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Analisi dei tempi e metodi per il miglioramento dell'efficienza produttiva di una ribobinatrice di cartiera: il caso di Essity PLD Italy S.p.A.
No full textL’elaborato di tesi si concentra sull’analisi dei tempi e dei metodi applicata al ciclo produttivo di una ribobinatrice presente nel reparto di cartiera dello stabilimento “Lucca 1” dell’azienda Essity S.p.A., società operante nel settore della produzione di carta tissue. L’obiettivo del progetto è stato quello di individuare opportunità di miglioramento dell’efficienza produttiva del ciclo operativo della ribobinatrice.
Nel primo capitolo viene presentato il contesto aziendale e descritto il processo di produzione della carta tissue. Nel secondo si procede poi con la descrizione tecnica della ribobinatrice, delle sue principali componenti, delle varie fasi del ciclo operativo e della macchina destinata alla fasciatura. Nel capitolo successivo vengono poi introdotti i concetti teorici fondamentali della Lean Manufacturing, con particolare attenzione alla riduzione degli sprechi. Sono inoltre descritte le metodologie proposte in letteratura per l’analisi dei tempi e metodi.
Nel quarto capitolo viene illustrata l’applicazione pratica delle metodologie al caso studio: sono presentati i dati raccolti sul campo, l'analisi effettuata su tali campioni ed i risultati ottenuti. L’analisi ha permesso di evidenziare margini di miglioramento e possibili sviluppi futuri in ottica di ottimizzazione del ciclo produttivo della ribobinatrice
Synthesis and Characterization of Spiropyran C-Glucoside
No full textQuesto progetto di tesi è focalizzato sulla sintesi e la caratterizzazione di un derivato C-glucosidico dello spiropirano, ideato per migliorarne la solubilità e conseguentemente la sua applicabilità in vivo.
Gli spiropirani sono molecole fotocromiche in grado di interconvertirsi reversibilmente tra una forma chiusa e neutra, definita Spiropirano (SP), e una forma aperta, polarizzata e colorata, detta Merocianina (MC). Tale transizione avviene in risposta a stimoli esterni quali principalmente luce UV, ma anche variazioni di pH, temperatura o polarità del solvente. Ciò, unito alla vasta gamma di funzionalizzazioni cui possono essere substrato, li rende candidati ideali in vari campi. Tuttavia, la loro elevata idrofobicità e scarsa solubilità in acqua limitano fortemente l'impiego in sistemi biologici.
Per superare questo limite, è stata progettata una molecola in cui la porzione idrofobica dello spiropirano è coniugata a una molecola polare quale il glucosio. Inoltre è stato introdotto un gruppo nitro in posizione para al fenolo per migliorare la stabilità della forma aperta (MC) tramite effetto elettron-attrattore.
Sebbene la molecola ottenuta non sia solubile in acqua, è da ritenersi interessante la strategia sintetica che è stata attuata. In primo luogo, è stato ottenuto il p-nitrofenolo C-glucoside mediante una reazione one-pot a partire da D-glucosio e acetilacetone, formando il D-glucosil propanone. A questo è stata successivamente addizionata la nitromalonaldeide sodica monoidrata per ottenere il p-nitrofenolo C-glucoside.
È noto che la via sintetica più semplice per ottenere gli Spiropirani prevede la condensazione di una salicilaldeide con una base di Fischer, pertanto è stata attuata una reazione di Duff per ottenere il prodotto formilato. Tuttavia, tale formilazione non è semplice da ottenere su un substrato disattivato come nel caso del p-nitro fenolo C-glucoside, in quanto il gruppo nitro in para, esercita un'azione elettron-attrattrice e disattivante dell'anello, ostacolando reazioni di sostituzione elettrofila tradizionali. Ne consegue la necessità di ricorrere a una reazione di Duff modificata, condotta in condizioni drastiche, impiegando acidi forti come TFA e alte temperature. Condizioni di reazione così spinte hanno portato alla formazione di esteri derivanti dalla reazione tra gli ossidrili del glucosio e il TFA. È stato quindi necessario proteggere selettivamente gli ossidrili del glucosio prima di procedere alla formilazione per mezzo della reazione di Duff.
Il composto formilato è stato poi deprotetto tramite deacetilazione di Zemplén, purificato, e successivamente fatto reagire con la base di Fischer (1,3,3-trimetilindolina) per formare il legame spiropiranico attraverso una tipica reazione di condensazione.
