First-year nursing students' attitudes towards artificial intelligence: Cross-sectional multi-center study.

AIM: To assess the attitudes of nursing students toward artificial intelligence. BACKGROUND: Possible applications of artificial intelligence-powered systems in nursing cover all aspects of nursing care, from patient care to risk management. Although the final acceptance of artificial intelligence in practice will depend on positive 'nurses' attitudes toward artificial intelligence, those attitudes have gained little attention so far. DESIGN: A cross-sectional multicenter study. METHODS: The study was performed at nursing schools of four Croatian universities, surveying a total of 336 first-year nursing students (response rate 69.7%) enrolled in 2021. A validated instrument, the General Attitudes towards Artificial Intelligence Scale, consisting of 20 Likert-type items, was chosen for the study. Where applicable, the items were contextualized for nursing. Four sub-scales were identified based on the outcomes of the factor analysis. RESULTS: The average attitude score was (mean ± standard deviation) 64.5 ± 11.7, out of a maximum of 100, which was significantly higher than the neutral score of 60.0 (p < 0.001). The attitude towards AI did not differ across the universities and was not associated with students' age. Male students scored slightly higher than their female colleagues. Scores on subscales "Benefits of artificial intelligence in nursing", "Willingness to use artificial intelligence in nursing practice", and "Dangers of artificial intelligence" were favorable of artificial intelligence-based solutions. However, scores on the subscale "Practical advantages of artificial intelligence" were somewhat unfavorable. CONCLUSIONS: First-year nursing students had slightly positive attitudes towards artificial intelligence in nursing, which should make it easier for the new generations of nurses to embrace and implement artificial intelligence systems. Reservations about artificial intelligence in daily nursing practice indicate that nursing students might benefit from education focused specifically on applications of artificial intelligence in nursing.

How does stellate ganglion block alleviate immunologically-linked disorders?

BACKGROUND: The stellate ganglion is an autonomic nervous ganglion, formed by the fusion of the inferior cervical sympathetic ganglion and the first thoracic sympathetic ganglion, which is present in about 80% of people. It is anterior to the neck of the first rib and contains neurons that supply sympathetic innervation to the head and neck. Injection of local anesthetics near the stellate ganglion (stellate ganglion block; SGB) has been used for multiple clinical indications including sympathetic-mediated pain and vascular insufficiency syndromes of the upper extremity. In addition, reports on SGB having significant impact on conditions linked to immune dysfunction have been published for a century, but the mechanisms of SGB action have been poorly understood. HYPOTHESIS: SGB hinders the sympathetic innervation of the immune organs, thus modulating the immune system activity and leading to the alleviation of the disease. EVIDENCE: All primary (thymus and bone marrow) and secondary immune organs (spleen, lymph nodes, mucosa-associated lymphoid tissue) receive a substantial sympathetic innervation, with norepinephrine (NE), as the main neurotransmitter. Complementarily, T and B lymphocytes express ß2-adrenergic receptors, while innate immune cells express both α- and ß-adrenergic receptors. The consequences of adrenergic receptor signaling can be summarized as immuno-modulatory. Activation of adrenergic receptors leads to decreased levels of pro-inflammatory cytokines (e.g. IL-1ß, IL-6, TNF-α) and increased levels of anti-inflammatory cytokines, like IL-10 or TGF-ß. Cellular changes include increase in the number of regulatory T cells and shift of the Th1/Th2 balance towards the Th2 response. Since the changes in immune response are global, the explanation has to include generalization of the SGB effect. A likely explanation includes centripetal neuronal pathways between the stellate ganglion and deep brain regions such as insula, amygdala, and hippocampus. Those, in turn, have reciprocal innervation with locus ceruleus, a brain-stem structure involved in the control of the autonomous nervous system. CONCLUSION: Various pathologic conditions have been shown to be SGB responsive, where the symptoms have been reduced or eliminated. Many of those clinical improvements have been mirrored by measurable immunologic changes. A plausible explanation, consistent with the evidence available so far, is that SGB exerts its effects by regulating the immune system, through a central, reflex-like pathway. Our hypothesis provides a theoretical framework for understanding the effects of SGB and could, thus lead to wider usage of the technique in immune-linked disorders such as ulcerative colitis.

