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Lurasidone augmentation to clozapine in treatment resistant schizophrenia: A pilot study
- V. Arienti, S. C. Civardi, F. Besana, F. Mazzoni, G. Carnevale Miacca, N. Brondino, P. Politi, M. Olivola
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S306-S307
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Introduction
Treatment resistant schizophrenia still represents a major clinical and pharmacological challenge.30% of patients diagnosed with schizophrenia is characterised by a poor response to at least two different antipsychotics administered for a proper period of time and at adequate doses. Clozapine still represents the gold standard for treatment resistant patients. Unfortunately, a significant percentage of these are only partial responders. Augmentation strategies must be set up and atypical antipsychotic drugs are used in clinical practice. Promising findings have been observed in patients treated with Lurasidone as an add-on therapy with Clozapine. This novel second-generation antipsychotic has a unique receptor profile, showing 5-HT1a partial agonism and 5HT7 antagonism. These properties could also explain its procognitive effect, as several preclinical studies in literature have demonstrated.
ObjectivesThe aim of our study is to highlight the advantages of add on therapy with Lurasidone compared with treatment as usual (i.e. Clozapine + another atypical antipsychotic) in treatment resistant schizophrenia patients.
MethodsWe conducted an observational study in a sample of 20 patients diagnosed with treatment resistant schizophrenia, based on DSM-5 diagnostic criteria and psychopharmacologic history. Treatment choices were taken independently by clinicians in charge of each patient. 10 subjects underwent Lurasidone augmentation of Clozapine, whereas the remaining 10 subjects were treated as usual with Clozapine and another atypical antipsychotic. PANSS and BPRS scales to assess general psychopathology and UKU side effects scale were administered both at baseline and at follow-up (T1= 1 month; T2=6 months).
ResultsAll patients treated with Lurasidone augmentation strategy achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported. In particular, Lurasidone showed no impact on metabolic parameters nor on ECG features, namely the QTc interval. The psychopathological improvement appeared higher in patients who received Lurasidone than in those treated as usual. This was particularly evident in cognitive domains.
ConclusionsOur observation suggests that augmentation strategy with Lurasidone to Clozapine can lead to clinically significant improvements in psychopathology when compared to Clozapine combined with another atypical antipsychotic, with a good tolerability profile. In future we will increase the number of our sample and the duration of follow-up time. In order to have more relevant statistical results, further research on this topic is needed.
Disclosure of InterestNone Declared
Looking at my body. Similarities and differences between anorexia nervosa patients and controls in body image visual processing
- G. Castellini, C. Polito, E. Bolognesi, A. D’Argenio, A. Ginestroni, M. Mascalchi, G. Pellicanò, L.N. Mazzoni, F. Rotella, C. Faravelli, A. Pupi, V. Ricca
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- European Psychiatry / Volume 28 / Issue 7 / September 2013
- Published online by Cambridge University Press:
- 15 April 2020, pp. 427-435
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Background
Body image distortion is a core symptom of eating disorders. Functional magnetic resonance imaging (fMRI) studies on body image processing, described different patterns of neural response, mainly involving the inferior and superior parietal lobules, and the dorsolateral prefrontal cortex (DLPFC), with conflicting results.
MethodsThe neural response to the view of their own body pictures (normal size and distorted) was evaluated in 18 female anorexia nervosa (AN) restricting type patients, and in 19 healthy female subjects (HC) using fMRI. Clinical assessment was performed by means of the structured clinical interview for DSM-IV and self-reported questionnaires.
ResultsIn response to the body image distortion, patients and controls showed an inverse pattern of activation, with the widest extent of activation in the oversize condition in AN, while in the undersize condition in HC. AN and HC showed a similar pattern of neural response to the view of their own body, with an increased activation in the extrastriate body area, superior and inferior parietal lobule and prefrontal areas, although the extent of activation in HC was more limited as compared with AN patients. Increased activity in AN patients, compared with HC, was observed in the DLPFC in response to the oversized body picture and a significant correlation was found in AN patients between DLPFC activation and eating disorder psychopathology.
ConclusionsOur findings suggest the existence of a continuum from normalcy to pathology in neural response to body image, and confirm the clinical relevance of body image distortion in AN, reinforcing the key role of attentive, executive and self-evaluation networks in AN visual processing of own distorted body image.
