Hand erosive osteoarthritis and distal interphalangeal involvement in psoriatic arthritis: the place of conservative therapy

Hand erosive osteoarthritis (HEOA) and Psoriatic Arthritis (PsA) with DIP involvement are common diseases affecting the hand. Both of them evolve with a progressive limitation in grip due to limited range of motion of the affected joints and stenosing tenosynovitis. Pharmacological options currently available (corticosteroids and clodronate or Idrossicloroquine) for the treatment of EHOA are mostly symptomatic and currently there are no effective drugs able to modify the course of the disease. In addition, data on drug effectiveness of PsA with DIP involvement are lacking. Conservative therapy should be considered in order to reduce pain and improve hand functionality. There are many studies debating a wide range of non-pharmacological intervention in the management of HEOA: joint protection program, range of motion and strengthening exercise, hand exercise with electromagnetic therapy, application of heat with paraffin wax or balneotherapy, occupational therapy and education. Concerning conservative treatment strategies to treat PsA, on the contrary, current evidence is still weak. Further research is needed to find the correct place of physical therapy to prevent stiffness and ankylosis due to the vicious circle of inflammation-pain-immobility-rigidity

The impact of recurrent Covid-19 waves on patients with Functional Movement Disorders: A follow-up study

Background: Functional Movement Disorders (FMDs) might exacerbate in stressful conditions. As the global health emergency due to Covid-19 rise and multiple waves hit the Italian population, the recurrent severe restrictions' periods imposed could represent important triggers and worsen the symptoms of FMDs. Through a follow-up study, we compare results on Motor Symptoms (MS), Non-Motor Symptoms (NMS), and Global Health Status (GHS) of two surveys, one referred to the first Covid-19 wave and the other to the third Covid-19 wave. Methods: 60 FMDs patients responded to an online survey after the first and the third Covid-19 waves in Italy. Questions regarding sociodemographic, clinical and Covid-19 information, MS, NMS, and GHS were collected to assess severity of symptoms and changes in comparison to a period with less severe social restrictions. Results: Patients showed minimal to mild motor symptoms' severity, and substantial stability through time in all collected measures, both for severity and changes of MS, NMS, and GHS in comparison at two time points (p > 0.050). The worsening of pain resulted as predictor factor for the worsening of Motor Symptoms (p = 0.042). Conclusions: Patients did not show a vulnerability due to the recurrent restrictions' periods: MS, NMS and GHS did not vary in comparison to the first wave, confirming the previous results and highlighting the role of the social context in those disorders. Further investigations are required to better disentangle the relationship between stressful events, motor symptoms, and pain

Characterization of hematite nanowire arrays synthesized by atmospheric plasma.

Hematite synthesized by low pressure oxygen plasma has been shown previously to exhibit promising characteristics as a photo-anode for a photoelectrochemical water splitting cell. It is cheap, stable and has a 2.1 eV bandgap and exhibits a significant photoactivity due to the presence of a thin interfacial layer and oxygen vacancy planes throughout the sample. Unfortunately, due to the nature of vacuum systems, this process would be difficult to scale-up and as such atmospheric plasma synthesis was explored. Photoactive hematite nanowire arrays were synthesized using an atmospheric microwave plasma jet reactor. They exhibited all of the characteristics of those synthesized under low pressure except for poor photoactivity due to a thin amorphous oxide layer on the surface layer. This oxide layer was removed by hydrofluoric acid etching and subsequently produced a significant photoactivity. Further synthesis improvements have yielded hematite nanowire arrays with no amorphous oxide layer present. Removal of nanowires from the nanowire array decreased the subsequent photoactivity of the electrode, indicating that photoactivity is due to the nanowires present on the sample and not due to the thin interfacial layer. Testing at different light intensities under constant voltage shows that photoactivity of hematite nanowire arrays is linearly dependent on light intensity

Performance validity tests in nonlitigant patients with functional motor disorder

