Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD)

Prevalence and time course of post-stroke pain: A multicenter prospective hospital-based study

OBJECTIVE: Pain prevalence data for patients at various stages after stroke. DESIGN: Repeated cross-sectional, observational epidemiological study. SETTING: Hospital-based multicenter study. SUBJECTS: Four hundred forty-three prospectively enrolled stroke survivors. METHODS: All patients underwent bedside clinical examination. The different types of post-stroke pain (central post-stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with χ(2)-tests. RESULTS: The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P < 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post-stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. CONCLUSIONS: Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated

Design and construction of Micromegas detectors for the ATLAS Muon Spectrometer Upgrade

Thanks to significant technological improvements, developed during a intensive R&D activity carried out in the last years, large-area Micromegas (MM) will be employed, for the first time, in the High Energy Physics field. Starting from 2019, they will cover a large surface of about 150m2 in the forward regions of the Muon Spectrometer. In this paper, the performances of MM chambers and, in particular, the spatial resolution and the efficiency, obtained using data from different test beam campaigns, will be described. Moreover, it will be shown the present status of the Micromegas chambers construction from the Italian INFN groups, focusing, especially, on the construction procedures and the methodologies developed to obtain the challenging required mechanical precision

Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

Quantitation of regional ejection fractions using gated tomographic imaging with Tc-99m-sestamibi

BACKGROUND: A new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT). AIM: To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT. METHODS: From May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks. OUTCOMES: The International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11-16), or mild (IIEF-15 score = 17-25). RESULTS: All patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = -0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5-4.5) and the median PGI-I score was 3.0 (IQR = 2.0-4.0). The median action time was 20.0 minutes (IQR = 15.0-30.0) and the median mouth time was 60.0 seconds (IQR = 30.0-120.0). CLINICAL IMPLICATIONS: The ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction. STRENGTHS AND LIMITATIONS: This is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the "additional" side effects of the ODF formulation compared with FCT are reported. CONCLUSION: The new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy. Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film. J Sex Med 2017;X:XXX-XXX

Rate capability and gamma rejection studies of thin-gap RPC detectors with thin phenolic glass electrodes

&lt;p&gt;Presented by Alessandro Rocchi at the &lt;strong&gt;&lt;em&gt;16th Topical Seminar on Innovative Particle and Radiation Detectors&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;&lt;span&gt;&lt;strong&gt;&lt;em&gt;(IPRD23) - &lt;/em&gt;&lt;/strong&gt;&lt;em&gt;Siena (Italy), 25-29 September 2023&lt;/em&gt;&lt;/span&gt;&lt;/p&gt

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy)

Objective: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. Methods: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. Results: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. Conclusions: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions

Authorization schemes for internet of things:Requirements, weaknesses, future challenges and trends

Scalable and secure authorization of smart things is of the crucial essence for the successful deployment of the Internet of Things (IoT). Unauthorized access to smart things could exacerbate the security and privacy concern, which could, in turn, lead to the reduced adoption of the IoT, and ultimately to the emergence of severe threats. Even though there are a variety of IoT solutions for secure authorization, authorization schemes in highly dynamic distributed environments remain a daunting challenge. Access rights can dynamically change due to the heterogeneous nature of shared IoT devices and, thus, the identity and access control management are challenging. This survey provides a comprehensive comparative analysis of the current state-of-the-art IoT authorization schemes to highlight their strengths and weaknesses. Then, it defines the most important requirements and highlights the authorization threats and weaknesses impacting authorization in the IoT. Finally, the survey presents the ongoing open authorization challenges and provides recommendations for future research