The influence of titanium dioxide nanoparticles (pure anatase and 15% N doped anatase) on the growth of Chlorella vulgaris, Haematococcus pluvialis, and Arthrospira platensis was investigated. ...Results showed that pure anatase can lead to a significant growth inhibition of C. vulgaris and A. platensis (17.0 and 74.1%, resp.), while for H. pluvialis the nanoparticles do not cause a significant inhibition. Since in these stress conditions photosynthetic microorganisms can produce antioxidant compounds in order to prevent cell damages, we evaluated the polyphenols content either inside the cells or released in the medium. Although results did not show a significant difference in C. vulgaris, the phenolic concentrations of two other microorganisms were statistically affected by the presence of titanium dioxide. In particular, 15% N doped anatase resulted in a higher production of extracellular antioxidant compounds, reaching the concentration of 65.2 and 68.0 mg g DB - 1 for H. pluvialis and A. platensis, respectively.
COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and ...potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March–April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients’ management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%;
p
< 0.0001) and diagnostic evaluations (16.4% vs. 42.2%;
p
< 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%;
p
< 0.0001) or urgent (20.4% vs. 38.5%;
p
< 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons’ personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID;
p
< 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon–patient/family communication. From the Italian surgeons’ perspective, COVID-related measures will continue to influence future surgical clinical practice.
Background: Membrane-assisted autologous chondrocyte transplantation is considered the gold standard surgical technique to treat greater than two millimetres diameter cartilage lesions in the knee in ...patients after conservative treatment failure. However, this technique is only available in developed countries of North America, Europe and Japan. According to Brazilian law, it is considered an advanced cell therapy product. There is currently no product of this type enabled for clinical use in Brazil. Following the request of the Brazilian regulatory agency (ANVISA), this phase 1 study was developed. The objective is to access feasibility and safety of a new membrane-assisted autologous chondrocyte product.
Methods: Three participants with a larger than two millimetres articular cartilage lesion in the distal femur or the patella, which did not improve their symptoms with conservative treatment, will be submitted to an arthroscopically assisted cartilage biopsy. After isolation and expansion in a good manufacturing practices facility, chondrocyte seeded collagen membranes will be surgically inserted in the lesion and fixed with fibrin glue. The follow-up period will last 1 year. Primary outcome will be incidence and severity of complications according to NCI-CTCAE version 4.0. Secondary outcomes will be Western-Ontario McMaster Universities Osteoarthritis Index scale, International Knee Documentation Committee subjective scale and magnetic resonance observation of cartilage repair tissue magnetic resonance scale.
Conclusions: This study, together with previous preclinical results and international experience, will allow patients in Latin America to have access to this advanced cell therapy.
Trial Registration: Brazilian registry of clinical trials RBR-6fgy76 (http://www.ensaiosclinicos.gov.br/rg/RBR-6fgy76/). Ethical approval: CAAE: 73911617.2.0000.0071.
We discuss some properties of a model Hamiltonian for a system of three bosons interacting via zero-range forces in three dimensions. In order to avoid the well known instability phenomenon, we ...consider the so-called Minlos-Faddeev regularization of such Hamiltonian, heuristically corresponding to the introduction of a three-body repulsion. We review the main concerning results recently obtained. In particular, starting from a suitable quadratic form \(Q\), the self-adjoint and bounded from below Hamiltonian \(\mathcal H\) can be constructed provided that the strength \(\gamma\) of the three-body force is larger than a threshold parameter \(\gamma_c\). Moreover, we give an alternative and much simpler proof of the above result whenever \(\gamma > \gamma'_c\), with \(\gamma'_c\) strictly larger than \(\gamma_c\). Finally, we show that the threshold value \(\gamma_c\) is optimal, in the sense that the quadratic form \(Q\) is unbounded from below if \(\gamma<\gamma_c\).
The current study was conducted to evaluate severe mucocutaneous toxicity during treatment with hydroxyurea (HU) in a large cohort of patients with Philadelphia chromosome-negative myeloproliferative ...neoplasms (MPN).
Among 993 consecutive patients newly diagnosed with MPN at 4 centers in Rome between January 1980 and December 2009, 614 patients (277 men and 337 women with a median age of 64.4 years interquartile range (IR), 54.4 years-72.7 years) received HU. HU was administered as first-line treatment in 523 patients (85.2%) and as ≥ second-line treatment in 91 patients (14.8%).
Mucocutaneous toxicity was reported in 51 patients (8.3%) after a median period from the initiation of HU treatment of 32.1 months (IR, 10.5 months-74.6 months) and a mean HU dose of 1085 mg (± 390 mg); 30 patients (58.8%) developed a painful ulcerative skin toxicity, mainly located in the perimalleolar area; 11 patients (21.6%) had oral aphthous ulcers; and 10 patients (19.6%) developed a nonulcerative skin toxicity with erythema and skin infiltration. After the mucocutaneous toxicity occurred, HU treatment was continued at the same dose in 5 patients (9.8%), reduced in 12 patients (23.5%), and temporarily discontinued in 7 patients (13.7%); the remaining 27 patients (52.9%) required a permanent drug discontinuation. After a median period of 4.3 months (IR, 2.4 months-9.0 months) from the onset of the skin toxicity, 39 patients (76.5%) had a complete resolution and 12 patients (23.5%) had improvement without complete resolution.
Mucocutaneous toxicity during HU treatment is more common than expected and may present with different clinical features. Moreover, it often requires a permanent drug discontinuation and only a partial resolution is reported to occur in approximately 25% of patients.
In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian ...administrative regions of taxa in the genera
Abies
,
Actinidia
,
Aloe
,
Amaryllis
,
Anredera
,
Arctotheca
,
Bidens
,
Cardiospermum
,
Celosia
,
Commelina
,
Cotoneaster
,
Cyclamen
,
Eclipta
,
Euphorbia
,
Grevillea
,
Hedera
,
Hibiscus
,
Impatiens
,
Juglans
,
Kalanchoe
,
Koelreuteria
,
Lindernia
,
Melinis
,
Myriophyllum
,
Nandina
,
Nicotiana
,
Oenothera
,
Oxalis
,
Parthenocissus
,
Phoenix
,
Phyllanthus
,
Physalis
,
Plumbago
,
Pteris
,
Quercus
,
Setaria
,
Symphytum
,
Tagetes
, and
Washingtonia
. Nomenclatural and distribution updates, published elsewhere are provided as Suppl. material 1.
Background: Knee osteoarthritis is a progressive degenerative joint disease and remains a leading cause of pain, physical impairment and decline in health-related quality of life in adults. Despite ...its incidence being amongst the highest in chronic diseases, effective biomarkers are not available to assist in its management. The main goal of this study is to identify mediators that serve as biomarkers and investigate if the levels of these biomarkers will be correlated to the efficacy of a rehabilitation program.
Methods: This is a prospective cohort study with 65 participants. Patients with mild-to-moderate symptomatic knee osteoarthritis will be recruited. The Rehabilitation Program will consist of three session/week during eight weeks. Assessment about functional evaluation will be performed before and after treatment, using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and EuroQOL-5D (Euro quality of life - five dimension) scales, Visual Analog Scale (VAS), and physical function tests (time up and go, isometric strength testing and kinematic gait analysis). Serum levels of classical pro-inflammatory cytokines, hyaluronan and high mobility group box 1 protein (HMGB-1) will be evaluated. The primary outcome is the change in WOMAC scale from baseline to end. Statistical analyses will be used to determine correlation of physical improvement and serum biomarkers. Adverse events will be monitored throughout the study.
Conclusions: This trial expect to study the correlation between the anti-inflammatory effects of rehabilitation program derived factors that may be involved in suppressing cytokine induction via suppressing HMGB-1.
Trial registration: Clinicaltrials.gov - NCT02964624.
Abstract
Diffuse intrinsic pontine glioma (DIPG) and pediatric glioblastoma (pGBM) are heterogeneous brain tumors characterized by different anatomical and molecular subgroups and the presence of ...genetically and phenotypically distinct subclonal cell populations. It is recognized that exosomes mediate cross-talk among tumor cells. We hypothesize that there are different exosome-mediated paracrine signaling promoting tumour progression in DIPG and pGBM. Our aim was to determine the specific DIPG and pGBM-derived exosome oncogenic signatures. We used a panel of fifteen patient primary-derived cell lines, which included nine DIPG (seven H3.3 K27M, one H3.3 K27M/ACVR1 and one H3.1 K27M/ACVR1), one diffuse midline glioma H3.3 K27M and three GBM (one H3.3 G34R and two histone WT). Conditioned medium was collected from cells maintained under stem-cell culture condition, adherent on laminin and/or as neurospheres (NS), and exosomes harvested through serial centrifugations. Electron microscopy demonstrated that the isolated microvescicles are exosomes sized between 50–80 nm. DIPG derived-exosomes appeared to have a variable cargo of total protein (µg)/106 cells, which was higher than for pGBM-exosomes. Proteomic analysis revealed that proteins associated with vesicle docking, exocytosis and synaptic transmission were exclusively enriched in pontine-derived exosomes, while cell-cell and cell-matrix interaction proteinswere exclusive tohemispheric ones. Proteins in common to the two locations were involved in metabolism and energy pathways. Interestingly, principle component analysis on the different molecular subgroups suggests that ACVR1 may be not implicated in the exosomal proteomic signature. Exosomal miRNA profile appeared to be driven by the two main histone mutated subgroups H3.3 K27M and H3.1 K27M with the latter overexpressing hypoxia and angiogenic-associated miRNAs, leading to distinct oncogenic programs with different specific potential therapeutic targets. This study aimed to development new diagnostic/prognostic tools for DIPG and pGBM patients. Further investigations are aimed to identify new therapeutic strategies to inhibit the cross-talk among glioma subpopulations.
