Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a ...precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient’s needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously.
In Britain at the turn of the century large scale social and economic changes, including the increasing size and influence of the service sector of the economy, the growing use of bureaucratic ...procedures in administrative organizations, the changing nature of success for individuals in a maturing industrial economy and the creation of an entirely new field of women's work, are all discernible in the changing nature of work in offices. Taking for its location Glasgow, the "second city of the British Empire," this work explores the physical and technological changes which occurred in the growing bureaucracies of business, finance and government as well as in the small and mid-size businesses of the city. The study of these changes provides a context within which to set the complementary experiences of the men and women who chose to seek a living in the wide array of constantly changing office jobs. This study reveals a diversity of experience in office occupations and careers which invites consideration of the consequent difficulties in regarding this occupational group as a single societal stratum. In addition the variety of individual responses to technological and organizational change illustrates the control which individuals exercised in their own lives. In the preparation of officeworkers, in the filling of office jobs, in the advancement or stagnation of men and women in office careers, and in the increasing presence of women on office staffs, the actions and decisions of both employees and employers guided the evolving relationships among individuals, work, and society.
ABSTRACTL’Aquila downtown (Central Italy) is situated in a highly seismic region, making it susceptible to numerous historical and recent earthquakes. Among these, the earthquake of Mw 6.3 on 6 April ...2009, and the one of Mw 6.7 on 2 February 1703, caused severe damage or complete destruction of the majority of buildings in the historical center. An integrated statistical analysis of A-DInSAR and seismic related building damage data is illustrated. By comparing the seismic damage maps from the 2009 and 1703 earthquakes with the A-DInSAR map produced with Cosmo-SkyMed descending orbit images (acquired between 2010 and 2021), a correlation between post-seismic deformations (in terms of average velocity) and building damage intensity has been identified. Furthermore, ground and building velocities have been separately examined, in order to evaluate the impact of building features and reconstruction efforts on ground deformations. The geostatistical analysis revealed a widespread subsidence motion (until −2 mm/year) across the whole study area. Notably, neighboring points did not exhibit consistent deformation velocities, indicating a lack of spatial correlation. Additionally, Cluster Analysis has allowed recognition of recurring subsidence/uplift trends, which, in terms of shape of curve displacement vs. time, appears independent on building damage intensity or reconstruction interventions. Our results pave the way for a novel utilization of long-term series of satellite SAR data in high-risk seismic zones, serving as a valuable tool to map the most susceptible areas and mitigate seismic risk.
Liquid biopsy has advantages over tissue biopsy, but also some technical limitations that hinder its wide use in clinical applications. In this study, we aimed to evaluate the usefulness of liquid ...biopsy for the clinical management of patients with advanced-stage oncogene-addicted non-small-cell lung adenocarcinomas. The investigation was conducted on a series of cases—641 plasma samples from 57 patients—collected in a prospective consecutive manner, which allowed us to assess the benefits and limitations of the approach in a real-world clinical context. Thirteen samples were collected at diagnosis, and the additional samples during the periodic follow-up visits. At diagnosis, we detected mutations in ctDNA in 10 of the 13 cases (77%). During follow-up, 36 patients progressed. In this subset of patients, molecular analyses of plasma DNA/RNA at progression revealed the appearance of mutations in 29 patients (80.6%). Mutations in ctDNA/RNA were typically detected an average of 80 days earlier than disease progression assessed by RECIST or clinical evaluations. Among the cases positive for mutations, we observed 13 de novo mutations, responsible for the development of resistance to therapy. This study allowed us to highlight the advantages and disadvantages of liquid biopsy, which led to suggesting algorithms for the use of liquid biopsy analyses at diagnosis and during monitoring of therapy response.
