Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis.

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF may negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover

DYSPHORIA AS A PSYCHIATRIC SYNDROME: A PRELIMINARY STUDY FOR A NEW TRANSNOSOGRAPHIC DIMENSIONAL APPROACH

Background: We currently define dysphoria as a complex and disorganized emotional state with proteiform phenomenology, characterized by a multitude of symptoms. Among them prevail irritability, discontent, interpersonal resentment and surrender. Dysphoria, in line with the most recent Interpersonal Dysphoria Model, could represent a “psychopathological organizer” of the Borderline Personality Disorder. We would like to extend this theoretical concept to other psychiatric disorders in order to consider dysphoria as a possible psychopathological nucleus, a syndrome on its own. This syndromic vision may open up the possibility of new paths both in the differential diagnosis and in the therapeutic approach to the various disorders. Aims: The goal of this paper is to understand if the dimensional spectrum that composes dysphoria differs from the different psychiatric disorders. Specifically, we would like to assess if the phenomenological expression of dysphoria differs in patients with Borderline Personality Disorder (BPD), Mixed State Bipolar Disorder (BDM) and Major Depressive Disorder (MDD) through an observational comparative study. Subjects and methods: In this study, 30 adult patients, males and females between the ages of 18 and 65, were enrolled from the Psychiatric Service of the Santa Maria della Misericordia Hospital in Perugia (PG), Italy, from January 1st to June 30th, 2018. The aim was to form 3 groups each one composed of 10 individuals affected respectively with Borderline Personality Disorder (BPD), with Bipolar Disorder, Mixed State (BPM) and Major Depression Disorder (MDD). After a preliminary assessment to exclude organic and psychiatric comorbidity, we administered them the Neapen Dysphoria Scale – Italian Version (NDS-I), a specific dimensional test for dysphoria. Starting from the dataset, with the aid of the statistical program SPSS 20, we have obtained graphs showing the comparison between disorders groups selected and NDS-I total score and subscales (irritability, discontent, interpersonal resentment, surrender). Finally, a comparison was made, taking two groups at a time, between the means of single groups for total scores and for single subscales considered into the NDS-I test. We made it using the Mann-Whitney U test, a nonparametric test with 2 independent samples, by setting a significance level =0.05. Conclusions: This study, through a transnosographic-dimensional approach, allowed us to explore dysphoria and its expressions in different psychopathological groups, despite analyzing a small sample. Differences between means of values obtained through NDS-I subscales were statistically significant in patients with BPD, BDM and MDD (p<0.05). Among the latter, the group of BPD patients has greater pervasiveness and severity of dysphoria symptoms

DYSPHORIA AS A PSYCHIATRIC SYNDROME: A PRELIMINARY STUDY FOR A NEW TRANSNOSOGRAPHIC DIMENSIONAL APPROACH

Background: We currently define dysphoria as a complex and disorganized emotional state with proteiform phenomenology, characterized by a multitude of symptoms. Among them prevail irritability, discontent, interpersonal resentment and surrender. Dysphoria, in line with the most recent Interpersonal Dysphoria Model, could represent a “psychopathological organizer” of the Borderline Personality Disorder. We would like to extend this theoretical concept to other psychiatric disorders in order to consider dysphoria as a possible psychopathological nucleus, a syndrome on its own. This syndromic vision may open up the possibility of new paths both in the differential diagnosis and in the therapeutic approach to the various disorders. Aims: The goal of this paper is to understand if the dimensional spectrum that composes dysphoria differs from the different psychiatric disorders. Specifically, we would like to assess if the phenomenological expression of dysphoria differs in patients with Borderline Personality Disorder (BPD), Mixed State Bipolar Disorder (BDM) and Major Depressive Disorder (MDD) through an observational comparative study. Subjects and methods: In this study, 30 adult patients, males and females between the ages of 18 and 65, were enrolled from the Psychiatric Service of the Santa Maria della Misericordia Hospital in Perugia (PG), Italy, from January 1st to June 30th, 2018. The aim was to form 3 groups each one composed of 10 individuals affected respectively with Borderline Personality Disorder (BPD), with Bipolar Disorder, Mixed State (BPM) and Major Depression Disorder (MDD). After a preliminary assessment to exclude organic and psychiatric comorbidity, we administered them the Neapen Dysphoria Scale – Italian Version (NDS-I), a specific dimensional test for dysphoria. Starting from the dataset, with the aid of the statistical program SPSS 20, we have obtained graphs showing the comparison between disorders groups selected and NDS-I total score and subscales (irritability, discontent, interpersonal resentment, surrender). Finally, a comparison was made, taking two groups at a time, between the means of single groups for total scores and for single subscales considered into the NDS-I test. We made it using the Mann-Whitney U test, a nonparametric test with 2 independent samples, by setting a significance level =0.05. Conclusions: This study, through a transnosographic-dimensional approach, allowed us to explore dysphoria and its expressions in different psychopathological groups, despite analyzing a small sample. Differences between means of values obtained through NDS-I subscales were statistically significant in patients with BPD, BDM and MDD (p<0.05). Among the latter, the group of BPD patients has greater pervasiveness and severity of dysphoria symptoms

The moderating role of just-in-time on sociotechnical practices' effect over quality and workers' health

Sociotechnical (ST) theory emphasizes the notion that the design and performance of new systems can be improved, and can only work satisfactorily within an organization if the social and the technical aspects are brought together and treated as interdependent aspects of a work system. The implementation of lean manufacturing (LM) principles and practices has become popular, despite increasing demand on the current and emerging workforce to achieve higher levels of quality and flexibility with lower costs. Exploratory studies that investigate how LM practices influence the effect of ST practices on performance are still scarce, and a holistic view of such a relationship is needed. In this context, this study aims at verifying the moderating effect of just-in-time (JIT) practices on the relationship between ST practices and the performance of quality and workers' health. We carried out a survey with 144 different companies from Southern Brazil that are undergoing a lean implementation. Results indicate that ST practices have a positive significant relationship with such performance, and the concurrent adoption of JIT does not undermine quality and workers' health

CANNABINOID-INDUCED PSYCHOSIS: A CROSS-SECTIONAL GENDER STUDY

Background: Gender is a crucial factor in the development of mental illnesses, with an essential influence on clinical characteristics and not only on the prevalence of each disorder. Gender differences in cannabinoid-related disorders are highlighted by different research fields (preclinical, clinical, socio-demographic studies), but few studies focused on differential symptom expression in cannabinoid-induced psychosis. This study aims at investigating qualitative and quantitative gender differences in specific psychopathological domains in a clinical sample of subjects affected by cannabinoid-induced psychotic disorder, without psychiatric comorbidity. Subjects and methods: The study was carried out at the Psychiatric Inpatient Service of General Hospital of Perugia (Italy). In this cross-sectional gender study, 28 inpatients were enrolled, 14 males (M) and 14 females (F). Participants were administered a psychometric battery consisting of 7 tests (PANSS, NDS-I, YMRS, HAM-D, HAM-A, AQ, SSI) in order to investigate 7 psychopathological domains (Psychosis, Dysphoria, Mania, Depression, Anxiety, Aggressive Behaviour and Suicide Ideation). Scores obtained at each test were compared between male and females by using Mann-Whitney U test (p<0.05). Results: In this study, we observed that males present higher severity of psychotic symptoms, with prominent scores in PANSS positive and general psychopathology scale (p<0.001), and an important expression of aggressive behavior (p<0.001) compared with females. Female sample, instead, shows a greater expression of dysphoria and depressive domains (p<0.001) and a lower, but statistically significant, prevalence in the anxiety domains expression (p=0.01). By these observations, we could assert that in male group thought disorders are prominent. On the other hand, in female group affective disorder are prominent. Conclusions: This study confirmed how gender influences the phenomenic expression of psychiatric disorders. In line with the precision medicine paradigm, a further clarification of different clinical profiles based on gender would allow the choice of a personalized treatment plan with better efficacy and accuracy indices