A questa prima fase sintetica è seguita una seconda fase dedicata alla caratterizzazione dello Spiropirano C-glucoside ottenuto. In particolare, le sue proprietà fotochimiche e solvato-cromatiche sono state studiate attraverso spettroscopia NMR e UV/Vis in diversi solventi (MeOH, DMSO, CH₃CN), variando pH e temperatura. È stato dimostrato che il p-nitrospiropirano C-glucoside presenta un fotocromismo comparabile a quello riportato in letteratura per altri derivati spiropiranici: in solventi polari e al buio, l’equilibrio si sposta spontaneamente verso la forma aperta e colorata MC, un processo ulteriormente favorito dall’irradiazione UV a 365 nm, mentre l’esposizione alla luce visibile (535 nm) induce il ritorno alla forma chiusa e meno intensamente colorata SP. Allo stesso modo, l’aumento della temperatura o del pH contribuisce a stabilizzare la forma MC.
Inoltre, è stato dimostrato che la cinetica dell’interconversione SP ⇄ MC è influenzata non solo dalla polarità del solvente, ma anche dalla sua capacità di stabilizzare specie cariche. In particolare, i solventi polari protici favoriscono la forma MC tramite interazioni a idrogeno, mentre i solventi polari aprotici come il DMSO tendono a stabilizzare la forma chiusa SP, evidenziando il ruolo cruciale delle interazioni specifiche tra soluto e solvente nel modulare le proprietà fotoattive del composto.
This thesis project focuses on the synthesis and characterization of a C-glucoside derivative of spiropyran, designed to improve its solubility and consequently its applicability in vivo.
Spiropyrans are photochromic molecules capable of reversibly interconverting between a closed, neutral form known as Spiropyran (SP), and an open, zwitterionic, and coloured form called Merocyanine (MC). This transition occurs in response to external stimuli such as mainly UV light, but also changes in pH, temperature, or solvent polarity. These features, along with their versatility in chemical functionalization, make spiropyrans promising candidates for various applications. However, their high hydrophobicity and poor water solubility severely limit their use in biological systems.
To address this limitation, a molecule was designed in which the hydrophobic portion of the spiropyran is conjugated to a polar moiety such as glucose. Additionally, a nitro group was introduced in the para position of the phenol ring to stabilise the open form (MC) through its electron-attractor effect. Although the final compound is not water-soluble, the synthetic strategy employed is of significant interest. First, p-nitrophenol C-glucoside was obtained by a one-pot reaction from D-glucose and acetylacetone, forming D-glucosyl propanone. This intermediate was then reacted with sodium nitromalonaldehyde monohydrate to obtain p-nitrophenol C-glucoside.
It is known that the simplest synthetic route to obtain spiropyrans involves the condensation of a salicylaldehyde with a Fischer base. Therefore, a Duff reaction was attempted to obtain the formylated intermediate. However, formylation on a deactivated substrate such as p-nitrophenol C-glucoside proved challenging, due to the strong electron-attracting and deactivating effect of the para-nitro group, which hinders traditional electrophilic substitution reactions. Consequently, a modified Duff reaction under drastic conditions was required, involving strong acids such as TFA and high temperatures. These conditions led to the formation of esters resulting from the reaction between the hydroxyl groups of glucose and TFA. Selective protection of glucose hydroxyl groups was thus necessary prior to the formylation by the Duff reaction.
The formylated compound was subsequently deprotected via Zemplén deacetylation, purified, and reacted with a Fischer base (1,3,3-trimethylindoline) to form the spiropyran bond through a typical condensation reaction. This first synthetic phase was followed by a second phase dedicated to the characterization of the synthesized C-glucoside spiropyran. In particular, its photochemical and solvatochromic properties were studied through NMR and UV/Vis spectroscopy in different
solvents (MeOH, DMSO, CH₃CN), varying both pH and temperature. It was shown that the p-nitrospiropyran C-glucoside exhibits photochromism comparable to other spiropyran derivatives reported in the literature: in polar solvents and in the dark, the equilibrium shifts spontaneously toward the open, coloured MC form, a process further promoted by UV irradiation at 365 nm, while exposure to visible light (535 nm) induces the return to the closed and less intensely coloured SP form. Likewise, increased temperature or pH stabilises the MC form.
Furthermore, it was demonstrated that the kinetics of the SP ⇄ MC interconversion is influenced not only by solvent polarity, but also by the solvent’s ability to stabilise charged species. In particular, polar protic solvents promote the MC form via hydrogen interactions, whereas polar aprotic solvents like DMSO tend to stabilise the closed SP form, highlighting the crucial role of specific solute–solvent interactions in modulating the photoactive properties of the compound
Unraveling the Role of Serotonin in Microglia Modulation in the Context of Amyotrophic Lateral Sclerosis
No full textAmyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that leads to the deterioration of motor neurons in the brain and in spinal cord. This causes muscle weakness, paralysis, and, eventually, death. The specific causes of ALS are unclear. However, research indicates that factors like neuroinflammation play a role. Microglia are the main immune cells in the central nervous system where they are involved in neuroinflammation and neuroprotection. Microglia plays a vital role in the first stages of ALS, however in the later stage microglia damaging role seems to be more prominent.
