocoele. Conclusion: Integrated total pelvic floor ultrasound may serve as a screening tool for pelvic floor defaecatory dysfunction; when normal, defaecatory MRI can be avoided, as rectocoele, intussusception and enterocoele are unlikely to be present. Advances in knowledge: This is the first study to compare integrated total pelvic floor ultrasound with defaecatory MRI. The results support the use of integrated total pelvic floor ultrasound as a screening tool for defaecatory dysfunction. PMID:27730818

CNGA3 deficiency affects cone synaptic terminal structure and function and leads to secondary rod dysfunction and degeneration.

PubMed

Xu, Jianhua; Morris, Lynsie M; Michalakis, Stylianos; Biel, Martin; Fliesler, Steven J; Sherry, David M; Ding, Xi-Qin

2012-03-01

To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3-/- mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3-/- mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3-/- retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%-40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3-/- retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised.

The diagnosis and management of progressive dysfunction of health care organizations.

PubMed

Chervenak, Frank A; McCullough, Laurence B

2005-04-01

This paper presents an ethically justified approach to the diagnosis and management of progressive dysfunction of health care organizational cultures. We explain the concept of professional integrity in terms of the ethical concept of the cofiduciary responsibility of physicians and health care organizations. We identify the ethical features of a healthy health care organization and the spectrum of progressive dysfunction of organizational cultures from cynical through wonderland and Kafkaesque to postmodern. Physicians should respond to cynical health care organizations by creating moral enclaves of professional integrity for the main purpose of confrontation and reform, to wonderland organizations by strengthening moral enclaves for the main purpose of resisting self-deception, to Kafkaesque organizations by strengthening moral enclaves still further for the main purpose of defending professional integrity (adopting a Machiavellian appearance of virtue as necessary), and to postmodern organizations by creating moral fortresses and, should these fail, quitting.

Pelvic floor complaints in gastroenterology practice: results of a survey in the netherlands

PubMed Central

Nicolai, Melianthe P J; Fidder, Herma H; Bekker, Milou D; Putter, Hein; Pelger, Rob C M; Elzevier, Henk W

2012-01-01

Objective The pelvic floor is an integrated structure; dysfunctions may lead to a wide range of symptoms, involving voiding, defecation and sexual functioning (SF). Functional symptoms such as constipation and lower abdominal pain are often caused by pelvic floor dysfunction (PFD), and they highly impact the quality of life. Multiple specialists are responsible for a specific part of the pelvic floor, but its treatment asks for a holistic approach. The authors are still unaware of gastroenterologists' knowledge on PFD or whether they are addressing pelvic floor complaints in their daily practice. Design A 42-itemed anonymous questionnaire was mailed to all 402 members of the Dutch Society of Gastroenterology (gastroenterologists and residents-in-training). Results 169 (42%) questionnaires were analysed. Most gastroenterologists address lower urinary tract symptoms in their history-taking, 92% in female patients and 84% in male patients. When patients indicate irritable bowel syndrome-like complaints, more than 60% of the physicians inquire about SF to their female patients, compared with 38% inquiries to male patients (p<0.001). A reason not to inquire about SF is a lack of knowledge about female and male sexuality (19% and 23%, respectively). Forty-six per cent of the respondents regard it rather important to receive more training on PFD in male patients versus 61% in female patients. Conclusion Awareness of PFD is not yet routinely integrated into the history taken by gastroenterologists. PMID:24124626

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

PubMed

Peter, Jessica; Lahr, Jacob; Minkova, Lora; Lauer, Eliza; Grothe, Michel J; Teipel, Stefan; Köstering, Lena; Kaller, Christoph P; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Reis, Janine; Klöppel, Stefan

2016-06-18

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.

Attention deficit/hyperactivity-disorder and obesity: A review and model of current hypotheses explaining their comorbidity.

PubMed

Hanć, Tomasz; Cortese, Samuele

2018-05-19

Available meta-analyses point to a significant association between attention-deficit/hyperactivity disorder (ADHD) and obesity. The possible mechanisms underlying this relationship are unclear. Here, we overview the studies aimed at identifying the factors contributing to the comorbidity between ADHD and obesity, including genetic factors, fetal programming, executive dysfunctions, psychosocial stress, factors directly related to energy balance, and sleep patterns alterations. The bulk of current research has focused on reduced physical activity and abnormal eating patterns as possible causes of weight gain in individuals with ADHD. Further research is needed to explore the specific role of executive dysfunctions. None of the available published studies have evaluated physiological mechanisms such as hormonal and metabolic disorders or inappropriate neurobiological regulation of appetite. Research exploring the genetic basis for the coexistence of ADHD and obesity and epigenetic mechanisms, with particular emphasis on stress, both pre- and postnatal, seems particularly promising. Here, we propose a biopsychosocial model to integrate current findings and move the field forward to gain insight into the ADHD-obesity relationship. Copyright © 2018 Elsevier Ltd. All rights reserved.

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

PubMed

Koster, Geert; Bekema, Hanneke J; Wetterslev, Jørn; Gluud, Christian; Keus, Frederik; van der Horst, Iwan C C

2016-09-01

Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction. This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria. A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76-1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data. The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

Interoceptive Dysfunction: Toward An Integrated Framework for Understanding Somatic and Affective Disturbance in Depression

PubMed Central

Harshaw, Christopher

2014-01-01

Depression is characterized by disturbed sleep and eating, a variety of other, nonspecific somatic symptoms, and significant somatic comorbidities. Why there is such close association between cognitive and somatic dysfunction in depression is nonetheless poorly understood. An explosion of research in the area of interoception—the perception and interpretation of bodily signals—over the last decade nonetheless holds promise for illuminating what have until now been obscure links between the social, cognitive-affective, and somatic features of depression. This paper reviews rapidly accumulating evidence that both somatic signaling and interoception are frequently altered in depression. This includes comparative studies showing vagus-mediated effects on depression-like behaviors in rodent models as well as studies in humans indicating both dysfunction in the neural substrates for interoception (e.g., vagus, insula, anterior cingulate cortex) and reduced sensitivity to bodily stimuli in depression. An integrative framework for organizing and interpreting this evidence is put forward which incorporates (a) multiple potential pathways to interoceptive dysfunction; (b) interaction with individual, gender, and cultural differences in interoception; and (c) a developmental psychobiological systems perspective, emphasizing likely differential susceptibility to somatic and interoceptive dysfunction across the lifespan. Combined with current theory and evidence, it is suggested that core symptoms of depression (e.g., anhedonia, social deficits) may be products of disturbed interoceptive-exteroceptive integration. More research is nonetheless needed to fully elucidate the relationship between mind, body, and social context in depression. PMID:25365763

Understanding Sensory Integration. ERIC Digest.

ERIC Educational Resources Information Center

DiMatties, Marie E.; Sammons, Jennifer H.

This brief paper summarizes what is known about sensory integration and sensory integration dysfunction (DSI). It outlines evaluation of DSI, treatment approaches, and implications for parents and teachers, including compensatory strategies for minimizing the impact of DSI on a child's life. Review of origins of sensory integration theory in the…

CNGA3 Deficiency Affects Cone Synaptic Terminal Structure and Function and Leads to Secondary Rod Dysfunction and Degeneration

PubMed Central

Xu, Jianhua; Morris, Lynsie M.; Michalakis, Stylianos; Biel, Martin; Fliesler, Steven J.; Sherry, David M.

2012-01-01

Purpose. To investigate rod function and survival after cone dysfunction and degeneration in a mouse model of cone cyclic nucleotide-gated (CNG) channel deficiency. Methods. Rod function and survival in mice with cone CNG channel subunit CNGA3 deficiency (CNGA3−/− mice) were evaluated by electroretinographic (ERG), morphometric, and Western blot analyses. The arrangement, integrity, and ultrastructure of photoreceptor terminals were investigated by immunohistochemistry and electron microscopy. Results. The authors found loss of cone function and cone death accompanied by impairment of rods and rod-driven signaling in CNGA3−/− mice. Scotopic ERG b-wave amplitudes were reduced by 15% at 1 month, 30% at 6 months, and 40% at 9 months and older, while scotopic a-wave amplitudes were decreased by 20% at 9 months, compared with ERGs of age-matched wild-type mice. Outer nuclear layer thickness in CNGA3−/− retina was reduced by 15% at 12 months compared with age-matched wild-type controls. This was accompanied by a 30%–40% reduction in expression of rod-specific proteins, including rhodopsin, rod transducin α-subunit, and glutamic acid-rich protein (GARP). Cone terminals in the CNGA3−/− retina showed a progressive loss of neurochemical and ultrastructural integrity. Abnormalities were observed as early as 1 month. Disorganized rod terminal ultrastructure was noted by 12 months. Conclusions. These findings demonstrate secondary rod impairment and degeneration after cone degeneration in mice with cone CNG channel deficiency. Loss of cone phototransduction accompanies the compromised integrity of cone terminals. With time, rod synaptic structure, function, and viability also become compromised. PMID:22247469

Treatment of Sexual Disorders in the 1990s: An Integrated Approach.

ERIC Educational Resources Information Center

Rosen, Raymond C.; Leiblum, Sandra R.

1995-01-01

Reviews existing data regarding the etiology and treatment of male and female sexual dysfunctions. Discusses the use of multidimensional assessment models, especially in the evaluation of erectile dysfunction and sexual pain disorders. Despite the conceptual and technological sophistication of current approaches, treatment outcomes are…

Distinguishing between Poor/Dysfunctional Parenting and Child Emotional Maltreatment

ERIC Educational Resources Information Center

Wolfe, David A.; McIsaac, Caroline

2011-01-01

Objective: This paper was intended to distinguish between poor parenting and child emotional maltreatment (CEM), to inform child welfare and public health policymakers of the need for differentiated responses. Methods: Scientific literature was integrated with current practice and assumptions relating to poor/dysfunctional parenting and child…

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction.

PubMed

Ansari, Uzair; Behnes, Michael; Hoffmann, Julia; Natale, Michele; Fastner, Christian; El-Battrawy, Ibrahim; Rusnak, Jonas; Kim, Seung Hyun; Lang, Siegfried; Hoffmann, Ursula; Bertsch, Thomas; Borggrefe, Martin; Akin, Ibrahim

2018-07-01

The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography. Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data. The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005). Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction. © The Korean Society for Laboratory Medicine.

Additional traditional Chinese medicine on gastrointestinal dysfunction in patients with sepsis: A systematic review and meta-analysis.

PubMed

Zhang, Yajing; Zhao, Zhiqiang; Tang, E; Hu, Yucai; Mao, Jingyuan

2016-03-01

To evaluate the clinical effect and safety of western medicine plus Traditional Chinese medicine for sepsis with gastrointestinal dysfunction. We searched CNKI (January 1979 to June 2014), VIP (January 1989 to June 2014), CBM (1978 to 2014), Wan Fang DATA (January 1990 to June 2014), PubMed (1978 to June 2014), The Cochrane Library (Issue 5, 2014), Embase (1974 to June 2014), and other relevant databases and journals to identify randomized controlled trials (RCTs) on western medicine plus Traditional Chinese medicine versus western medicine only for sepsis with gastrointestinal dysfunction. The methodological quality was assessed and the data was extracted according to the Cochrane Reviewer's Handbook and related methods. Meta-analyses were performed by RevMan 5.1.0 software. Five eligible studies included 278 patients. The results of meta-analyses showed that western medicine plus Traditional Chinese medicine therapy can improve the APACHEII score, the peristaltic sound score and SIRS score, improve abdominal distension, decreased white blood cell count, reduce DAO in sepsis patients with gastrointestinal dysfunction. 3 studies reported adverse reactions, there was no significant difference between two groups. Western medicine plus Traditional Chinese medicine can improve gastrointestinal dysfunction in sepsis.

Prevalence of intellectual dysfunctioning and its correlates in a community-residing elderly population.

PubMed

Nakanishi, N; Tatara, K; Shinsho, F; Takatorige, T; Murakami, S; Fukuda, H

1998-09-01

To examine the prevalence of intellectual dysfunctioning and its correlates in community-residing elderly people, a randomly selected sample of 1,405 people aged 65 and over living in Settsu, Osaka, were investigated in October 1992. Data for assessing intellectual dysfunctioning were obtained from 1,364 people (97.1%), excluding 21 clinically demented people (1.5%); 17.6/100, 5.6/100, and 3.3/100 of the population showed minor, moderate, and appreciable intellectual dysfunctioning, respectively, and the prevalence of intellectual dysfunctioning increased with age. By multivariate analyses using logistic regression, age over 75, poor general health, including current medical treatment, and psychosocial conditions such as no participation in social activities, no life worth living (no Ikigai), and anxiety about the future were independent risk factors for intellectual dysfunctioning. We conclude that intellectual dysfunctioning is closely associated with health and psychosocial conditions.

Anterior Temporal Lobe Connectivity Correlates with Functional Outcome after Aphasic Stroke

ERIC Educational Resources Information Center

Warren, Jane E.; Crinion, Jennifer T.; Ralph, Matthew A. Lambon; Wise, Richard J. S.

2009-01-01

Focal brain lesions are assumed to produce language deficits by two basic mechanisms: local cortical dysfunction at the lesion site, and remote cortical dysfunction due to disruption of the transfer and integration of information between connected brain regions. However, functional imaging studies investigating language outcome after aphasic…

Coping, subjective burden and anxiety among family caregivers of older dependents.

PubMed

del-Pino-Casado, Rafael; Pérez-Cruz, Margarita; Frías-Osuna, Antonio

2014-12-01

To investigate relationships between anxiety and stressors,coping and subjective burden and to contribute to defining factors related to anxiety among family caregivers of older dependents. Despite the studies analysing factors related to anxiety in caregivers, there is not enough evidence about this issue. Cross-sectional design. Data from 140 family caregivers (convenience sample) were analysed using descriptive statistics, correlation coefficients and path analysis. Socio-demographic data and several scales (Barthel Index, Short Portable Mental Status Questionnaire, Cummings Neuropsychiatric Inventory, Brief COPE, Caregiver Strain Index and Hamilton Anxiety Rating Scale) were used to collect data. Stressors (psychiatric and psychological symptoms and number of assisted activities of daily living), emotion-focused coping, dysfunctional coping and subjective burden were related to greater anxiety. Subjective burden mediated the effects of psychiatric and psychological symptoms on anxiety and partially mediated the effects of dysfunctional coping on anxiety. Stressors, dysfunctional coping and subjective burden were identified as factors related to anxiety. The mediating role of subjective burden in the relationship between dysfunctional coping and anxiety was supported. The effect of dysfunctional coping on anxiety was independent of the stressors. These conclusions justify several recommendations regarding nursing interventions for family caregivers of older dependents: (1) stressors,dysfunctional coping and subjective burden can be used in clinical practice for early detection of and early intervention for anxiety; (2) to prevent subjective burden and anxiety,approach-coping skills should be promoted through interventions such as problem-solving,positive reappraisal, assertiveness and control of negative thoughts; (3) these interventions for dysfunctional coping should be systematically developed for individuals with dysfunctional coping regardless of the level of stressors and/or the possibility of respite.

Examining the Role of Anxiety Sensitivity in Sleep Dysfunction Across Anxiety Disorders.

PubMed

Baker, Amanda W; Keshaviah, Aparna; Goetter, Elizabeth M; Bui, Eric; Swee, Michaela; Rosencrans, Peter L; Simon, Naomi M

2017-01-01

Anxiety Sensitivity (AS) has been associated with sleep difficulties in certain anxiety disorder populations, but no studies have examined cross-diagnostically the role of anxiety sensitivity in sleep dysfunction. Three hundred one participants with generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD) completed an ancillary questionnaire-based study. Linear regression was used to examine AS and sleep dysfunction, and mediation analyses were used to examine whether AS was a mediator of the effect of primary diagnosis on sleep. AS was associated with increased sleep dysfunction across anxiety disorders, and primary anxiety disorder diagnosis was significantly associated with sleep dysfunction. However, after controlling for AS, primary diagnosis was no longer significant. AS significantly mediated the effects of PD versus SAD and of PD versus GAD on sleep dysfunction, but did not significantly mediate the effect of GAD versus SAD on sleep dysfunction. Taken together, AS appears to be a more important predictor of sleep dysfunction overall, emphasizing the cross-diagnostic nature of AS and bolstering the RDoC initiative approach for treating psychological dysfunction.

Integrated analysis of long noncoding RNA and mRNA profiling ox-LDL-induced endothelial dysfunction after atorvastatin administration.

PubMed

Jiang, Ling-Yu; Jiang, Yue-Hua; Qi, Ying-Zi; Shao, Lin-Lin; Yang, Chuan-Hua

2018-06-01

Long noncoding RNAs (lncRNAs) play a key role in the development of endothelial dysfunction. However, few lncRNAs associated with endothelial dysfunction after atorvastatin administration have been reported. In the present study, differentially expressed (DE) genes in ox-LDL versus control and ox-LDL + atorvastatin versus control were detected. Bioinformatics analysis and integrated analysis of mRNAs and lncRNAs were conducted to study the mechanisms of endothelial dysfunction after atorvastatin administration and to explore the regulation functions of lncRNAs. Here, 532 DE mRNAs and 532 DE lncRNAs were identified (among them, 195 mRNAs and 298 lncRNAs were upregulated, 337 mRNAs and 234 lncRNAs were downregulated) after ox-LDL treatment for 24 hours (fold change ≥2.0, P < .05). After ox-LDL treatment following atorvastatin administration, 750 DE mRNAs and 502 DE lncRNAs were identified (among them, 149 mRNAs and 218 lncRNAs were upregulated and 601 mRNAs and 284 lncRNAs were downregulated). After atorvastatin administration, 167 lncRNAs and 262 mRNAs were still DE. Q-PCR validated the results of microarrays. Chronic inflammatory response, nitric oxide biosynthetic process, microtubule cytoskeleton, cell proliferation and cell migration are regulated by lncRNAs, which also participated in the mainly molecular function and biological processes underlying endothelial dysfunction. Atorvastatin partly improved endothelial dysfunction, but the aspects beyond recovery were mainly concentrated in cell cycle, mitosis, and metabolism. Further exploration is required to explicit the mechanism by which lncRNAs participate in endothelial dysfunction.

[Dysfunctional family in the context of alcoholism: concept analysis].

PubMed

Mangueira, Suzana de Oliveira; Lopes, Marcos Venícios de Oliveira

2014-01-01

Alcoholism is considered an associated factor to the family dysfunction, revealing the need for health professionals to overcome the purely individual perspective to offer a systemic focus. The aim of this study was to analyze the concept dysfunctional family in the context of alcoholism. The study followed the Concept Analysis Model and steps of integrative literature review. It was identifi ed the antecedents of alcoholism, the attributes and the consequent dysfunctional family and it was reported a model case which illustrated the presence of these elements. It was observed that this is a broad concept, subjective and complex, with emphasis on studies on the consequents related to children of alcoholics.

ApoptoProteomics, an integrated database for analysis of proteomics data obtained from apoptotic cells.

PubMed

Arntzen, Magnus Ø; Thiede, Bernd

2012-02-01

Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt-KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no.

ApoptoProteomics, an Integrated Database for Analysis of Proteomics Data Obtained from Apoptotic Cells*

PubMed Central

Arntzen, Magnus Ø.; Thiede, Bernd

2012-01-01

Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt-KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no. PMID:22067098

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical trial design for women. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.

PubMed

Raththagala, Madushi; Brewer, M Kathryn; Parker, Matthew W; Sherwood, Amanda R; Wong, Brian K; Hsu, Simon; Bridges, Travis M; Paasch, Bradley C; Hellman, Lance M; Husodo, Satrio; Meekins, David A; Taylor, Adam O; Turner, Benjamin D; Auger, Kyle D; Dukhande, Vikas V; Chakravarthy, Srinivas; Sanz, Pascual; Woods, Virgil L; Li, Sheng; Vander Kooi, Craig W; Gentry, Matthew S

2015-01-22

Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Disrupted neural processing of emotional faces in psychopathy.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Bosque, Javier; Ibern-Regàs, Immaculada; Hernández-Ribas, Rosa; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2014-04-01

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.

Managing Perceived Stress among College Students: The Roles of Social Support and Dysfunctional Coping

ERIC Educational Resources Information Center

Chao, Ruth Chu-Lien

2012-01-01

The author examined the conditions (i.e., social support and dysfunctional coping) under which perceived stress predicted psychological well-being in 459 college students. Hierarchical regression analyses indicated a significant 2-way interaction (Perceived Stress x Social Support) and a significant 3-way interaction (Perceived Stress x Social…

Patterns of language and auditory dysfunction in 6-year-old children with epilepsy.

PubMed

Selassie, Gunilla Rejnö-Habte; Olsson, Ingrid; Jennische, Margareta

2009-01-01

In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y-6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y-6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.

Parental psychological control and dysfunctional separation-individuation: a tale of two different dynamics.

PubMed

Kins, Evie; Soenens, Bart; Beyers, Wim

2012-10-01

This study examined associations between psychologically controlling parenting and two possible manifestations of problematic separation-individuation (i.e., dysfunctional dependence and dysfunctional independence). To explain these associations, it has been argued that psychological control is an inherently independence-stifling parenting dimension that gives rise to a dysfunctional dependent orientation. In this study, it was argued that psychological control may relate to dysfunctional dependence and dysfunctional independence, depending on whether parents' use of psychological control is driven by issues of interpersonal closeness (i.e., dependency-oriented psychological control) or by issues of achievement (i.e., achievement-oriented psychological control). A Belgian sample of 232 emerging adults, involved in the process of home leaving, and their parents completed self-report questionnaires. Regression analyses indicated that domain-specific expressions of psychological control were related differentially to dysfunctional dependent and dysfunctional independent manifestations of problematic separation-individuation. Emerging adults' residential status did not moderate these associations. Implications and directions for future research are discussed. Copyright © 2012 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Multidisciplinary Management of Sexual Dysfunction, Perineal Pain, and Elimination Dysfunction in a Woman with Multiple Sclerosis

PubMed Central

Bogliatto, Fabrizio; Bacchio, Leonardo

2017-01-01

Background: Multiple sclerosis (MS) is a chronic disease that commonly affects young women and is associated with sexual dysfunction (SD) and lower anourogenital dysfunction, which affect quality of life. We evaluated the importance of an integrated multidisciplinary approach in the Lower Female Ano-Uro-Genital Network (LFAUGN) to manage a variety of complex symptoms. Methods: A 40-year-old woman with MS and primary concerns about perineal pain and SD was treated by a trained midwife from the LFAUGN and a physical therapist after a multidisciplinary diagnostic process that included gynecologic evaluation for perineal pain and SD, physiatric assessment, urologic assessment for bladder retention (BR), and surgical examination for obstructed defecation syndrome (ODS). Physical therapy was integrated with pharmacologic therapy for ODS and with self-catheterization for BR. Results: After 5 months of treatment, the patient reported improvement in functional perineal parameters and perineal pain (visual analogue scale score: 9 at T1 vs. 5 at T2), with resolution of pelvic floor hypertonia. Furthermore, ODS and BR symptoms improved (5-item score: 18 of 20 at T1 vs. 10 of 20 at T2; 1 self-catheterization daily, with postvoid residual volume [PRV] <200 mL at T1 vs. 1 self-catheterization weekly, with PRV <100 mL at T2) and sexual satisfaction increased (Female Sexual Function Index score: 18 of 36 at T1 vs. 23 of 36 at T2). Conclusions: These results suggest that physical therapy, as an integral component of a multidisciplinary approach in a multiprofessional network, may play a pivotal role in improving anourogenital dysfunction and sexual satisfaction. PMID:28243183

Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction.

PubMed

Yamasue, Hidenori; Yee, Jason R; Hurlemann, René; Rilling, James K; Chen, Frances S; Meyer-Lindenberg, Andreas; Tost, Heike

2012-10-10

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled "Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction." This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.

Heading in Soccer: Integral Skill or Grounds for Cognitive Dysfunction?

ERIC Educational Resources Information Center

Kirkendall, Donald T.; Garrett, William E., Jr.

2001-01-01

Discusses how purposeful heading of soccer balls and head injuries affect soccer players' cognitive dysfunction. Cognitive deficits may occur for many reasons. Heading cannot be blamed when details of the actual event and impact are unknown. Concussions are the most common head injury in soccer and a factor in cognitive deficits and are probably…

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

2009-01-01

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia.

PubMed

Skeldon, Sean C; Detsky, Allan S; Goldenberg, S Larry; Law, Michael R

2015-01-01

We investigated whether erectile dysfunction, a marker for future cardiovascular disease, is associated with undiagnosed cardiometabolic risk factors among US men. Identifying the presence of these risk factors could lead to earlier initiation of treatment for primary prevention of cardiovascular disease. We analyzed cross-sectional data from men aged 20 years and older who participated in the National Health and Nutrition Examination Survey during 2001-2004. Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes. After multivariate adjustment, men with erectile dysfunction had more than double the odds of having undiagnosed diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the presence of erectile dysfunction. Our results underscore the importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile dysfunction should be a trigger to initiate diabetes screening, particularly among middle-aged men. © 2015 Annals of Family Medicine, Inc.

Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.

PubMed

Gavini, S; Borges, L F; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2017-05-01

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF. This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic. Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction. MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF. © 2016 John Wiley & Sons Ltd.

Pyrano-isoflavones with erectile-dysfunction activity from Eriosema kraussianum.

PubMed

Drewes, Siegfried E; Horn, Marion M; Munro, Orde Q; Dhlamini, Jabu T B; Meyer, J J Marion; Rakuambo, N Christopher

2002-04-01

Five pyrano-isoflavones have been isolated from the rootstock of Eriosema kraussianum N. E. Br (Papilionaceae). Spectral data and single crystal X-ray analyses were used for structural elucidation. The most active of the compounds had an activity of 75% of that found in Viagra in the erectile dysfunction test on rabbit penile smooth muscle.

Functional illness in primary care: dysfunction versus disease

PubMed Central

Williams, Nefyn; Wilkinson, Clare; Stott, Nigel; Menkes, David B

2008-01-01

Background The Biopsychosocial Model aims to integrate the biological, psychological and social components of illness, but integration is difficult in practice, particularly when patients consult with medically unexplained physical symptoms or functional illness. Discussion This Biopsychosocial Model was developed from General Systems Theory, which describes nature as a dynamic order of interacting parts and processes, from molecular to societal. Despite such conceptual progress, the biological, psychological, social and spiritual components of illness are seldom managed as an integrated whole in conventional medical practice. This is because the biomedical model can be easier to use, clinicians often have difficulty relinquishing a disease-centred approach to diagnosis, and either dismiss illness when pathology has been excluded, or explain all undifferentiated illness in terms of psychosocial factors. By contrast, traditional and complementary treatment systems describe reversible functional disturbances, and appear better at integrating the different components of illness. Conventional medicine retains the advantage of scientific method and an expanding evidence base, but needs to more effectively integrate psychosocial factors into assessment and management, notably of 'functional' illness. As an aid to integration, pathology characterised by structural change in tissues and organs is contrasted with dysfunction arising from disordered physiology or psychology that may occur independent of pathological change. Summary We propose a classification of illness that includes orthogonal dimensions of pathology and dysfunction to support a broadly based clinical approach to patients; adoption of which may lead to fewer inappropriate investigations and secondary care referrals and greater use of cognitive behavioural techniques, particularly when managing functional illness. PMID:18482442

A Prorating Method for Estimating MMPI-2-RF Scores From MMPI Responses: Examination of Score Fidelity and Illustration of Empirical Utility in the PERSEREC Police Integrity Study Sample.

PubMed

Tarescavage, Anthony M; Corey, David M; Ben-Porath, Yossef S

2016-04-01

The purpose of the current study was to identify Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) correlates of police officer integrity violations and other problem behaviors in an archival database with original MMPI item responses and collateral information regarding integrity violations obtained for 417 male officers. In Study 1, we estimated MMPI-2-RF scores from the MMPI item pool (which includes approximately 80% of the MMPI-2-RF items) in a normative sample, a psychiatric inpatient sample, and a police officer sample, and conducted analyses that demonstrated the comparability of estimated and full scale scores for 41 of the 51 MMPI-2-RF scales. In Study 2, we correlated estimated MMPI-2-RF scores with information about subsequent integrity violations and problem behaviors from the integrity violation data set. Several meaningful associations were obtained, predominately with scales from the emotional, thought, and behavioral dysfunction domains of the MMPI-2-RF. Application of a correction for range restriction yielded substantially improved validity estimates. Finally, we calculated relative risk ratios for the statistically significant findings using cutoffs lower than 65T, which is traditionally used to identify clinically significant elevations, and found several meaningful relative risk ratios. © The Author(s) 2015.

Common and unique gray matter correlates of episodic memory dysfunction in frontotemporal dementia and Alzheimer's disease.

PubMed

Irish, Muireann; Piguet, Olivier; Hodges, John R; Hornberger, Michael

2014-04-01

Conflicting evidence exists regarding the integrity of episodic memory in the behavioral variant of frontotemporal dementia (bvFTD). Recent converging evidence suggests that episodic memory in progressive cases of bvFTD is compromised to the same extent as in Alzheimer's disease (AD). The underlying neural substrates of these episodic memory deficits, however, likely differ contingent on dementia type. In this study we sought to elucidate the neural substrates of episodic memory performance, across recall and recognition tasks, in both patient groups using voxel-based morphometry (VBM) analyses. We predicted that episodic memory dysfunction would be apparent in both patient groups but would relate to divergent patterns of neural atrophy specific to each dementia type. We assessed episodic memory, across verbal and visual domains, in 19 bvFTD, 18 AD patients, and 19 age- and education-matched controls. Behaviorally, patient groups were indistinguishable for immediate and delayed recall, across verbal and visual domains. Whole-brain VBM analyses revealed regions commonly implicated in episodic retrieval across groups, namely the right temporal pole, right frontal lobe, left paracingulate gyrus, and right anterior hippocampus. Divergent neural networks specific to each group were also identified. Whereas a widespread network including posterior regions such as the posterior cingulate cortex, parietal and occipital cortices was exclusively implicated in AD, the frontal and anterior temporal lobes underpinned the episodic memory deficits in bvFTD. Our results point to distinct neural changes underlying episodic memory decline specific to each dementia syndrome. Copyright © 2013 Wiley Periodicals, Inc.

The enteroinsular axis and endocrine pancreatic function in chronic alcohol consumers: evidence for early beta-cell hypofunction.

PubMed

Patto, R J; Russo, E K; Borges, D R; Neves, M M

1993-09-01

Chronic alcohol consumers may have, as judged by functional criteria, exocrine as well as endocrine pancreatic dysfunction, the latter represented by a decreased insulin response to an oral glucose load. To investigate whether this decreased insulin response was due to an ethanol-induced beta-cell dysfunction or to an ethanol-induced dysfunction of the enteroinsular axis, we determined glucose, insulin, and C-peptide plasma concentrations following an oral and an intravenous glucose load in 16 healthy volunteer nonalcohol consumers and in 10 chronic alcohol consumers. In each group, total integrated response for glucose did not significantly change whether glucose was given orally or intravenously, indicating isoglycemic glucose loads. The total integrated response values for insulin in the alcoholic group following both glucose loads as well as C-peptide plasma concentrations were significantly lower than in the control group. Moreover, in both groups the insulin TIR values following the oral glucose load were significantly greater than the values obtained following the intravenous glucose load, indicating an incretin effect. These results indicate that the decreased insulin response observed in alcoholics was not caused by a dysfunction of the enteroinsular axis because it also occurred following an intravenous glucose load, but by an ethanol-induced beta-cell dysfunction because C-peptide and insulin were proportionally decreased in this group.

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

PubMed

Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2016-12-13

Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

The General Assessment of Personality Disorder (GAPD) as an instrument for assessing the core features of personality disorders.

PubMed

Berghuis, Han; Kamphuis, Jan H; Verheul, Roel; Larstone, Roseann; Livesley, John

2013-01-01

This study presents a psychometric evaluation of the General Assessment of Personality Disorder (GAPD), a self-report questionnaire for assessing the core components of personality dysfunction on the basis of Livesley's (2003) adaptive failure model. Analysis of samples from a general (n = 196) and a clinical population (n = 280) from Canada and the Netherlands, respectively, found a very similar two-component structure consistent with the two core components of personality dysfunction proposed by the model, namely, self-pathology and interpersonal dysfunction. Moreover, the GAPD discriminated between patients diagnosed with and without Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) personality disorder(s) and demonstrated discriminative power in detecting the severity of personality pathology. Correlations with a DSM-IV symptom measure and a pathological traits model suggest partial conceptual overlap. Although further testing is indicated, the present findings suggest the GAPD is suitable for assessing the core components of personality dysfunction. It may contribute to a two-step integrated assessment of personality pathology that assesses both personality dysfunction and personality traits. The core features of personality disorder can be defined as disorders in the self and in the capacity for interpersonal functioning. A clinically useful operationalization of disordered functioning of personality is needed to determine the maladaptivity of personality traits. An integrated assessment of personality (dys)functioning and personality traits provides a more comprehensive clinical picture of the patient, which may aid treatment planning. Copyright © 2012 John Wiley & Sons, Ltd.

Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors

PubMed Central

Ullrich, Nicole J.; Whelen, Megan J.; Lange, Beverly J.

2014-01-01

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes. PMID:25080574

Pelvic Muscle Rehabilitation: A Standardized Protocol for Pelvic Floor Dysfunction

PubMed Central

Pedraza, Rodrigo; Nieto, Javier; Ibarra, Sergio; Haas, Eric M.

2014-01-01

Introduction. Pelvic floor dysfunction syndromes present with voiding, sexual, and anorectal disturbances, which may be associated with one another, resulting in complex presentation. Thus, an integrated diagnosis and management approach may be required. Pelvic muscle rehabilitation (PMR) is a noninvasive modality involving cognitive reeducation, modification, and retraining of the pelvic floor and associated musculature. We describe our standardized PMR protocol for the management of pelvic floor dysfunction syndromes. Pelvic Muscle Rehabilitation Program. The diagnostic assessment includes electromyography and manometry analyzed in 4 phases: (1) initial baseline phase; (2) rapid contraction phase; (3) tonic contraction and endurance phase; and (4) late baseline phase. This evaluation is performed at the onset of every session. PMR management consists of 6 possible therapeutic modalities, employed depending on the diagnostic evaluation: (1) down-training; (2) accessory muscle isolation; (3) discrimination training; (4) muscle strengthening; (5) endurance training; and (6) electrical stimulation. Eight to ten sessions are performed at one-week intervals with integration of home exercises and lifestyle modifications. Conclusions. The PMR protocol offers a standardized approach to diagnose and manage pelvic floor dysfunction syndromes with potential advantages over traditional biofeedback, involving additional interventions and a continuous pelvic floor assessment with management modifications over the clinical course. PMID:25006337

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness.

PubMed

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A C; de Man, Frances S

2016-07-01

The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. © 2016 The Authors.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

2016-01-01

Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

A feminist perspective on sexuality and body image in females with colorectal cancer: an integrative review.

PubMed

Li, Chia-Chun; Rew, Lynn

2010-01-01

Women often experience sexual dysfunction following colorectal cancer surgery. The purpose of this integrative review is to explore changes in body image and sexuality associated with colorectal cancer and its treatment in women. We used a feminist perspective to explore differences in gender role, in body image, and sexuality in the context of women who are treated for colorectal cancer. Results of our review suggest that additional studies and interventions are needed to better understand and assist women with sexual dysfunction associated with colorectal cancer. Research should focus on how age, physical, psychosocial factors influence sexual function in particular.

Telerehabilitation for addressing executive dysfunction after traumatic brain injury.

PubMed

Ng, Edith M W; Polatajko, Helene J; Marziali, Elsa; Hunt, Anne; Dawson, Deirdre R

2013-01-01

To investigate the feasibility of implementing the Cognitive Orientation to daily Occupational Performance approach (CO-OP) in a telerehabilitation format and to examine its impact on community integration and executive dysfunction for adults with traumatic brain injury (TBI). A pilot series of three case studies with 3-month follow-up was conducted. Three adults (all males, >10 years post-TBI) and their significant others were recruited. The CO-OP intervention, a meta-cognitive approach, was delivered through videoconferencing via Internet to train three of five participant-identified goals. Two goals were not trained to allow examination of transfer. Outcome measures included the Canadian Occupational Performance Measure, the Mayo-Portland Adaptability Inventory-4 Participation Index, and the Dysexecutive Questionnaire. Descriptive statistical analysis was used. The CO-OP approach administered in a telerehabilitation format was found to be feasible. All participants indicated self-reported improvement in both trained and untrained goals. Trends toward fewer symptoms of executive dysfunction and greater community integration were demonstrated. All participants expressed satisfaction with the Internet delivery method. Telerehabilitation shows promise as a way to deliver the CO-OP approach and may help promote community integration of individuals living with TBI. Further study is warranted.

The Dual Edema-Preventing Molecular Mechanism of the Crataegus Extract WS 1442 Can Be Assigned to Distinct Phytochemical Fractions.

PubMed

Fuchs, Simone; Bischoff, Iris; Willer, Elisabeth A; Bräutigam, Jacqueline; Bubik, Martin F; Erdelmeier, Clemens A J; Koch, Egon; Faleschini, Maria T; De Mieri, Maria; Bauhart, Milena; Zahler, Stefan; Hensel, Andreas; Hamburger, Matthias; Potterat, Olivier; Fürst, Robert

2017-05-01

The hawthorn ( Crataegus spp.) extract WS 1442 is used against mild forms of chronic heart failure. This disease is associated with endothelial barrier dysfunction and edema formation. We have recently shown that WS 1442 protects against this dysfunction by a dual mechanism: it both promotes endothelial barrier integrity by activation of a barrier-enhancing pathway (cortactin activation) and inhibits endothelial hyperpermeability by blocking a barrier disruptive pathway (calcium signaling). In this study, we aimed to identify the bioactive compounds responsible for these actions by using a bioactivity-guided fractionation approach. From the four fractions generated from WS 1442 by successive elution with water, 95 % ethanol, methanol, and 70 % acetone, only the water fraction was inactive, whereas the other three triggered a reduction of endothelial hyperpermeability. Analyses of intracellular calcium levels and cortactin phosphorylation were used as readouts to estimate the bioactivity of subfractions and isolated compounds. Interestingly, only the ethanolic fraction interfered with the calcium signaling, whereas only the methanolic fraction led to an activation of cortactin. Thus, the dual mode of action of WS 1442 could be clearly assigned to two distinct fractions. Although the identification of the calcium-active substance(s) was not successful, we could exclude an involvement of phenolic compounds. Cortactin activation, however, could be clearly attributed to oligomeric procyanidins with a distinct degree of polymerization. Taken together, our study provides the first approach to identify the active constituents of WS 1442 that address different cellular pathways leading to the inhibition of endothelial barrier dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart

PubMed Central

Croston, Tara L.; Thapa, Dharendra; Holden, Anthony A.; Tveter, Kevin J.; Lewis, Sara E.; Shepherd, Danielle L.; Nichols, Cody E.; Long, Dustin M.; Olfert, I. Mark; Jagannathan, Rajaganapathi

2014-01-01

The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination of cardiac mitochondria is complicated by the existence of spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to cardiac SSM has been reported in murine models of type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not been explored in type 2 diabetic human heart. The goal of this study was to determine the impact of type 2 diabetes mellitus on cardiac mitochondrial function in the human patient. Mitochondrial subpopulations from atrial appendages of patients with and without type 2 diabetes were examined. Complex I- and fatty acid-mediated mitochondrial respiration rates were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with no change in IFM. Electron transport chain (ETC) complexes I and IV activities were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with a concomitant decline in their levels (P ≤ 0.05 for both). Regression analyses comparing comorbidities determined that diabetes mellitus was the primary factor accounting for mitochondrial dysfunction. Linear spline models examining correlative risk for mitochondrial dysfunction indicated that patients with diabetes display the same degree of state 3 and electron transport chain complex I dysfunction in SSM regardless of the extent of glycated hemoglobin (HbA1c) and hyperglycemia. Overall, the results suggest that independent of other pathologies, mitochondrial dysfunction is present in cardiac SSM of patients with type 2 diabetes and the degree of dysfunction is consistent regardless of the extent of elevated HbA1c or blood glucose levels. PMID:24778174

Racial differences in sexual dysfunction among postdeployed Iraq and Afghanistan veterans

PubMed Central

Monawar Hosain, G. M.; Latini, David M.; Kauth, Micahel R.; Goltz, Heather Honoré; Helmer, Drew A.

2015-01-01

This study examined the racial/ethnic differences in prevalence and risk factors of sexual dysfunction among postdeployed Iraqi/Afghanistan veterans. A total of 3,962 recently deployed veterans were recruited from Houston Veterans Affairs medical center. The authors examined sociodemographic, medical, mental-health, and lifestyle-related variables. Sexual dysfunction was diagnosed by ICD9-CM code and/or medicines prescribed for sexual dysfunction. Analyses included chi-square, analysis of variance, and multivariate logistic regression. Sexual dysfunction was observed 4.7% in Whites, 7.9% in African Americans, and 6.3% in Hispanics. Age, marital status, smoking, and hypertension were risk factors for Whites, whereas age, marital status, posttraumatic stress disorder and hypertension were significant for African Americans. For Hispanics, only age and posttraumatic stress disorder were significant. This study identified that risk factors of sexual dysfunction varied by race/ethnicity. All postdeployed veterans should be screened; and psychosocial support and educational materials should address race/ethnicity-specific risk factors. PMID:23300201

Toward an Integration of Psychologic, Social, and Biologic Factors in Depression: Effects on Outcome and Course of Cognitive Therapy.

ERIC Educational Resources Information Center

Simons, Anne D.; And Others

1995-01-01

Integrates key variables from three major domains (cognition, stress, and psychobiology) that are typically studied separately. Dysfunctional attitudes, negative life events, or sleep electroencephalogram were assessed in 53 outpatients before treatment with cognitive therapy. Results are discussed in terms of the promise of integrative research.…

Learning about Sensory Integration Dysfunction: Strategies to Meet Young Children's Sensory Needs at Home

ERIC Educational Resources Information Center

Thompson, Stacy D.; Rains, Kari W.

2009-01-01

Practitioners and parents are seeking ways to help children who are not able to integrate sensory information; this has generated recent media attention. A child's inability to integrate sensory information can have implications for the whole family and their everyday routines. Research conducted by occupational therapists has provided a rich…

TU-FG-201-09: Predicting Accelerator Dysfunction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Able, C; Nguyen, C; Baydush, A

Purpose: To develop an integrated statistical process control (SPC) framework using digital performance and component data accumulated within the accelerator system that can detect dysfunction prior to unscheduled downtime. Methods: Seven digital accelerators were monitored for twelve to 18 months. The accelerators were operated in a ‘run to failure mode’ with the individual institutions determining when service would be initiated. Institutions were required to submit detailed service reports. Trajectory and text log files resulting from a robust daily VMAT QA delivery were decoded and evaluated using Individual and Moving Range (I/MR) control charts. The SPC evaluation was presented in amore » customized dashboard interface that allows the user to review 525 monitored parameters (480 MLC parameters). Chart limits were calculated using a hybrid technique that includes the standard SPC 3σ limits and an empirical factor based on the parameter/system specification. The individual (I) grand mean values and control limit ranges of the I/MR charts of all accelerators were compared using statistical (ranked analysis of variance (ANOVA)) and graphical analyses to determine consistency of operating parameters. Results: When an alarm or warning was directly connected to field service, process control charts predicted dysfunction consistently on beam generation related parameters (BGP)– RF Driver Voltage, Gun Grid Voltage, and Forward Power (W); beam uniformity parameters – angle and position steering coil currents; and Gantry position accuracy parameter: cross correlation max-value. Control charts for individual MLC – cross correlation max-value/position detected 50% to 60% of MLCs serviced prior to dysfunction or failure. In general, non-random changes were detected 5 to 80 days prior to a service intervention. The ANOVA comparison of BGP determined that each accelerator parameter operated at a distinct value. Conclusion: The SPC framework shows promise. Long term monitoring coordinated with service will be required to definitively determine the effectiveness of the model. Varian Medical System, Inc. provided funding in support of the research presented.« less

Blood-brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone.

PubMed

Zhou, Ting; Zhao, Lei; Zhan, Rui; He, Qihua; Tong, Yawei; Tian, Xiaosheng; Wang, Hecheng; Zhang, Tao; Fu, Yaoyun; Sun, Yang; Xu, Feng; Guo, Xiangyang; Fan, Dongsheng; Han, Hongbin; Chui, Dehua

2014-10-24

Blood-brain barrier (BBB) dysfunction is a key event in the development of many central nervous system (CNS) diseases, such as septic encephalopathy and stroke. 4,4'-Diaminodiphenylsulfone (DDS, Dapsone) has displayed neuroprotective effect, but whether DDS has protective role on BBB integrity is not clear. This study was designed to examine the effect of DDS on lipopolysaccharide (LPS)-induced BBB disruption and oxidative stress in brain vessels. Using in vivo multiphoton imaging, we found that DDS administration significantly restored BBB integrity compromised by LPS. DDS also increased the expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Level of reactive oxygen species (ROS) was reduced by DDS treatment, which may due to decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NOX2 expression. Our results showed that LPS-induced BBB dysfunction could be attenuated by DDS, indicated that DDS has a therapeutic potential for treating CNS infection and other BBB related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

External self-representations improve self-awareness in a child with autism.

PubMed

Root, Nicholas B; Case, Laura K; Burrus, Caley J; Ramachandran, V S

2015-01-01

We have previously suggested that the social symptoms of autism spectrum disorder (ASD) could be caused in part by a dysfunctional mirror neuron system (MNS). Since the recursive activity of a functioning MNS might enable the brain to integrate visual and motor sensations into a coherent body schema, the deficits in self-awareness often seen in ASD might be caused by the same mirror neuron dysfunction. CL is an autistic adolescent who is profoundly fascinated with his reflection, looking in mirrors at every opportunity. We demonstrate that CL's abnormal gait improves significantly when using a mirror for visual feedback. We also show that both the fascination and the happiness that CL derives from looking at a computer-generated reflection diminish when a delay is introduced between the camera input and screen output. We believe that immediate, real-time visual feedback allows CL to integrate motor sensations with external visual ones into a coherent body schema that he cannot internally generate, perhaps due to a dysfunctional MNS.

Sexual dysfunction in women with ESRD requiring hemodialysis.

PubMed

Strippoli, Giovanni F M; Vecchio, Mariacristina; Palmer, Suetonia; De Berardis, Giorgia; Craig, Jonathan; Lucisano, Giuseppe; Johnson, David; Pellegrini, Fabio; Nicolucci, Antonio; Sciancalepore, Michela; Saglimbene, Valeria; Gargano, Letizia; Bonifati, Carmen; Ruospo, Marinella; Navaneethan, Sankar D; Montinaro, Vincenzo; Stroumza, Paul; Zsom, Marianna; Torok, Mariatta; Celia, Eduardo; Gelfman, Ruben; Bednarek-Skublewska, Anna; Dulawa, Jan; Graziano, Giusi; Gentile, Giorgio; Ferrari, Juan Nin; Santoro, Antonio; Zucchelli, Annalisa; Triolo, Giorgio; Maffei, Stefano; Hegbrant, Jörgen; Wollheim, Charlotta; De Cosmo, Salvatore; Manfreda, Valeria M

2012-06-01

The few existing studies of sexual dysfunction in women on hemodialysis are limited by small sample size. This large, cross-sectional study evaluated the prevalence and correlates of female sexual dysfunction in advanced kidney disease. DESIGN, SETTING, PARTICIPANTS, METHODS: A total of 1472 women with ESRD undergoing hemodialysis were recruited to a multinational, cross-sectional study conducted within a collaborative dialysis network in Europe and South America. Sexual dysfunction was identified by the Female Sexual Function Index. Correlates of self-reported sexual dysfunction were identified by regression analyses. Of the 1472 women, 659 completed questionnaires (45%). More than half (362 of 659 [55%]) lived with a partner, and 232 of 659 (35%) reported being sexually active. Of these 659 respondents, 555 (84%) reported sexual dysfunction. Women with a partner (282 of 362 [78%]) were less likely to report sexual dysfunction than those without a partner (273 of 297 [92%]) (P<0.001). Sexual dysfunction was independently associated with age, depressive symptoms, less education, menopause, diabetes, and diuretic therapy. Nearly all women who were not wait-listed for a kidney transplant and were living without a partner (249 of 260 [96%]) reported sexual dysfunction. More than half (128 of 232 [55%]) of sexually active women reported sexual dysfunction, associated with age, depressive symptoms, menopause, low serum albumin, and diuretic therapy. This descriptive study suggests most women on hemodialysis experience sexual problems. Additional research on the relevance of sexual dysfunction to symptom burden and quality of life in these women is needed.

Audiovisual speech integration in the superior temporal region is dysfunctional in dyslexia.

PubMed

Ye, Zheng; Rüsseler, Jascha; Gerth, Ivonne; Münte, Thomas F

2017-07-25

Dyslexia is an impairment of reading and spelling that affects both children and adults even after many years of schooling. Dyslexic readers have deficits in the integration of auditory and visual inputs but the neural mechanisms of the deficits are still unclear. This fMRI study examined the neural processing of auditorily presented German numbers 0-9 and videos of lip movements of a German native speaker voicing numbers 0-9 in unimodal (auditory or visual) and bimodal (always congruent) conditions in dyslexic readers and their matched fluent readers. We confirmed results of previous studies that the superior temporal gyrus/sulcus plays a critical role in audiovisual speech integration: fluent readers showed greater superior temporal activations for combined audiovisual stimuli than auditory-/visual-only stimuli. Importantly, such an enhancement effect was absent in dyslexic readers. Moreover, the auditory network (bilateral superior temporal regions plus medial PFC) was dynamically modulated during audiovisual integration in fluent, but not in dyslexic readers. These results suggest that superior temporal dysfunction may underly poor audiovisual speech integration in readers with dyslexia. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

[Clinical use of neurostimulation].

PubMed

Schmidt, R A; Tanagho, E A

1990-07-01

Our experience is broad-based and covers a number of difficult conditions that urologists deal with regularly. In patients who have been followed for several years, consistency of stimulation response has been observed. Even after use of the stimulator for several months or years, symptoms often return as soon as the stimulation ceases in cases of a malfunction or electrode movement. Neurostimulation, however, is no panacea. Patients with specific muscular dysfunction, determined urodynamically, must be carefully selected. They must also be willing to cooperate actively in their care. Test stimulation of the sacral nerves has provided invaluable insight into the neuromuscular responses mediated by the S2-4 nerves and has thus helped identify dysfunction that is specifically associated with each of these nerves. It has also helped discern differences between the integrity of pelvic muscles and the capability of the patient to use these muscles. This information allows the urologist to focus on a specific muscular dysfunction and to re-educate the patient to use the pelvic musculature properly or, failing this, to use neurostimulation via an implant to modulate the dysfunction. There must be a strong commitment on the part of the physician. No two patients are alike. Attention to patients' symptoms, the pattern of muscle dysfunction found in the pelvis, the responses to test stimulation, the urodynamic findings with and without stimulation, and the underlying anxieties of patients, which can contribute to symptoms, are all important considerations. Neurostimulation is an exciting and fascinating addition to the urologist's armamentarium. Most important, urologists are now able to test the functional integrity of the pelvic musculature and specifically identify weakness and dysfunction. Therapy can now be based on an assessment of the functional capabilities of the nervous system involved in micturition control.

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Ultrasound tissue characterization does not differentiate genotype, but indexes ejection fraction deterioration in becker muscular dystrophy.

PubMed

Giglio, Vincenzo; Puddu, Paolo Emilio; Holland, Mark R; Camastra, Giovanni; Ansalone, Gerardo; Ricci, Enzo; Mela, Julia; Sciarra, Federico; Di Gennaro, Marco

2014-12-01

The aims of the study were, first, to assess whether myocardial ultrasound tissue characterization (UTC) in Becker muscular dystrophy (BMD) can be used to differentiate between patients with deletions and those without deletions; and second, to determine whether UTC is helpful in diagnosing the evolution of left ventricular dysfunction, a precursor of dilated cardiomyopathy. Both cyclic variation of integrated backscatter and calibrated integrated backscatter (cIBS) were assessed in 87 patients with BMD and 70 controls. The average follow-up in BMD patients was 48 ± 12 mo. UTC analysis was repeated only in a subgroup of 40 BMD patients randomly selected from the larger overall group (15 with and 25 without left ventricular dysfunction). Discrimination between BMD patients with and without dystrophin gene deletion was not possible on the basis of UTC data: average cvIBS was 5.2 ± 1.2 and 5.5 ± 1.4 dB, and average cIBS was 29.9 ± 4.7 and 29.6 ± 5.8, respectively, significantly different (p < 0.001) only from controls (8.6 ± 0.5 and 24.6 ± 1.2 dB). In patients developing left ventricular dysfunction during follow-up, cIBS increased to 31.3 ± 5.4 dB, but not significantly (p = 0.08). The highest cIBS values (34.6 ± 5.3 dB, p < 0.09 vs. baseline, p < 0.01 vs BMD patients without left ventricular dysfunction) were seen in the presence of severe left ventricular dysfunction. Multivariate statistics indicated that an absolute change of 6 dB in cIBS is associated with a high probability of left ventricular dysfunction. UTC analysis does not differentiate BMD patients with or without dystrophin gene deletion, but may be useful in indexing left ventricular dysfunction during follow-up. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Competing endogenous RNA and interactome bioinformatic analyses on human telomerase.

PubMed

Arancio, Walter; Pizzolanti, Giuseppe; Genovese, Swonild Ilenia; Baiamonte, Concetta; Giordano, Carla

2014-04-01

We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT. The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex. Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres. Telomere dysfunctions have been widely reported to be involved in aging, cancer, and cellular senescence. The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid.org/) and related analysis tools such as Osprey (http://biodata.mshri.on.ca/osprey/servlet/Index) and GeneMANIA (http://genemania.org/). The network of interaction of hTERT transcripts has been further analyzed following the competing endogenous (ce) RNA hypotheses (messenger [m] RNAs cross-talk via micro [mi] RNAs) using the miRWalk database and tools (www.ma.uni-heidelberg.de/apps/zmf/mirwalk/). These analyses suggest a role for Akt, nuclear factor-κB (NF-κB), heat shock protein 90 (HSP90), p70/p80 autoantigen, 14-3-3 proteins, and dynein in telomere functions. Roles for histone acetylation/deacetylation and proteoglycan metabolism are also proposed.

MEG-based detection and localization of perilesional dysfunction in chronic stroke.

