Artificial intelligence and the doctor-patient relationship expanding the paradigm of shared decision making

Artificial intelligence (AI) based clinical decision support systems (CDSS) arebecoming ever more widespread in healthcare and could play an important role indiagnostic and treatment processes. For this reason, AI‐based CDSS has an impacton the doctor-patient relationship, shaping their decisions with its suggestions. Wemay be on the verge of a paradigm shift, where the doctor-patient relationship is nolonger a dual relationship, but a triad. This paper analyses the role of AI‐based CDSSfor shared decision‐making to better comprehend its promises and associated ethicalissues. Moreover, it investigates how certain AI implementations may instead fosterthe inappropriate paradigm of paternalism. Understanding how AI relates to doctorsand influences doctor-patient communication is essential to promote more ethicalmedical practice. Both doctors' and patients' autonomy need to be considered in thelight of AI

Photobiomodulation at Defined Wavelengths Regulates Mitochondrial Membrane Potential and Redox Balance in Skin Fibroblasts

Starting from the discovery of phototherapy in the beginning of the last century, photobiomodulation (PBM) has been defined in late 1960s and, since then, widely described in different in vitro models. Robust evidence indicates that the effect of light exposure on the oxidative state of the cells and on mitochondrial dynamics, suggesting a great therapeutic potential. The translational scale-up of PBM, however, has often given contrasting and confusing results, mainly due to light exposure protocols which fail to adequately control or define factors such as emitting device features, emitted light characteristics, exposure time, cell target, and readouts. In this in vitro study, we describe the effects of a strictly controlled light-emitting diode (LED)-based PBM protocol on human fibroblasts, one of the main cells involved in skin care, regeneration, and repair. We used six emitter probes at different wavelengths (440, 525, 645, 660, 780, and 900 nm) with the same irradiance value of 0.1 mW/cm2, evenly distributed over the entire surface of the cell culture well. The PBM was analyzed by three main readouts: (i) mitochondrial potential (MitoTracker Orange staining), (ii) reactive oxygen species (ROS) production (CellROX staining); and (iii) cell death (nuclear morphology). The assay was also implemented by cell-based high-content screening technology, further increasing the reliability of the data. Different exposure protocols were also tested (one, two, or three subsequent 20 s pulsed exposures at 24 hr intervals), and the 645 nm wavelength and single exposure chosen as the most efficient protocol based on the mitochondrial potential readout, further confirmed by mitochondrial fusion quantification. This protocol was then tested for its potential to prevent H2O2-induced oxidative stress, including modulation of the light wave frequency. Finally, we demonstrated that the controlled PBM induced by the LED light exposure generates a preconditioning stimulation of the mitochondrial potential, which protects the cell from oxidative stress damage

Machine learning applications in healthcare and the role of informed consent: Ethical and practical considerations

Informed consent is at the core of the clinical relationship. With the introduction of machine learning (ML) in healthcare, the role of informed consent is challenged. This paper addresses the issue of whether patients must be informed about medical ML applications and asked for consent. It aims to expose the discrepancy between ethical and practical considerations, while arguing that this polarization is a false dichotomy: in reality, ethics is applied to specific contexts and situations. Bridging this gap and considering the whole picture is essential for advancing the debate. In the light of the possible future developments of the situation and the technologies, as well as the benefits that informed consent for ML can bring to shared decision-making, the present analysis concludes that it is necessary to prepare the ground for a possible future requirement of informed consent for medical ML

Neuroprotection and neuroregeneration: roles for the white matter

Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system. Over the last few decades, a great deal of attention has been focused on white matter as a potential therapeutic target, mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system, a cell type able to fully repair myelin damage, and to the development of advanced imaging techniques to visualize and measure white matter lesions. The combination of these two events has greatly increased the body of research into white matter alterations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair, thus indirectly contributing to neuroprotection. This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system. Pivot conditions are discussed, specifically multiple sclerosis as a white matter disease; spinal cord injury, the acute lesion of a central nervous system component where white matter prevails over the gray matter, and Alzheimer's disease, where the white matter was considered an ancillary component until recently. We first describe oligodendrocyte precursor cell biology and developmental myelination, and its regulation by thyroid hormones, then briefly describe white matter imaging techniques, which are providing information on white matter involvement in central nervous system lesions and degenerative diseases. Finally, we discuss pathological mechanisms which interfere with myelin repair in adulthood

Ozone-elicited secondary metabolites in shoot cultures of Melissa officinalis L.

