Role of endocannabinoids and TRPV1 channels in the bioelectric activity of hippocampal neurons

It has been reported that endocannabinoid system is an important player in the regulation of neuronal bioelectrical activity, relying on receptor-mediated mechanisms. Amongst these, Cannabinoid receptor type 1 (CB1r) and Transient Receptor Potential Vanilloid type 1 (TRPV1) are both modulated by endocannabinoids, involved in the transduction of stimuli in the pre-synaptic neuron and prompt downstream pathways in the post-synaptic neuron. To investigate the role of CB1r/TRPV1 interplay, we applied whole-cell patch clamp technique to visualize the eventual variations in terms of membrane current and action potentials induced by pharmacological manipulation in rat hippocampal neurons. We modulated the activity of the CB1r and TRPV1 exploiting anandamide (AEA), CB1r and TRPV1 agonist, capsaicin (CAP), a TRPV1 agonist and capsazepine (CPZ), a TRPV1 antagonist. Our data show that AEA influences steady membrane current with respect to controls. Furthermore, drug application significantly modifies action potentials amplitude, duration and frequency. In particular, the co-treatment of AEA and CPZ increases the amplitude of action potentials, reduces their duration and thus increases their frequency. These preliminary results support the involvement of TRPV1 in the cannabinoid modulation of the bioelectrical activity in rat hippocampal neurons. Indeed, the concurrent blockade of these channels and activation of CBr influences basic properties of neuronal function

Quantification of the resilience of primary care networks by stress testing the health care system

There are practically no quantitative tools for understanding how much stress a health care system can absorb before it loses its ability to provide care. We propose to measure the resilience of health care systems with respect to changes in the density of primary care providers. We develop a computational model on a 1-to-1 scale for a countrywide primary care sector based on patient-sharing networks. Nodes represent all primary care providers in a country; links indicate patient flows between them. The removal of providers could cause a cascade of patient displacements, as patients have to find alternative providers. The model is calibrated with nationwide data from Austria that includes almost all primary care contacts over 2 y. We assign 2 properties to every provider: the “CareRank” measures the average number of displacements caused by a provider’s removal (systemic risk) as well as the fraction of patients a provider can absorb when others default (systemic benefit). Below a critical number of providers, large-scale cascades of patient displacements occur, and no more providers can be found in a given region. We quantify regional resilience as the maximum fraction of providers that can be removed before cascading events prevent coverage for all patients within a district. We find considerable regional heterogeneity in the critical transition point from resilient to nonresilient behavior. We demonstrate that health care resilience cannot be quantified by physician density alone but must take into account how networked systems respond and restructure in response to shocks. The approach can identify systemically relevant providers

Nitric oxide-active compounds modulate the intensity of glutamate-evoked responses in the globus pallidus of the rat

Aim The effects of local applied NO-active compounds on glutamate (GLU)-evoked responses were investigated in globus pallidus (GP) neurons. Main methods Extracellularly recorded single units from anesthetized rats were treated with GLU before and during the microiontophoretic application of S-nitrosoglutathione (SNOG), a NO donor, and Nω-nitro-l-arginine methyl ester (L-NAME), a NOS inhibitor. Key findings Most GP cells were excited by SNOG whereas administration of L-NAME induced decrease of GP neurons activity. Nearly all neurons responding to SNOG and/or L-NAME showed significant modulation of their excitatory responses to the administration of iontophoretic GLU. In these cells, the changes induced by NO-active drugs in the magnitude of GLU-evoked responses were used as indicators of NO modulation. In fact, when a NO-active drug was co-iontophoresed with GLU, significant changes in GLU-induced responses were observed: generally, increased magnitudes of GLU-evoked responses were observed during SNOG ejection, whereas the administration of L-NAME decreased responses to GLU. Significance The results suggest that the NO-active drugs modulate the response of GP neurons to glutamatergic transmission. Nitrergic modulation of glutamatergic transmission could play an important role in the control of GP bioelectric activity, considered a fundamental key in the BG function

The Hippo Kinase Pathway: a master regulator of proliferation, development and differentiation

