Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

PURPOSE: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. RESULTS: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. CONCLUSION: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.     

Conservative surgery for Stage I ovarian carcinoma in women of childbearing age

Objective To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas.
Design Retrospective study.
Participants Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere.
Methods Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour.
Results Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery.
Conclusion After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage IC tumours.     

Concentrations of PM10 and PM2.5 particulate material in the atmosphere of Rome

Starting from 1993, various monitoring campaigns were carried out in Rome to determine PM10 and PM2.5. Their results are presented here cumulatively, with the aim of obtaining preliminary information on relationships among these size fractions, in various seasonal periods and in two sites with different characteristics (a road site and an urban background site in a public park). Particles were collected on filter and gravimetrically determined. Both PM10 and PM2.5 concentrations show temporal fluctuations with higher values during winter months. Background concentrations are lower than those contemporaneously measured at the road site only to a limited extent (10-17%). The contribution of PM2.5 to PM10 during the winter semester is higher than during the summer one (67 vs. 52%), with no substantial intersite differences.     

Enhancement of Radiation Response by Paclitaxel in Mice According to Different Treatment Schedules

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo.

Materials and methods: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD₅₀, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD₅₀, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed.

Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols.

Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.     

Estimation of Nanoporous Au Young’s Modulus from Serial Block Face-SEM 3D-Characterisation

Nanoporous Au has been subjected to serial block face-scanning electron microscopy (SBF-SEM) 3D-characterisation. Corresponding sections have been digitalized and used to evaluate the associated mechanical properties. Our investigation demonstrates that the sample is homogeneous and isotropic. The effective Young’s modulus estimated by an analytical multiscale approach agrees remarkably well with the values stated in the literature.     

Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study

Sentinox (STX) is an acid-oxidizing solution containing hypochlorous acid in spray whose virucidal activity against SARS-CoV-2 has been demonstrated. In this paper, results of a randomized controlled trial (RCT) on the efficacy of STX in reducing viral load in mild COVID-19 patients ({"type":"clinical-trial","attrs":{"text":"NCT04909996","term_id":"NCT04909996"}}NCT04909996) and a complementary in vitro study on its activity against different respiratory viruses are reported. In the RCT, 57 patients were randomized (1:1:1) to receive STX three (STX-3) or five (STX-5) times/day plus standard therapy or standard therapy only (controls). Compared with controls, the log₁₀ load reduction in groups STX-3 and STX-5 was 1.02 (p = 0.14) and 0.18 (p = 0.80), respectively. These results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20–30, STX-3 showed a significant (p = 0.016) 2.01 log₁₀ reduction. The proportion of subjects that turned negative by the end of treatment (day 5) was significantly higher in the STX-3 group than in controls, suggesting a shorter virus clearance time. STX was safe and well-tolerated. In the in vitro study, ≥99.9% reduction in titers against common respiratory viruses was observed. STX is a safe device with large virucidal spectrum and may reduce viral loads in mild COVID-19 patients.     

Impaired saccadic eye movement in diabetic patients: the relationship with visual pathways function

The aim of this study was to evaluate whether a correlation existed between saccadic eye movements and visual pathways function in diabetic patients. Saccadic or fast Eye Movement System (EMS) and Visual Evoked Potentials (VEPs) were assessed in 20 insulin-dependent diabetic mellitus (IDDM) patients without long-term complications and in stable metabolic control and in 21 age-matched control subjects. In IDDM patients we observed significantly (p<0.01) longer EMS latency, while EMS velocity and accuracy were similar to those of controls; VEPs showed a significant delay in N75, P100, N145 latencies and significant reduction of N75-P100 and P100-N145 amplitudes. In IDDM patients no relationships between EMS and VEP parameters were found. In conclusion, EMS latency delay suggests an impairment of the saccadic eye movement system, while impaired VEPs may be ascribed to a dysfunction of the visual pathways. The lack of correlation between VEPs impairment and EMS latency delay suggests that in our IDDM patients the delay of saccadic latency cannot be exclusively related to a visual pathways dysfuction and could be ascribed to a diffuse neuronal involvement. This revised version was published online in July 2006 with corrections to the Cover Date.     

Characterization of Carbon Nanostructures by Photoelectron Spectroscopies

Recently, the scientific community experienced two revolutionary events. The first was the synthesis of single-layer graphene, which boosted research in many different areas. The second was the advent of quantum technologies with the promise to become pervasive in several aspects of everyday life. In this respect, diamonds and nanodiamonds are among the most promising materials to develop quantum devices. Graphene and nanodiamonds can be coupled with other carbon nanostructures to enhance specific properties or be properly functionalized to tune their quantum response. This contribution briefly explores photoelectron spectroscopies and, in particular, X-ray photoelectron spectroscopy (XPS) and then turns to the present applications of this technique for characterizing carbon nanomaterials. XPS is a qualitative and quantitative chemical analysis technique. It is surface-sensitive due to its limited sampling depth, which confines the analysis only to the outer few top-layers of the material surface. This enables researchers to understand the surface composition of the sample and how the chemistry influences its interaction with the environment. Although the chemical analysis remains the main information provided by XPS, modern instruments couple this information with spatial resolution and mapping or with the possibility to analyze the material in operando conditions at nearly atmospheric pressures. Examples of the application of photoelectron spectroscopies to the characterization of carbon nanostructures will be reviewed to present the potentialities of these techniques.     

Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients: a study of resting-state functional networks

IntroductionSeveral functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks.MethodsBefore and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features.ResultsBefore visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura.ConclusionsIn individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.     

Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer

While PI3K/AKT/mTOR pathway is altered in a variety of cancers including non small cell lung cancer, abnormalities in this pathway are more common in squamous cell lung carcinoma than in adenocarcinoma of the lung. Moreover, aberrant activation of PI3K/AKT/mTOR pathway is one of the mechanisms of acquired resistance to EGFR-TK inhibitors in patients with adenocarcinoma carrying EGFR activating mutations.