Disease burden and quality of life of in children with sickle cell disease in Italy: time to be considered a priority

The objective of the present article is to highlight the need for attention to Quality of Life of patients with Sickle Cell Disease living in Italy. The transformation of sickle cell disease from a severe life-threatening disease of childhood into a chronic, lifelong condition due to the significant improvements in care and treatment options, imposes increasing new challenges to health care providers and patients. Patients now face physical, psychosocial and emotional challenges throughout their lives. They generally have to receive chronic treatments and regular multidisciplinary monitoring which increase social and emotional burden rendering adherence to treatment sometimes complicated. A chronic disease impacts all aspects of patients’ lives, not only the physical one, but also the social and emotional aspects as well as the educational and working life. The entire “Quality of Life” is affected and recent evidence demonstrates the importance quality of life has for patients with chronic illness. The results of this review focus on emerging data regarding quality of life across the lifespan of patients with Sickle Cell Disease, and highlight the need for more action in this field in Italy, where recent immigration and improved care determine an increasing population of children with sickle cell disease being taken into long term care

Atmospheric Stability & Turbulence from Temperature Profiles over Sicily During Summer 2002 & 2003 HASI Balloon Campaigns

Experimental results and interpretation of the temperature measurements data retrieved during the balloon campaigns (in 2002 and in 2003) for testing HASI (Huygens Atmospheric Structure Instrument), launched from the Italian Space Agency Base in Trapani (Sicily), are presented. Both ascending and descending phases are analysed; data reveal interesting features near the tropopause (present in the region between 11km-14km), where temperature cooling can be related to layers with strong winds (2002 flight); in the troposphere a multistratified structure of the temperature field is observed and discussed (particularly in the 2003 flight) Finally, stability and turbulence of the atmosphere are analysed; the buoyancy N2 parameters for both the flights show lowers value respect to standard tropospheric values corresponding to a lower stability of the atmosphere; still there is a higher stability above the tropopause. The energy spectrum of temperature data is consistent with the Kolmogorov theory: the characteristic k(sup -5/3) behaviour is reproduced

Exomars entry and descent science

The entry, descent and landing of ExoMars offer a rare (once-per-mission) opportunity to perform in situ investigation of the martian environment over a wide altitude range. We present an initial assessment of the atmospheric science that can be performed using sensors of the Entry, Descent and Landing System (EDLS), over and above the expected engineering information. This is intended to help fulfill the concept of an Atmospheric Parameters Package (APP), as mentioned in the ExoMars draft Science Management Plan [ESA, 2005]. Mars' atmosphere is highly variable in time and space, due to phenomena including inertio-gravity waves, thermal tide effects, dust, solar wind conditions, and diurnal, seasonal and topographic effects. Atmospheric profile measurements, drawing on heritage from the Huygens Atmospheric Structure Instrument (HASI), which encountered Titan's atmosphere in 2005 [1], should allow us to address questions of the martian atmosphere's structure, dynamics and variability

ExoMars entry, descent and landing science

The entry, descent and landing of ExoMars offer a rare (once-per-mission) opportunity to perform in situ investigation of the martian environment over a wide altitude range. Entry, Descent and Landing System (EDLS) measurements can provide essential data for atmospheric scientific investigations. We intend to perform atmospheric science measurements by exploiting data from EDLS engineering sensors and exploiting their readings beyond the expected engineering information

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

The location of regions that regulate transcription of the murine Emilin1 gene was investigated in a DNA fragment of 16.8 kb, including the entire gene and about 8.7 and 0.6 kb of 5'- and 3'-flanking sequences, respectively. The 8.7-kb segment contains the 5'-end of the putative 2310015E02Rik gene and the sequence that separates it from Emilin1, whereas the 0.6-kb fragment covers the region between Emilin1 and Ketohexokinase genes. Sequence comparison between species identified several conserved regions in the 5'-flanking sequence. Most of them contained chromatin DNase I-hypersensitive sites, which were located at about -950 (HS1), -3100 (HS2), -4750 (HS3), and -5150 (HS4) in cells expressing Emilin1 mRNA. Emilin1 transcription initiates at multiple sites, the major of which correspond to two Initiator sequences. Promoter assays suggest that core promoter activity was mainly dependent on Initiator1 and on Sp1-binding sites close to the Initiators. Moreover, one important regulatory region was contained between -1 and -169 bp and a second one between -630 bp and -1.1 kb. The latter harbors a putative binding site for transcription factor AP1 matching the location of HS1. The function of different regions was studied by expressing lacZ constructs in transgenic mice. The results show that the 16.8-kb segment contains regulatory sequences driving high level transcription in all the tissues where Emilin1 is expressed. Moreover, the data suggest that transcription in different tissues is achieved through combinatorial cooperation between various regions, rather than being dependent on a single cis-activating region specific for each tissue

PSMA-Specific CAR-Engineered T Cells Eradicate Disseminated Prostate Cancer in Preclinical Models.

Immunology-based interventions have been proposed as a promising curative chance to effectively attack postoperative minimal residual disease and distant metastatic localizations of prostate tumors. We developed a chimeric antigen receptor (CAR) construct targeting the human prostate-specific membrane antigen (hPSMA), based on a novel and high affinity specific mAb. As a transfer method, we employed last-generation lentiviral vectors (LV) carrying a synthetic bidirectional promoter capable of robust and coordinated expression of the CAR molecule, and a bioluminescent reporter gene to allow the tracking of transgenic T cells after in vivo adoptive transfer. Overall, we demonstrated that CAR-expressing LV efficiently transduced short-term activated PBMC, which in turn were readily stimulated to produce cytokines and to exert a relevant cytotoxic activity by engagement with PSMA+ prostate tumor cells. Upon in vivo transfer in tumor-bearing mice, CAR-transduced T cells were capable to completely eradicate a disseminated neoplasia in the majority of treated animals, thus supporting the translation of such approach in the clinical setting

Huygens HASI servo accelerometer: a review and lessons learned

The Servo accelerometer constituted a vital part of the Huygens Atmospheric Structure Instrument (HASI): flown aboard the Huygens probe, it operated successfully during the probe's entry, descent, and landing on Titan, on 14th January 2005. This paper reviews the Servo accelerometer, starting from its development/assembly in the mid-1990s, to monitoring its technical performance through its seven-year long in-flight (or cruise) journey, and finally its performance in measuring acceleration (or deceleration) upon encountering Titan's atmosphere. The aim of this article is to review the design, ground tests, in-flight tests and operational performance of the Huygens Servo accelerometer. Techniques used for data analysis and lessons learned that may be useful for accelerometry payloads on future planetary missions are also addressed. The main finding of this review is that the conventional approach of having multiple channels to cover a very broad measurement range: from 10-6 g to the order of 10 g (where g = Earth's surface gravity, 9.8 m/s2), with on-board software deciding which of the channels to telemeter depending on the magnitude of the measured acceleration, works well. However, improvements in understanding the potential effects of the sensor drifts and ageing on the measurements can be achieved in future missions by monitoring the 'scale factor' – a measure of such sensors' sensitivity, along with the already implemented monitoring of the sensor's offset during the in-flight phase

Varietal differences in protein polymer built-up of wheat at different temperature and nitrogen regimes during grain filling

Both radionuclide imaging and near-infrared fluorescent (NIRF) imaging have a high sensitivity to detect tumors in vivo. The combination of these modalities using dual-labeled antibodies may allow both preoperative and intraoperative tumor localization and may be used in image-guided surgery to ensure complete resection of tumor tissue. Here, we evaluated the potential of dual-modality imaging of prostate cancer with the monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). For these studies, D2B was labeled both with (111)In and with the NIRF dye IRDye800CW.D2B was conjugated with N-hydroxysuccinimide-IRDye800CW and p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (ITC-DTPA) and subsequently radiolabeled with (111)In. For biodistribution and NIRF imaging, (111)In-DTPA-D2B-IRDye800CW (2 μg, 0.55 MBq/mouse) was injected intravenously into BALB/c nude mice with subcutaneous PSMA-expressing LNCaP tumors (right flank) and PSMA-negative PC3 tumors (left flank). The biodistribution was determined at 1, 2, 3, and 7 d after injection. In addition, micro-SPECT/CT and NIRF imaging with (111)In-DTPA-D2B-IRDye800CW (3 μg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors.(111)In-DTPA-D2B-IRDye800CW specifically accumulated in subcutaneous PSMA-positive LNCaP tumors (45.8 ± 8.0 percentage injected dose per gram at 168 h after injection), whereas uptake in subcutaneous PSMA-negative PC3 tumors was significantly lower (6.6 ± 1.3 percentage injected dose per gram at 168 h after injection). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both micro-SPECT/CT and NIRF imaging at 2 d after injection, and the feasibility of image-guided resection of intraperitoneal tumors was demonstrated in this model.Dual-labeled (111)In-DTPA-D2B-IRDye800CW enables specific and sensitive detection of prostate cancer lesions in vivo with micro-SPECT/CT and NIRF imaging. In addition to preoperative micro-SPECT/CT imaging to detect tumors, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant clinical studies with (111)In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients

Physical Activity and Natural Anti-VIP Antibodies: Potential Role in Breast and Prostate Cancer Therapy

BACKGROUND: There is convincing evidence from numerous clinical and epidemiological studies that physical activity can reduce the risk for breast and prostate cancer. The biological mechanisms underlying this phenomenon remain elusive. Herein we suggest a role for naturally produced antibodies reactive with the vasoactive intestinal peptide (VIP) in the suppression of breast and prostate cancer, which we believe could offer a possible molecular mechanism underlying control of these cancers by physical exercise. METHODOLOGY AND RESULTS: We found that sera from individuals having breast and prostate cancers have decreased titers of VIP natural antibodies as demonstrated by a lower reactivity against peptide NTM1, having similar informational and structural properties as VIP. In contrast, sera collected from elite athletes, exhibited titers of natural NTM1-reactive antibodies that are significantly increased, suggesting that physical activity boosts production of these antibodies. SIGNIFICANCE: Presented results suggest that physical exercise stimulates production of natural anti-VIP antibodies and likely results in suppression of VIP. This, in turn, may play a protective role against breast and prostate cancers. Physical exercise should be further investigated as a potential tool in the treatment of these diseases