Activation of PKC-ε counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members

Protein kinase C (PKC)-ε, a component of the serine/threo-nine PKC family, has been shown to influence the survival and differentiation pathways of normal hematopoietic cells. Here, we have modulated the activity of PKC-ε with specific small molecule activator or inhibitor peptides. PKC-ε inhibitor and activator peptides showed modest effects on HL-60 maturation when added alone, but PKC-ε activator peptide significantly counteracted the pro-maturative activity of tumor necrosis factor (TNF)-α towards the monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression and morphological analyses. Moreover, while PKC-ε inhibitor peptide showed a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis, PKC-ε activator peptide potently counteracted the pro-apoptotic activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic activities of PKC-ε envision a potentially important proleukemic role of this PKC family member

Permeability and hydraulic condictivity of faulted micashist in the Eastern Elba Island exhumed geothermal system (Tyrrhenian sea, Italy): insights from Cala Stagnone

Estimating values of permeability (k), ef cient porosity (P) and hydraulic conductivity (K) by analysing eld outcrops as analogue of geothermal reservoirs, is a timely theme useful for predictions during geothermal ex- ploration programs. In this paper we present a methodology providing k, P and K values, based on geomet- ric analysis of quartz-tourmaline faults-vein arrays hosted in micaschist exposed in south-eastern Elba Island (Tuscan Archipelago, Italy), considered as the analogue of rock hosting the so-called “deep reservoir” in the Larderello geothermal eld. The methodology is based on the integration among structural geology, uid inclu- sions results and numerical analyses. Through a detailed structural mapping, scan-lines and scan-boxes analy- ses, we have reconstructed three superposed faulting events, developed in an extensional setting and framed in the Neogene evolution of inner Northern Apennines. Geometrical data of the fault-veins array were processed by reviewing the basic parallel-plate-model-equation for k evaluation. Fluid inclusion analyses provided those salinity and pressure-temperature values necessary for de ning density and viscosity of the parent geothermal uids. Then, permeability, density and viscosity were joined to get hydraulic conductivity (K). Permeability is estimated between 5 × 10− 13 and 5 × 10− 17 m2 with variations among the different generation of faults, while the hydraulic conductivity is encompassed between 1.31 × 10− 8 and 2.4 × 10− 13 m/s. The obtained permeabil- ity and hydraulic conductivity values are comparable with those from several geothermal areas, and in particular from the Larderello geothermal eld. The main conclusion is that the proposed integrated approach provides a reliable methodology to obtain crucial values, normally obtained after drilling, for developing numerical ow models of geothermal uid path in active geothermal systems by eld and laboratory analyses of analogue, ex- humed, geothermal systems

Transverse momentum distributions and their forward- backward correlations in the percolating colour string approach

The forward-backward correlations in the $p_T$ distributions, which present a clear signature of non-linear effects in particle production, are studied in the model of percolating colour strings. Quantitative predictions are given for these correlations at SPS, RHIC and LHC energies. Interaction of strings also naturally explains the flattening of $p_T$ distributions and increase of $$ with energy and atomic number for nuclear collisionsComment: 6 pages in LaTex, 3 figures in Postscrip

Auditive direct in utero observation (Audio): A randomized controlled trial for a prenatal demonstration of fetal hearing

Introduction: The objective of this randomized controlled study was to demonstrate whether acoustic stimulation in utero is associated with fetal reactivity which is documentable by car-diotocography. Materials and methods: A monocentric randomized controlled trial was performed at a single university tertiary hospital between September 2016 and July 2017. This study was registered as a randomized clinical trial on clinicaltrail.gov (registration number NCT04622059). Unselected pregnancies at term of gestation were consecutively recruited for the purpose of this study. After 10 min of normal cardiotocography without accelerations (non-stress-test with a basal frequency between 110 and 150 beats/min, normal variability between 6 and 15 b/min, no accelerations, and no fetal movements), fetuses were randomized at a 1:1 ratio to either of the two groups. Fetuses in group A (n = 105) received acoustic stimulation after 10 min from the beginning of the CTG, whereas fetuses in group B received no stimulation (n = 105). The outcome variables investigated were the lapse of time between the beginning of the CTG and the occurrence of the first accelera-tion, and the lapse of time between the beginning of the CTG and the first fetal movement noticed. Results: The lapse of time between the beginning of the CTG and the occurrence of the first acceleration was significantly shorter in the group with acoustic stimulation compared to the other group (14.87 ± 5.01 vs. 21.90 ± 6.94 min, p-value < 0.001 log-rank test). Similarly, the lapse of time between the beginning of the CTG and the occurrence of the first fetal movement was significantly shorter in group A compared to group B (17.77 ± 7.62 vs. 23.28 ± 7.61 min, p-value < 0.001, log-rank test). Fetal cardiac acceleration and the occurrence of a fetal movement during the first 20 min of the CTG were more frequently recorded in group A compared to group B (respectively, 15% vs. 5% and 20% vs. 8%). Conclusion: This RCT showed an early fetal reaction following auditive stimulus, documentable by cardiotocography. Further research is needed to investigate a possible role of acoustic stimulation in utero for the prenatal diagnosis of congenital hypoacusis

Endoscopy during the Covid-19 outbreak : experience and recommendations from a single center in a high-incidence scenario

A dramatic SARS-Cov-2 outbreak is hitting Italy hard. To face the new scenario all the hospitals have been re-organised in order to reduce all the outpatient services and to devote almost all their personnel and resources to the management of Covid-19 patients. As a matter of fact, all the services have undergone a deep re-organization guided by: the necessity to reduce exams, to create an environment that helps reduce the virus spread, and to preserve the medical personnel from infection. In these days a re-organization of the endoscopic unit, sited in a high-incidence area, has been adopted, with changes to logistics, work organization and patients selection. With the present manuscript, we want to support gastroenterologists and endoscopists in the organization of a \u201cnew\u201d endoscopy unit that responds to the \u201cnew\u201d scenario, while remaining fully aware that resources, availability and local circumstances may extremely vary from unit to unit

Ex vivo experimental study on the Thulium laser system : new horizons for interventional endoscopy (with videos)

BACKGROUND AND STUDY AIMS: The Thulium laser system (TLS) is an emerging interventional tool adopted in many surgical specialties. Its 2.0-\u3bcm wavelength allows precise coagulation (0.2\u200a-\u200a0.4\u200amm in depth) and cutting, limiting the possibilities of collateral injuries. We tested the impact of the TLS for gastric endoscopic submucosal dissection (ESD) and per oral endoscopic myotomy (POEM) ex vivo in pigs. MATERIALS AND METHODS: Ex vivo porcine stomach and esophagus models underwent 2 POEMs, and 3 ESDs (mean diameter 3.5\u200acm) with TLS using a 272-\ub5m and a 365-\ub5m thick optical fibers. Both continuous and pulsed laser emission were evaluated. Subsequent histopathological analysis was performed by an expert GI pathologist on the whole porcine models. RESULTS: Complete POEMs and gastric ESDs were successfully performed in all cases in 30 to 70 and 15 to 20 minutes. Both optical fibers were equally effective and precise. The best power output for mucosal incision was 25 to 30\u200aW during ESD and 25\u200aW for POEM using continuous laser emission. During submucosal dissection and tunneling the favorite power output was 20\u200aW and 15 to 20\u200aW, respectively, operating in continuous mode. No transmural perforation occurred throughout the operations and histopathology confirmed the absence of accidental muscular layer damage. CONCLUSIONS: The TLS stands out as a precise and manageable instrument in ex vivo models. This technique appears to be a promising tool for advanced interventional endoscopy