Introduction
The “original” traction-free Kocher’s method to perform the reduction of shoulder dislocation has been recently reviewed and some authors speculated that it can be self performed by ...patients under the guide of the physician. In this way, as an “assisted self-reduction” technique, it is also effective and simple to perform. The aim is to study the effectiveness of the assisted self-reduction technique, in comparison to the well known and largely used traction–countertraction method.
Materials and methods
From a consecutive series of 237 uncomplicated anterior shoulder dislocations, a total of 61 were managed by the residents of our institution under the supervision of the senior authors using the assisted self-reduction method and 176 were managed by other orthopaedic consultants on duty in the Emergency Department using the traction–countertraction technique. Only the senior authors used the assisted self-reduction technique, whereas the other orthopaedic consultants used the traction–countertraction method. The need for intravenous sedation or general anaesthesia to perform the assisted self-reduction was considered a failure. Recorded variables were demographic data, previous dislocation, traumatic mechanism and medication use during shoulder reduction, time to perform the reduction.
Results
Ninety-eight percent of the acute dislocation treated with the assisted self-reduction technique and 81 % treated with the traction–countertraction method were reducible without recourse to intravenous sedation.
Conclusions
The assisted self-reduction technique is simple, effective and gentle. Physicians on duty in the Emergency Departments should therefore be encouraged to use it.
There is widespread concern about a possible higher prevalence of extramedullary relapse (EMR) in patients with multiple myeloma (MM) in the era of novel biological agents.
Aims of this study were: ...i) to assess the prevalence of treatment-emergent EMR in a cohort of patients extensively exposed to biological drugs; ii) to investigate the association between previous exposure to biological drugs and subsequent EMR.
Following approval by our institutional Ethics Committee, we reviewed clinical and hematologic data of 456 MM patients (pts) who were consecutively observed in our Department between 2000-2010. This time frame allowed us to study the effect of the introduction of the novel biological agents (bortezomib, thalidomide, lenalidomide) in addition to standard chemotherapy and high-dose therapy (HDT) on EMR occurrence. Extramedullary disease was categorized as follows: a) soft tissues masses adjacent to bone; b) localizations in extra-osseous organs. Survival and extramedullary disease prevalence were compared with an historical cohort of 182 patients observed in our Department between 1994-1999, when only HDT was available Ann Oncol 2010, 21(2):325-30. Table 1 summarizes the main characteristics of the new cohort at diagnosis. After a median follow-up of 39 months (range 0-150 months), 63 (13%) patients remained asymptomatic. In symptomatic patients (n=393, 87%), first line therapy included HDT in 199 (51%) cases, and novel agents in 137 (35%). In relapsing patients (n=271), the median number of subsequent treatments was 2 (1-8); 40 (14%) patients were treated with chemotherapy alone, the remaining 231 (86%) received various treatments including at least one biological agent
The prevalence of extramedullary disease at clinical onset was 14% in the recent cohort vs 6% in the historical cohort (p=0.004). The prevalence of EMR in patients of the new cohort without extramedullary disease at diagnosis was 24% (92 patients). Sites involved included soft tissue adjacent to bone in 47%, and extraosseous organs in 53% of cases. When compared to the historical cohort, MM patients had a better outcome (median OS 6.4 vs 3.9 years, P<0.001), but higher cumulative incidence of EMR (23.9% vs 5.6% at 5 years; HR 3.1, 95%CI: 1.8-5.4, P<0.001). Median time to first EMR was not statistically different (26 months vs 32 months in the historical cohort, P=0.322). Cox regression for repeated events was performed to investigate the association between previous exposure to novel agents and subsequent EMR occurrence. Patients previously exposed at least twice to the novel biological agents had a higher risk of EMR (HR 2.9, 95% CI 2.0-4.1, p<0.001). In multivariate analysis, no effect of previous HDT was detected (HR=1.13, p=0.541), while the exposure to novel biological agents retained the same effect.
In conclusion, this analysis shows an increased occurrence of EMR in the last decade, which appears to be independent from the better survival. Sequential exposure to novel biological agents emerges as a risk factor for EMR occurrence.Table 1Characteristics at diagnosis of the 456 patients treated from 2000 to 2010CRAB Symptoms:63 (13%)· Absent393 (87%)· PresentMedian Age61 (28-86) yearsMyeloma Type:268 (59%)· IgG100 (22%)· IgA79 (17%)· Light chain5 (1%)· Non-secretory4 (1%)· Other (IgD/IgM)D&S42 (9%)• I132 (30%)• II• III267 (61%)ISS(n=347)· I93 (27%)· II6 (2%)· III248 (71%)Extramedullary disease at diagnosis391 (86%)• No65 (14%)• Yes· Adjacent to bone51 (78%)14 (22%)· Extraosseous organs
No relevant conflicts of interest to declare.
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