Emotional crisis in a naturalistic context: characterizing outpatient profiles and treatment effectiveness.

Crisis happens daily yet its understanding is often limited, even in the field of psychiatry. Indeed, a challenge is to assess the potential for change of patients so as to offer appropriate therapeutic interventions and enhance treatment program efficacy. This naturalistic study aimed to identify the socio-demographical characteristics and clinical profiles at admission of patients referred to a specialized Crisis Intervention Center (CIC) and to examine the effectiveness of the intervention. The sample was composed of 352 adult outpatients recruited among the referrals to the CIC. Assessment completed at admission and at discharge examined psychiatric symptoms, defense mechanisms, recovery styles and global functioning. The crisis intervention consisted in a psychodynamically oriented multimodal approach associated with medication. Regarding the clinical profiles at intake, patients were middle-aged (M = 38.56, SD = 10.91), with a higher proportion of women (62.22%). They were addressed to the CIC because they had attempted to commit suicide or had suicidal ideation or presented depressed mood related to interpersonal difficulties. No statistical differences were found between patients dropping out (n = 215) and those attending the crisis intervention (n = 137). Crisis intervention demonstrated a beneficial effect (p < 0.01) on almost all variables, with Effect Sizes (ES) ranging from small to large (0.12 < ES < 0.75; median = 0.49). However, the Reliable Change Index indicated that most of the issues fall into the undetermined category (range 41.46 to 96.35%; median = 66.20%). This study establishes the profile of patients referred to the CIC and shows that more than half of the patients dropped out from the crisis intervention before completion. Our findings suggest that people presenting an emotional crisis benefit from crisis intervention. However, given methodological constraints, these results need to be considered with caution. Moreover, the clinical significance of the improvements is not confirmed. Thus, the effectiveness of crisis intervention in naturalistic context is not fully determined and should be more rigorously studied in future research

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

Immune checkpoint mechanisms are important molecular cell systems that maintain tolerance toward autoantigens in order to prevent immunity-mediated accidental damage. It is well known that cancer cells may exploit these molecular and cellular mechanisms to escape recognition and elimination by immune cells. Programmed cell death protein-1 (PD-1) and its natural ligand programmed cell death ligand-1 (PD-L1) form the PD-L1/PD-1 axis, a well-known immune checkpoint mechanism, which is considered an interesting target in cancer immunotherapy. In fact, the expression of PD-L1 was found in various solid malignancies and the overactivation of PD-L1/PD-1 axis results in a poor patient survival rate. Breaking PD-L1/PD-1 axis, by blocking either the cancer side or the immune side of the axis, is currently used as anti-cancer strategy to re-establish a tumor-specific immune response. For this purpose, several blocking antibodies are now available. To date, three anti-PD-L1 antibodies have been approved by the FDA, namely atezolizumab, durvalumab and avelumab. The main advantages of anti-PD-L1 antibodies arise from the overexpression of PD-L1 antigen by a high number of tumor cells, also deriving from different tissues; this makes anti-PD-L1 antibodies potential pan-specific anti-cancer molecules. Despite the good results reported in clinical trials with anti-PD-L1 antibodies, there is a significant number of patients that do not respond to the therapy. In fact, it should be considered that, in some neoplastic patients, reduced or absent infiltration of cytotoxic T cells and natural killer cells in the tumor microenvironment or presence of other immunosuppressive molecules make immunotherapy with anti-PD-L1 blocking antibodies less effective. A strategy to improve the efficacy of antibodies is to use them as carriers for toxic payloads (toxins, drugs, enzymes, radionuclides, etc.) to form immunoconjugates. Several immunoconjugates have been already approved by FDA for treatment of malignancies. In this review, we focused on PD-L1 targeting antibodies utilized as carrier to construct immunoconjugates for the potential elimination of neoplastic cells, expressing PD-L1. A complete examination of the literature regarding anti-PD-L1 immunoconjugates is here reported, describing the results obtained in vitro and in vivo. The real potential of anti-PD-L1 antibodies as carriers for toxic payload delivery is considered and extensively discussed

Evaluation of Ocular Outcomes in Two 14-day Bed Rest Studies

No abstract availabl

Long Duration Head-Down Tilt Bed Rest Studies: Safety Considerations Regarding Vision Health

Visual symptoms reported in astronauts returning from long duration missions in low Earth orbit, including hyperopic shift, choroidal folds, globe flattening and papilledema, are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, safety considerations have been raised regarding the ocular health of head-down tilt (HDT) bed rest subjects. HDT is a widely used ground ]based analog that simulates physiological changes of spaceflight, including fluid shifts. Thus, vision monitoring has been performed in bed rest subjects in order to evaluate the safety of HDT with respect to vision health. Here we report ocular outcomes in 9 healthy subjects (age range: 27-48 years; Male/Female ratio: 8/1) completing bed rest Campaign 11, an integrated, multidisciplinary 70-day 6 degrees HDT bed rest study. Vision examinations were performed on a weekly basis, and consisted of office-based (2 pre- and 2 post-bed rest) and in-bed testing. The experimental design was a repeated measures design, with measurements for both eyes taken for each subject at each planned time point. Findings for the following tests were all reported as normal in each testing session for every subject: modified Amsler grid, red dot test, confrontational visual fields, color vision and fundus photography. Overall, no statistically significant differences were observed for any of the measures, except for both near and far visual acuity, which increased during the course of the study. This difference is not considered clinically relevant as may result from the effect of learning. Intraocular pressure results suggest a small increase at the beginning of the bed rest phase (p=0.059) and lesser increase at post-bed rest with respect to baseline (p=0.046). These preliminary results provide the basis for further analyses that will include correlations between intraocular pressure change pre- and post-bed rest, and optical coherence tomography measurements of the retina

