Landau-Zener evolution under weak measurement: Manifestation of the Zeno effect under diabatic and adiabatic measurement protocols

The time evolution and the asymptotic outcome of a Landau-Zener-Stueckelberg-Majorana (LZ) process under continuous weak non-selective measurement is analyzed. We compare two measurement protocols in which the populations of either the adiabatic or the non-adiabatic levels are (continuously and weakly) monitored. The weak measurement formalism, described using a Gaussian Kraus operator, leads to a time evolution characterized by a Markovian dephasing process, which, in the non-adiabatic measurement protocol is similar to earlier studies of LZ dynamics in a dephasing environment. Casting the problem in the language of measurement theory makes it possible for us to compare diabatic and adiabatic measurement scenarios, to consider engineered dephasing as a control device and to examine the manifestation of the Zeno effect under the different measurement protocols. In particular, under measurement of the non- adiabatic populations, the Zeno effect is manifested not as a freezing of the measured system in its initial state, but rather as an approach to equal asymptotic populations of the two diabatic states. This behavior can be traced to the way by which the weak measurement formalism behaves in the strong measurement limit, with a built-in relationship between measurement time and strength.Comment: 21 pages, 3 figures, submitted to New J. Phy

Not only a problem of fatigue and sleepiness: Changes in psychomotor performance in Italian nurses across 8-h rapidly rotating shifts

Although many studies have detailed the consequences of shift work in nurses concerning health, fatigue, sleepiness, or medical errors, no study has been carried out trying to disentangle the contribution of sleepiness and fatigue associated to shift work from the attentional performance. The aim of this pilot study is (A) to investigate the effects of an 8-h rapidly rotating shift on fatigue and sleepiness among staff nurses and (B) how these factors affect their psychomotor performance. Fourteen nurses were selected for a within-subject cross-sectional study according to this sequence of shifts: morning–afternoon–night, which were compared as function of tiredness, sleepiness, and performance at the Psychomotor Vigilance Task (PVT). Subsequently, a within-subject Analysis of Covariance (ANCOVA) evaluated if the observed differences between shifts persist when the contribution of sleepiness is controlled. Our results clearly indicate that night shifts are associated with significant greater sleepiness and tiredness, and worsened performance at the PVT. As hypothesized, ANCOVA showed that these differences disappear when the contribution of sleepiness is controlled. Results point to a lower psychomotor performance in night compared to day shifts that depends on sleepiness. Hence, interventions to minimize the consequences of the night shift should consider a reduction of sleepiness

Venetoclax in relapsed/refractory blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement : a case report and review of the literature

Background: We describe a patient with blastic plasmacytoid dendritic cell neoplasm with central nervous system involvement and the outcome of venetoclax use in this setting. Case presentation: A 54-year-old Caucasian male was referred to the Haematology Unit with an enlarged inguinal lymph node which was diagnostic of a blastic plasmacytoid dendritic cell neoplasm. The staging revealed disseminated disease (skin, visceral, lymph nodes, and bone marrow). He received chemotherapy with an acute myeloid leukaemia-like regime. Afterwards, he underwent allogeneic haematopoietic stem cell transplantation, though it was not successful, showing a relapse 14 months later with hepatic and central nervous system dissemination. Intrathecal chemotherapy was administered, and venetoclax (anti-bcl2 agent) was started in an off-label indication based on most recent literature. The disease halted its course for 3 months. In the end, the patient's disease progressed and so he succumbed due to infectious complications. Conclusions: Venetoclax monotherapy seems not enough to control the disease progression under CNS involvement and other treatments should be investigated

Exploring chitosan-shelled nanobubbles to improve HER2 + immunotherapy via dendritic cell targeting

Immunotherapy is a valuable approach to cancer treatment as it is able to activate the immune system. However, the curative methods currently in clinical practice, including immune checkpoint inhibitors, present some limitations. Dendritic cell vaccination has been investigated as an immunotherapeutic strategy, and nanotechnology-based delivery systems have emerged as powerful tools for improving immunotherapy and vaccine development. A number of nanodelivery systems have therefore been proposed to promote cancer immunotherapy. This work aims to design a novel immunotherapy nanoplatform for the treatment of HER2 + breast cancer, and specially tailored chitosan-shelled nanobubbles (NBs) have been developed for the delivery of a DNA vaccine. The NBs have been functionalized with anti-CD1a antibodies to target dendritic cells (DCs). The NB formulations possess dimensions of approximately 300 nm and positive surface charge, and also show good physical stability up to 6 months under storage at 4 °C. In vitro characterization has confirmed that these NBs are capable of loading DNA with good encapsulation efficiency (82%). The antiCD1a-functionalized NBs are designed to target DCs, and demonstrated the ability to induce DC activation in both human and mouse cell models, and also elicited a specific immune response that was capable of slowing tumor growth in mice in vivo. These findings are the proof of concept that loading a tumor vaccine into DC-targeted chitosan nanobubbles may become an attractive nanotechnology approach for the future immunotherapeutic treatment of cancer. GRAPHICAL ABSTRACT: [Image: see text

A new synthetic dual agonist of GPR120/GPR40 induces GLP-1 secretion and improves glucose homeostasis in mice.

Abstract G-protein coupled receptors 40 and 120 (GPR40 and GPR120) are increasingly emerging as potential therapeutic targets for the treatment of altered glucose homeostasis, and their agonists are under evaluation for their glucagon-like peptide-1 (GLP-1)-mediated therapeutic effects on insulin production and sensitivity. Here, we characterized a new dual GPR40 and GPR120 agonist (DFL23916) and demonstrated that it can induce GLP-1 secretion and improve glucose homeostasis. Resulting from a rational drug design approach aimed at identifying new dual GPR120/40 agonists able to delay receptor internalization, DFL23916 had a good activity and a very high selectivity towards human GPR120 (long and short isoforms) and GPR40, as well as towards their mouse orthologous, by which it induced both Gαq/11-initiated signal transduction pathways with subsequent Ca2+ intracellular spikes and G protein-independent signaling via β-arrestin with the same activity. Compared to the endogenous ligand alpha-linolenic acid (ALA), a selective GPR120 agonist (TUG-891) and a well-known dual GPR40 and GPR120 agonist (GW9508), DFL23916 was the most effective in inducing GLP-1 secretion in human and murine enteroendocrine cells, and this could be due to the delayed internalization of the receptor (up to 3 h) that we observed after treatment with DFL23916. With a good pharmacokinetic/ADME profile, DFL23916 significantly increased GLP-1 portal vein levels in healthy mice, demonstrating that it can efficiently induce GLP-1 secretion in vivo. Contrary to the selective GPR120 agonist (TUG-891), DFL23916 significantly improved also glucose homeostasis in mice undergoing an oral glucose tolerance test (OGTT)

Towards pancreatic cancer diagnosis using EIS biochips

n/

In vitro correction of cystic fibrosis epithelial cell lines by small fragment homologous replacement (SFHR) technique

BACKGROUND: SFHR (small fragment homologous replacement)-mediated targeting is a process that has been used to correct specific mutations in mammalian cells. This process involves both chemical and cellular factors that are not yet defined. To evaluate potential of this technique for gene therapy it is necessary to characterize gene transfer efficacy in terms of the transfection vehicle, the genetic target, and the cellular processing of the DNA and DNA-vehicle complex. METHODS: In this study, small fragments of genomic cystic fibrosis (CF) transmembrane conductance regulator (CFTR) DNA, that comprise the wild-type and ΔF508 sequences, were transfected into immortalized CF and normal airway epithelial cells, respectively. Homologous replacement was evaluated using PCR and sequence-based analyses of cellular DNA and RNA. Individual stages of cationic lipid-facilitated SFHR in cultured cell lines were also examined using transmission electron microscopy (TEM). RESULTS: We demonstrated that the lipid/DNA (+/-) ratio influences the mode of entry into the cell and therefore affects the efficacy of SFHR-mediated gene targeting. Lipid/DNA complexes with more negative ratios entered the cell via a plasma membrane fusion pathway. Transfer of the DNA that relies on an endocytic pathway appeared more effective at mediating SFHR. In addition, it was also clear that there is a correlation between the specific cell line transfected and the optimal lipid/DNA ratio. CONCLUSIONS: These studies provide new insights into factors that underlie SFHR-mediated gene targeting efficacy and into the parameters that can be modulated for its optimization

Correlation of mesolevel characteristics of the healthcare system and socioeconomic inequality in healthcare use: a scoping review protocol

Introduction Although the impact of macrolevel characteristics of health systems on socioeconomic inequity in health has been studied extensively, the impact of access characteristics on a smaller scale of health systems has received less attention. These mesolevel characteristics can influence access to healthcare and might have the potential to moderate or aggravate socioeconomic inequity in healthcare use. This scoping review aims to map the existing evidence of the association of socioeconomic inequity in healthcare use and mesolevel access characteristics of the health system. Methods and analysis In conducting the scoping review, we follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Extension for Scoping Reviews. The search will be carried out in four scientific databases: MEDLINE (via PubMed), Web of Science, Scopus and PsycINFO. Main eligibility criteria are inclusion in the analysis of a measure of socioeconomic position, a measure of individual healthcare use and a mesolevel determinant of access to healthcare services. The selection process consists of two consecutive screening stages (first: title/abstract; second: full text). At both stages, two reviewers independently assess the eligibility of studies. In case of disagreement, a third reviewer will be involved. Cohen’s kappa will be calculated to report inter-rater agreement between reviewers. Results are synthesised narratively, as a high heterogeneity of studies is expected. Ethics and dissemination No primary data are collected for the presented scoping review. Therefore, ethical approval is not necessary. The scoping review will be published in an international peer-reviewed journal, and findings will be presented on national and international conferences.Peer Reviewe

Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons. We tested DF2755A antinociceptive effects in a cyclophosphamide (CYP)-induced non-ulcerative IC rat model characterized by severe peripheral neuropathy in the absence of bladder inflammatory infiltrate, urothelial hyperplasia, and hemorrhage. Treatment with DF2755A prevented the onset of peripheral neuropathy and reversed its development in CYP-induced IC rats, showing a strong and long-lasting anti-hyperalgesic effect. Ex vivo and in vitro studies showed that DF2755A treatment strongly inhibited the expression of CXCR2 agonists, CXCL1/KC, and CXCL5 and of transient receptor potential vanilloid 1 (TRPV1) compared to vehicle, suggesting that its effects can be due to the inhibition of the nociceptive signaling passing through the CXCL1/CXCR1-2 axis and TRPV1. In conclusion, our results highlight the key pathophysiological role played by the CXCL1/CXCR1-2 axis and TRPV1 in the onset and development of peripheral neuropathy in non-Hunner IC and propose DF2755A as a potential therapeutic approach for the treatment of not only inflammatory painful conditions but also neuropathic ones and in particular non-Hunner IC/BPS