The effects of ozone treatment (200 ppb, 3 h) on the accumulation of main secondary metabolites have been investigated in Melissa officinalis (lemon balm) aseptic shoot cultures in order to evaluate the biotechnological application of this gas for improving the yield of secondary metabolites of medicinal plants. During the treatment, we found (i) an activation of enzymes involved in phenolic metabolism [as confirmed by the increase of shikimate dehydrogenase, phenylalanine ammonia-lyase and cinnamyl alcohol dehydrogenase activities (about twofold higher than controls)], (ii) a development of cellular barriers with a higher degree of polymerization of monolignols [as indicated by the increase of lignin (+23% compared to controls)], (iii) an accumulation of phenolic compounds, in particular rosmarinic acid (about fourfold compared to control plants cultivated in filtered air) and (iv) an increase of antioxidant capacity [as documented by the improved 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity]. The effect of ozone as elicitor of the production of secondary metabolites in lemon balm shoot cultures was dependent on the specific regime, the time of exposure and the concentration of the stressor. After the end of the treatment, we found cell death and hydrogen peroxide (H2O2) deposition concomitant with a prolonged superoxide anion-generation suggesting that a transient oxidative burst had occurre

In vitro exposure to very low-level laser modifies expression level of extracellular matrix protein RNAs and mitochondria dynamics in mouse embryonic fibroblasts

BACKGROUND: Low-level lasers working at 633 or 670 nm and emitting extremely low power densities (Ultra Low Level Lasers - ULLL) exert an overall effect of photobiostimulation on cellular metabolism and energy balance. In previous studies, it was demonstrated that ULLL pulsed emission mode regulates neurite elongation in vitro and exerts protective action against oxidative stress. METHODS: In this study the action of ULLL supplied in both pulsed and continuous mode vs continuous LLL on fibroblast cultures (Mouse Embryonic Fibroblast-MEF) was tested, focusing on mitochondria network and the expression level of mRNA encoding for proteins involved in the cell-matrix adhesion. RESULTS: It was shown that ULLL at 670 nm, at extremely low average power output (0.21 mW/ cm(2)) and dose (4.3 mJ/ cm(2)), when dispensed in pulsed mode (PW), but not in continuous mode (CW) supplied at both at very low (0.21 mW/cm(2)) and low levels (500 mW/cm(2)), modifies mitochondria network dynamics, as well as expression level of mRNA encoding for selective matrix proteins in MEF, e.g. collagen type 1α1 and integrin α5. CONCLUSIONS: We suggest that pulsatility, but not energy density, is crucial in regulating expression level of collagen I and integrin α5 in fibroblasts by ULLL

Plasma pharmacokinetics tissue concentration and urine elimination after cephalotin intravenous administration to cats under surgical conditions

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high (Cp(0), 353.79±118.92 μg/mL), with fast and moderately wide distribution (T1⁄2(d) 0.14±0.10 h) (V(d(ss)) 0.19±0.03 L/kg) and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1⁄2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 μg/g (testicle tissue) to 25.63 μg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a MIC≥1μg/mL up to 5.5 hours in all the studied cats. However, for MIC≥8μg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours.Fil: Albarellos, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Montoya, Laura. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lupi, Martin Pablo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lorenzini, Paula Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Time-Course Changes of Extracellular Matrix Encoding Genes Expression Level in the Spinal Cord Following Contusion Injury: A Data-Driven Approach

The involvement of the extracellular matrix (ECM) in lesion evolution and functional outcome is well recognized in spinal cord injury. Most attention has been dedicated to the "core" area of the lesion and scar formation, while only scattered reports consider ECM modification based on the temporal evolution and the segments adjacent to the lesion. In this study, we investigated the expression profile of 100 genes encoding for ECM proteins at 1, 8 and 45 days post-injury, in the spinal cord segments rostral and caudal to the lesion and in the scar segment, in a rat model. During both the active lesion phases and the lesion stabilization, we observed an asymmetric gene expression induced by the injury, with a higher regulation in the rostral segment of genes involved in ECM remodeling, adhesion and cell migration. Using bioinformatic approaches, the metalloproteases inhibitor Timp1 and the hyaluronan receptor Cd44 emerged as the hub genes at all post-lesion times. Results from the bioinformatic gene expression analysis were then confirmed at protein level by tissue analysis and by cell culture using primary astrocytes. These results indicated that ECM regulation also takes place outside of the lesion area in spinal cord injury

The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2) and an increased synthesis of prostaglandin E2 (PGE2). The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN) and/or nucleot(s)ide analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ''historical'' interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies