The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study

BackgroundAutonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated.ObjectivesWe aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment.MethodsData were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society—Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively.ResultsFollow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = −0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004).ConclusionsAutonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis

Hands-feet wireless devices: Test-retest reliability and discriminant validity of motor measures in Parkinson's disease telemonitoring

Background Telemonitoring, a branch of telemedicine, involves the use of technological tools to remotely detect clinical data and evaluate patients. Telemonitoring of patients with Parkinson's disease (PD) should be performed using reliable and discriminant motor measures. Furthermore, the method of data collection and transmission, and the type of subjects suitable for telemonitoring must be well defined. Objective To analyze differences in patients with PD and healthy controls (HC) with the wearable inertial device SensHands-SensFeet (SH-SF), adopting a standardized acquisition mode, to verify if motor measures provided by SH-SF have a high discriminating capacity and high intraclass correlation coefficient (ICC). Methods Altogether, 64 patients with mild-to-moderate PD and 50 HC performed 14 standardized motor activities for assessing bradykinesia, postural and resting tremors, and gait parameters. SH-SF inertial devices were used to acquire movements and calculate objective motor measures of movement (total: 75). For each motor task, five or more biomechanical parameters were measured twice. The results were compared between patients with PD and HC. Results Fifty-eight objective motor measures significantly differed between patients with PD and HC; among these, 32 demonstrated relevant discrimination power (Cohen's d > 0.8). The test-retest reliability was excellent in patients with PD (median ICC = 0.85 right limbs, 0.91 left limbs) and HC (median ICC = 0.78 right limbs, 0.82 left limbs). Conclusion In a supervised environment, the SH-SF device provides motor measures with good results in terms of reliability and discriminant ability. The reliability of SH-SF measurements should be evaluated in an unsupervised home setting in future studies

Biogeochemical and microbial community structure differently modulates CO2 and CH4 dynamics in two adjacent volcanic lakes (Monticchio, Italy)

By hosting significant amounts of extra-atmospheric dissolved gases, including geogenic CO2 and CH4, volcanic lakes provide relevant ecosystem services through the key role the aquatic microbial community in mediating freshwater carbon fluxes. In view of elucidating the mechanisms governing the microbial spatial distribution and the possible implications for ecosystem functioning, we compared the hydrogeochemical features and the microbial community structure of two adjacent stratified volcanic lakes (Lake Grande - LG and Lake Piccolo - LP). Water chemistry, gases and their isotopic composition were coupled with microbial pigment profiling, cell counting, and phylogenetic analyses. LP showed transparent waters with low concentrations of chlorophyll-a and the occurrence of phycoerytrin-rich cyanobacteria. LG was relatively more eutrophic with a higher occurrence of diatoms and phycocyanine-rich cyanobacteria. Considering the higher concentrations of CO2 and CH4 in bottom waters, the oligotrophic LP was likely a more efficient sink of geogenic CO2 in comparison to the adjacent eutrophic LG. The prokaryotic community was dominated by the mixothrophic hgcI clade (family Sporichthyaceae) in the LG surface waters, while in LP this taxon was dominant down to -15 m. Moreover, in LP, the bottom dark waters harbored a unique strictly anaerobic bacterial assemblage associated with methanogenic Archaea (i.e. Methanomicrobiales), resulting in a high biogenic methane concentration. Water layering and light penetration were confirmed as major factors affecting the microbial distribution patterns. The observed differences in the geochemical and trophic conditions reflected the structure of the aquatic microbial community, with direct consequences on the dynamics of dissolved greenhouse gases

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

La disfunzione del sistema serotoninergico nella malattia di Parkinson: follow up di coorte di pazienti arruolati nello studio PPMI

La malattia di Parkinson è una patologia neurodegenerativa caratterizzata da una grave perdita neuronale in numerose sedi del sistema nervoso centrale. Oltre alla degenerazione dei neuroni nigro-striatali, studi post-mortem e di neuroimaging indicano un coinvolgimento del sistema serotoninergico che origina dai nuclei del rafe al livello del tronco encefalico. Questo potrebbe contribuire alla comparsa del tremore e dei sintomi non motori, che sono ancora solo parzialmente spiegati dalla degenerazione del sistema dopaminergico. La metodica SPECT con l’utilizzo del tracciante 123I-FP-CIT rappresenta un marker dell’espressione dei trasportatori della dopamina e della serotonina. Mentre al livello dello striato questo tracciante si lega principalmente ai trasportatori della dopamina, al livello dei nuclei del rafe il suo legame rappresenta la disponibilità dei trasportatori della serotonina. Un recente studio ha evidenziato che una coorte di pazienti arruolati nello studio Parkinson’s Progression Markers Initiative (PPMI) con malattia di Parkinson in fase iniziale ha una significativa riduzione del trasportatore della serotonina al livello dei nuclei del rafe. Tuttavia, solo il 13% di questi pazienti presenta un segnale ridotto (< -1.5 DS) rispetto ai controlli. Nel medesimo studio è stata segnalata la presenza di una correlazione inversa statisticamente significativa tra i valori di captazione del tracciante 123I-FP-CIT al livello dei nuclei del rafe e i valori di tremore a riposo rilevati con la scala MDS-UPDRS. Tale correlazione era particolarmente evidente nel sottogruppo di pazienti tremorigeni e si manteneva significativa anche all’interno dell’intera coorte. L’obiettivo di questa tesi è quello di valutare l’evoluzione sintomatologica e di neuroimaging in questa coorte di pazienti dopo un follow up di 2 anni. Al follow up erano presenti 194 pazienti; di questi il 39% (75 pazienti) presenta una significativa riduzione (< -1.5 DS) del trasportatore della serotonina al livello dei nuclei del rafe rispetto ai controlli. Nei pazienti tremorigeni (TD) è stata riscontrata una correlazione inversa statisticamente significativa tra i valori di captazione del tracciante 123I-FP-CIT al livello dei nuclei del rafe e i valori di continuità del tremore a riposo (beta = -0.208, p < 0.05), di ampiezza del tremore a riposo (beta = -0.191, p < 0.05) e dell’indice del tremore a riposo (beta = -0.196, p < 0.05). Nell’intera coorte di pazienti tale correlazione non è statisticamente significativa; tuttavia, quando i valori di captazione dei nuclei del rafe vengono rapportati a quelli del putamen, ovvero si valuta il rapporto tra la captazione del tracciante da parte dei neuroni serotoninergici e quella da parte dei neuroni dopaminergici nigro-striatali (rapporto rafe / putamen), si osserva una correlazione inversa statisticamente significativa tra questa variabile e i parametri relativi al tremore di riposo (ampiezza del tremore di riposo: beta = - 0,209, p < 0,01; continuità del tremore di riposo beta = - 0,261, p < 0,001; indice del tremore di riposo beta = - 0,261, p < 0,001). Poiché nelle fasi iniziali della malattia di Parkinson i valori di captazione al livello del putamen sono più elevati nei pazienti tremorigeni e più bassi nei pazienti rigido-acinetici, tale risultato sembra indicare che il sistema serotoninergico assuma un ruolo importante nella determinazione del fenotipo clinico della malattia, e in particolare del tremore, soprattutto quando la degenerazione della via nigrostriatale si presenti in forma “lieve-moderata”. Pertanto il presente studio conferma anche nel follow-up clinico e strumentale di un’ampia coorte di pazienti con malattia di Parkinson de novo il ruolo centrale della denervazione serotoninergica nella genesi del tremore di riposo parkinsoniano

Automatic generation of documents

This paper describes a natural interaction between Stata and markup languages. Stata’s programming and analysis features, together with the flexibility in output formatting of the markup languages, allow generation and/or update of whole documents (e.g., reports, presentations on screen or web). We give examples for both LaTeX and HTML

Automatic generation of documents

This paper describes a natural interaction between Stata and markup languages. Stata’s programming and analysis features, together with the flexibility in output formatting of the markup languages, allow generation and/or update of whole documents (e.g., reports, presentations on screen or web). We give examples for both LATEX and HTML. Copyright 2006 by StataCorp LP.doutput, format, report, LATEX, HTML, markup language