PubMed

Chu, Ron K O; Braun, Allen R; Meltzer, Jed A

2015-01-01

Post-stroke impairment is associated not only with structural lesions, but also with dysfunction in surviving perilesional tissue. Previous studies using equivalent current dipole source localization of MEG/EEG signals have demonstrated a preponderance of slow-wave activity localized to perilesional areas. Recent studies have also demonstrated the utility of nonlinear analyses such as multiscale entropy (MSE) for quantifying neuronal dysfunction in a wide range of pathologies. The current study utilized beamformer-based reconstruction of signals in source space to compare spectral and nonlinear measures of electrical activity in perilesional and healthy cortices. Data were collected from chronic stroke patients and healthy controls, both young and elderly. We assessed relative power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (15-30 Hz) frequency bands, and also measured the nonlinear complexity of electrical activity using MSE. Perilesional tissue exhibited a general slowing of the power spectrum (increased delta/theta, decreased beta) as well as a reduction in MSE. All measures tested were similarly sensitive to changes in the posterior perilesional regions, but anterior perilesional dysfunction was detected better by MSE and beta power. The findings also suggest that MSE is specifically sensitive to electrophysiological dysfunction in perilesional tissue, while spectral measures were additionally affected by an increase in rolandic beta power with advanced age. Furthermore, perilesional electrophysiological abnormalities in the left hemisphere were correlated with the degree of language task-induced activation in the right hemisphere. Finally, we demonstrate that single subject spectral and nonlinear analyses can identify dysfunctional perilesional regions within individual patients that may be ideal targets for interventions with noninvasive brain stimulation.

Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction.

PubMed

Rodiño-Janeiro, Bruno K; Martínez, Cristina; Fortea, Marina; Lobo, Beatriz; Pigrau, Marc; Nieto, Adoración; González-Castro, Ana María; Salvo-Romero, Eloísa; Guagnozzi, Danila; Pardo-Camacho, Cristina; Iribarren, Cristina; Azpiroz, Fernando; Alonso-Cotoner, Carmen; Santos, Javier; Vicario, Maria

2018-02-02

Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBS-D. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS.

An Empirical Typology of Perfectionism in Academically Talented Children.

ERIC Educational Resources Information Center

Parker, Wayne D.

1997-01-01

A national sample of 820 academically talented children took the Multidimensional Perfectionism Scale. Cluster analyses of scores found a three-cluster solution. Further analyses indicated that these clusters were: nonperfectionistic (32.%), healthy perfectionistic (41.7%), and dysfunctional perfectionistic (25.5%). The construct of perfectionism…

Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

PubMed

Kolbe, Scott C; Kilpatrick, Trevor J; Mitchell, Peter J; White, Owen; Egan, Gary F; Fielding, Joanne

2014-05-01

Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Copyright © 2013 Wiley Periodicals, Inc.

Lack of basic and luxury goods and health-related dysfunction in older persons; Findings from the longitudinal SMILE study

PubMed Central

Groffen, Daniëlle AI; Bosma, Hans; van den Akker, Marjan; Kempen, Gertrudis IJM; van Eijk, Jacques TM

2008-01-01

Background More so than the traditional socioeconomic indicators, such as education and income, wealth reflects the accumulation of resources and makes socioeconomic ranking manifest and explicitly visible to the outside world. While the lack of basic goods, such as a refrigerator, may affect health directly, via biological pathways, the lack of luxury goods, such as an LCD television, may affect health indirectly through psychosocial mechanisms. We set out to examine, firstly, the relevance of both basic and luxury goods in explaining health-related dysfunction in older persons, and, secondly, the extent to which these associations are independent of traditional socioeconomic indicators. Methods Cross-sectional and longitudinal data from 2067 men and women aged 55 years and older who participated in the Study on Medical Information and Lifestyles Eindhoven (SMILE) were gathered. Logistic regression analyses were used to study the relation between a lack of basic and luxury goods and health-related function, assessed with two sub-domains of the SF-36. Results The lack of basic goods was closely related to incident physical (OR = 2.32) and mental (OR = 2.12) dysfunction, even when the traditional measures of socioeconomic status, i.e. education or income, were taken into account. Cross-sectional analyses, in which basic and luxury goods were compared, showed that the lack of basic goods was strongly associated with mental dysfunction. Lack of luxury goods was, however, not related to dysfunction. Conclusion Even in a relatively wealthy country like the Netherlands, the lack of certain basic goods is not uncommon. More importantly, lack of basic goods, as an indicator of wealth, was strongly related to health-related dysfunction also when traditional measures of socioeconomic status were taken into account. In contrast, no effects of luxury goods on physical or mental dysfunction were found. Future longitudinal research is necessary to clarify the precise mechanisms underlying these effects. PMID:18637182

Lack of basic and luxury goods and health-related dysfunction in older persons; findings from the longitudinal SMILE study.

PubMed

Groffen, Daniëlle A I; Bosma, Hans; van den Akker, Marjan; Kempen, Gertrudis I J M; van Eijk, Jacques T M

2008-07-17

More so than the traditional socioeconomic indicators, such as education and income, wealth reflects the accumulation of resources and makes socioeconomic ranking manifest and explicitly visible to the outside world. While the lack of basic goods, such as a refrigerator, may affect health directly, via biological pathways, the lack of luxury goods, such as an LCD television, may affect health indirectly through psychosocial mechanisms. We set out to examine, firstly, the relevance of both basic and luxury goods in explaining health-related dysfunction in older persons, and, secondly, the extent to which these associations are independent of traditional socioeconomic indicators. Cross-sectional and longitudinal data from 2067 men and women aged 55 years and older who participated in the Study on Medical Information and Lifestyles Eindhoven (SMILE) were gathered. Logistic regression analyses were used to study the relation between a lack of basic and luxury goods and health-related function, assessed with two sub-domains of the SF-36. The lack of basic goods was closely related to incident physical (OR = 2.32) and mental (OR = 2.12) dysfunction, even when the traditional measures of socioeconomic status, i.e. education or income, were taken into account. Cross-sectional analyses, in which basic and luxury goods were compared, showed that the lack of basic goods was strongly associated with mental dysfunction. Lack of luxury goods was, however, not related to dysfunction. Even in a relatively wealthy country like the Netherlands, the lack of certain basic goods is not uncommon. More importantly, lack of basic goods, as an indicator of wealth, was strongly related to health-related dysfunction also when traditional measures of socioeconomic status were taken into account. In contrast, no effects of luxury goods on physical or mental dysfunction were found. Future longitudinal research is necessary to clarify the precise mechanisms underlying these effects.

Attachment anxiety and avoidance as mediators of the association between childhood maltreatment and adult personality dysfunction.

PubMed

Cohen, Lisa J; Ardalan, Firouz; Tanis, Thachell; Halmi, Winter; Galynker, Igor; Von Wyl, Agnes; Hengartner, Michael P

2017-02-01

This paper tests the hypothesis that the association between childhood maltreatment and adult personality dysfunction is at least partially attributable to insecure attachment, that is that attachment style mediates the relationship between childhood maltreatment and adult personality dysfunction. Associations between childhood trauma, as measured by the Childhood Trauma Questionnaire (CTQ), anxious and avoidant attachment in romantic relationships, as measured by the Experiences in Close Relationships-Revised (ECR-R), and five personality domains, as measured by the Severity Indices of Personality Problems (SIPP-118), were examined in a sample of 72 psychiatric inpatients. The SIPP-118 domains included relational capacities, identity integration, self-control, responsibility, and social concordance. The direct effect of childhood trauma on all SIPP-118 domains was not significant after controlling for the indirect effect of attachment. In regression modeling, a significant indirect effect of childhood trauma via adult attachment style was found for SIPP-118 relational capacities, identity integration, self-control, and social concordance. Specifically, anxious attachment was a significant mediator of the effect of childhood trauma on self-control, identity integration, and relational domains. These results suggest that childhood trauma impacts a broad range of personality domains and does so in large part through the pathway of anxious romantic attachment style.

Multidisciplinary, interdisciplinary, or dysfunctional? Team working in mixed-methods research.

PubMed

O'Cathain, Alicia; Murphy, Elizabeth; Nicholl, Jon

2008-11-01

Combining qualitative and quantitative methods in a single study-otherwise known as mixed-methods research-is common. In health research these projects can be delivered by research teams. A typical scenario, for example, involves medical sociologists delivering qualitative components and researchers from medicine or health economics delivering quantitative components. We undertook semistructured interviews with 20 researchers who had worked on mixed-methods studies in health services research to explore the facilitators of and barriers to exploiting the potential of this approach. Team working emerged as a key issue, with three models of team working apparent: multidisciplinary, interdisciplinary, and dysfunctional. Interdisciplinary research was associated with integration of data or findings from the qualitative and quantitative components in both the final reports and the peer-reviewed publications. Methodological respect between team members and a principal investigator who valued integration emerged as essential to achieving integrated research outcomes.

Long-term social integration and community support.

PubMed

Gordon, Wayne A; Cantor, Joshua; Kristen, Dams-O'Connor; Tsaousides, Theodore

2015-01-01

TBI often results in reduced social participation. This decrease in social participation is independent of injury severity and time since injury. Thus, it is one of the many stable hallmarks of TBI. Changes in social participation have been related to many factors, including emotional dysregulation and disturbance and executive dysfunction. While there are evidenced-based treatments available to improve mood and executive functioning, none of the research has examined the impact of the various treatments on social participation or social integration. Therefore, while it is reasonable to expect that individuals who are feeling better about themselves and who improve their approach to day-to-day function will also experience increased social contact, there is no evidence to support this claim. This chapter reviews the literature on post-TBI social integration and its relationship to depression and executive dysfunction. In addition the intervention research in this area is briefly examined. © 2015 Elsevier B.V. All rights reserved.

Comparison of Prediction Model for Cardiovascular Autonomic Dysfunction Using Artificial Neural Network and Logistic Regression Analysis

PubMed Central

Zeng, Fangfang; Li, Zhongtao; Yu, Xiaoling; Zhou, Linuo

2013-01-01

Background This study aimed to develop the artificial neural network (ANN) and multivariable logistic regression (LR) analyses for prediction modeling of cardiovascular autonomic (CA) dysfunction in the general population, and compare the prediction models using the two approaches. Methods and Materials We analyzed a previous dataset based on a Chinese population sample consisting of 2,092 individuals aged 30–80 years. The prediction models were derived from an exploratory set using ANN and LR analysis, and were tested in the validation set. Performances of these prediction models were then compared. Results Univariate analysis indicated that 14 risk factors showed statistically significant association with the prevalence of CA dysfunction (P<0.05). The mean area under the receiver-operating curve was 0.758 (95% CI 0.724–0.793) for LR and 0.762 (95% CI 0.732–0.793) for ANN analysis, but noninferiority result was found (P<0.001). The similar results were found in comparisons of sensitivity, specificity, and predictive values in the prediction models between the LR and ANN analyses. Conclusion The prediction models for CA dysfunction were developed using ANN and LR. ANN and LR are two effective tools for developing prediction models based on our dataset. PMID:23940593

Behavioral and Psychodynamic Dimensions of the New Sex Therapy

ERIC Educational Resources Information Center

Sollod, Robert N.

1975-01-01

The new sex therapy, a brief outpatient treatment of sexual dysfunction consisting of structured sexual exercises and conjoint therapeutic sessions, is a systematic integration of behavioral and psychodynamic elements. The integration of approaches in the new sex therapy has general significance for psychotherapeutic theory and practice. (Author)

Visual-Auditory Integration during Speech Imitation in Autism

ERIC Educational Resources Information Center

Williams, Justin H. G.; Massaro, Dominic W.; Peel, Natalie J.; Bosseler, Alexis; Suddendorf, Thomas

2004-01-01

Children with autistic spectrum disorder (ASD) may have poor audio-visual integration, possibly reflecting dysfunctional "mirror neuron" systems which have been hypothesised to be at the core of the condition. In the present study, a computer program, utilizing speech synthesizer software and a "virtual" head (Baldi), delivered speech stimuli for…

Improving sexual health in men with prostate cancer: randomised controlled trial of exercise and psychosexual therapies

PubMed Central

2014-01-01

Background Despite being a critical survivorship care issue, there is a clear gap in current knowledge of the optimal treatment of sexual dysfunction in men with prostate cancer. There is sound theoretical rationale and emerging evidence that exercise may be an innovative therapy to counteract sexual dysfunction in men with prostate cancer. Furthermore, despite the multidimensional aetiology of sexual dysfunction, there is a paucity of research investigating the efficacy of integrated treatment models. Therefore, the purpose of this study is to: 1) examine the efficacy of exercise as a therapy to aid in the management of sexual dysfunction in men with prostate cancer; 2) determine if combining exercise and brief psychosexual intervention results in more pronounced improvements in sexual health; and 3) assess if any benefit of exercise and psychosexual intervention on sexual dysfunction is sustained long term. Methods/Design A three-arm, multi-site randomised controlled trial involving 240 prostate cancer survivors will be implemented. Participants will be randomised to: 1) ‘Exercise’ intervention; 2) ‘Exercise + Psychosexual’ intervention; or 3) ‘Usual Care’. The Exercise group will receive a 6-month, group based, supervised resistance and aerobic exercise intervention. The Exercise + Psychosexual group will receive the same exercise intervention plus a brief psychosexual self-management intervention that addresses psychological and sexual well-being. The Usual Care group will maintain standard care for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (post-intervention) and 1 year follow-up. The primary endpoint is sexual health and secondary endpoints include key factors associated with sexual health in men with prostate cancer. Discussion Sexual dysfunction is one of the most prevalent and distressing consequences of prostate cancer. Despite this, very little is known about the management of sexual dysfunction and current health care services do not adequately meet sexual health needs of survivors. This project will examine the potential role of exercise in the management of sexual dysfunction and evaluate a potential best-practice management approach by integrating pharmacological, physiological and psychological treatment modalities to address the complex and multifaceted aetiology of sexual dysfunction following cancer. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001179729. PMID:24641777

The frequency of sexual dysfunctions in male partners of women with vaginismus in a Turkish sample.

PubMed

Dogan, S; Dogan, M

2008-01-01

The aim of this investigation is to determine the sexual history traits, sexual satisfaction level and frequency of sexual dysfunctions in men whose partners have vaginismus. The study included 32 male partners of vaginismic patients, who presented at a psychiatry department. Subjects were evaluated by a semi-structured questionnaire. The questionnaire was developed by researchers for assessing sexually dysfunctional patients and included detailed questions with regard to socio-demographic variables, general medical and sexual history. All participants also received the Golombok Rust Inventory of Sexual Satisfaction (GRISS). According to DSM-IV-TR criteria, 65.6% of the investigated males were diagnosed with one or more sexual dysfunctions. The most common problem was premature ejaculation (50%) and the second one was erectile dysfunction (28%). The transformed GRISS subscale scores provided similar data. It is concluded that the assessment of sexual functions of males who have vaginismic partners should be an integral part of the management procedure of vaginismus for optimal outcome.

[Family dysfunction and paediatric patients with asthma].

PubMed

Guzmán-Pantoja, Jaime Eduardo; Reyes Barajas-Mendoza, Eduardo; Luce-González, Elba Graciela; Valadez-Toscano, Francisco Javier; Gutiérrez-Román, Elsa Armida; Robles-Romero, Miguel Angel

2008-11-01

To determine family function of pediatric patients with asthma. Cross-sectional study. Family medicine clinic number 51, Mexican Institute of Social Security, Primary Care, in Guadalajara, Jalisco, Mexico. Fifty families were studied; 25 of which had a pediatric patient previously diagnosed with asthma, and a control group of 25 with pediatric patients without asthma. From September 2006 to February 2007 family function was evaluated using family APGAR and associations were estimated using odds ratio (OR) and 95% confidence interval (CI). Family dysfunction was more often present in families with asthmatic patients compared to those without; OR=3.7 (95% CI, 1.1-13). Severe dysfunction is markedly higher in families with asthmatic members. Family dysfunction is more frequent in families with asthmatic children; family functionality should be seen as an important part of the integral approach in those families.

Altered learning, memory, and social behavior in type 1 taste receptor subunit 3 knock-out mice are associated with neuronal dysfunction.

PubMed

Martin, Bronwen; Wang, Rui; Cong, Wei-Na; Daimon, Caitlin M; Wu, Wells W; Ni, Bin; Becker, Kevin G; Lehrmann, Elin; Wood, William H; Zhang, Yongqing; Etienne, Harmonie; van Gastel, Jaana; Azmi, Abdelkrim; Janssens, Jonathan; Maudsley, Stuart

2017-07-07

The type 1 taste receptor member 3 (T1R3) is a G protein-coupled receptor involved in sweet-taste perception. Besides the tongue, the T1R3 receptor is highly expressed in brain areas implicated in cognition, including the hippocampus and cortex. As cognitive decline is often preceded by significant metabolic or endocrinological dysfunctions regulated by the sweet-taste perception system, we hypothesized that a disruption of the sweet-taste perception in the brain could have a key role in the development of cognitive dysfunction. To assess the importance of the sweet-taste receptors in the brain, we conducted transcriptomic and proteomic analyses of cortical and hippocampal tissues isolated from T1R3 knock-out (T1R3KO) mice. The effect of an impaired sweet-taste perception system on cognition functions were examined by analyzing synaptic integrity and performing animal behavior on T1R3KO mice. Although T1R3KO mice did not present a metabolically disrupted phenotype, bioinformatic interpretation of the high-dimensionality data indicated a strong neurodegenerative signature associated with significant alterations in pathways involved in neuritogenesis, dendritic growth, and synaptogenesis. Furthermore, a significantly reduced dendritic spine density was observed in T1R3KO mice together with alterations in learning and memory functions as well as sociability deficits. Taken together our data suggest that the sweet-taste receptor system plays an important neurotrophic role in the extralingual central nervous tissue that underpins synaptic function, memory acquisition, and social behavior. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

White Matter Correlates of Neuropsychological Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Jung, Rex E.; Chavez, Robert S.; Flores, Ranee A.; Qualls, Clifford; Sibbitt, Wilmer L.; Roldan, Carlos A.

2012-01-01

Patients diagnosed with Systemic Lupus Erythematosus have similar levels of neuropsychological dysfunction (i.e., 20–50%) as those with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). We hypothesized a gradient between cognition and white matter integrity, such that strongest brain-behavior relationships would emerge in NPSLE, intermediate in non-NPSLE, and minimal in controls. We studied thirty-one patients (16 non-NPSLE; 15 NPSLE), ranging in age from 18 to 59 years old (100% female), and eighteen age and gender matched healthy controls. DTI examinations were performed on a 1.5T scanner. A broad neuropsychological battery was administered, tapping attention, memory, processing speed, and executive functioning. The Total z-score consisted of the combined sum of all neuropsychological measures. In control subjects, we found no significant FA-Total z-score correlations. NPSLE, non-NPSLE, and control subjects differed significantly in terms of Total z-score (NPSLE = −2.25+/−1.77, non-NPSLE = −1.22+/−1.03, Controls = −0.10+/−.57; F = 13.2, p<.001). In non-NPSLE subjects, FA within the right external capsule was significantly correlated with Total z-score. In NPSLE subjects, the largest FA-Total z-score clusters were observed within the left anterior thalamic radiation and right superior longitudinal fasciculus. In subsequent analyses the largest number of significant voxels linked FA with the Processing Speed z-score in NPSLE. The current results reflect objective white matter correlates of neuropsychological dysfunction in both NPSLE and (to a lesser degree) in non-NPSLE. non-NPSLE and NPSLE subjects did not differ significantly in terms of depression, as measured by the GDI; thus, previous hypotheses suggesting moderating effects of depression upon neuropsychological performance do not impact the current FA results. PMID:22291880

Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets.

PubMed

Krumm, Sabine; Kivisaari, Sasa L; Monsch, Andreas U; Reinhardt, Julia; Ulmer, Stephan; Stippich, Christoph; Kressig, Reto W; Taylor, Kirsten I

2017-05-01

The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes' contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.e. early Alzheimer's Disease) to 56 healthy control participants in an immediate paired and delayed single item object memory task. Additionally, we performed voxel-based morphometry analyses to investigate the functional-neuroanatomic relationships between performance and voxel-based estimates of atrophy in whole-brain analyses. Behaviorally, all participants performed better identifying targets than rejecting distractors. The voxel-based morphometry analyses associated atrophy in the right ventral parietal cortex with fewer correct responses to familiar items (i.e. hits) in the immediate and delayed conditions. Additionally, medial temporal lobe integrity correlated with better performance in rejecting distractors, but not in identifying targets, in the immediate paired-associate task. Our findings suggest that the parietal lobe critically supports successful immediate and delayed target recognition memory, and that the ventral aspect of the parietal cortex and the medial temporal lobe may have complementary preferences for identifying targets and rejecting distractors, respectively, during recognition memory. Copyright © 2017. Published by Elsevier Inc.

Impact of Social Processes in Online Health Communities on Patient Empowerment in Relationship With the Physician: Emergence of Functional and Dysfunctional Empowerment.

PubMed

Petrič, Gregor; Atanasova, Sara; Kamin, Tanja

2017-03-13

Substantial research demonstrates the importance of online health communities (OHCs) for patient empowerment, although the impact on the patient-physician relationship is understudied. Patient empowerment also occurs in relationship with the physician, but studies of OHCs mostly disregard this. The question also remains about the nature and consequences of this empowerment, as it might be based on the limited validity of some information in OHCs. The main purpose of this study was to examine the impact of social processes in OHCs (information exchange with users and health professional moderators, social support, finding meaning, and self-expressing) on functional and dysfunctional patient empowerment in relationship with the physician (PERP). This impact was investigated by taking into account moderating role of eHealth literacy and physician's paternalism. An email list-based Web survey on a simple random sample of 25,000 registered users of the most popular general OHC in Slovenia was conducted. A total of 1572 respondents completed the survey. The analyses were conducted on a subsample of 591 regular users, who had visited a physician at least once in the past 2 years. To estimate the impact of social processes in OHC on functional and dysfunctional PERP, we performed a series of hierarchical regression analyses. To determine the moderating role of eHealth literacy and the perceived physician characteristics, interactions were included in the regression analyses. The mean age of the respondents in the sample was 37.6 years (SD 10.3) and 83.3% were females. Factor analyses of the PERP revealed a five-factor structure with acceptable fit (root-mean-square error of approximation =.06). Most important results are that functional self-efficacy is positively predicted by information exchange with health professional moderators (beta=.12, P=.02), information exchange with users (beta=.12, P=.05), and giving social support (beta=.13, P=.02), but negatively predicted with receiving social support (beta=-.21, P<.001). Functional control is also predicted by information exchange with health professional moderators (beta=.16, P=.005). Dysfunctional control and competence are inhibited by information exchanges with health professionals (beta=-.12, P=.03), whereas dysfunctional self-efficacy is inhibited by self-expressing (beta=-.12, P=.05). The process of finding meaning likely leads to the development of dysfunctional competences and control if the physician is perceived to be paternalistic (beta=.14, P=.03). Under the condition of high eHealth literacy, the process of finding meaning will inhibit the development of dysfunctional competences and control (beta=-.17, P=.01). Social processes in OHCs do not have a uniform impact on PERP. This impact is moderated by eHealth literacy and physician paternalism. Exchanging information with health professional moderators in OHCs is the most important factor for stimulating functional PERP as well as diminishing dysfunctional PERP. Social support in OHCs plays an ambiguous role, often making patients behave in a strategic, uncooperative way toward physicians. ©Gregor Petrič, Sara Atanasova, Tanja Kamin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 13.03.2017.

Impact of Social Processes in Online Health Communities on Patient Empowerment in Relationship With the Physician: Emergence of Functional and Dysfunctional Empowerment

PubMed Central

Atanasova, Sara; Kamin, Tanja

2017-01-01

Background Substantial research demonstrates the importance of online health communities (OHCs) for patient empowerment, although the impact on the patient-physician relationship is understudied. Patient empowerment also occurs in relationship with the physician, but studies of OHCs mostly disregard this. The question also remains about the nature and consequences of this empowerment, as it might be based on the limited validity of some information in OHCs. Objective The main purpose of this study was to examine the impact of social processes in OHCs (information exchange with users and health professional moderators, social support, finding meaning, and self-expressing) on functional and dysfunctional patient empowerment in relationship with the physician (PERP). This impact was investigated by taking into account moderating role of eHealth literacy and physician’s paternalism. Method An email list–based Web survey on a simple random sample of 25,000 registered users of the most popular general OHC in Slovenia was conducted. A total of 1572 respondents completed the survey. The analyses were conducted on a subsample of 591 regular users, who had visited a physician at least once in the past 2 years. To estimate the impact of social processes in OHC on functional and dysfunctional PERP, we performed a series of hierarchical regression analyses. To determine the moderating role of eHealth literacy and the perceived physician characteristics, interactions were included in the regression analyses. Results The mean age of the respondents in the sample was 37.6 years (SD 10.3) and 83.3% were females. Factor analyses of the PERP revealed a five-factor structure with acceptable fit (root-mean-square error of approximation =.06). Most important results are that functional self-efficacy is positively predicted by information exchange with health professional moderators (beta=.12, P=.02), information exchange with users (beta=.12, P=.05), and giving social support (beta=.13, P=.02), but negatively predicted with receiving social support (beta=−.21, P<.001). Functional control is also predicted by information exchange with health professional moderators (beta=.16, P=.005). Dysfunctional control and competence are inhibited by information exchanges with health professionals (beta=−.12, P=.03), whereas dysfunctional self-efficacy is inhibited by self-expressing (beta=−.12, P=.05). The process of finding meaning likely leads to the development of dysfunctional competences and control if the physician is perceived to be paternalistic (beta=.14, P=.03). Under the condition of high eHealth literacy, the process of finding meaning will inhibit the development of dysfunctional competences and control (beta=−.17, P=.01). Conclusions Social processes in OHCs do not have a uniform impact on PERP. This impact is moderated by eHealth literacy and physician paternalism. Exchanging information with health professional moderators in OHCs is the most important factor for stimulating functional PERP as well as diminishing dysfunctional PERP. Social support in OHCs plays an ambiguous role, often making patients behave in a strategic, uncooperative way toward physicians. PMID:28288953

Psychological and interpersonal dimensions of sexual function and dysfunction.

PubMed

Althof, Stanley E; Leiblum, Sandra R; Chevret-Measson, Marie; Hartmann, Uwe; Levine, Stephen B; McCabe, Marita; Plaut, Michael; Rodrigues, Oswaldo; Wylie, Kevan

2005-11-01

There are limited outcome data on the efficacy of psychological interventions for male and female sexual dysfunction and the role of innovative combined treatment paradigms. To highlight the salient psychological and interpersonal issues contributing to sexual health and dysfunction; to offer a four-tiered paradigm for understanding the evolution and maintenance of sexual symptoms; and to offer recommendations for clinical management and research. An International Consultation assembled over 200 multidisciplinary experts from 60 countries into 17 committees. The recommendations of committee members represent state-of-the-art knowledge and opinions of experts from five continents were developed in a process over a 2-year period. Concerning the Psychological and Interpersonal Committee of Sexual Function and Dysfunction, there were nine experts from five countries. Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. Medical and psychological therapies for sexual dysfunctions should address the intricate biopsychosocial influences of the patient, the partner, and the couple. The biopsychosocial model provides a compelling reason for skepticism that any single intervention (i.e., a phosphodiesterase type 5 inhibitor, supraphysiological doses of a hormone, processing of childhood victimization, marital therapy, pharmacotherapy of depression, etc.) will be sufficient for most patients or couples experiencing sexual dysfunction. There is need for collaboration between healthcare practitioners from different disciplines in evaluation, treatment, and education issues surrounding sexual dysfunction. In many cases, neither psychotherapy alone nor medical intervention alone is sufficient for the lasting resolution of sexual problems. Assessment of male, female, and couples' sexual dysfunction should ideally include inquiry about: predisposing, precipitating, maintaining, and contextual factors. Treatment of lifelong and/or chronic dysfunction will be different from acquired or recent dysfunction. Research is needed to identify efficacious combined and/or integrated treatments for sexual dysfunction.

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence.

PubMed

Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh

2015-01-01

People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05) there were no significant differences among both the groups except above findings. Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

Diabetes, vestibular dysfunction, and falls: analyses from the National Health and Nutrition Examination Survey.

PubMed

Agrawal, Yuri; Carey, John P; Della Santina, Charles C; Schubert, Michael C; Minor, Lloyd B

2010-12-01

Patients with diabetes are at increased risk both for falls and for vestibular dysfunction, a known risk factor for falls. Our aims were 1) to further characterize the vestibular dysfunction present in patients with diabetes and 2) to evaluate for an independent effect of vestibular dysfunction on fall risk among patients with diabetes. National cross-sectional survey. Ambulatory examination centers. Adults from the United States aged 40 years and older who participated in the 2001-2004 National Health and Nutrition Examination Survey (n = 5,86). Diagnosis of diabetes, peripheral neuropathy, and retinopathy. Vestibular function measured by the modified Romberg Test of Standing Balance on Firm and Compliant Support Surfaces and history of falling in the previous 12 months. We observed a higher prevalence of vestibular dysfunction in patients with diabetes with longer duration of disease, greater serum hemoglobin A1c levels and other diabetes-related complications, suggestive of a dose-response relationship between diabetes mellitus severity and vestibular dysfunction. We also noted that vestibular dysfunction independently increased the odds of falling more than 2-fold among patients with diabetes (odds ratio, 2.3; 95% confidence interval, 1.1-5.1), even after adjusting for peripheral neuropathy and retinopathy. Moreover, we found that including vestibular dysfunction, peripheral neuropathy, and retinopathy in multivariate models eliminated the significant association between diabetes and fall risk. Vestibular dysfunction may represent a newly recognized diabetes-related complication, which acts as a mediator of the effect of diabetes mellitus on fall risk.

Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression.

PubMed

Cannon, B; Mulroy, R; Otto, M W; Rosenbaum, J F; Fava, M; Nierenberg, A A

1999-09-01

Hopelessness is a significant predictor of suicidality, but not all depressed patients feel hopeless. If clinicians can predict hopelessness, they may be able to identify those patients at risk of suicide and focus interventions on factors associated with hopelessness. In this study, we examined potential predictors of hopelessness in a sample of depressed outpatients. In this study, we examined potential demographic, diagnostic, and symptom predictors of hopelessness in a sample of 138 medication-free outpatients (73 women and 65 men) with a primary diagnosis of major depression. The significance of predictors was evaluated in both simple and multiple regression analyses. Consistent with previous studies, we found no significant associations between demographic and diagnostic variables and greater hopelessness. Hopelessness was significantly associated with greater depression severity, poor problem solving abilities as assessed by the Problem Solving Inventory, and each of two measures of dysfunctional cognitions (the Dysfunctional Attitudes Scale and the Cognitions Questionnaire). In a stepwise multiple regression equation, however, only dysfunctional cognitions and poor problem solving offered non-redundant prediction of hopelessness scores, and accounted for 20% of the variance in these scores. This study is based on depressed patients entering into an outpatient treatment protocol. All analyses were correlational in nature, and no causal links can be concluded. Our findings, identifying clinical correlates of hopelessness, provide clinicians with potential additional targets for assessment and treatment of suicidal risk. In particular, clinical attention to dysfunctional attitudes and problem solving skills may be important for further reduction of hopelessness and perhaps suicidal risk.

Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity.

PubMed

Rivera, José Carlos; Madaan, Ankush; Zhou, Tianwei Ellen; Chemtob, Sylvain

2016-12-01

Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder. Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Handwriting, Visuomotor Integration, and Neurological Condition at School Age

ERIC Educational Resources Information Center

Van Hoorn, Jessika F.; Maathuis, Carel G. B.; Peters, Lieke H. J.; Hadders-Algra, Mijna

2010-01-01

Aim: The study investigated the relationships between handwriting, visuomotor integration, and neurological condition. We paid particular attention to the presence of minor neurological dysfunction (MND). Method : Participants were 200 children (131 males, 69 females; age range 8-13y) of whom 118 received mainstream education (mean age 10y 5mo, SD…

Sensory integration functions of children with cochlear implants.

PubMed

Koester, AnjaLi Carrasco; Mailloux, Zoe; Coleman, Gina Geppert; Mori, Annie Baltazar; Paul, Steven M; Blanche, Erna; Muhs, Jill A; Lim, Deborah; Cermak, Sharon A

2014-01-01

OBJECTIVE. We investigated sensory integration (SI) function in children with cochlear implants (CIs). METHOD. We analyzed deidentified records from 49 children ages 7 mo to 83 mo with CIs. Records included Sensory Integration and Praxis Tests (SIPT), Sensory Processing Measure (SPM), Sensory Profile (SP), Developmental Profile 3 (DP-3), and Peabody Developmental Motor Scales (PDMS), with scores depending on participants' ages. We compared scores with normative population mean scores and with previously identified patterns of SI dysfunction. RESULTS. One-sample t tests revealed significant differences between children with CIs and the normative population on the majority of the SIPT items associated with the vestibular and proprioceptive bilateral integration and sequencing (VPBIS) pattern. Available scores for children with CIs on the SPM, SP, DP-3, and PDMS indicated generally typical ratings. CONCLUSION. SIPT scores in a sample of children with CIs reflected the VPBIS pattern of SI dysfunction, demonstrating the need for further examination of SI functions in children with CIs during occupational therapy assessment and intervention planning. Copyright © 2014 by the American Occupational Therapy Association, Inc.

Right ventricular dysfunction in acute pulmonary embolism: NT-proBNP vs. troponin T.

PubMed

Cotugno, Marilena; Orgaz-Molina, Jacinto; Rosa-Salazar, Vladimir; Guirado-Torrecillas, Leticia; García-Pérez, Bartolomé

2017-04-21

Dysfunction of the right ventricle (RV) is a parameter of severity in acute pulmonary embolism (PE). Echocardiographic assessment is not always possible in accident and emergency, hence the need to predict the presence of RV dysfunction using easily measurable parameters. To analyse the value of NT-proBNP and troponin T as markers of RV dysfunction in patients with acute PE. Secondarily, to assess the relationship between RV failure and clinical parameters related to PE. Analytical, observational, cross-sectional and retrospective study comparing the values NT-proBNP, troponin T and presenting symptoms of PE among patients with and without RV dysfunction. One hundred seventy-two patients (52 with RV failure,120 without) were included. All symptoms occurred with similar frequency between the 2groups except dyspnea and syncope (more common in the group with RV failure). Both NT-proBNP and troponin T had significantly higher values in the group of patients with RV dysfunction. However, in the multivariate analysis, NT-proBNP had a higher explanatory value for RV failure than troponin T. NT-proBNP is a diagnostic parameter of RV dysfunction with higher sensitivity in the context of acute PE. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Examining Sexual Dysfunction in Non-Muscle-Invasive Bladder Cancer: Results of Cross-Sectional Mixed-Methods Research

PubMed Central

Kowalkowski, Marc A; Chandrashekar, Aravind; Amiel, Gilad E; Lerner, Seth P; Wittmann, Daniela A; Latini, David M; Goltz, Heather Honoré

2014-01-01

Introduction More than 70,000 new cases of bladder cancer are diagnosed in the United States annually; with 75% being non-muscle-invasive (NMIBC). Research examining sexual dysfunction in bladder cancer survivors is limited, and previous studies have focused on cystectomy patients. Aims To evaluate the impact of sexual dysfunction on NMIBC survivors. Methods Mixed-methods data collection integrated a quantitative survey (Study 1; n = 117) and semi-structured qualitative interviews (Study 2; n = 26) from a non-overlapping sample of NMIBC survivors. We performed descriptive and classification and regression tree (CART) analyses of survey data and qualitative analysis of interviews. Main Outcome Measures Self-reported sexual activity, interest in sex, and physiologic symptoms (e.g., male erectile/ejaculatory difficulties, female vaginal dryness) over the previous 4 weeks; partner communication about sexuality; contamination concerns; illness intrusiveness. Results Participants in these studies averaged 65 years of age (mean and median) and were male (77%), white (91%), and married (75%). Survey (Study 1) results linked NMIBC treatment to sexual symptoms and relationship issues. Many participants reported sexual inactivity (38.8%). Sexually active participants reported erectile difficulties (60.0%), vaginal dryness (62.5%), and worry about contaminating partner with treatment agents (23.2%). While almost one-half reported the usefulness of talking with partners about sexual function, only one-fifth of participants reported sharing all concerns with their partners. CART analysis supported the importance of communication. One-half of interviewees (Study 2) reported sexual dysfunction. Two-thirds reported negative impacts on their relationships, including perceived loss of intimacy and divorce; over one-third were sexually inactive for fear of contaminating their partner or spreading NMIBC. Conclusions Survivors' sexual symptoms may result from NMIBC, comorbidities, or both. These results inform literature and practice by raising awareness about the frequency of symptoms and the impact on NMIBC survivors' intimate relationships. Further work is needed to design symptom management education programs to dispel misinformation about contamination post-treatment and improve quality of life. Kowalkowski MA, Chandrashekar A, Amiel GE, Lerner SP, Wittmann DA, Latini DM, and Goltz HH. Examining sexual dysfunction in non-muscle-invasive bladder cancer: Results of cross-sectional mixed-methods research. Sex Med 2014;2:141–151. PMID:25356311

It ain't what you do (it's the way that you do it).

PubMed

Aitken, Kenneth John

2013-08-01

Knowledge of the complexity of human communication comes from three main sources - (i) studies of the linguistics and neuropsychology of dysfunction after brain injury; (ii) studies of the development of social communication in infancy, and its dysfunction in developmental psychopathologies; and (iii) the evolutionary history of human communicative interaction. Together, these suggest the need for a broad, integrated theory of communication of which language forms a small but critical component.

Pericyte function in the physiological central nervous system.

PubMed

Muramatsu, Rieko; Yamashita, Toshihide

2014-01-01

Damage to the central nervous system (CNS) leads to disruption of the vascular network, causing vascular dysfunction. Vascular dysfunction is the major event in the pathogenesis of CNS diseases and is closely associated with the severity of neuronal dysfunction. The suppression of vascular dysfunction has been considered a promising avenue to limit damage to the CNS, leading to efforts to clarify the cellular and molecular basis of vascular homeostasis maintenance. A reduction of trophic support and oxygen delivery due to circulatory insufficiency has long been regarded as a major cause of vascular damage. Moreover, recent studies provide a new perspective on the importance of the structural stability of blood vessels in CNS diseases. This updated article discusses emerging information on the key role of vascular integrity in CNS diseases, specially focusing on pericyte function. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Telomeres and Mitochondria in the Aging Heart

PubMed Central

Moslehi, Javid; DePinho, Ronald A.; Sahin, Ergün

2013-01-01

Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. PMID:22539756

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

PubMed

Sachs, G; Katschnig, H

2001-03-01

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model

PubMed Central

Nahidi, Lily; Leach, Steven T.; Mitchell, Hazel M.; Kaakoush, Nadeem O.; Lemberg, Daniel A.; Munday, John S.; Huinao, Karina; Day, Andrew S.

2013-01-01

Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn's disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10−/− mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-α and myeloperoxidase plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls P < 0.05). Conclusion. H. trogontum infection in IL-10−/− mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes. PMID:24027765

Modification of dysfunctional thoughts about caregiving in dementia family caregivers: description and outcomes of an intervention programme.

PubMed

Márquez-González, M; Losada, A; Izal, M; Pérez-Rojo, G; Montorio, I

2007-11-01

Among the diverse group of interventions developed to help dementia family caregivers cognitive-behavioural approaches show especially promising results. This study describes a cognitive-behavioural group intervention aimed principally at the modification of dysfunctional thoughts associated with caregiving (MDTC). The efficacy of the MDTC intervention in reducing caregivers' depressive symptomatology, together with the frequency and appraisal of problem behaviours, is compared to that of a waiting-list control group (WL). Furthermore, the potential mediating role of the dysfunctional thoughts in the relationship between this intervention and caregivers' depressive symptomatology is analyzed. Of the 74 dementia caregivers who were randomized to one of two conditions (MDTC and WL), 39 completed the post-intervention assessment. Statistical analyses were performed on an intention-to-treat basis, using last observation carried forward. The results reveal that the MDTC intervention is successful in reducing caregivers' level of depressive symptomatology and dysfunctional thoughts about caregiving, as well as in modifying their appraisal of their relative's problem behaviours. Furthermore, a mediating role for dysfunctional thoughts was found in the relationship between the MDTC intervention and levels of depressive symptomatology. The relevance of addressing dysfunctional thoughts and cognitive distortions in group interventions with caregivers is highlighted.

Development and validation of a five-factor sexual satisfaction and distress scale for women: the Sexual Satisfaction Scale for Women (SSS-W).

PubMed

Meston, Cindy; Trapnell, Paul

2005-01-01

This article presents data based on the responses of over 800 women who contributed to the development of the Sexual Satisfaction Scale for Women (SSS-W). The aim of this study was to develop a comprehensive, multifaceted, valid, and reliable self-report measure of women's sexual satisfaction and distress. Phase I involved the initial selection of items based on past literature and on interviews of women diagnosed with sexual dysfunction and an exploratory factor analysis. Phase II involved an additional administration of the questionnaire, factor analyses, and refinement of the questionnaire items. Phase III involved administration of the final questionnaire to a sample of women with clinically diagnosed sexual dysfunction and controls. Psychometric evaluation of the SSS-W conducted in a sample of women meeting DSM-IV-TR criteria for female sexual dysfunction and in a control sample provided preliminary evidence of reliability and validity. The ability of the SSS-W to discriminate between sexually functional and dysfunctional women was demonstrated for each of the SSS-W domain scores and total score. The SSS-W is a brief, 30-item measure of sexual satisfaction and sexual distress, composed of five domains supported by factor analyses: contentment, communication, compatibility, relational concern, and personal concern. It exhibits sound psychometric properties and has a demonstrated ability to discriminate between clinical and nonclinical samples.

SU-D-204-06: Integration of Machine Learning and Bioinformatics Methods to Analyze Genome-Wide Association Study Data for Rectal Bleeding and Erectile Dysfunction Following Radiotherapy in Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, J; Deasy, J; Kerns, S

Purpose: We investigated whether integration of machine learning and bioinformatics techniques on genome-wide association study (GWAS) data can improve the performance of predictive models in predicting the risk of developing radiation-induced late rectal bleeding and erectile dysfunction in prostate cancer patients. Methods: We analyzed a GWAS dataset generated from 385 prostate cancer patients treated with radiotherapy. Using genotype information from these patients, we designed a machine learning-based predictive model of late radiation-induced toxicities: rectal bleeding and erectile dysfunction. The model building process was performed using 2/3 of samples (training) and the predictive model was tested with 1/3 of samples (validation).more » To identify important single nucleotide polymorphisms (SNPs), we computed the SNP importance score, resulting from our random forest regression model. We performed gene ontology (GO) enrichment analysis for nearby genes of the important SNPs. Results: After univariate analysis on the training dataset, we filtered out many SNPs with p>0.001, resulting in 749 and 367 SNPs that were used in the model building process for rectal bleeding and erectile dysfunction, respectively. On the validation dataset, our random forest regression model achieved the area under the curve (AUC)=0.70 and 0.62 for rectal bleeding and erectile dysfunction, respectively. We performed GO enrichment analysis for the top 25%, 50%, 75%, and 100% SNPs out of the select SNPs in the univariate analysis. When we used the top 50% SNPs, more plausible biological processes were obtained for both toxicities. An additional test with the top 50% SNPs improved predictive power with AUC=0.71 and 0.65 for rectal bleeding and erectile dysfunction. A better performance was achieved with AUC=0.67 when age and androgen deprivation therapy were added to the model for erectile dysfunction. Conclusion: Our approach that combines machine learning and bioinformatics techniques enabled designing better models and identifying more plausible biological processes associated with the outcomes.« less

Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

PubMed

Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

2017-07-04

This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

Myeloperoxidase Oxidized LDL Interferes with Endothelial Cell Motility through miR-22 and Heme Oxygenase 1 Induction: Possible Involvement in Reendothelialization of Vascular Injuries

PubMed Central

Daher, Jalil; Martin, Maud; Rousseau, Alexandre; Nuyens, Vincent; Fayyad-Kazan, Hussein; Van Antwerpen, Pierre; Courbebaisse, Guy; Martiat, Philippe; Badran, Bassam; Dequiedt, Frank

2014-01-01

Cardiovascular disease linked to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is mainly linked to dysfunction in vascular endothelial cells and subendothelial accumulation of oxidized forms of LDL. In the present study, we investigated the role of myeloperoxidase oxidized LDL (Mox-LDL) in endothelial cell dysfunction. We studied the effect of proinflammatory Mox-LDL treatment on endothelial cell motility, a parameter essential for normal vascular processes such as angiogenesis and blood vessel repair. This is particularly important in the context of an atheroma plaque, where vascular wall integrity is affected and interference with its repair could contribute to progression of the disease. We investigated in vitro the effect of Mox-LDL on endothelial cells angiogenic properties and we also studied the signalling pathways that could be affected by analysing Mox-LDL effect on the expression of angiogenesis-related genes. We report that Mox-LDL inhibits endothelial cell motility and tubulogenesis through an increase in miR-22 and heme oxygenase 1 expression. Our in vitro data indicate that Mox-LDL interferes with parameters associated with angiogenesis. They suggest that high LDL levels in patients would impair their endothelial cell capacity to cope with a damaged endothelium contributing negatively to the progression of the atheroma plaque. PMID:25530680

Integrating Prospective Longitudinal Data: Modeling Personality and Health in the Terman Life Cycle and Hawaii Longitudinal Studies

PubMed Central

Kern, Margaret L.; Hampson, Sarah E.; Goldberg, Lewis R.; Friedman, Howard S.

2013-01-01

The present study used a collaborative framework to integrate two long-term prospective studies: the Terman Life Cycle Study and the Hawaii Personality and Health Longitudinal Study. Using a five-factor personality-trait framework, teacher assessments of child personality were rationally and empirically aligned to establish similar factor structures across samples. Comparable items related to adult self-rated health, education, and alcohol use were harmonized, and data were pooled on harmonized items. A structural model was estimated, allowing paths to differ by sample. Harmonized child personality factors were then used to examine markers of physiological dysfunction in the Hawaii sample and mortality risk in the Terman sample. Harmonized conscientiousness predicted less physiological dysfunction in the Hawaii sample and lower mortality risk in the Terman sample. These results illustrate how collaborative, integrative work with multiple samples offers the exciting possibility that samples from different cohorts and ages can be linked together to directly test lifespan theories of personality and health. PMID:23231689

Influence of neural monitoring during thyroid surgery on nerve integrity and postoperative vocal function.

PubMed

Engelsman, A F; Warhurst, S; Fraser, S; Novakovic, D; Sidhu, S B

2018-06-01

Integrity of the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (EBSLN) can be checked by intraoperative nerve monitoring (IONM) after visualization. The aim of this study was to determine the prevalence and nature of voice dysfunction following thyroid surgery with routine IONM. Thyroidectomies were performed with routine division of strap muscles and nerve monitoring to confirm integrity of the RLN and EBSLN following dissection. Patients were assessed for vocal function before surgery and at 1 and 3 months after operation. Assessment included use of the Voice Handicap Index (VHI) 10, maximum phonation time, fundamental frequency, pitch range, harmonic to noise ratio, cepstral peak prominence and smoothed cepstral peak prominence. A total of 172 nerves at risk were analysed in 102 consecutive patients undergoing elective thyroid surgery. In 23·3 per cent of EBSLNs and 0·6 per cent of RLNs nerve identification required the assistance of IONM in addition to visualization. Nerve integrity was confirmed during surgery for 98·8 per cent of EBSLNs and 98·3 per cent of RLNs. There were no differences between preoperative and postoperative VHI-10 scores. Acoustic voice assessment showed small changes in maximum phonation time at 1 and 3 months after surgery. Where there is routine division of strap muscles, thyroidectomy using nerve monitoring confirmation of RLN and EBSLN function following dissection results in no clinically significant voice change.

A Place for Sexual Dysfunctions in an Empirical Taxonomy of Psychopathology

PubMed Central

Forbes, Miriam K.; Baillie, Andrew J.; Eaton, Nicholas R.; Krueger, Robert F.

2017-01-01

Sexual dysfunctions commonly co-occur with various depressive and anxiety disorders. An emerging framework for understanding the classification of mental disorders suggests that such comorbidity is a manifestation of underlying dimensions of psychopathology (or “spectra”). In this review, we synthesize the evidence that sexual dysfunctions should be included in the empirical taxonomy of psychopathology as part of the internalizing spectrum, which accounts for comorbidity among the depressive and anxiety disorders. The review has four parts. Part 1 summarizes the empirical basis and utility of the empirical taxonomy of psychopathology. Part 2 reviews the prima facie evidence for the hypothesis that sexual dysfunctions are part of the internalizing spectrum (i.e., high rates of comorbidity; shared cognitive, affective, and temperament characteristics; common neural substrates and biomarkers; shared course and treatment response; and the lack of causal relationships between them). Part 3 critically analyzes and integrates the results of the eight studies that have addressed this hypothesis. Finally, Part 4 examines the implications of reconceptualizing sexual dysfunctions as part of the internalizing spectrum, and explores avenues for future research. PMID:28121167

A Place for Sexual Dysfunctions in an Empirical Taxonomy of Psychopathology.

PubMed

Forbes, Miriam K; Baillie, Andrew J; Eaton, Nicholas R; Krueger, Robert F

Sexual dysfunctions commonly co-occur with various depressive and anxiety disorders. An emerging framework for understanding the classification of mental disorders suggests that such comorbidity is a manifestation of underlying dimensions of psychopathology (or "spectra"). In this review, we synthesize the evidence that sexual dysfunctions should be included in the empirical taxonomy of psychopathology as part of the internalizing spectrum, which accounts for comorbidity among the depressive and anxiety disorders. The review has four parts. Part 1 summarizes the empirical basis and utility of the empirical taxonomy of psychopathology. Part 2 reviews the prima facie evidence for the hypothesis that sexual dysfunctions are part of the internalizing spectrum (i.e., high rates of comorbidity; shared cognitive, affective, and temperament characteristics; common neural substrates and biomarkers; shared course and treatment response; and the lack of causal relationships between them). Part 3 critically analyzes and integrates the results of the eight studies that have addressed this hypothesis. Finally, Part 4 examines the implications of reconceptualizing sexual dysfunctions as part of the internalizing spectrum, and explores avenues for future research.

Feeding & Motor Functioning: Start at the Hips to Get to the Lips

ERIC Educational Resources Information Center

Donato, Jessica; Fox, Cathy; Mormon, Johnnie; Mormon, Mike

2008-01-01

Swallowing is one of the most complex movement patterns that people must use accurately throughout the day and night from the time they are born. These movement patterns are very closely integrated with breathing and movement of food through the aerodigestive tract. Malalignment or dysfunction in any part of these integrated patterns and systems…

Risk factors of hepatic dysfunction in patients with Graves’ hyperthyroidism and the efficacy of 131iodine treatment

PubMed Central

Wang, Renfei; Tan, Jian; Zhang, Guizhi; Zheng, Wei; Li, Chengxia

2017-01-01

Abstract Hepatic dysfunction is often observed in patients with Graves’ hyperthyroidism. The aims of this study were to investigate the risk factors for hepatic dysfunction and to analyze the efficacy of 131I (radioactive iodine-131) treatment. In total, 2385 patients with Graves’ hyperthyroidism (478 males, 1907 females; age 42.8 ± 13.5 years) were involved in our study. Of these, 1552 cases with hepatic dysfunction received 131I treatment. All clinical data were retrospectively reviewed to explore the risk factors associated with hepatic dysfunction using logistic regression analysis. Furthermore, we observed thyroid and liver function indices for the 1552 subjects at 3, 6 and 12 months after 131I treatment, in order to evaluate efficacy. Overall, 65% patients were affected by hepatic dysfunction. The most common abnormality was elevated alkaline phosphatase (ALP), of which the prevalence was 52.3%. The percentages of hepatocellular injury type, bile stasis, and mixed type were 45.8%, 32.4%, and 21.8%, respectively. Both univariate and multivariate analyses demonstrated that age, duration of Graves hyperthyroidism, free triiodothyronine (FT3)level, and thyrotrophin receptor antibody (TRAb) concentration were the most significant risk factors predicting hepatic dysfunction. Additionally, the patients with mild hepatic dysfunction, or hepatocellular injury type were more likely to attain normal liver function after 131I treatment. Furthermore, after 131I treatment, liver function was more likely to return to normal in the cured group of patients compared with the uncured group. Older patients and cases with a longer history of Graves’ hyperthyroidism, higher FT3 or TRAb concentration were more likely to be associated with hepatic dysfunction, and the prognosis of hepatic dysfunction was closely associated with the outcomes of Graves’ hyperthyroidism after 131I treatment. PMID:28151911

Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

PubMed Central

Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh

2015-01-01

Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05) there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses. PMID:26257480

Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles.

PubMed

Blasczyk-Schiep, Sybilla; Sokoła, Kaja; Fila-Witecka, Karolina; Kazén, Miguel

2016-06-01

We investigated dysfunctional cognitions about eating and body image in relation to personality styles in a group of professional models. Dysfunctional cognitions in professional models (n = 43) and a control group (n = 43) were assessed with the 'Eating Disorder Cognition Questionnaire' (EDCQ), eating attitudes with the 'Eating Attitudes Test' (EAT), and personality with the 'Personality Styles and Disorders Inventory' (PSDI-S). Models had higher scores than controls on the EDCQ and EAT and on nine scales of the PSDI-S. Moderation analyses showed significant interactions between groups and personality styles in predicting EDCQ scales: The ambitious/narcissistic style was related to "negative body and self-esteem", the conscientious/compulsive style to "dietary restraint", and the spontaneous/borderline style to "loss of control in eating". The results indicate that not all models are susceptible to dysfunctional cognitions about eating and body image. Models are at a higher risk of developing negative automatic thoughts and dysfunctional assumptions relating to body size, shape and weight, especially if they have high scores on the above personality styles.

Pharmacologic management of sexual dysfunction: benefits and limitations.

PubMed

Segraves, Robert Taylor

2003-03-01

What is the current knowledge concerning the pharmacologic treatment of human sexual dysfunction? A number of interventions, including oral phophodiesterase inhibitors and intracorporeal agents with vasodilatory effects, are available to treat male erectile disorder. Serotonergic drugs have been shown to be effective in the treatment of rapid ejaculation. Various lines of research suggest that high dosages of androgenic agents may eventually have a role in the treatment of decreased libido in females. There may be a role for phophodiesterase inhibitors in the treatment of a subgroup of women with arousal disorders. Normal sexual function involves successful integration of biological, psychological, and interpersonal influences. Clinical psychiatry with its biopsychosocial model should incorporate the treatment of human sexual dysfunction within its purview.

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Applying a cognitive neuroscience perspective to the disorder of psychopathy.

PubMed

Blair, R J R

2005-01-01

Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered.

Diagnostic yield of lumbosacral magnetic resonance imaging requested by paediatric urology consultations.

PubMed

Fernández-Ibieta, M; Rojas Ticona, J; Villamil, V; Guirao Piñera, M J; López García, A; Zambudio Carmona, G

2017-11-01

In the historical series, the diagnostic yield of lumbosacral magnetic resonance imaging to rule out occult spinal dysraphism (or occult myelodysplasia), requested by paediatric urology, ranged from 2% to 15%. The aim of this study was to define our cost-effectiveness in children with urinary symptoms and to define endpoints that increase the possibility of finding occult spinal dysraphism. A screening was conducted on patients with urinary dysfunction for whom an magnetic resonance imaging was requested by the paediatric urology clinic, for persistent symptoms after treatment, voiding dysfunction or other clinical or urodynamic findings. We analysed clinical (UTI, daytime leaks, enuresis, voiding dysfunction, urgency, renal ultrasonography, lumbosacral radiography, history of acute urine retention, skin stigma and myalgia) and urodynamic endpoints (hyperactivity or areflexia, voiding dysfunction, interrupted pattern, accommodation value and maximum flow). A univariate analysis was conducted with SPSS 20.0. We analysed 21 patients during the period 2011-2015. The median age was 6 years (3-10). Three patients (14.3%) had occult spinal dysraphism: one spinal lipoma, one filum lipomatosus and one caudal regression syndrome with channel stenosis. The endpoints with statistically significant differences were the myalgias and the history of acute urine retention (66.7% vs. 5.6%, P=.04; OR= 34; 95%CI: 1.5-781 for both endpoints). The diagnostic yield of magnetic resonance imaging requested for children with urinary dysfunctions without skin stigma or neuro-orthopaedic abnormalities is low, although nonnegligible. In this group, the patients with a history of acute urine retention and muscle pain (pain, «cramps») can experience a greater diagnostic yield or positive predictive value. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A biopsychosocial approach to women’s sexual function and dysfunction at midlife: A narrative review

PubMed Central

Thomas, Holly N.; Thurston, Rebecca C.

2016-01-01

A satisfying sex life is an important component of overall well-being, but sexual dysfunction is common, especially in midlife women. The aim of this review is (a) to define sexual function and dysfunction, (b) to present theoretical models of female sexual response, (c) to examine longitudinal studies of how sexual function changes during midlife, and (d) to review treatment options. Four types of female sexual dysfunction are currently recognized: Female Orgasmic Disorder, Female Sexual Interest/Arousal Disorder, Genito-Pelvic Pain/Penetration Disorder, and Substance/Medication-Induced Sexual Dysfunction. However, optimal sexual function transcends the simple absence of dysfunction. A biopsychosocial approach that simultaneously considers physical, psychological, sociocultural, and interpersonal factors is necessary to guide research and clinical care regarding women’s sexual function. Most longitudinal studies reveal an association between advancing menopause status and worsening sexual function. Psychosocial variables, such as availability of a partner, relationship quality, and psychological functioning, also play an integral role. Future directions for research should include deepening our understanding of how sexual function changes with aging and developing safe and effective approaches to optimizing women’s sexual function with aging. Overall, holistic, biopsychosocial approaches to women’s sexual function are necessary to fully understand and treat this key component of midlife women’s well-being. PMID:27013288

A biopsychosocial approach to women's sexual function and dysfunction at midlife: A narrative review.

PubMed

Thomas, Holly N; Thurston, Rebecca C

2016-05-01

A satisfying sex life is an important component of overall well-being, but sexual dysfunction is common, especially in midlife women. The aim of this review is (a) to define sexual function and dysfunction, (b) to present theoretical models of female sexual response, (c) to examine longitudinal studies of how sexual function changes during midlife, and (d) to review treatment options. Four types of female sexual dysfunction are currently recognized: Female Orgasmic Disorder, Female Sexual Interest/Arousal Disorder, Genito-Pelvic Pain/Penetration Disorder, and Substance/Medication-Induced Sexual Dysfunction. However, optimal sexual function transcends the simple absence of dysfunction. A biopsychosocial approach that simultaneously considers physical, psychological, sociocultural, and interpersonal factors is necessary to guide research and clinical care regarding women's sexual function. Most longitudinal studies reveal an association between advancing menopause status and worsening sexual function. Psychosocial variables, such as availability of a partner, relationship quality, and psychological functioning, also play an integral role. Future directions for research should include deepening our understanding of how sexual function changes with aging and developing safe and effective approaches to optimizing women's sexual function with aging. Overall, holistic, biopsychosocial approaches to women's sexual function are necessary to fully understand and treat this key component of midlife women's well-being. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

PubMed

Hamarneh, Sulaiman R; Mohamed, Mussa M Rafat; Economopoulos, Konstantinos P; Morrison, Sara A; Phupitakphol, Tanit; Tantillo, Tyler J; Gul, Sarah S; Gharedaghi, Mohammad Hadi; Tao, Qingsong; Kaliannan, Kanakaraju; Narisawa, Sonoko; Millán, José L; van der Wilden, Gwendolyn M; Fagenholz, Peter J; Malo, Madhu S; Hodin, Richard A

2014-10-01

To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

PubMed

Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

ASSOCIATIONS OF MACRO- AND MICROVASCULAR ENDOTHELIAL DYSFUNCTION WITH SUBCLINICAL VENTRICULAR DYSFUNCTION IN END-STAGE RENAL DISEASE

PubMed Central

Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita; Mills, Claire; Donovan, Catherine; Beussink, Lauren; Scherzer, Rebecca; Ganz, Peter; Shah, Sanjiv J

2016-01-01

Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. In order to evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral (VTI) of hyperemic blood flow following cuff deflation. Impaired FMD was associated with higher LV mass, independently of age and blood pressure: per two-fold lower FMD, LV mass was 4.1% higher (95%CI [0.49, 7.7], p=0.03). After adjustment for demographics, blood pressure, comorbidities and medications, a two-fold lower VTI was associated with 9.5% higher E/e’ ratio (95% CI [1.0, 16], p=0.03) and 6.7% lower absolute RV longitudinal strain (95% CI [2.0, 12], p=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well-controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. PMID:27550915

Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia.

PubMed

Horan, William P; Rassovsky, Yuri; Kern, Robert S; Lee, Junghee; Wynn, Jonathan K; Green, Michael F

2010-06-01

According to A.T. Beck and colleagues' cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues' formulation, modeling analyses indicated a significant indirect pathway from functional capacity-->dysfunctional attitudes-->negative symptoms-->real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery. (c) 2009 Elsevier Ltd. All rights reserved.

Metabolic Profiling in Association with Vascular Endothelial Cell Dysfunction Following Non-Toxic Cadmium Exposure

PubMed Central

Li, Xiaofei; Nong, Qingjiao; Mao, Baoyu; Pan, Xue

2017-01-01

This study aimed to determine the metabolic profile of non-toxic cadmium (Cd)-induced dysfunctional endothelial cells using human umbilical vein endothelial cells (HUVECs). HUVECs (n = 6 per group) were treated with 0, 1, 5, or 10 μM cadmium chloride (CdCl2) for 48 h. Cell phenotypes, including nitric oxide (NO) production, the inflammatory response, and oxidative stress, were evaluated in Cd-exposed and control HUVECs. Cd-exposed and control HUVECs were analysed using gas chromatography time-of-flight/mass spectrometry. Compared to control HUVECs, Cd-exposed HUVECs were dysfunctional, exhibiting decreased NO production, a proinflammatory state, and non-significant oxidative stress. Further metabolic profiling revealed 24 significantly-altered metabolites in the dysfunctional endothelial cells. The significantly-altered metabolites were involved in the impaired tricarboxylic acid (TCA) cycle, activated pyruvate metabolism, up-regulated glucogenic amino acid metabolism, and increased pyrimidine metabolism. The current metabolic findings further suggest that the metabolic changes linked to TCA cycle dysfunction, glycosylation of the hexosamine biosynthesis pathway (HBP), and compensatory responses to genomic instability and energy deficiency may be generally associated with dysfunctional phenotypes, characterized by decreased NO production, a proinflammatory state, and non-significant oxidative stress, in endothelial cells following non-toxic Cd exposure. PMID:28872622

The exploratory power of sleep effort, dysfunctional beliefs and arousal for insomnia severity and polysomnography-determined sleep.

PubMed

Hertenstein, Elisabeth; Nissen, Christoph; Riemann, Dieter; Feige, Bernd; Baglioni, Chiara; Spiegelhalder, Kai

2015-08-01

Differences between subjective sleep perception and sleep determined by polysomnography (PSG) are prevalent, particularly in patients with primary insomnia, indicating that the two measures are partially independent. To identify individualized treatment strategies, it is important to understand the potentially different mechanisms influencing subjective and PSG-determined sleep. The aim of this study was to investigate to what extent three major components of insomnia models, i.e., sleep effort, dysfunctional beliefs and attitudes about sleep, and presleep arousal, are associated with subjective insomnia severity and PSG-determined sleep. A sample of 47 patients with primary insomnia according to DSM-IV criteria and 52 good sleeper controls underwent 2 nights of PSG and completed the Glasgow Sleep Effort Scale, the Dysfunctional Beliefs and Attitudes about Sleep Scale, the Pre-Sleep Arousal Scale and the Insomnia Severity Index. Regression analyses were conducted to investigate the impact of the three predictors on subjective insomnia severity and PSG- determined total sleep time. All analyses were adjusted for age, gender, depressive symptoms and group status. The results showed that subjective insomnia severity was associated positively with sleep effort. PSG-determined total sleep time was associated negatively with somatic presleep arousal and dysfunctional beliefs and attitudes about sleep. This pattern of results provides testable hypotheses for prospective studies on the impact of distinct cognitive and somatic variables on subjective insomnia severity and PSG-determined total sleep time. © 2015 European Sleep Research Society.

Evaluative beliefs as mediators of the relationship between parental bonding and symptoms of paranoia and depression.

PubMed

Valiente, Carmen; Romero, Nuria; Hervas, Gonzalo; Espinosa, Regina

2014-01-30

This study was aimed to explore the distinct pathways that lead to depression and paranoia. We first examined the association of dysfunctional parenting experiences and negative self-evaluations in depression and paranoia. Furthermore, we also examined whether different self-evaluative beliefs could mediate the relationships between dysfunctional parenting experiences (i.e. parental overprotection or lack of care) and the development of depression and paranoia. A sample composed of 55 paranoid patients, 38 depressed patients and 44 healthy controls completed the Parental Bonding Instrument (PBI), the Evaluative Beliefs Scale (EBS) and some clinical scales. Our analyses revealed that lack of parental care and negative self-self evaluations were associated with depression symptoms. Analyses also revealed that parental overprotection and negative other-self evaluations were associated with paranoid symptoms. Furthermore, negative self-self and other-self evaluations fully mediated the relationship of parental overprotection and paranoia, whereas negative self-self evaluations partially mediated the relationship between lack of parental care and depression. These findings suggest that distinct patterns of parental practices may contribute to the development of different dysfunctional schemas which in turn may lead to either depression or paranoia. © 2013 Published by Elsevier Ireland Ltd.

On categorization and quantification of women's sexual dysfunctions: an epidemiological approach.

PubMed

Oberg, K; Fugl-Meyer, A R; Fugl-Meyer, K S

2004-06-01

The objectives of this study are to compare the two definitions of female sexual dysfunction, namely dysfunction per se (A category) and personal distress caused by dysfunction (B category), and to gauge their associations with some sociodemographic aspects and level of sexual well-being. The subjects were a nationally representative sample of sexually active Swedish women (n: 1056) aged 18-65 y, who participated in a combined structured interview/questionnaire investigation. The functions analysed were: self-reported sexual desire, interest, lubrication, orgasm, genital pain and vaginism, which were subclassified for the A and B categories into no, mild (sporadically occurring) and manifest dysfunction. Sexual well-being was reported along a six-grade scale ranging from very satisfied to very dissatisfied. The sociodemographic items registered were: education, occupation, financial situation, social group, immigrant status, location of domicile and church-going. Aggregated mild and manifest dysfunction per se of sexual interest, orgasm and vaginal lubrication were reported by about 60-90%. More than one-third had dyspareunia, but few reported vaginism. Mild dysfunctions were clearly more common than manifest dysfunctions. Not fully 45% of those with manifest low interest and orgasm perceived these dysfunctions as manifestly distressing, while in 60-70% lubricational insufficiency of dyspareunia led to manifest distress. Age and the included sociodemographic variables had marginal or no influence on sexual functions. A four-factor sexual function pattern was identified, closely linking A and B categories in a pairwise manner. Three factors, labelled sexual desire, orgasm and genital function were powerful classifiers (discriminant analysis) of level of sexual well-being. Hence, it is a matter of taste whether to use the A or the B category. Together, they can explain the gross level of satisfaction with sexual life to an adequate extent.

Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research.

PubMed

Allen, Mark S; Walter, Emma E

2018-04-01

Sexual dysfunction is a common problem among men and women and is associated with negative individual functioning, relationship difficulties, and lower quality of life. To determine the magnitude of associations between 6 health-related lifestyle factors (cigarette smoking, alcohol intake, physical activity, diet, caffeine, and cannabis use) and 3 common sexual dysfunctions (erectile dysfunction, premature ejaculation, and female sexual dysfunction). A comprehensive literature search of 10 electronic databases identified 89 studies that met the inclusion criteria (452 effect sizes; N = 348,865). Pooled mean effects (for univariate, age-adjusted, and multivariable-adjusted estimates) were computed using inverse-variance weighted random-effects meta-analysis and moderation by study and population characteristics were tested using random-effects meta-regression. Mean effect sizes from 92 separate meta-analyses provided evidence that health-related lifestyle factors are important for sexual dysfunction. Cigarette smoking (past and current), alcohol intake, and physical activity had dose-dependent associations with erectile dysfunction. Risk of erectile dysfunction increased with greater cigarette smoking and decreased with greater physical activity. Alcohol had a curvilinear association such that moderate intake was associated with a lower risk of erectile dysfunction. Participation in physical activity was associated with a lower risk of female sexual dysfunction. There was some evidence that a healthy diet was related to a lower risk of erectile dysfunction and female sexual dysfunction, and caffeine intake was unrelated to erectile dysfunction. Publication bias appeared minimal and findings were similar for clinical and non-clinical samples. Modification of lifestyle factors would appear to be a useful low-risk approach to decreasing the risk of erectile dysfunction and female sexual dysfunction. Strengths include the testing of age-adjusted and multivariable-adjusted models and tests of potential moderators using meta-regression. Limitations include low statistical power in models testing diet, caffeine, and cannabis use as risk factors. Results provide compelling evidence that cigarette smoking, alcohol, and physical activity are important for sexual dysfunction. Insufficient research was available to draw conclusions regarding risk factors for premature ejaculation or for cannabis use as a risk factor. These findings should be of interest to clinicians treating men and women with complaints relating to symptoms of sexual dysfunction. Allen MS, Walter EE. Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research. J Sex Med 2018;15:458-475. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Abnormal brain structure as a potential biomarker for venous erectile dysfunction: evidence from multimodal MRI and machine learning.

PubMed

Li, Lingli; Fan, Wenliang; Li, Jun; Li, Quanlin; Wang, Jin; Fan, Yang; Ye, Tianhe; Guo, Jialun; Li, Sen; Zhang, Youpeng; Cheng, Yongbiao; Tang, Yong; Zeng, Hanqing; Yang, Lian; Zhu, Zhaohui

2018-03-29

To investigate the cerebral structural changes related to venous erectile dysfunction (VED) and the relationship of these changes to clinical symptoms and disorder duration and distinguish patients with VED from healthy controls using a machine learning classification. 45 VED patients and 50 healthy controls were included. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS) and correlation analyses of VED patients and clinical variables were performed. The machine learning classification method was adopted to confirm its effectiveness in distinguishing VED patients from healthy controls. Compared to healthy control subjects, VED patients showed significantly decreased cortical volumes in the left postcentral gyrus and precentral gyrus, while only the right middle temporal gyrus showed a significant increase in cortical volume. Increased axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) values were observed in widespread brain regions. Certain regions of these alterations related to VED patients showed significant correlations with clinical symptoms and disorder durations. Machine learning analyses discriminated patients from controls with overall accuracy 96.7%, sensitivity 93.3% and specificity 99.0%. Cortical volume and white matter (WM) microstructural changes were observed in VED patients, and showed significant correlations with clinical symptoms and dysfunction durations. Various DTI-derived indices of some brain regions could be regarded as reliable discriminating features between VED patients and healthy control subjects, as shown by machine learning analyses. • Multimodal magnetic resonance imaging helps clinicians to assess patients with VED. • VED patients show cerebral structural alterations related to their clinical symptoms. • Machine learning analyses discriminated VED patients from controls with an excellent performance. • Machine learning classification provided a preliminary demonstration of DTI's clinical use.

Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

PubMed

Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

2010-06-27

The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

Specific personality traits and general personality dysfunction as predictors of the presence and severity of personality disorders in a clinical sample.

PubMed

Berghuis, Han; Kamphuis, Jan H; Verheul, Roel

2014-01-01

This study examined the associations of specific personality traits and general personality dysfunction in relation to the presence and severity of Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) personality disorders in a Dutch clinical sample. Two widely used measures of specific personality traits were selected, the Revised NEO Personality Inventory as a measure of normal personality traits, and the Dimensional Assessment of Personality Pathology-Basic Questionnaire as a measure of pathological traits. In addition, 2 promising measures of personality dysfunction were selected, the General Assessment of Personality Disorder and the Severity Indices of Personality Problems. Theoretically predicted associations were found between the measures, and all measures predicted the presence and severity of DSM-IV personality disorders. The combination of general personality dysfunction models and personality traits models provided incremental information about the presence and severity of personality disorders, suggesting that an integrative approach of multiple perspectives might serve comprehensive assessment of personality disorders.

Integrated Immunomodulatory Mechanisms through which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction

PubMed Central

Liddle, Danyelle M.; Wellings, Hannah R.; Power, Krista A.; Robinson, Lindsay E.; Monk, Jennifer M.

2017-01-01

Obesity is a global health concern with rising prevalence that increases the risk of developing other chronic diseases. A causal link connecting overnutrition, the development of obesity and obesity-associated co-morbidities is visceral adipose tissue (AT) dysfunction, characterized by changes in the cellularity of various immune cell populations, altered production of inflammatory adipokines that sustain a chronic state of low-grade inflammation and, ultimately, dysregulated AT metabolic function. Therefore, dietary intervention strategies aimed to halt the progression of obese AT dysfunction through any of the aforementioned processes represent an important active area of research. In this connection, fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to attenuate obese AT dysfunction through multiple mechanisms, ultimately affecting AT immune cellularity and function, adipokine production, and metabolic signaling pathways, all of which will be discussed herein. PMID:29186929

Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

PubMed

Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

2013-11-01

Cognitive impairment in amyotrophic lateral sclerosis is characterized by deficits on tests of executive function; however, the contribution of abnormal processing speed is unknown. Methods are confounded by tasks that depend on motor speed in patients with physical disability. Structural and functional magnetic resonance imaging studies have revealed multi-system cerebral involvement, with evidence of reduced white matter volume and integrity in predominant frontotemporal regions. The current study has two aims. First, to investigate whether cognitive impairments in amyotrophic lateral sclerosis are due to executive dysfunction or slowed processing speed using methodology that accommodates motor disability. This is achieved using a dual-task paradigm and tasks that manipulate stimulus presentation times and do not rely on response motor speed. Second, to identify relationships between specific cognitive impairments and the integrity of distinct white matter tracts. Thirty patients with amyotrophic lateral sclerosis and 30 age- and education-matched control subjects were administered an experimental dual-task procedure that combined a visual inspection time task and digit recall. In addition, measures of executive function (including letter fluency) and processing speed (visual inspection time and rapid serial letter identification) were administered. Integrity of white matter tracts was determined using region of interest analyses of diffusion tensor magnetic resonance imaging data. Patients with amyotrophic lateral sclerosis did not show impairments on tests of processing speed, but executive deficits were revealed once visual inspection time was combined with digit recall (dual-task) and in letter fluency. In addition to the corticospinal tracts, significant differences in fractional anisotropy and mean diffusivity were found between groups in a number of prefrontal and temporal white matter tracts including the anterior cingulate, anterior thalamic radiation, uncinate fasciculus and hippocampal portion of the cingulum bundles. Significant differences also emerged in the anterior corona radiata as well as in white matter underlying the superior, medial and inferior frontal gyri and the temporal gyri. Dual-task performance significantly correlated with fractional anisotropy measures in the middle frontal gyrus white matter and anterior corona radiata. Letter fluency indices significantly correlated with fractional anisotropy measures of the inferior frontal gyrus white matter and corpus callosum in addition to the corticospinal tracts and mean diffusivity measures in the white matter of the superior frontal gyrus. The current study demonstrates that cognitive impairment in amyotrophic lateral sclerosis is not due to generic slowing of processing speed. Moreover, different executive deficits are related to distinct prefrontal tract involvement in amyotrophic lateral sclerosis with dual-task impairment associating with dorsolateral prefrontal dysfunction and letter fluency showing greater dependence on inferolateral prefrontal dysfunction.

Analysing UK clinicians' understanding of cognitive symptoms in major depression: A survey of primary care physicians and psychiatrists.

PubMed

McAllister-Williams, R Hamish; Bones, Kate; Goodwin, Guy M; Harrison, John; Katona, Cornelius; Rasmussen, Jill; Strong, Sarah; Young, Allan H

2017-01-01

Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians. A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research. There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic. Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers. UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Association Between Second Metatarsal Length and Forefoot Loading Under the Second Metatarsophalangeal Joint.

PubMed

Fleischer, Adam E; Hshieh, Shenche; Crews, Ryan T; Waverly, Brett J; Jones, Jacob M; Klein, Erin E; Weil, Lowell; Weil, Lowell Scott

2018-05-01

Metatarsal length is believed to play a role in plantar plate dysfunction, although the mechanism through which progressive injury occurs is still uncertain. We aimed to clarify whether length of the second metatarsal was associated with increased plantar pressure measurements in the forefoot while walking. Weightbearing radiographs and corresponding pedobarographic data from 100 patients in our practice walking without a limp were retrospectively reviewed. Radiographs were assessed for several anatomic relationships, including metatarsal length, by a single rater. Pearson correlation analyses and multiple linear regression models were used to determine whether metatarsal length was associated with forefoot loading parameters. The relative length of the second to first metatarsal was positively associated with the ratio of peak pressure beneath the respective metatarsophalangeal joints ( r = 0.243, P = .015). The relative length of the second to third metatarsal was positively associated with the ratios of peak pressure ( r = 0.292, P = .003), pressure-time integral ( r = 0.249, P = .013), and force-time integral ( r = 0.221, P = .028) beneath the respective metatarsophalangeal joints. Although the variability in loading predicted by the various regression analyses was not large (4%-14%), the relative length of the second metatarsal (to the first and to the third) was maintained in each of the multiple regression models and remained the strongest predictor (highest standardized β-coefficient) in each of the models. Patients with longer second metatarsals exhibited relatively higher loads beneath the second metatarsophalangeal joint during barefoot walking. These findings provide a mechanism through which elongated second metatarsals may contribute to plantar plate injuries. Level III, comparative study.

Visual integration dysfunction in schizophrenia arises by the first psychotic episode and worsens with illness duration.

PubMed

Keane, Brian P; Paterno, Danielle; Kastner, Sabine; Silverstein, Steven M

2016-05-01

Visual integration dysfunction characterizes schizophrenia, but prior studies have not yet established whether the problem arises by the first psychotic episode or worsens with illness duration. To investigate the issue, we compared chronic schizophrenia patients (SZs), first episode psychosis patients (FEs), and well-matched healthy controls on a brief but sensitive psychophysical task in which subjects attempted to locate an integrated shape embedded in noise. Task difficulty depended on the number of noise elements co-presented with the shape. For half of the experiment, the entire display was scaled down in size to produce a high spatial frequency (HSF) condition, which has been shown to worsen patient integration deficits. Catch trials-in which the circular target appeared without noise-were also added so as to confirm that subjects were paying adequate attention. We found that controls integrated contours under noisier conditions than FEs, who, in turn, integrated better than SZs. These differences, which were at times large in magnitude (d = 1.7), clearly emerged only for HSF displays. Catch trial accuracy was above 95% for each group and could not explain the foregoing differences. Prolonged illness duration predicted poorer HSF integration across patients, but age had little effect on controls, indicating that the former factor was driving the effect in patients. Taken together, a brief psychophysical task efficiently demonstrates large visual integration impairments in schizophrenia. The deficit arises by the first psychotic episode, worsens with illness duration, and may serve as a biomarker of illness progression. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Attachment to parents and peers as a risk factor for adolescent depressive disorders: the mediating role of emotion regulation.

PubMed

Kullik, Angelika; Petermann, Franz

2013-08-01

This study examined emotion regulation as a mediator in the relationship of attachment and depression in adolescents. Participants (N girls = 127; M age = 14.50; N boys = 121; M age = 14.31) completed self-report questionnaires of attachment to parents and peers, emotion regulation and depression. Models with dysfunctional emotion regulation as a mediation variable were tested via hierarchical multiple regression analyses and bootstrapping procedure. Results revealed significant relations between attachment to parents and peers, dysfunctional emotion regulation and depression. For girls, internal-dysfunctional emotion regulation was a mediator in the relation of attachment to parents and depression and partly mediated the association of attachment to peers. For boys, internal- and external-dysfunctional emotion regulation acted as partly mediators in association of attachment to parents and depression. Results indicate important mechanisms that contribute to the refinement of conceptual models and provide indications for gender specific prevention and intervention for depressive disorders.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

PubMed

Mutlak, Haitham; Reyher, Christian; Meybohm, Patrick; Papadopoulos, Nestoras; Hanke, Alexander Alfons; Zacharowski, Kai; Weber, Christian Friedrich

2015-02-01

There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

PubMed

Brown, Stephen; Hutton, Brian; Clifford, Tammy; Coyle, Doug; Grima, Daniel; Wells, George; Cameron, Chris

2014-09-29

The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.

Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

PubMed Central

Clark, Duncan B.; Chung, Tammy; Martin, Christopher S.; Hasler, Brant P.; Fitzgerald, Douglas H.; Luna, Beatriz; Brown, Sandra A.; Tapert, Susan F.; Brumback, Ty; Cummins, Kevin; Pfefferbaum, Adolf; Sullivan, Edith V.; Pohl, Kilian M.; Colrain, Ian M.; Baker, Fiona C.; De Bellis, Michael D.; Nooner, Kate B.; Nagel, Bonnie J.

2017-01-01

During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use. PMID:29180956

Sexual Problems Among Older Women by Age and Race.

PubMed

Hughes, Anne K; Rostant, Ola S; Pelon, Sally

2015-08-01

The purpose of our study was to examine the prevalence of sexual problems by age and race among older women in the United States and to examine quality of life correlates to sexual dysfunction among non-Hispanic white and African American older women. A cross-sectional study using self-report surveys was conducted among community-dwelling U.S. women, aged 60 years and over. A total of 807 women aged 61-89 years were included. Self-administered questionnaires assessed sexual dysfunction, satisfaction with life, depressive symptomatology, and self-rated health. Analyses included multivariate logistic regression. The mean age of the sample was 66 years. Two-thirds of the sample had at least one sexual dysfunction; the most common for both African American and non-Hispanic white women were lack of interest in sex and vaginal dryness. Prevalence varied by age for each of the sexual dysfunctions. The odds of experiencing sexual dysfunction varied with age and race. Compared with non-Hispanic white women, African American women had lower odds of reporting lack of interest in sex or vaginal dryness. Poor self-rated health, depressive symptomatology, and lower satisfaction with life were associated with higher odds of having some sexual dysfunction. Improved understanding of how sexual dysfunction affects women across multiple age ranges and racial/ethnic groups can assist providers in making recommendations for care that are patient centered. The associations that we identified with quality of life factors highlight the need to assess sexual health care in the aging female population.

Integrating prospective longitudinal data: modeling personality and health in the Terman Life Cycle and Hawaii Longitudinal Studies.

PubMed

Kern, Margaret L; Hampson, Sarah E; Goldberg, Lewis R; Friedman, Howard S

2014-05-01

The present study used a collaborative framework to integrate 2 long-term prospective studies: the Terman Life Cycle Study and the Hawaii Personality and Health Longitudinal Study. Within a 5-factor personality-trait framework, teacher assessments of child personality were rationally and empirically aligned to establish similar factor structures across samples. Comparable items related to adult self-rated health, education, and alcohol use were harmonized, and data were pooled on harmonized items. A structural model was estimated as a multigroup analysis. Harmonized child personality factors were then used to examine markers of physiological dysfunction in the Hawaii sample and mortality risk in the Terman sample. Harmonized conscientiousness predicted less physiological dysfunction in the Hawaii sample and lower mortality risk in the Terman sample. These results illustrate how collaborative, integrative work with multiple samples offers the exciting possibility that samples from different cohorts and ages can be linked together to directly test life span theories of personality and health. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Olfactory Dysfunction Is Associated with the Intake of Macronutrients in Korean Adults

PubMed Central

Kong, Il Gyu; Kim, So Young; Kim, Min-Su; Park, Bumjung; Kim, Jin-Hwan

2016-01-01

Background Olfactory function can impact food selection. However, few large population-based studies have investigated this effect across different age groups. The objective of this study was to assess the association between subjective olfactory dysfunction (anosmia or hyposmia) and macronutrient intake. Methods A total of 24,990 participants aged 20 to 98 years were evaluated based on data collected through the Korea National Health and Nutrition Examination Survey from 2008 through 2012. Olfactory dysfunction was surveyed using a self-reported questionnaire, and the nutritional status was assessed through a validated 24-hour recall method. Simple and multiple linear regression analyses with complex sampling were performed to evaluate the relationships between olfactory dysfunction and protein intake (daily protein intake/recommended protein intake [%]), carbohydrate intake (daily carbohydrate intake/total calories [%]), and fat intake (daily fat intake/total calories [%]) after adjusting for age, sex, body mass index, income, smoking history, alcohol consumption, and stress level. Results Olfactory dysfunction was reported by 5.4% of Korean adults and was found to be associated with decreased fat consumption (estimated value [EV] of fat intake [%] = -0.57, 95% confidence interval [CI] = -1.13 to -0.13, P = 0.045). A subgroup analysis according to age and sex revealed that among young females, olfactory dysfunction was associated with reduced fat consumption (EV = -2.30, 95% CI = -4.16 to -0.43, P = 0.016) and increased carbohydrate intake (EV = 2.80, 95% CI = 0.55 to 5.05, P = 0.015), and that among middle-aged females, olfactory dysfunction was also associated with reduced fat intake (EV = -1.26, 95% CI = -2.37 to -0.16, P = 0.025). In contrast, among young males, olfactory dysfunction was associated with reduced protein intake (EV = -26.41 95% CI = -45.14 to -7.69, P = 0.006). Conclusion Olfactory dysfunction was associated with reduced fat intake. Moreover, olfactory dysfunction exerted differential effects on eating behavior depending on age and sex. PMID:27723843

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.

PubMed

Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L

2016-08-01

The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

PubMed

Tarantini, Stefano; Valcarcel-Ares, M Noa; Yabluchanskiy, Andriy; Tucsek, Zsuzsanna; Hertelendy, Peter; Kiss, Tamas; Gautam, Tripti; Zhang, Xin A; Sonntag, William E; de Cabo, Rafael; Farkas, Eszter; Elliott, Michael H; Kinter, Michael T; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-14

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

Complementary Therapies for Significant Dysfunction from Tinnitus: Treatment Review and Potential for Integrative Medicine.

PubMed

Wolever, Ruth Q; Price, Rebecca; Hazelton, A Garrett; Dmitrieva, Natalia O; Bechard, Elizabeth M; Shaffer, Janet K; Tucci, Debara L

2015-01-01

Tinnitus is a prevalent and costly chronic condition; no universally effective treatment exists. Only 20% of patients who report tinnitus actually seek treatment, and when treated, most patients commonly receive sound-based and educational (SBE) therapy. Additional treatment options are necessary, however, for nonauditory aspects of tinnitus (e.g., anxiety, depression, and significant interference with daily life) and when SBE therapy is inefficacious or inappropriate. This paper provides a comprehensive review of (1) conventional tinnitus treatments and (2) promising complementary therapies that have demonstrated some benefit for severe dysfunction from tinnitus. While there has been no systematic study of the benefits of an Integrative Medicine approach for severe tinnitus, the current paper reviews emerging evidence suggesting that synergistic combinations of complementary therapies provided within a whole-person framework may augment SBE therapy and empower patients to exert control over their tinnitus symptoms without the use of medications, expensive devices, or extended programs.

The Impact of Intimate Male Partner Violence on Women's Sexual Function: A Study in Iran.

PubMed

Jamali, Safieh; Javadpour, Shohreh

2016-12-01

Sexuality is an integral part of a woman's life. A variety of factors can affect a woman's sexuality, among them physical disorders, social-religious beliefs, age, psychological factors, depression, mental tension, disbelief, an unfulfilling relationship with one's spouse and emotional and physical violence. The present study aimed to explore the rate of domestic violence against women and its impact on women's sexuality. This cross-sectional study was conducted on 813 women referring to the gynaecology clinics of Jahrom, Iran, from April to October 2015. Data were collected using a demographics questionnaire, a violence questionnaire and Female Sexual Function Index (FSFI). The collected data were analysed using Student's t-test and logistic regression. The prevalence of violence was found to be 43.2%. Also, there was a significant relationship between violence and age (OR=1.33 95% CI=2.22-7.95, p<0.001). The rate of violence was found to increase by 3.1 times with an increase in the length of marriage (OR=3.1595% CI=1.42-4.12, p<0.001). Moreover, domestic violence significantly correlated with women's education level (OR=11.75 95% CI=2.15-64.12, p=0.002) and their husband's education level (OR=0.194, 95%CI=0.329-0.919, p=0.02). The results showed that the sexual function mean score of non-abused women and abused women were 17.74±8.82 and 14.59±10.63, respectively. However, a significant difference was found between the two groups regarding the domains of sexual function (p<0.05). This study showed that the frequency of domestic violence is rather high and that can increase the risk of sexual dysfunction. Thus, routine screening for violence and sexual dysfunction is recommended for early detection of violence and sexual dysfunction.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Chronic periodontitis is associated with erectile dysfunction. A case-control study in european population.

PubMed

Martín, Amada; Bravo, Manuel; Arrabal, Miguel; Magán-Fernández, Antonio; Mesa, Francisco

2018-07-01

To determine the association between chronic periodontitis and erectile dysfunction adjusting for biochemical markers and other comorbidities. A case-control study was conducted on 158 male patients; 80 cases with erectile dysfunction according to the International Index of Erectile Function and 78 controls. Sociodemographic data were gathered, and a periodontal examination was performed. Testosterone, lipid profile, C-reactive protein and glycaemic parameters were assessed. All variables were compared between groups, and multivariate logistic regression analyses were performed. 74% of the cases were diagnosed with chronic periodontitis. Number of sites with pocket probing depth 4-6 mm (p = 0.05) and number of sites with clinical attachment loss >3 mm (p < 0.01) were higher in the cases. Triglycerides (p < 0.01), C-reactive protein (p = 0.02) and glycosylated haemoglobin (p = 0.04) were also higher in the cases. Logistic regression showed that patients with chronic periodontitis were more likely to have erectile dysfunction (OR=2.17; 95% CI (1.06-4.43); p = 0.03) independently of other confounders. Patients with erectile dysfunction showed worse periodontal condition. Chronic periodontitis seems to play a key role as a risk factor in the pathogenesis of erectile dysfunction independently of other morbidities. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma

PubMed Central

Denk, Stephanie; Wiegner, Rebecca; Hönes, Felix M.; Messerer, David A. C.; Radermacher, Peter; Kalbitz, Miriam; Braumüller, Sonja; McCook, Oscar; Gebhard, Florian; Weckbach, Sebastian; Huber-Lang, Markus

2015-01-01

Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction. PMID:26556956

[Kinematic movement analyses and their application in psychiatry].

PubMed

Juckel, Georg; Mergl, Roland; Hegerl, Ulrich

2005-04-01

There is a long tradition to develop valid instruments for the exact assessment of psycho-motor dysfunctions in psychiatry. However, progress is hampered by the complexity of emotionally driven movements in psychiatric patients. Methods used up to now either remains unspecific due to only qualitative measurements or focus on the neurophysiological aspects too much. Thus, the results accomplished so far are only very general unspecific concerning different groups of psychiatric patients. In this paper, two own methods are presented which are aimed to avoid the two poles above mentioned. Kinematic analyses of facial expressions as well as handwriting movements provide quantitative and quite specific informations about psycho-motor dysfunctions of psychiatric patients and the effects of psychotropic substances. Thus, these methods are well suitable for relating them to other neurobiological parameters in order to contribute to the pathophysiological understanding of psycho-motor symptoms in psychiatric patients.

Comparison of the clinical utility of atrial and B type natriuretic peptide measurement for the diagnosis of systolic dysfunction in a low‐risk population

PubMed Central

Galasko, Gavin; Collinson, Paul O; Barnes, Sophie C; Gaze, David; Lahiri, Arjivit; Senior, Roxy

2007-01-01

Background Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high‐throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro‐atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care. Methods 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45–89, interquartile range 51–67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton–Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at −70°C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2–2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6–10.1%). Echocardiography was used as the diagnostic “gold standard”, with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of ⩽40%. Patients were dichotomised by ejection fraction from 50% to 30%, and receiver operating characteristic curves constructed and the area under the curve (AUC) compared. Results At 40% ejection fraction, NTproANP and NTproBNP showed AUCs of, respectively, 0.738 (0.601–0.875) and 0.973 (0.958–0.989), p<0.004. Conclusion NTproBNP is superior to NTproANP for detection of systolic dysfunction. PMID:17513518

Development and initial validation of a brief self-report measure of cognitive dysfunction in fibromyalgia.

PubMed

Kratz, Anna L; Schilling, Stephen G; Goesling, Jenna; Williams, David A

2015-06-01

Pain is often the focus of research and clinical care in fibromyalgia (FM); however, cognitive dysfunction is also a common, distressing, and disabling symptom in FM. Current efforts to address this problem are limited by the lack of a comprehensive, valid measure of subjective cognitive dysfunction in FM that is easily interpretable, accessible, and brief. The purpose of this study was to leverage cognitive functioning item banks that were developed as part of the Patient Reported Outcomes Measurement Information System (PROMIS) to devise a 10-item short form measure of cognitive functioning for use in FM. In study 1, a nationwide (U.S.) sample of 1,035 adults with FM (age range = 18-82, 95.2% female) completed 2 cognitive item pools. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. A recommended 10-item measure, called the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) was created. In study 2, 232 adults with FM completed the MISCI and a legacy measure of cognitive functioning that is used in FM clinical trials, the Multiple Ability Self-Report Questionnaire (MASQ). The MISCI showed excellent internal reliability, low ceiling/floor effects, and good convergent validity with the MASQ (r = -.82). This paper presents the MISCI, a 10-item measure of cognitive dysfunction in FM, developed through classical test theory and item response theory. This brief but comprehensive measure shows evidence of excellent construct validity through large correlations with a lengthy legacy measure of cognitive functioning. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.

2009-10-15

Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterationsmore » in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 {mu}M Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E{sub 2} (PGE{sub 2}). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F{sub 2}-IsoPs and PGE{sub 2} in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.« less

Macrophage functions measured by magnetic microparticles in vivo and in vitro

NASA Astrophysics Data System (ADS)

Möller, Winfried; Kreyling, Wolfgang G.; Kohlhäufl, Martin; Häussinger, Karl; Heyder, Joachim

2001-01-01

Monodisperse ferrimagnetic iron-oxide particles of 1.4 μm geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs.

What's your relationship with computerized manufacturing technologies -- functional, dysfunctional or non-existent?

Treesearch

Jan Wiedenbeck; Jeff Parsons; Bruce Beeken

2009-01-01

Computer-aided manufacturing (CAM), in which computer-aided design (CAD) and computer numerically controlled (CNC) machining are integrated for the production of parts, became a viable option for the woodworking industry in the 1980s.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL

PubMed Central

2014-01-01

Background The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. Methods We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL’s interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. Results We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Conclusions Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based. PMID:25267416

Association of left ventricular longitudinal and circumferential systolic dysfunction with diastolic function in hypertension: a nonlinear analysis focused on the interplay with left ventricular geometry.

PubMed

Ballo, Piercarlo; Nistri, Stefano; Cameli, Matteo; Papesso, Barbara; Dini, Frank Lloyd; Galderisi, Maurizio; Zuppiroli, Alfredo; Mondillo, Sergio

2014-02-01

The relationships of left ventricular (LV) longitudinal and circumferential systolic dysfunction with diastolic performance in hypertensive patients have never been compared. In 532 asymptomatic hypertensive patients, circumferential function was assessed with the use of midwall fractional shortening (mFS) and stress-corrected mFS (SCmFS), whereas longitudinal function was assessed with the use of left atrioventricular plane displacement (AVPD) and systolic mitral annulus velocity (s'). Early diastolic annular velocity (e') and the E/e' ratio were measured. Global longitudinal and circumferential strain were determined in a subset of 210 patients. e' was linearly related to all systolic indexes (AVPD: R = 0.40; s': R = 0.39; mFS: R = 0.16; SCmFS: R = 0.17; all P < .0001), but the correlations were stronger with longitudinal indexes than with circumferential ones (P < .0001). E/e' was nonlinearly related to AVPD (R = -0.49; P < .0001) and s' (R = -0.34; P < .0001) and showed no relationship with mFS and SCmFS. Longitudinal indexes were superior to circumferential ones in predicting e' <8 cm/s, E/e' <8, and E/e' ≥13. The effect of LV geometry on LV diastolic function was evident among patients with preserved systolic longitudinal function, but was blunted among patients with impaired longitudinal function. In multivariable analyses, only longitudinal indexes remained associated with e' and E/e'. Analyses using strains provided similar results. In asymptomatic hypertensive subjects, LV diastolic performance is independently associated with longitudinal systolic dysfunction, but not with circumferential systolic dysfunction. Subtle longitudinal systolic impairment plays a role in mediating the effect of LV geometry on diastolic performance. These findings may support the need of critically revising the concept of isolated diastolic dysfunction in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Executive dysfunction predicts social cognition impairment in amyotrophic lateral sclerosis.

PubMed

Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Catherine M; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H

2015-07-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor system with recognised extra-motor and cognitive involvement. This cross-sectional study examined ALS patients' performance on measures requiring social inference, and determined the relationship between such changes and variations in mood, behaviour, personality, empathy and executive function. Fifty-five ALS patients and 49 healthy controls were compared on tasks measuring social cognition and executive function. ALS patients also completed measures examining mood, behaviour and personality. Regression analyses explored the contribution of executive function, mood, behaviour and personality to social cognition scores within the ALS sample. A between-group MANOVA revealed that, the ALS group was impaired relative to controls on two composite scores for social cognition and executive function. Patients also performed worse on individual tests of executive function measuring cognitive flexibility, response inhibition and concept formation, and on individual aspects of social cognition assessing the attribution of emotional and mental states. Regression analyses indicated that ALS-related executive dysfunction was the main predictor of social cognition performance, above and beyond demographic variables, behaviour, mood and personality. On at least some aspects of social cognition, impaired performance in ALS appears to be secondary to executive dysfunction. The profile of cognitive impairment in ALS supports a cognitive continuum between ALS and frontotemporal dementia.

Does alcohol craving mediate the impulsivity-aggression relationship in recently detoxified alcohol-dependent patients?

PubMed

Roozen, H G; Wetering, B J M van de; Franken, I H A

2013-01-01

The relationship between the use of alcohol and aggression is complex and represents major public health issues. Delving into the nature of this association is vital, since various underlying factors may contribute to the expression of aggression. This study examined trait aggression by assessing correlates and, subsequently, the unique contribution of alcohol craving, and dysfunctional impulsivity, by means of correlational and mediational analyses. Forty inpatient detoxified alcohol-dependent patients were recruited. These participants completed the Desire for Alcohol Questionnaire (DAQ), Dickman Impulsivity Inventory (DII), and the Aggression Questionnaire (AQ). The findings indicated that aggression, dysfunctional impulsivity, and alcohol craving were all positively intercorrelated. The association between dysfunctional impulsivity and aggression was robust. The mediational analyses yielded that craving partially mediated this relationship, although not very substantial. It was shown that impulsivity, as a personality characteristic, is strongly associated with aggressive behaviors, whereby the impact of craving on the relationship between impulsivity and trait aggression in alcohol-dependent inpatients was weak. Since it has been posited that factors such as impulsivity and craving may contribute to the lucid association between substance use and aggression, these findings mirror previous research on stimulant users and, subsequently, substantiates that craving exerts only a minor weight on the strong impulsivity-aggression relationship.

Identification of Psychological Dysfunctions and Eating Disorders in Obese Women Seeking Weight Loss: Cross-Sectional Study

PubMed Central

Panchaud Cornut, Maude; Szymanski, Jennifer; Marques-Vidal, Pedro; Giusti, Vittorio

2014-01-01

Objective. The aim of this study is to analyse associations between eating behaviour and psychological dysfunctions in treatment-seeking obese patients and identify parameters for the development of diagnostic tools with regard to eating and psychological disorders. Design and Methods. Cross-sectional data were analysed from 138 obese women. Bulimic Investigatory Test of Edinburgh and Eating Disorder Inventory-2 assessed eating behaviours. Beck Depression Inventory II, Spielberger State-Trait Anxiety Inventory, form Y, Rathus Assertiveness Schedule, and Marks and Mathews Fear Questionnaire assessed psychological profile. Results. 61% of patients showed moderate or major depressive symptoms and 77% showed symptoms of anxiety. Half of the participants presented with a low degree of assertiveness. No correlation was found between psychological profile and age or anthropometric measurements. The prevalence and severity of depression, anxiety, and assertiveness increased with the degree of eating disorders. The feeling of ineffectiveness explained a large degree of score variance. It explained 30 to 50% of the variability of assertiveness, phobias, anxiety, and depression. Conclusion. Psychological dysfunctions had a high prevalence and their severity is correlated with degree of eating disorders. The feeling of ineffectiveness constitutes the major predictor of the psychological profile and could open new ways to develop screening tools. PMID:24737999

Sensory Dysfunction and Sexuality in the U.S. Population of Older Adults.

PubMed

Zhong, Selena; Pinto, Jayant M; Wroblewski, Kristen E; McClintock, Martha K

2018-04-01

The sexual experience is shaped by sensory function; with aging, sensory dysfunction may interfere with sexuality and sexual behavior between partners. Specifically, older adults with age-related sensory dysfunction may have less sexual activity than those with better sensory function. In addition, since sexual desire and attraction rests in part upon sensory function, sensory dysfunction may also be associated with less sexual motivation. To test the association between sexual activity and motivation in older adults and their sensory dysfunction. Sensory dysfunction was measured both by global sensory impairment (a validated measure of dysfunction shared among the 5 classic senses: olfaction, vision, taste, touch, hearing) and by total sensory burden (cumulative sensory loss). Sexual activity was quantified by frequency and type of sexual behavior. Sexual motivation was measured by the frequency of sexual ideation and the importance of sex to the respondent. We used cross-sectional data from a nationally representative sample of community-dwelling older adults (aged 57-85 years) in the United States (National Social Life, Health, and Aging Project, N = 3,005) in logistic regression analyses. Sexual activity, sexual motivation, and satisfaction with the sexual relationship were self-reported. Older adults with sensory dysfunction were less likely to be sexually active-an association that persisted when accounting for other factors that also affected sexual activity (age, gender, partnered status, mental and physical health, and relationship satisfaction). Nonetheless, sensory dysfunction did not impair sexual motivation, nor affect the physical and emotional satisfaction with the sexual relationship. Among currently sexually active older adults, sensory dysfunction did not affect the frequency of sex or the type of sexual activity (foreplay, vaginal intercourse, or oral sex). These results were the same for 2 different measures of sensory dysfunction. This is the first nationally representative study of sexuality and multisensory dysfunction in community-dwelling older adults. 4 of the 5 classic senses were measured with objective tests, and hearing was rated by interviewers in the context of their conversation. Medical and health care interventions that can reduce the burden of sensory dysfunction may improve older adults' sexual experience. Sensory dysfunction is associated with sexual inactivity, but not with sexual motivation. Among those who are sexually active, sensory dysfunction did not interfere with sexual expression. Improving the sexual experience of older adults requires a focus on sensory dysfunction as an impediment to sexual activity given that older adults remain sexually motivated. Zhong S, Pinto JM, Wroblewski KE, et al. Sensory Dysfunction and Sexuality in the U.S. Population of Older Adults. J Sex Med 2018;15:502-509. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Hypothyroidism Side Effect in Patients Treated with Sunitinib or Sorafenib: Clinical and Structural Analyses

PubMed Central

Shu, Mao; Zai, Xiaoli; Zhang, Beina; Wang, Rui; Lin, Zhihua

2016-01-01

Tyrosine kinase inhibitors (TKIs) provide more effective targeted treatments for cancer, but are subject to a variety of adverse effects, such as hypothyroidism. TKI-induced hypothyroidism is a highly complicated issue, because of not only the unrealized toxicological mechanisms, but also different incidences of individual TKI drugs. While sunitinib is suspected for causing thyroid dysfunction more often than other TKIs, sorafenib is believed to be less risky. Here we integrated clinical data and in silico drug-protein interactions to examine the pharmacological distinction between sunitinib and sorafenib. Statistical analysis on the FDA Adverse Event Reporting System (FAERS) confirmed that sunitinib is more concurrent with hypothyroidism than sorafenib, which was observed in both female and male patients. Then, we used docking method and identified 3 proteins specifically binding to sunitinib but not sorafenib, i.e., retinoid X receptor alpha, retinoic acid receptors beta and gamma. As potential off-targets of sunitinib, these proteins are well known to assemble with thyroid hormone receptors, which can explain the profound impact of sunitinib on thyroid function. Taken together, we established a strategy of integrated analysis on clinical records and drug off-targets, which can be applied to explore the molecular basis of various adverse drug reactions. PMID:26784451

Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

PubMed

Bonfiglio, Luca; Bocci, Tommaso; Minichilli, Fabrizio; Crecchi, Alessandra; Barloscio, Davide; Spina, Donata Maria; Rossi, Bruno; Sartucci, Ferdinando

2017-01-01

As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Sexual Problems Among Older Women by Age and Race

PubMed Central

Rostant, Ola S.; Pelon, Sally

2015-01-01

Abstract Background: The purpose of our study was to examine the prevalence of sexual problems by age and race among older women in the United States and to examine quality of life correlates to sexual dysfunction among non-Hispanic white and African American older women. Methods: A cross-sectional study using self-report surveys was conducted among community-dwelling U.S. women, aged 60 years and over. A total of 807 women aged 61–89 years were included. Self-administered questionnaires assessed sexual dysfunction, satisfaction with life, depressive symptomatology, and self-rated health. Analyses included multivariate logistic regression. Results: The mean age of the sample was 66 years. Two-thirds of the sample had at least one sexual dysfunction; the most common for both African American and non-Hispanic white women were lack of interest in sex and vaginal dryness. Prevalence varied by age for each of the sexual dysfunctions. The odds of experiencing sexual dysfunction varied with age and race. Compared with non-Hispanic white women, African American women had lower odds of reporting lack of interest in sex or vaginal dryness. Poor self-rated health, depressive symptomatology, and lower satisfaction with life were associated with higher odds of having some sexual dysfunction. Conclusions: Improved understanding of how sexual dysfunction affects women across multiple age ranges and racial/ethnic groups can assist providers in making recommendations for care that are patient centered. The associations that we identified with quality of life factors highlight the need to assess sexual health care in the aging female population. PMID:26061291

The Mechanisms of Movement Control and Time Estimation in Cervical Dystonia Patients

PubMed Central

Lungu, Ovidiu V.; Shaw, Daniel J.; Kasparek, Tomas; Bareš, Martin

2013-01-01

Traditionally, the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in the basal ganglia. Recently, however, substantial evidence has emerged for cerebellar involvement. While the absence of neurological “cerebellar signs” in most dystonia patients may be considered at least provoking, there are more subtle indications of cerebellar dysfunction in complex, demanding tasks. Specifically, given the role of the cerebellum in the neural representation of time, in the millisecond range, dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia. In the current study, we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellum, namely, the interception of a moving target with changing parameters (speed, acceleration, and angle) with a simple response (pushing a button). The cervical dystonia patients achieved significantly worse results than a sample of healthy controls. Our results suggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses during the prediction of upcoming actions, an impairment we interpret as evidence of cerebellar dysfunction. PMID:24198973

Psychological interventions for delayed ejaculation/orgasm.

PubMed

Althof, S E

2012-01-01

Of all the male sexual dysfunctions, delayed ejaculation (DE) is the least understood, least common and least studied. This paper aims to review and integrate the diverse psychological theories and proposed psychological interventions for DE. Clinicians will then be able to more clearly discern the relevant psychological/interpersonal issues of the patient/couple and implement systematically based effective interventions. After reviewing the literature, it is clear that no one theory accounts for all the varied presentations of DE, and no theory by itself has strong empirical support. However, awareness of the diverse points of view helps clinicians conduct better assessments and broaden their understanding of the patient's ejaculatory dysfunction. Similarly, no one psychological intervention works for all patients, nor will unsystematic random selection of interventions. This paper stresses on the need to clearly identify the source of the dysfunction and select treatments based upon the precipitating and maintaining factors. Much work remains to be done with regard to our understanding and treatment of DE. Specifically, we need to craft an evidence-based definition, assess the true prevalence of the dysfunction, demonstrate the efficacy of psychological interventions and design validated outcome measures.

Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis

NASA Astrophysics Data System (ADS)

Li, Yuanyuan; Jin, Suoqin; Lei, Lei; Pan, Zishu; Zou, Xiufen

2015-03-01

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

PubMed

Hoskote, Aparna; Burch, Michael

2015-06-01

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

Frequency of sexual dysfunction in patients with a psychotic disorder receiving antipsychotics.

PubMed

Montejo, Angel L; Majadas, Susana; Rico-Villademoros, Fernando; Llorca, Ginés; De La Gándara, Jesús; Franco, Manuel; Martín-Carrasco, Manuel; Aguera, Luis; Prieto, Nieves

2010-10-01

Although it is a troublesome side effect, information on antipsychotic-induced sexual dysfunction is limited. To evaluate the frequency of sexual dysfunction and its impact on treatment adherence in patients with a psychotic disorder treated with various antipsychotics under routine clinical conditions. Subjects included were sexually active male and female patients 18 years of age or older with a diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or other psychotic disorder. This was a multicenter, cross-sectional, and naturalistic study conducted by 18 investigators. In addition to sexual functioning, we recorded demographic data, psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and medication history. Pyschotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SalSex). All the analyses were performed in the 243 evaluable patients. Most patients were males (71%), and the most common diagnosis was schizophrenia (71%). Overall, 46% of the patients exhibited sexual dysfunction according to the assessment with the SalSex (50% of the males and 37% of the females). Only 37% of the patients with sexual dysfuntion spontaneously reported it. Among the patients exhibiting sexual dysfunction, 32% reported to have poor tolerance to the disturbance. With the exception of conventionals depot, which had a very important and greater effect on females' sexual funtioning, the severity and tolerance of sexual dysfunction were worse in males than in females regardless of the antipsychotic studied. In the univariate logistic regression analysis, using olanzapine as a reference category, risperidone (odds ratio [OR] 7.45, 95% confidence interval [CI] 3.73-14.89) and conventionals, depot (OR 4.57, 95% CI 1.72-12.13) and nondepot (OR 4.92, 95% CI 1.43-16.93), showed a significant increased risk of sexual dysfunction. Our results show that sexual dysfunction is very common in patients receiving long-term treatment with antipsychotics, and it is associated with a great impact in a substantial proportion of patients. © 2010 International Society for Sexual Medicine.

Foot segmental motion and coupling in stage II and III tibialis posterior tendon dysfunction.

PubMed

Van de Velde, Maarten; Matricali, Giovanni Arnoldo; Wuite, Sander; Roels, Charlotte; Staes, Filip; Deschamps, Kevin

2017-06-01

Classification systems developed in the field of posterior tibialis tendon dysfunction omit to include dynamic measurements. Since this may negatively affect the selection of the most appropriate treatment modality, studies on foot kinematics are highly recommended. Previous research characterised the foot kinematics in patients with posterior tibialis tendon dysfunction. However, none of the studies analysed foot segmental motion synchrony during stance phase, nor compared the kinematic behaviour of the foot in presence of different posterior tibialis tendon dysfunction stages. Therefore, we aimed at comparing foot segmental motion and coupling in patients with posterior tibialis tendon dysfunction grade 2 and 3 to those of asymptomatic subjects. Foot segmental motion of 11 patients suffering from posterior tibialis tendon dysfunction stage 2, 4 patients with posterior tibialis tendon dysfunction stage 3 and 15 asymptomatic subjects was objectively quantified with the Rizzoli foot model using an instrumented walkway and a 3D passive motion capture system. Dependent variables were the range of motion occurring at the different inter-segment angles during subphases of stance and swing phase as well as the cross-correlation coefficient between a number of segments. Significant differences in range of motion were predominantly found during the forefoot push off phase and swing phase. In general, both patient cohorts demonstrated a reduced range of motion compared to the control group. This hypomobility occurred predominantly in the rearfoot and midfoot (p<0.01). Significant differences between both posterior tibialis tendon dysfunction patient cohorts were not revealed. Cross-correlation coefficients highlighted a loss of joint coupling between rearfoot and tibia as well as between rearfoot and forefoot in both posterior tibialis tendon dysfunction groups. The current evidence reveals considerable mechanical alterations in the foot which should be considered in the decision making process since it may help explaining the success and failure of certain conservative and surgical interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

PubMed

de Sá, Francine Gomes; de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; da Silva, Odair Alves; Moreira, Hicla Stefany; Leal, Geórgia Andrade; da Rocha, Marcelo Aurélio; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-08-01

What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg -1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A 2 release was analysed with commercial kits and superoxide anion (O 2 - ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the aorta and mesenteric resistance arteries from female O-DR of all ages. Pre-incubation with tempol, superoxide dismutase, indomethacin, NS-398, furegrelate or SQ29548 decreased contraction in response to phenylephrine and potentiated relaxation in response to acetylcholine in 12-month-old male O-DR aorta. In this artery, thromboxane A 2 release and O 2 - generation were greater in O-DR than O-CR groups. In conclusion, exposure to hyperglycaemia in utero results in sex-specific and age-dependent hypertension. The fact that vascular function is preserved in female O-DR may in part explain the absence of hypertension in this group. In contrast, the peripheral artery dysfunction associated with increased cyclooxygenase-2-derived production of vasoconstrictor prostanoids could underlie the increased blood pressure in male O-DR. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Specificity of spontaneous EEG associated with different levels of cognitive and communicative dysfunctions in children.

PubMed

Kozhushko, Nadezhda Ju; Nagornova, Zhanna V; Evdokimov, Sergey A; Shemyakina, Natalia V; Ponomarev, Valery A; Tereshchenko, Ekaterina P; Kropotov, Jury D

2018-06-01

This study aimed to reveal electrophysiological markers of communicative and cognitive dysfunctions of different severity in children with autism spectrum disorder (ASD). Eyes-opened electroencephalograms (EEGs) of 42 children with ASD, divided into two groups according to the severity of their communicative and cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and 70 age-matched controls aged 4-9 years were examined by means of spectral and group independent component (gIC) analyses. A predominance of theta and beta EEG activity in both groups of children with ASD compared to the activity in the control group was found in the global gIC together with a predominance of beta EEG activity in the right occipital region. The quantity of local gICs with enhanced slow and high-frequency EEG activity (within the frontal, temporal, and parietal cortex areas) in children 4-9 years of age might be considered a marker of cognitive and communicative dysfunction severity. Copyright © 2018 Elsevier B.V. All rights reserved.

Guidelines on experimental methods to assess mitochondrial dysfunction in cellular models of neurodegenerative diseases.

PubMed

Connolly, Niamh M C; Theurey, Pierre; Adam-Vizi, Vera; Bazan, Nicolas G; Bernardi, Paolo; Bolaños, Juan P; Culmsee, Carsten; Dawson, Valina L; Deshmukh, Mohanish; Duchen, Michael R; Düssmann, Heiko; Fiskum, Gary; Galindo, Maria F; Hardingham, Giles E; Hardwick, J Marie; Jekabsons, Mika B; Jonas, Elizabeth A; Jordán, Joaquin; Lipton, Stuart A; Manfredi, Giovanni; Mattson, Mark P; McLaughlin, BethAnn; Methner, Axel; Murphy, Anne N; Murphy, Michael P; Nicholls, David G; Polster, Brian M; Pozzan, Tullio; Rizzuto, Rosario; Satrústegui, Jorgina; Slack, Ruth S; Swanson, Raymond A; Swerdlow, Russell H; Will, Yvonne; Ying, Zheng; Joselin, Alvin; Gioran, Anna; Moreira Pinho, Catarina; Watters, Orla; Salvucci, Manuela; Llorente-Folch, Irene; Park, David S; Bano, Daniele; Ankarcrona, Maria; Pizzo, Paola; Prehn, Jochen H M

2018-03-01

Neurodegenerative diseases are a spectrum of chronic, debilitating disorders characterised by the progressive degeneration and death of neurons. Mitochondrial dysfunction has been implicated in most neurodegenerative diseases, but in many instances it is unclear whether such dysfunction is a cause or an effect of the underlying pathology, and whether it represents a viable therapeutic target. It is therefore imperative to utilise and optimise cellular models and experimental techniques appropriate to determine the contribution of mitochondrial dysfunction to neurodegenerative disease phenotypes. In this consensus article, we collate details on and discuss pitfalls of existing experimental approaches to assess mitochondrial function in in vitro cellular models of neurodegenerative diseases, including specific protocols for the measurement of oxygen consumption rate in primary neuron cultures, and single-neuron, time-lapse fluorescence imaging of the mitochondrial membrane potential and mitochondrial NAD(P)H. As part of the Cellular Bioenergetics of Neurodegenerative Diseases (CeBioND) consortium ( www.cebiond.org ), we are performing cross-disease analyses to identify common and distinct molecular mechanisms involved in mitochondrial bioenergetic dysfunction in cellular models of Alzheimer's, Parkinson's, and Huntington's diseases. Here we provide detailed guidelines and protocols as standardised across the five collaborating laboratories of the CeBioND consortium, with additional contributions from other experts in the field.

Antidepressant-Induced Female Sexual Dysfunction.

PubMed

Lorenz, Tierney; Rullo, Jordan; Faubion, Stephanie

2016-09-01

Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Psychological and psychosexual aspects of vulvar vestibulitis.

PubMed Central

Nunns, D; Mandal, D

1997-01-01

AIMS: To objectively assess the psychological and psychosexual morbidity of patients with vulvar vestibulitis. METHODS: 30 patients with variable degrees of vulvar vestibulitis were recruited from a vulval clinic. Each patient underwent a detailed history and clinical examination. Friedrich's criteria were used for the diagnosis of vulvar vestibulitis. Standardised questionnaires to assess psychological and psychosexual function were completed by the patient before review. These questionnaires were the STAI and a modified psychosexual questionnaire introduced by Campion. RESULTS: Patients experienced considerable psychological dysfunction compared with controls. All aspects of psychosexual dysfunction were affected. CONCLUSIONS: When managing patients, psychosexual and psychological issues must be considered in addition to other conventional types of therapy. Vulvar vestibulitis may be a risk factor for developing psychosexual complications including vaginismus, low libido, and orgasmic dysfunction. Consideration of these factors must be an integral part of the management of patients with all chronic vulval conditions. PMID:9582478

Integration of ultra-high field MRI and histology for connectome based research of brain disorders

PubMed Central

Yang, Shan; Yang, Zhengyi; Fischer, Karin; Zhong, Kai; Stadler, Jörg; Godenschweger, Frank; Steiner, Johann; Heinze, Hans-Jochen; Bernstein, Hans-Gert; Bogerts, Bernhard; Mawrin, Christian; Reutens, David C.; Speck, Oliver; Walter, Martin

2013-01-01

Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods can be effectively combined at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time) the feasibility and quality of ultra-high spatial resolution (150 μm isotopic) imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information. PMID:24098272

A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

PubMed Central

Jansen, Diane; Zerbi, Valerio; Janssen, Carola I. F.; Dederen, Pieter J. W. C.; Mutsaers, Martina P. C.; Hafkemeijer, Anne; Janssen, Anna-Lena; Nobelen, Cindy L. M.; Veltien, Andor; Asten, Jack J.; Heerschap, Arend; Kiliaan, Amanda J.

2013-01-01

Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer’s disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis. PMID:23717459

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder

PubMed Central

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Background: Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. Materials and Methods: This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. Results: The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). Conclusion: These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings. PMID:24516853

Types of Sensory Integrative Dysfunction among Disabled Learners

ERIC Educational Resources Information Center

Ayres, A. Jean

1972-01-01

R-technique factor analysis was used to correlate results of sensorimotor, psycholinguistic and cognitive tests given to California children with learning disabilities. Results show not all children with specific neural disorders perform poorly on related tests where low scores would be expected. (PD)

Male erectile dysfunction: integrating psychopharmacology and psychotherapy.

PubMed

Simopoulos, Eugene F; Trinidad, Anton C

2013-01-01

Erectile dysfunction (ED), defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance, is the most common sexual problem in men. ED arises when there is disruption of the complex interplay between vascular, neurologic, hormonal and psychologic factors necessary for normal erectile function. It may have a significant effect on quality of life and portend undetected cardiovascular disease. Risk factors for development of ED include advancing age, tobacco use, a history of pelvic irradiation or surgery and antipsychotic use (Table 1) [1]. Treatment guidelines continue to evolve for optimal management of ED. In this article, we review diagnostic and treatment strategies for ED relevant to psychiatrists. We present an integrative approach to the treatment of ED based on a review of the urologic and psychiatric literature. ED is multifactorial in origin and responsive to a variety of therapeutic interventions, including psychopharmacology and psychotherapy in which cognitive underpinnings of poor sexual performance, including diminished self-esteem, lack of confidence and perceived failures in the male role, are examined. Psychiatrists can readily perform a basic workup for ED as they integrate both a medical and therapeutic model when confronted with such patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

PubMed Central

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

PubMed Central

Oniki, Kentaro; Saruwatari, Junji; Izuka, Tomoko; Kajiwara, Ayami; Morita, Kazunori; Sakata, Misaki; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

2015-01-01

In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11–8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction. PMID:26200108

Transient Receptor Potential Vanilloid 1 Expression Mediates Capsaicin-Induced Cell Death.

PubMed

Ramírez-Barrantes, Ricardo; Córdova, Claudio; Gatica, Sebastian; Rodriguez, Belén; Lozano, Carlo; Marchant, Ivanny; Echeverria, Cesar; Simon, Felipe; Olivero, Pablo

2018-01-01

The transient receptor potential (TRP) ion channel family consists of a broad variety of non-selective cation channels that integrate environmental physicochemical signals for dynamic homeostatic control. Involved in a variety of cellular physiological processes, TRP channels are fundamental to the control of the cell life cycle. TRP channels from the vanilloid (TRPV) family have been directly implicated in cell death. TRPV1 is activated by pain-inducing stimuli, including inflammatory endovanilloids and pungent exovanilloids, such as capsaicin (CAP). TRPV1 activation by high doses of CAP (>10 μM) leads to necrosis, but also exhibits apoptotic characteristics. However, CAP dose-response studies are lacking in order to determine whether CAP-induced cell death occurs preferentially via necrosis or apoptosis. In addition, it is not known whether cytosolic Ca 2+ and mitochondrial dysfunction participates in CAP-induced TRPV1-mediated cell death. By using TRPV1-transfected HeLa cells, we investigated the underlying mechanisms involved in CAP-induced TRPV1-mediated cell death, the dependence of CAP dose, and the participation of mitochondrial dysfunction and cytosolic Ca 2+ increase. Together, our results contribute to elucidate the pathophysiological steps that follow after TRPV1 stimulation with CAP. Low concentrations of CAP (1 μM) induce cell death by a mechanism involving a TRPV1-mediated rapid and transient intracellular Ca 2+ increase that stimulates plasma membrane depolarization, thereby compromising plasma membrane integrity and ultimately leading to cell death. Meanwhile, higher doses of CAP induce cell death via a TRPV1-independent mechanism, involving a slow and persistent intracellular Ca 2+ increase that induces mitochondrial dysfunction, plasma membrane depolarization, plasma membrane loss of integrity, and ultimately, cell death.

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

PubMed

Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

2012-09-01

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management.

PubMed

Roca, Josep; Vargas, Claudia; Cano, Isaac; Selivanov, Vitaly; Barreiro, Esther; Maier, Dieter; Falciani, Francesco; Wagner, Peter; Cascante, Marta; Garcia-Aymerich, Judith; Kalko, Susana; De Mas, Igor; Tegnér, Jesper; Escarrabill, Joan; Agustí, Alvar; Gomez-Cabrero, David

2014-11-28

Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Theory of mind difficulties in patients with alcohol dependence: beyond the prefrontal cortex dysfunction hypothesis.

PubMed

Maurage, François; de Timary, Philippe; Tecco, Juan Martin; Lechantre, Stéphane; Samson, Dana

2015-06-01

Previous studies have shown that alcohol-dependent (AD) individuals have difficulties inferring other people's emotion, understanding humor, and detecting a faux pas. This study aimed at further understanding the nature of such "Theory of Mind" (ToM) difficulties. A total of 34 recently detoxified AD and 34 paired controls were compared based on 2 nonverbal and video-based false belief tasks. These tasks were designed to identify 3 different types of deficits: (i) a deficit in dealing with the general task demands, (ii) a selective deficit in self-perspective inhibition, and (iii) a deficit in tracking the other person's mental state. (i) and (ii) are compatible with the hypothesis of a prefrontal cortex dysfunction being at the origin of AD individuals' social difficulties, while (iii) would suggest the possible contribution of a dysfunction of the temporo-parietal junction in explaining the social difficulties. Group analyses highlighted that AD individuals performed worse on the 2 false belief tasks than controls. Individual analyses showed, however, that just under half of the AD individuals were impaired compared to controls. Moreover, most of the AD individuals who were impaired showed a deficit in tracking the other person's belief. This deficit was linked to disease-related factors such as illness duration, average alcohol consumption, and craving but not to general reasoning abilities, depression, anxiety, or demographic variables. Just under half of the AD individuals tested showed a ToM deficit, and in most cases, the deficit concerned the tracking of other people's mental states. Such a type of deficit has previously been associated with lesions to the temporo-parietal brain areas, indicating that a prefrontal cortex dysfunction may not be the sole origin of the social cognition deficits observed in alcohol dependence. Copyright © 2015 by the Research Society on Alcoholism.

Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD).

PubMed

Winterberg, Pamela D; Jiang, Rong; Maxwell, Josh T; Wang, Bo; Wagner, Mary B

2016-03-01

Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 ± 4.2% vs. -29 ± 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 ± 0.15 vs. 1.9 ± 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Loss of integrity and atrophy in cingulate structural covariance networks in Parkinson's disease.

PubMed

de Schipper, Laura J; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2017-01-01

In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data. 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD. The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = - 0.265, η p 2  = 0.070) and p = 0.001 (β = - 0.264, η p 2  = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks. We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness.

Metabolic Abnormalities and Viral Replication is Associated with Biomarkers of Vascular Dysfunction in HIV-Infected Children

PubMed Central

Miller, Tracie L.; Borkowsky, William; DiMeglio, Linda A.; Dooley, Laurie; Geffner, Mitchell E.; Hazra, Rohan; McFarland, Elizabeth J.; Mendez, Armando J.; Patel, Kunjal; Siberry, George K.; Van Dyke, Russell B.; Worrell, Carol J.; Jacobson, Denise L.

2011-01-01

Objectives Human immunodeficiency virus (HIV)-infected children may be at risk for premature cardiovascular disease. We compared levels of biomarkers of vascular dysfunction among HIV-infected children with and without hyperlipidemia to HIV-exposed, uninfected children (HEU) enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS), and determined factors associated with these biomarkers. Design Prospective cohort study Methods Biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP1)); coagulant dysfunction (fibrinogen and P-selectin); endothelial dysfunction (soluble intracellular cell adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), and E-selectin); and metabolic dysfunction (adiponectin) were measured in 226 HIV-infected and 140 HEU children. Anthropometry, body composition, lipids, glucose, insulin, HIV disease severity, and antiretroviral therapy were recorded. Results The median ages were 12.3 y (HIV-infected) and 10.1 y (HEU). Body mass index (BMI) Z-scores, waist and hip circumference, and percent body fat were lower among HIV-infected. Total and non-HDL cholesterol and triglycerides were higher in HIV-infected children. HIV-infected children had higher MCP-1, fibrinogen, sICAM, and sVCAM levels. In multivariable analyses in the HIV-infected children alone, BMI z-score was associated with higher CRP and fibrinogen, but lower MCP-1 and sVCAM. Unfavorable lipid profiles were positively associated with IL6, MCP1, fibrinogen, and P- and E-selectin, whereas increased HIV viral load was associated with markers of inflammation (MCP1 and CRP) and endothelial dysfunction (sICAM and sVCAM). Conclusions HIV-infected children have higher levels of biomarkers of vascular dysfunction than do HEU children. Risk factors associated with higher biomarkers include unfavorable lipid levels and active HIV replication. PMID:22136114

Pelvic floor assessment after delivery: how should women be selected?

PubMed

Soligo, Marco; Livio, Stefania; De Ponti, Elena; Scebba, Ileana; Carpentieri, Federica; Serati, Maurizio; Ferrazzi, Enrico

2016-11-01

Pelvic floor dysfunction after delivery is quite common. New mothers deserve to receive targeted care for pelvic floor dysfunction, but how should women who are at risk be identified and selected for treatment? This study investigated risk factors and puerperal health-seeking behaviours to develop a restrictive patient selection model for postpartum pelvic floor dysfunction assessment. This prospective observational study involved women who were at ≥32 weeks gestational age when they delivered in a tertiary referral maternity hospital in Milan, Italy, between July and December 2014. Eligible women were scheduled for a 3-month postnatal pelvic floor clinic. The adherence rate to the pelvic floor clinic and the prevalence of pelvic floor dysfunctions at 3 months postpartum were recorded. Univariable and logistic multivariable analyses were performed to select risk factors for pelvic floor dysfunctions. Risk factors were then tested for sensitivity and specificity for 3-month postpartum pelvic floor dysfunctions. Of 1606 eligible women, 1293 (80.5%) were included in the analysis; 685 puerperal women (53.0%) adhered to the 3-month postnatal pelvic floor clinic; pelvic floor dysfunctions were detected in 238 women (34.7%). Four elements emerged as risk factors: symptoms before pregnancy (OR 1.72, 95% CI 1.15-2.56; p=0.008), symptoms during pregnancy (OR 2.13, 95% CI 1.49-3.06; p<0.0001), vacuum extractor use (OR 1.62, 95% CI 1.04-2.54; p=0.034), and severe perineal tears (OR 19.45, 95% CI 2.42-156.15; p=0.005). The combined sensitivity and specificity for the 4 risk factors were 82% and 39%, respectively. Internal risk factors analysis offers the potential to efficiently restrict patient selection for follow-up. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive dysfunction in patients with Systemic Lupus Erythematosus.

PubMed

Butt, Bilal Azeem; Farman, Sumaira; Khan, Saira Elaine Anwer; Saeed, Muhammad Ahmed; Ahmad, Nighat Mir

2017-01-01

To determine the frequency of cognitive dysfunction in patients with Systemic Lupus Erythematosus in a Pakistani population, presenting at a tertiary care Rheumatology setting. This cross-sectional study was conducted at the Division of Rheumatology, Fatima Memorial Hospital, Lahore, from March to June 2016. A total of 43 consecutive patients, who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for Systemic Lupus Erythematosus (SLE), were enrolled. Cognitive function was assessed using Montréal Cognitive Assessment (MoCA) questionnaire. Demographic data and disease dynamics were collected in a proforma. Cognitive dysfunction was defined as score < 26/30, adjusted for duration of formal education. SPSS version 16.0 for windows was used to analyse data and to calculate frequency of cognitive dysfunction. Out of 43 enrolled patients, 95.3% were females and 4.7% were males, with mean age of 28.72 ± 9.25 years and mean formal education duration of 10.98 ± 3.29 years. The mean disease duration was 24.21 ± 30.46 months. Anti-nuclear antibodies (ANA) were present in all patients and anti-ds DNA in 93% patients. Cognitive dysfunction according to MoCA score was found in 65.1% (n=28) patients. For patients with disease duration more than two years, cognitive dysfunction was found in 60% patients [p>0.05] and for duration of formal education less than 12 years in 74.1% patients [p>0.05]. In this study, two third of SLE patients had Cognitive dysfunction. Hence, there is an increasing need to recognise and initiate early therapy for this overlooked aspect of SLE with an aim to achieve better quality of life.

Implication of Posture Analysing Software to Evaluate the Postural Changes after Corrective Exercise Strategy on Subjects with Upper Body Dysfunction-A Randomized Controlled Trial

PubMed Central

Sudhakar, S; Porcelvan, S; Francis, T.G. Tilak; Rathnamala, D; Radhakrishnan, R

2017-01-01

Introduction The postural adaptation is very common now a days in school going children, office desk oriented job, computer users and frequent mobile users, and in all major industrial workers. Several studies have documented a high incidence of postural abnormalities in a given population; however, methods of postural measurement were poorly defined. The implication of postural pro software to analyse the postural imbalance of upper body dysfunction is very rare and literature studies says that the kinematic changes in particular segment will produce pain/discomfort and thereby lesser productivity of subjects. Aim To evaluate the postural changes in subjects with upper body dysfunction after a corrective exercise strategy using postural analysis software and pectoralis minor muscle length testing. Materials and Methods After explaining the procedure and benefits, informed consent was taken from the participating subjects (age 25-55 years). Subjects with upper body dysfunction were randomly allocated into two groups (each group 30 subjects). The Group–A received the corrective exercise strategy and Group-B received the conventional exercise for eight weeks of study duration (15 reps each exercise, total duration of 40 min; four days/week. Pre and Post posture analysis were analysed using posture pro software along with flexibility of pectoralis minor was assessed using ruler scale method. Results After interpretation of data, both the group showed the postural alteration and pectoralis minor muscle length changes, p-value (p<0.01) of both group showed highly significant changes. But comparing the both groups, the subjects who received the corrective exercise strategy shown more percentage of improvement in posture alteration (56.25%), pectoralis minor muscle length changes (68.69%) than the conventional exercise received subjects in posture alteration (24.86%) and pectoralis minor muscle length changes (21.9%). Conclusion Altered postural changes and pectoralis minor muscle flexibility before and after the corrective exercise strategy evaluated by postural analysis software method shown to be a significant tool in clinical practice, which is easier and reproducible method. PMID:28893030

Post-Translational Modification of Constitutive Nitric Oxide Synthase in the Penis

PubMed Central

Musicki, Biljana; Ross, Ashley E.; Champion, Hunter C.; Burnett, Arthur L.; Bivalacqua, Trinity J.

2009-01-01

Erectile dysfunction (ED) is a common men's health problem characterized by the consistent inability to sustain an erection sufficient for sexual intercourse. Basic science research on erectile physiology has been devoted to investigating the pathogenesis of ED and has led to the conclusion that ED is predominately a disease of vascular origin and/or neurogenic dysfunction. The constitutive forms of nitric oxide synthase [NOS; endothelial NOS (eNOS) and neuronal NOS (nNOS)] are important enzymes involved in the production of nitric oxide (NO) and thus regulate penile vascular homeostasis. Given the impact of endothelial- and neuronal-derived NO in penile vascular biology, a great deal of research over the past decade has focused on the role of NO synthesis from the endothelium and nitrergic nerve terminal in normal erectile physiology as well as in disease states. Loss of the functional integrity of the endothelium and subsequent endothelial dysfunction plays an integral role in the occurrence of ED. Therefore, molecular mechanisms involved in dysregulation of these NOS isoforms in the development of ED are essential to discovering the pathogenesis of ED in various disease states. This communication reviews the role of eNOS and nNOS in erectile physiology and discusses the alterations in eNOS and nNOS via post-translation modification in various vascular diseases of the penis. PMID:19342700

Disrupted Small-World Networks in Schizophrenia

ERIC Educational Resources Information Center

Liu, Yong; Liang, Meng; Zhou, Yuan; He, Yong; Hao, Yihui; Song, Ming; Yu, Chunshui; Liu, Haihong; Liu, Zhening; Jiang, Tianzi

2008-01-01

The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of "dysfunctional connectivity" among the brain regions in…

An Integrative Dimensional Classification of Personality Disorder

ERIC Educational Resources Information Center

Widiger, Thomas A.; Livesley, W. John; Clark, Lee Anna

2009-01-01

Psychological assessment research concerns how to describe psychological dysfunction in ways that are both valid and useful. Recent advances in assessment research hold the promise of facilitating significant improvements in description and diagnosis. One such contribution is in the classification of personality disorder symptomatology. The…

Cognitive Theories of Autism

ERIC Educational Resources Information Center

Rajendran, Gnanathusharan; Mitchell, Peter

2007-01-01

This article considers three theories of autism: The Theory of Mind Deficit, Executive Dysfunction and the Weak Central Coherence accounts. It outlines each along with studies relevant to their emergence, their expansion, their limitations and their possible integration. Furthermore, consideration is given to any implication from the theories in…

Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism.

PubMed

Skotte, Niels H; Andersen, Jens V; Santos, Alberto; Aldana, Blanca I; Willert, Cecilie W; Nørremølle, Anne; Waagepetersen, Helle S; Nielsen, Michael L

2018-05-15

Huntington's disease is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry to establish a spatial brain proteome from late-stage R6/2 mice and compared this with wild-type littermates. We observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13 C labeling studies confirmed a compromised astrocytic metabolism and regulation of glutamate-GABA-glutamine cycling, resulting in impaired release of glutamine and GABA synthesis. In recent years, increasing attention has been focused on the role of astrocytes in HD, and our data support that therapeutic strategies to improve astrocytic glutamine homeostasis may help ameliorate symptoms in HD. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

PubMed

Chennen, Kirsley; Scerbo, Maria Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

2014-11-01

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity. © 2014 médecine/sciences – Inserm.

Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

PubMed

Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

2016-03-01

Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

PubMed

Paul, Sandra; Beucke, Jan C; Kaufmann, Christian; Mersov, Anna; Heinzel, Stephan; Kathmann, Norbert; Simon, Daniela

2018-04-06

Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Computational medical imaging and hemodynamics framework for functional analysis and assessment of cardiovascular structures.

PubMed

Wong, Kelvin K L; Wang, Defeng; Ko, Jacky K L; Mazumdar, Jagannath; Le, Thu-Thao; Ghista, Dhanjoo

2017-03-21

Cardiac dysfunction constitutes common cardiovascular health issues in the society, and has been an investigation topic of strong focus by researchers in the medical imaging community. Diagnostic modalities based on echocardiography, magnetic resonance imaging, chest radiography and computed tomography are common techniques that provide cardiovascular structural information to diagnose heart defects. However, functional information of cardiovascular flow, which can in fact be used to support the diagnosis of many cardiovascular diseases with a myriad of hemodynamics performance indicators, remains unexplored to its full potential. Some of these indicators constitute important cardiac functional parameters affecting the cardiovascular abnormalities. With the advancement of computer technology that facilitates high speed computational fluid dynamics, the realization of a support diagnostic platform of hemodynamics quantification and analysis can be achieved. This article reviews the state-of-the-art medical imaging and high fidelity multi-physics computational analyses that together enable reconstruction of cardiovascular structures and hemodynamic flow patterns within them, such as of the left ventricle (LV) and carotid bifurcations. The combined medical imaging and hemodynamic analysis enables us to study the mechanisms of cardiovascular disease-causing dysfunctions, such as how (1) cardiomyopathy causes left ventricular remodeling and loss of contractility leading to heart failure, and (2) modeling of LV construction and simulation of intra-LV hemodynamics can enable us to determine the optimum procedure of surgical ventriculation to restore its contractility and health This combined medical imaging and hemodynamics framework can potentially extend medical knowledge of cardiovascular defects and associated hemodynamic behavior and their surgical restoration, by means of an integrated medical image diagnostics and hemodynamic performance analysis framework.

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

PubMed Central

2013-01-01

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches. PMID:24289502

Diabetic ketoacidosis elicits systemic inflammation associated with cerebrovascular endothelial cell dysfunction.

PubMed

Close, Taylor E; Cepinskas, Gediminas; Omatsu, Tatsushi; Rose, Keeley L; Summers, Kelly; Patterson, Eric K; Fraser, Douglas D

2013-08-01

To determine if the DKA-induced inflammation in juvenile mice provokes activation and dysfunction of CVECs. DKA in juvenile mice was induced with administration of STZ and ALX. Blood from DKA mice was assessed for cytokines and soluble cell adhesion proteins, and either DKA plasma or exogenous compounds were applied to immortalized bEND3. DKA increased circulating levels of IL-6, IL-8(KC), MCP-1, IL-10, sE-selectin, sICAM-1, and sVCAM-1. Stimulation of bEND3 with DKA plasma caused cellular activation (increased ROS and activation of NF-κΒ), upregulation of a proadhesive phenotype (E-selectin, ICAM-1, and VCAM-1), and increased leukocyte-bEND3 interaction (leukocyte rolling/adhesion). TEER, a measure of bEND3 monolayer integrity, was decreased by DKA plasma. Activation and dysfunction of bEND3 with DKA plasma were suppressed by plasma heat treatment (56°C, 1 hour) and replicated with the application of DKA recombinant cytomix (IL-6, IL-8[KC], MCP-1, and IL-10), implicating circulating inflammatory protein(s) as mediators. Treatment of bEND3 with β-OH-butyrate, the main ketone elevated in DKA, failed to mimic the DKA plasma-induced activation and dysfunction of bEND3. DKA elicits systemic inflammation associated with CVEC activation and dysfunction, possibly contributing to DKA-associated intracranial microvascular complications. © 2013 John Wiley & Sons Ltd.

Abuse, cancer and sexual dysfunction in women: A potentially vicious cycle.

PubMed

Lees, Brittany F; Stewart, Taylor P; Rash, Joanne K; Baron, Shirley R; Lindau, Stacy Tessler; Kushner, David M

2018-04-13

More than 30% of women have a history of abuse. Women with cancer may be at substantially increased risk for abuse, but this issue is rarely discussed in the course of oncology care. Women with a history of abuse who present for cancer care commonly have a high prevalence of co-morbid illness. Sexual dysfunction, a highly prevalent but under-recognized condition among women of all ages, is also more common among both women with a history of abuse and women with cancer. Although common after cancer, sexual dysfunction, like abuse, can be stigmatizing and often goes undiagnosed and untreated. This review first examines the literature for evidence of a relationship between any history of abuse and cancer among women, addressing two questions: 1) How does abuse promote or create risk for developing cancer? 2) How does cancer increase a woman's susceptibility to abuse? We then examine evidence for a relationship between abuse and female sexual dysfunction, followed by an investigation of the complex relationship between all three factors: abuse, sexual dysfunction and cancer. The literature is limited by a lack of harmonization of measures across studies, retrospective designs, and small and idiosyncratic samples. Despite these limitations, it is imperative that providers integrate the knowledge of this complex relationship into the care of women with cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

PubMed

Srisurapanont, Manit; Mok, Yee Ming; Yang, Yen Kuang; Chan, Herng-Nieng; Della, Constantine D; Zainal, Nor Zuraida; Jambunathan, Stephen; Amir, Nurmiati; Kalita, Pranab

2018-05-01

Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ± 6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ± 16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes.

PubMed

Baker, Nathaniel L; Hunt, Kelly J; Stevens, Danielle R; Jarai, Gabor; Rosen, Glenn D; Klein, Richard L; Virella, Gabriel; Lopes-Virella, Maria F

2018-01-01

To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up. © 2017 by the American Diabetes Association.

The application of quantitative methods for identifying and exploring the presence of bias in systematic reviews: PDE-5 inhibitors for erectile dysfunction.

PubMed

Bekkering, G E; Abou-Setta, A M; Kleijnen, J

2008-01-01

A systematic review of PDE-5 inhibitors for erectile dysfunction was performed to evaluate the utility of quantitative methods for identifying and exploring the influence of bias and study quality on pooled outcomes from meta-analyses. We included 123 randomized controlled trials (RCTs). Methodological quality was poorly reported. All three drugs appeared highly effective. Indirect adjusted analyses showed no differences between the three drugs. Funnel plots and statistical tests showed no evidence of small-study effects for sildenafil whereas there was evidence of such bias for tadalafil and vardenafil. Adjustment for missing studies using trim and fill techniques did not alter the pooled estimates substantially. The exclusion of previous sildenafil nonresponders was associated with larger treatment effects for tadalafil. This investigation was hampered by poor reporting of methodological quality, a low number of studies, heterogeneity and large effect sizes. Despite such limitations, a comprehensive assessment of biases should be a routine in systematic reviews.

Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease.

PubMed

Nixon, Ralph A

2017-07-01

Abnormalities of the endosomal-lysosomal network (ELN) are a signature feature of Alzheimer's disease (AD). These include the earliest known cytopathology that is specific to AD and that affects endosomes and induces the progressive failure of lysosomes, each of which are directly linked by distinct mechanisms to neurodegeneration. The origins of ELN dysfunction and β-amyloidogenesis closely overlap, which reflects their common genetic basis, the established early involvement of endosomes and lysosomes in amyloid precursor protein (APP) processing and clearance, and the pathologic effect of certain APP metabolites on ELN functions. Genes that promote β-amyloidogenesis in AD (APP, PSEN1/2, and APOE4) have primary effects on ELN function. The importance of primary ELN dysfunction to pathogenesis is underscored by the mutations in more than 35 ELN-related genes that, thus far, are known to cause familial neurodegenerative diseases even though different pathogenic proteins may be involved. In this article, I discuss growing evidence that implicates AD gene-driven ELN disruptions as not only the antecedent pathobiology that underlies β-amyloidogenesis but also as the essential partner with APP and its metabolites that drive the development of AD, including tauopathy, synaptic dysfunction, and neurodegeneration. The striking amelioration of diverse deficits in animal AD models by remediating ELN dysfunction further supports a need to integrate APP and ELN relationships, including the role of amyloid-β, into a broader conceptual framework of how AD arises, progresses, and may be effectively therapeutically targeted.-Nixon, R. A. Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease. © FASEB.

Craniopharyngioma in Children: Long-term Outcomes

PubMed Central

STEINBOK, Paul

2015-01-01

The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

Cognitive medicine - a new approach in health care science.

PubMed

Wallin, Anders; Kettunen, Petronella; Johansson, Per M; Jonsdottir, Ingibjörg H; Nilsson, Christer; Nilsson, Michael; Eckerström, Marie; Nordlund, Arto; Nyberg, Lars; Sunnerhagen, Katharina S; Svensson, Johan; Terzis, Beata; Wahlund, Lars-Olof; Georg Kuhn, H

2018-02-08

The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course. Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction. Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.

Salivary gland dysfunction markers in type 2 diabetes mellitus patients.

PubMed

Aitken-Saavedra, Juan; Rojas-Alcayaga, Gonzalo; Maturana-Ramírez, Andrea; Escobar-Álvarez, Alejandro; Cortes-Coloma, Andrea; Reyes-Rojas, Montserrat; Viera-Sapiain, Valentina; Villablanca-Martínez, Claudia; Morales-Bozo, Irene

2015-10-01

Diabetes mellitus (DM) is a chronic disease of the carbohydrate metabolism that, when not rigorously controlled, compromises systemic and organ integrity, thereby causing renal diseases, blindness, neuropathy, arteriosclerosis, infections, and glandular dysfunction, including the salivary glands. The aim of this study was to determine the relationship between the qualitative and quantitative parameters of salivary alteration, which are indicators of salivary gland dysfunction, and the level of metabolic control of type 2 diabetes patients. A convenience sample of 74 voluntary patients with type 2 DM was selected, each of whom donated a sample of unstimulated saliva. Salivary parameters such as salivary flow rate, protein concentration, pH, and xerostomia were studied. There is a positive relationship between the level of metabolic control measured with HbA1 and the protein concentration in saliva (Spearman rho = 0.329 and p = 0.004). The same assay showed an inverse correlation between HbA1 and pH (Spearman rho = -0.225 and p = 0.05). The protein concentration in saliva and, to a lesser extent, the pH may be useful as glandular dysfunction indicators in DM2 patients. Saliva, type 2 diabetes mellitus, pH, protein concentration, xerostomia.

Adding a Systemic Touch to Rational-Emotive Therapy for Families.

ERIC Educational Resources Information Center

Russell, Todd T.; Morrill, Correen M.

1989-01-01

Proposes a theoretical and practical hybrid model for family counseling based on integrating the rational-emotive and family systems approach. Notes that these combined approaches offer the counselor a systematic theoretical structure for conceptualizing family dysfunction, from which additional strategies for changing inappropriate belief systems…

Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction.

PubMed

Hoel, Hedda; Hove-Skovsgaard, Malene; Hov, Johannes R; Gaardbo, Julie Christine; Holm, Kristian; Kummen, Martin; Rudi, Knut; Nwosu, Felix; Valeur, Jørgen; Gelpi, Marco; Seljeflot, Ingebjørg; Ueland, Per Magne; Gerstoft, Jan; Ullum, Henrik; Aukrust, Pål; Nielsen, Susanne Dam; Trøseid, Marius

2018-04-30

HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.

Early Immune Function and Duration of Organ Dysfunction in Critically Ill Septic Children.

PubMed

Muszynski, Jennifer A; Nofziger, Ryan; Moore-Clingenpeel, Melissa; Greathouse, Kristin; Anglim, Larissa; Steele, Lisa; Hensley, Josey; Hanson-Huber, Lisa; Nateri, Jyotsna; Ramilo, Octavio; Hall, Mark W

2018-02-22

Late immune suppression is associated with nosocomial infection and mortality in septic adults and children. Relationships between early immune suppression and outcomes in septic children remain unclear. Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis/septic shock. Methods, Measurements and Main Results: Children aged < 18 years meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy controls were sampled once. Innate immune function was quantified by whole blood ex vivo lipopolysaccharide-induced TNFα production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFNγ production capacity. 102 septic children and 35 healthy children were enrolled. Compared to healthy children, septic children demonstrated lower LPS-induced TNFα production (p < 0.0001) and lower PHA-induced IFNγ production (p<0.0001). Among septic children, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction (MODS) and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased MODS days [aRR 1.2 (1.03, 1.5)] and organ dysfunction days [aRR 1.2 (1.1, 1.3)]. Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early suppression of both innate and adaptive immunity are associated with longer duration of organ dysfunction and may be useful markers to guide investigations of immunomodulatory therapies in septic children.

Meanings of thinness and dysfunctional eating in black South African females: a qualitative study.

PubMed

Morris, P F; Szabo, C P

2013-09-01

This study qualitatively explored local meanings of thinness and dysfunctional eating in black adolescent females in the rapidly westernizing socio-cultural context of post-apartheid South Africa. Four (n=4) urban state highschools in KwaZulu-Natal were selected from which 40 subjects were sampled from Grades 9-12. Focus groups were conducted following a semi-structured interview and analysed using Constant Comparative Analysis. Subjects reported a wide range of different meanings for thinness, which included traditional idioms of distress and typically western pressures towards thinness, which was particularly evident in the multicultural schools. Subjects also reported a wide range of dysfunctional eating practices (such as purging) which were underscored by a wide range of motivations, including traditional practices and western body image concern; and which did not tend to follow patterns of 'dieting' that are typical in affluent, western societies. Western pressures towards thinness may be blending with traditional idioms of distress and culturally sanctioned rituals of remedial purging and social over-eating, thereby placing this group at particular risk for a range of dysfunctional eating patterns that may not follow typically western paradigms or diagnostic systems.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

PubMed

Takiguchi, Kazuo; Uezato, Akihito; Itasaka, Michio; Atsuta, Hidenori; Narushima, Kenji; Yamamoto, Naoki; Kurumaji, Akeo; Tomita, Makoto; Oshima, Kazunari; Shoda, Kosaku; Tamaru, Mai; Nakataki, Masahito; Okazaki, Mitsutoshi; Ishiwata, Sayuri; Ishiwata, Yasuyoshi; Yasuhara, Masato; Arima, Kunimasa; Ohmori, Tetsuro; Nishikawa, Toru

2017-07-12

It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

Association of cultured myotubes and fasting plasma metabolite profiles with mitochondrial dysfunction in type 2 diabetes subjects.

PubMed

Abu Bakar, Mohamad Hafizi; Sarmidi, Mohamad Roji

2017-08-22

Accumulating evidence implicates mitochondrial dysfunction-induced insulin resistance in skeletal muscle as the root cause for the greatest hallmarks of type 2 diabetes (T2D). However, the identification of specific metabolite-based markers linked to mitochondrial dysfunction in T2D has not been adequately addressed. Therefore, we sought to identify the markers-based metabolomics for mitochondrial dysfunction associated with T2D. First, a cellular disease model was established using human myotubes treated with antimycin A, an oxidative phosphorylation inhibitor. Non-targeted metabolomic profiling of intracellular-defined metabolites on the cultured myotubes with mitochondrial dysfunction was then determined. Further, a targeted MS-based metabolic profiling of fasting blood plasma from normal (n = 32) and T2D (n = 37) subjects in a cross-sectional study was verified. Multinomial logical regression analyses for defining the top 5% of the metabolites within a 95% group were employed to determine the differentiating metabolites. The myotubes with mitochondrial dysfunction exhibited insulin resistance, oxidative stress and inflammation with impaired insulin signalling activities. Four metabolic pathways were found to be strongly associated with mitochondrial dysfunction in the cultured myotubes. Metabolites derived from these pathways were validated in an independent pilot investigation of the fasting blood plasma of healthy and diseased subjects. Targeted metabolic analysis of the fasting blood plasma with specific baseline adjustment revealed 245 significant features based on orthogonal partial least square discriminant analysis (PLS-DA) with a p-value < 0.05. Among these features, 20 significant metabolites comprised primarily of branched chain and aromatic amino acids, glutamine, aminobutyric acid, hydroxyisobutyric acid, pyroglutamic acid, acylcarnitine species (acetylcarnitine, propionylcarnitine, dodecenoylcarnitine, tetradecenoylcarnitine hexadecadienoylcarnitine and oleylcarnitine), free fatty acids (palmitate, arachidonate, stearate and linoleate) and sphingomyelin (d18:2/16:0) were identified as predictive markers for mitochondrial dysfunction in T2D subjects. The current study illustrates how cellular metabolites provide potential signatures associated with the biochemical changes in the dysregulated body metabolism of diseased subjects. Our finding yields additional insights into the identification of robust biomarkers for T2D associated with mitochondrial dysfunction in cultured myotubes.

Integrated Immune Experiment

NASA Technical Reports Server (NTRS)

Crucian, Brian

2009-01-01

This viewgraph presentation reviews NASA's Integrated Immune Experiment. The objectives include: 1) Address significant lack of data regarding immune status during flight; 2) Replace several recent immune studies with one comprehensive study that will include in-flight sampling; 3) Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation; 4) Determine the clinical risk related to immune dysregulation for exploration class spaceflight; and 5) Determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Integration of Female Pilots in the 160th Special Operations Aviation Regiment (Airborne) - A Culture Already Set-Up for Success

DTIC Science & Technology

2014-02-14

Margosian, Mary A , and Judith M; Vendrzyk. “Policies, Practices, and the Effect of Gender Discrimination on the Integration of Women Officers in the...are unable to perform , for whatever reason, individual and group survival are jeopardized. Cohesion is therefore essentially based upon the...presence of TRUST among group members … if too many group members are unable to perform adequately, the group becomes dysfunctional.” 25 Any degradation in

A close relationship between verbal memory and SN/VTA integrity in young and older adults.

PubMed

Düzel, Sandra; Schütze, Hartmut; Stallforth, Sabine; Kaufmann, Jörn; Bodammer, Nils; Bunzeck, Nico; Münte, Thomas F; Lindenberger, Ulman; Heinze, Hans-Jochen; Düzel, Emrah

2008-11-01

Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR)--a measure of structural integrity--of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.

The molecular turn in psychiatry: a philosophical analysis.

PubMed

Rudnick, Abraham

2002-06-01

Biological psychiatry has been dominated by a psychopharmacologically-driven neurotransmitter dysfunction paradigm. The objective of this paper is to explore a reductionist assumption underlying this paradigm, and to suggest an improvement on it. The methods used are conceptual analysis with a comparative approach, particularly using illustrations from the history of both biological psychiatry and molecular biology. The results are that complete reduction to physicochemical explanations is not fruitful, at least in the initial stages of research in the medical and life sciences, and that an appropriate (non-reducible) integrative principle--addressing a property of the whole system under study--is required for each domain of research. This is illustrated in Pauling's use of a topological integrative principle for the discovery of the functioning of proteins and in Watson and Crick's use of the notion of a genetic code as an integrative principle for the discovery of the structure of genes. The neurotransmitter dysfunction paradigm addresses single molecules and their neural pathways, yet their interactions within the CNS as a whole seem most pertinent to mental disorders such as schizophrenia. The lack within biological psychiatry of an integrative principle addressing a property of the CNS as a whole may be responsible for the empirical failure of orthomolecular psychiatry, as well as for the central role that serendipity has played in the study of mental disorders, which is dominated by the neurotransmitter paradigm. The conclusion is that research in biological psychiatry may benefit from using, at least initially, some integrative principle(s) addressing a property of the CNS as a whole, such as connectionism or a hierarchical notion.

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

ERIC Educational Resources Information Center

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity

USDA-ARS?s Scientific Manuscript database

Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD+-dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress rema...

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity.

PubMed

Anderson, Rachel C; MacGibbon, Alastair K H; Haggarty, Neill; Armstrong, Kelly M; Roy, Nicole C

2018-01-01

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity

PubMed Central

MacGibbon, Alastair K. H.; Haggarty, Neill; Armstrong, Kelly M.; Roy, Nicole C.

2018-01-01

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation. PMID:29304106

Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

PubMed

Brock, Gerald; Ni, Xiao; Oelke, Matthias; Mulhall, John; Rosenberg, Matt; Seftel, Allen; D'Souza, Deborah; Barry, Jane

2016-05-01

Various factors play a role in the development of erectile dysfunction (ED). To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Combined analysis of transcriptome and proteome data as a tool for the identification of candidate biomarkers in renal cell carcinoma

PubMed Central

Seliger, Barbara; Dressler, Sven P.; Wang, Ena; Kellner, Roland; Recktenwald, Christian V.; Lottspeich, Friedrich; Marincola, Francesco M.; Baumgärtner, Maja; Atkins, Derek; Lichtenfels, Rudolf

2012-01-01

Results obtained from expression profilings of renal cell carcinoma using different “ome”-based approaches and comprehensive data analysis demonstrated that proteome-based technologies and cDNA microarray analyses complement each other during the discovery phase for disease-related candidate biomarkers. The integration of the respective data revealed the uniqueness and complementarities of the different technologies. While comparative cDNA microarray analyses though restricted to upregulated targets largely revealed genes involved in controlling gene/protein expression (19%) and signal transduction processes (13%), proteomics/PROTEOMEX-defined candidate biomarkers include enzymes of the cellular metabolism (36%), transport proteins (12%) and cell motility/structural molecules (10%). Candidate biomarkers defined by proteomics and PROTEOMEX are frequently shared, whereas the sharing rate between cDNA microarray and proteome-based profilings is limited. Putative candidate biomarkers provide insights into their cellular (dys)function and their diagnostic/prognostic value but still warrant further validation in larger patient numbers. Based on the fact that merely 3 candidate biomarkers were shared by all applied technologies, namely annexin A4, tubulin alpha-1A chain and ubiquitin carboxyl-terminal hydrolase L1 the analysis at a single hierarchical level of biological regulation seems to provide only limited results thus emphasizing the importance and benefit of performing rather combinatorial screenings which can complement the standard clinical predictors. PMID:19235166

Mapping grey matter reductions in schizophrenia: an anatomical likelihood estimation analysis of voxel-based morphometry studies.

PubMed

Fornito, A; Yücel, M; Patti, J; Wood, S J; Pantelis, C

2009-03-01

Voxel-based morphometry (VBM) is a popular tool for mapping neuroanatomical changes in schizophrenia patients. Several recent meta-analyses have identified the brain regions in which patients most consistently show grey matter reductions, although they have not examined whether such changes reflect differences in grey matter concentration (GMC) or grey matter volume (GMV). These measures assess different aspects of grey matter integrity, and may therefore reflect different pathological processes. In this study, we used the Anatomical Likelihood Estimation procedure to analyse significant differences reported in 37 VBM studies of schizophrenia patients, incorporating data from 1646 patients and 1690 controls, and compared the findings of studies using either GMC or GMV to index grey matter differences. Analysis of all studies combined indicated that grey matter reductions in a network of frontal, temporal, thalamic and striatal regions are among the most frequently reported in literature. GMC reductions were generally larger and more consistent than GMV reductions, and were more frequent in the insula, medial prefrontal, medial temporal and striatal regions. GMV reductions were more frequent in dorso-medial frontal cortex, and lateral and orbital frontal areas. These findings support the primacy of frontal, limbic, and subcortical dysfunction in the pathophysiology of schizophrenia, and suggest that the grey matter changes observed with MRI may not necessarily result from a unitary pathological process.

Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging.

PubMed

Lancellotti, Patrizio; Pibarot, Philippe; Chambers, John; Edvardsen, Thor; Delgado, Victoria; Dulgheru, Raluca; Pepi, Mauro; Cosyns, Bernard; Dweck, Mark R; Garbi, Madalina; Magne, Julien; Nieman, Koen; Rosenhek, Raphael; Bernard, Anne; Lowenstein, Jorge; Vieira, Marcelo Luiz Campos; Rabischoffsky, Arnaldo; Vyhmeister, Rodrigo Hernández; Zhou, Xiao; Zhang, Yun; Zamorano, Jose-Luis; Habib, Gilbert

2016-06-01

Prosthetic heart valve (PHV) dysfunction is rare but potentially life-threatening. Although often challenging, establishing the exact cause of PHV dysfunction is essential to determine the appropriate treatment strategy. In clinical practice, a comprehensive approach that integrates several parameters of valve morphology and function assessed with 2D/3D transthoracic and transoesophageal echocardiography is a key to appropriately detect and quantitate PHV dysfunction. Cinefluoroscopy, multidetector computed tomography, cardiac magnetic resonance imaging, and to a lesser extent, nuclear imaging are complementary tools for the diagnosis and management of PHV complications. The present document provides recommendations for the use of multimodality imaging in the assessment of PHVs. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Vascular dysfunction in preeclampsia.

PubMed

Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

2014-01-01

Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review. © 2013 John Wiley & Sons Ltd.

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

Understanding the role of the primary somatosensory cortex: Opportunities for rehabilitation

PubMed Central

Borich, M.R.; Brodie, S.M.; Gray, W.A.; Ionta, S.; Boyd, L.A.

2016-01-01

Emerging evidence indicates impairments in somatosensory function may be a major contributor to motor dysfunction associated with neurologic injury or disorders. However, the neuroanatomical substrates underlying the connection between aberrant sensory input and ineffective motor output are still under investigation. The primary somatosensory cortex (S1) plays a critical role in processing afferent somatosensory input and contributes to the integration of sensory and motor signals necessary for skilled movement. Neuroimaging and neurostimulation approaches provide unique opportunities to non-invasively study S1 structure and function including connectivity with other cortical regions. These research techniques have begun to illuminate casual contributions of abnormal S1 activity and connectivity to motor dysfunction and poorer recovery of motor function in neurologic patient populations. This review synthesizes recent evidence illustrating the role of S1 in motor control, motor learning and functional recovery with an emphasis on how information from these investigations may be exploited to inform stroke rehabilitation to reduce motor dysfunction and improve therapeutic outcomes. PMID:26164474

Systems Biology and Biomechanical Model of Heart Failure

PubMed Central

Louridas, George E; Lourida, Katerina G

2012-01-01

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies. PMID:22935019

Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes

PubMed Central

Arruda, Ana Paula; Hotamisligil, Gökhan S.

2015-01-01

Summary A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer cluster together to present the greatest threat to human health. As research in this field has advanced, it has become clear that unresolved metabolic inflammation, organelle dysfunction, and other cellular and metabolic stresses underlie the development of these chronic metabolic diseases. However, the relationship between these systems and pathological mechanisms is poorly understood. Here, we will discuss the role of cellular Ca2+ homeostasis as a critical mechanism integrating the myriad of cellular and subcellular dysfunctional networks found in metabolic tissues such as liver and adipose tissue in the context of metabolic disease particularly in obesity and diabetes. PMID:26190652

Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

PubMed

Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

2012-06-20

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction.

PubMed

Goa, K L; Balfour, J A; Zuanetti, G

1996-10-01

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.

Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.

PubMed

Capani, Francisco; Saraceno, Gustavo Ezequiel; Botti, Valeria; Aon-Bertolino, Laura; de Oliveira, Diêgo Madureira; Barreto, George; Galeano, Pablo; Giraldez-Alvarez, Lisandro Diego; Coirini, Héctor

2009-10-01

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

Psychometric Properties of the German Version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER).

PubMed

de Haan, Anke; Petermann, Franz; Meiser-Stedman, Richard; Goldbeck, Lutz

2016-02-01

Dysfunctional trauma-related cognitions are associated with posttraumatic stress disorder (PTSD). The psychometric properties of the German version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223 children and adolescents (7-16 years) with a history of different traumatic events. Confirmatory factor analyses supported the original two-factor structure--permanent and disturbing change (CPTCI-PC) and fragile person in a scary world (CPTCI-SW). The total scale and both subscales showed good internal consistency. Participants with PTSD had significantly more dysfunctional trauma-related cognitions than those without PTSD. Dysfunctional posttraumatic cognitions correlated significantly with posttraumatic stress symptoms (PTSS; r = .62), depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric properties and may facilitate evaluation of treatments and further research on the function of trauma-related cognitions in children and adolescents. (Partial) correlations provide empirical support for the combined DSM-5 symptom cluster negative alterations in cognitions and mood.

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

PubMed Central

ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

PubMed

Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

The extracellular matrix protein laminin-10 promotes blood-brain barrier repair after hypoxia and inflammation in vitro.

PubMed

Kangwantas, Korakoch; Pinteaux, Emmanuel; Penny, Jeffrey

2016-02-01

The blood-brain barrier (BBB) of the central nervous system (CNS) is essential for normal brain function. However, the loss of BBB integrity that occurs after ischaemic injury is associated with extracellular matrix (ECM) remodelling and inflammation, and contributes to poor outcome. ECM remodelling also contributes to BBB repair after injury, but the precise mechanisms and contribution of specific ECM molecules involved are unknown. Here, we investigated the mechanisms by which hypoxia and inflammation trigger loss of BBB integrity and tested the hypothesis ECM changes could contribute to BBB repair in vitro. We used an in vitro model of the BBB, composed of primary rat brain endothelial cells grown on collagen (Col) I-, Col IV-, fibronectin (FN)-, laminin (LM) 8-, or LM10-coated tissue culture plates, either as a single monolayer culture or on Transwell® inserts above mixed glial cell cultures. Cultures were exposed to oxygen-glucose deprivation (OGD) and/or reoxygenation, in the absence or the presence of recombinant interleukin-1β (IL-1β). Cell adhesion to ECM molecules was assessed by cell attachment and cell spreading assays. BBB dysfunction was assessed by immunocytochemistry for tight junction proteins occludin and zona occludens-1 (ZO-1) and measurement of trans-endothelial electrical resistance (TEER). Change in endothelial expression of ECM molecules was assessed by semi-quantitative RT-PCR. OGD and/or IL-1 induce dramatic changes associated with loss of BBB integrity, including cytoplasmic relocalisation of membrane-associated tight junction proteins occludin and ZO-1, cell swelling, and decreased TEER. OGD and IL-1 also induced gene expression of key ECM molecules associated with the BBB, including FN, Col IV, LM 8, and LM10. Importantly, we found that LM10, but not FN, Col IV, nor LM8, plays a key role in maintenance of BBB integrity and reversed most of the key hallmarks of BBB dysfunction induced by IL-1. Our data unravel new mechanisms of BBB dysfunction induced by hypoxia and inflammation and identify LM10 as a key ECM molecule involved in BBB repair after hypoxic injury and inflammation.

Usefulness of Mitral Valve Prosthetic or Bioprosthetic Time Velocity Index Ratio to Detect Prosthetic or Bioprosthetic Mitral Valve Dysfunction.

PubMed

Luis, Sushil Allen; Blauwet, Lori A; Samardhi, Himabindu; West, Cathy; Mehta, Ramila A; Luis, Chris R; Scalia, Gregory M; Miller, Fletcher A; Burstow, Darryl J

2017-10-15

This study aimed to investigate the utility of transthoracic echocardiographic (TTE) Doppler-derived parameters in detection of mitral prosthetic dysfunction and to define optimal cut-off values for identification of such dysfunction by valve type. In total, 971 TTE studies (647 mechanical prostheses; 324 bioprostheses) were compared with transesophageal echocardiography for evaluation of mitral prosthesis function. Among all prostheses, mitral valve prosthesis (MVP) ratio (ratio of time velocity integral of MVP to that of left ventricular outflow tract; odds ratio [OR] 10.34, 95% confidence interval [95% CI] 6.43 to 16.61, p<0.001), E velocity (OR 3.23, 95% CI 1.61 to 6.47, p<0.001), and mean gradient (OR 1.13, 95% CI 1.02 to 1.25, p=0.02) provided good discrimination of clinically normal and clinically abnormal prostheses. Optimal cut-off values by receiver operating characteristic analysis for differentiating clinically normal and abnormal prostheses varied by prosthesis type. Combining MVP ratio and E velocity improved specificity (92%) and positive predictive value (65%) compared with either parameter alone, with minimal decline in negative predictive value (92%). Pressure halftime (OR 0.99, 95% CI 0.98 to 1.00, p=0.04) did not differentiate between clinically normal and clinically abnormal prostheses but was useful in discriminating obstructed from normal and regurgitant prostheses. In conclusion, cut-off values for TTE-derived Doppler parameters of MVP function were specific to prosthesis type and carried high sensitivity and specificity for identifying prosthetic valve dysfunction. MVP ratio was the best predictor of prosthetic dysfunction and, combined with E velocity, provided a useful parameter for determining likelihood of dysfunction and need for further assessment. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

MK-801-Treated Oligodendrocytes as a Cellular Model to Study Schizophrenia.

PubMed

Brandão-Teles, Caroline; Martins-de-Souza, Daniel; Guest, Paul C; Cassoli, Juliana S

2017-01-01

Glutamate is the most important excitatory neurotransmitter in the brain. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is found both in neurons and glial cells such as oligodendrocytes, which have been shown to be dysfunctional in schizophrenia. For this reasons, the oligodendrocyte MO3.13 cell line has been used to study glutamatergic dysfunction as a model of schizophrenia using the NMDA receptor antagonists such as MK-801 to block receptor function. Here, we describe a comprehensive protocol for culturing and carrying out proteomic analyses of MK-801-treated MO3.13 cells as a means of identifying potential new biomarkers and targets for drug discovery in schizophrenia research.

Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.

PubMed

Canuet, Leonides; Pusil, Sandra; López, María Eugenia; Bajo, Ricardo; Pineda-Pardo, José Ángel; Cuesta, Pablo; Gálvez, Gerardo; Gaztelu, José María; Lourido, Daniel; García-Ribas, Guillermo; Maestú, Fernando

2015-07-15

Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aβ42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aβ42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas. Copyright © 2015 the authors 0270-6474/15/3510326-06$15.00/0.

Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence

PubMed Central

Blevins, Tana; Aliev, Fazil; Adkins, Amy; Hack, Laura; Bigdeli, Tim; D. van der Vaart, Andrew; Web, Bradley Todd; Bacanu, Silviu-Alin; Kalsi, Gursharan; Kendler, Kenneth S.; Miles, Michael F.; Dick, Danielle; Riley, Brien P.; Dumur, Catherine; Vladimirov, Vladimir I.

2015-01-01

Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome-wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p≤ 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p≤ 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (χ2 test p≤ 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PMID:26381263

The multinational Men's Attitudes to Life Events and Sexuality (MALES) Study Phase II: understanding PDE5 inhibitor treatment seeking patterns, among men with erectile dysfunction.

PubMed

Fisher, William A; Rosen, Raymond C; Eardley, Ian; Niederberger, Craig; Nadel, Andrea; Kaufman, Joel; Sand, Michael

2004-09-01

The aim of Phase II of the Men's Attitudes to Life Events and Sexuality (MALES) Study is to explore PDE5 inhibitor treatment seeking among men with erectile dysfunction (ED). Phase II of the MALES study involved 2,912 men, aged 20-75 years, from 8 countries (U.S., U.K., Germany, France, Italy, Spain, Mexico, and Brazil), who reported ED. Participants were recruited from the MALES Phase I sample [1] and via booster methods (e.g., physician referral, street interception), and completed self-report questionnaires concerning the characteristics of their ED, their efforts to seek PDE5 inhibitor treatment for their sexual dysfunction, and attitudinal and referent influences that potentially affect treatment-seeking. Statistical analyses focus on identification of correlates of PDE5 inhibitor treatment seeking. PDE5 inhibitor utilization is strongly associated with ED sufferers' assessment of the severity of their sexual dysfunction, with their belief that medication for ED is dangerous, and with their perceptions of whether physicians, other professionals, and spouses or family members are supportive of their seeking treatment. ED sufferers who evaluate their sexual dysfunction as severe, who believe that medication for ED is not dangerous, and who perceive support for treatment seeking from referent others, are more likely to utilize PDE5 inhibitor treatment. Findings indicate that perceived ED severity, beliefs about ED medication, and referent influences are strongly correlated with utilization of PDE5 inhibitor therapy. These findings aid our understanding of factors that may incline men with ED to seek-or to avoid-PDE5 inhibitor therapy for their sexual dysfunction, and provide a basis for clinical and educational interventions to assist men with ED to seek appropriate treatment.

Endothelium-derived contracting factors mediate the Ang II-induced endothelial dysfunction in the rat aorta: preventive effect of red wine polyphenols.

PubMed

Kane, Modou O; Etienne-Selloum, Nelly; Madeira, Soccoro V F; Sarr, Mamadou; Walter, Allison; Dal-Ros, Stéphanie; Schott, Christa; Chataigneau, Thierry; Schini-Kerth, Valérie B

2010-04-01

Angiotensin II (Ang II)-induced hypertension is associated with vascular oxidative stress and an endothelial dysfunction. This study examined the role of reactive oxygen species (ROS) and endothelium-derived contracting factors in Ang II-induced endothelial dysfunction and whether these effects are prevented by red wine polyphenols (RWPs), a rich source of natural antioxidants. Rats were infused with Ang II for 14 days. RWPs were administered in the drinking water 1 week before and during the Ang II infusion. Arterial pressure was measured in conscious rats. Vascular reactivity was assessed in organ chambers and cyclooxygenase-1 (COX-1) and COX-2 expression by Western blot and immunofluorescence analyses. Ang II-induced hypertension was associated with blunted endothelium-dependent relaxations and induction of endothelium-dependent contractions in the presence of nitro-L-arginine in response to acetylcholine (Ach). These effects were not affected by the combination of membrane permeant analogs of superoxide dismutase and catalase but were abolished by the thromboxane A(2) (TP) receptor antagonist GR32191B and the COX-2 inhibitor NS-398. The COX-1 inhibitor SC-560 also prevented contractile responses to Ach. Ang II increased the expression of COX-1 and COX-2 in the aortic wall. RWPs prevented Ang II-induced hypertension, endothelial dysfunction, and upregulation of COX-1 and COX-2. Thus, Ang II-induced endothelial dysfunction cannot be explained by an acute formation of ROS reducing the bioavailability of nitric oxide but rather by COX-dependent formation of contracting factors acting on TP receptors. RWPs are able to prevent the Ang II-induced endothelial dysfunction mostly due to their antioxidant properties.

Perioperative Non-Invasive Indocyanine Green-Clearance Testing to Predict Postoperative Outcome after Liver Resection

PubMed Central

Haegele, Stefanie; Reiter, Silvia; Wanek, David; Offensperger, Florian; Pereyra, David; Stremitzer, Stefan; Fleischmann, Edith; Brostjan, Christine; Gruenberger, Thomas; Starlinger, Patrick

2016-01-01

Background Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting. Study Design 137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests. Results Preoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome. Conclusion PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications. PMID:27812143

Physical examination of dizziness in athletes after a concussion: A descriptive study.

PubMed

Reneker, Jennifer C; Cheruvu, Vinay K; Yang, Jingzhen; James, Mark A; Cook, Chad E

2018-04-01

Dizziness is commonly reported after concussion. With the forces experienced at the time of the injury, several anatomical locations may have been altered, causing dizziness. Describe an objective examination and the types of impairment/dysfunction implicated by the results of clinical examination tests in subjects with dizziness after a concussion. Cross-Sectional. Athletes between ages 10-23 were enrolled with a diagnosis of concussion. An examination was completed to identify areas potentially contributing to dizziness, including tests of oculomotor control, the vestibular system, neuromotor control, and musculoskeletal components of the cervical spine. Descriptive analyses were completed to define the anatomical areas/types of dysfunction identified by positive findings of the examination tests. All (n = 41; 100%) subjects had examination findings consistent with central dysfunction. Of these, 36 (97.8%) had oculomotor control deficits; 29 (70.7%) demonstrated motion sensitivity; and 6 (15%) had central vestibular deficits. Nineteen (46.3%) had peripheral dysfunction, including 18 (43.9%) with unilateral hypofunction, and 2 (4.9%) with Benign Paroxysmal Positional Vertigo. Thirty-four (82.9%) had cervical dysfunction, with 11 (26.8%) presenting with cervicogenic dizziness, and 31 (75.6%) with altered neuromotor control. Functional injury to centrally-mediated pathways, specifically oculomotor control, and afferent and efferent pathways in the cervical spine are commonly identified through clinical examination tests in individuals with a complaint of dizziness post-concussion. According to results presented here, a high majority (90%) of the participants demonstrated dizziness that appeared to be multifactorial in nature and was not attributable to one main type of dysfunction. The common pathways between the systems make it difficult to isolate only one anatomical area as a contributor to dizziness. Copyright © 2017 Elsevier Ltd. All rights reserved.

A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction.

PubMed

Dording, Christina M; Fisher, Lauren; Papakostas, George; Farabaugh, Amy; Sonawalla, Shamsah; Fava, Maurizio; Mischoulon, David

2008-01-01

We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (P<0.05) for the ITT and completer groups based on ASEX item #1, but not by dosing groups. Maca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.

Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: A theoretical review of the evidence and future directions for clinical translation

PubMed Central

Williams, Leanne M

2016-01-01

Complex emotional, cognitive and self-reflective functions rely on the activation and connectivity of large-scale neural circuits. These circuits offer a relevant scale of focus for conceptualizing a taxonomy for depression and anxiety based on specific profiles (or biotypes) of neural circuit dysfunction. Here, the theoretical review first outlined the current consensus as to what constitutes the organization of large-scale circuits in the human brain identified using parcellation and meta-analysis. The focus is on neural circuits implicated in resting reflection (“default mode”), detection of “salience”, affective processing (“threat” and “reward”), “attention” and “cognitive control”. Next, the current evidence regarding which type of dysfunctions in these circuits characterize depression and anxiety disorders was reviewed, with an emphasis on published meta-analyses and reviews of circuit dysfunctions that have been identified in at least two well-powered case:control studies. Grounded in the review of these topics, a conceptual framework is proposed for considering neural circuit-defined “biotypes”. In this framework, biotypes are defined by profiles of extent of dysfunction on each large-scale circuit. The clinical implications of a biotype approach for guiding classification and treatment of depression and anxiety is considered. Future research directions will develop the validity and clinical utility of a neural circuit biotype model that spans diagnostic categories and helps to translate neuroscience into clinical practice in the real world. PMID:27653321

[Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity].

PubMed

Candel Pau, Júlia; Castillo Salinas, Félix; Perapoch López, Josep; Carrascosa Lezcano, Antonio; Sánchez García, Olga; Llurba Olivé, Elisa

2016-10-01

Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study.

PubMed

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M; Cappola, Anne R; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs > or =65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P<.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P<.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61+/-6.88 vs 24.72+/-4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.

Predictive factors of Gastrointestinal motility Dysfunction after gastrojejunostomy for peptic ulcer stenosis.

PubMed

Ayadi, Sofiene; Daghfous, Amine; Saidani, Ahmed; Haddad, Anis; Magherbi, Houcine; Jouini, Mohamed; Kacem, Montassar; Ben Safta, Zoubeir

2014-10-01

Despite the establishment of effective medical therapies in peptic ulcer disease, gastric outlet obstruction remains one of the most common health problem in Tunisia. Various operations have been attempted, which may lead to postoperative morbidity. Gastrointestinal (GI) motility dysfunction is the most common complications. to determine the predictive factor of gastrointestinal motility dysfunction after gastrojejunostomy for peptic ulcer stenosis. We carried out a retrospective study to evaluate the postoperative recovery of the motility of the upper gastrointestinal tract after gastrojejunostomy for peptic ulcer stenosis. During the 9- year study, 138 patients underwent operations for ulcer peptic stenosis. Among the patients, 116 (84,1%) were treated with gastrojejunostomy. Descriptive statistics, univariate and multivariate analyses were performed. The mean age of patients was 47.85 years (range: 19- 92years) and most. Were male (84, 5 %). Ninety two (79.3%) patients had a documented history of peptic ulcer disease. The duration of symptoms ranged from 10 to 372 days (mean: 135.86 days). Eighty two (71%) patients were operated on through laparotomy. Laparoscopic procedure was performed in 29% of the patients. There was no operative mortality. Perioperative morbidity occurred in 12.4% (14 patients). Gastrointestinal motility dysfunction occurred in 12 patients (10.3%). It was treated by nasogastric aspiration and prokinetics. By univariate analysis; diabetes (0,010), cachexia (0,049), ASA class (0.05) were all statistically associated with gastrointestinal motility dysfunction in this series. Multivariate logistic regression analysis (table 2) showed that the cachexia (0,009), ASA class (0.02) were the main predictors of gastrointestinal motility dysfunction after gastrojejunostomy for peptic ulcer stenosis in the followed patients. Gastrointestinal motility dysfunction is the most common complications after gastrojejunostomy for pyloric adult stenosis. Surgery must be preceded by careful medical preparation. It is more likely to occur in patients with an ASA class 2 or greater. Those patients should be considered for other treatment options, such as endoscopic balloon dilation.

Adult Outcome of Children Reared for Long-Term Periods in Foster Families.

ERIC Educational Resources Information Center

Dumaret, Annick-Camille; Coppel-Batsch, Marthe; Couraud, Simone

1997-01-01

Assessment of adult outcomes of 59 children from severely psychosocially dysfunctional families, who were placed in foster families for at least five years, found most had overcome their childhood adversities with 56% well-integrated socially and only 10% in situations of failure. Difficulties were linked to multiple family disturbances, traumatic…

Helping Children with Sensory Processing Disorders: The Role of Occupational Therapy

ERIC Educational Resources Information Center

Sweet, Margarita

2010-01-01

Normally functioning sensory systems develop through sensory experiences. Children are stimulated through their senses in many different ways. Even though a person's sensory system is intact, he or she may have a sensory processing disorder (SPD), also known as sensory integration dysfunction. This means the person's brain does not correctly…

Behaviour Change Policy Agendas for "Vulnerable" Subjectivities: The Dangers of Therapeutic Governance and Its New Entrepreneurs

ERIC Educational Resources Information Center

Ecclestone, Kathryn

2017-01-01

Apocalyptic crisis discourses of mental health problems and psycho-emotional dysfunction are integral to behaviour change agendas across seemingly different policy arenas. Bringing these agendas together opens up new theoretical and empirical lines of enquiry about the symbioses and contradictions surrounding the human subjects they target. The…

Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects.

PubMed

Rice, David A; McNair, Peter J; Lewis, Gwyn N

2011-01-01

A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether γ-loop dysfunction contributes to AMI in people with knee joint OA. Fifteen subjects with knee joint OA and 15 controls with no history of knee joint pathology participated in this study. Quadriceps and hamstrings peak isometric torque (Nm) and electromyography (EMG) amplitude were collected before and after 20 minutes of 50 Hz vibration applied to the infrapatellar tendon. Between-group differences in pre-vibration torque were analysed using a one-way analysis of covariance, with age, gender and body mass (kg) as the covariates. If the γ-loop is intact, vibration should decrease torque and EMG levels in the target muscle; if dysfunctional, then torque and EMG levels should not change following vibration. One-sample t tests were thus undertaken to analyse whether percentage changes in torque and EMG differed from zero after vibration in each group. In addition, analyses of covariance were utilised to analyse between-group differences in the percentage changes in torque and EMG following vibration. Pre-vibration quadriceps torque was significantly lower in the OA group compared with the control group (P = 0.005). Following tendon vibration, quadriceps torque (P < 0.001) and EMG amplitude (P ≤0.001) decreased significantly in the control group but did not change in the OA group (all P > 0.299). Hamstrings torque and EMG amplitude were unchanged in both groups (all P > 0.204). The vibration-induced changes in quadriceps torque and EMG were significantly different between the OA and control groups (all P < 0.011). No between-group differences were observed for the change in hamstrings torque or EMG (all P > 0.554). γ-loop dysfunction may contribute to AMI in individuals with knee joint OA, partially explaining the marked quadriceps weakness and atrophy that is often observed in this population.

Mechanisms of quadriceps muscle weakness in knee joint osteoarthritis: the effects of prolonged vibration on torque and muscle activation in osteoarthritic and healthy control subjects

PubMed Central

2011-01-01

Introduction A consequence of knee joint osteoarthritis (OA) is an inability to fully activate the quadriceps muscles, a problem termed arthrogenic muscle inhibition (AMI). AMI leads to marked quadriceps weakness that impairs physical function and may hasten disease progression. The purpose of the present study was to determine whether γ-loop dysfunction contributes to AMI in people with knee joint OA. Methods Fifteen subjects with knee joint OA and 15 controls with no history of knee joint pathology participated in this study. Quadriceps and hamstrings peak isometric torque (Nm) and electromyography (EMG) amplitude were collected before and after 20 minutes of 50 Hz vibration applied to the infrapatellar tendon. Between-group differences in pre-vibration torque were analysed using a one-way analysis of covariance, with age, gender and body mass (kg) as the covariates. If the γ-loop is intact, vibration should decrease torque and EMG levels in the target muscle; if dysfunctional, then torque and EMG levels should not change following vibration. One-sample t tests were thus undertaken to analyse whether percentage changes in torque and EMG differed from zero after vibration in each group. In addition, analyses of covariance were utilised to analyse between-group differences in the percentage changes in torque and EMG following vibration. Results Pre-vibration quadriceps torque was significantly lower in the OA group compared with the control group (P = 0.005). Following tendon vibration, quadriceps torque (P < 0.001) and EMG amplitude (P ≤0.001) decreased significantly in the control group but did not change in the OA group (all P > 0.299). Hamstrings torque and EMG amplitude were unchanged in both groups (all P > 0.204). The vibration-induced changes in quadriceps torque and EMG were significantly different between the OA and control groups (all P < 0.011). No between-group differences were observed for the change in hamstrings torque or EMG (all P > 0.554). Conclusions γ-loop dysfunction may contribute to AMI in individuals with knee joint OA, partially explaining the marked quadriceps weakness and atrophy that is often observed in this population. PMID:21933392

Radioisotope penile plethysmography: A technique for evaluating corpora cavernosal blood flow during early tumescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, A.N.; Graham, M.M.; Ferency, G.F.

1989-04-01

Radioisotope penile plethysmography is a nuclear medicine technique which assists in the evaluation of patients with erectile dysfunction. This technique attempts to noninvasively quantitate penile corpora cavernosal blood flow during early penile tumescence using technetium-99m-labeled red blood cells. Penile images and counts were acquired in a steady-state blood-pool phase prior to and after the administration of intracorporal papaverine. Penile counts, images, and time-activity curves were computer analyzed in order to determine peak corporal flow and volume changes. Peak corporal flow rates were compared to arterial integrity (determined by angiography) and venosinusoidal corporal leak (determined by cavernosometry). Peak corporal flow correlatedmore » well with arterial integrity (r = 0.91) but did not correlate with venosinusoidal leak parameters (r = 0.01). This report focuses on the methodology and the assumptions which form the foundation of this technique. The strong correlation of peak corporal flow and angiography suggests that radioisotope penile plethysmography could prove useful in the evaluation of arterial inflow disorders in patients with erectile dysfunction.« less

Treatment of severe fluoroacetamide poisoning in patient with combined multiple organ dysfunction syndrome by evidence-based integrated Chinese and Western medicines: A case report.

PubMed

Wen, Wanxin; Gao, Hongxia; Kang, Nini; Lu, Aili; Qian, Caiwen; Zhao, Yuanqi

2017-07-01

Fluoroacetamide poisoning is the acute and severe disease of human, which leads to nervous, digestive, and cardiovascular system damage or even death in a short period of time. We report a case of a 65-year-old woman with loss of consciousness, nausea, and vomiting who was sent to the hospital by passers-by. She was diagnosed with severe fluoroacetamide poisoning with combined multiple organ dysfunction syndrome. When the diagnosis was unclear, we gave gastric lavage, support and symptomatic treatment, and closely with the vital sign. When the diagnosis was clear, based on the evidence of retrieved, muscle injection of acetamide, calcium gluconate, and vitamin C. Traditional Chinese medicine aspect, oral administration of mung bean soup of glycyrrhizae and Da-Cheng-Qi decoction enema. By setting reasonable treatment for patients, she had no special discomfort and complications after treatment. Besides, through 1-month follow-up, it was confirmed that the treatments were effective. Evidence-based integrated Chinese and Western medicines can effectively improve the therapeutic effects in severe fluoroacetamide-poisoned patients with combined MODS.

Reflecting on the mirror neuron system in autism: a systematic review of current theories.

PubMed

Hamilton, Antonia F de C

2013-01-01

There is much interest in the claim that dysfunction of the mirror neuron system in individuals with autism spectrum condition causes difficulties in social interaction and communication. This paper systematically reviews all published studies using neuroscience methods (EEG/MEG/TMS/eyetracking/EMG/fMRI) to examine the integrity of the mirror system in autism. 25 suitable papers are reviewed. The review shows that current data are very mixed and that studies using weakly localised measures of the integrity of the mirror system are hard to interpret. The only well localised measure of mirror system function is fMRI. In fMRI studies, those using emotional stimuli have reported group differences, but studies using non-emotional hand action stimuli do not. Overall, there is little evidence for a global dysfunction of the mirror system in autism. Current data can be better understood under an alternative model in which social top-down response modulation is abnormal in autism. The implications of this model and future research directions are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: more than frontal lobe dysfunction.

PubMed

Tsermentseli, Stella; Leigh, P Nigel; Goldstein, Laura H

2012-02-01

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be significant heterogeneity. This article will review the current state of knowledge regarding the neuropathological and neuroanatomical basis for cognitive dysfunction in ALS. Neuropathological findings suggest that ALS does not selectively affect the frontotemporal network but rather is part of a broad clinico-pathological spectrum now known as TAR-DNA binding protein (TDP)-43 proteinopathies. Functional neuroimaging has supported neuropsychological findings of frontotemporal dysfunction but has also implied the involvement of somatosensory areas. Structural neuroimaging has not been able to establish a specific hypothesis of extra-motor cortical atrophy beyond the combination of various frontal, temporal and limbic areas. The finding of reduction in the integrity of white matter in the frontal, temporal and parietal lobes including long association fibers suggests that subcortical involvement may underlie both cognitive and functional changes in ALS. Future perspectives for further investigations are highlighted. Copyright © 2011 Elsevier Srl. All rights reserved.

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phosphorus and proton magnetic resonance spectroscopy demonstrates mitochondrial dysfunction in early and advanced Parkinson's disease.

PubMed

Hattingen, Elke; Magerkurth, Jörg; Pilatus, Ulrich; Mozer, Anne; Seifried, Carola; Steinmetz, Helmuth; Zanella, Friedhelm; Hilker, Rüdiger

2009-12-01

Mitochondrial dysfunction hypothetically contributes to neuronal degeneration in patients with Parkinson's disease. While several in vitro data exist, the measurement of cerebral mitochondrial dysfunction in living patients with Parkinson's disease is challenging. Anatomical magnetic resonance imaging combined with phosphorus and proton magnetic resonance spectroscopic imaging provides information about the functional integrity of mitochondria in specific brain areas. We measured partial volume corrected concentrations of low-energy metabolites and high-energy phosphates with sufficient resolution to focus on pathology related target areas in Parkinson's disease. Combined phosphorus and proton magnetic resonance spectroscopic imaging in the mesostriatal region was performed in 16 early and 13 advanced patients with Parkinson's disease and compared to 19 age-matched controls at 3 Tesla. In the putamen and midbrain of both Parkinson's disease groups, we found a bilateral reduction of high-energy phosphates such as adenosine triphophosphate and phosphocreatine as final acceptors of energy from mitochondrial oxidative phosphorylation. In contrast, low-energy metabolites such as adenosine diphophosphate and inorganic phosphate were within normal ranges. These results provide strong in vivo evidence that mitochondrial dysfunction of mesostriatal neurons is a central and persistent phenomenon in the pathogenesis cascade of Parkinson's disease which occurs early in the course of the disease.

Salivary gland dysfunction markers in type 2 diabetes mellitus patients

PubMed Central

Aitken-Saavedra, Juan; Rojas-Alcayaga, Gonzalo; Maturana-Ramírez, Andrea; Escobar-Álvarez, Alejandro; Cortes-Coloma, Andrea; Reyes-Rojas, Montserrat; Viera -Sapiain, Valentina; Villablanca-Martínez, Claudia

2015-01-01

Background Diabetes mellitus (DM) is a chronic disease of the carbohydrate metabolism that, when not rigorously controlled, compromises systemic and organ integrity, thereby causing renal diseases, blindness, neuropathy, arteriosclerosis, infections, and glandular dysfunction, including the salivary glands. The aim of this study was to determine the relationship between the qualitative and quantitative parameters of salivary alteration, which are indicators of salivary gland dysfunction, and the level of metabolic control of type 2 diabetes patients. Material and Methods A convenience sample of 74 voluntary patients with type 2 DM was selected, each of whom donated a sample of unstimulated saliva. Salivary parameters such as salivary flow rate, protein concentration, pH, and xerostomia were studied. Results There is a positive relationship between the level of metabolic control measured with HbA1 and the protein concentration in saliva (Spearman rho = 0.329 and p = 0.004). The same assay showed an inverse correlation between HbA1 and pH (Spearman rho = -0.225 and p = 0.05). Conclusions The protein concentration in saliva and, to a lesser extent, the pH may be useful as glandular dysfunction indicators in DM2 patients. Key words:Saliva, type 2 diabetes mellitus, pH, protein concentration, xerostomia. PMID:26535097

TRANSDIAGNOSTIC DIMENSIONS OF ANXIETY AND DEPRESSION MODERATE MOTIVATION-RELATED BRAIN NETWORKS DURING GOAL MAINTENANCE

PubMed Central

Spielberg, Jeffrey M.; Miller, Gregory A.; Warren, Stacie L.; Sutton, Bradley P.; Banich, Marie; Heller, Wendy

2015-01-01

Background Advancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. Methods Participants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color-word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition-dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). Results Anxious arousal was positively associated with amygdala↔right dlPFC coupling. Depression was positively associated with OFC↔right dlPFC coupling and negatively associated with OFC↔left dlPFC coupling. Conclusions Findings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/depression while networks are challenged. PMID:24753242

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

PubMed

Klemann, Cornelius J H M; Xicoy, Helena; Poelmans, Geert; Bloem, Bas R; Martens, Gerard J M; Visser, Jasper E

2018-07-01

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

PubMed

Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

2011-08-01

The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge. © 2011 John Wiley & Sons A/S.

Questionnaires in the assessment of sexual function in women with urinary incontinence and pelvic organ prolapse.

PubMed

Mestre, M; Lleberia, J; Pubill, J; Espuña-Pons, M

2015-04-01

Integrating sexual health in clinical practice is important. In women with pelvic floor disorders, the evaluation of the anatomical defects, lower urinary tract function and the anorectal function often receives more attention than the sexual function. Review of Medline using defined search terms to identify articles related to sexual health assessment in urogynecology and manual analyses was performed. Only articles published in English or Spanish were included. Only 50% of women attending urogynecological clinics are sexually active. Of those, 60% present with some sort of sexual sexual dysfunction (FSD). Questionnaires and sexuality scales would facilitate discussion of sexual matters between the Health Care professionals and the women, and may increase the likelihood of FSD being diagnosed. The Pelvic Organ Prolapse Incontinence Sexual Questionnaire (PISQ) and the PISQ-IR (IUGA-Revised) are the only female sexual function specific questionnaires currently validated and developed specifically to assess sexual function in women with urinary incontinence and/or pelvic organ prolapse. Furthermore, the PISQ-IR also allows evaluation of the outcomes of women who are not sexually active when requiring urogynecologic care. PISQ-IR is also designed for international validation. In order to use the PISQ-IR in Spain, a proper interpretation and validation of the questionnaire is needed. The evaluation of sexual function through specific questionnaires facilitates the identification of the sexual dysfunctions associated to the pelvic floor disorders. The inclusion of sexuality questionnaires as an outcome measure allows to analyze the impact in the sexual life of women treated for an urogynecological problem. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Transdiagnostic dimensions of anxiety and depression moderate motivation-related brain networks during goal maintenance.

PubMed

Spielberg, Jeffrey M; Miller, Gregory A; Warren, Stacie L; Sutton, Bradley P; Banich, Marie; Heller, Wendy

2014-10-01

Advancing research on the etiology, prevention, and treatment of psychopathology requires the field to move beyond modular conceptualizations of neural dysfunction toward understanding disturbance in key brain networks. Although some studies of anxiety and depression have begun doing so, they typically suffer from several drawbacks, including: (1) a categorical approach ignoring transdiagnostic processes, (2) failure to account for substantial anxiety and depression comorbidity, (3) examination of networks at rest, which overlooks disruption manifesting only when networks are challenged. Accordingly, the present study examined relationships between transdiagnostic dimensions of anxiety/depression and patterns of functional connectivity while goal maintenance was challenged. Participants (n = 179, unselected community members and undergraduates selected to be high/low on anxiety/depression) performed a task in which goal maintenance was challenged (color-word Stroop) while fMRI data were collected. Analyses examined moderation by anxiety/depression of condition-dependent coupling between regions of dorsolateral prefrontal cortex (dlPFC) previously associated with approach and avoidance motivation and amygdala/orbitofrontal cortex (OFC). Anxious arousal was positively associated with amygdala↔right dlPFC coupling. Depression was positively associated with OFC↔right dlPFC coupling and negatively associated with OFC↔left dlPFC coupling. Findings advance the field toward an integrative model of the neural instantiation of anxiety/depression by identifying specific, distinct dysfunctions associated with anxiety and depression in networks important for maintaining approach and avoidance goals. Specifically, findings shed light on potential neural mechanisms involved in attentional biases in anxiety and valuation biases in depression and underscore the importance of examining transdiagnostic dimensions of anxiety/depression while networks are challenged. © 2014 Wiley Periodicals, Inc.

Age of onset and the subclassification of conduct/dissocial disorder

PubMed Central

Silberg, Judy; Moore, Ashlee A.; Rutter, Michael

2015-01-01

Background Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. Methods The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Results Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Conclusions Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. PMID:25359313

Age of onset and the subclassification of conduct/dissocial disorder.

PubMed

Silberg, Judy; Moore, Ashlee A; Rutter, Michael

2015-07-01

Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood. © 2014 Association for Child and Adolescent Mental Health.

Dysfunctional metacognition and drive for thinness in typical and atypical anorexia nervosa.

PubMed

Davenport, Emily; Rushford, Nola; Soon, Siew; McDermott, Cressida

2015-01-01

Anorexia nervosa is complex and difficult to treat. In cognitive therapies the focus has been on cognitive content rather than process. Process-oriented therapies may modify the higher level cognitive processes of metacognition, reported as dysfunctional in adult anorexia nervosa. Their association with clinical features of anorexia nervosa, however, is unclear. With reclassification of anorexia nervosa by DSM-5 into typical and atypical groups, comparability of metacognition and drive for thinness across groups and relationships within groups is also unclear. Main objectives were to determine whether metacognitive factors differ across typical and atypical anorexia nervosa and a non-clinical community sample, and to explore a process model by determining whether drive for thinness is concurrently predicted by metacognitive factors. Women receiving treatment for anorexia nervosa (n = 119) and non-clinical community participants (n = 100), aged between 18 and 46 years, completed the Eating Disorders Inventory (3(rd) Edition) and Metacognitions Questionnaire (Brief Version). Body Mass Index (BMI) of 18.5 kg/m(2) differentiated between typical (n = 75) and atypical (n = 44) anorexia nervosa. Multivariate analyses of variance and regression analyses were conducted. Metacognitive profiles were similar in both typical and atypical anorexia nervosa and confirmed as more dysfunctional than in the non-clinical group. Drive for thinness was concurrently predicted in the typical patients by the metacognitive factors, positive beliefs about worry, and need to control thoughts; in the atypical patients by negative beliefs about worry and, inversely, by cognitive self-consciousness, and in the non-clinical group by cognitive self-consciousness. Despite having a healthier weight, the atypical group was as severely affected by dysfunctional metacognitions and drive for thinness as the typical group. Because metacognition concurrently predicted drive for thinness in both groups, a role for process-oriented therapy in adults is suggested. Implications are discussed.

Error behaviors associated with loss of competency in Alzheimer's disease.

PubMed

Marson, D C; Annis, S M; McInturff, B; Bartolucci, A; Harrell, L E

1999-12-10

To investigate qualitative behavioral changes associated with declining medical decision-making capacity (competency) in patients with AD. Qualitative measures can yield clinical information about functional changes in neurologic disease not available through quantitative measures. Normal older controls (n = 21) and patients with mild and moderate probable AD (n = 72) were compared using a standardized competency measure and neuropsychological measures. A system of 16 qualitative error scores representing conceptual domains of language, executive dysfunction, affective dysfunction, and compensatory responses was used to analyze errors produced on the competency measure. Patterns of errors were examined across groups. Relationships between error behaviors and competency performance were determined, and neurocognitive correlates of specific error behaviors were identified. AD patients demonstrated more miscomprehension, factual confusion, intrusions, incoherent responses, nonresponsive answers, loss of task, and delegation than controls. Errors in the executive domain (loss of task, nonresponsive answer, and loss of detachment) were key predictors of declining competency performance by AD patients. Neuropsychological analyses in the AD group generally confirmed the conceptual domain assignments of the qualitative scores. Loss of task, nonresponsive answers, and loss of detachment were key behavioral changes associated with declining competency of AD patients and with neurocognitive measures of executive dysfunction. These findings support the growing linkage between executive dysfunction and competency loss.

Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

PubMed Central

Guachalla, Luis Miguel; Ju, Zhenyu; Koziel, Rafal; von Figura, Guido; Song, Zhangfa; Fusser, Markus; Epe, Bernd; Jansen-Dűrr, Pidder; Rudolph, K. Lenhard

2009-01-01

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction. PMID:20195488

Maternal Thyroid Dysfunction and Risk of Seizure in the Child: A Danish Nationwide Cohort Study

PubMed Central

Laurberg, Peter; Wu, Chun Sen; Olsen, Jørn

2013-01-01

Thyroid hormones are essential for brain development, and maternal thyroid disease may affect child neurocognitive development. Some types of seizures may also depend upon early exposure of the developing central nervous system, and we hypothesized that maternal thyroid dysfunction could increase the risk of seizure in the child. In a Danish population-based study we included 1,699,693 liveborn singletons, and from the Danish National Hospital Register we obtained information on maternal diagnosis of hyper- or hypothyroidism and neonatal seizure, febrile seizure, and epilepsy in the child. Maternal diagnosis of thyroid dysfunction before or after birth of the child was registered in two percent of the singleton births. In adjusted analyses, maternal hyperthyroidism and hypothyroidism first time diagnosed after birth of the child were associated with a significant increased risk of epilepsy in the child. Moreover, hypothyroidism diagnosed after birth of the child was associated with a significant increased risk of neonatal and febrile seizures. No significant association was seen for maternal diagnosis prior to birth of the child. We speculate if some degree of maternal thyroid dysfunction was already present during the pregnancy in mothers diagnosed after birth of the child and if this untreated condition may present a neurodevelopmental risk. PMID:23984072

Maternal thyroid dysfunction and risk of seizure in the child: a Danish nationwide cohort study.

PubMed

Andersen, Stine Linding; Laurberg, Peter; Wu, Chun Sen; Olsen, Jørn

2013-01-01

Thyroid hormones are essential for brain development, and maternal thyroid disease may affect child neurocognitive development. Some types of seizures may also depend upon early exposure of the developing central nervous system, and we hypothesized that maternal thyroid dysfunction could increase the risk of seizure in the child. In a Danish population-based study we included 1,699,693 liveborn singletons, and from the Danish National Hospital Register we obtained information on maternal diagnosis of hyper- or hypothyroidism and neonatal seizure, febrile seizure, and epilepsy in the child. Maternal diagnosis of thyroid dysfunction before or after birth of the child was registered in two percent of the singleton births. In adjusted analyses, maternal hyperthyroidism and hypothyroidism first time diagnosed after birth of the child were associated with a significant increased risk of epilepsy in the child. Moreover, hypothyroidism diagnosed after birth of the child was associated with a significant increased risk of neonatal and febrile seizures. No significant association was seen for maternal diagnosis prior to birth of the child. We speculate if some degree of maternal thyroid dysfunction was already present during the pregnancy in mothers diagnosed after birth of the child and if this untreated condition may present a neurodevelopmental risk.

Relationship between maladaptive cognitions about sleep and recovery in patients with borderline personality disorder

PubMed Central

Plante, David T.; Frankenburg, Frances R.; Fitzmaurice, Garrett M.; Zanarini, Mary C.

2013-01-01

Borderline personality disorder (BPD) has been associated with maladaptive cognitive processes including dysfunctional attitudes and a negative attribution style. Comorbid insomnia affects the course of multiple psychiatric disorders, and has been associated with absence of recovery from BPD. Because dysfunctional beliefs and attitudes are common among patients with insomnia, the purpose of this study was to evaluate the association between maladaptive sleep-related cognitions and recovery status (symptomatic remission plus good concurrent psychosocial functioning) in patients with BPD. 223 BPD patients participating in the McLean Study of Adult Development (MSAD) were administered the Dysfunctional Beliefs and Attitudes about Sleep questionnaire (DBAS-16) as part of the 16-year follow-up wave. Maladaptive sleep cognitions were compared between recovered (n=105) and non-recovered (n=118) BPD participants, in analyses that adjusted for age, sex, depression, anxiety, and primary sleep disorders. Results demonstrated non-recovered BPD patients had significantly more severe maladaptive sleep-related cognitions as measured by the overall DBAS-16 score. These results demonstrate an association between dysfunctional beliefs and attitudes about sleep and recovery status among BPD patients. Further research is warranted to evaluate treatments targeted towards maladaptive sleep-related cognitions, and their subsequent effects on the course of BPD. PMID:23972789

Effects of low sleep quality on sexual function, in women with fibromyalgia.

PubMed

Amasyali, A S; Taştaban, E; Amasyali, S Y; Turan, Y; Kazan, E; Sari, E; Erol, B; Cengiz, M; Erol, H

2016-01-01

Sexual dysfunction is a common experience in women with fibromyalgia. However, the physiopathology of this association is unclear. We aimed to evaluate whether sleep disturbance has an influence on sexual function in women with fibromyalgia. Fifty-four sexually active premenopausal women with fibromyalgia were enrolled in the study. The following questionnaires were used: the Female Sexual Function Index (FSFI), the Pittsburgh Sleep Quality Index (PSQI), the Fibromyalgia Impact Questionnaire (FIQ) and the Beck Depression Inventory (BDI). Appropriate statistical analyses were used by using SPSS 18. The mean FSFI score was 25.344 ± 6.52 and showed no correlation with age, body mass index, BDI or duration of fibromyalgia. However, a positive correlation between sexual dysfunction and low sleep quality was found (r=0.43; P=0.001). In addition, the median FSFI score was 29.2 (27.2-32.4) in patients with higher sleep quality (PSQI⩽5), whereas it was 21.4 (18.9-25.3) in patients with lower sleep quality (PSQI>5) (P<0.001). There was a positive correlation between sexual dysfunction and symptoms of fibromyalgia as indicated by a higher FIQ score (r=0.37; P=0.006). Sexual dysfunction in female patients with fibromyalgia may be due to low sleep quality. Treatment of the sleep disorder may improve female sexual function.

A young patient with atypical type-B Wolff–Parkinson–White syndrome accompanied by left ventricular dysfunction

PubMed Central

Takeuchi, Takahiro; Tomita, Takeshi; Kasai, Hiroki; Kashiwagi, Daisuke; Yoshie, Koji; Yaguchi, Tomonori; Oguchi, Yasutaka; Kozuka, Ayako; Gautam, Milan; Motoki, Hirohiko; Okada, Ayako; Shiba, Yuji; Aizawa, Kazunori; Izawa, Atsushi; Miyashita, Yusuke; Koyama, Jun; Hongo, Minoru; Ikeda, Uichi

2014-01-01

A 15-year-old asymptomatic male patient presented with an electrocardiographic abnormality and left ventricular (LV) dysfunction (left ventricle ejection fraction of 40%) in a physical examination performed 2 years previously. LV dysfunction did not improve despite optimal medical therapy for dilated cardiomyopathy. Twelve-lead electrocardiography revealed a normal PR interval (138 ms) with a small delta-like wave in V2, but not a typical diagnostic wave that could be diagnosed as Wolff–Parkinson–White (WPW) syndrome by an electrocardiogram auto-analysis. Transthoracic echocardiography showed a remarkable asynchronous septal motion. An electrophysiological study was performed to exclude WPW syndrome. An accessory pathway (AP) was revealed on the lateral wall of the right ventricle, and radiofrequency catheter ablation was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and LV function improved. The intrinsic atrioventricular nodal conduction was very slow (A-H, 237 ms). The results of electrocardiogram auto-analysis could not be used to confirm the diagnosis of WPW syndrome because of the atypical delta wave. Conduction via the right lateral AP caused electrical dyssynchrony in the LV. This case suggests that atypical delta waves should be evaluated without depending on electrocardiographic auto-analyses in patients with LV dysfunction accompanied by dyssynchrony. PMID:26336525

Immunological dysfunction in periparturient cows: evidence, causes and ramifications

USDA-ARS?s Scientific Manuscript database

With a $35.7 billion Gross Domestic Value for milk produced in the U.S. during 2007, the dairy industry was the largest commodity group of the 2007 U.S. animal agriculture economic engine. The economic value of controlling mastitis pathogens is immense. Most economic analyses of the cost of mastit...

Risk of Intimate Partner Violence among Young Adult Males with Childhood ADHD

ERIC Educational Resources Information Center

Wymbs, Brian; Molina, Brooke; Pelham, William; Cheong, JeeWon; Gnagy, Elizabeth; Belendiuk, Kat; Walther, Christine; Babinski, Dara; Waschbusch, Dan

2012-01-01

Objective: Research has clearly documented the social dysfunction of youth with ADHD. However, little is known about the interpersonal relationships of adults diagnosed with ADHD in childhood, including rates of intimate partner violence (IPV). Method: Using data from the Pittsburgh ADHD Longitudinal Study, analyses compared the level of IPV…

Neurotrophin Expression in Lymphocytes: a Powerful Indicator of Degeneration in Parkinson's Disease, Amyotrophic Lateral Sclerosis and Ataxia.

PubMed

Sadanand, Anjana; Janardhanan, Anjali; Vanisree, A J; Pavai, Thamil

2018-02-01

Deregulated neurotrophin is an etiological factor in the pathology of neurodegenerative diseases (ND) that are clinically different entities but characterised by similar limb dysfunction. Earlier validation of peripheral biomarkers can provide significant translational benefit to ND patients. We analysed brain-derived neurotrophic factor (BDNF)-tropomyosin possessing tyrosine-related kinase (Trk B) and its key downstream proteins which are implicated in ND such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and ataxia. Blood from ND patients with PD, ALS and Ataxia with movement dysfunctions were obtained to analyse mRNA and protein expressions of the above mentioned factors in lymphocytes. The mRNA and protein expression of BDNF-Trk B and its key downstream molecules showed a significant variation when compared to control and among NDs. The study intends to show that on identifying the variation of these key molecules in the blood samples of patients with ND can serve as early diagnostic candidates. Thus by intervening, the neurotrophins and their pathways can help in early diagnosis and optimising levels of diagnostic certainty.

[What the family doctor must know about lung transplantation. Complications, health promotion, and outcomes (Part 2)].

PubMed

Zurbano, L; Zurbano, F

2017-10-01

The lung transplantation is a therapeutic procedure indicated for lung diseases that are terminal and irreversible (except lung cancer) despite the best medical current treatment. It is an emergent procedure in medical care. In this review, an analyse is made of the most frequent complications of lung transplant related to the graft (rejection and chronic graft dysfunction), immunosuppression (infections, arterial hypertension, renal dysfunction, and diabetes), as well as others such as gastrointestinal complications, osteoporosis. The most advisable therapeutic options are also included. Specific mention is made of the reviews and follow-up for monitoring the graft and the patients, as well as the lifestyle recommended to improve the prognosis and quality of life. An analysis is also made on the outcomes in the Spanish and international registries, their historical evolution and the most frequent causes of death, in order to objectively analyse the usefulness of the transplant. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Application of updated guidelines on diastolic dysfunction in patients with severe sepsis and septic shock.

PubMed

Clancy, David J; Scully, Timothy; Slama, Michel; Huang, Stephen; McLean, Anthony S; Orde, Sam R

2017-12-19

Left ventricular diastolic dysfunction is suggested to be associated with higher mortality in severe sepsis and septic shock, yet the methods of diagnosis described in the literature are often inconsistent. The recently published 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) guidelines offer the opportunity to apply a simple pragmatic diagnostic algorithm for the detection of diastolic dysfunction; however, it has not been tested in this cohort. We sought to assess the applicability in septic patients of recently published 2016 ASE/EACVI guidelines on diastolic dysfunction compared with the 2009 ASE guidelines. Our hypothesis was that there would be poor agreement in classifying patients. Prospective observational study includes patients identified as having severe sepsis and septic shock. Patients underwent transthoracic echocardiography on day 1 and day 3 of their ICU admission. Patients with normal and abnormal (ejection fraction < 52%) systolic function had their diastolic function stratified according to both the 2009 ASE and 2016 ASE/EACVI guidelines. On day 1 echocardiography, of the 62 patients analysed, 37 (60%) had diastolic dysfunction according to the 2016 ASE/EACVI guideline with a further 23% having indeterminate diastolic function, compared to the 2009 ASE guidelines where only 13 (21%) had confirmed diastolic dysfunction with 46 (74%) having indeterminate diastolic dysfunction. On day 3, of the 55 patients studied, 22 patients (40%) were defined as having diastolic dysfunction, with 6 (11%) having indeterminate diastolic dysfunction according to the 2016 ASE/EACVI guidelines, compared to the 2009 guidelines where 11 (20%) were confirmed to have diastolic dysfunction and 41 (75%) had indeterminate diastolic function. Systolic dysfunction was identified in 18 of 62 patients (29%) on day 1 and 18 of 55 (33%) on day 3. These patients were classified as having abnormal diastolic function in 94 and 89% with the 2016 guidelines on day 1 and day 3, respectively, compared with 50 and 28% using the 2009 guidelines. The 2016 guidelines had less patients with indeterminate diastolic function on days 1 and 3 (11 and 6%) compared to the 2009 guidelines (50 and 72%). Normal systolic function was identified in 44 patients on day 1 and 37 on day 3. In this group, abnormal diastolic function was present in 45 and 54% on days 1 and 3 according to the 2016 ASE/EACVI guidelines, compared with 9 and 16% using the 2009 guidelines, respectively. In those with normal systolic function, the 2016 guidelines had less indeterminate patients with 30 and 16% on days 1 and 3, respectively, compared to 84 and 76% in the 2009 guidelines. The 2016 ASE/EACVI diastolic function guidelines identify a significantly higher incidence of dysfunction in patients with severe sepsis and septic shock compared to the previous 2009 guidelines. Although the new guidelines seem to be an improvement, issues remain with the application of guidelines using traditional measures of diastolic dysfunction in this cohort.

Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation.

PubMed

Matt, Stephanie M; Johnson, Rodney W

2016-02-01

Microglia, the resident immune cells of the brain, are at the center of communication between the central nervous system and immune system. While these brain-immune interactions are balanced in healthy adulthood, the ability to maintain homeostasis during aging is impaired. Microglia develop a loss of integrated regulatory networks including aberrant signaling from other brain cells, immune sensors, and epigenetic modifiers. The low-grade chronic neuroinflammation associated with this dysfunctional activity likely contributes to cognitive deficits and susceptibility to age-related pathologies. A better understanding of the underlying mechanisms responsible for neuro-immune dysregulation with age is crucial for providing targeted therapeutic strategies to support brain repair and healthy aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Focusing on situation-specific expectations in major depression as basis for behavioural experiments - Development of the Depressive Expectations Scale.

PubMed

Kube, Tobias; D'Astolfo, Lisa; Glombiewski, Julia A; Doering, Bettina K; Rief, Winfried

2017-09-01

Dysfunctional expectations are considered to be core features of various mental disorders. The aim of the study was to develop the Depressive Expectations Scale (DES) as a depression-specific measure for the assessment of dysfunctional expectations. Whereas previous research primarily focused on general cognitions and attitudes, the DES assesses 25 future-directed expectations (originally 75 items) which are situation-specific and falsifiable. To evaluate the psychometric properties of the DES, the scale was completed by 175 participants with and without severe depressive symptoms in an online survey. Participants additionally completed the Patient Health Questionnaire modules for depression (PHQ-9) and anxiety (GAD-7). People experiencing depressive symptoms were informed about the study with the help of self-help organizations. Reliability analyses indicated excellent internal consistency of the scale. An exploratory factor analyses revealed four factors: social rejection, social support, mood regulation, and ability to perform. The DES sum score strongly correlated with the severity of depressive symptoms. The DES sum score also significantly correlated with symptoms of generalized anxiety. The DES was shown to have excellent reliability; validity analyses were promising. As the DES items are situation-specific and falsifiable, they can be tested by the individual using behavioural experiments and may therefore facilitate cognitive restructuring. Thus, a structured assessment of patients' expectation with help of the DES can provide a basis for interventions within cognitive-behavioural treatment of depression. Assessing situation-specific expectations in patients experiencing depressive symptoms can provide a basis for the conduction of behavioural experiments to test patients' expectations. For the use of behavioural experiments, therapists should choose those dysfunctional expectations which a patient strongly agrees on. To modify patients' expectations, they should be exposed to situations where the discrepancy between patients' expectations and actual situational outcomes can be maximized. The Depressive Expectations Scale can be completed repeatedly to monitor a patient's progress within cognitive-behavioural treatment. © 2016 The British Psychological Society.

Contributing factors for therapeutic diet adherence in patients receiving haemodialysis treatment: an integrative review.

PubMed

Oquendo, Lissete González; Asencio, José Miguel Morales; de Las Nieves, Candela Bonill

2017-12-01

The objective of this integrative review is to identify the factors that contribute to diet adherence in people suffering from kidney disease who are receiving haemodialysis treatment. Adherence to the therapeutic regimen determines therapeutic success, quality of life and survival in patients on haemodialysis. Lack of diet adherence ranges from 25%-86% in patients receiving haemodialysis treatment and affects patient morbidity and mortality. An integrative literature review was conducted based on the criteria of Whittemore & Knafl. A literature review was performed by two members of the team using twelve databases including PubMed, CUIDEN, CINAHL, The Cochrane Library and ScienceDirect. The main issues identified after analysing the results were as follows: the intrinsic barriers (age, dialysis time, motivation, perceived benefit, distorted perception of adherence) and facilitators (self-efficacy, perception of disease, perception of control), extrinsic barriers (family dysfunction, lack of social support, cultural patterns of consumption of food) and facilitators (social support, relationship with healthcare providers), and interventions to encourage diet adherence, such as the use of motivational interviewing in educational interventions, and the training and education of relevant professionals in communication skills. Diet nonadherence remains a serious health problem and suffers from a lack of solid criteria to identify this condition. The onset of depression signs and the level of social support available to the patient should be assessed, because these are important factors that determine adherence to treatment. Professionals should be trained in health education and communication techniques to contribute to the patient's self-management and motivation for diet adherence. Controlled and randomised clinical studies involving predialysis stages should be performed to investigate the impact of the assessment and control of barriers to diet adherence. © 2017 John Wiley & Sons Ltd.

Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase

PubMed Central

Martin, Carolina; Leyton, Luis; Hott, Melissa; Arancibia, Yennyfer; Spichiger, Carlos; McNiven, Mark A.; Court, Felipe A.; Concha, Margarita I.; Burgos, Patricia V.; Otth, Carola

2017-01-01

Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance. Immunofluorescence analyses showed that HSV-1 productive neuronal infection caused a scattered and fragmented distribution of the GA through the cytoplasm, contrasting with the uniform perinuclear distribution pattern observed in control cells. In addition, transmission electron microscopy revealed swollen cisternae and disorganized stacks in HSV-1 infected neurons compared to control cells. Interestingly, PP2, a selective inhibitor for Src-family kinases markedly reduced these morphological alterations of the GA induced by HSV-1 infection strongly supporting the possible involvement of Src tyrosine kinase. Finally, we showed that HSV-1 tegument protein VP11/12 is necessary but not sufficient to induce Dyn2 phosphorylation. Altogether, these results show that HSV-1 neuronal infection triggers activation of Src tyrosine kinase, phosphorylation of Dynamin 2 GTPase, and perturbation of GA integrity. These findings suggest a possible neuropathogenic mechanism triggered by HSV-1 infection, which could involve dysfunction of the secretory system in neurons and central nervous system. PMID:28879169

Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase.

PubMed

Martin, Carolina; Leyton, Luis; Hott, Melissa; Arancibia, Yennyfer; Spichiger, Carlos; McNiven, Mark A; Court, Felipe A; Concha, Margarita I; Burgos, Patricia V; Otth, Carola

2017-01-01

Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen that establishes a latent persistent neuronal infection in humans. The pathogenic effects of repeated viral reactivation in infected neurons are still unknown. Several studies have reported that during HSV-1 epithelial infection, the virus could modulate diverse cell signaling pathways remodeling the Golgi apparatus (GA) membranes, but the molecular mechanisms implicated, and the functional consequences to neurons is currently unknown. Here we report that infection of primary neuronal cultures with HSV-1 triggers Src tyrosine kinase activation and subsequent phosphorylation of Dynamin 2 GTPase, two players with a role in GA integrity maintenance. Immunofluorescence analyses showed that HSV-1 productive neuronal infection caused a scattered and fragmented distribution of the GA through the cytoplasm, contrasting with the uniform perinuclear distribution pattern observed in control cells. In addition, transmission electron microscopy revealed swollen cisternae and disorganized stacks in HSV-1 infected neurons compared to control cells. Interestingly, PP2, a selective inhibitor for Src-family kinases markedly reduced these morphological alterations of the GA induced by HSV-1 infection strongly supporting the possible involvement of Src tyrosine kinase. Finally, we showed that HSV-1 tegument protein VP11/12 is necessary but not sufficient to induce Dyn2 phosphorylation. Altogether, these results show that HSV-1 neuronal infection triggers activation of Src tyrosine kinase, phosphorylation of Dynamin 2 GTPase, and perturbation of GA integrity. These findings suggest a possible neuropathogenic mechanism triggered by HSV-1 infection, which could involve dysfunction of the secretory system in neurons and central nervous system.

Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

PubMed

Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

2018-06-01

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy.

PubMed

A Yassine, Imane; M Eldeeb, Waleed; A Gad, Khaled; A Ashour, Yossri; A Yassine, Inas; O Hosny, Ahmed

2018-07-01

Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of an Integrated Sensorimotor Countermeasure Suite for Spaceflight Operations

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Batson, C. D.; Caldwell, E. E. (Inventor); Feiveson, A. H.; Kreutzberg, G. A.; Miller, C. A.; Mulavara, A. P.; Oddsson, L. I. E.; Peters, B. T.; Ploutz-Synder, L. L.;

Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

PubMed

Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

2016-02-01

Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Increased waist circumference is independently associated with hypothyroidism in Mexican Americans: replicative evidence from two large, population-based studies

PubMed Central

2014-01-01

Background Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans. Methods We conducted association testing for 18 MS traits in two large studies on Mexican Americans – the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007–10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007–10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) – a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007–10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions. Results TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007–10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007–10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age. Conclusions WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies. PMID:24913450

Increased waist circumference is independently associated with hypothyroidism in Mexican Americans: replicative evidence from two large, population-based studies.

PubMed

Mamtani, Manju; Kulkarni, Hemant; Dyer, Thomas D; Almasy, Laura; Mahaney, Michael C; Duggirala, Ravindranath; Comuzzie, Anthony G; Samollow, Paul B; Blangero, John; Curran, Joanne E

2014-06-10

Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans. We conducted association testing for 18 MS traits in two large studies on Mexican Americans - the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007-10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007-10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) - a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007-10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions. TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007-10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007-10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age. WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.

Rotigotine transdermal patch and sleep in Parkinson's disease: where are we now?

PubMed

Rosa-Grilo, Miguel; Qamar, Mubasher A; Taddei, Raquel N; Pagonabarraga, Javier; Kulisevsky, Jaime; Sauerbier, Anna; Chaudhuri, K Ray

2017-01-01

A wide range of sleep dysfunction complicates Parkinson's disease during its course from prodromal to palliative stage. It is now increasingly acknowledged that sleep disturbances are thus integral to the disease and pose a significant burden impacting on quality of life of patients. Sleep fragmentation, restless legs syndrome, nocturia, and nocturnal pain are regarded as one of the main components of night-time sleep dysfunction with possible secondary impact on cognition and well-being. The role of dopaminergic therapies, particularly using a continuous drug delivery strategy in managing some of these sleep issues, have been reported but the overall concept remains unclear. This review provides an overview of several aspects of night-time sleep dysfunction in Parkinson's disease and describes all available published open-label and blinded studies that investigated the use of rotigotine transdermal patch targeting sleep. Blinded studies have suggested beneficial effects of rotigotine transdermal patch on maintenance insomnia and restless legs syndrome in Parkinson's disease patients. Open-label studies support these observations and also suggest beneficial effects on nocturia and nocturnal pain.

Symptomatology associated with accommodative and binocular vision anomalies.

PubMed

García-Muñoz, Ángel; Carbonell-Bonete, Stela; Cacho-Martínez, Pilar

2014-01-01

To determine the symptoms associated with accommodative and non-strabismic binocular dysfunctions and to assess the methods used to obtain the subjects' symptoms. We conducted a scoping review of articles published between 1988 and 2012 that analysed any aspect of the symptomatology associated with accommodative and non-strabismic binocular dysfunctions. The literature search was performed in Medline (PubMed), CINAHL, PsycINFO and FRANCIS. A total of 657 articles were identified, and 56 met the inclusion criteria. We found 267 different ways of naming the symptoms related to these anomalies, which we grouped into 34 symptom categories. Of the 56 studies, 35 employed questionnaires and 21 obtained the symptoms from clinical histories. We found 11 questionnaires, of which only 3 had been validated: the convergence insufficiency symptom survey (CISS V-15) and CIRS parent version, both specific for convergence insufficiency, and the Conlon survey, developed for visual anomalies in general. The most widely used questionnaire (21 studies) was the CISS V-15. Of the 34 categories of symptoms, the most frequently mentioned were: headache, blurred vision, diplopia, visual fatigue, and movement or flicker of words at near vision, which were fundamentally related to near vision and binocular anomalies. There is a wide disparity of symptoms related to accommodative and binocular dysfunctions in the scientific literature, most of which are associated with near vision and binocular dysfunctions. The only psychometrically validated questionnaires that we found (n=3) were related to convergence insufficiency and to visual dysfunctions in general and there no specific questionnaires for other anomalies. Copyright © 2014. Published by Elsevier Espana.

Applying an Evidence-Based Assessment Model to Identify Students at Risk for Perceived Academic Problems following Concussion.

PubMed

Ransom, Danielle M; Burns, Alison R; Youngstrom, Eric A; Vaughan, Christopher G; Sady, Maegan D; Gioia, Gerard A

2016-11-01

The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Latent class analysis categorized participants into "high" (44%) and "low" (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038-1049).

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

Thyroid Function Abnormalities and Cognitive Impairment in the Elderly. Results of the InCHIANTI Study

PubMed Central

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M.; Cappola, Anne R.; Valenti, Giorgio; Ferrucci, Luigi

2008-01-01

Objectives To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Design Cross-sectional study Setting Community-based Participants 1171 men and women aged 23-102 yrs Measurements Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated by the Mini Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 versus ≥65 years). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association of thyroid dysfunction with MMSE score was evaluated adjusting for confounders. Results Both subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (Subclinical hypothyroidism, 0.4 % vs 3.5 % in younger vs older participants, respectively, P<.03 Subclinical hyperthyroidism, 1.9 % vs 7.8 % in younger vs older participants, respectively, P<.002). In euthyroid participants TSH and FT3 declined with age while FT4 increased. Old participants with subclinical hyperthyroidism had a lower MMSE score than euthyroid subjects (22.61 ± 6.88 vs 24.72 ± 4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (HR: 2.26, P= .003). Conclusion Subtle age-related changes in FT3, FT4 and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. PMID:19054181

The effects and prospects of the integration of traditional Chinese medicine and Western medicine on andrology in China.

PubMed

Ma, Wei-Guo; Jia, Jin-Ming

2011-07-01

Andrology has a long history in traditional Chinese medicine (TCM) discussions concerning andropathies, and documentation of relevant therapeutic methods abound in the ancient literature on TCM. Integrated treatment combining TCM and Western medicine has seen both broad and in-depth development, with formidable status in the field of modern andrology in China. This article attempts to demonstrate the unique advantage of integrated treatment in the therapy of andropathies through a review of the ancient literature on andrology in the field of TCM and on the integrative treatment of prostatic diseases, sexual dysfunction, male infertility and late-onset hypogonadism. There is a need for the advancement of a medical theory that integrates TCM and Western medicine practices to create a new therapeutic system with standardized therapeutic and evaluative protocols for diseases involving male sexual health.

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy.

PubMed

Sussman, Eric S; Kellner, Christopher P; Mergeche, Joanna L; Bruce, Samuel S; McDowell, Michael M; Heyer, Eric J; Connolly, E Sander

2014-09-01

Approximately 25% of patients exhibit cognitive dysfunction 24 hours after carotid endarterectomy (CEA). One of the purported mechanisms of early cognitive dysfunction (eCD) is hypoperfusion due to inadequate collateral circulation during cross-clamping of the carotid artery. The authors assessed whether poor collateral circulation within the circle of Willis, as determined by preoperative CT angiography (CTA) or MR angiography (MRA), could predict eCD. Patients who underwent CEA after preoperative MRA or CTA imaging and full neuropsychometric evaluation were included in this study (n = 42); 4 patients were excluded due to intraoperative electroencephalographic changes and subsequent shunt placement. Thirty-eight patients were included in the statistical analyses. Patients were stratified according to posterior communicating artery (PCoA) status (radiographic visualization of at least 1 PCoA vs of no PCoAs). Variables with p < 0.20 in univariate analyses were included in a stepwise multivariate logistic regression model to identify predictors of eCD after CEA. Overall, 23.7% of patients exhibited eCD. In the final multivariate logistic regression model, radiographic absence of both PCoAs was the only independent predictor of eCD (OR 9.64, 95% CI 1.43-64.92, p = 0.02). The absence of both PCoAs on preoperative radiographic imaging is predictive of eCD after CEA. This finding supports the evidence for an underlying ischemic etiology of eCD. Larger studies are justified to verify the findings of this study. Clinical trial registration no.: NCT00597883 ( http://www.clinicaltrials.gov ).

The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

PubMed

van Rijsbergen, M W A; Mark, R E; Kop, W J; de Kort, P L M; Sitskoorn, M M

2017-03-01

Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (β = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (β = -0.34, P < 0.001). Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke. © 2016 EAN.

Contributions of dysglycemia, obesity and insulin resistance to impaired endothelium-dependent vasodilation in humans

PubMed Central

Han, KA; Patel, Y; Lteif, AA; Chisholm, R; Mather, KJ

2011-01-01

Background Individual effects of hyperglycemia and obesity to impair vascular health are recognized. However, the relative contributions of dysglycemia versus other obesity-related traits to vascular dysfunction have not been systematically evaluated. Methods We undertook a cross-sectional evaluation of factors contributing to vascular function in 271 consecutive subjects, categorized as non-obese normal glucose tolerant (n=115), non-obese dysglycemic (n=32), obese normal glucose tolerant (n=57), obese dysglycemic (n=38), or type 2 diabetic (n=29). Vascular function was measured invasively as leg blood flow responses to methacholine chloride, an endothelium-dependent vasodilator. Categorical and continuous analyses were used to assess the contributions of hyperglycemia to vascular dysfunction. Results Even among normoglycemic subjects, obese subjects had impaired vascular function compared to non-obese subjects (p=0.004). Vascular function was also impaired in non-obese dysglycemic subjects (p=0.04 versus non-obese normoglycemic subjects), to a level comparable to normoglycemic obese subjects. Within obese subject groups, gradations of dysglycemia including the presence of diabetes were not associated with further worsening of these vascular responses beyond the effect of obesity alone (p=NS comparing all obese groups, p<0.001 versus lean normoglycemic subjects). In univariate and multivariable modeling analyses we found that effects of glycemia were less powerful than effects of insulin resistance and obesity on vascular dysfunction. Conclusions Dysglycemia contributes to impaired vascular function in non-obese subjects, but obesity and insulin resistance are more important determinants of vascular function in obese and diabetic subjects. PMID:21309061

Predictors of the Effect of Cognitive Behavioral Therapy for Chronic Insomnia Comorbid with Breast Cancer

ERIC Educational Resources Information Center

Tremblay, Valerie; Savard, Josee; Ivers, Hans

2009-01-01

Prior studies have supported the efficacy of cognitive behavioral therapy (CBT) for insomnia comorbid with cancer. This article reports secondary analyses that were performed on one of these studies to investigate the predictive role of changes in dysfunctional beliefs about sleep, adherence to behavioral strategies, and some nonspecific factors…

From Bingeing Booze Bird to Gilded Cage: Teaching Girls Gender and Class on "Ladette to Lady"

ERIC Educational Resources Information Center

Redden, Guy; Brown, Rebecca

2010-01-01

One genre of reality television constructs working-class youth as the dysfunctional antithesis of the aspirational middle-class consumer who normally features in lifestyle media. Sent to boot camps, unruly youths undergo makeover by education into ways of living deemed to accrue superior cultural capital. This article analyses how one lifestyle…

Introduction of a conceptual model for integrating the MMPI-2-RF into HCR-20V3 violence risk assessments and associations between the MMPI-2-RF and institutional violence.

PubMed

Tarescavage, Anthony M; Glassmire, David M; Burchett, Danielle

2016-12-01

Reflecting the need to prevent violence, structured professional judgment assessment tools have been developed specifically to assess the likelihood of future violence. These tools typically integrate data from clinical interviews and collateral records to assist in the conceptualization of violence risk, but objective psychological testing may also be useful in completing the instruments. The authors describe the advantages of using the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) in this manner with the Historical Clinical Management-20 Version 3 (HCR-20 V3 ). Accordingly, they have 2 purposes. First, they sought to identify conceptual links between the constructs measured by the tools and introduce a model to integrate MMPI-2-RF findings into an HCR-20 V3 risk assessment. Second, although the authors did not have collateral HCR-20 V3 ratings, they sought to examine associations between the MMPI-2-RF scales and future violence in a sample of 303 psychiatric patients (233 males, 70 females) adjudicated as not guilty by reason of insanity. The authors found that the MMPI-2-RF scales demonstrated significant, meaningful associations with a count of future violent acts at the hospital. The largest associations involved scales measuring emotional dysregulation and externalizing dysfunction. These associations were qualified by relative risk ratio analyses indicating that patients producing elevations on these scales were at 1.5 to 2.5 times greater risk of future violence than those without elevations. Overall, the findings indicated that most MMPI-2-RF scales conceptually linked to the HCR-20 V3 risk factors were associated with future violence. In light of these findings, the authors discuss recommendations for integrating the MMPI-2-RF when interpreting HCR-20 V3 risk factors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The adaptive significance of adult neurogenesis: an integrative approach

PubMed Central

Konefal, Sarah; Elliot, Mick; Crespi, Bernard

2013-01-01

Adult neurogenesis in mammals is predominantly restricted to two brain regions, the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting that these two brain regions uniquely share functions that mediate its adaptive significance. Benefits of adult neurogenesis across these two regions appear to converge on increased neuronal and structural plasticity that subserves coding of novel, complex, and fine-grained information, usually with contextual components that include spatial positioning. By contrast, costs of adult neurogenesis appear to center on potential for dysregulation resulting in higher risk of brain cancer or psychological dysfunctions, but such costs have yet to be quantified directly. The three main hypotheses for the proximate functions and adaptive significance of adult neurogenesis, pattern separation, memory consolidation, and olfactory spatial, are not mutually exclusive and can be reconciled into a simple general model amenable to targeted experimental and comparative tests. Comparative analysis of brain region sizes across two major social-ecological groups of primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large social groups) and solitary (mainly noctural, territorial, and highly reliant on olfaction, as in most rodents) suggest that solitary species, but not gregarious species, show positive associations of population densities and home range sizes with sizes of both the hippocampus and OB, implicating their functions in social-territorial systems mediated by olfactory cues. Integrated analyses of the adaptive significance of adult neurogenesis will benefit from experimental studies motivated and structured by ecologically and socially relevant selective contexts. PMID:23882188

Progress in Defining Disease: Improved Approaches and Increased Impact.

PubMed

Schwartz, Peter H

2017-08-01

In a series of recent papers, I have made three arguments about how to define "disease" and evaluate and apply possible definitions. First, I have argued that definitions should not be seen as traditional conceptual analyses, but instead as proposals about how to define and use the term "disease" in the future. Second, I have pointed out and attempted to address a challenge for dysfunction-requiring accounts of disease that I call the "line-drawing" problem: distinguishing between low-normal functioning and dysfunctioning. Finally, I have used a dysfunction-requiring approach to argue that some extremely prevalent conditions, such as high blood pressure, high cholesterol, and ductal carcinoma in situ, are not diseases, but instead are risk factors. Four of the papers in this issue directly engage my previous work. In this commentary, I applaud the advances these authors make, address points of disagreement, and make suggestions about where the discussion should go next. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Perceptual Training in Beach Volleyball Defence: Different Effects of Gaze-Path Cueing on Gaze and Decision-Making

PubMed Central

Klostermann, André; Vater, Christian; Kredel, Ralf; Hossner, Ernst-Joachim

2015-01-01

For perceptual-cognitive skill training, a variety of intervention methods has been proposed, including the so-called “color-cueing method” which aims on superior gaze-path learning by applying visual markers. However, recent findings challenge this method, especially, with regards to its actual effects on gaze behavior. Consequently, after a preparatory study on the identification of appropriate visual cues for life-size displays, a perceptual-training experiment on decision-making in beach volleyball was conducted, contrasting two cueing interventions (functional vs. dysfunctional gaze path) with a conservative control condition (anticipation-related instructions). Gaze analyses revealed learning effects for the dysfunctional group only. Regarding decision-making, all groups showed enhanced performance with largest improvements for the control group followed by the functional and the dysfunctional group. Hence, the results confirm cueing effects on gaze behavior, but they also question its benefit for enhancing decision-making. However, before completely denying the method’s value, optimisations should be checked regarding, for instance, cueing-pattern characteristics and gaze-related feedback. PMID:26648894

Parental and Family Factors as Predictors of Threat Bias in Anxious Youth

PubMed Central

Blossom, Jennifer B.; Ginsburg, Golda S.; Birmaher, Boris; Walkup, John T.; Kendall, Philip C.; Keeton, Courtney P.; Langley, Audra K.; Piacentini, John C.; Sakolsky, Dara; Albano, Anne Marie

2014-01-01

The present study examined the relative predictive value of parental anxiety, parents' expectation of child threat bias, and family dysfunction on child's threat bias in a clinical sample of anxious youth. Participants (N = 488) were part of the Child/Adolescent Anxiety Multi-modal study (CAMS), ages 7–17 years (M = 10.69; SD = 2.80). Children met diagnostic criteria for generalized anxiety disorder, separation anxiety and/or social phobia. Children and caregivers completed questionnaires assessing child threat bias, child anxiety, parent anxiety and family functioning. Child age, child anxiety, parental anxiety, parents' expectation of child's threat bias and child-reported family dysfunction were significantly associated with child threat bias. Controlling for child's age and anxiety, regression analyses indicated that parents' expectation of child's threat bias and child-reported family dysfunction were significant positive predictors of child's self-reported threat bias. Findings build on previous literature by clarifying parent and family factors that appear to play a role in the development or maintenance of threat bias and may inform etiological models of child anxiety. PMID:25328258

The management of patients with aortic regurgitation and severe left ventricular dysfunction: a systematic review.

PubMed

Badar, Athar A; Brunton, Alan P T; Mahmood, Ammad H; Dobbin, Stephen; Pozzi, Andrea; McMinn, Jenna F; Sinclair, Andrew J E; Gardner, Roy S; Petrie, Mark C; Curry, Phil A; Al-Attar, Nawwar H K; Pettit, Stephen J

2015-01-01

A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

Gender differences in eating behavior and eating pathology: The mediating role of rumination.

PubMed

Opwis, Mareile; Schmidt, Jennifer; Martin, Alexandra; Salewski, Christel

2017-03-01

Rumination is a maladaptive emotion regulation strategy which contributes to psychopathology and is more frequently used by women than men. It has been found to mediate the relationship between gender and the occurrence of anxiety disorders or depression. Since gender differences also appear in dysfunctional eating, the aim of the study is to test, whether rumination mediates the association between gender and several facets of eating pathology. A total of 295 participants (205 women) completed an online-questionnaire including the assessment of different facets of dysfunctional eating and rumination. Mediation analyses were conducted with PROCESS. Women reported significantly higher levels in both, rumination and eating pathology. Moreover, rumination mediated the relationship between gender and all assessed aspects of dysfunctional eating. The present study extends findings on the mediating role of rumination accounting for gender differences in psychopathology to eating pathology in a community sample. Results suggest that cognitive factors play a substantial role in explaining gender differences in eating pathology which tend to be reduced to biologicals factors and beauty ideals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dysfibrinogen Kagoshima with the amino acid substitution gammaThr-314 to Ile: analyses of molecular abnormalities and thrombophilic nature of this abnormal molecule.

PubMed

Niwa, Kazuki; Mimuro, Jun; Miyata, Masaaki; Sugo, Teruko; Ohmori, Tsukasa; Madoiwa, Seiji; Tei, Chuwa; Sakata, Yoichi

2008-01-01

Emerging lines of evidence have suggested that certain dysfibrinogens present a significant risk of thrombosis. The thrombophilic nature of a new-type of dysfibrinogen Kagoshima identified in a 36-year-old female with deep vein thrombosis during the postpartum period was studied. Based on the analyses of the patient fibrinogen and the fibrinogen genes, fibrinogen Kagoshima was shown to have the amino acid substitution of gammaThr-314 to Ile that resulted in impaired function and hypofibrinogenemia. Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium ions, causing very low clottability and delayed cross-linking of patient fibrin catalyzed by activated factor XIII. Because of the low clottability, a large amount of soluble fibrin was formed upon thrombin treatment, resulting in an increase of thrombin in the soluble fraction. Additionally, tPA-mediated plasmin generation on fibrin was impaired and calcium-ion-dependent integrity of the gamma-chain D domain of Kagoshima fibrinogen was perturbed. The presence of many tapered-fiber ends inside the tangled fibrin networks, observed by scanning electron microscopy, suggested early termination of fibrin polymerization and the structural alteration. These data suggest that fibrinogen Kagoshima is dysfunctional, giving rise to formation of fibrinolysis-resistant soluble fibrin polymers and entrance of soluble fibrin associating with thrombin to the circulation, partly accounting for the thrombophilic nature of the affected fibrinogen and fibrin molecules.

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

PubMed

Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Standard operating procedures for neurophysiologic assessment of male sexual dysfunction.

PubMed

Giuliano, Francois; Rowland, David L

2013-05-01

Can neurophysiological testing in male patients with sexual dysfunction benefit the decision-making process? The answer remains unclear. To provide standard operating procedures for the neurophysiologic assessment of male sexual dysfunction. Medical literature was reviewed and combined with expert opinion of the authors. Bulbocavernosus reflex latency time, pudendal somatosensory evoked potentials, and sympathetic skin responses have been considered as potential candidates for the diagnosis and assessment of erectile dysfunction (ED). Currently, there is no consensus on a standardized methodology for these neurophysiological investigations in the overall assessment of ED. These procedures are unable to assess the integrity of the efferent parasympathetic proerectile penile innervation; accordingly, none of these assessment procedures is recommended for ED patients. Corpus cavernosum electromyography (CC-EMG) can detect abnormalities in cavernous smooth muscle although these alterations can be attributed both to damage to autonomic penile innervation and to degenerative processes of the cavernous smooth muscle. CC-EMG is still considered experimental. Evidence does not support that men with premature ejaculation (PE) are consistently characterized by penile hypersensitivity; accordingly, penile threshold determination is not recommended to in the diagnosis of PE. Neurophysiological investigation of other components of the penile sensory pathways in PE patients has not provided any definitive contribution to the diagnosis. No neurophysiological assessment procedures yield additional information that consistently aids in the assessment of PE and ED. © 2013 International Society for Sexual Medicine.

EEG evidence for mirror neuron dysfunction in autism spectrum disorders.

PubMed

Oberman, Lindsay M; Hubbard, Edward M; McCleery, Joseph P; Altschuler, Eric L; Ramachandran, Vilayanur S; Pineda, Jaime A

2005-07-01

Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.

Treatment Approaches for Interoceptive Dysfunctions in Drug Addiction

PubMed Central

Paulus, Martin P.; Stewart, Jennifer L.; Haase, Lori

2013-01-01

There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g., adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature showing that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a insula changes that may provide a window to attenuate the increased interoceptive response to drug-related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction. PMID:24151471

Treatment approaches for interoceptive dysfunctions in drug addiction.

PubMed

Paulus, Martin P; Stewart, Jennifer L; Haase, Lori

2013-10-18

There is emerging evidence that individuals with drug addiction have dysfunctions in brain systems that are important for interoceptive processing, which include, among others, the insular and the anterior cingulate cortices. These individuals may not be expending sufficient neural resources to process perturbations of the interoceptive state but may exert over-activation of these systems when processing drug-related stimuli. As a consequence, insufficient detection and processing of interoceptive state changes may result in inadequate anticipation and preparation to adapt to environmental challenges, e.g., adapt to abstinence in the presence of withdrawal symptoms. Here, we integrate interoceptive dysfunction in drug-addicted individuals, with the neural basis for meditation and exercise to develop a heuristic to target the interoceptive system as potential treatments for drug addiction. First, it is suggested that mindfulness-based approaches can modulate both interoceptive function and insular activation patterns. Second, there is an emerging literature showing that the regulation of physical exercise in the brain involves the insula and anterior cingulate cortex and that intense physical exercise is associated with a insula changes that may provide a window to attenuate the increased interoceptive response to drug-related stimuli. It is concluded that the conceptual framework of interoceptive dysfunctions in drug addiction and the experimental findings in meditation and exercise provide a useful approach to develop new interventions for drug addiction.

Empirical evidence of cognitive vulnerability for depression among children and adolescents: A cognitive science and developmental perspective

PubMed Central

Jacobs, Rachel H.; Reinecke, Mark A.; Gollan, Jackie K.; Kane, Peter

2008-01-01

We summarize and integrate research on cognitive vulnerability to depression among children and adolescents. We first review prospective longitudinal studies of the most researched cognitive vulnerability factors (attributional style, dysfunctional attitudes, and self-perception) and depression among youth. We next review research on information processing biases in youth. We propose that the integration of these two literatures will result in a more adequate test of cognitive vulnerability models. Last, we outline a program of research addressing methodological, statistical, and scientific limitations in the cognitive vulnerability literature. PMID:18068882

Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis.

PubMed

Ferret-Sena, Véronique; Capela, Carlos; Sena, Armando

2018-06-01

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) probably caused, in most cases, by the interaction of genetic and environmental factors. This review first summarizes some clinical, epidemiological and pathological characteristics of MS. Then, the involvement of biochemical pathways is discussed in the development and repair of the CNS lesions and the immune dysfunction in the disease. Finally, the potential roles of peroxisome proliferator-activated receptors (PPAR) in MS are discussed. It is suggested that metabolic mechanisms modulated by PPAR provide a window to integrate the systemic and neurological events underlying the pathogenesis of the disease. In conclusion, the reviewed data highlight molecular avenues of understanding MS that may open new targets for improved therapies and preventive strategies for the disease.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response.

PubMed

Zhong, Hong; Ma, Minjuan; Liang, Tingming; Guo, Li

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction.

Mitochondrial dysfunction as a trigger of innate immune responses and inflammation.

PubMed

West, A Phillip

2017-11-01

A growing literature indicates that mitochondria are key participants in innate immune pathways, functioning as both signaling platforms and contributing to effector responses. In addition to regulating antiviral signaling and antibacterial immunity, mitochondria are also important drivers of inflammation caused by sterile injury. Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system. When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases. Here, I review the emerging knowledge of mitochondrial dysfunction in innate immune responses and discuss how environmental exposures may induce mitochondrial damage to potentiate inflammation and human disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of MicroRNAs in Obesity-Induced Metabolic Disorder and Immune Response

PubMed Central

Zhong, Hong; Ma, Minjuan

2018-01-01

In all living organisms, metabolic homeostasis and the immune system are the most fundamental requirements for survival. Recently, obesity has become a global public health issue, which is the cardinal risk factor for metabolic disorder. Many diseases emanating from obesity-induced metabolic dysfunction are responsible for the activated immune system, including innate and adaptive responses. Of note, inflammation is the manifest accountant signal. Deeply studied microRNAs (miRNAs) have participated in many pathways involved in metabolism and immune responses to protect cells from multiple harmful stimulants, and they play an important role in determining the progress through targeting different inflammatory pathways. Thus, immune response and metabolic regulation are highly integrated with miRNAs. Collectively, miRNAs are the new targets for therapy in immune dysfunction. PMID:29484304

PubMed

Madeira, João; Parreira, Leonor; Amador, Pedro; Soares, Luís

2013-10-14

Riata and Riata ST silicone defibrillation leads are prone to externalization of conductors due to inside-out abrasion in the high-voltage system, causing structural damage which may be accompanied by electrical failure. These situations are easily detected by fluoroscopy or radiology and by inspection of intracardiac electrograms and/or measurement of impedance. However, older pulse generators do not automatically perform all the measurements needed to assess the integrity of the high-voltage electrical system, nor do they have patient notifier alerts in case of dysfunction. The authors describe the case of a patient in whom structural damage was detected on fluoroscopy during pulse generator replacement. They discuss the best strategy in these patients, considering current knowledge of this dysfunction. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial.

PubMed

Clayton, Anita H; Gommoll, Carl; Chen, Dalei; Nunez, Rene; Mathews, Maju

2015-07-01

Sexual dysfunction commonly occurs with major depressive disorder (MDD). Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist antidepressant approved for the treatment of MDD in adults, was evaluated to determine its effects on sexual function. The primary study was a double-blind, randomized, controlled trial comparing vilazodone 20 and 40 mg/day with placebo; citalopram 40 mg/day was an active control (NCT01473381; http://www.clinicaltrials.gov). Post-hoc analyses evaluated change from baseline to week 10 on the Changes in Sexual Functioning Questionnaire (CSFQ); no inferential statistics were performed. CSFQ scores increased for women [1.2 (citalopram) to 3.0 (vilazodone 40 mg)] and men [1.2 (vilazodone 40 mg) to 3.5 (placebo)] in all treatment groups. Greater changes in CSFQ scores were seen in responders [women: 2.33 (citalopram) to 5.06 (vilazodone 40 mg); men: 2.26 (vilazodone 40 mg) to 4.35 (placebo)] versus nonresponders. CSFQ change from baseline was small for patients with normal baseline sexual function; in patients with baseline sexual dysfunction, CSFQ scores improved across groups [women: 2.35 (citalopram) to 4.52 (vilazodone 40 mg); men 2.83 (vilazodone 40 mg) to 6.43 (placebo)]. Across treatment groups, baseline sexual function improved in women and men, MDD responders, and patients with baseline sexual dysfunction.

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Case report: severe heat stroke with multiple organ dysfunction – a novel intravascular treatment approach

PubMed Central

Broessner, Gregor; Beer, Ronny; Franz, Gerhard; Lackner, Peter; Engelhardt, Klaus; Brenneis, Christian; Pfausler, Bettina; Schmutzhard, Erich

2005-01-01

Introduction We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. Methods A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Results Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard® and CoolLine®) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. Conclusion In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result. PMID:16285034

Murder and psychosis: Neuropsychological profiles of homicide offenders with schizophrenia.

PubMed

Stratton, John; Brook, Michael; Hanlon, Robert E

2017-04-01

Neurocognitive dysfunction, a core feature of schizophrenia, is thought to contribute to the impulsive violent aggression manifested by some individuals with schizophrenia, but not enough is known about how homicidal individuals with schizophrenia perform on neuropsychological measures. The primary aim of our study was to describe the neuropsychological profiles of homicide offenders with schizophrenia. Supplementary analyses compared the criminal, psychiatric and neuropsychological features of schizophrenic homicide offenders with and without God/Satan/demon-themed psychotic symptoms. Twenty-five men and women diagnosed with schizophrenia who had killed another person - 21 convicted of first-degree murder and 4 found not guilty by reason of insanity - completed neuropsychological testing during forensic evaluations. The sample was characterised by extensive neurocognitive impairments, involving executive dysfunction (60%), memory dysfunction (68%) and attentional dysfunction (50%), although those with God/Satan/demon-themed psychotic symptoms performed better than those with nonreligious psychotic content. Our findings indicate that impaired cognition may play an important role in the commission of homicide by individuals with schizophrenia. A subgroup with God/Satan/demon delusions seem sufficiently less impaired that they might be able to engage in metacognitive treatment approaches, aimed at changing their relationship to their psychotic symptoms, thus reducing the perception of power and omnipotence of hallucinated voices and increasing their safety. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

PubMed

Di Paola, Margherita; Phillips, Owen; Costa, Alberto; Ciurli, Paola; Bivona, Umberto; Catani, Sheila; Formisano, Rita; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-01-01

Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. Neuropsychological scores and hippocampal volumes. We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

PubMed Central

Bradley, Kailyn A. L.; Mao, Xiangling; Case, Julia A. C.; Kang, Guoxin; Shungu, Dikoma C.; Gabbay, Vilma

2016-01-01

Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID:26802978

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

PubMed Central

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

Obsessive-compulsive disorder. Diagnosis and management.

PubMed Central

Ladouceur, R.; Freeston, M.; Gagnon, F.

1996-01-01

We present three diagnostic tools to identify overt compulsive rituals, obsessional thinking, and neutralizing behaviours in obsessive-compulsive disorder (OCD) and describe the most effective cognitive-behavioural technique for treating obsessional thinking without overt rituals. Basic dysfunctional beliefs that lead to OCD are explained and integrated in the treatment model. We suggest how combined therapy can be used to tread OCD. PMID:8704492

Preserved Self-Other Distinction during Empathy in Autism Is Linked to Network Integrity of Right Supramarginal Gyrus

ERIC Educational Resources Information Center

Hoffmann, Ferdinand; Koehne, Svenja; Steinbeis, Nikolaus; Dziobek, Isabel; Singer, Tania

2016-01-01

Autism spectrum disorder (ASD) shows deficits in self-other distinction during theory of mind (ToM). Here we investigated whether ASD patients also show difficulties in self-other distinction during empathy and if potential deficits are linked to dysfunctional resting-state connectivity patterns. In a first study, ASD patients and controls…

Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes.

PubMed

Wolters, Jarno E J; van Breda, Simone G J; Grossmann, Jonas; Fortes, Claudia; Caiment, Florian; Kleinjans, Jos C S

2018-06-01

We performed a multiple 'omics study by integrating data on epigenomic, transcriptomic, and proteomic perturbations associated with mitochondrial dysfunction in primary human hepatocytes caused by the liver toxicant valproic acid (VPA), to deeper understand downstream events following epigenetic alterations in the mitochondrial genome. Furthermore, we investigated persistence of cross-omics changes after terminating drug treatment. Upon transient methylation changes of mitochondrial genes during VPA-treatment, increasing complexities of gene-interaction networks across time were demonstrated, which normalized during washout. Furthermore, co-expression between genes and their corresponding proteins increased across time. Additionally, in relation to persistently decreased ATP production, we observed decreased expression of mitochondrial complex I and III-V genes. Persistent transcripts and proteins were related to citric acid cycle and β-oxidation. In particular, we identified a potential novel mitochondrial-nuclear signaling axis, MT-CO2-FN1-MYC-CPT1. In summary, this cross-omics study revealed dynamic responses of the mitochondrial epigenome to an impulse toxicant challenge resulting in persistent mitochondrial dysfunctioning. Moreover, this approach allowed for discriminating between the toxic effect of VPA and adaptation. Copyright © 2018 Elsevier B.V. All rights reserved.

New insights into the gut as the driver of critical illness and organ failure.

PubMed

Meng, Mei; Klingensmith, Nathan J; Coopersmith, Craig M

2017-04-01

The gut has long been hypothesized to be the 'motor' of multiple organ dysfunction syndrome. This review serves as an update on new data elucidating the role of the gut as the propagator of organ failure in critical illness. Under basal conditions, the gut absorbs nutrients and serves as a barrier that prevents approximately 40 trillion intraluminal microbes and their products from causing host injury. However, in critical illness, gut integrity is disrupted with hyperpermeability and increased epithelial apoptosis, allowing contamination of extraluminal sites that are ordinarily sterile. These alterations in gut integrity are further exacerbated in the setting of preexisting comorbidities. The normally commensal microflora is also altered in critical illness, with increases in microbial virulence and decreases in diversity, which leads to further pathologic responses within the host. All components of the gut are adversely impacted by critical illness. Gut injury can not only propagate local damage, but can also cause distant injury and organ failure. Understanding how the multifaceted components of the gut interact and how these are perturbed in critical illness may play an important role in turning off the 'motor' of multiple organ dysfunction syndrome in the future.

MONITORING OF WATERWAYS FOR EMERGING ...

EPA Pesticide Factsheets

Assessing the potential impact to the aquatic environment from emerging contaminants, entails monitoring a complex mixture (pharmaceuticals, polar pesticides, industrial by- products and degradation products) in natural waters. The presence of these chemicals, often at ultra-trace levels, may be responsible for development of sub-lethal toxic effects in aquatic organisms (i.e., reproductive dysfunction, immune dysfunction, neurological disorders). Conventional sampling techniques (i.e., grab sampling) often are insufficient for detecting these trace levels. An integrative sampler, the Polar Organic Chemical Integrative Sampler (POCIS), developed by the USGS Columbia Environmental Research Center, provided a way to measure the time-weighted average concentrations of these complex mixtures of contaminants. When POCIS was combined with liquid chromatography/mass spectrometry (LC/MS), it proved to be a powerful tool in identification and quantification of polar anthropogenic contaminants. Data from a pilot study showed the antibiotic azithromycin, illicit drugs [methamphetamine and MDMA (Ecstasy)], polyfluorinated organic acids (PFOA and PFOS) (essential ingredients in the manufacture of fluoropolymers), and surfactants [i.e., diethanolamine polyethylene glycols (DAPGs), polyethylene glycols (PEGs), and nonylphenol ethoxylates (NPEOs)] were all present in the extracts from the effluents of three wastewater treatment plants and other bodies of natural waters. Althoug

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.

PubMed

Gao, Jin-Hang; Wen, Shi-Lei; Tong, Huan; Wang, Chun-Hui; Yang, Wen-Juan; Tang, Shi-Hang; Yan, Zhao-Ping; Tai, Yang; Ye, Cheng; Liu, Rui; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Tang, Cheng-Wei

2016-06-01

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis. Copyright © 2016 the American Physiological Society.

Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats.

PubMed

Qiu, Linan; Luo, Yuju; Chen, Xiaojuan

2018-07-01

Despite the severity of osteoarthritis (OA), current medical therapy strategies for OA aim at symptom control and pain reduction, as there is no ideal drug for effective OA treatment. OA rat model was used to explore the therapeutic function of quercetin on remission of OA, by determining the reactive oxygen species (ROS) levels, mitochondrial function and extracellular matrix integrity. Quercetin could attenuate ROS generation and augment the glutathione (GSH) and glutathione peroxidase (GPx) expression levels in OA rat. Quercetin not only enhanced mitochondrial membrane potential, oxygen consumption, adenosine triphosphate (ATP) levels in mitochondria, but also increased the mitochondrial copy number. Furthermore, the interlukin (IL)-1β-induced accumulation of nitric oxide (NO), matrixmetalloproteinase (MMP)-3) and MMP-13 could be suppressed by quercetin. Finally, we confirmed that the therapeutic properties of quercetin on OA might function through the adenosine monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1) signaling pathway. In summary, quercetin could alleviate OA through attenuating the ROS levels, reversing the mitochondrial dysfunction and keeping the integrality of extracellular matrix of joint cartilage. The underlying mechanism might involve the regulation of AMPK/SIRT1 signaling pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

A prospective study on association of prostatic calcifications with sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

PubMed

Zhao, Zhigang; Xuan, Xujun; Zhang, Jingwei; He, Jun; Zeng, Guohua

2014-10-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common debilitating condition of unclear etiology. Sexual dysfunction is an important component of the clinical phenotype of CP/CPPS. Patients often have prostatic calcifications, but a link to sexual dysfunction is unknown. The aim of this study was to evaluate the association of prostatic calcifications with sexual dysfunction in this condition. A total of 358 males with CP/CPPS were consecutively enrolled, and a prospectively maintained database of these patients was analyzed. Calcifications were diagnosed using ultrasound imaging of the prostate. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (CPSI). Sexual dysfunction was evaluated using the validated 15-item International Index of Erectile Function (IIEF-15) questionnaire and 5-item Premature Ejaculation Diagnostic Tool scales. The variables were compared between patients with prostatic calcifications and those without using the Student's t-test, Wilcoxon unpaired test, or chi-square test. Logistic regression models were developed to explore a possible association between prostatic calcifications and sexual dysfunction. Measurable calcifications in the prostate were found in 175 (48.9%) of the 358 patients. Patients with calcifications were more likely to have higher white blood cell counts or positive bacteria cultures in their prostatic fluid, longer symptoms duration, and lower scores for the total IIEF-15, IIEF-erectile function, and IIEF-intercourse satisfaction domains (P < 0.001 for each). However, the scores for CPSI, premature ejaculation, and IIEF-orgasmic function, IIEF-sexual desire, and IIEF-overall satisfaction domains were identical between men with and without calcifications (P > 0.05 for each). Furthermore, logistic regression analyses revealed that intraprostatic calcification is significantly associated with self-assessed erectile dysfunction (ED) (odds ratio:3.632, 95% confidence interval: 2.405-5.822, P < 0.001). Our results showed that prostatic calcifications are significantly associated with the presence of ED in CP/CPPS males. © 2014 International Society for Sexual Medicine.

Right ventricular systolic dysfunction and vena cava dilatation precede alteration of renal function in adult patients undergoing cardiac surgery: An observational study.

PubMed

Guinot, Pierre Grégoire; Abou-Arab, Osama; Longrois, Dan; Dupont, Herve

2015-08-01

Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients. We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms. A single-centre, prospective observational study. Amiens University Hospital, France. All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed. Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1. All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI). These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

Enhancement of the Initial Rate of Ethanol Fermentation Due to Dysfunction of Yeast Stress Response Components Msn2p and/or Msn4p▿ †

PubMed Central

Watanabe, Daisuke; Wu, Hong; Noguchi, Chiemi; Zhou, Yan; Akao, Takeshi; Shimoi, Hitoshi

2011-01-01

Sake yeasts (strains of Saccharomyces cerevisiae) produce high concentrations of ethanol in sake fermentation. To investigate the molecular mechanisms underlying this brewing property, we compared gene expression of sake and laboratory yeasts in sake mash. DNA microarray and reporter gene analyses revealed defects of sake yeasts in environmental stress responses mediated by transcription factors Msn2p and/or Msn4p (Msn2/4p) and stress response elements (STRE). Furthermore, we found that dysfunction of MSN2 and/or MSN4 contributes to the higher initial rate of ethanol fermentation in both sake and laboratory yeasts. These results provide novel insights into yeast stress responses as major impediments of effective ethanol fermentation. PMID:21131516

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

PubMed Central

Merrill, Liana

2014-01-01

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant (P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant (P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 μM), a TRPV4 antagonist, HC067047 (1 μM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly (P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders. PMID:24965792

Low prevalence of renal dysfunction in HIV-infected pregnant women: implications for guidelines for the prevention of mother-to-child transmission of HIV.

PubMed

Myer, Landon; Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail

2013-11-01

Emerging international guidelines for the prevention of mother-to-child transmission of HIV infection across sub-Saharan Africa call for the initiation of a triple-drug antiretroviral regimen containing tenofovir, a potentially nephrotoxic agent, in all HIV-infected pregnant women at the first antenatal clinic visit. While there are significant benefits to the rapid initiation of antiretroviral therapy (ART) in pregnancy, there are few data on the prevalence of pre-existing renal disease in HIV-infected pregnant women and in turn, the potential risks of this approach are not well understood. We analysed data on renal function in consecutive patients eligible for ART at a large primary healthcare clinic in Cape Town. All individuals were screened for renal dysfunction via serum creatinine and estimation of creatinine clearance via the Cockroft-Gault equation. Over a 2-year period, 238 pregnant women, 1014 non-pregnant women and 609 men were screened to initiate ART. Pregnant women eligible were significantly younger, in earlier stages of HIV disease, had higher CD4 cell counts and lower HIV viral loads, than non-pregnant adults. The median serum creatinine in pregnant women (46 µmol/L) was significantly lower and the median creatinine clearance (163 ml/min/1.73 m(2) ) was significantly higher than other groups (P < 0.001 and P = 0.004, respectively). Fewer than 1% of pregnant women had moderate renal dysfunction before ART initiation, with no instances of severe dysfunction observed, compared to 7% moderate or severe renal dysfunction in non-pregnant women or men (P < 0.001). Renal dysfunction in HIV-infected pregnant women is significantly less common than in other HIV-infected adults eligible for ART. The risks associated with initiating tenofovir immediately in pregnant women before reviewing serum creatinine results may be limited, and the benefits of rapid ART initiation in pregnancy may outweigh possible risks of nephrotoxicity. © 2013 John Wiley & Sons Ltd.

Protein Changes Contributing to Right Ventricular Cardiomyocyte Diastolic Dysfunction in Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Bos, Denielli da Silva Goncalves; Handoko, M. Louis; Westerhof, Nico; Stienen, Ger; Ottenheijm, Coen; Goebel, Max; Dorfmüller, Peter; Guignabert, Christophe; Humbert, Marc; Bogaard, Harm‐Jan; dos Remedios, Cris; Saripalli, Chandra; Hidalgo, Carlos G.; Granzier, Henk L.; Vonk‐Noordegraaf, Anton; van der Velden, Jolanda; de Man, Frances S.

2014-01-01

Background Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results RV samples from PAH patients undergoing heart‐lung transplantation were compared to non‐failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western‐blot analyses using antibodies to protein‐kinase‐A (PKA), Cα (PKCα) and Ca2+/calmoduling‐dependent‐kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA‐, PKCα‐, and CamKIIδ‐mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIIδ activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA‐mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca2+‐handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05). Conclusions Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2+ handling proteins contribute to RV diastolic dysfunction in PAH. PMID:24895160

Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats

PubMed Central

Musicki, Biljana; Hannan, Johanna L.; Lagoda, Gwen; Bivalacqua, Trinity J.; Burnett, Arthur L.

2016-01-01

Men with type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) have greater risk of cardiovascular events than T2DM men without ED, suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2DM involves earlier redox imbalance and endothelial nitric oxidase synthase (eNOS) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2DM by high-fat diet for 2 weeks, followed by an injection with low-dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S-glutathionylation, oxidative stress (4-hydroxy-2-nonenal, 4-HNE), protein expression of NADPH oxidase subunit gp91phox, endothelium-dependent vasodilation in the carotid artery, and non-andrenergic, non-cholinergic (NANC) mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC mediated cavernosal relaxation were decreased (p<0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2DM rats. eNOS monomerization, protein expressions of 4-HNE and gp91phox, and protein S-glutathionylation, were increased (p<0.05) in the penis, but not in the carotid artery, of T2DM compared to nondiabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2DM in the penis, but not in the carotid artery. These molecular changes contribute to T2DM ED, while vascular function in the systemic vasculature remains preserved. PMID:27153512

Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study.

PubMed

van Bussel, B C T; Henry, R M A; Schalkwijk, C G; Dekker, J M; Nijpels, G; Feskens, E J M; Stehouwer, C D A

2018-06-01

Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals. Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups. Moderate [β (95% CI) -0.13 (-0.33; 0.07)] and high [-0.22 (-0.45; -0.003)] alcohol consumption, and red wine [-0.16 (-0.30; -0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [-0.18 (-0.33; -0.04)]. Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis.

Remote Traumatic Brain Injury Is Associated with Motor Dysfunction in Older Military Veterans.

PubMed

Gardner, Raquel C; Peltz, Carrie B; Kenney, Kimbra; Covinsky, Kenneth E; Diaz-Arrastia, Ramon; Yaffe, Kristine

2017-09-01

Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD. This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year. In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function. Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prevalence of 'obesity-associated gonadal dysfunction' in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis.

PubMed

Escobar-Morreale, Hector F; Santacruz, Elisa; Luque-Ramírez, Manuel; Botella Carretero, José I

2017-07-01

Sexual dimorphism manifests noticeably in obesity-associated gonadal dysfunction. In women, obesity is associated with androgen excess disorders, mostly the polycystic ovary syndrome (PCOS), whereas androgen deficiency is frequently present in obese men in what has been termed as male obesity-associated secondary hypogonadism (MOSH). Obesity-associated gonadal dysfunction, consisting of PCOS in women and MOSH in men, is a frequent finding in patients with severe obesity and it may be ameliorated or even resolve with marked weight loss, especially after bariatric surgery. We aimed to obtain an estimation of the prevalence of obesity-associated gonadal dysfunction among women and men presenting with severe obesity and to evaluate the response to bariatric surgery in terms of resolution and/or improvement of this condition and changes in circulating sex hormone concentrations. We searched PubMed and EMBASE for articles published up to June 2016. After deleting duplicates, the abstract of 757 articles were analyzed. We subsequently excluded 712 articles leaving 45 studies for full-text assessment of eligibility. Of these, 16 articles were excluded. Hence, 29 studies were included in the quantitative synthesis and in the different meta-analyses. Quality of the studies was assessed using the Quality index for prevalence studies and the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group available from the National Heart, Lung and Blood Institute. For meta-analyses including more than 10 studies, we used funnel and Doi plots to estimate publication bias. In severely obese patients submitted to bariatric surgery, obesity-associated gonadal dysfunction was very prevalent: PCOS was present in 36% (95CI 22-50) of women and MOSH was present in 64% (95CI 50-77) of men. After bariatric surgery, resolution of PCOS was found in 96% (95CI 89-100) of affected women and resolution of MOSH occurred in 87% (95CI 76-95) of affected men. Sex hormone-binding globulin concentrations increased after bariatric surgery in women (22 pmol/l, 95CI 2-47) and in men (22 pmol/l, 95CI 19-26) and serum estradiol concentrations decreased in women (-104 pmol/l, 95CI -171 to -39) and to a lesser extent in men (-22 pmol/l, 95CI -38 to -7). On the contrary, sex-specific changes were observed in serum androgen concentrations: for example, total testosterone concentration increased in men (8.1 nmol/l, 95CI 6-11) but decreased in women (-0.7 nmol/l, 95CI -0.9 to -0.5). The latter was accompanied by resolution of hirsutism in 53% (95CI 29-76), and of menstrual dysfunction in 96% (95CI 88-100), of women showing these symptoms before surgery. Obesity-associated gonadal dysfunction is among the most prevalent comorbidities in patients with severe obesity and should be ruled out routinely during their initial diagnostic workup. Considering the excellent response regarding both PCOS and MOSH, bariatric surgery should be offered to severely obese patients presenting with obesity-associated gonadal dysfunction. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

PubMed

Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; Vermeij, Wilbert P; Hoeijmakers, Jan H J; Essers, Jeroen; van der Pluijm, Ingrid; Danser, A H Jan; Roks, Anton J M

2017-08-01

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1 Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1 Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser 1177 -eNOS were compromised in Ercc1 Δ / - DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1 Δ/- mice. Ercc1 Δ/ - mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Analyses of selenotranscriptomes and selenium concentrations in response to dietary selenium deficiency and age reveal common and distinct patterns by tissue and sex in telomere-dysfunctional mice

USDA-ARS?s Scientific Manuscript database

Background: While sex and aging are known to impact mRNA abundance of several selenoproteins, this has not been examined comprehensively or in aged mice. By employing telomerase RNA component knockout (Terc-/-) mice carrying humanized telomeres, long-term dietary selenium (Se) deprivation has recent...

Increased Dynamics of Tricarboxylic Acid Cycle and Glutamate Synthesis in Obese Adipose Tissue

PubMed Central

Nagao, Hirofumi; Nishizawa, Hitoshi; Bamba, Takeshi; Nakayama, Yasumune; Isozumi, Noriyoshi; Nagamori, Shushi; Kanai, Yoshikatsu; Tanaka, Yoshimitsu; Kita, Shunbun; Fukuda, Shiro; Funahashi, Tohru; Maeda, Norikazu; Fukusaki, Eiichiro; Shimomura, Iichiro

2017-01-01

Obesity is closely associated with various metabolic disorders. However, little is known about abnormalities in the metabolic change of obese adipose tissue. Here we use static metabolic analysis and in vivo metabolic turnover analysis to assess metabolic dynamics in obese mice. The static metabolic analyses showed that glutamate and constitutive metabolites of the TCA cycle were increased in the white adipose tissue (WAT) of ob/ob and diet-induced obesity mice but not in the liver or skeletal muscle of these obese mice. Moreover, in vivo metabolic turnover analyses demonstrated that these glucose-derived metabolites were dynamically and specifically produced in obese WAT compared with lean WAT. Glutamate rise in obese WAT was associated with down-regulation of glutamate aspartate transporter (GLAST), a major glutamate transporter for adipocytes, and low uptake of glutamate into adipose tissue. In adipocytes, glutamate treatment reduced adiponectin secretion and insulin-mediated glucose uptake and phosphorylation of Akt. These data suggest that a high intra-adipocyte glutamate level potentially relates to adipocyte dysfunction in obesity. This study provides novel insights into metabolic dysfunction in obesity through comprehensive application of in vivo metabolic turnover analysis in two obese animal models. PMID:28119455

Creative thinking in schizophrenia: the role of executive dysfunction and symptom severity.

PubMed

Abraham, Anna; Windmann, Sabine; McKenna, Peter; Güntürkün, Onur

2007-05-01

This study examines the notion of enhanced creative thinking in schizophrenia and determines the mediating role of executive dysfunction and symptom severity in this relationship. Patients with chronic schizophrenia (n=28) were assessed on varied facets of creative cognition and standard tests of executive control relative to matched healthy control participants (n=18). Multivariate analyses revealed poorer performance by the patient group across almost all creative and executive function measures, except in the ability to be unconstrained by the influence of restrictive examples. Symptom-based contrasts using partial correlations revealed that differences were most extensive in the presence of thought disorder. Using hierarchical regression analyses, performance on the executive function tasks was found to play a mediatory role on specific aspects of creative cognition. Results are at odds with the popular notion of enhanced creative thinking in schizophrenia, but elucidate complex interactions between executive control and certain facets of creative thinking. In particular, performance of the schizophrenia group on measures that tap creativity elements of fluency and relevance were either partially or fully mediated by their performance on the executive control tasks, but this was not true of measures of originality.

Event-Related Oscillations in Alcoholism Research: A Review

PubMed Central

Pandey, Ashwini K; Kamarajan, Chella; Rangaswamy, Madhavi; Porjesz, Bernice

2013-01-01

Alcohol dependence is characterized as a multi-factorial disorder caused by a complex interaction between genetic and environmental liabilities across development. A variety of neurocognitive deficits/dysfunctions involving impairments in different brain regions and/or neural circuitries have been associated with chronic alcoholism, as well as with a predisposition to develop alcoholism. Several neurobiological and neurobehavioral approaches and methods of analyses have been used to understand the nature of these neurocognitive impairments/deficits in alcoholism. In the present review, we have examined relatively novel methods of analyses of the brain signals that are collectively referred to as event-related oscillations (EROs) and show promise to further our understanding of human brain dynamics while performing various tasks. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying responses to sensory and cognitive events, thus providing a closer link to the physiology underlying them. Here, we have reviewed EROs in the study of alcoholism, their usefulness in understanding dynamical brain functions/dysfunctions associated with alcoholism as well as their utility as effective endophenotypes to identify and understand genes associated with both brain oscillations and alcoholism. PMID:24273686

A specific amino acid formula prevents alcoholic liver disease in rodents.

PubMed

Tedesco, Laura; Corsetti, Giovanni; Ruocco, Chiara; Ragni, Maurizio; Rossi, Fabio; Carruba, Michele O; Valerio, Alessandra; Nisoli, Enzo

2018-05-01

Chronic alcohol consumption promotes mitochondrial dysfunction, oxidative stress, defective protein metabolism, and fat accumulation in hepatocytes (liver steatosis). Inadequate amino acid metabolism is worsened by protein malnutrition, frequently present in alcohol-consuming patients, with reduced circulating branched-chain amino acids (BCAAs). Here we asked whether dietary supplementation with a specific amino acid mixture, enriched in BCAAs (BCAAem) and able to promote mitochondrial function in muscle of middle-aged rodents, would prevent mitochondrial dysfunction and liver steatosis in Wistar rats fed on a Lieber-DeCarli ethanol (EtOH)-containing liquid diet. Supplementation of BCAAem, unlike a mixture based on the amino acid profile of casein, abrogated the EtOH-induced fat accumulation, mitochondrial impairment, and oxidative stress in liver. These effects of BCAAem were accompanied by normalization of leucine, arginine, and tryptophan levels, which were reduced in liver of EtOH-consuming rats. Moreover, although the EtOH exposure of HepG2 cells reduced mitochondrial DNA, mitochondrial transcription factors, and respiratory chain proteins, the BCAAem but not casein-derived amino acid supplementation halted this mitochondrial toxicity. Nicotinamide adenine dinucleotide levels and sirtuin 1 (Sirt1) expression, as well as endothelial nitric oxide (eNOS) and mammalian/mechanistic target of rapamycin (mTOR) signaling pathways, were downregulated in the EtOH-exposed HepG2 cells. BCAAem reverted these molecular defects and the mitochondrial dysfunction, suggesting that the mitochondrial integrity obtained with the amino acid supplementation could be mediated through a Sirt1-eNOS-mTOR pathway. Thus a dietary activation of the mitochondrial biogenesis and function by a specific amino acid supplement protects against the EtOH toxicity and preserves the liver integrity in mammals. NEW & NOTEWORTHY Dietary supplementation of a specific amino acid formula prevents both fat accumulation and mitochondrial dysfunction in hepatocytes of alcohol-consuming rats. These effects are accompanied also by increased expression of anti-reactive oxygen species genes. The amino acid-protective effects likely reflect activation of sirtuin 1-endothelial nitric oxide synthase-mammalian target of rapamycin pathway able to regulate the cellular energy balance of hepatocytes exposed to chronic, alcoholic damage.

The integration of depressive behaviors and cardiac dysfunction during an operational measure of depression: investigating the role of negative social experiences in an animal model.

PubMed

Grippo, Angela J; Moffitt, Julia A; Sgoifo, Andrea; Jepson, Amanda J; Bates, Suzanne L; Chandler, Danielle L; McNeal, Neal; Preihs, Kristin

2012-01-01

There is a bidirectional association between depression and cardiovascular disease. The neurobiological mechanisms underlying this association may involve an inability to cope with disrupted social bonds. This study investigated in an animal model the integration of depressive behaviors and cardiac dysfunction after a disrupted social bond and during an operational measure of depression, relative to the protective effects of intact social bonds. Depressive behaviors in the forced swim test and continuous electrocardiographic parameters were measured in 14 adult, female socially monogamous prairie voles (rodents), after 4 weeks of social pairing or isolation. After social isolation, animals exhibited (all values are mean ± standard error of the mean; isolated versus paired, respectively) increased heart rate (416 ± 14 versus 370 ± 14 bpm, p < .05) and reduced heart rate variability (3.3 ± 0.2 versus 3.9 ± 0.2 ln(ms(2))). During the forced swim test, isolated animals exhibited greater helpless behavior (immobility = 106 ± 11 versus 63 ± 11 seconds, p < .05), increased heart rate (530 ± 22 versus 447 ± 15 bpm, p < .05), reduced heart rate variability (1.8 ± 0.4 versus 2.7 ± 0.2 ln(ms(2)), p < .05), and increased arrhythmias (arrhythmic burden score = 181 ± 46 versus 28 ± 12, p < .05). The display of depressive behaviors during an operational measure of depression is coupled with increased heart rate, reduced heart rate variability, and increased arrhythmias, indicative of dysfunctional behavioral and physiological stress coping abilities as a function of social isolation. In contrast, social pairing with a sibling is behaviorally protective and cardioprotective. The present results can provide insight into a possible social mechanism underlying the association between depression and cardiovascular disease in humans.

Longitudinal effects of dysfunctional perfectionism and avoidant personality style on postpartum mental disorders: Pathways through antepartum depression and anxiety.

PubMed

Oddo-Sommerfeld, Silvia; Hain, Sarah; Louwen, Frank; Schermelleh-Engel, Karin

2016-02-01

There is first evidence that some personality characteristics raise the risk of postpartum depression (PPD). The present longitudinal study investigates whether dysfunctional perfectionism and avoidant personality style predict PPD, postpartum anxiety (PPA) and bonding impairment (BI) directly or indirectly through antepartum anxiety (APA) and antepartum depression (APD). Pregnant women were recruited in two obstetric departments in Germany. The assessment occurred at two measurement time points: In the third trimester of pregnancy (N=297) and twelve weeks postpartum (N=266). Six questionnaires were administered during pregnancy: perfectionism, personality styles, anxiety, and depression. Postpartum, data on PPA, PPD and BI were collected. We conducted two path analyses in order to examine direct and indirect effects of the two personality characteristics on postpartum disorders. Testing for direct effects of dysfunctional perfectionism and avoidant personality style on PPD, PPA, and BI did not yield significant results. Instead, significant indirect effects were found: PPD, PPA, and BI were influenced indirectly by dysfunctional perfectionism and avoidant personality style via APD and APA. This model explained high portions of the variance of PPD, PPA, and impaired bonding. Each of the two personality characteristics explained a unique part of the outcome measures. The influence on BI was mediated by PPD. APD affected PPD and PPA more strongly than APA. Path models with manifest (observed) variables may lead to measurement errors. Self-rating questionnaires may raise the problem of social desirability. Dysfunctional perfectionism and avoidant personality style are significant risk factors for PPD, PPA, and BI. Screenings of both variables, as well as of APA and APD, which mediated the effect of personality traits on postpartum syndromes, are necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition.

PubMed

Stip, Emmanuel; Caron, Jean; Tousignant, Michel; Lecomte, Yves

2017-10-01

To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders.

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

PubMed

Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

2013-12-01

Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Impact of perioperative liver dysfunction on in-hospital mortality and long-term survival in infective endocarditis patients.

PubMed

Diab, M; Sponholz, C; von Loeffelholz, C; Scheffel, P; Bauer, M; Kortgen, A; Lehmann, T; Färber, G; Pletz, M W; Doenst, T

2017-12-01

Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD. We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation. Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p < 0.001). 5-year survival was worse in patients with pre- or postoperative LD compared to patients without LD (20.1, 37.1, and 57.0% respectively). A landmark analysis revealed similar 5-year survival between groups after patient discharge. Quality of life was similar between groups when patients survived the perioperative period. Logistic regression analysis identified duration of cardiopulmonary bypass and S. aureus infection as independent predictors of postoperative LD. Perioperative liver dysfunction in patients with infective endocarditis is an independent predictor of short- and long-term mortalities. After surviving the hospital stay, 5-year prognosis is not different and quality of life is not affected by LD. S. aureus and duration of cardiopulmonary bypass represent risk factors for postoperative LD.

Effects of hypo- and hyperthyroidism on proliferation, angiogenesis, apoptosis and expression of COX-2 in the corpus luteum of female rats.

PubMed

Silva, J F; Ocarino, N M; Vieira, A L S; Nascimento, E F; Serakides, R

2013-08-01

Although thyroid dysfunction occurs frequently in humans and some animal species, the mechanisms by which hypo- and hyperthyroidism affect the corpus luteum have not been thoroughly elucidated. This study evaluated the levels of proliferative activity, angiogenesis, apoptosis and expression of cyclooxygenase-2 in the corpus luteum of female rats with thyroid dysfunction. These processes may be important in understanding the reproductive changes caused by thyroid dysfunction. A total of 18 adult female rats were divided into three groups (control, hypothyroid and hyperthyroid) with six animals per group. Three months after treatment to induce thyroid dysfunction, the rats were euthanized in the dioestrus phase. The ovaries were collected and immunohistochemically analysed for expression of the cell proliferation marker CDC-47, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1 and cyclooxygenase-2 (COX-2). Apoptosis was evaluated using the TUNEL assay. Hypothyroidism reduced the intensity and area of COX-2 expression in the corpus luteum (p < 0.05), while hyperthyroidism did not alter COX-2 expression in the dioestrus phase. Hypothyroidism significantly reduced the expression of CDC-47 in endothelial cells and pericytes in the corpus luteum, whereas hyperthyroidism did not induce a detectable change in CDC-47 expression (p > 0.05). Hypothyroidism reduced the level of apoptosis in luteal cells (p < 0.05) and increased VEGF expression in the corpus luteum. In contrast, hyperthyroidism increased the level of apoptosis in the corpus luteum (p < 0.05). In conclusion, thyroid dysfunction differentially affects the levels of proliferative activity, angiogenesis and apoptosis and COX-2 expression in the corpus luteum of female rats. © 2013 Blackwell Verlag GmbH.

CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

PubMed

Cao, Li; Qin, Xing; Peterson, Matthew R; Haller, Samantha E; Wilson, Kayla A; Hu, Nan; Lin, Xin; Nair, Sreejayan; Ren, Jun; He, Guanglong

2016-03-01

Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition

PubMed Central

Stip, Emmanuel; Caron, Jean; Tousignant, Michel

2017-01-01

Objective: To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. Method: The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. Results: The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). Conclusion: The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders. PMID:28673099

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity

PubMed Central

Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J.; Miranda, Melroy X.; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F.; Verrey, François; Matter, Christian M.

2013-01-01

Received 22 July 2012; revised 29 January 2013; accepted 4 March 2013 Aims Aldosterone plays a crucial role in cardiovascular disease. ‘Systemic’ inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the ‘endothelial’ MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. Methods and results C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high ‘endogenous’ aldosterone) and in ‘exogenous’ aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Conclusion Obesity-induced endothelial dysfunction depends on the ‘endothelial’ MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications. PMID:23594590

Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

PubMed Central

2013-01-01

Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting. No significant differences were detected in other CatWalk parameters, motor evoked potentials, open field locomotor (Basso, Beattie, and Bresnahan locomotion score (BBB)) score or ladder climbing test. Magnetic resonance imaging volume reconstruction and immunofluorescence analysis of grafted cell survival showed near complete injury-cavity-filling by grafted cells and development of putative GABA-ergic synapses between grafted and host neurons. Conclusions Peri-acute intraspinal grafting of HSSC can represent an effective therapy which ameliorates motor and sensory deficits after traumatic spinal cord injury. PMID:23710605

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction.

PubMed

Beltrami, Matteo; Palazzuoli, Alberto; Padeletti, Luigi; Cerbai, Elisabetta; Coiro, Stefano; Emdin, Michele; Marcucci, Rossella; Morrone, Doralisa; Cameli, Matteo; Savino, Ketty; Pedrinelli, Roberto; Ambrosio, Giuseppe

2018-02-01

Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies. © 2017 John Wiley & Sons Ltd.

Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy.

PubMed

Blair, Laura J; Frauen, Haley D; Zhang, Bo; Nordhues, Bryce A; Bijan, Sara; Lin, Yen-Chi; Zamudio, Frank; Hernandez, Lidice D; Sabbagh, Jonathan J; Selenica, Maj-Linda B; Dickey, Chad A

2015-01-31

The blood-brain barrier (BBB) is damaged in tauopathies, including progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is thought to contribute to pathogenesis later in the disease course. In AD, BBB dysfunction has been associated with amyloid beta (Aß) pathology, but the role of tau in this process is not well characterized. Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage. Longitudinal evaluation of brain tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model showed progressive IgG, T cell and red blood cell infiltration. The Evans blue (EB) dye that is excluded from the brain when the BBB is intact also permeated the brains of rTg4510 mice following peripheral administration, indicative of a bonafide BBB defect, but this was only evident later in life. Thus, despite the marked brain atrophy and inflammation that occurs earlier in this model, BBB integrity is maintained. Interestingly, BBB dysfunction emerged at the same time that perivascular tau emerged around major hippocampal blood vessels. However, when tau expression was suppressed using doxycycline, BBB integrity was preserved, suggesting that the BBB can be stabilized in a tauopathic brain by reducing tau levels. For the first time, these data demonstrate that tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation. Moreover, the BBB can recover integrity when tau levels are reduced. Thus, late stage interventions targeting tau may slow the vascular contributions to cognitive impairment and dementia that occur in tauopathies.

The Integral Theory System Questionnaire: an anatomically directed questionnaire to determine pelvic floor dysfunctions in women.

PubMed

Wagenlehner, Florian Martin Erich; Fröhlich, Oliver; Bschleipfer, Thomas; Weidner, Wolfgang; Perletti, Gianpaolo

2014-06-01

Anatomical damage to pelvic floor structures may cause multiple symptoms. The Integral Theory System Questionnaire (ITSQ) is a holistic questionnaire that uses symptoms to help locate damage in specific connective tissue structures as a guide to reconstructive surgery. It is based on the integral theory, which states that pelvic floor symptoms and prolapse are both caused by lax suspensory ligaments. The aim of the present study was to psychometrically validate the ITSQ. Established psychometric properties including validity, reliability, and responsiveness were considered for evaluation. Criterion validity was assessed in a cohort of 110 women with pelvic floor dysfunctions by analyzing the correlation of questionnaire responses with objective clinical data. Test-retest was performed with questionnaires from 47 patients. Cronbach's alpha and "split-half" reliability coefficients were calculated for inner consistency analysis. Psychometric properties of ITSQ were comparable to the ones of previously validated Pelvic Floor Questionnaires. Face validity and content validity were approved by an expert group of the International Collaboration of Pelvic Floor surgeons. Convergent validity assessed using Bayesian method was at least as accurate as the expert assessment of anatomical defects. Objective data measurement in patients demonstrated significant correlations with ITSQ domains fulfilling criterion validity. Internal consistency values ranked from 0.85 to 0.89 in different scenarios. The ITSQ proofed accurate and is able to serve as a holistic Pelvic Floor Questionnaire directing symptoms to site-specific pelvic floor reconstructive surgery.

[Social integration of women operated for obstetric urogenital fistula].

PubMed

Diarra, A; Tembely, A; Berthe, H J G; Diakité, M L; Traoré, B; Ouattara, K

2013-10-01

To study the social integration of women supported in the urology department of the University Hospital of Point G for obstetric urogenital fistula. Prospective study conducted over a period of 13 months from June 2008 to June 2009 in the Department of Urology at the University Hospital of Point G. The study included all patients who have been operated on at least twice for obstetric fistula genitourinary. Records of surgical, medical records and tracking sheets for each patient were the media database. Situation before treatment: before surgical treatment, 76.92% of patients were rejected by their spouses. The family attended the patient in 84.62% of cases. Situation after treatment: after treatment, 90.31% of women with fistula lived in the matrimonial home or family. The resumption of business activity was announced by 11.2% of patients. Among the women, 93.7% participated in housework. The number of patient intervention ranged from two to five. Healing (fistula closed and no sphincter dysfunction) was complete in 50% of cases. Among the women, 11.54% had sphincter dysfunction after closure of the fistula, which makes a total of fistula closed more than 61% after at least two attempts. The urogenital fistulas are not a fatal disease but is a real handicap for women who suffer to conduct a socio-cultural and economic mainstream. Generally excluded from the ongoing operations of the company, these women are more integrated after successful surgical treatment of the fistula. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Pharmacological modulation of dietary lipid-induced cerebral capillary dysfunction: Considerations for reducing risk for Alzheimer's disease.

PubMed

Pallebage-Gamarallage, Menuka; Takechi, Ryusuke; Lam, Virginie; Elahy, Mina; Mamo, John

2016-01-01

An increasing body of evidence suggests that cerebrovascular dysfunction and microvessel disease precede the evolution of hallmark pathological features that characterise Alzheimer's disease (AD), consistent with a causal association for onset or progression. Recent studies, principally in genetically unmanipulated animal models, suggest that chronic ingestion of diets enriched in saturated fats and cholesterol may compromise blood-brain barrier (BBB) integrity resulting in inappropriate blood-to-brain extravasation of plasma proteins, including lipid macromolecules that may be enriched in amyloid-β (Aβ). Brain parenchymal retention of blood proteins and lipoprotein bound Aβ is associated with heightened neurovascular inflammation, altered redox homeostasis and nitric oxide (NO) metabolism. Therefore, it is a reasonable proposition that lipid-lowering agents may positively modulate BBB integrity and by extension attenuate risk or progression of AD. In addition to their robust lipid lowering properties, reported beneficial effects of lipid-lowering agents were attributed to their pleiotropic properties via modulation of inflammation, oxidative stress, NO and Aβ metabolism. The review is a contemporary consideration of a complex body of literature intended to synthesise focussed consideration of mechanisms central to regulation of BBB function and integrity. Emphasis is given to dietary fat driven significant epidemiological evidence consistent with heightened risk amongst populations consuming greater amounts of saturated fats and cholesterol. In addition, potential neurovascular benefits associated with the use of hypolipidemic statins, probucol and fenofibrate are also presented in the context of lipid-lowering and pleiotropic properties.

Linking magnetite in the abdomen of honey bees to a magnetoreceptive function

PubMed Central

Lambinet, Veronika; Hayden, Michael E.; Reigl, Katharina; Gomis, Surath

2017-01-01

Previous studies of magnetoreception in honey bees, Apis mellifera, focused on the identification of magnetic material, its formation, the location of the receptor and potential underlying sensory mechanisms, but never directly linked magnetic material to a magnetoreceptive function. In our study, we demonstrate that ferromagnetic material consistent with magnetite plays an integral role in the bees' magnetoreceptor. Subjecting lyophilized and pelletized bee tagmata to analyses by a superconducting quantum interference device generated a distinct hysteresis loop for the abdomen but not for the thorax or the head of bees, indicating the presence of ferromagnetic material in the bee abdomen. Magnetic remanence of abdomen pellets produced from bees that were, or were not, exposed to the 2.2-kOe field of a magnet while alive differed, indicating that magnet exposure altered the magnetization of this magnetite in live bees. In behavioural two-choice field experiments, bees briefly exposed to the same magnet, but not sham-treated control bees, failed to sense a custom-generated magnetic anomaly, indicating that magnet exposure had rendered the bees' magnetoreceptor dysfunctional. Our data support the conclusion that honey bees possess a magnetite-based magnetoreceptor located in the abdomen. PMID:28330921

Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH)

PubMed Central

Kim, Eun Young; Kim, Hyunjin; Lee, Yoonjeong; Min, Boram; Son, Jin H.; Park, Hwan Tae; Chung, Jongkyeong

2017-01-01

DJ-1 is one of the causative genes for early onset familiar Parkinson’s disease (PD) and is also considered to influence the pathogenesis of sporadic PD. DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species (ROS) levels. In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP+-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into α-ketoglutarate, was detected. Loss of IDH induced hyper-sensitivity to oxidative stress accompanying age-dependent mitochondrial defects and dopaminergic (DA) neuron degeneration in Drosophila, indicating its critical roles in maintaining mitochondrial integrity and DA neuron survival. Further genetic analysis suggested that DJ-1 controls IDH gene expression through nuclear factor-E2-related factor2 (Nrf2). Using Drosophila and mammalian DA models, we found that IDH suppresses intracellular and mitochondrial ROS level and subsequent DA neuron loss downstream of DJ-1. Consistently, trimethyl isocitrate (TIC), a cell permeable isocitrate, protected mammalian DJ-1 null DA cells from oxidative stress in an IDH-dependent manner. These results suggest that isocitrate and its derivatives are novel treatments for PD associated with DJ-1 dysfunction. PMID:28827794

Linking magnetite in the abdomen of honey bees to a magnetoreceptive function.

PubMed

Lambinet, Veronika; Hayden, Michael E; Reigl, Katharina; Gomis, Surath; Gries, Gerhard

2017-03-29

Previous studies of magnetoreception in honey bees, Apis mellifera , focused on the identification of magnetic material, its formation, the location of the receptor and potential underlying sensory mechanisms, but never directly linked magnetic material to a magnetoreceptive function. In our study, we demonstrate that ferromagnetic material consistent with magnetite plays an integral role in the bees' magnetoreceptor. Subjecting lyophilized and pelletized bee tagmata to analyses by a superconducting quantum interference device generated a distinct hysteresis loop for the abdomen but not for the thorax or the head of bees, indicating the presence of ferromagnetic material in the bee abdomen. Magnetic remanence of abdomen pellets produced from bees that were, or were not, exposed to the 2.2-kOe field of a magnet while alive differed, indicating that magnet exposure altered the magnetization of this magnetite in live bees. In behavioural two-choice field experiments, bees briefly exposed to the same magnet, but not sham-treated control bees, failed to sense a custom-generated magnetic anomaly, indicating that magnet exposure had rendered the bees' magnetoreceptor dysfunctional. Our data support the conclusion that honey bees possess a magnetite-based magnetoreceptor located in the abdomen. © 2017 The Authors.

New advances in targeted gastric cancer treatment

PubMed Central

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-01-01

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

Nurse managers' strategies for feeling less drained by their work: an action research and reflection project for developing emotional intelligence.

PubMed

Taylor, Bev; Roberts, Sue; Smyth, Therese; Tulloch, Moira

2015-10-01

To raise nurse managers' critical awareness of practice problems; uncover practice constraints and improve work effectiveness. Nurse management requires skills and knowledge, underscored by emotional intelligence. The research improved participants' practice and personal insights. Purposive sampling targeted nurse managers interested in improving their practice. Three experienced female nurse managers met fortnightly in a group, for 1 hour, for 10 meetings. The methods included: writing and sharing de-identified journal reflections; critically analysing practice stories; identifying a thematic concern; generating action strategies; and instituting and revising the action plan. Phase One resulted in the identification of the issue of 'being drained by the intensity of nurse managers' work'. The participants adopted five strategies: debriefing problematic situations; deflecting multiple requests; diffusing issues; naming dysfunctional behaviours; and regrouping. In Phase Two, participants implemented and revised the action plan strategies, which resulted in them feeling less drained by their work. Strategies can lessen nurse managers' sense of personal depletion. However, strategies cannot guarantee success every time because the emotional intelligence is integral to nurse management. Action research and reflection assist nurse managers to improve their practice and develop their emotional intelligence. © 2014 John Wiley & Sons Ltd.

New advances in targeted gastric cancer treatment.

PubMed

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-08-14

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

Associations between psychological constructs and cardiac biomarkers following acute coronary syndrome

PubMed Central

Celano, Christopher M.; Beale, Eleanor E.; Beach, Scott R.; Belcher, Arianna M.; Suarez, Laura; Motiwala, Shweta R.; Gandhi, Parul U.; Gaggin, Hanna; Januzzi, James L.; Healy, Brian C.; Huffman, Jeff C.

2016-01-01

Objective Psychological constructs are associated with cardiovascular health, but the biological mechanisms mediating these relationships are unknown. We examined relationships between psychological constructs and markers of inflammation, endothelial function, and myocardial strain in a cohort of post-acute coronary syndrome (ACS) patients. Methods Participants (N=164) attended study visits 2 weeks and 6 months post-ACS. During these visits, they completed self-report measures of depressive symptoms, anxiety, optimism, and gratitude, and blood samples were collected for measurement of biomarkers reflecting inflammation, endothelial function, and myocardial strain. Generalized estimating equations and linear regression analyses were performed to examine concurrent and prospective relationships between psychological constructs and biomarkers. Results In concurrent analyses, depressive symptoms were associated with elevated markers of inflammation (interleukin-17: β=.047, 95% confidence interval [.010, .083]), endothelial dysfunction (endothelin-1: β=.020, [.004, .037]), and myocardial strain (N-terminal pro-B-type natriuretic peptide: β=.045, [.008, .083]), independent of age, sex, medical variables, and anxiety, while anxiety was not associated with these markers in multivariable adjusted models. Optimism and gratitude were associated with lower levels of markers of endothelial dysfunction (endothelin-1: gratitude: β=−.009, [−.017, −.001]; optimism: β=−.009, [−.016, −.001]; soluble intercellular adhesion molecule-1: gratitude: β=−.007, [−.014, −.000]), independent of depressive and anxiety symptoms. Psychological constructs at 2 weeks were not prospectively associated with biomarkers at 6 months. Conclusions Depressive symptoms were associated with more inflammation, myocardial strain, and endothelial dysfunction in the 6 months post-ACS, while positive psychological constructs were linked to better endothelial function. Larger, prospective studies may clarify the directionality of these relationships. PMID:27749683

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

F229. THE BIOLOGICAL UNDERPINNINGS OF TREATMENT RESPONSE IN DELUSIONAL DISORDER: A SYSTEMATIC REVIEW OF QUALITATIVE EVIDENCE-TO-DATE

PubMed Central

González-Rodríguez, Alexandre; Estrada, Francesc; Montalvo, Itziar; Monreal, José Antonio; Palao, Diego; Labad, Javier

2018-01-01

Abstract Background The dopamine hypothesis of schizophrenia has been extensively proposed as a neurobiological mechanism that explains the relationship between schizophrenic symptoms and hyperdopaminergic states. This hypothesis is supported by direct and indirect evidence, and it mainly postulates that antipsychotics act blocking dopamine receptors. When focusing on delusional disorder patients, especially delusional disorder somatic type, a great effort towards the search for a biological basis of treatment response has been recently demonstrated. Thus, the main goal of this systematic review was to examine the evidence explaining the biological underpinnings of treatment response in delusional disorder. Methods A systematic review was performed using Pubmed, Scopus and PsycINFO databases (from 1990 to October 2017), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The following search terms were used: [(‘treat*’ OR ‘therap*’ OR ‘biol*’) AND (‘delusional disorder’)]. This systematic computerized search was completed by additional studies hand-checked through reference lists from the included studies and review articles. Studies were only included if the met our inclusion criteria: (a) the International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis for delusional disorder, (b) be published in peer-reviewed journals, (c) in English, German or Spanish, (d) and reporting a hypothesis for the biological basis of treatment response in delusional disorder, irrespective of method and study design. Exclusion criteria were: (a) studies including organic delusional disorder or (b) somatic delusions secondary to other psychiatric diagnoses. The literature search strategy, data extraction and synthesis was conducted independently by two authors (A.G.R, F.E.). When disagreement, it was solved by consensus. Results A total of 59 articles were identified, of which 12 met our inclusion criteria. Four hypotheses were addressed: (1) Dopaminergic dysfunction (n=4): ziprasidone-induced supersensitivity psychosis by chronic blockade of D2 Dopamine Receptor (DRD2) (n=1); pretreatment levels of plasma homovallinic acid (pHVA) (n=1); dopamine transporter (DAT) dysfunction (n=1) and effectiveness of aripiprazole (DRD2 agonist) (n=1). (2) Serotonergic dysfunction (n=6): drug occupancy in 5-HT1A and 5-HT2A receptors (n=3) and efficacy of 5-HT2 antagonists (n=3). Brain dysfunction (n=7): hypoperfusion in cerebral blood flow in temporal and parietal lobes, left side (n=5), right side (n=1) and lack of basal ganglia and subcortical gray matter lesions (n=1). Genetic evidence (n=1): implications of DRD2 Ser311Cys, DRD3 Ser9Gly and TH VNTR polymorphisms. Discussion The strongests biological contributors for treatment response in delusional disorder seem to be those implicating monoaminergic systems, particularly dopamine and serotonergic neurotransmitters. Although the low level of evidence, the serotonergic dysfunction may be associated with response rates, especially in delusional disorder somatic type. The link between genetic variants of dopamine receptors and neuroimaging findings in delusional disorder may open new avenues for the search of the biological underpinnings of treatment response. The evidence for an integrated model involving dopamine and serotonin systems bears further investigations.

Do Planning and Visual Integration Difficulties Underpin Motor Dysfunction in Autism? A Kinematic Study of Young Children with Autism

ERIC Educational Resources Information Center

Dowd, Ariane M.; McGinley, Jennifer L.; Taffe, John R.; Rinehart, Nicole J.

2012-01-01

This paper examines the upper-limb movement kinematics of young children (3-7 years) with high-functioning autism using a point-to-point movement paradigm. Consistent with prior findings in older children, a difference in movement preparation was found in the autism group (n = 11) relative to typically developing children. In contrast to typically…

Time perception impairs sensory-motor integration in Parkinson’s disease

PubMed Central

2013-01-01

It is well known that perception and estimation of time are fundamental for the relationship between humans and their environment. However, this temporal information processing is inefficient in patients with Parkinson’ disease (PD), resulting in temporal judgment deficits. In general, the pathophysiology of PD has been described as a dysfunction in the basal ganglia, which is a multisensory integration station. Thus, a deficit in the sensorimotor integration process could explain many of the Parkinson symptoms, such as changes in time perception. This physiological distortion may be better understood if we analyze the neurobiological model of interval timing, expressed within the conceptual framework of a traditional information-processing model called “Scalar Expectancy Theory”. Therefore, in this review we discuss the pathophysiology and sensorimotor integration process in PD, the theories and neural basic mechanisms involved in temporal processing, and the main clinical findings about the impact of time perception in PD. PMID:24131660

Psychopathic traits modulate microstructural integrity of right uncinate fasciculus in a community population.

PubMed

Sobhani, Mona; Baker, Laura; Martins, Bradford; Tuvblad, Catherine; Aziz-Zadeh, Lisa

2015-01-01

Individuals with psychopathy possess emotional and behavioral abnormalities. Two neural regions, involved in behavioral control and emotion regulation, are often implicated: amygdala and ventromedial prefrontal cortex (VMPFC). Recently, in studies using adult criminal populations, reductions in microstructural integrity of the white matter connections (i.e., uncinate fasciculus (UF)) between these two neural regions have been discovered in criminals with psychopathy, supporting the notion of neural dysfunction in the amygdala-VMPFC circuit. Here, a young adult, community sample is used to assess whether psychopathic traits modulate microstructural integrity of UF, and whether this relationship is dependent upon levels of trait anxiety, which is sometimes used to distinguish subtypes of psychopathy. Results reveal a negative association between psychopathic traits and microstructural integrity of UF, supporting previous findings. However, no moderation of the relationship by trait anxiety was discovered. Findings provide further support for the notion of altered amygdala-VMPFC connectivity in association with higher psychopathic traits.

Cost-effectiveness of minimally invasive sacroiliac joint fusion.

PubMed

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée Jg; Polly, David W

2016-01-01

Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. To determine the cost-effectiveness of minimally invasive SIJ fusion. Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162-$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption.

Cost-effectiveness of minimally invasive sacroiliac joint fusion

PubMed Central

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée JG; Polly, David W

2016-01-01

Background Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. Objective To determine the cost-effectiveness of minimally invasive SIJ fusion. Methods Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. Results SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162–$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Conclusion Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption. PMID:26719717

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury.

PubMed

Abiko, Kagari; Ikoma, Katsunori; Shiga, Tohru; Katoh, Chietsugu; Hirata, Kenji; Kuge, Yuji; Kobayashi, Kentaro; Tamaki, Nagara

2017-12-01

Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients. The subjects of this study were seven patients who suffered from neurobehavioral disability. They underwent IMZ SPECT and FMZ PET. Nondisplaceable binding potential (BP ND ) was calculated from FMZ PET images. The uptake of IMZ was evaluated on the basis of lesion-to-pons ratio (LPR). The locations of low uptake levels were visually evaluated both in IMZ SPECT and FMZ PET images. We compared FMZ BP ND and (LPR-1) of IMZ SPECT. In the visual assessment, FMZ BP ND decreased in 11 regions. In IMZ SPECT, low uptake levels were observed in eight of the 11 regions. The rate of concordance between FMZ PET and IMZ SPECT was 72.7%. The mean values IMZ (LPR-1) (1.95 ± 1.01) was significantly lower than that of FMZ BP ND (2.95 ± 0.80 mL/mL). There was good correlation between FMZ BP ND and IMZ (LPR-1) (r = 0.80). IMZ SPECT findings were almost the same as FMZ PET findings in TBI patients. The results indicated that IMZ SPECT is useful for evaluating the loss of neuronal integrity. Because IMZ SPECT can be performed in various facilities, IMZ SPECT may become widely adopted for evaluating the loss of neuronal integrity.

Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism.

PubMed

Garcia-Junco-Clemente, Pablo; Chow, David K; Tring, Elaine; Lazaro, Maria T; Trachtenberg, Joshua T; Golshani, Peyman

2013-11-05

De novo phosphatase and tensin homolog on chromosome ten (PTEN) mutations are a cause of sporadic autism. How single-copy loss of PTEN alters neural function is not understood. Here we report that Pten haploinsufficiency increases the expression of small-conductance calcium-activated potassium channels. The resultant augmentation of this conductance increases the amplitude of the afterspike hyperpolarization, causing a decrease in intrinsic excitability. In vivo, this change in intrinsic excitability reduces evoked firing rates of cortical pyramidal neurons but does not alter receptive field tuning. The decreased in vivo firing rate is not associated with deficits in the dendritic integration of synaptic input or with changes in dendritic complexity. These findings identify calcium-activated potassium channelopathy as a cause of cortical dysfunction in the PTEN model of autism and provide potential molecular therapeutic targets.

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness

PubMed Central

Klingensmith, Nathan J.; Coopersmith, Craig M.

2015-01-01

Synopsis All elements of the gut – the epithelium, the immune system, and the microbiome – are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU. PMID:27016162

The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness.

PubMed

Klingensmith, Nathan J; Coopersmith, Craig M

2016-04-01

All elements of the gut - the epithelium, the immune system, and the microbiome - are impacted by critical illness and can, in turn, propagate a pathologic host response leading to multiple organ dysfunction syndrome. Preclinical studies have demonstrated that this can occur by release of toxic gut-derived substances into the mesenteric lymph where they can cause distant damage. Further, intestinal integrity is compromised in critical illness with increases in apoptosis and permeability. There is also increasing recognition that microbes alter their behavior and can become virulent based upon host environmental cues. Gut failure is common in critically ill patients; however, therapeutics targeting the gut have proven to be challenging to implement at the bedside. Numerous strategies to manipulate the microbiome have recently been used with varying success in the ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

Cingulate, Frontal and Parietal Cortical Dysfunction in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bush, George

2011-01-01

Functional and structural neuroimaging have identified abnormalities of the brain that are likely to contribute to the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD). In particular, hypofunction of the brain regions comprising the cingulo-frontal-parietal (CFP) cognitive-attention network have been consistently observed across studies. These are major components of neural systems that are relevant to ADHD, including cognitive/attention networks, motor systems and reward/feedback-based processing systems. Moreover, these areas interact with other brain circuits that have been implicated in ADHD, such as the “default mode” resting state network. ADHD imaging data related to CFP network dysfunction will be selectively highlighted here to help facilitate its integration with the other information presented in this special issue. Together, these reviews will help shed light on the neurobiology of ADHD. PMID:21489409

Clinical competence of Guatemalan and Mexican physicians for family dysfunction management.

PubMed

Cabrera-Pivaral, Carlos Enrique; Orozco-Valerio, María de Jesús; Celis-de la Rosa, Alfredo; Covarrubias-Bermúdez, María de Los Ángeles; Zavala-González, Marco Antonio

2017-01-01

To evaluate the clinical competence of Mexican and Guatemalan physicians to management the family dysfunction. Cross comparative study in four care units first in Guadalajara, Mexico, and four in Guatemala, Guatemala, based on a purposeful sampling, involving 117 and 100 physicians, respectively. Clinical competence evaluated by validated instrument integrated for 187 items. Non-parametric descriptive and inferential statistical analysis was performed. The percentage of Mexican physicians with high clinical competence was 13.7%, medium 53%, low 24.8% and defined by random 8.5%. For the Guatemalan physicians'14% was high, average 63%, and 23% defined by random. There were no statistically significant differences between healthcare country units, but between the medium of Mexicans (0.55) and Guatemalans (0.55) (p = 0.02). The proportion of the high clinical competency of Mexican physicians' was as Guatemalans.

Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

PubMed Central

Pappas, Samuel S.; Leventhal, Daniel K.; Albin, Roger L.; Dauer, William T.

2014-01-01

This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function. PMID:24947237

Vaginal Testosterone for Management of Aromatase Inhibitor-Related Sexual Dysfunction: An Integrative Review.

PubMed

Lemke, Emily A; Madsen, Lydia T; Dains, Joyce E

2017-05-01

Women taking aromatase inhibitors (AIs) as part of the management of hormone receptor-positive breast cancer experience more symptoms of sexual dysfunction, including vaginal atrophy, as opposed to postmenopausal women and women treated with tamoxifen (Nolvadex®). Vaginal testosterone could be an alternative to estrogen, which is contraindicated in this population.
. A systematic review was completed by searching PubMed and Scopus databases.
. 64 search results were reduced to a final sample of 3 articles after applying inclusion and exclusion criteria.
. Published results suggest that vaginally applied testosterone doses of 150 mcg and 300 mcg improve symptoms of sexual dysfunction in women taking AIs. Minimal side effects are observed, and estradiol levels are not affected by vaginally applied testosterone. Additional research is needed to evaluate vaginal testosterone in women taking AIs.
. Vaginal testosterone shows preliminary promise as an option to manage sexual side effects of AI therapy in postmenopausal cancer survivors; however, available data are too limited to draw practice-changing conclusions.
. Large-scale randomized, controlled trials need to be completed to evaluate the efficacy and safety of vaginal testosterone in women taking AIs.

Perceptual Anomalies in Schizophrenia: Integrating Phenomenology and Cognitive Neuroscience

PubMed Central

Uhlhaas, Peter J.; Mishara, Aaron L.

2007-01-01

From phenomenological and experimental perspectives, research in schizophrenia has emphasized deficits in “higher” cognitive functions, including attention, executive function, as well as memory. In contrast, general consensus has viewed dysfunctions in basic perceptual processes to be relatively unimportant in the explanation of more complex aspects of the disorder, including changes in self-experience and the development of symptoms such as delusions. We present evidence from phenomenology and cognitive neuroscience that changes in the perceptual field in schizophrenia may represent a core impairment. After introducing the phenomenological approach to perception (Husserl, the Gestalt School), we discuss the views of Paul Matussek, Klaus Conrad, Ludwig Binswanger, and Wolfgang Blankenburg on perception in schizophrenia. These 4 psychiatrists describe changes in perception and automatic processes that are related to the altered experience of self. The altered self-experience, in turn, may be responsible for the emergence of delusions. The phenomenological data are compatible with current research that conceptualizes dysfunctions in perceptual processing as a deficit in the ability to combine stimulus elements into coherent object representations. Relationships of deficits in perceptual organization to cognitive and social dysfunction as well as the possible neurobiological mechanisms are discussed. PMID:17118973

Mitochondria and heart failure.

PubMed

Murray, Andrew J; Edwards, Lindsay M; Clarke, Kieran

2007-11-01

Energetic abnormalities in cardiac and skeletal muscle occur in heart failure and correlate with clinical symptoms and mortality. It is likely that the cellular mechanism leading to energetic failure involves mitochondrial dysfunction. Therefore, it is crucial to elucidate the causes of mitochondrial myopathy, in order to improve cardiac and skeletal muscle function, and hence quality of life, in heart failure patients. Recent studies identified several potential stresses that lead to mitochondrial dysfunction in heart failure. Chronically elevated plasma free fatty acid levels in heart failure are associated with decreased metabolic efficiency and cellular insulin resistance. Tissue hypoxia, resulting from low cardiac output and endothelial impairment, can lead to oxidative stress and mitochondrial DNA damage, which in turn causes dysfunction and loss of mitochondrial mass. Therapies aimed at protecting mitochondrial function have shown promise in patients and animal models with heart failure. Despite current therapies, which provide substantial benefit to patients, heart failure remains a relentlessly progressive disease, and new approaches to treatment are necessary. Novel pharmacological agents are needed that optimize substrate metabolism and maintain mitochondrial integrity, improve oxidative capacity in heart and skeletal muscle, and alleviate many of the clinical symptoms associated with heart failure.

Brain imaging research in autism spectrum disorders: in search of neuropathology and health across the lifespan.

PubMed

Lainhart, Janet E

2015-03-01

Advances in brain imaging research in autism spectrum disorders (ASD) are rapidly occurring, and the amount of neuroimaging research has dramatically increased over the past 5 years. In this review, advances during the past 12 months and longitudinal studies are highlighted. Cross-sectional neuroimaging research provides evidence that the neural underpinnings of the behavioral signs of ASD involve not only dysfunctional integration of information across distributed brain networks but also basic dysfunction in primary cortices.Longitudinal studies of ASD show abnormally enlarged brain volumes and increased rates of brain growth during early childhood in only a small minority of ASD children. There is evidence of disordered development of white matter microstructure and amygdala growth, and at 2 years of age, network inefficiencies in posterior cerebral regions.From older childhood into adulthood, atypical age-variant and age-invariant changes in the trajectories of total and regional brain volumes and cortical thickness are apparent at the group level. There is evidence of abnormalities in posterior lobes and posterior brain networks during the first 2 years of life in ASD and, even in older children and adults, dysfunction in primary cortical areas.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States

PubMed Central

Hopp, Lydia; Löffler-Wirth, Henry; Binder, Hans

2015-01-01

Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. PMID:26371046

Medical and surgical management of esophageal and gastric motor dysfunction.

PubMed

Awad, R A

2012-09-01

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.

Top-Down Targeted Proteomics Reveals Decrease in Myosin Regulatory Light-Chain Phosphorylation That Contributes to Sarcopenic Muscle Dysfunction.

PubMed

Gregorich, Zachery R; Peng, Ying; Cai, Wenxuan; Jin, Yutong; Wei, Liming; Chen, Albert J; McKiernan, Susan H; Aiken, Judd M; Moss, Richard L; Diffee, Gary M; Ge, Ying

2016-08-05

Sarcopenia, the loss of skeletal muscle mass and function with advancing age, is a significant cause of disability and loss of independence in the elderly and thus, represents a formidable challenge for the aging population. Nevertheless, the molecular mechanism(s) underlying sarcopenia-associated muscle dysfunction remain poorly understood. In this study, we employed an integrated approach combining top-down targeted proteomics with mechanical measurements to dissect the molecular mechanism(s) in age-related muscle dysfunction. Top-down targeted proteomic analysis uncovered a progressive age-related decline in the phosphorylation of myosin regulatory light chain (RLC), a critical protein involved in the modulation of muscle contractility, in the skeletal muscle of aging rats. Top-down tandem mass spectrometry analysis identified a previously unreported bis-phosphorylated proteoform of fast skeletal RLC and localized the sites of decreasing phosphorylation to Ser14/15. Of these sites, Ser14 phosphorylation represents a previously unidentified site of phosphorylation in RLC from fast-twitch skeletal muscle. Subsequent mechanical analysis of single fast-twitch fibers isolated from the muscles of rats of different ages revealed that the observed decline in RLC phosphorylation can account for age-related decreases in the contractile properties of sarcopenic fast-twitch muscles. These results strongly support a role for decreasing RLC phosphorylation in sarcopenia-associated muscle dysfunction and suggest that therapeutic modulation of RLC phosphorylation may represent a new avenue for the treatment of sarcopenia.

Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy.

PubMed

Mottram, Philip M; Haluska, Brian; Yuda, Satoshi; Leano, Rodel; Marwick, Thomas H

2004-03-03

We sought to determine if a hypertensive response to exercise (HRE) is associated with myocardial changes consistent with early hypertensive heart disease. An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical stage of HT. Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were recruited into three matched groups: 41 patients (age 56 +/- 10 years) with HRE (>210/105 mm Hg in men; >190/105 in women), comprising 22 patients with (HT+) and 19 without resting hypertension (HT-); and 17 matched control subjects without HRE. Long-axis function was determined by measurement of the strain rate (SR), peak systolic strain, and cyclic variation (CV) of integrated backscatter in three apical views. An HRE was not associated with significant differences in LV mass index. Exercise performance and diastolic function were reduced in HRE(HT+) patients, but similar in HRE(HT-) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV) was significantly reduced in HRE patients (p < 0.001 for all). These reductions were equally apparent in patients with and without a history of resting HT (p = NS) and were independent of LV mass index and blood pressure (p < 0.01). An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT. These changes occur before the development of LV hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease.

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Treating SCA1 Mice with Water-Soluble Compounds to Non-Specifically Boost Mitochondrial Function.

PubMed

Ferro, Austin; Carbone, Emily; Marzouk, Evan; Siegel, Asher; Nguyen, Donna; Polley, Kailen; Hartman, Jessilyn; Frederick, Kimberley; Ives, Stephen; Lagalwar, Sarita

2017-01-22

Mitochondrial dysfunction plays a significant role in the aging process and in neurodegenerative diseases including several hereditary spinocerebellar ataxias and other movement disorders marked by progressive degeneration of the cerebellum. The goal of this protocol is to assess mitochondrial dysfunction in Spinocerebellar ataxia type 1 (SCA1) and assess the efficacy of pharmacological targeting of metabolic respiration via the water-soluble compound succinic acid to slow disease progression. This approach is applicable to other cerebellar diseases and can be adapted to a host of water-soluble therapies. Ex vivo analysis of mitochondrial respiration is used to detect and quantify disease-related changes in mitochondrial function. With genetic evidence (unpublished data) and proteomic evidence of mitochondrial dysfunction in the SCA1 mouse model, we evaluate the efficacy of treatment with the water-soluble metabolic booster succinic acid by dissolving this compound directly into the home cage drinking water. The ability of the drug to pass the blood brain barrier can be deduced using high performance liquid chromatography (HPLC). The efficacy of these compounds can then be tested using multiple behavioral paradigms including the accelerating rotarod, balance beam test and footprint analysis. Cytoarchitectural integrity of the cerebellum can be assessed using immunofluorescence assays that detect Purkinje cell nuclei and Purkinje cell dendrites and soma. These methods are robust techniques for determining mitochondrial dysfunction and the efficacy of treatment with water-soluble compounds in cerebellar neurodegenerative disease.

Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism

PubMed Central

Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.

2010-01-01

Objective To investigate the functional integrity of cerebellar and frontal system in autism using oculomotor paradigms. Background Cerebellar and neocortical systems models of autism have been proposed. Courchesne and colleagues have argued that cognitive deficits such as shifting attention disturbances result from dysfunction of vermal lobules VI and VII. Such a vermal deficit should be associated with dysmetric saccadic eye movements because of the major role these areas play in guiding the motor precision of saccades. In contrast, neocortical models of autism predict intact saccade metrics, but impairments on tasks requiring the higher cognitive control of saccades. Methods A total of 26 rigorously diagnosed nonmentally retarded autistic subjects and 26 matched healthy control subjects were assessed with a visually guided saccade task and two volitional saccade tasks, the oculomotor delayed-response task and the antisaccade task. Results Metrics and dynamic of the visually guided saccades were normal in autistic subjects, documenting the absence of disturbances in cerebellar vermal lobules VI and VII and in automatic shifts of visual attention. Deficits were demonstrated on both volitional saccade tasks, indicating dysfunction in the circuitry of prefrontal cortex and its connections with the parietal cortex, and associated cognitive impairments in spatial working memory and in the ability to voluntarily suppress context-inappropriate responses. Conclusions These findings demonstrate intrinsic neocortical, not cerebellar, dysfunction in autism, and parallel deficits in higher order cognitive mechanisms and not in elementary attentional and sensorimotor systems in autism. PMID:10102406

Redefining the gut as the motor of critical illness

PubMed Central

Mittal, Rohit; Coopersmith, Craig M.

2013-01-01

The gut is hypothesized to play a central role in the progression of sepsis and multiple organ dysfunction syndrome. Critical illness alters gut integrity by increasing epithelial apoptosis and permeability and by decreasing epithelial proliferation and mucus integrity. Additionally, toxic gut-derived lymph induces distant organ injury. Although the endogenous microflora ordinarily exist in a symbiotic relationship with the gut epithelium, severe physiologic insults alter this relationship, leading to induction of virulence factors in the microbiome, which, in turn, can perpetuate or worsen critical illness. This review highlights newly discovered ways in which the gut acts as the motor that perpetuates the systemic inflammatory response in critical illness. PMID:24055446

Integration of sensory force feedback is disturbed in CRPS-related dystonia.

PubMed

Mugge, Winfred; van der Helm, Frans C T; Schouten, Alfred C

2013-01-01

Complex regional pain syndrome (CRPS) is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. The origin of this movement disorder is poorly understood, although recent insights suggest involvement of disturbed force feedback. Assessment of sensorimotor integration may provide insight into the pathophysiology of fixed dystonia. Sensory weighting is the process of integrating and weighting sensory feedback channels in the central nervous system to improve the state estimate. It was hypothesized that patients with CRPS-related dystonia bias sensory weighting of force and position toward position due to the unreliability of force feedback. The current study provides experimental evidence for dysfunctional sensory integration in fixed dystonia, showing that CRPS-patients with fixed dystonia weight force and position feedback differently than controls do. The study shows reduced force feedback weights in CRPS-patients with fixed dystonia, making it the first to demonstrate disturbed integration of force feedback in fixed dystonia, an important step towards understanding the pathophysiology of fixed dystonia.

Is language impairment more common than executive dysfunction in amyotrophic lateral sclerosis?

PubMed

Taylor, Lorna J; Brown, Richard G; Tsermentseli, Stella; Al-Chalabi, Ammar; Shaw, Christopher E; Ellis, Catherine M; Leigh, P Nigel; Goldstein, Laura H

2013-05-01

Systematic explorations of language abilities in patients with amyotrophic lateral sclerosis (ALS) are lacking in the context of wider cognitive change. Neuropsychological assessment data were obtained from 51 patients with ALS and 35 healthy controls matched for age, gender and IQ. Composite scores were derived for the domains of language and executive functioning. Domain impairment was defined as a composite score ≤5th centile relative to the control mean. Cognitive impairment was also classified using recently published consensus criteria. The patients with ALS were impaired on language and executive composite scores. Language domain impairment was found in 43% of patients with ALS, and executive domain impairment in 31%. Standardised language and executive composite scores correlated in the ALS group (r=0.68, p<0.001). Multiple regression analyses indicated that scores on the executive composite accounted for 44% of the variance in language composite scores. Language impairments are at least as prevalent as executive dysfunction in ALS. While the two domains are strongly associated, executive dysfunction does not fully account for the profile of language impairments observed, further highlighting the heterogeneity of cognitive impairment in non-demented patients with ALS.

Do ventilated packs reduce post-operative eustachian tube dysfunction?

PubMed

Morgan, N J; Soo, G; Frain, I; Nunez, D A

1995-10-01

Nasal packing is associated with post-operative Eustachian tube dysfunction in patients undergoing nasal surgical procedures. The effect of cannulated nasal packs which may improve nasopharyngeal ventilation was investigated in a prospective randomized controlled trial. Adult elective patients without tympanometric evidence of pre-operative Eustachian tube dysfunction were recruited. All subjects underwent single or combined intranasal surgical procedures and were randomized to receive either bilateral cannulated or non-cannulated Merocel nasal packs. Middle ear pressures (MEP) were recorded pre-operatively and post-operatively before nasal pack removal. Left and right ear results were amalgamated for analysis and 40 adults, 20 in each group were analysed. There was no difference in pre-operative MEP, -15 dPa (median value) in both groups. Post-operatively the MEP changed in both groups P < 0.0001. There was no significant inter group difference in the post-operative median MEP, -85 dPa in the cannulated and -70 dPa in the control groups, (95% c.i. for the difference in the medians -25-55 dPa). Nasal surgery with post-operative packing leads to an objective reduction in MEP which is not altered by venting the packs.

The Structure of Adult ADHD

PubMed Central

Adler, Lenard A.; Faraone, Stephen V.; Spencer, Thomas J.; Berglund, Patricia; Alperin, Samuel; Kessler, Ronald C.

2017-01-01

Although DSM-5 stipulates that symptoms of attention-deficit/hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limited in ways addressed in the current study, which analyzes the structure of an expanded set of adult ADHD symptoms in 3 pooled U.S. samples: a national household sample, a sample of health plan members, and a sample of adults referred for evaluation at an adult ADHD clinic. Exploratory factor analysis found 4 factors representing executive dysfunction/inattention (including, but not limited to, all the DSM-5 inattentive symptoms, with non-DSM symptoms having factor loadings comparable to those of DSM symptoms), hyperactivity, impulsivity, and emotional dyscontrol. Empirically-derived multivariate symptom profiles were broadly consistent with the DSM-5 inattentive-only, hyperactive/impulsive-only, and combined presentations, but with inattention including executive dysfunction/inattention and hyperactivity-only limited to hyperactivity without high symptoms of impulsivity. These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but prominent resent in the combined presentation of adult ADHD. PMID:28211596

Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95).

PubMed

Chen, Qiwei; Pandi, Sudha Priya Soundara; Kerrigan, Lauren; McElvaney, Noel G; Greene, Catherine M; Elborn, J Stuart; Taggart, Clifford C; Weldon, Sinéad

2018-02-24

Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells. Apoptosis and associated caspase activity were analysed in non-CF and CF tracheal and bronchial epithelial cell lines. Basal levels of apoptosis and activity of caspase-3 and caspase-8 were significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings from CF patients compared to non-CF controls. Neutralisation of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. In addition, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway, which may be associated with dysfunctional CFTR. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

Family Drawings before and after Treatment for Child Conduct Problems: Fluidity of Family Dysfunction.

PubMed

Kloft, Lilian; Hawes, David; Moul, Caroline; Sultan, Sonia; Dadds, Mark

2017-01-01

Children's drawings have previously been found to reflect their representations of family relationships. The present study examined whether evidence-based parent training for child conduct problems impacts on representations of family functioning using the Family Drawing Paradigm (FDP). N  = 53 clinic-referred children (aged 3-15) with conduct problems and their families were assessed pre-treatment and at 6-month follow-up on a modified version of the FDP. Analyses of changes in the FDP revealed improvements in family functioning but not tone of language (as indicated by written descriptors) following treatment. Higher family dysfunction scores were associated with increased levels of callous-unemotional (CU) traits in the children pre-treatment. Children with high levels of CU, however, demonstrated greater change in FDP dysfunction than a low CU group, resulting in similar levels at follow-up. CU traits also moderated the association between change in family warmth and conduct problem severity, with increased FDP warmth more strongly related to improved conduct problems in the high vs. the low CU group. FDP drawings are sensitive to changes in family functioning arising from parent training, accounting for unique variance in child outcomes independent of verbal reports.

Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes.

PubMed

Calkins, Monica E; Iacono, William G; Ones, Deniz S

2008-12-01

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.

How to recognize late-onset hypogonadism in men with sexual dysfunction

PubMed Central

Corona, Giovanni; Rastrelli, Giulia; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2012-01-01

Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels. PMID:22286862

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

PubMed

Karri, Venkatanaidu; Schuhmacher, Marta; Kumar, Vikas

2016-12-01

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. Copyright © 2016 Elsevier B.V. All rights reserved.

The relationship between arterial wall stiffness and left ventricular dysfunction.

PubMed

Hu, Y; Li, L; Shen, L; Gao, H

2013-05-01

The purpose of this study was to explore the relationship between left ventricular (LV) dysfunction and arterial wall stiffening. A total of 218 patients over the age of 45 diagnosed with hypertension in Jinan City and hospitalised between 2010 and 2011 were included in this study. LV function was evaluated using echocardiography (ECHO). Blood pressure was monitored with an automated tonometric device, and the parameters of arterial wall stiffness were measured. In addition, the metabolic parameters of blood samples, such as glucose and lipids, were also determined using the Cobas E601 analyser. Stiffness parameter beta positively correlated with LV diastolic function (E/Em ratio) (r = 0.255, p < 0.001). LV end-diastolic diameter not only related to the E/Em ratio (r = 0.196, p = 0.009) but also with beta (r = 0.220, p = 0.002). The stiffness parameter beta was an early indicator of E/Em ratio as determined by multiple regression analysis (R (2) = 0.381, p < 0.01). Age, blood pressure and fasting blood glucose contributed to stiffness parameter beta (p < 0.05), as well as the E/Em ratio (p < 0.01). Our findings suggested that LV dysfunction may have a direct relationship to arterial stiffening, independently of having similar risk factors. In addition, arterial stiffness can be an independent predictor of LV diastolic function, suggesting that the severity of arterial stiffness directly correlates with the severity of LV dysfunction.

[Thyroid hormones and cardiovascular system].

PubMed

Límanová, Zdeňka; Jiskra, Jan

Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

Increasing Orgasm and Decreasing Dyspareunia by a Manual Physical Therapy Technique

PubMed Central

Wurn, Lawrence J; Wurn, Belinda F; Roscow, Amanda S; King, C Richard; Scharf, Eugenia S; Shuster, Jonathan J

2004-01-01

Context Female sexual pain and dysfunction Objective To evaluate the effectiveness of a new site-specific, manual soft-tissue therapy in increasing orgasm and reducing dyspareunia (painful intercourse) in women with histories indicating abdominopelvic adhesion formation. Design and Intervention A total of 29 new patients presenting with infertility or abdominopelvic pain-related problems, and also indicating sexual pain or dysfunction, received a series of treatments (mean, 19.5 hours) designed to address biomechanical dysfunction and restricted mobility due to adhesions affecting the reproductive organs and adjacent structures. Outcome Measures Primary outcome measures were post-test vs pretest scores on: (1) the Female Sexual Function Index (FSFI) full scale, orgasm domain, and pain domain; and (2) 3 supplemental 10-point rating scales of sexual pain levels. Secondary outcome measures were post-test vs pretest scores in the other 4 FSFI domains (desire, arousal, lubrication, and satisfaction). The Wilcoxon signed-rank test was used for all statistical analyses. Results For the 23 patients available for follow-up, the paired FSFI post-test vs pretest scores were significant (P ≤ .003) on all measures. Of the 17 patients who completed the 3 sexual pain scales, the paired post-test vs pretest scores were significant (P ≤ .002) Conclusions Many cases of inhibited orgasm, dyspareunia, and other aspects of sexual dysfunction seem to be treatable by a distinctive, noninvasive manual therapy with no risks and few, if any, adverse effects. The therapy should be considered a new adjunct to existing gynecologic and medical treatments. PMID:15775874

Regulation of Mitochondrial Function and Glutamatergic System Are the Target of Guanosine Effect in Traumatic Brain Injury.

PubMed

Dobrachinski, Fernando; da Rosa Gerbatin, Rogério; Sartori, Gláubia; Ferreira Marques, Naiani; Zemolin, Ana Paula; Almeida Silva, Luiz Fernando; Franco, Jeferson Luis; Freire Royes, Luiz Fernando; Rechia Fighera, Michele; Antunes Soares, Félix Alexandre

2017-04-01

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca 2+ homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.

The impact of ejaculatory dysfunction upon the sufferer and his partner

PubMed Central

2016-01-01

Ejaculatory function cannot be evaluated outside the dyadic process and without taking into account the men’s and women’s cognition of the condition and how their subjective perception impacts on the evaluation of the relationship and sexual quality. Although the distress of the sufferer and his partner has been a motivating factor in leading men with ejaculatory dysfunction to seek medical help, few objective or prospective evaluations of the effects on the couple have been reported. Specialized literature has been dealing with ejaculatory disorders in a heterogeneous manner. Comparatively, there are far more studies on premature ejaculation (PE) than on delayed ejaculation (DE) and even fewer studies on other male orgasm disorders. Therefore, the review focuses on the literature of the two most studied ejaculatory disorders. The matter presented in this article can also be considered for other ejaculatory disorders, since all of them relate to a failure of control, changing the intravaginal ejaculatory latency time (IELT), with consequences for men and their partners. There are multiple psychological explanations as to why a man develops PE or DE. Unfortunately, none of the theories evolve from evidence-based studies. The common final pathway of these factors is the irrational fear of ejaculating intravaginally. These sexual disorders may also cause personal distress for the sexual partner and decreased sexual satisfaction for the couple. An association between pre-existing anxiety disorders and sexual performance anxiety has been found in men and couples with ejaculatory dysfunction. This could reflect a process in which pre-existing anxiety triggers sexual dysfunction, causing performance anxiety and leading to a vicious cycle: anxiety, sexual dysfunction, more anxiety. Men with DE are similar to men with other sexual dysfunctions. They show the same elevated level of sexual dissatisfaction and they also show lower levels of coital frequency. To a lower extent, they use more masturbatory activity relative to controls. The burden of PE for the patient is revealed in three different levels: the emotional burden, the health burden, and the burden on the relationship. In terms of the emotional burden, there is often a sense of embarrassment and shame at not being able to satisfy their partner, and patients often have low self-esteem, feelings of inferiority, anxiety, anger, and disappointment. Men feel frustrated about their PE and how it affects their intimacy with their partners and the sexual relationship. In conclusion, ejaculatory dysfunction has a negative impact on both the man and his female partner and, consequently, it has implications for the couple as a whole. Additionally, ejaculatory dysfunction extending beyond a year elevates the risk of depression in these patients. Although partner perceptions of PE generally indicated less dysfunction than those of subjects, partner outcomes measures play a part in the assessment of PE. Ejaculatory dysfunction involves the integration of physiological, psychobehavioral, cultural, and relationship dimensions. All these elements need to be considered in the treatment. PMID:27652218

[KON-2006--Neurotic Personality Questionnaire].

PubMed

Aleksandrowicz, Jerzy W; Klasa, Katarzyna; Sobański, Jerzy A; Stolarska, Dorota

2007-01-01

Construction of a questionnaire describing personality traits connected to the occurrence and persistence of neurotic disorders. Responses of 794 patients (before treatment) and 520 persons from the control group on items of the constructed personality questionnaire and the symptom checklist "0". Analyses of subscales reliability and item-scale correlations, test-retest and split-half reliability. Factor analyses estimating internal reliability of the questionnaire. Cross-validation with the KO"0". symptom checklist Psychometric properties of KON-2006 questionnaire indicate that it is consistent and reliable enough. Validity analyses indicate a large probability that the X-KON coefficient informs on personality dysfunctions related to neurotic disorders. The Neurotic Personality Questionnaire KON-2006 may serve to estimate personality traits connected to the occurrence and persistence of neurotic disorders as well as changes resulting from psychotherapy.

Neurological signs and morphological cerebral changes in schizophrenia: An analysis of NSS subscales in patients with first episode psychosis.

PubMed

Heuser, Mark; Thomann, Philipp A; Essig, Marco; Bachmann, Silke; Schröder, Johannes

2011-05-31

Neurological soft signs (NSS) comprise a broad range of minor motor and sensory deficits which are frequently found in schizophrenia. However, the cerebral changes underlying NSS are only partly understood. We therefore investigated the cerebral correlates of NSS by using magnetic resonance imaging (MRI) in 102 patients with first episode schizophrenia. NSS were assessed after remission of acute psychotic symptoms using the Heidelberg scale (HS), which consists of five NSS subscales ("motor coordination", "complex motor tasks", "orientation", "integrative functions", and "hard signs"). Correlations between NSS scores and cerebral changes were established by optimized voxel-based morphometry. NSS total scores were significantly associated with reduced gray matter densities in the precentral and postcentral gyri, the inferior parietal lobule and the inferior occipital gyrus. Both of the NSS subscales "motor coordination" and "complex motor tasks", referred to motor strip changes but showed differential correlations with parietal, insular, cerebellar or frontal sites, respectively. The NSS subscales "orientation" and "integrative functions" were associated with left frontal, parietal, and occipital changes or bihemispheric frontal changes, respectively. The NSS subscale "hard signs" was associated with deficits in the right cerebellum and right parastriate cortex. Repeated analyses for white matter changes revealed similar results. These findings confirm the associations between NSS and cerebral changes in areas important for motor and sensory functioning. This variety of cerebral sites corresponds to the heterogeneity of NSS and are consistent with the hypothesis that NSS reflect both a rather generalized cerebral dysfunction and localized deficits specific for particular signs. 2010 Elsevier Ireland Ltd. All rights reserved.

Altered connections on the road to psychopathy.

PubMed

Craig, M C; Catani, M; Deeley, Q; Latham, R; Daly, E; Kanaan, R; Picchioni, M; McGuire, P K; Fahy, T; Murphy, D G M

2009-10-01

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

Command Dysfunction: Minding the Cognitive War

DTIC Science & Technology

1996-06-01

failure sometimes resulted from the physical test of arms in combat, leading to a mortal wound. At other times the fall was psychological , brought...for the attack and protection of command and control. The doctrinal definition follows: C2W is the integrated use of psychological operations (PSYOP... psychological , components of C2W. The problem of emphasizing direct attack C2W targeting is that it potentially underplays the complementary aspect of

Elucidating the Role of Hyposalivation and Autoimmunity in Oral Candidiasis

PubMed Central

Billings, Monisha; Dye, Bruce A.; Iafolla, Timothy; Grisius, Margaret; Alevizos, Ilias

2016-01-01

Introduction Oral candidiasis (OC) is a potential oral complication in Sjögren’s Syndrome (SS). Some studies indicate that the low stimulated salivary flow and not low unstimulated salivary flow is associated with OC in SS, while others report that the underlying autoimmune disorders contributes to OC, based solely on correlation coefficients. Given the conflicting and limited existing evidence, we purposed to ascertain the role of both salivary gland dysfunction (hyposalivation based on unstimulated and stimulated flow rates) and autoimmunity (SS, other autoimmune disorders) in OC among those with SS, other salivary gland dysfunction and non-salivary gland dysfunction controls (NSGD). Methods A nested case-control study was designed within a larger NIH/NIDCR cohort. Descriptive analyses, non-parametric tests, comparative analyses, and multivariate logistic regression analyses were undertaken. Results Data on 1,526 subjects (701 SS, 247 ISS, 355 Sicca, and 223 NSGD) were obtained from the source cohort of 2,046 and analyzed for this current study. The median whole unstimulated salivary flow rate (WUS, ml/15min) was lower in SS (0.8, interquartile range (IQR) 1.8) compared to ISS (5.5, IQR 5.2, p<0.001) and NSGD (3.8, IQR 3.8, p<0.001) but comparable with that of Sicca (1.0, IQR 1.5, p=0.777) participants. The median total stimulated salivary flow rate (TSS, ml/15min) was lowest in SS (7.0, IQR 12.4, p<0.001) compared to other groups. Of the 45 OC cases in this cohort, 71.1% (n=32) were from the SS group. The prevalence of OC was highest in the SS group (4.6%, p=0.008). SS group had twice the risk of OC than NSGD (OR =2.2, 95%CI: 1.1–4.2,p=0.02 ) and Sicca (OR =2.2, 95%CI:1.0–4.8, p=0.03 ), adjusting for confounders; hyposalivation [WUS (OR=5.1, 95%CI: 2.5–10.4, p<0.001), TSS (OR=1.9, 95%CI:1.0–3.5, p=0.04)], history of other autoimmune disorders (OR=4.4, 95%CI:1.7–11.3, p=0.002), medications for extraglandular manifestations (OR=2.3, 95%CI:1.1–4.9, p=0.03), and diabetes mellitus (4.2, 95%CI:1.2–15.2, p=0.02) were independent predictors of OC; females had a lower risk than males (OR =0.29, 95%CI:0.13–0.67,p=0.004). Age, race, anti-SSA/SSB autoantibodies, focus score, other medications, anxiety, fatigue, cigarette smoking, alcohol, and caffeine use were not associated with oral candidiasis. Conclusion Salivary gland dysfunction (hyposalivation with WUS being a stronger predictor than TSS) and autoimmunity (SS, other autoimmune disorders, medications i.e., DMARDS) are both independent predictors of OC. Diabetes mellitus is an independent predictor of OC among those with salivary gland dysfunction. Our findings suggest that these independent predictors should be considered in the prevention and management of OC in this population. PMID:27998016

Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study.

PubMed

Sörensen, Ben M; Houben, Alfons J H M; Berendschot, Tos T J M; Schouten, Jan S A G; Kroon, Abraham A; van der Kallen, Carla J H; Henry, Ronald M A; Koster, Annemarie; Sep, Simone J S; Dagnelie, Pieter C; Schaper, Nicolaas C; Schram, Miranda T; Stehouwer, Coen D A

2016-11-01

Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P<0.001 and standardized B=-0.13 [-0.19 to -0.07], P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 [-0.15 to -0.04], P<0.001 and standardized B=-0.10 [-0.15 to -0.04], P=0.002, respectively). Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure. © 2016 American Heart Association, Inc.

Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.

PubMed

Atallah, Afnan; Mhaouty-Kodja, Sakina; Grange-Messent, Valérie

2017-09-01

A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

PubMed Central

Sajja, Ravi K; Rahman, Shafiqur

2015-01-01

Psychostimulants and nicotine are the most widely abused drugs with a detrimental impact on public health globally. While the long-term neurobehavioral deficits and synaptic perturbations are well documented with chronic use of methamphetamine, cocaine, and nicotine, emerging human and experimental studies also suggest an increasing incidence of neurovascular complications associated with drug abuse. Short- or long-term administration of psychostimulants or nicotine is known to disrupt blood-brain barrier (BBB) integrity/function, thus leading to an increased risk of brain edema and neuroinflammation. Various pathophysiological mechanisms have been proposed to underlie drug abuse-induced BBB dysfunction suggesting a central and unifying role for oxidative stress in BBB endothelium and perivascular cells. This review discusses drug-specific effects of methamphetamine, cocaine, and tobacco smoking on brain microvascular crisis and provides critical assessment of oxidative stress-dependent molecular pathways focal to the global compromise of BBB. Additionally, given the increased risk of human immunodeficiency virus (HIV) encephalitis in drug abusers, we have summarized the synergistic pathological impact of psychostimulants and HIV infection on BBB integrity with an emphasis on unifying role of endothelial oxidative stress. This mechanistic framework would guide further investigations on specific molecular pathways to accelerate therapeutic approaches for the prevention of neurovascular deficits by drugs of abuse. PMID:26661236

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function.

PubMed

Cabib, Christopher; Ortega, Omar; Kumru, Hatice; Palomeras, Ernest; Vilardell, Natalia; Alvarez-Berdugo, Daniel; Muriana, Desirée; Rofes, Laia; Terré, Rosa; Mearin, Fermín; Clavé, Pere

2016-09-01

Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction. © 2016 New York Academy of Sciences.

The interleukin-1 receptor antagonist anakinra improves endothelial dysfunction in streptozotocin-induced diabetic rats.

PubMed

Vallejo, Susana; Palacios, Erika; Romacho, Tania; Villalobos, Laura; Peiró, Concepción; Sánchez-Ferrer, Carlos F

2014-12-18

Endothelial dysfunction is a crucial early phenomenon in vascular diseases linked to diabetes mellitus and associated to enhanced oxidative stress. There is increasing evidence about the role for pro-inflammatory cytokines, like interleukin-1β (IL-1β), in developing diabetic vasculopathy. We aimed to determine the possible involvement of this cytokine in the development of diabetic endothelial dysfunction, analysing whether anakinra, an antagonist of IL-1 receptors, could reduce this endothelial alteration by interfering with pro-oxidant and pro-inflammatory pathways into the vascular wall. In control and two weeks evolution streptozotocin-induced diabetic rats, either untreated or receiving anakinra, vascular reactivity and NADPH oxidase activity were measured, respectively, in isolated rings and homogenates from mesenteric microvessels, while nuclear factor (NF)-κB activation was determined in aortas. Plasma levels of IL-1β and tumor necrosis factor (TNF)-α were measured by ELISA. In isolated mesenteric microvessels from control rats, two hours incubation with IL-1β (1 to 10 ng/mL) produced a concentration-dependent impairment of endothelium-dependent relaxations, which were mediated by enhanced NADPH oxidase activity via IL-1 receptors. In diabetic rats treated with anakinra (100 or 160 mg/Kg/day for 3 or 7 days before sacrifice) a partial improvement of diabetic endothelial dysfunction occurred, together with a reduction of vascular NADPH oxidase and NF-κB activation. Endothelial dysfunction in diabetic animals was also associated to higher activities of the pro-inflammatory enzymes cyclooxygenase (COX) and the inducible isoform of nitric oxide synthase (iNOS), which were markedly reduced after anakinra treatment. Circulating IL-1β and TNF-α levels did not change in diabetic rats, but they were lowered by anakinra treatment. In this short-term model of type 1 diabetes, endothelial dysfunction is associated to an IL-1 receptor-mediated activation of vascular NADPH oxidase and NF-κB, as well as to vascular inflammation. Moreover, endothelial dysfunction, vascular oxidative stress and inflammation were reduced after anakinra treatment. Whether this mechanism can be extrapolated to a chronic situation or whether it may apply to diabetic patients remain to be established. However, it may provide new insights to further investigate the therapeutic use of IL-1 receptor antagonists to obtain vascular benefits in patients with diabetes mellitus and/or atherosclerosis.

Clinical and psychosocial factors associated with quality of life in alcohol-dependent men with erectile dysfunction.

PubMed

Ponizovsky, Alexander M

2008-10-01

Men with alcohol dependence (AD) commonly suffer from alcohol-induced sexual (erectile) dysfunction (ED) and have poor quality of life (Qol). Knowledge about the factors associated with Qol in such patients is lacking. To identify in men who sought medical help for both AD and ED the variables that best predicted feelings of satisfaction with life and with specific life domains. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Secondary study measures were the International Index of Erectile Function (IIEF), Beck Depression Inventory (BDI-13), General Health Questionnaire (GHQ-12), Rosenberg's General Self-Esteem Scale (RGSES), and the Multidimensional Scale of Perceived Social Support (MSPSS). Within an open-label sildenafil trial, 101 men aged 18-50 years with an International Classification of Diseases, Tenth Edition diagnosis of AD and concomitant ED were interviewed and completed the questionnaires. Multivariate analyses were applied to establish predictors of life satisfaction and factors mediating the relation between ED and life satisfaction. ED and self-rated depressive symptoms, emotional distress, self-esteem, and perceived social support were found to be significantly associated with Qol and its component domains. Altogether they explained 18-38% of the variance in the Qol ratings. Depressive symptomatology, distress, and self-esteem, individually, demonstrated a mediating effect on the relation between ED and Qol. Finally, self-esteem was shown to be the primary mediator in this relationship. The results of the study show that self-esteem is the primary factor, and depressive symptoms and severe emotional distress are secondary factors mediating the effects of ED on Qol in male patients seeking medical help for both AD and ED. An integrated pharmacopsychosocial approach targeting the underlying ED as well as the mediating emotional conditions could improve Qol of these patients and thus help them to stop using alcohol.

Erectile dysfunction (ED) is a shared sexual concern of couples II: association of female partner characteristics with male partner ED treatment seeking and phosphodiesterase type 5 inhibitor utilization.

PubMed

Fisher, William A; Eardley, Ian; McCabe, Marita; Sand, Michael

2009-11-01

Erectile dysfunction (ED) is a prevalent condition that impacts on both patients and their female partners. ED may therefore be regarded as a shared sexual concern for couples. The current analysis of the Female Experience of Men's Attitudes to Life Events and Sexuality (FEMALES) study data addresses women's perceptions, beliefs, and attitudes concerning their partner's ED, and whether these are associated with the likelihood of the male partner seeking medical advice and utilizing phosphodiesterase type 5 inhibitors. The current research sought to explore the association of female partners' perceptions of male partners' ED and male partners' medical consultation and treatment seeking for ED. Questionnaires were sent to partners of men who participated in the Men's Attitudes to Life Events and Sexuality (MALES) 2004 study, and who consented to their partner's involvement. A modified version of the questionnaire used in the MALES study was developed for the FEMALES study, reflecting the female partner's perspective. A 65-item questionnaire assessing women's perceptions, beliefs, and attitudes regarding various aspects of ED. Women's perceptions of the nature and causes of their partner's ED were significantly associated with men's treatment seeking and utilization. Significant associations were observed between women's level of satisfaction with the relationship before ED onset; perceptions of the impact of ED on quality of life; desire to deal with ED; attitudes to ED treatment; and the treatment-seeking behavior of the male partner. Multivariate regression analyses identified a mixture of female and male partner perceptions and attitudes that uniquely accounted for >30% of the variance in men's ED treatment-seeking behavior and treatment utilization. This study illustrates the importance of the female partner's attitudes to ED in men's ED treatment-seeking behavior. These findings strongly support the potential benefits of partner integration into ED consultation and treatment strategies.

Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction.

PubMed

Kiss, Márton; Kiss, András A; Radics, Monika; Popovics, Nikoletta; Hermesz, Edit; Csiszár, Katalin; Mink, Mátyás

2016-01-01

The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that aberrant structure and function of the COL4A1 protein may also be a significant factor in modulating immunity.

The Effect of Chronic Antipsychotic Drug on Hypothalamic Expression of Neural Nitric Oxide Synthase and Dopamine D2 Receptor in the Male Rat

PubMed Central

Zhang, Zhi Jun; Li, Lei; Reynolds, Gavin P.

2012-01-01

Antipsychotic-induced sexual dysfunction is a common and serious clinical side effect. It has been demonstrated that both neuronal nitric oxide (nNOS) and dopamine D2 receptor (DRD2) in the medial preoptic area (MPOA) and the paraventricular nucleus (PVN) of the hypothalamus have important roles in the regulation of sexual behaviour. We investigated the influences of 21 days’ antipsychotic drug administration on expression of nNOS and DRD2 in the rat hypothalamus. Haloperidol (0.5 mg/kg/day i.p.) significantly decreased nNOS integrated optical density in a sub-nucleus of the MPOA, medial preoptic nucleus (MPN), and decreased the nNOS integrated optical density and cell density in another sub-nucleus of the MPOA, anterodorsal preoptic nucleus (ADP). Risperidone (0.25 mg/kg) inhibited the nNOS integrated optical density in the ADP. nNOS mRNA and protein in the MPOA but not the PVN was also significantly decreased by haloperidol. Haloperidol and risperidone increased DRD2 mRNA and protein expression in both the MPOA and the PVN. Quetiapine (20 mg/kg/day i.p.) did not influence the expression of nNOS and DRD2 in either the MPOA or the PVN. These findings indicate that hypothalamic nNOS and DRD2 are affected to different extents by chronic administration of risperidone and haloperidol, but are unaffected by quetiapine. These central effects might play a role in sexual dysfunction induced by certain antipsychotic drugs. PMID:22514604

Eplerenone : a pharmacoeconomic review of its use in patients with post-myocardial infarction heart failure.

PubMed

Croom, Katherine F; Plosker, Greg L

2005-01-01

Eplerenone (Inspra) is a selective aldosterone blocker. When added to standard medical therapy, eplerenone significantly improved morbidity and mortality in patients with left ventricular (LV) systolic dysfunction and clinical evidence of heart failure following acute myocardial infarction (MI), in a well designed, placebo-controlled trial known as EPHESUS (Eplerenone Post-acute myocardial infarction Heart failure Efficacy and SUrvival Study). Although eplerenone was generally well tolerated, it was associated with a higher incidence of hyperkalaemia than placebo.Cost-effectiveness analyses based on this trial have been performed in the US, The Netherlands, Germany, France and Spain. Direct medical costs were analysed based on prospectively collected resource-use data with local costs applied; modelling was conducted to calculate incremental costs per life-year or QALY gained, with survival curves assumed to remain parallel after treatment ended. Eplerenone was associated with a gain of 0.0304 life-years (approximately 11 days) compared with placebo during the study period. Based on these analyses, eplerenone was cost effective compared with placebo in patients with LV systolic dysfunction and heart failure after an MI when added to standard therapy for 16 months. The incremental cost per life-year gained for eplerenone versus placebo (for a range of three different life-expectancy projections) was 10,402-21,876 US dollars in the US (year 2001 costs, except for eplerenone [2004]) [equivalent to 12,274-25,814 euro; mid-2001 exchange rate], 5,365-12,795 euro for The Netherlands (year 2003 costs), 6,956-14,628 euro for Germany, 5,432-11,423 euro for France and 8,626-18,141 euro for Spain (year of costing not reported). The US, Dutch, French and Spanish analyses estimated that >90% of observations for incremental cost per life-year gained were below a threshold of 50,000 US dollars or 50,000 euro. Incremental costs per QALY gained for eplerenone versus placebo in the US, Dutch, French and Spanish analyses were 15,330-32,405 US dollars (18,089-38,238 euro), 12,148, 8,005-16,922 euro and 12,713-26, 873 euro, respectively. Clinical and pharmacoeconomic data comparing eplerenone with another active drug, such as spironolactone, in this patient population are not available. In conclusion, when added to standard therapy in patients with LV systolic dysfunction and heart failure after an acute MI, eplerenone was associated with significant reductions in mortality and morbidity compared with placebo. Despite some inherent limitations, available pharmacoeconomic data from Europe and the US indicate that eplerenone is a cost-effective treatment compared with placebo in terms of incremental cost per life-year gained in this patient population.

Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy.

PubMed

Glennon, Jennifer M; Weiss-Croft, Louise; Harrison, Sue; Cross, J Helen; Boyd, Stewart G; Baldeweg, Torsten

2016-09-01

The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder.

PubMed

Richey, John A; Rittenberg, Alison; Hughes, Lauren; Damiano, Cara R; Sabatino, Antoinette; Miller, Stephanie; Hanna, Eleanor; Bodfish, James W; Dichter, Gabriel S

2014-03-01

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

PubMed

Loganathan, Rajprasad; Bilgen, Mehmet; Al-Hafez, Baraa; Alenezy, Mohammed D; Smirnova, Irina V

2006-04-04

Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Pathological anxiety in animals.

PubMed

Ohl, Frauke; Arndt, Saskia S; van der Staay, F Josef

2008-01-01

Selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a consequence, compromise welfare and quality of life. In this review it is proposed that various behavioural dysfunctions in animals are due to pathological anxiety. Although several approaches have been undertaken to specify the diagnostic criteria of pathological anxiety as a behavioural disorder in animals, the causal aetiology largely remains unknown. This is mainly due to the fact that integrated concepts, combining the behavioural syndrome and (neuro-) physiological processes, are widely lacking. Moreover, even the term anxiety itself represents a poorly defined concept or category. A definition is suggested and the potential causes of pathological anxiety are explored with a plea for developing adequate diagnostic tools and therapies to fight pathological anxiety in animals based on insight from scientific research.

Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions.

PubMed

Lacivita, Enza; Perrone, Roberto; Margari, Lucia; Leopoldo, Marcello

2017-11-22

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.

Articulatory rehearsal in verbal working memory: a possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder.

PubMed

Gruber, Oliver; Gruber, Eva; Falkai, Peter

2006-09-11

Recent fMRI studies have identified brain systems underlying different components of working memory in healthy individuals. The aim of this study was to compare the functional integrity of these neural networks in terms of behavioural performance in patients with schizophrenia, schizoaffective disorder and healthy controls. In order to detect specific working memory deficits based on dysfunctions of underlying brain circuits we used the same verbal and visuospatial Sternberg item-recognition tasks as in previous neuroimaging studies. Clinical and performance data from matched groups consisting of 14 subjects each were statistically analyzed. Schizophrenic patients exhibited pronounced impairments of both verbal and visuospatial working memory, whereas verbal working memory performance was preserved in schizoaffective patients. The findings provide first evidence that dysfunction of a brain system subserving articulatory rehearsal could represent a biological marker which differentiates between schizophrenia and schizoaffective disorder.

Effect of agmatine on experimental vascular endothelial dysfunction.

PubMed

Nader, M A; Gamiel, N M; El-Kashef, H; Zaghloul, M S

2016-05-01

This study was designed to investigate the effect of agmatine sulfate (AG, CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in rabbits. NIC was administered to produce VED in rabbits with or without AG for 6 weeks. Serum lipid profile, serum thiobarbituric acid reactive substances, reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate, serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor κB (NF-κB) levels were analyzed.Treatment with AG markedly improves lipid profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG in improving NIC-induced VED may be due to the significant reduction in serum VCAM-1 levels and aortic NF-κB. Thus, it may be concluded that AG reduces the oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-κB expression, thereby consequently improving the integrity of vascular endothelium. © The Author(s) 2015.

New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy.

PubMed

Gopal, Deepa M; Sam, Flora

2013-08-01

Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers--known as "biomarkers"--allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

PubMed

Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

2016-09-01

Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

Music and Autonomic Nervous System (Dys)function

PubMed Central

Ellis, Robert J.; Thayer, Julian F.

2010-01-01

Despite a wealth of evidence for the involvement of the autonomic nervous system (ANS) in health and disease and the ability of music to affect ANS activity, few studies have systematically explored the therapeutic effects of music on ANS dysfunction. Furthermore, when ANS activity is quantified and analyzed, it is usually from a point of convenience rather than from an understanding of its physiological basis. After a review of the experimental and therapeutic literatures exploring music and the ANS, a “Neurovisceral Integration” perspective on the interplay between the central and autonomic nervous systems is introduced, and the associated implications for physiological, emotional, and cognitive health are explored. The construct of heart rate variability is discussed both as an example of this complex interplay and as a useful metric for exploring the sometimes subtle effect of music on autonomic response. Suggestions for future investigations using musical interventions are offered based on this integrative account. PMID:21197136

Regulation of Coronary Blood Flow in Health and Ischemic Heart Disease

PubMed Central

Duncker, Dirk J.; Koller, Akos; Merkus, Daphne; Canty, John M.

2018-01-01

The major factors determining myocardial perfusion and oxygen delivery have been elucidated over the past several decades, and this knowledge has been incorporated into the management of patients with ischemic heart disease (IHD). The basic understanding of the fluid mechanical behavior of coronary stenoses has also been translated to the cardiac catheterization laboratory where measurements of coronary pressure distal to a stenosis and coronary flow are routinely obtained. However, the role of perturbations in coronary microvascular structure and function, due to myocardial hypertrophy or coronary microvascular dysfunction, in IHD is becoming increasingly recognized. Future studies should therefore be aimed at further improving our understanding of the integrated coronary microvascular mechanisms that control coronary blood flow, and of the underlying causes and mechanisms of coronary microvascular dysfunction. This knowledge will be essential to further improve the treatment of patients with IHD. PMID:25475073

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

PubMed

Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

Nmnat mitigates sensory dysfunction in a Drosophila model of paclitaxel-induced peripheral neuropathy.

PubMed

Brazill, Jennifer M; Cruz, Beverley; Zhu, Yi; Zhai, R Grace

2018-06-12

Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many commonly used chemotherapeutic agents, including paclitaxel. Currently, there are no neuroprotective or effective symptomatic treatments for CIPN. Lack of understanding of the in vivo mechanisms of CIPN has greatly impeded the identification of therapeutic targets. Here, we optimized a model of paclitaxel-induced peripheral neuropathy using Drosophila larvae that recapitulates aspects of chemotherapy-induced sensory dysfunction . We showed that nociceptive sensitivity is associated with disrupted organization of microtubule-associated MAP1B/Futsch and aberrant stabilization of peripheral sensory dendrites. These findings establish a robust and amenable model for studying peripheral mechanisms of CIPN. Using this model, we uncovered a critical role for nicotinamide mononucleotide adenylyltransferase (Nmnat) in maintaining the integrity and function of peripheral sensory neurons and uncovered Nmnat's therapeutic potential against diverse sensory symptoms of CIPN. © 2018. Published by The Company of Biologists Ltd.

Fragility fracture risk and skeletal muscle function.

PubMed

Pérez-López, F R; Ara, I

2016-01-01

Low-intensity fractures are closely related with age-related musculoskeletal disorders, including osteoporosis, muscle dysfunction and sarcopenia, age-related chronic diseases, and pharmacological treatments. During the last years, a huge amount of information and recommendations has been released in relation to bone metabolism and mineral content. Muscle dysfunction and sarcopenia are highly prevalent during the second half of life, especially in older subjects. The development of sarcopenia may be slowed through healthy lifestyle changes, which include adequate dietary protein, vitamin D and mineral intakes, and regular physical activity. Prevention of falls should be integral, including correction in major involved factors in order to reduce fragility fracture, improve quality of life and appropriately focus clinical and economic resources. Therefore, to obtain better results a global approach is needed to prevent age-related fractures in frail patients that is not only centered on bone metabolism and antiresorptive drugs.

Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima-Media Thickness: The Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study.

PubMed

Hertle, Elisabeth; Arts, Ilja C W; van der Kallen, Carla J H; Feskens, Edith J M; Schalkwijk, Casper G; Hoffmann-Petersen, Ingeborg T; Thiel, Steffen; Stehouwer, Coen D A; van Greevenbroek, Marleen M J

2016-06-01

Previous studies suggested that the lectin-complement pathway plays a complex role in cardiovascular disease (CVD). To date, no prospective human studies have investigated the relationship between the initiating factor of the lectin pathway, that is, mannose-binding lectin (MBL), and low-grade inflammation, endothelial dysfunction, or carotid intima-media thickness (cIMT). Moreover, MBL-associated proteases (MASPs) and MBL-associated proteins (MAps), which mediate downstream complement activation, have not been studied in the development of CVD. In a prospective cohort (n=574; age 60±7 years; 7-year follow-up), we investigated longitudinal associations of plasma MBL, MASP-1, MASP-2, MASP-3, and MAp44 with biomarker scores that reflect low-grade inflammation and endothelial dysfunction, respectively, and with cIMT. We also investigated their associations with incident CVD (n=73). In adjusted analyses, low-grade inflammation was lowest in the middle tertile (TMiddle) of MBL, that is, TMiddle was 0.19 SD (0.03 to 0.34) lower than TLow, and 0.15 SD (-0.02 to 0.31) lower than THigh. cIMT was 28 μm (-50 to -5) lower in the highest MBL tertile (THigh) than in TMiddle and did not differ between TLow and TMiddle. MBL was not associated with endothelial dysfunction or CVD. MASP-1 and MASP-2 were not associated with any cardiovascular outcomes. MASP-3 and MAp44 were, independently of MBL levels, associated with endothelial dysfunction (per 1 SD higher MASP-3: β=0.10 SD [0.02 to 0.18]; per 1 SD higher MAp44 β=0.12 SD [0.04 to 0.20]) but not with low-grade inflammation, cIMT, or CVD. High MBL may contribute to low cIMT, whereas the association of MBL with low-grade inflammation was nonlinear. MASP-1 and MASP-2 were not associated with adverse cardiovascular outcomes. MASP-3 and MAp44 may play a role in endothelial dysfunction, potentially independent of lectin-pathway activation. © 2016 American Heart Association, Inc.

Effect of biocompatible polymers on the structural integrity of lipid bilayers under external stimuli

NASA Astrophysics Data System (ADS)

Wang, Jia-Yu; Kausik, Ravinath; Chen, Chi-Yuan; Han, Song-I.; Marks, Jeremy; Lee, Ka Yee

2010-03-01

Cell membrane dysfunction due to loss of structural integrity is the pathology of tissue death in trauma and common diseases. It is now established that certain biocompatible polymers, such as Poloxamer 188, Poloxamine 1107 and polyethylene glycol (PEG), are effective in sealing of injured cell membranes, and able to prevent acute necrosis. Despite these broad applications of these polymers for human health, the fundamental mechanisms by which these polymers interact with cell membranes are still under debate. Here, the effects of a group of biocompatible polymers on phospholipid membrane integrity under osmotic and oxidative stress were explored using giant unilamellar vesicles as model cell membranes. Our results suggest that the adsorption of the polymers on the membrane surface is responsible for the cell membrane resealing process due to its capability of slowing down the surface hydration dynamics.

Obsessions and worry beliefs in an inpatient OCD population.

PubMed

Calleo, Jessica S; Hart, John; Björgvinsson, Thröstur; Stanley, Melinda A

2010-12-01

Dysfunctional beliefs in obsessive-compulsive disorder (OCD) and worry are thought to contribute to vulnerability and maintenance of pathological anxiety. In this study, five belief domains concerning responsibility/threat estimation, perfectionism, intolerance of uncertainty, importance/control of thoughts and thought-action fusion were examined to see whether they differentially predicted worry and obsession severity in patients with severe OCD. Correlational analysis revealed that perfectionism and intolerance of uncertainty were associated with worry, whereas beliefs in the importance and control of thoughts and thought-action fusion were associated with obsession severity when obsession severity and worry, respectively, were controlled. In regression analyses, thought-action fusion and intolerance of uncertainty predicted OCD severity. The relation between dysfunctional beliefs and specific subtypes of OCD symptoms was also examined. Specific relationships were identified, including perfectionism with ordering, obsessions with control/importance of thoughts and checking and washing with threat estimation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Episodic memory and executive functioning in currently depressed patients compared to healthy controls.

PubMed

Pauls, Franz; Petermann, Franz; Lepach, Anja Christina

2015-01-01

At present, little is still known about the link between depression, memory and executive functioning. This study examined whether there are memory-related impairments in depressed patients and whether the size of such deficits depends on the age group and on specific types of cognitive measures. Memory performances of 215 clinically depressed patients were compared to the data of a matched control sample. Regression analyses were performed to determine the extent to which executive dysfunctions contributed to episodic memory impairments. When compared with healthy controls, significantly lower episodic memory and executive functioning performances were found for depressed patients of all age groups. Effect sizes appeared to vary across different memory and executive functioning measures. The extent to which executive dysfunctions could explain episodic memory impairments varied depending on the type of measure examined. These findings emphasise the need to consider memory-related functioning of depressed patients in the context of therapeutic treatments.

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

PubMed Central

Torchen, Laura C.

2018-01-01

Purpose of Review Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well-established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent Findings Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. Summary PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed. PMID:29128916

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder.

PubMed

Torchen, Laura C

2017-11-11

Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.

Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Jian; Zhang, Lin; Dai, Weiqi

Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and alsomore » prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.« less

Fundamentals of Embouchure in Brass Players: Towards a Definition and Clinical Assessment.

PubMed

Woldendorp, Kees H; Boschma, Hans; Boonstra, Anne M; Arendzen, Hans J; Reneman, Michiel F

2016-12-01

Brass players may experience problems producing an optimal sound (or range of sounds) in their instrument. Assessing and treating dysfunctional embouchure requires knowledge of functional embouchure, but peer-reviewed literature on dysfunctional and functional embouchure is scarce. This study aimed to provide a narrative overview of embouchure based on information from different scientific and clinical fields. This should be regarded as a first step in constructing a reliable, valid, and practical multi-item method to assess embouchure for brass players. Literature reviews were conducted concerning: 1) the definition of embouchure, 2) physics and acoustics of embouchure, 3) functioning of embouchure-related structures, and 4) instruments to assess embouchure. Also, embouchure experts (clinicians, scientists, and elite wind players) were consulted for information and discussion. A proposal for a new definition of embouchure, an overview of the relevant physics and acoustics, functions of embouchure-related body structures, and the main methods to measure embouchure in brass playing are presented. Peer-reviewed information about the fundamentals of dysfunctional embouchure is scarce and sometimes contradictory. A new definition for embouchure is proposed: embouchure is the process needed to adjust the amount, pressure, and direction of the air flow (generated by the breath support) as it travels through the mouth cavity and between the lips, by the position and/or movements of the tongue, teeth, jaws, cheeks, and lips, to produce a tone in a wind instrument. An integrative overview is presented which can serve as a transparent foundation for the present understanding of functional and dysfunctional embouchure and for developing an evidence-based multi-item assessment instrument.

Stress-Induced Synaptic Dysfunction and Neurotransmitter Release in Alzheimer's Disease: Can Neurotransmitters and Neuromodulators be Potential Therapeutic Targets?

PubMed

Jha, Saurabh Kumar; Jha, Niraj Kumar; Kumar, Dhiraj; Sharma, Renu; Shrivastava, Abhishek; Ambasta, Rashmi K; Kumar, Pravir

2017-01-01

The communication between neurons at synaptic junctions is an intriguing process that monitors the transmission of various electro-chemical signals in the central nervous system. Albeit any aberration in the mechanisms associated with transmission of these signals leads to loss of synaptic contacts in both the neocortex and hippocampus thereby causing insidious cognitive decline and memory dysfunction. Compelling evidence suggests that soluble amyloid-β (Aβ) and hyperphosphorylated tau serve as toxins in the dysfunction of synaptic plasticity and aberrant neurotransmitter (NT) release at synapses consequently causing a cognitive decline in Alzheimer's disease (AD). Further, an imbalance between excitatory and inhibitory neurotransmission systems induced by impaired redox signaling and altered mitochondrial integrity is also amenable for such abnormalities. Defective NT release at the synaptic junction causes several detrimental effects associated with altered activity of synaptic proteins, transcription factors, Ca2+ homeostasis, and other molecules critical for neuronal plasticity. These detrimental effects further disrupt the normal homeostasis of neuronal cells and thereby causing synaptic loss. Moreover, the precise mechanistic role played by impaired NTs and neuromodulators (NMs) and altered redox signaling in synaptic dysfunction remains mysterious, and their possible interlink still needs to be investigated. Therefore, this review elucidates the intricate role played by both defective NTs/NMs and altered redox signaling in synaptopathy. Further, the involvement of numerous pharmacological approaches to compensate neurotransmission imbalance has also been discussed, which may be considered as a potential therapeutic approach in synaptopathy associated with AD.

Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

PubMed Central

Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

2016-01-01

Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

The interaction of working memory and emotion in persons clinically at risk for psychosis: an fMRI pilot study.

PubMed

Pauly, Katharina; Seiferth, Nina Y; Kellermann, Thilo; Ruhrmann, Stephan; Daumann, Bianca; Backes, Volker; Klosterkötter, Joachim; Shah, N Jon; Schneider, Frank; Kircher, Tilo T; Habel, Ute

2010-07-01

Subtle emotional and cognitive dysfunctions may already be apparent in individuals at risk for psychosis. However, there is a paucity of research on the neural correlates of the interaction of both domains. It remains unclear whether those correlates are already dysfunctional before a transition to psychosis. We used functional magnetic resonance imaging to examine the interaction of working memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and 12 healthy subjects individually matched for age, gender and parental education. Participants performed an n-back task while negative or neutral emotion was induced by olfactory stimulation. Although healthy and psychosis-prone subjects did not differ in their working memory performance or the evaluation of the induced emotion, decreased activations were found in CHR subjects in the superior parietal lobe and the precuneus during working memory and in the insula during emotion induction. Looking at the interaction, CHR subjects, showed decreased activation in the right superior temporal gyrus, which correlated negatively with psychopathological scores. Decreased activation was also found in the thalamus. However, an increase of activation emerged in several cerebellar regions. Dysfunctions in areas associated with controlling whether incoming information is linked to emotional content and in the integration of multimodal information might lead to compensatory activations of cerebellar regions known to be involved in olfactory and working memory processes. Our study underlines that cerebral dysfunctions related to cognitive and emotional processes, as well as their interaction, can emerge in persons with CHR, even in absence of behavioral differences. (c) 2009 Elsevier B.V. All rights reserved.

Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

PubMed

Patterson, Emily J; Wilk, Melissa; Langlo, Christopher S; Kasilian, Melissa; Ring, Michael; Hufnagel, Robert B; Dubis, Adam M; Tee, James J; Kalitzeos, Angelos; Gardner, Jessica C; Ahmed, Zubair M; Sisk, Robert A; Larsen, Michael; Sjoberg, Stacy; Connor, Thomas B; Dubra, Alfredo; Neitz, Jay; Hardcastle, Alison J; Neitz, Maureen; Michaelides, Michel; Carroll, Joseph

2016-07-01

Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

Redefining the gut as the motor of critical illness.

PubMed

Mittal, Rohit; Coopersmith, Craig M

2014-04-01

The gut is hypothesized to play a central role in the progression of sepsis and multiple organ dysfunction syndrome. Critical illness alters gut integrity by increasing epithelial apoptosis and permeability and by decreasing epithelial proliferation and mucus integrity. Additionally, toxic gut-derived lymph induces distant organ injury. Although the endogenous microflora ordinarily exist in a symbiotic relationship with the gut epithelium, severe physiological insults alter this relationship, leading to induction of virulence factors in the microbiome, which, in turn, can perpetuate or worsen critical illness. This review highlights newly discovered ways in which the gut acts as the motor that perpetuates the systemic inflammatory response in critical illness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Primary Respiratory Chain Disease Causes Tissue-Specific Dysregulation of the Global Transcriptome and Nutrient-Sensing Signaling Network

PubMed Central

Zhang, Zhe; Tsukikawa, Mai; Peng, Min; Polyak, Erzsebet; Nakamaru-Ogiso, Eiko; Ostrovsky, Julian; McCormack, Shana; Place, Emily; Clarke, Colleen; Reiner, Gail; McCormick, Elizabeth; Rappaport, Eric; Haas, Richard; Baur, Joseph A.; Falk, Marni J.

2013-01-01

Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. Mechanism(s) by which RC dysfunction causes global cellular sequelae are poorly understood. To identify a common cellular response to RC disease, integrated gene, pathway, and systems biology analyses were performed in human primary RC disease skeletal muscle and fibroblast transcriptomes. Significant changes were evident in muscle across diverse RC complex and genetic etiologies that were consistent with prior reports in other primary RC disease models and involved dysregulation of genes involved in RNA processing, protein translation, transport, and degradation, and muscle structure. Global transcriptional and post-transcriptional dysregulation was also found to occur in a highly tissue-specific fashion. In particular, RC disease muscle had decreased transcription of cytosolic ribosomal proteins suggestive of reduced anabolic processes, increased transcription of mitochondrial ribosomal proteins, shorter 5′-UTRs that likely improve translational efficiency, and stabilization of 3′-UTRs containing AU-rich elements. RC disease fibroblasts showed a strikingly similar pattern of global transcriptome dysregulation in a reverse direction. In parallel with these transcriptional effects, RC disease dysregulated the integrated nutrient-sensing signaling network involving FOXO, PPAR, sirtuins, AMPK, and mTORC1, which collectively sense nutrient availability and regulate cellular growth. Altered activities of central nodes in the nutrient-sensing signaling network were validated by phosphokinase immunoblot analysis in RC inhibited cells. Remarkably, treating RC mutant fibroblasts with nicotinic acid to enhance sirtuin and PPAR activity also normalized mTORC1 and AMPK signaling, restored NADH/NAD+ redox balance, and improved cellular respiratory capacity. These data specifically highlight a common pathogenesis extending across different molecular and biochemical etiologies of individual RC disorders that involves global transcriptome modifications. We further identify the integrated nutrient-sensing signaling network as a common cellular response that mediates, and may be amenable to targeted therapies for, tissue-specific sequelae of primary mitochondrial RC disease. PMID:23894440

Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Com, Emmanuelle, E-mail: emmanuelle.com@univ-rennes1.fr; INSERM U625, Proteomics Core Facility Biogenouest, Rennes; Boitier, Eric

2012-01-01

Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 andmore » 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic data turned out to be complementary and are integrated. ► A more comprehensive putative model of nephrotoxicity of gentamicin is presented.« less

Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

PubMed

Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

2012-01-13

To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

Effect of Area-Level Socioeconomic Deprivation on Risk of Cognitive Dysfunction in Older Adults.

PubMed

McCann, Adrian; McNulty, Helene; Rigby, Jan; Hughes, Catherine F; Hoey, Leane; Molloy, Anne M; Cunningham, Conal J; Casey, Miriam C; Tracey, Fergal; O'Kane, Maurice J; McCarroll, Kevin; Ward, Mary; Moore, Katie; Strain, J J; Moore, Adrian

2018-02-12

To investigate the relationship between area-level deprivation and risk of cognitive dysfunction. Cross-sectional analysis. The Trinity, Ulster, and Department of Agriculture (TUDA) study from 2008 to 2012. Community-dwelling adults aged 74.0 ± 8.3 without dementia (N = 5,186; 67% female). Adopting a cross-jurisdictional approach, geo-referenced address-based information was used to map and link participants to official socioeconomic indicators of deprivation within the United Kingdom and the Republic of Ireland. Participants were assigned an individual deprivation score related to the smallest administrative area in which they lived. These scores were categorized into comparable quintiles, that were then used to integrate the datasets from both countries. Cognitive health was assessed using the Mini-Mental State Examination (MMSE); cognitive dysfunction was defined as a MMSE score of 24 or less. Approximately one-quarter of the cohort resided within the most-deprived districts in both countries. Greater area-level deprivation was associated with significantly lower MMSE scores; fewer years of formal education; greater anxiety, depression, smoking and alcohol use, and obesity; and more adverse outcomes, including higher blood pressure and diabetes risk. After adjustment for relevant covariates, area deprivation was associated with significantly higher risk of cognitive dysfunction (odds ratio =1.40, 95% confidence interval = 1.05-1.87, P = .02, for most vs least deprived). This analysis combining data from two health systems shows that area deprivation is an independent risk factor for cognitive dysfunction in older adults. Adults living in areas of greatest socioeconomic deprivation may benefit from targeted strategies aimed at improving modifiable risk factors for dementia. Further cross-national analysis investigating the impact of area-level deprivation is needed to address socioeconomic disparities and shape future policy to improve health outcomes in older adults. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.

PubMed

Sag, Can M; Wolff, Hendrik A; Neumann, Kay; Opiela, Marie-Kristin; Zhang, Juqian; Steuer, Felicia; Sowa, Thomas; Gupta, Shamindra; Schirmer, Markus; Hünlich, Mark; Rave-Fränk, Margret; Hess, Clemens F; Anderson, Mark E; Shah, Ajay M; Christiansen, Hans; Maier, Lars S

2013-11-01

Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative stress and persistently activated CaMKII. Our findings suggest impaired cardiac myocytes Ca handling as a so far unknown mediator of IR-dependent cardiac damage that might be of relevance for radiation-induced cardiac dysfunction.