Massive Upper Body and Cervicofacial Subcutaneous Emphysema Following Robotic Myomectomy.

Subcutaneous emphysema is defined as the unintentional introduction of air or carbon dioxide in the subcutaneous tissues. The use of robotic surgical techniques has greatly expanded over the past decade specifically to treat intraperitoneal pathology. In general, advantages of these minimally invasive procedures are reported to decrease operating time, patient morbidity, and shorten hospital stay providing a safe alternative to traditional surgery. However, as with any surgery, potential complications may occur. We describe an unusual case of massive subcutaneous emphysema involving the upper body and cervicofacial region, with bilateral pneumothoraces following robotic intraperitoneal surgery. Written authorization was obtained from the patient.

Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy.

This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na(v)1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy.

Macrophage migration inhibitory factor (MIF) and manganese superoxide dismutase (MnSOD) as early predictors for survival in patients with severe sepsis or septic shock.

BACKGROUND: Severe sepsis, septic shock, and resulting organ failure appear as the most common cause of death in intensive care medicine. Inflammatory mediators (interleukin-6/IL-6), cell adhesion molecules (intercellular adhesion molecule-1/ICAM-1, vascular cell adhesion molecule-1/VCAM-1), and redox active substances (manganese superoxide dismutase/MnSOD, macrophage migration inhibitory factor/MIF) must be considered to be central hubs in the inflammatory process. However, their exact pathophysiologic function and prognostic value are still poorly understood. MATERIALS AND METHODS: In total, 133 individuals (87 patients with severe sepsis or septic shock, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled in the study. Blood samples from septic patients were collected within 24 h after the time of sepsis diagnosis, and 48 and 120 h later; samples from healthy volunteers were collected once, and samples from postoperative patients once immediately after surgery. In all patients we measured plasma levels of IL-6, sICAM-1, sVCAM-1, MnSOD, and MIF using enzyme linked immunosorbent assay (ELISA) kits. RESULTS: Healthy volunteers and postoperative patients showed comparable levels of cell adhesion molecules. Furthermore, their redox system was activated in a comparable manner, whereas in postoperative patients IL-6 was significantly elevated. Plasma levels of inflammatory mediators, cell adhesion molecules and redox active substances were significantly elevated in septic patients. In patients with sepsis who had died, plasma levels of MIF and MnSOD were significantly elevated in comparison with survivors. CONCLUSIONS: Our results therefore demonstrate that redox active substances may play an important role in the septic inflammatory response. MIF and MnSOD appear to be early predictors for survival in septic patients.

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo.

The receptor for advanced glycation end products (RAGE) contributes to the inflammatory response in many acute and chronic diseases. In this context, RAGE has been identified as a ligand for the beta(2)-integrin Mac-1 under static in vitro conditions. Because intercellular adhesion molecule (ICAM)-1 also binds beta(2)-integrins, we studied RAGE(-/-), Icam1(-/-), and RAGE(-/-) Icam1(-/-) mice to define the relative contribution of each ligand for leukocyte adhesion in vivo. We show that trauma-induced leukocyte adhesion in cremaster muscle venules is strongly dependent on RAGE and ICAM-1 acting together in an overlapping fashion. Additional in vivo experiments in chimeric mice lacking endothelium-expressed RAGE and ICAM-1 located the adhesion defect to the endothelial compartment. Using microflow chambers coated with P-selectin, CXCL1, and soluble RAGE (sRAGE) demonstrated that sRAGE supports leukocyte adhesion under flow conditions in a Mac-1- but not LFA-1-dependent fashion. A static adhesion assay revealed that wild-type and RAGE(-/-) neutrophil adhesion and spreading were similar on immobilized sRAGE or fibrinogen. These observations indicate a crucial role of endothelium-expressed RAGE as Mac-1 ligand and uncover RAGE and ICAM-1 as a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute trauma-induced inflammatory response in vivo.

AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis.

HSA preparations for i.v. use are administered in critically ill patients. Although increasing intravascular osmotic pressure seems to be a pathophysiologically orientated treatment, clinical trials do not indicate a benefit for mortality in HSA-treated patients. Instead, there is evidence for inflammatory reactions upon infusion of different HSA batches. A neglected issue concerning the safety and quality of these therapeutics is processing-related post-transcriptional protein modifications, such as AGEs. We therefore tested the hypothesis that commercially available infusion solutions contain AGEs and studied whether these protein modifications influence outcome and inflammation in a murine model of sepsis induced by CLP. Screening of different HSA and Ig preparations in this study revealed an up to approximate tenfold difference in the amount of AGE modifications. Application of clinically relevant concentrations of CML-modified HSA in CLP led to increased inflammation and enhanced mortality in wild-type mice but not in mice lacking the RAGE. Lethality was paralleled by increased activation of the proinflammatory transcription factor NF-kappaB, NF-kappaB-dependent gene expression, and infiltration of inflammatory cells in the peritoneal cavity. This study implies that infusion solutions containing a high load of the AGE-modified protein have the potential to activate RAGE/NF-kappaB-mediated inflammatory reactions, causing increased mortality in experimental peritonitis.

High-mobility group box-1 in ischemia-reperfusion injury of the heart.

BACKGROUND: High-mobility group box-1 (HMGB1) is a nuclear factor released by necrotic cells and by activated immune cells. HMGB1 signals via members of the toll-like receptor family and the receptor for advanced glycation end products (RAGE). Although HMGB1 has been implicated in ischemia/reperfusion (I/R) injury of the liver and lung, its role in I/R injury of the heart remains unclear. METHODS AND RESULTS: Here, we demonstrate that HMGB1 acts as an early mediator of inflammation and organ damage in I/R injury of the heart. HMGB1 levels were already elevated 30 minutes after hypoxia in vitro and in ischemic injury of the heart in vivo. Treatment of mice with recombinant HMGB1 worsened I/R injury, whereas treatment with HMGB1 box A significantly reduced infarct size and markers of tissue damage. In addition, HMGB1 inhibition with recombinant HMGB1 box A suggested an involvement of the mitogen-activated protein kinases jun N-terminal kinase and extracellular signal-regulated kinase 1/2, as well as the nuclear transcription factor nuclear factor-kappaB in I/R injury. Interestingly, infarct size and markers of tissue damage were not affected by administration of recombinant HMGB1 or HMGB1 antagonists in RAGE(-/-) mice, which demonstrated significantly reduced damage in reperfused hearts compared with wild-type mice. Coincubation studies using recombinant HMGB1 in vitro induced an inflammatory response in isolated macrophages from wild-type mice but not in macrophages from RAGE(-/-) mice. CONCLUSIONS: HMGB1 plays a major role in the early event of I/R injury by binding to RAGE, resulting in the activation of proinflammatory pathways and enhanced myocardial injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy in I/R injury.

The RAGE pathway: activation and perpetuation in the pathogenesis of diabetic neuropathy.

The molecular mechanisms underlying loss of pain perception in diabetic neuropathy are poorly understood. Experimental diabetic neuropathy models recently provided evidence that engagement of the receptor for advanced glycation end products (RAGE) and RAGE-dependent sustained activation of the proinflammatory transcription factor nuclear factor kappa B might significantly contribute to reduced nociception. Most importantly, diabetes-induced loss of pain perception is largely prevented in RAGE-deficient mice compared to RAGE-bearing wild-type mice. Identifying RAGE-dependent inflammation as one pathomechanism underlying neuronal dysfunction might provide the basis for new therapeutic approaches.

Pharmacologic cholinesterase inhibition improves survival in experimental sepsis.

OBJECTIVE: Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic anti-inflammatory pathway. Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo. DESIGN: Prospective, randomized laboratory investigation that used an established murine sepsis model. SETTING: Research laboratory in a university hospital. SUBJECTS: Female C57BL/6 mice. INTERVENTIONS: Sepsis in mice was induced by cecal ligation and puncture. Animals were treated immediately with intraperitoneal injections of nicotine (400 microg/kg), physostigmine (80 microg/kg), neostigmine (80 microg/kg), or solvent three times daily for 3 days. MEASUREMENTS AND MAIN RESULTS: Treatment with physostigmine significantly reduced lethality (p < or = .01) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p < or = .05). Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-kappaB (p < or = .05) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (p < or = .001), and pulmonary neutrophil invasion (p < or = .05). Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. CONCLUSIONS: Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use.