A peptide found in human serum, derived from the c-terminus of albumin, shows antifungal activity in vitro and in vivo

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources

Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

Reports of astronauts' visual changes have raised concern about ocular health during long-duration spaceflight. Some of these findings include globe flattening with hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, it is hypothesized that, in predisposed individuals, hypertension in the brain may follow cephalad fluid shifts during spaceflight. This possible mechanism of ocular changes may also apply to analogous cases of idiopathic intracranial hypertension (IIH) or pseudotumor cerebri on Earth patients. Head-down t ilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. Previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP) but the conditions of bed rest varied among experiments, making it difficult to compare data and draw conclusions. For these reasons, vision evaluation of bed rest subjects was implemented for NASA bed rest studies since 2010, in an attempt to monitor vision health in subjects subjected to bed rest. Vision monitoring is thus currently performed in all NASA-conducted bed rest campaign

The ATLAS Barrel Level-1 Muon Trigger Calibration

The ATLAS experiment uses a system of three concentric Resistive Plate Chambers detectors layers for the level-1 muon trigger in the air-core barrel toroid region. The trigger classifies muons within different programmable transverse momentum ranges, and tags the identified tracks with the corresponding bunch crossing number. The algorithm looks for hit coincidences within different detector layers inside the programmed geometrical road which defines the transverse momentum cut. The on-detector electronics providing the trigger and detector readout functionalities collects input signals coming from the RPC front-end. Because of the different time-of-flights and cables and optical fibres lengths, signals have to be adjusted in time in order to be correctly aligned before being processed. Programmable delay logics are provided in the trigger and readout system to allow for time adjustment, for hit signals as well as for LHC Timing, Trigger and Control signals. The trigger calibration provides the set of numbers used during electronics initialization for correctly aligning signals inside the trigger and readout system. The functionality scheme and the algorithm of the calibration are presented

Large Eddy Simulations of sediment entrainment induced by a lock-exchange gravity current

Large Eddy simulations of lock-exchange gravity currents propagating over a mobile reach are presented. The numerical setting allows to investigate the sediment pick up induced by the currents and to study the underlying mechanisms leading to sediment entrainment for different Grashof numbers and grain sizes. First, the velocity field and the bed shear-stress distribution are investigated, along with turbulent structures formed in the flow, before the current reaches the mobile bed. Then, during the propagation of the current above the erodible section of the bed the contour plots of the entrained material are pre- sented as well as the time evolution of the areas covered by the current and by the sediment at this section. The numerical outcomes are compared with experimental data showing a very good agreement. Overall, the study confirms that sediment pick up is prevalent at the head of the current where the strongest turbulence occurs. Further, above the mobile reach of the bed, settling process seems to be of minor importance, with the entrained material being advected downstream by the current. Additionally, the study shows that, although shear stress is the main mechanism that sets particles in motion, turbu- lent bursts as well as vertical velocity fluctuations are also necessary to counteract the falling velocity of the particles and maintain them into suspension. Finally, the analysis of the stability conditions of the current shows that, from one side, sediment concentration gives a negligible contribution to the stability of the front of the current and from the other side, the stability conditions provided by the current do not allow sediments to move into the ambient fluid

A novel experimental approach for the detection of the dynamic Casimir effect

The Casimir effect is a well-known macroscopic consequence of quantum vacuum fluctuations, but whereas the static effect (Casimir force) has long been observed experimentally, the dynamic Casimir effect is up to now undetected. From an experimental viewpoint a possible detection would imply the vibration of a mirror at gigahertz frequencies. Mechanical motions at such frequencies turn out to be technically unfeasible. Here we present a different experimental scheme where mechanical motions are avoided, and the results of laboratory tests showing that the scheme is practically feasible. We think that at present this approach gives the only possibility of detecting this phenomenon.Comment: Submitted to the Physical Review Letters. RevTeX. 4 pages, 2 figure

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Mean IOP significantly increased while at 6deg HDT and returned towards pre-bed rest values upon leaving bed rest. While mean IOP increased during bed rest, it remained within the normal limits for subject safety. A diuretic shift and cardiovascular deconditioning occurs during in-bed rest, as expected. There was no demonstrable correlation between the largest change in IOP (pre/post) and cardiovascular measure changes (pre/post). Additional mixed effects linear regression modeling may reveal some subclinical physiological changes that might assist in describing the VIIP syndrome pathophysiology