Automatic generation of documents

This paper describes a natural interaction between Stata and markup languages. Stata’s programming and analysis features, together with the flexibility in output formatting of markup languages, allow generation and/or update of whole documents (reports, presentations on screen or web, etc.). Examples are given for both LaTeX and HTML. Stata’s commands are mainly dedicated to analysis of data on a computer screen and output of analysis stored in a log file available to researchers for later reading. However, users may need to produce output in different formats and to cooperate with professionals who are not familiar with log files. An elegant solution to this problem is exporting output in the format of a markup language, such as LaTeX or HTML. The most common means for presenting the results of one or several analyses are text on paper, screen presentations, and web sites. While it is common to generate such outputs by visual programs, such as MS Office or OpenOffice, it is impossible for Stata to produce documents this way, as it lacks eyes to format a table and hands to hold a mouse to cut and paste graphs. Nevertheless, each of those presentation formats can also be obtained with use of a markup language. Wikipedia defines a markup language as “a kind of text encoding that represents text as well as details about the structure and appearance of the text”. To publish on the web, HTML is one of the best and most compatible formats. On other hand, LaTeX is a complete language for editing and text formatting on either paper or screen (most commonly via PDF files). Both languages are easy to learn, free, and well documented. Now Stata happens to be perfectly capable of writing text, such as the instructions for a markup language to write a report, a sequence of slides, or the pages of a web site containing tables and graphs. The problem of formatting the output of a command in LaTeX and/or HTML has been addressed in various ways by several authors. The most comprehensive reference to this issue is Newson (2003), who also provides a suite of tools aimed at printing in markup language the list of a Stata dataset, in such a way that variable labels, value labels, significant figures, and so forth are formatted the way one would wish. More generally, we can exploit Stata’s ability to write text files to make it produce virtually any piece of markup language code: tables and graphs, but also other kind of objects, like lists, trees, etc. Finally, by further printing some code putting together all of the ingredients, we make Stata produce a whole document, which is then browsable, printable, or showable on a screen, according to the kind of document. The key feature of this method is that the document automatically produced can be completely updated as soon as the figures in the data change. This is particularly suitable when the user needs to produce a large amount of output or routinely performs analyses on the same dataset structure, such as administrative data bases or collection of data from a long-lasting study. For an example of those facilities, we describe a do-file automatically constructing a web site for the Regional Agency for Public Health of Tuscany. Finally, we remark that to apply this method, Stata commands must store in memory their results—at least as many as necessary to reproduce the screen output. This is generally the case, with some notable counterexamples (dstdize, svyprop,...).

Marketing e Comunicazione. Strategie, strumenti, casi pratici

Negli ultimi anni, in seguito all'avvento del digitale, il marketing e la comunicazione hanno conosciuto trasformazioni talmente radicali da averne cambiato in profondità gli approcci, le strategie, le tecniche. Da qui la nuova visione d'insieme che questo libro cerca di fornire. Il volume prende le mosse dalle teorie e dalle definizioni classiche, nella consapevolezza che i grandi studiosi del passato sono ancora fondamentali per comprendere oggi le dinamiche di marketing e comunicazione. I capisaldi della comunicazione d'impresa, comunque aggiornati alla luce della trasformazione digitale, sono trattati in profondità: dal branding alla pubblicità, dalle ricerche di mercato alle relazioni pubbliche, fino agli eventi. L'ultima parte ha come focus proprio l'ecosistema digitale e illustra come l'ottimizzazione delle pagine web in funzione del loro posizionamento sui motori di ricerca o il design dell'esperienza dell'utente siano, insieme a un approccio strategico ai social media, imprescindibili per chiunque voglia fare marketing e comunicazione. A partire dall'esperienza del Master in Comunicazione d'impresa dell'Università di Siena, i diversi temi sono affrontati da studiosi provenienti da numerosi atenei nazionali e internazionali, nonché da professionisti di primo piano che operano all'interno di imprese, agenzie di comunicazione e società di consulenza. Ciascun capitolo è poi arricchito da schede di approfondimento e interviste a esperti del settore. Una pluralità di voci e discipline che ha l'obiettivo di definire un framework completo, indispensabile per chi si affaccia per la prima volta al mondo del marketing e della comunicazione, ma anche per chi, in questo mondo, opera già a livello professionale