Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC). Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0. Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules. Conclusions. This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients

Asynchronous earthquake strong motion and RC bridges response

The dynamic response of long structures (e.g., bridges) is sensitive to the spatial variability of strong ground motion (asynchronous motion). Ground motion differences increase from point to point with increasing foundation distance. This latter is due to two physical phenomena: soil-wave interaction, that causes the loss of coherence and local amplification; wave traveling with finite velocity, that causes signals time lag. This ground motion variability produces a different structural demand compared to the synchronous one, which is the only one considered by designers in the majority of cases. A few codes consider this type of actions, therefore further research efforts are necessary. In this study, asynchronous ground motions are generated by means of a new generation procedure implemented in the software GAS 2.0 using as input the simultaneous strong motion records from the April 6th, 2009, L'Aquila (Italy) at the seismic stations AQA and AQV, located in the Aterno River valley. These records are used to calibrate the generation model and to produce sets of asynchronous earthquake sampling. The asynchronous earthquake sets are applied on a typical highway reinforced concrete bridge to study its dynamic response considering two different configurations: non-isolated with traditional supports and isolated bridge with lead rubber bearings. The bridge is placed in two positions along the wave propagation direction: a position near one recording station and a position between the two stations to consider local soil effects. The response parameters investigated are the maximum relative displacements of soil and deck. The results show that there is an important variation of relative displacement along the direction of wave propagation due to asynchronous motion with effects that designer should consider for the structural details design of isolated and non-isolated bridges. Keywords: Asynchronous motion, Bridges, Seismic response, Earthquake spatial variabilit

Intravenous immunoglobulin therapy in the treatment of the acute phase of chronic idiopathic thrombocytopenic purpura in adults

A prospective, open-label phase III study was carried out to evaluate the efficacy and tolerability of a preparation of virus-inactivated normal human intravenous immunoglobulin. Fifteen adult patients suffering from chronic idiopathic thrombocytopenic purpura (ITP), (basal platelet count <20x109/l), received 0.4 g/kg daily for 5 days. The increase in platelet count, reduction in hemorrhagic events, duration of platelet response, and incidence of adverse events were recorded. Fourteen out of 15 patients achieved a platelet count ?50x109/l (response rate was 93.3%), and only 2 out of 10 patients with positive baseline Rumple-Leed test remained positive after treatment (p =0.0022). Interestingly, a close inverse correlation between platelet counts and haemoglobin levels was observed. No side effects were recorded. This study provides evidence of therapeutic efficacy and the good tolerability of the immunoglobulin preparation we used in this trial, and suggests the role of haemolysis as a mechanism for the increase in platelet count

Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa

<p>Abstract</p> <p>Background</p> <p>The <it>Anopheles gambiae </it>gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector <it>A. gambiae</it>. However, malaria transmission in tropical Africa is sustained by three main vectors (<it>A. gambiae</it>, <it>Anopheles arabiensis </it>and <it>Anopheles funestus</it>) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the <it>A. gambiae </it>species complex whereas the <it>A. funestus </it>homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6.</p> <p>Methods</p> <p>The <it>A. funestus </it>SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large <it>A. gambiae </it>prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed.</p> <p>Results</p> <p>According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level.</p> <p>Conclusions</p> <p>Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The <it>Anopheles stephensi </it>SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the <it>A. gambiae </it>protein may also be useful to assess human exposure to several Asian malaria vectors.</p

Time-dependent cyclic behavior of reinforced concretebridge columns under chlorides-induced corrosion andrebars buckling

This study presents the results of a refined numerical investigation meant at understanding the time-dependent cyclic behavior of reinforced concrete (RC) bridge columns under chlorides-induced corrosion. The chloride ingress in the cross-section of the bridge column is simulated, taking into account the effects of temperature, humidity, aging, and corrosion-induced cover cracking. Once the partial differential equations governing such multiphysics problem are solved through the finite-element method, the loss of reinforcement steel bars cross-section is calculated based on the estimated corrosion current density. The nonlinear cyclic response of the RC bridge column under corrosion is, thus, determined by discretizing its cross-sections into several unidirectional fibers. In particular, the nonlinear modeling of the corroded longitudinal rebars exploits a novel proposal for the estimation of the ultimate strain in tension and also accounts for buckling under compression. A parametric numerical study is finally conducted for a real case study to unfold the role of corrosion pattern and buckling mode of the longitudinal rebars on the time variation of capacity and ductility of RC bridge columns

One hour-post-load plasma glucose ≥155 mg/dl in healthy glucose normotolerant subjects is associated with subcortical brain MRI alterations and impaired cognition. A pilot study

Background: Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions. Methods: We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value &gt; or &lt; 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests. Results: NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10−4 mm2s−1). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)—immediate-recall and Free and Cued Selective Reminding Test (FCSRT)—delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively). Conclusions: One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests

Remote Working and Home Learning: How the Italian Academic Population Dealt with Changes Due to the COVID-19 Pandemic Lockdown

The COVID-19 pandemic introduced changes in people's lives that affected their mental health. Our study aimed to explore the level of psychological distress in the academic population during the lockdown period and investigate its association with the new working or studying conditions. The study sample included 9364 students and 2159 employees from five Italian universities from the study IO CONTO 2020. We applied linear regression models to investigate the association between home learning or remote working conditions and psychological distress, separately for students and employees. Psychological distress was assessed using the Hospital Anxiety and Depression Scale (HADS). In both students and employees, higher levels of distress were significantly associated with study/work-family conflicts, concerns about their future careers, and inadequacy of equipment; in employees, higher levels of distress were significantly associated with a lack of clarity on work objectives. Our results are in line with previous research on the impact of spaces and equipment in remote working/studying from home. Moreover, the study contributes to deepening the association between well-being and telework-family conflict, which in the literature is still equivocal. Practical implications require academic governance to promote sustainable environments both in remote and hybrid work conditions, by referring to a specific management by objectives approach

Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation

Abstract Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy