CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients

Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy

Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications

Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics

A Modular, Low Latency, A2B-based Architecture for Distributed Multichannel Full-Digital Audio Systems

Despite the increasing demand for multichannel audio systems, existing solutions are still mainly analog or audio-over-IP based, leading to well-known limitations: bulky wiring, high latency (0.5-2 ms), and expensive devices for protocol stack management. This paper presents a cost-effective, low latency, full-digital solution that overcomes all the previously mentioned problems. The proposed architecture is based on the new Automotive Audio Bus (A2B) protocol. It guarantees deterministic latency of 2 samples, 32 downstream/upstream channels over a single Unshielded Twisted Pair (UTP) cable and phase-aligned signals. A single A2B chip is required for each node, reducing dramatically the system cost. The developed architecture is composed by a main board and an A2B network. The main board handles up to 64 channels, and it converts standard protocols usually employed for audio signal delivery, such as AES10, AVB and AES67, into A2B streams and vice versa. The A2B network can include a series of devices, for instance power amplifiers, codecs, DSPs, and transducers. There are many application examples including, but not limited to, transducer arrays (e.g., microphone, loudspeaker, accelerometer arrays), audio distribution in meeting rooms, Wave Field Synthesis (WFS), Ambisonics immersive audio systems and Active Noise Control (ANC). A modular and portable WFS system was developed employing the above-described architecture. It is based on eight channels soundbars, which can be daisy-chained in reconfigurable geometries and featuring up to 192 channels

Rapid and sound assessment of well-being within a multi-dimensional approach: The Well-being Numerical Rating Scales (WB-NRSs)

The assessment of well-being remains an important topic for many disciplines including medical, psychological, social, educational, and economic fields. The present study assesses the reliability and validity of a five-item instrument for evaluating physical, psychological, spiritual, relational, and general well-being. This measure uniquely utilizes a segmented numeric version of the visual analog scale in which a respondent selects a whole number that best reflects the intensity of the investigated characteristic. In study one, 939 clinical (i.e., diagnosed with cancer and liver disease with cirrhosis) and non-clinical (i.e., undergraduate students and their family and acquaintances) participants between the ages of 18 to 87 years (M = 47.20 years, SD = 19.62, 54% males) were recruited. Results showed items have strong discriminant ability and the spread of threshold parameters attests to the appropriateness of the response categories. Moreover, convergent and discriminant validity were found with other self-report measures (e.g., depression, anxiety, optimism, well-being) and the measure showed responsiveness to two separate interventions for clinical populations. In study two, 287 Canadian (ages ranged from 18 to 30 years; M = 20.78, SD = 3.32; 23% males) and 342 Italian undergraduate psychology students (age ranged from 18 to 29 years, M = 21.21 years, SD = 1.73, 38% males) were recruited to complete self-report questionnaires. IRT-based differential item functioning analyses provided evidence that the item properties were similar for the Italian and English versions of the scale. Additionally, the validity results obtained in study one were replicated and similar relationships between criterion variables were found when comparing the Italian- and the English-speaking samples. Overall, the current study provides evidence that the Italian and English versions of the WB-NRSs offer added value in research focused on well-being and in assessing well-being changes prompted by intervention programs

Time to Virological Failure of 3 Classes of Antiretrovirals after Initiation of Highly Active Antiretroviral Therapy: Results from the EuroSIDA Study Group

Objective. The purpose of the present study was to determine the prevalence and incidence of virological triple drug-class failure (TCF) and to summarize the clinical outcome for patients who started receiving highly active antiretroviral therapy (HAART). Methods. The present study is an observational longitudinal study of 3496 treatment-experienced (TE) and treatment-naive (TN) patients monitored from the time they started receiving HAART (baseline) until TCF occurred (as determined on the basis of viral loads), until AIDS was newly diagnosed, or until death. Results. Four hundred forty-five patients (12.7%) had TCF; 370 (16.6%) of 2230 patients were TE, and 75 (5.9%) of 1266 patients were TN. At 6 years after starting HAART, 21.4% of TE and 11.2% of TN patients had TCF (P < .0001). The prevalence of TCF at or after 2002 was 15.5% in TE patients and 4.8% in TN patients. TN patients had a 32% annual increase in the incidence of TCF (95% confidence interval [CI], 14%-54%; P < .0001); at 5 years after starting HAART, the rate was comparable for TE and TN patients (3.3 and 3.4 cases/100 person-years of follow-up [PYFU], respectively). The incidence of new cases of AIDS or death was 2.7 cases/100 PYFU in patients who did not experience TCF and 5.0 cases/100 PYFU in patients who did experience TCF, an estimated 36% increase with each category of TCF (95% CI, 19%-56%; P < .0001). Conclusion. The prevalence of TCF was low after patients started receiving HAART, particularly among TN patients. Despite the influx of patients who had started receiving HAART more recently, the prevalence of TCF increased over calendar time. Patients with TCF had a higher incidence of newly diagnosed AIDS or death. Treatment of patients with TCF deserves further investigatio

Linguistic and content validation of the translated and culturally adapted patient-generated subjective global assessment (PG-SGA)

The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument to screen, assess and monitor malnutrition and risk factors, and to triage for interventions. After having translated and culturally adapted the original PG-SGA for the Italian setting, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles, we tested linguistic validity, i.e., perceived comprehensibility and difficulty, and content validity (relevance) of the Italian version of the PG-SGA in patients with cancer and a multidisciplinary sample of healthcare professionals (HCPs). Methods: After the translation and cultural adaptation of the original PG-SGA for the Italian setting, the patient component (i.e., PG-SGA Short Form (SF) was tested for linguistic validity (i.e., comprehensibility ad difficulty) in 120 Italian patients with cancer and 81 Italian HCPs. The full PG-SGA, i.e., patient and professional component of the PG-SGA, was tested for content validity, i.e., relevance, in 81 Italian HCPs. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Through item and scale indices we evaluated the comprehensibility (I–CI, S–CI), difficulty (I-DI, S-DI) and content validity (I-CVI, S-CVI). Scale indices 0.80–0.89 were considered acceptable, and scale indices ≥0.90 were considered excellent. Results: Patients perceived comprehensibility and difficulty of the PG-SGA SF (Boxes) as excellent (S–CI = 0.98, S-DI = 0.96). Professionals perceived comprehensibility of the professional component (Worksheets) as excellent (S–CI = 0.92), difficulty as acceptable (S-DI = 0.85), and content validity of the full PG-SGA as excellent (S-CVI = 0.92). Dietitians gave higher scores (indicating better scores) on comprehensibility, difficulty, and content validity of Worksheet 4 (physical exam) than the other professions. In Worksheet 4, four items were considered most difficult to complete and were considered below acceptable range. Relevance was perceived as excellent by professionals for both the patient component (S-CVI = 0.93) and the professional component (S-CVI = 0.90), resulting in S-CVI = 0.92 for the full PG-SGA. Slight textual modifications were implemented resulting in the final version of the Italian PG-SGA. Conclusions: Translation and cultural adaptation of the original PG-SGA resulted in the Italian version of the PG-SGA that maintained its original purpose and meaning and can be completed adequately and easily by patients and professionals. The Italian PG-SGA is considered relevant for screening, assessing and monitoring malnutrition and risk factors, as well as triaging for interventions by Italian HCPs.</p

(Hydroxyphenyl)oxazoline: a Novel and Remarkably Facile Entry into the Area of Chiral Cationic Alkylzirconium Complexes Which Serve as Polymerization Catalysts

How can the entry into the area of chiral cationic alkyl derivatives of group 4 metals be simplified? We succeeded in, using readily available amino alcohols, which have been converted into chiral (hydroxyphenyl)oxazolines. These compounds have been employed in the organometallic derivatization of early transition metals