The neurotransmitter serotonin (5- hydroxytryptamine, 5-HT) has gained interest for its potential involvement in the pathogenesis of ALS. In fact, microglia express the serotonergic receptor 5-HT- 2BR, and published data show that antagonizing or blocking 5-HT2BR modulates microglia behavior; this suggests that interfering with this receptor might allow us to control how microglia respond to a certain stimulus. Microglia are the macrophages of the central nervous system (CNS), and macrophages express the 5-HT2BR receptor which has been suggested to mediate the response to serotonin by promoting an anti-inflammatory phenotype. This suggests that serotonin can help to reduce microglia-mediated inflammation through this receptor. The relationship between serotonin signaling and microglial function is a key research focus, likely providing insights into ALS progression and potential treatments.
The objective of the thesis is to address three principal aims pertaining to the role of serotonin in neuroinflammation and the degeneration of motor neurons within the framework of ALS.
The first aim is to analyze if the presence or absence of CNS serotonin influences the inflammatory response. This is tested in knockout (KO) mice. Inflammation is induced via the administration of lipopolysaccharide (LPS), and the levels of inflammatory cytokines are studied. The data collected will provide insights into serotonin’s potential role in modulating an immune response.
Second, to investigate the expression and distribution of serotonergic neurons within the brain of ALS mice. The network of serotonergic neurons of WT mice is compared to that of ALS mice. A transgenic mice model is created where one allele for the Tph2 gene (Tryptophan hydroxylase 2) codifies a recombinant Tph2 labeled with the green fluorescent protein, GFP. Tph2 is an enzyme necessary to produce serotonin, therefore these transgenic mice behave like WT mice, but they have the serotonergic neurons GFP-positive. These heterozygous mice are then crossed with the SOD1 mouse. This crossbreeding produces a transgenic SOD1 mouse that produces GFP in the serotonergic neurons, allowing easy visualization of the serotonergic neuron morphology.
The final aim is to evaluate the influence of serotonin modulation on ALS by boosting the production of serotonin. This aim will concentrate on discerning whether the increase of serotonin levels can alleviate motor neuron degeneration and microglia activation in the context of ALS. We will use a chemogenetic mouse model tool specifically expressing the human M3 muscarinic receptor (hM3Dq) in serotonergic neurons. hM3Dq receptor allows specific stimulation of the cells expressing it. This strategy allows to selectively boost serotonin levels in SOD1G93A mice by using the hM3Dq agonist clozapine-N-oxide (CNO)
The Link between Addictions, Deficit of Attention, and Executive Functions: From an Epidemiological to a Clinical Perspective
No full textLe dipendenze, in particolare quelle da sostanze, possono essere considerate a tutti gli effetti condizioni problematiche nell’ambito della salute pubblica. Nello specifico, queste condizioni possono comportate effetti avversi e multipli sulla salute di un individuo, di natura sia fisica sia psicologica, includendo tra le potenziali problematiche i deficit dell’attenzione e l’impairment delle funzioni esecutive.
Ad oggi, la maggior parte dei lavori in letteratura si è focalizzata sullo studio delle potenziali relazioni tra deficit dell’attenzione, funzionamento esecutivo e dipendenze da un punto di vista prevalentemente clinico. Di conseguenza, il presente lavoro ha avuto come obiettivo primario l’approfondimento dei possibili legami tra i fenomeni di cui sopra all’interno della popolazione generale al fine di fornire un quadro rappresentativo del fenomeno, includendo anche le così dette popolazioni nascoste.
La prima parte del progetto si è focalizzata sulla conduzione di revisioni sistematiche della letteratura e meta-analisi al fine di osservare la co-occorrenza di ADHD e dipendenze (sia da sostanza sia comportamentali), nonché la presenza di attentional bias tra le persone con uso problematico di sostanze o coinvolte in attività rischiose per l’insorgenza di dipendenze comportamentali.
Successivamente, grazie allo studio Italian Population Survey on Alcohol and Other Drugs (IPSAD®), sono stati raccolti dati all’interno della popolazione generale relativi al funzionamento esecutivo, a una sua potenziale compromissione, ai pattern di consumo di sostanze e di comportamenti a rischio quali il gioco d’azzardo e l’utilizzo problematico di Internet.
Questo lavoro ha inoltre permesso di validare una scala per la misurazione del funzionamento esecutivo nella popolazione generale. I risultati hanno evidenziato come all’interno della popolazione italiana il consumo problematico di cannabis e alcol, il gioco d’azzardo problematico e l’utilizzo problematico di Internet siano associati ad un impairment del funzionamento esecutivo, con particolare riferimento alla working memory e alle capacità inibitorie. Oltre a questo, i risultati ottenuti hanno inoltre rilevato altri fattori che possono concorrere a una compromissione dei processi cognitivi che riguardano sia le abitudini quotidiane (ad esempio, le ore di sonno per notte) sia l’esperienza di eventi traumatici nell’arco della propria vita.
Infine, con l’obiettivo di validare uno strumento efficace per l’assessment delle funzioni esecutive e discriminare la presenza o meno della sintomatologia ADHD, sono stati estratti i cut-off di ADEXI and delle sue sottoscale (memoria di lavoro e inibizione). Questo ha permesso di introdurre in letteratura un utile strumento self-report di screening, utilizzabile anche nelle survey di popolazione.
In conclusione, i risultati complessivi ottenuti in questo progetto mettono in evidenza l’esistenza di un’associazione tra un impairment del funzionamento esecutivo e comportamenti a rischio di dipendenza anche all’interno della popolazione generale. I risultati del presente progetto forniscono inoltre le basi per lo sviluppo di studi futuri nell’ambito della salute pubblica, nonché uno strumento efficace per la misurazione del funzionamento esecutivo mediante survey di popolazione.
Addictions, particularly substance-related addictions, can be considered problematic conditions in the public health field. Specifically, these conditions can involve multiple adverse effects on an individual's physical and psychological health, including the deficit of attention and impairment of executive functions.
To date, most of the literature has focused on the potential relationships between deficit of attention, executive functioning impairment, and addictions from a primarily clinical perspective. Accordingly, the main aim of the present work was to investigate the possible links between the above phenomena within the general population to provide a representative picture of the phenomenon, including the so-called hidden populations.
The first part of the project focused on conducting systematic literature reviews and meta-analyses in order to observe the co-occurrence of ADHD and addictions (both substance-related and behavioral), as well as the presence of attentional bias among people with problematic substance use or involved in risky activities for the onset of behavioral addiction.
Subsequently, through the Italian Population Survey on Alcohol and Other Drugs (IPSAD®) study, data were collected within the general population regarding executive functioning, patterns of substance use, and other risky behaviours such as gambling.
This work also made it possible to validate a scale for measuring executive functioning in the general population. The results showed that within the Italian population, problematic cannabis and alcohol use, problematic gambling, and problematic Internet use are associated with impaired executive functioning, with particular reference to working memory and inhibition. In addition, the findings also revealed other factors that may contribute to impaired cognitive processes that relate to both daily habits (e.g., hours of sleep per night) and the experience of traumatic events over one's lifetime.
Finally, to validate an effective tool for executive function assessment and to discriminate the presence or absence of ADHD symptomatology, the cut-offs of ADEXI and its sub-scales (working memory and inhibition) were extracted. This made it possible to introduce a useful self-report screening tool into the literature, which can also be used in population surveys.
In conclusion, the overall results obtained in this project highlight the existence of an association between impaired executive functioning and addiction risk behaviors even within the general population. The results of the present project also provide a groundwork for the development of future studies in the field of public health and an effective tool for measuring executive functioning through population surveys
Recupero motorio dell’arto superiore in fase cronica di ictus indotto da trattamento combinato con tossina botulinica e riabilitazione robotica
No full textLa compromissione sensorimotoria dell’arto superiore è una delle condizioni di maggior disabilità a lungo termine nei pazienti che sopravvivono all’ictus.
Il deficit del controllo motorio, in particolare, persiste nei due terzi dei pazienti in fase cronica di malattia, con conseguente limitazione funzionale nelle attività di vita quotidiana, restrizione della partecipazione sociale e peggioramento della qualità di vita.
La riabilitazione gioca un ruolo fondamentale nel favorire il miglioramento funzionale dell’arto superiore paretico; tuttavia, ad oggi, non esistono protocolli personalizzati che siano in grado di assicurare un reale recupero motorio.
Per recupero motorio si intende la riacquisizione della capacità di effettuare un determinato movimento, utilizzando gli stessi effettori e lo stesso pattern motorio con cui veniva effettuato prima dell’evento lesionale.
Nelle fasi croniche dell’ictus il recupero del controllo motorio, unitamente alla gestione della spasticità, è classicamente tra i principali obiettivi a cui si rivolgono gli interventi riabilitativi.
La spasticità è un disordine del movimento che compare già nelle fasi sub-acute di malattia e può impattare negativamente il recupero motorio durante tutto il decorso evolutivo di una lesione del SNC.
Il trattamento della spasticità focale con tossina botulinica di tipo A (BoNT-A), soprattutto quando associato a specifici trattamenti riabilitativi, è attualmente una terapia ben validata per la sua efficacia nel ridurre l’iperattivazione muscolare, nel ridurre la coattivazione tra muscoli agonisti ed antagonisti e nell’aumentare il Range of Motion. Tuttavia, ad oggi, non vi sono sufficienti evidenze sull’efficacia di tale trattamento nel determinare un miglioramento funzionale dell’arto paretico- spastico.