Historical and recent earthquakes have struck the city of L'Aquila, located in the axial zone of the Central Apennines, Italy, causing severe damage to the historic centre. Recent studies have shown ...that higher intensity of damage to buildings in L’Aquila downtown, both in the case of the 2009 earthquake (Mw: 6.29) and the 1703 earthquake (Mw: 6.7), is associated with higher post-seismic subsidence rates, detected through A-DInSAR maps, in the time range 2010–2021. This finding suggests the existence of geological factors that drive deformation (and building damage). The availability of long time series of InSAR data acquired from the Cosmo-SkyMed and Sentinel-1 missions, has enabled us to analyze the relationships between ground deformations and geological, hydrogeological, and geomorphological factors that may affect them. The correlation analysis between predisposing factors and SAR deformation has highlighted an increase in subsidence strongly conditioned by the outcropping lithology, showing how compositional variations within lithology can significantly influence ground deformations. Furthermore, hydrogeology has been recognized as playing an important role in determining deformation processes: the water table depth locally influences long-term subsidence, while seasonal fluctuations in the water table may be responsible for secondary areal variations in ground deformations.
Nanotechnology is rapidly growing with nanoparticles produced and utilized in a wide range of commercial products worldwide. Among the different types of nanomaterials produced, silver nanoparticles ...(AgNPs) occupy a predominant position and they are used in electronics, clothing, food industry, cosmetics and medical devices. Nanosilver has also showed excellent performance in antibacterial application. Nowadays, the increasing use of AgNPs has put the evidence on their possible toxicity to the human health and the impact on the environment. This paper focus on adverse effects of AgNPs in adult of
. Fishes exposed to increasing concentrations (8, 45, and 70 μg/l) silver nanoparticles (AgNPs, 25 nm in average diameter) and after treatment for 30 days, was quickly euthanized in MS-222. We have evaluated bioaccumulation of AgNPs using ICP-MS and analyzed histological changes, biomarkers of oxidative damage and gene expression in the gut, liver and gills tissues of AgNPs-treated zebrafish. The histological analysis showed lesions of secondary lamellae of the gills with different degrees of toxicity such as hyperplasia, lamellar fusion, subepithelial edema, and even in some cases telangiectasia. Huge necrosis of the intestinal villi was found in the gut. No lesion was detected in the liver. The analysis revealed a high expression of metallothioneins 1 (MTs 1) in animals exposed to AgNPs compared to the control group. The ICP-MS analysis shows that the amount of particles absorbed in all treated samples is almost the same. We can affirm that AgNPs toxicity linked more to their size and state of aggregation than to their concentrations. Silver nanoparticles can damage gills and gut because they are able to pass through the mucosal barrier thanks to their small size. The damage is still reversible because it is not documented injury to the basal membrane.
Uterine sarcomas are very rare tumours with different histotypes, molecular features and clinical outcomes; therefore, it is difficult to carry out prospective clinical trials, and this often results ...in heterogeneous management of patients in the clinical practice.
We planned to set up an Italian consensus conference on these diseases in order to provide recommendations on treatments and quality of care in our country.
Early-stage uterine sarcomas are managed by hysterectomy + bilateral salpingo-oophorectomy according to menopausal status and histology; lymphadenectomy is not indicated in patients without bulky nodes, and morcellation must be avoided. The postoperative management is represented by observation, even though chemotherapy can be considered in some high-risk patients. In early-stage low-grade endometrial stromal sarcoma and adenosarcomas without sarcomatous overgrowth, hormonal adjuvant treatment can be offered based on hormone receptor expression. In selected cases, external beam radiotherapy ± brachytherapy can be considered to increase local control only.
Patients with advanced disease involving the abdomen can be offered primary chemotherapy (or hormonal therapy in the case of low-grade endometrial stromal sarcoma and adenosarcoma without sarcomatous overgrowth), even if potentially resectable in the absence of residual disease in order to test the chemosensitivity (or hormonosensitivity); debulking surgery can be considered in patients with clinical and radiological response. Chemotherapy is based on anthracyclines ± ifosfamide or dacarbazine. Palliative radiotherapy can be offered for symptom control, and stereotactic radiotherapy can be used for up to five isolated metastatic lesions.
Treatment of uterine sarcoma should be centralised at referral centres and managed in a multidisciplinary setting.
•The consensus conference analysed many issues relative to uterine sarcoma management.•The member panel provided recommendations based on the level of available evidence.•Uterine sarcoma should be managed in referral centres by multidisciplinary boards.
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