Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients' overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis

ELMB Microcontroller Firmware and SCADA Integration for the LHCb Muon Detector Readout Control System

The LHCb system requires high efficiency muon detection into LHC bunch crossing: 95% into a 25 ns time window. To reach such efficiency many parameters of the detector readout apparatus have to be calibrated and adjusted and its channels must be aligned in time. In addition, essential characteristics must be monitored to guarantee a good working condition of the apparatus (to avoid loss of efficiency and to minimize systematic errors). As the number of the muon readout parameters is extremely high (∼700000 registers), a system able to process information in parallel is required: 122000 readout channels will be controlled by about 600 microcontrollers and 6 computers. The complexity of such an apparatus requires the use of a distributed system. For this a Supervisory Control And Data Acquisition (SCADA) based system is being developed to control the entire detector readout equipment. Moreover, a Finite State Machine (FSM) implementation is being developed to integrate the Detector Readout Control (DRC) into the LHC Experiment Control System (ECS)

An energy budget for the subtidal bivalve Modiolus barbatus (Mollusca) at different temperatures

Clearance rates, respiration rates and food absorption efficiencies of the commercially interesting subtidal bivalve Modiolus barbatus were measured at different temperatures under laboratory conditions and scope for growth calculated. Clearance rates were highest at temperatures from 20°C to 28°C, whereas respiration rate was maximal at 9°C and minimal at 26°C. Highest mean values of absorbed energy occurred at 20°C and 26°C. Scope for growth trend had negative values at 9°C, 15°C and 28°C and positive values at temperatures 20°C and 26°C. The profitable thermal window for M. barbatus to have energy sufficient for growth and reproduction corresponded to <5 months per year. Seawater temperature increases will potentially impact the ecophysiological responses of subtidal M. barbatus causing life history traits to change with important repercussions for subtidal biodiversity in the Mediterranea

Synergistic effect induced by gold nanoparticles with polyphenols shell during thermal therapy: Macrophage inflammatory response and cancer cell death assessment

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment

Reduced GABA(B) receptor subunit expression and paired-pulse depression in a genetic model of absence seizures

Neocortical networks play a major role in the genesis of generalized spike-and-wave (SW) discharges associated with absence seizures in humans and in animal models, including genetically predisposed WAG/Rij rats. Here, we tested the hypothesis that alterations in GABAB receptors contribute to neocortical hyperexcitability in these animals. By using Real-Time PCR we found that mRNA levels for most GABAB(1) subunits are diminished in epileptic WAG/Rij neocortex as compared with age-matched non-epileptic controls (NEC), whereas GABAB(2) mRNA is unchanged. Next, we investigated the cellular distribution of GABAB(1) and GABAB(2) subunits by confocal microscopy and discovered that GABAB(1) subunits fail to localize in the distal dendrites of WAG/Rij neocortical pyramidal cells. Intracellular recordings from neocortical cells in an in vitro slice preparation demonstrated reduced paired-pulse depression of pharmacologically isolated excitatory and inhibitory responses in epileptic WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC slices was diminished by a GABAB receptor antagonist to a greater extent than in WAG/Rij rats further suggesting GABAB receptor dysfunction. In conclusion, our data identify changes in GABAB receptor subunit expression and distribution along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex. We propose that these alterations may contribute to neocorticalhyperexcitability and thus to SW generation in absence epilepsy

Transoral robotic surgery in the management of head and neck tumours.

The article reviews the use of robotic technology for head and neck tumours. The authors discuss the development of transoral robotic surgery (TORS), the current status of the technology, and the set-up in the operating room. The article provides a review of the literature, highlighting the applications, advantages, functional outcomes, and disadvantages of TORS for each anatomic subsite (oropharynx, hypopharynx, larynx, parapharyngeal space, and skull base). New challenges related to reconstruction are also presented. Overall early functional and oncologic outcome data are promising; further long-term prospective trials are still needed to confirm the oncological safety of TORS. Copyright

Total knee arthroplasty in valgus knee deformity: is it still a challenge in 2021?

Total knee arthroplasty in valgus knee deformities continues to be a challenge for a surgeon. Approximately 10% of patients who undergo total knee arthroplasty have a valgus deformity. While performing total knee arthroplasty in a severe valgus knee, one should aware with the technical aspects of surgical exposure, bone cuts of the distal femur and proximal tibia, medial and lateral ligament balancing, flexion and extension gap balancing, creating an appropriate tibiofemoral joint line, balancing the patellofemoral joint, preserving peroneal nerve function, and selection of the implant regarding constraint. Restoration of neutral mechanical axis and correct ligament balance are important factors for stability and longevity of the prosthesis and for good functional outcome. Thus, our review aims to provide step by step comprehensive knowledge about different surgical techniques for the correction of severe valgus deformity in total knee arthroplasty

Aloe vera silver nanoparticles addition in chitosan films: improvement of physicochemical properties for eco-friendly food packaging material

In recent times, the searches for alternative materials to plastic is a popular topic, due to the danger that synthetic materials cause to the environment and humans. Among the promising natural polymers, chitosan (CS) is certainly one of the most suitable since it it is edible, non-toxic and derives from crustacean waste.- However, it is necessary to improve its physical properties to be widely applied in food packaging, whose market is dominated by synthetic plastic. In this work we have synthesized silver nanoparticles (AgNPs) using hot-plate and microwaves-based techniques, using Aloe Vera leaves extracts. The synthetic process follows the principles of green chemistry, since no toxic substance is used to obtain nanomaterials. These NPs, having dimensions <20 nm, were characterized by TEM, zeta potential, UV-vis, FTIR, and then added to CS having low and medium molecular weight to develop thin films after its polymerization. These films were evaluated in terms of swelling ratio, optical properties, thermal stability, wettability, roughness, and friction coefficient, understanding that the physical properties of the films improved after the intercalation of the AgNPs, albeit differences were observed using the two NPs type. Subsequently, the release of silver ions from films using different pH as well as in vitro toxicity tests were carried out to evaluate their applicability. Largely, the excellent properties of new com- posite materials make them promising materials for packaging of different kinds of foods

UPO Biobank: The Challenge of Integrating Biobanking into the Academic Environment to Support Translational Research

Biobanks are driving motors of precision and personalized medicine by providing high-quality biological material/data through the standardization and harmonization of their collection, preservation, and distribution. UPO Biobank was established in 2020 as an institutional, disease, and population biobank within the University of Piemonte Orientale (UPO) for the promotion and support of high-quality, multidisciplinary studies. UPO Biobank collaborates with UPO researchers, sustaining academic translational research, and supports the Novara Cohort Study, a longitudinal cohort study involving the population in the Novara area that will collect data and biological specimens that will be available for epidemiological, public health, and biological studies on aging. UPO Biobank has been developed by implementing the quality standards for the field and the ethical and legal issues and normative about privacy protection, data collection, and sharing. As a member of the "Biobanking and Biomolecular Resources Research Infrastructure" (BBMRI) network, UPO Biobank aims to expand its activity worldwide and launch cooperation with new national and international partners and researchers. The objective of this manuscript is to report an institutional and operational experience through the description of the technical and procedural solutions and ethical and scientific implications associated with the establishment of this university research biobank