Background: Performance Validity Tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual's abilities. Data on Functional motor disorder (FMD) are currently poor and conflicting. Objectives: We aimed to examine the rate of failure at three different PVTs of non-litigant, non-compensation seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators). Methods: We enrolled 29 non-litigant, non-compensation seeking patients with a clinical diagnosis of FMD, 29 healthy controls and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15-item Test (REY) and the Finger Tapping Test (FTT), were employed. Results: FMD Patients showed low rates of failure at the CIH and REY tests (7% and 10%, respectively) and slightly higher at the FTT (15%, n=26) test, which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p<0.001). 93% of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests. Conclusions: PVT performance of non-litigant, non-compensation seeking patients with FMD ranged from 7 to 15%. Patient's performance was comparable to controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice

Linguistic and cultural adaptation of the EARP Questionnaire to European Portuguese

OBJECTIVE: This study aims at the linguistic and cultural adaptation of the Early ARthritis for Psoriatic Patients (EARP) questionnaire into European Portuguese, for psoriatic patients attending dermatology medical examination. METHODS: Firstly, we performed a process of translation and back-translation of the English version of the EARP Questionnaire to European Portuguese, with interim and final harmonization. The resulting Portuguese version was approved by the EARP original author. Secondly, individual interviews were conducted to complete the linguistic and cultural adaptation of the initial translated Portuguese version, with the think-aloud and probe methods. At this stage, we conducted eight interviews, four with rheumatology and dermatology doctors (experts), and four with patients with psoriasis and psoriatic arthritis. Finally, the version resulting from the adaptation process was back-translated from Portuguese to English. RESULTS: Our results showed that EARP Questionnaire's items are easy to understand and do not raise comprehension concerns in experts or patients. Our findings suggested that items demanding health literacy from patients and that do not include a precise cue to signal the inflammatory nature of the joint pain may lead to confusion while answering, potentially leading to the patient's need for assistance. CONCLUSION: The Portuguese version of the EARP Questionnaire demonstrated adequate comprehension properties. Our findings support the use of this measure in clinical practice and future research, however, a validation study with Portuguese patients is needed.publishersversionpublishe

Voxel-based morphometry and task functional magnetic resonance imaging in essential tremor: evidence for a disrupted brain network

The pathophysiology of essential tremor (ET) is controversial and might be further elucidated by advanced neuroimaging. Focusing on homogenous ET patients diagnosed according to the 2018 consensus criteria, this study aimed to: (1) investigate whether task functional MRI (fMRI) can identify networks of activated and deactivated brain areas, (2) characterize morphometric and functional modulations, relative to healthy controls (HC). Ten ET patients and ten HC underwent fMRI while performing two motor tasks with their upper limb: (1) maintaining a posture (both groups); (2) simulating tremor (HC only). Activations/deactivations were obtained from General Linear Model and compared across groups/tasks. Voxel-based morphometry and linear regressions between clinical and fMRI data were also performed. Few cerebellar clusters of gray matter loss were found in ET. Conversely, widespread fMRI alterations were shown. Tremor in ET (task 1) was associated with extensive deactivations mainly involving the cerebellum, sensory-motor cortex, and basal ganglia compared to both tasks in HC, and was negatively correlated with clinical tremor scales. Homogeneous ET patients demonstrated deactivation patterns during tasks triggering tremor, encompassing a network of cortical and subcortical regions. Our results point towards a marked cerebellar involvement in ET pathophysiology and the presence of an impaired cerebello-thalamo-cortical tremor network

Changes in Corticospinal Circuits During Premovement Facilitation in Physiological Conditions.

Changes in corticospinal excitability have been well documented in the preparatory period before movement, however, their mechanisms and physiological role have not been entirely elucidated. We aimed to investigate the functional changes of excitatory corticospinal circuits during a reaction time (RT) motor task (thumb abduction) in healthy subjects (HS). 26 HS received single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). After a visual go signal, we calculated RT and delivered TMS at three intervals (50, 100, and 150 ms) within RT and before movement onset, recording motor evoked potentials (MEP) from the abductor pollicis brevis (APB) and the task-irrelevant abductor digiti minimi (ADM). We found that TMS increased MEPAPB amplitude when delivered at 150, 100, and 50 ms before movement onset, demonstrating the occurrence of premovement facilitation (PMF). MEP increase was greater at the shorter interval (MEP50) and restricted to APB (no significant effects were detected recording from ADM). We also reported time-dependent changes of the RT and a TMS side-dependent effect on MEP amplitude (greater on the dominant side). In conclusion, we here report changes of RT and side-dependent, selective and facilitatory effects on the MEPAPB amplitude when TMS is delivered before movement onset (PMF), supporting the role of excitatory corticospinal mechanisms at the basis of the selective PMF of the target muscle during the RT protocol

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Epithelial cells undergoing Epithelial Mesenchymal Transition in Systemic Sclerosis lack caveolin-1 and modulate WNT signaling in the dermis by secreting SFRP4

La Graft Versus Host Disease cronica (cGVHD) con interessamento cutaneo si presenta nel 5-15% dei casi con un fenotipo fibrotico. Questa variante \ue8 definita sclerotic-cGVHD ed \ue8 stato suggerito essere un modello utile per studiare l\u2019immunopatogenesi della sclerodermia. In primis abbiamo analizzato gli aspetti istopatologici della GVHD cronica e della sclerotic-GVHD concentrandoci sulla quantificazione della matrice extracellulare e sul diametro dei vasi da una parte e sugli aspetti molecolari-immunologici peculiari della sclerodermia dall\u2019altra, come la riduzione di espressione di caveolina-1. Inoltre, ci siamo proposti di identificare i geni che possono legare l\u2019attivazione del sistema immunitario con la risposta fibrotica nella sclerodermia attraverso l\u2019analisi comparativa del trascriptoma delle biopsie cutanee ricavate dai pazienti affetti da sclerodermia, GVHD cronica fibrotica e non fibrotica. Abbiamo arruolato 13 pazienti affetti da GVHD cronica, 93 pazienti sclerodermici e 3 volontari sani. Le biopsie cutanee unitamente ai dati clinici e ai campioni di siero sono state effettuate su 5 pazienti affetti da GVHD cronica non fibrotica, 9 pazienti con fenotipo fibrotico, 8 pazienti affetti da sclerodermia e 3 soggetti sani; I dati clinici e un campione di siero \ue8 stato invece raccolto da 80 pazienti sclerodermici seguiti presso il DH della Reumatologia dell\u2019Azienda Ospedaliera Integrata di Verona. Le biopsie cutanee sono state divise in due parti: una parte \ue8 stata conservata in RNA later fino all\u2019utilizzo, l\u2019altra fissata in paraformaldeide per I preparati istologici. Abbiamo poi scelto di analizzare l\u2019espressione genica sulla cute affetta dei pazienti con GVHD cronica di 84 geni derivanti dalla metanalisi dei lavori di microarray effettuati sulla cute sclerodermica su un totale di 36 pazienti. La PCR real time \ue8 stata utilizzata per studiare l\u2019espressione di questi geni che abbiamo chiamato \u201cscleroderma signature\u201d nelle biopsie cutanee dei pazienti con il fenotipo fibrotico e non fibrotico di GVHD cronica. I risultati sono stati quindi validati mediante esperimenti di Immunofluorescenza sulle biopsie cutanee e con seguente analisi con microscopio confocale. I livelli di proteine circolati prodotto dei geni testate sono state misurate nel siero con test ELISA. Per la validazione funzionale abbiamo eseguito studi in vitro sulle cellule epiteliali. La correlazione dei livelli proteici risultati dagli ELISA e i parametri clinici \ue8 stata analizzata utilizzando il software SPSS 18. Abbiamo dimostrato come sulle cuti affette da Scl-GVHD vi fosse un incremento di spessore dovuto al deposito di matrice extracellulare del tutto simile alla sclerodermia, mentre nella Scl- GVHD non si osservava la riduzione del lume dei vasi epidermici. Inoltre l\u2019espressione di caveolina-1 \ue8 risultata notevolmente diminuita nella GVHD cronica con fenotipo fibrotico rispetto ai soggetti sani e alla GVHD cronica senza fibrosi, tale riduzione era stata osservata in maniera simile nella sclerodermia. La RT-PCR dei 86 geni tipicamente disregolati nella sclerodermia ha dimostrato che solo 4 geni presentano un\u2019espressione specifica e concordante nella sclerodermia e nella scl-GVHD; tra questi Secreted Frizzled Receptor 4. Esperimenti di doppia immunofluorescenza, seguiti da analisi con microscopia confocale sulle biopsie cutanee dei pazienti affetti da scl-GVHD e sclerodermia hanno evidenziato come fonte di aumentata espressione di SFRP4 i fibroblasti, le cellule epiteliali dello strato basale e germinale dell\u2019epidermide e i melanociti. Le cellule esprimenti SFRP4 nello strato basale dell\u2019epidermide risultavano positive alla vimentina e negative alla caveolina. Dagli studi in vitro \ue8 stato poi dimostrato che le cellule epiteliali indotte in transizione mesenchimale grazie alla stimolazione con TGF- beta riducevano l\u2019espressione di caveolina 35%, aumentavano l\u2019espressione di SFRP4 del 52% come mRNA e del 68% come proteina. Inoltre I livelli sierici di SFRP4 correlavano inversamente con la Diffusion lung capacity (r=0.234 p=0.001) e correlavano direttamente con il Rodnann skin score (mRSS) nei pazienti con funzione polmonare normale.Chronic Graft Versus Host Disease (cGVHD) can present in 5-15% of cases with fibrotic skin involvement. This variant is defined as sclerotic-cGVHD and it has been suggested as a useful model to study the immunopathogenesis of systemic sclerosis (SSc) fibrosis. We analysed the histopathological features of cGVHD and scl-GVHD focusing on amount of extracellular matrix and vessel lumen ratio as well as immunohistochemical features peculiar of SSc like decreased expression of the lipid raft protein caveolin-1. Additionally, we aimed to identify the genes that may bridge the immune activation and the fibrotic response in SSc by comparative analysis of the transcriptome of skin biopsies from SSc, cGVHD and scl-GVHD. Thirteen patients with diagnosis of cGVHD, 93 with SSc and 3 healthy volunteers were enrolled in the University Hospital of Verona, Italy. Skin biopsies, serum samples and clinical data were collected for 5 Patients with cGVHD, 9 with scl-GVHD, 8 with SSc and 3 from healthy controls, only sera and clinical data were collected from 80 SSc patients. Biopsies were split in two halves, one stored in RNA later and the other one fixed in parafolmadehide for paraffin embedding. We selected 84 genes as intrinsic scleroderma signature from a metanalysis of microarray data from skin biopsies of 36 SSc patients. Real time PCR of all the genes was performed in cGVHD and scl-GVHD skin biopsies. Results were validated by Immunofluorescence followed by confocal laser scanning microscopy on skin biopsies and ELISA on serum. In vitro studies on epithelial cells were performed for functional validation. Correlation of the ELISA results and clinical parameters was performed using SPSS 18 software. Scl-GVHD skin biopsies showed a thickened dermis with increased ECM and reduction of total vessel lumen similar to SSc, whereas cGVHD did not. Moreover the expression of caveolin-1 was markedly decreased in scl-GVHD compared to healthy skin or cGVHD, similarly to SSc. RT-PCR of the 86 genes of the intrinsic SSc signature showed that only 4 genes had a specific and concordant pattern of expression in scl-GVHD and SSc, among these Secreted Frizzled Receptor 4. Double-immunofluorescence followed by confocal laser scanning microscopy of scl-GVHD and SSc skin biopsies showed that the source of increased expression of SFRP4 were dermal fibroblasts, epithelial cells in the germinal layer of the epidermis and Melanocytes. Further characterization of SFRP4 positive cells in the germinal layer indicated that these cells were vimentin positive and caveolin-1 negative. In vitro studies on epithelial cells indicated that TGF-\u3b2 induced epithelial to Mesenchymal transition was indeed associated with decrease by 35% in caveolin-1 expression and increase of SFRP4 expression of 52% at mRNA level and 68% at protein level. Additionally, The serum levels of SFRP4 correlated inversely with Diffusion lung capacity (r=0.234 p=0.001) and positively with mRSS in patients with normal lung function