Personal exposure to airborne ultrafine particles in the urban area of Milan

The relevance of health effects related to ultrafine particles (UFPs; aerodynamic diameter < 100 nm) can be better evaluated using high-resolution strategies for measuring particle number concentrations. In this study, two different portable Condensation Particle Counters (CPCs) were used to measure personal exposure to UFPs in the central area of Milan for one week period during spring, with three sampling sessions per day. Experimental data were continuously collected along an established urban pathway, moving afoot or by different private and public means of transport. Correlation analysis between data measured by two CPCs was performed and general results showed a good agreement, especially at concentrations lower than 2 7105 particles /cm3. UFPs measures were divided on the basis of crossed environments or micro-environments, days of the week and day time (hours). The highest measured mean concentrations and data variability were observed during walking time and moving on motorized vehicles (bus and car), indicating that the highest exposure to UFPs can be reached near motorized traffic. The lowest exposures were observed in green areas and in office microenvironments. An appreciable difference between working and non-working days was observed. Concentration patterns and variation by days of the week and time periods appears related to time trends in traffic intensity

Fine and ultrafine particle levels determined during everyday activities : the PM-CARE project

Exposure to particle number (particles >0.02 \u3bcm in aerodynamic diameter, a.d.) and particle mass levels (PM0.5 , PM1 , PM2.5 and PM10) were determined on 82 non-smoking senior volunteers living in urban and suburban areas of Milan, during the warm and cold seasons of 2005-2006. Measuring devices, comprehending optical counters (6-channel OPC and CPC), a 4-stage cascade impactor, CO and O3 monitors and a NO2 passive sampler, were mounted on trolleys (25kg), especially equipped to provide 24h self-contained air monitoring. Subjects\u2019 activities were individually recorded on timetables, used also for clinical purposes (see Fanetti et al.). When required, outdoor transfers by car or afoot were assisted by project personnel. 24h-average particle number and mass (PM10) concentration means were 19.500 #/cm3 and 41.4 \ub5g/m3 in summer (1913 hours) and 26.600 #/cm3 and 62.0 \ub5g/m3 in winter (1894 hours), with a mean seasonal contribution of PM0.5 to PM10 of 54% and 68%, respectively. Data plots logged by particle counters were apportioned and separately examined according to the most common activities emerging from the timetable. Resulting particle number concentrations are here presented as the mean percent deviation from individual 24h-averaged levels, given as Activity: [a.d. 0.3\u20130.5 \ub5m] and [a.d. >0.02] (total hours monitored; number of subjects). Home at rest: -1% and -20% (1419; 76), Domestic activities: +6% and +7% (307; 75), Flame cooking: +14% and +97% (293; 72), Workplace activities: +18% and -10% (104; 12), Sleep: -7% and -51% (1170; 78), Moving by car: +46% and +141% (103; 81), Promenade: +52% and +27% (66; 32). With the exception of domestic and workplace activities, which could not be better specified, the results reported are indicative of human PM exposure pattern experienced in urban and suburban areas. Substantial increases of overall particle counts are associated with flame cooking and vehicle displacements, whereas PM0.5 levels seem to be mainly associated with outdoor sources

IMMU-01. TEM-GBM: AN OPEN-LABEL, PHASE I/IIA DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND EFFICACY OF GENETICALLY MODIFIED TIE-2 EXPRESSING MONOCYTES TO DELIVER IFN-A WITHIN GLIOBLASTOMA TUMOR MICROENVIRONMENT

Abstract Temferon is a macrophage-based treatment relying on ex-vivo transduction of autologous HSPCs to express immune-payloads within the TME. Temferon targets the immune-modulatory molecule IFN-a, to a subset of tumor infiltrating macrophages known as Tie-2 expressing macrophages (TEMs) due to the Tie2 promoter and a post-transcriptional regulation layer represented by miRNA-126 target sequences. As of 31st May 2021, 15-patients received Temferon (D+0) with follow-up of 3 – 693 days. After conditioning neutrophil and platelet engraftment occurred at D+13 and D+13.5, respectively. Temferon-derived differentiated cells, as determined be the number of vector copy per genome, were found within 14 days post treatment and persisted albeit at lower levels up to 18-months. Very low concentrations of IFN-a in the plasma (8.7 pg/ml-D+30) and in the CSF (1.6 pg/ml-D+30) were detected, suggesting tight regulation of transgene expression. Five-deaths occurred at D+322, +340, +402, +478 and +646 due to PD, and one at D+60 due to complications following the conditioning regimen. Eight-patients had progressive disease (range: D-11 to +239) as expected for this tumor type. SAEs include GGT elevation (possibly related to Temferon) and infections, venous thromboembolism, brain abscess, hemiparesis, seizures, anemia and general physical condition deterioration, compatible with ASCT, concomitant medications and PD. Four-patients underwent 2ndsurgery. Recurrent tumors had gene-marked cells and increased expression of ISGs compared to first surgery, indicative of local IFNa release by TEMs. In one patient, a stable lesion had a higher proportion of T cells and TEMs within the myeloid infiltrate and an increased ISGs than in the progressing lesion, detected in the same patient. Tumor-associated clones expanded in the periphery. TME characterization by scRNA and TCR-sequencing is ongoing. To date, Temferon is well tolerated, with no DLTs identified. The results provide initial evidence of Temferon potential to activate the immune system of GBM patients, as predicted by preclinical studies

Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data

Background: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer’s disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods: Following the initiative of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings

Functional autonomy in dementia of the Alzheimer’s type, mild cognitive impairment, and healthy aging: a meta-analysis

Background: Activities of daily living (ADL) are fundamental skills required to independently care for oneself and are categorized in basic (BADLs) and instrumental (IADLs) activities of daily living. ADL evaluation is of paramount importance in clinical practice to discriminate between healthy individuals (HC) and patients with mild cognitive impairment (MCI) or Alzheimer’s disease (AD). However, it is unclear whether and to what extent BADL and IADL deficits occur in MCI, when compared with AD. Therefore, the present study aimed at comparing performance on both BADLs and IADLs in HC, MCI, and AD. Methods: Three electronic databases were consulted for studies comparing total BADLs/IADLs, and single BADLs/IADLs in AD, MCI, and HC (comparisons: AD versus MCI, AD versus HC, MCI versus HC). Ninety-six studies were included in the meta-analysis with random effect models (Hedges’ g). Meta-regression was performed to evaluate the effect of clinical variables on ESs. Results: AD group had more difficulties in BADLs and IADLs than HC and MCI groups; people with MCI showed more difficulties in both IADLs and BADLs than HC. The meta-regression analysis revealed that the percentage of males in the samples was a significant predictor of the ES in the meta-analysis comparing total BADL scores between MCI and HC; in the comparison between AD and HC, age at evaluation predicted the ES on some single IADLs: preparing food, handling medication, and finances. Conclusions: In MCI, it should be considered not only a decline of IADLs but also subtle decline of BADL abilities