Di recente si è mostrata promettente l’integrazione tra terapia robotica ad alta intensità e il trattamento della spasticità con tossina botulinica nella riabilitazione dell’arto superiore.
Il lavoro presentato in questa tesi ha come scopo principale quindi quello di valutare se il trattamento della spasticità, quando associato ad uno specifico trattamento riabilitativo, possa contribuire ad un recupero “reale” del controllo motorio, piuttosto che a una facilitazione di meccanismi di compenso. In particolare in questo lavoro abbiamo voluto indagare le modificazioni cliniche, cinematiche ed elettromiografiche dell’arto superiore in un gruppo di pazienti affetti da emiparesi spastica in fase cronica di ictus, prima e dopo trattamento con training robotico task-oriented, confrontandole con le modifiche rilevate in un gruppo analogo di pazienti in cui il training robotico veniva combinato al trattamento della spasticità con tossina botulinica.
Sono stati finora reclutati 14 pazienti, di cui 7 sottoposti a trattamento robotico task-oriented e 7 a trattamento combinato. Le misure di outcome, registrate prima del trattamento (T0), al termine dello stesso (T1) e a 2 mesi dal termine (T2), comprendevano scale funzionali, analisi della cinematica durante l’esecuzione di task motori predefiniti e registrazione dell’attività muscolare tramite elettromiografia di superficie. Tutti i pazienti sono stati sottoposti a trattamento robotico con esoscheletro bilaterale per arto superiore (ALEX-RS), per un totale di 12 sedute. Ai pazienti per i quali era previsto il trattamento combinato, immediatamente prima dell’inizio del training robotico, è stata inoltre effettuata l’inoculazione tossina botulinica di tipo A.
I risultati preliminari fin qui prodotti mostrano un miglioramento funzionale di entrambi i gruppi, ma con differenze a favore del gruppo sottoposto a trattamento combinato, che mostra una maggiore riduzione della spasticità, un maggior guadagno funzionale in termini di qualità del movimento ed un miglioramento nei parametri cinematici rispetto al gruppo di controllo.
Dall’analisi dei dati elettromiografici non sono emerse differenze nette tra i due gruppi.
Tuttavia, sia nel gruppo sottoposto a terapia combinata che nel gruppo di controllo è stato osservato un trend di miglioramento della qualità dell’attivazione muscolare che, successivamente al trattamento, tende a diventare più simile a quella dei soggetti sani.
In conclusione, questi risultati sembrano incoraggianti nel confermare l’ipotesi iniziale che il trattamento combinato possa essere più efficace nel determinare un recupero funzionale sostenuto da un reale recupero motorio.
Sensorimotor impairment of the upper limb is one of the conditions of greatest long-term disability in stroke survivors.
Motor control deficit, in particular, persists in two-thirds of patients in the chronic phase of the disease, resulting in functional limitation in activities of daily living, restriction of social participation, and worsening quality of life.
Rehabilitation plays a key role in promoting functional improvement of the paretic upper limb; however, to date, there are no individualized protocols that are able to ensure real motor recovery.
Motor recovery refers to the regaining of the ability to perform a given movement, using the same effectors and motor pattern with which it was performed before the injury event.
In the chronic stages of stroke, the recovery of motor control, together with the management of spasticity, is classically among the main goals to which rehabilitation interventions are directed.
Spasticity is a movement disorder that appears as early as the subacute stages of disease and can negatively impact motor recovery throughout the developmental course of a CNS injury.
Treatment of focal spasticity with botulinum toxin type A (BoNT-A), especially when combined with specific rehabilitation treatments, is currently a well-validated therapy for its efficacy in reducing muscle hyperactivation, reducing co-activation between agonist and antagonist muscles, and increasing Range of Motion. However, to date, there is insufficient evidence on the effectiveness of this treatment in bringing about functional improvement in the paretic-spastic limb.
Recently, the integration of high-intensity robotic therapy and the treatment of spasticity with botulinum toxin in upper limb rehabilitation has shown promise.
The main purpose of the work presented in this thesis is therefore to evaluate whether the treatment of spasticity, when combined with a specific rehabilitation treatment, can contribute to a “real” recovery of motor control, rather than a facilitation of compensation mechanisms.
Specifically, in this work we aimed to investigate the clinical, kinematic, and electromyographic changes of the upper extremity in a group of patients with spastic hemiparesis in the chronic phase of stroke, before and after treatment with task-oriented robotic training, comparing them with the changes found in a similar group of patients in whom robotic training was combined with treatment of spasticity with botulinum toxin.
Fourteen patients have been recruited so far, of whom 7 underwent task-oriented robotic treatment and 7 combined treatment. Outcome measures, recorded before treatment (T0), at the end of treatment (T1), and 2 months after completion (T2), included functional scales, analysis of kinematics while performing predefined motor tasks, and recording of muscle activity by surface electromyography. All patients underwent robotic treatment with a bilateral upper limb exoskeleton (ALEX-RS) for a total of 12 sessions. Patients for whom combined treatment was planned were also given botulinum toxin type A inoculation immediately before the start of robotic training.
Preliminary results produced so far show functional improvement in both groups, but with differences in favor of the combined treatment group, which shows greater reduction in spasticity, greater functional gain in quality of movement and improvement in kinematic parameters than the control group.
Analysis of electromyographic data showed no clear differences between the two groups.
However, a trend of improvement in the quality of muscle activation was observed in both the group undergoing combination therapy and the control group, which, following treatment, tended to become more similar to that of healthy subjects.
In conclusion, these results seem encouraging in confirming the initial hypothesis that combination treatment may be more effective in bringing about functional recovery supported by real motor recovery
Unlocking the Potential of Radiomics in Identifying Fibrosing and Inflammatory Patterns in Interstitial Lung Disease
No full textThe purpose of this thesis is to develop a system capable of segmenting interstitial involvement in chest CT scans and identifying radiomic features characteristic of distinct patterns of lung disease. Specifically, the study focuses on differentiating fibrotic patterns, such as Usual Interstitial Pneumonia (UIP), from inflammatory patterns like Non-Specific Interstitial Pneumonia (NSIP) and distinguishing NSIP from viral pneumonia, including COVID-19. By leveraging advanced image analysis and machine learning techniques, the proposed system aims to enhance diagnostic accuracy and provide automated tools to assist clinicians in differentiating these complex and overlapping conditions
Applicazione di sequenze Arterial Spin Labeling (ASL) in Risonanza Magnetica per la determinazione della perfusione cerebrale nella Malattia di Parkinson e nei parkinsonismi atipici
No full textLa diagnosi differenziale tra parkinsonismi e l’identificazione di nuovi biomarker rimane un problema aperto nei disordini del movimento. Il presente studio ha valutato l’applicazione di sequenze di Risonanza Magnetica perfusionale secondo metodica Arterial Spin Labeling (RM-ASL) in pazienti con Malattia di Parkinson (MP), Paralisi Sopranucleare Progressiva (PSP) e Atrofia Multisistemica (MSA). Preliminarmente, è stato effettuato un confronto morfometrico con analisi automatica Voxel based (VBM). E’ stata riscontrata una significativa ipoperfusione in alcune regioni corticali frontali nella PSP rispetto ad MSA e MP, in assenza di concomitanti differenze nel trofismo, mentre non sono state identificate differenze tra MSA e MP. Questo risultato evidenzia un possibile ruolo della RM-ASL nei parkinsonismi, soprattutto nella PSP dove l’ipoperfusione potrebbe precedere la degenerazione strutturale.
The differential diagnosis among parkinsonisms and the identification of new biomarkers is a current issue in movement disorders. The current study investigated the role of perfusional MRI employing Arterial Spin Labeling sequences (ASL-MRI) in Parkinson’s disease (PD), Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA). A morphometric analysis with a voxel based approach (VBM) was performed too. A significant difference in perfusion of some frontal cortical regions was demonstrated in PSP patients, without finding significant differences with the VBM approach. No differences were found between MSA and MP. This result highlight a potential role of ASL MRI in the field of parkinsonisms, especially PSP, since hypoperfusion might anticipate structural neurodegeneration in this condition
Clinical characteristics, psychopharmacological treatment and duration of hospitalization in patients with delirium: a liaison psychiatry study conducted at the General University Hospital of Pisa.
No full textDelirium is a complex, multifactorial and potentially transient neuropsychiatric syndrome characterised by acute alterations in mental status with a fluctuating course. This makes it difficult to diagnose and manage in hospital. Because of the difficulty of diagnosis and therefore treatment due to the heterogeneity of its manifestations, and because of its high impact on duration of hospital stay, ward workload and clinical outcomes of patients, this condition represents a major challenge for clinicians. The aim of this retrospective observational study was to analyse the clinical characteristics, psychopharmacological treatments and duration of hospital stay of 168 patients hospitalised between May 2020 and May 2021 with a diagnosis of delirium confirmed by a psychiatric consultation, carried out at the University General Hospital of Pisa.
With a mean age of 72 years and a higher prevalence of women, the cohort was predominantly elderly. They were mainly from medical departments and to a lesser extent from surgical departments. The most common medical diagnoses included cardiovascular disease, nephro-uropathy and diabetes mellitus, showing a profile of chronic co-morbidities that are often present in patients with delirium. The most common neuropsychiatric comorbidities were anxiety, depression and dementia supporting the interaction between cognitive and psychiatric predisposition in the risk of delirium.
The average duration of stay was 13.3 days with surgical patients tending to stay longer than medical patients. This finding reflects the increased complexity of managing post-operative patients where factors such as pain, use of sedatives and surgical complications can increase the risk of delirium. Patients with traumatic injuries and nephrouropathies had the longest average duration of stay, while those with chronic infections and dementia had shorter average duration of stay, probably due to management strategies aimed at transfer to long-term care facilities or home.
First- and second-generation antipsychotics were the most commonly used pharmacological treatments followed by mood stabilisers, benzodiazepines and trazodone. Although there were not statistically significant associations between the use of particular drugs and duration of hospital stay, more complex therapeutic combinations such as benzodiazepines and mood stabilizers were associated with longer hospital stays. This finding, which reflects the severity of the clinical picture rather than direct efficacy in reducing length of stay, suggests that such combinations may be preferred in more clinically severe and resistant cases or those with complex psychiatric comorbidities.
Underdiagnosis of the hypokinetic form of delirium, which is often confused with other conditions such as depression, asthenia or cognitive impairment, has emerged as a critical element. This diagnostic gap highlights the need for greater use of standardised tools such as the Confusion Assessment Method (CAM) in routine clinical practice to improve early recognition, particularly in elderly and frail patients. In order to implement appropriate interventions that reduce the risk of duration of stay, in-hospital complications and mortality early diagnosis of delirium is crucial. Using validated tools can also help differentiate delirium from other neurocognitive conditions, such as dementia, and psychiatric disorders, such as psychosis and depression.
The study has some limitations including its retrospective nature, lack of post-discharge follow-up, and lack of detailed data on drug dosages and duration. In addition, excluding patients with unconfirmed diagnoses or who did not receive a psychiatric consultation may have limited the representativeness of the sample by reducing the generalisability of the results. In conclusion, by highlighting the challenges of early diagnosis and pharmacological management of this complex syndrome this study provides an overview of the clinical and therapeutic dynamics of delirium in hospital. Results emphasise the need for common diagnostic and therapeutic strategies complemented by multidisciplinary approaches to improve outcomes. Further prospective studies are essential to develop more effective and personalised management models and to further investigate the relationships between clinical features, treatments and outcomes. This research provides an important foundation for future initiatives to improve the quality of care and to optimise the use of health care resources in patients with delirium
Disordered eating behaviors, impulsivity and affective temperaments in a sample of obese candidates for bariatric surgery: which linkage?
No full textBackground: Obesity represents one of the main public health challenges of the 21st century, with a prevalence of affected people that has steadily and dramatically increased worldwide over time. Within the context of obesity, disordered eating behaviors play a pivotal role, further complicating the clinical management of this condition and representing a maintaining factor of the disorder. Indeed, evidence from the literature highlights how emotional eating (EE) rates reach up to 65-75% of subjects in overweight or obese adult samples, and how as many as 54% of patients seeking bariatric surgery exhibit symptoms indicative of food dependence. This represents an obstacle for long-term outcome in people with severe obesity, such as weight loss maintenance after bariatric surgery.
Evidence from literature highlighted how pathological overeating may be a manifestation of a disrupted brain reward system, and this has been related to phenotypic expressions characterized by with high emotional dysregulation and impulsivity. The impulsiveness dimension observed in eating disorders and obesity has been accounted for by a deficient top–down cognitive inhibitory control over salience stimuli with a subsequent imbalance between impulsive and reflective systems.
The association between problematic eating behaviors and obesity has been investigated but limited studies have explored the role of affective temperaments as an innate and stable emotion-related traits influencing energy level, mood and responses to external stimuli.
Aim: Considering the above, the aim of this study is to investigate the relationship between emotional eating, impulsivity dimension, and affective temperaments in a sample of obese patients’ candidate for bariatric surgery.
Methods: A total sample of 304 obese outpatients were consecutively enrolled at the Psychiatry Clinic of the Department of Clinical and Experimental Medicine of the University of Pisa between September 2018 and June 2024, during the presurgical mental health evaluation routinely performed before the bariatric intervention in the framework of psychiatric, presurgical and medical assessment. Sociodemographic and clinical data were collected by psychiatrists during a single consultation. Assessments also included the following psychometric tests: the Structured Clinical Interview (SCID-5), the Emotional Eating Scale (EES), the Barratt Impulsivity Scale-Version 11 (BIS-11), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Auto-questionnaire (TEMPS-A).
Results: In our sample, a significant correlation was observed between the EES total score and the BIS total score (p=0.003), as well as with the sub-dimensions of attentional impulsivity (p<0.001) and motor impulsivity (p=0.024). In addition, a significant correlation has been found between the total score of EES and the cyclothymic (p<0.001), depressive (p<0.001), irritable (p=0.013), and anxious (0.020) temperaments. When comparing obese patients with (EE) and without (No-EE) emotional eating, higher rates of both current (p=0.007) and lifetime (p=0.024) psychiatric comorbidities have been observed in the EE-group, namely for anxiety disorders (p=0.008) and eating disorders (p=0.014).
Limitations: The cross-sectional study design, the self-reported questionnaires, and the lack of inquire about GLP-1 agonists therapy.
Conclusions: Our study highlights a significant association of emotional eating in obese patients with the cyclothymic-irritable-anxious-depressive temperaments and impulsivity dimension. Thus, problematic eating behaviors and temperamental traits may have a bidirectional psychopathological influence in obese patients, and need to be carefully evaluated in subject seeking for bariatric surgery. Further study with longitudinal design including follow-up after surgery are needed to evaluate the long-term effects on outcome
Investigating the relationship between autistic traits, post-traumatic stress symptoms and catatonic features among patients with Feeding and Eating Disorders and Borderline personality disorder
No full textBackground: growing literature has recently focused on subthreshold autistic traits (AT), traumatic events and catatonic features among individuals with borderline personality disorder (BPD) and feeding and eating disorders (FED). It is known that autistic individuals are often exposed to traumatic events because of their difficulties in social cognition and in mentalization. Meanwhile, AT themselves as well as a story of traumatic events could represent vulnerability factors for the development of other psychiatric conditions, including eating disorders, mood disorders and catatonia. In this framework, the aim of this work is to analyse the presence of AT, catatonic and post traumatic symptoms among individuals with BPD and FED, as well as their reciprocal relationships.
Methods: 159 individuals (18 males and 141 females) were recruited from Psychiatric Clinic of Pisa. They were divided into three main diagnostic groups: BPD (n= 49), FED (n=55), healthy controls (HCs) (n=55). The FED group was divided into two other groups: the one made by individuals with Anorexia Nervosa (n=15), the other by subjects with Bulimia Nervosa or Binge Eating Disorder (BN/BED) (n=40). The Structured Clinical Interview for the fifth edition of diagnostic and statistical manual of mental disorders (DSM-5) (SCID-5) was employed for full-blown diagnosis of psychiatric disorders; additionally, in order to assess, according to a dimensional approach, various subthreshold and over threshold symptomatology, the following questionnaire were employed: the Adult Autism Subthreshold Spectrum (AdAS Spectrum), the Catatonia Spectrum (CS), and the Trauma and Loss Spectrum Self-Report (TALS-SR).
Results: our results showed a significantly higher score at the AdAS, CS and TALS-SR in both FED and BPD than healthy controls, except from the TALS-SR “Personal Characteristics and Risk Factors” domain in which BPD had higher scores than FED group, who, in turn, scored higher than HCs. We reported that AN individual significantly differed from BN/BED in the AdAS Non Verbal Communication and Child Adolescence domains and in the CS Automatism, Response to Instruction. Spearman correlation revealed a positive correlation between all AdAS domains and CS and TALS-SR domains. Meanwhile, all CS domains were correlated with TALS-SR ones. Multinomial regression analysis pointed out that both AdAS and CS total score were significant predictors for the inclusion in BPD or FED group. Specifically, AdAS Childhood Adolescence and Non verbal communication domains predicted the inclusion in both BPD or FED groups, with the first being slight more predictive of the inclusion in BPD group, while the second in FED group. About CS, Psychomotor activity predicted the inclusion in both BPD and FED groups, while Impulsivity only for inclusion in BPD one. Finally, linear regression pointed out that for the FED group, only AdAS symptoms predicted greater catatonic symptoms, while for the BPD one, both AdAS and TALS-SR were predictors of greater catatonic fetaures.
Conclusions: our findings indicate that both BPD and FED subjects exhibit more frequent AT, stress-related symptoms, and catatonic manifestations compared to controls, underscoring the complex interplay between neurodevelopmental vulnerabilities and psychiatric disorders. However, the two disorders seem to differ, each being associated with a specific pattern of autistic-catatonic features, while a closer association between personal characteristic of vulnerability and risk factors for trauma and stress related conditions seem to be associated with BPD. Moreover, our results support the hypothesis that BPD and FED may often be associated with the presence of AT, with potential pathways leading to the emergence of catatonic features. In particular, our results further confirm the predictive role of AT in the development of catatonia, while the predictive role of post-traumatic symptoms on catatonia in BPD, but not in FED, highlight the potential differences in the relationship between neurodevelopmental and environmental factors in the illness trajectories of these disorders