Implications of white striping and spaghetti meat abnormalities on meat quality and histological features in broilers
- G. Baldi, F. Soglia, M. Mazzoni, F. Sirri, L. Canonico, E. Babini, L. Laghi, C. Cavani, M. Petracci
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During the past few years, there has been an increasing prevalence of broiler breast muscle abnormalities, such as white striping (WS) and wooden breast conditions. More recently, a new muscular abnormality termed as spaghetti meat (SM) because of the altered structural integrity of the Pectoralis major muscle often associated with WS has emerged. Thus, this study aimed at evaluating the effects of WS and SM conditions, occurring alone or combined within the same P. major muscle, on meat quality traits and muscle histology. In two replications, 96 P. major muscles were classified into four classes: normal (N), WS, SM and WS/SM. The whole fillet was used for weight assessment and morphometric measurements, then each sample was cut in order to separate the superficial layer from the deep one and used to evaluate proximate composition, histological features, nuclear magnetic resonance relaxation times, functional properties and both myofibrillar and sarcoplasmic proteins profile. Fillets affected by WS and SM abnormalities exhibited higher weights and increased thickness and length. SM condition was associated with a relevant decrease in protein content coupled with a significant increase in moisture level, whereas fat content was affected only by the simultaneous presence of WS. Histological evaluations revealed that abnormal samples were characterized by several degenerative aspects that almost completely concerned the superficial layer of the fillets. White striped fillets exhibited necrosis and lysis of fibers, fibrosis, lipidosis, loss of cross striation and vacuolar degeneration. Moreover, SM samples were characterized by poor fiber uniformity and a progressive rarefaction of the endo- and peri-mysial connective tissue, whereas WS/SM fillets showed intermediate histological features. Nuclear magnetic resonance relaxation analysis revealed a higher proportion of extra-myofibrillar water in the superficial section of all the abnormal fillets, especially in SM samples, which consequently led to a reduction of the water holding capacity of meat. As for functional properties, abnormal fillets exhibited a lower protein solubility and higher ultimate pH values on both the superficial and deep sections. Although abnormal fillets exhibited higher yellowness values, no relevant effect on meat color was observed. The occurrence of WS and SM abnormalities led to increased carbonylation levels and more intense proteolytic processes. Overall, muscle abnormalities mainly affect the superficial layer of P. major muscle and particularly the occurrence of SM myopathy seems to implicate a more pronounced modification of meat quality traits than the mere presence of WS.
Prevalence and risk factors for gastric ulceration in pigs slaughtered at 170 kg
- F. Gottardo, A. Scollo, B. Contiero, M. Bottacini, C. Mazzoni, S. A. Edwards
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Oesophago-gastric ulcers (OGU) are a production and welfare problem in pigs. Stomach condition was scored for 22 551 pigs in 228 batches over a 7-month period at an abattoir in Italy processing heavy pigs for ham production. Mild or severe ulceration was observed in 20.7% of pigs, of which 13% had scar tissue. Variation between batches was high (0% to 36% prevalence of severe ulcers) and showed a significant effect of farm of origin (P<0.001). Overnight lairage increased the prevalence of mild ulcers (P<0.001), but not severe or scarred ulcers. Scarred ulcers increased in the hottest summer months. Prevalence of ulcers showed only few and weak correlations at batch level with pathologies of the pleura, lungs and liver, but a strong correlation with on-farm mortality of the batch. Analysis of farm risk factors for OGU was assessed by questionnaire with a response rate of 17% of farms. Risk factors retained in a multivariable model included a protective effect of anthelmintic treatment (risk ratio (RR)=5.1, P=0.03), increased risk in farms using Mycoplasma vaccination (RR=5.6, P=0.04) and a tendency for association with type of flooring (P=0.06). Univariable analyses also highlighted possible influences of other stress-inducing factors including lack of enrichment objects and mixing of pigs during fattening, suggesting that the role of on-farm stressors merits further investigation. It is concluded that abattoir screening of OGU in future programmes for the assessment of well-being on farm should encompass only severe lesions and scarring, and results be returned to farmers to facilitate improvement of production and welfare.
Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds
- S. Bovo, G. Mazzoni, G. Galimberti, D. G. Calò, F. Fanelli, M. Mezzullo, G. Schiavo, A. Manisi, P. Trevisi, P. Bosi, S. Dall’Olio, U. Pagotto, L. Fontanesi
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In pigs, many production traits are known to vary among breeds or lines. These traits can be considered end phenotypes or external traits as they are the final results of complex biological interactions and processes whose fine biological mechanisms are still largely unknown. This study was designed to compare plasma and serum metabolomic profiles between animals of two heavy pig breeds (12 Italian Large White and 12 Italian Duroc), testing indirectly the hypothesis that different genetic backgrounds might be the determining factors of differences observed on the level of metabolites in the analyzed biofluids between breeds. We used a targeted metabolomic approach based on mass spectrometric detection of about 180 metabolites and applied a statistical validation pipeline to identify differences in the metabolomic profiles of the two heavy pig breeds. Blood samples were collected after jugulation at the slaughterhouse and prepared for metabolomics analysis that was carried out using the Biocrates AbsoluteIDQ p180 Kit, covering five different biochemical classes: glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines. A statistical pipeline that included the selection of the most relevant metabolites differentiating the two breeds by sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was coupled with a stability test and significance test determined with leave one out and permutation procedures. sPLS-DA plots clearly separated the pigs of the two investigated breeds. A few metabolites (a total of five metabolites considering the two biofluids) involved in key metabolic pathways largely contributed to these differences between breeds. In particular, a higher level of the sphingomyelins SM (OH) C14:1 (both in plasma and serum), SM (OH) C16:1 (in serum) and SM C16:0 (in serum) were observed in Italian Duroc than in Italian Large White pigs and the inverse was for the biogenic amine kynurenine (in plasma). The level of another biogenic amine (acetylornithine) was higher in Italian Large White than in Italian Duroc pigs in both analysed biofluids. These results provided biomarkers that could be important to understand the biological differences between these two heavy pig breeds. In particular, according to the functional role played by sphingomyelins in obesity-induced inflammatory responses, it could be possible to speculate that a higher level of sphingomyelins in Italian Duroc might be related to the higher interrmuscular fat deposition of this breed compared with the Italian Large White. Additional studies will be needed to evaluate the relevance of these biomarkers for practical applications in pig breeding and nutrition.
The courtship song of fanning males in the fruit fly parasitoid Psyttalia concolor (Szépligeti) (Hymenoptera: Braconidae)
- A. Canale, G. Benelli, F. Lanzo, P. Giannotti, V. Mazzoni, A. Lucchi
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- Journal:
- Bulletin of Entomological Research / Volume 103 / Issue 3 / June 2013
- Published online by Cambridge University Press:
- 10 January 2013, pp. 303-309
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In this paper we describe acoustically the wing-fanning behaviour showed by the male of the braconid Psyttalia concolor towards females and other conspecific males. Psyttalia concolor is a synovigenic koinobiont larval–pupal endoparasitoid of many Tephritidae, used in olive crops to control the olive fruit fly, Bactrocera oleae. In this braconid male wing fanning produces a courtship song characterised by sequences of homogenous pulses with harmonic structure and a fundamental frequency of about 180 Hz. Song parameters can vary according to the behavioural context. Statistically significant differences, both in terms of pulse frequency and duration, characterise fanning towards females in comparison with male–male approaches. Moreover, the pulse duration is associated with the fanning song displayed before a successful courtship. Our observations allowed us to define the airborne component of the sound and to definitely confirm the exclusive role of the wings in signal production within sexual communication in P. concolor.
Dietary addition of Lactobacillus rhamnosus GG impairs the health of Escherichia coli F4-challenged piglets
- P. Trevisi, L. Casini, F. Coloretti, M. Mazzoni, G. Merialdi, P. Bosi
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Lactobacillus rhamnosus GG (LGG) is a probiotic for humans and is normally not found in pigs; however, it has been shown to protect the human-derived intestinal Caco-2 cells against the damage induced by an important intestinal pathogen, enterotoxigenic Escherichia coli F4 (ETEC). An experiment was conducted to test whether the dietary addition of LGG improves the growth and health of weaned pigs when orally challenged by E. coli F4. Thirty-six pigs were weaned at 21 days and assigned to a standard weaning diet with or without 1010 CFU LGG (ATCC 53103) per day. The pigs, individually penned, were orally challenged with 1.5 ml of a 1010 CFU E. coli F4 suspension on day 7 and slaughtered on day 12 or 14. With the addition of LGG, the average daily gain and the average daily feed intake were reduced after the challenge with ETEC and for the entire trial (P < 0.05). The average faecal score tended to worsen from day 11 to the end of the trial and the concentration of ETEC in the faeces tended to increase (P = 0.07) with the LGG supplementation. The counts of lactic acid bacteria, enterobacteria and yeasts in the colonic digesta were not affected. The pH values in ileal, colonic and caecal digesta, and the small intestine size were also unchanged. Regardless of the site of measurement (duodenum, jejunum or ileum), a trend of decreased villus height was seen with LGG (P = 0.10). Crypt depth and villus to crypt ratio were unchanged by the diet. A gradual increase of total seric IgA was seen after 1 week and after the challenge, in the control (P < 0.05), but not in the treated group. After the challenge, the LGG reduced the total IgA in the blood serum (P < 0.05), v. the control. The total IgA in the saliva and in the jejunum secretion were not affected by the diet. The F4-specific IgA activity was not affected by the diet at all the samplings. Our result shows that, the administration of LGG do not prevent or reduce the detrimental effect of the E. coli F4 infection on the growth performance and health status of weaned piglet.