DYSPHORIA DIMENSIONAL MODEL FOR FEEDING AND EATING DISORDERS: A PRELIMINARY STUDY

Background: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED) are severe psychiatric illnesses which represent the main expression of Feeding and Eating Disorders (FED). Clinicians agree that emotional and behavioural dysregulation play a crucial role in FED. Dysphoria could help us to better understand these components. Indeed, we define dysphoria as a generic state of dissatisfaction and emotional instability, without any specific features. Among the multitude of symptoms, we find that irritability, discontent, interpersonal resentment and surrender prevail. These dimensions correspond to the four subscales of Neapean Dysphoria Scale - Italian version (NDS-I). Dysphoria role in FED has not yet been investigated. Using this test, we can characterize dysphoria both in quantitative and qualitative terms. Accordingly, domain evaluation could discriminate these disorders allowing us to assess possible differential phenomenological expressions. Aims: The aim of this paper is to understand in which way the dimensional spectrum that composes dysphoria differs between Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorders through an observational comparative study. Subjects and methods: The enrolled sample (30 patients) is represented by patients with a history of FED (AN, BN or BED). Patients were males and females between the ages of 13 and 45 with a good knowledge of Italian language. Patients with severe cognitive impairment (MMSE <19) and civil incapacitation were excluded. Patients were recruited from the Psychiatric Service of the Santa Maria della Misericordia Hospital in Perugia (PG), and other residential and semi residential structures specialized in FED treatment (FED specialized center at Palazzo Francisci in Todi (PG), Nido delle Rondini in Todi (PG), BED (Binge Eating Disorders) center in Città della Pieve (PG) and ambulatory services for FED in Umbertide (PG)). We administered them the Neapen Dysphoria Scale – Italian Version (NDS-I), a specific dimensional test for dysphoria. Starting from the dataset, with the aid of the statistical program SPSS 20, we have carried out a comparison between disorders groups selected and NDS-I total score and subscales (irritability, discontent, interpersonal resentment, surrender). For this we have used the Mann-Whitney U test, a nonparametric test with 2 independent samples, by setting a significance level p<0.05. Conclusions: This study allowed us to better understand and characterize the most common Eating Disorders. Beyond that, despite the small sample size, we found in our analysis statistically significant difference in the expression of various dysphoria dimension spectrum inside our 3 groups

Visual evoked potentials in succinate semialdehyde dehydrogenase (SSADH) deficiency

In mammals, increased GABA in the central nervous system has been associated with abnormalities of visual evoked potentials (VEPs), predominantly manifested as increased latency of the major positive component P100. Accordingly, we hypothesized that patients with a defect in GABA metabolism, succinate semialdehyde dehydrogenase (SSADH) deficiency (in whom supraphysiological levels of GABA accumulate), would manifest VEP anomalies. We evaluated VEPs on two patients with confirmed SSADH deficiency. Whereas the P100 latencies and amplitudes for binocular VEP analyses were within normal ranges for both patients, the P100 latencies were markedly delayed for left eye (OS) (and right eye (OD), patient 1) and monocular OS (patient 2): 134-147 ms; normal <118 ms. We hypothesize that elevated GABA in ocular tissue of SSADH patients leads to a use-dependent downregulation of the major GABAergic receptor in eye, GABA(C), and that the VEP recordings' abnormalities, as evidenced by P100 latency and/or amplitude measurements, may be reflective of abnormalities within visual systems. This is a preliminary finding that may suggest the utility of performing VEP analysis in a larger sample of SSADH-deficient patients, and encourage a neurophysiological assessment of GABA(C) receptor function in Aldh5a1(-/-) mice to reveal new pathophysiological mechanisms of this rare disorder of GABA degradation

DYSPHORIA DIMENSIONAL MODEL FOR FEEDING AND EATING DISORDERS: A PRELIMINARY STUDY

Background: Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED) are severe psychiatric illnesses which represent the main expression of Feeding and Eating Disorders (FED). Clinicians agree that emotional and behavioural dysregulation play a crucial role in FED. Dysphoria could help us to better understand these components. Indeed, we define dysphoria as a generic state of dissatisfaction and emotional instability, without any specific features. Among the multitude of symptoms, we find that irritability, discontent, interpersonal resentment and surrender prevail. These dimensions correspond to the four subscales of Neapean Dysphoria Scale - Italian version (NDS-I). Dysphoria role in FED has not yet been investigated. Using this test, we can characterize dysphoria both in quantitative and qualitative terms. Accordingly, domain evaluation could discriminate these disorders allowing us to assess possible differential phenomenological expressions. Aims: The aim of this paper is to understand in which way the dimensional spectrum that composes dysphoria differs between Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorders through an observational comparative study. Subjects and methods: The enrolled sample (30 patients) is represented by patients with a history of FED (AN, BN or BED). Patients were males and females between the ages of 13 and 45 with a good knowledge of Italian language. Patients with severe cognitive impairment (MMSE <19) and civil incapacitation were excluded. Patients were recruited from the Psychiatric Service of the Santa Maria della Misericordia Hospital in Perugia (PG), and other residential and semi residential structures specialized in FED treatment (FED specialized center at Palazzo Francisci in Todi (PG), Nido delle Rondini in Todi (PG), BED (Binge Eating Disorders) center in Città della Pieve (PG) and ambulatory services for FED in Umbertide (PG)). We administered them the Neapen Dysphoria Scale – Italian Version (NDS-I), a specific dimensional test for dysphoria. Starting from the dataset, with the aid of the statistical program SPSS 20, we have carried out a comparison between disorders groups selected and NDS-I total score and subscales (irritability, discontent, interpersonal resentment, surrender). For this we have used the Mann-Whitney U test, a nonparametric test with 2 independent samples, by setting a significance level p<0.05. Conclusions: This study allowed us to better understand and characterize the most common Eating Disorders. Beyond that, despite the small sample size, we found in our analysis statistically significant difference in the expression of various dysphoria dimension spectrum inside our 3 groups

Bioinformatics and mathematical modelling in the study of receptor-receptor interactions and receptor oligomerization: focus on adenosine receptors.

none8sìThe concept of intra-membrane receptor-receptor interactions (RRIs) between different types of G protein-coupled receptors (GPCRs) and evidence for their existence was introduced by Agnati and Fuxe in 1980/81 through the biochemical analysis of the effects of neuropeptides on the binding characteristics of monoamine receptors in membrane preparations from discrete brain regions and functional studies of the interactions between neuropeptides and monoamines in the control of specific functions such as motor control and arterial blood pressure control in animal models. Whether GPCRs can form high-order structures is still a topic of an intense debate. Increasing evidence, however, suggests that the hypothesis of the existence of high-order receptor oligomers is correct. A fundamental consequence of the view describing GPCRs as interacting structures, with the likely formation at the plasma membrane of receptor aggregates of multiple receptors (Receptor Mosaics) is that it is no longer possible to describe signal transduction simply as the result of the binding of the chemical signal to its receptor, but rather as the result of a filtering/integration of chemical signals by the Receptor Mosaics (RMs) and membrane-associated proteins. Thus, in parallel with experimental research, significant efforts were spent in bioinformatics and mathematical modelling. We review here the main approaches that have been used to assess the interaction interfaces allowing the assembly of GPCRs and to shed some light on the integrative functions emerging from the complex behaviour of these RMs. Particular attention was paid to the RMs generated by adenosine A(2A), dopamine D-2, cannabinoid CB1, and metabotropic glutamate mGlu(5) receptors (A(2A). D-2, CB1, and mGlu(5), respectively), and a possible approach to model the interplay between the D-2-A(2A)-CB1 and D-2-A(2A)-mGlu(5) trimers is proposed. This article is part of a Special Issue entitled: "Adenosine Receptors". (C) 2010 Elsevier B.V. All rights reserved.openD. GUIDOLIN; F. CIRUELA; S. GENEDANI; M. GUESCINI; C. TORTORELLA; G. ALBERTIN; K. FUXE; L.F. AGNATID., Guidolin; F., Ciruela; S., Genedani; Guescini, Michele; C., Tortorella; G., Albertin; K., Fuxe; L. F., Agnat