Analysis of Kinematic Response of Pediatric Occupants Seated in Naturalistic Positions in Simulated Frontal Small Offset Impacts: With and Without Automatic Emergency Braking.

Naturalistic driving studies have shown that pediatric occupants do not assume ideal seating positions in real-world scenarios. Current vehicle assessment programs and child restraint system (CRS) sled tests, such as FMVSS No. 213, do not account for a wide range of seating postures that are typically observed during real-world trips. Therefore, this study aims to analyze the kinematic and kinetic response of a pediatric human body model in various naturalistic seating positions in booster seats when subjected to a frontal offset impact in a full-vehicle environment, with and without the application of pre-crash automatic emergency braking (AEB). A 6YO (seated on a lowback and highback booster) and a 10YO (seated in no-CRS and on a lowback booster) PIPER pediatric human body model's response was explored in a reference, and two most commonly observed seating postures: forward-leaning and forward-inboard-leaning. The vehicle environment with a side-curtain airbag (SCAB) was subjected to a small offset barrier impact (25% overlap at 40MPH), with and without the application of a pre-crash automatic emergency braking (AEB). 24 conditions were simulated using finite element analysis. Cases with a pre-crash AEB resulted in relatively lower kinematic and kinetic values due to the occupant being in a more flexed position before impact compared to without-AEB cases, coupled with the increased ride-down effect due to AEB. Moreover, different seating postures resulted in substantially different kinematics and kinetics, the injury metrics crossing the injury assessment reference values in some cases. Therefore, to design a passive safety standard test for pediatric occupants, it is important to consider the possible postural changes that may occur.

Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept.

The aim of this study was to demonstrate that oligo-branched peptides can be effective either for spotlighting tumor cells that overexpress peptide receptors, or for killing them, simply by exchanging the functional moiety coupled to the conserved receptor-targeting core. Tetra-branched peptides containing neurotensin (NT) sequence are described here as selective targeting agents for human colon, pancreas and prostate cancer. Fluorophore-conjugated peptides were used to measure tumor versus healthy tissue binding in human surgical samples, resulting in validation of neurotensin receptors as highly promising tumor-biomarkers. Drug-armed branched peptides were synthesized with different conjugation methods, resulting in uncleavable adducts or drug-releasing molecules. Cytotoxicity on human cell lines from colon (HT-29), pancreas (PANC-1) or prostate (PC-3) carcinoma indicated branched NT conjugated with MTX and 5-FdU as the most active agents on PANC-1 (EC(50) 4.4e-007 M) and HT-29 (1.1e-007 M), respectively. Tetra-branched NT armed with 5-FdU was used for in vivo experiments in HT-29-xenografted mice and produced a 50% reduction in tumor growth with respect to animals treated with the free drug. An unrelated branched peptide carrying the same drug was completely ineffective. In vitro and in vivo results indicated that branched peptides are valuable tools for tumor selective targeting.

Verapamil acute administration: a new dynamic test in hyperprolactinemic states.

We studied the effect of acute administration of the calcium-channel blocker verapamil (VER) in 27 patients with tumoral hyperprolactinemia ([THPRL] prolactinomas and pseudoprolactinomas). We also studied the effect of VER in seven patients with idiopathic hyperprolactinemia (IHPRL) and a small group of patients with normal prolactin (PRL) levels and minimal incidental anomalies shown by magnetic resonance imaging (MRI). The study was performed on 2 separate days: on the first day, all subjects received VER, and on the second they received placebo. Acute administration of VER evoked a remarkable increase in serum PRL in IHPRL (as in normal healthy subjects used as controls), but no response was shown in THPRL, with no overlap between the two conditions. Acute administration of VER stimulated PRL secretion in patients with minimal incidental lesions shown by MRI; however, this increase was smaller in patients whose PRL level consistently reached the upper-normal limit. Although the meaning of such minimal anomalies shown by MRI is unknown, this could suggest that the test is precociously altered. To further elucidate the action of VER on lactotropes, we investigated the effect of VER given intravenously (IV) and compared different oral formulations in healthy subjects. Our data show that the VER test is effective in distinguishing between THPRL and IHPRL, but unfortunately, like other tests, it is not able to individualize patients in whom THPRL is the result of diminished dopaminergic tone (pseudoprolactinoma). From a pathophysiological point of view, calcium influx would appear less important in PRL regulation in chronic disorders of PRL secretion. VER given IV did not stimulate PRL release in normal subjects. This suggests that IV administration could produce a peak with an inadequate duration or that oral formulations may act also by metabolites formed on first-pass metabolism in the liver.

[Comparison, using RAST-inhibition, of the allergenic potency of Dermatophagoides pteronyssinus extracts obtained from: whole mite culture, fraction of enriched mite culture, fraction of feces enriched culture, purified mite bodies, commercial extracts]. / Comparazione, mediante RAST-inibizione, della potenza allergenica degli estratti di Dermatophagoides pteronyssinus ottenuti da: coltura intera di acari, frazione di coltura arricchita di acari, frazione di coltura arricchita di particelle fecali, corpi purificati di acari, estratto del commercio.

The RAST-inhibition potency has been obtained from five extracts prepared by: whole mite culture, mites-enriched culture, faeces-enriched culture, purified mite bodies, commercial extract. The present study demonstrates that extracts of: a) purified bodies, and b) faeces-enriched culture are both potent preparations in RAST-inhibition.