Hippo signaling transduction pathway is widely conserved through evolution and controls cell growth, homeostasis, apoptosis, commitment, differentiation and senescence. It consists of a conserved kinase cascade whose final targets are the transcriptional coactivator Yorkie (Yki) in Drosophila and the homologues YAP and TAZ in mammals. These transcriptional coactivators are unable to bind DNA per se, and can regulate the activity of their target genes only in association with transcription factors. In Drosophila, Yki associates with the transcription factors Sd and Hth regulating pro-proliferative and anti-apoptotic genes. In mammals instead, YAP/TAZ can associate with several distinct transcription factors. This depends from the type of signals to which cells are subjected, the cell type and the developmental stage. The transcriptional outcome resulting from this association can be either pro-apoptotic or pro-proliferative. Hippo pathway dysregulation has been associated with several pathologic conditions (tissue overgrowth, developmental defects and cancer). In particular, solid tumors show an upregulation or hyperactivation of YAP/TAZ, while several hematologic tumors are associated with YAP downregulation. This might suggest that the Hippo pathway holds the potential to be an attractive target for novel therapeutic approaches for cancer

Guarding net effects on landings and discards in Mediterranean trammel net fishery: Case analysis of Egadi Islands Marine Protected Area (Central Mediterranean Sea, Italy)

Discards remain among the main negative impacts of fishing activities, and their reductions are strengthened by the European Common Fisheries Policy (European Regulation 1380/2013). Trammel net fisheries appear more sustainable compared with other fishing techniques, especially from an ecological viewpoint. Despite this, reports show that trammel net fisheries deliver discard quantities between 10% and 43% of the total catch biomass. To supplement existing information, this current work attempts to address the discard reduction using guarding net in the small-scale fisheries of Egadi Islands MPA (Western Sicily, Central Mediterranean Sea). To assess the reduction of unwanted catches, 48 experimental fishing trials were conducted within a 6-month period. The experimental fishing trial employed a trammel net made up of 20 panels alternated with two different net configurations. The control panels (CN) held a large outer (180 mm) and small inner (31.25 mm) meshes. The test panels (GN) with guarding net constituted a three-mesh-high (50-mm mesh size) net placed between trammel net panels and a lead line. A total of 3,310 individuals belonging to 106 taxa and nine phyla were caught. Crustaceans were the most abundant unwanted catches in the control panels, whereas bioconstructions occurred in the guarding net panels. The discard ratios of CN and GN panels were statistically different (t-value = -2.55; p< 0.05). The analysis of catch per unit effort showed higher catches of CN panels for both commercial and discard fractions (p< 0.05). Moreover, the guarding net panels caught the main discarded species at 20% lower compared with the control. The overall value of the catch at the CN panels (euro 3,366.90) was higher than the total income (euro 2,043.70) generated using the GN panels, which suggests a significant commercial loss of 40% (p< 0.05)

Guarding net effects on landings and discards in Mediterranean trammel net fishery: Case analysis of Egadi Islands Marine Protected Area (Central Mediterranean Sea, Italy)

Discards remain among the main negative impacts of fishing activities, and their reductions are strengthened by the European Common Fisheries Policy (European Regulation 1380/2013). Trammel net fisheries appear more sustainable compared with other fishing techniques, especially from an ecological viewpoint. Despite this, reports show that trammel net fisheries deliver discard quantities between 10% and 43% of the total catch biomass. To supplement existing information, this current work attempts to address the discard reduction using guarding net in the small-scale fisheries of Egadi Islands MPA (Western Sicily, Central Mediterranean Sea). To assess the reduction of unwanted catches, 48 experimental fishing trials were conducted within a 6-month period. The experimental fishing trial employed a trammel net made up of 20 panels alternated with two different net configurations. The control panels (CN) held a large outer (180 mm) and small inner (31.25 mm) meshes. The test panels (GN) with guarding net constituted a three-mesh-high (50-mm mesh size) net placed between trammel net panels and a lead line. A total of 3,310 individuals belonging to 106 taxa and nine phyla were caught. Crustaceans were the most abundant unwanted catches in the control panels, whereas bioconstructions occurred in the guarding net panels. The discard ratios of CN and GN panels were statistically different (t-value = –2.55; p< 0.05). The analysis of catch per unit effort showed higher catches of CN panels for both commercial and discard fractions (p< 0.05). Moreover, the guarding net panels caught the main discarded species at 20% lower compared with the control. The overall value of the catch at the CN panels (€ 3,366.90) was higher than the total income (€ 2,043.70) generated using the GN panels, which suggests a significant commercial loss of 40% (p< 0.05)

Assessing the Stock Dynamics of Elasmobranchii off the Southern Coast of Sicily by Using Trawl Survey Data

Elasmobranchii (sharks and rays), which have peculiar and vulnerable life-history traits, are highly threatened by fishing activities. Indeed, between 53% and 71% of Mediterranean elasmobranch species are at risk of extinction. In this context, using the abundance MSY (AMSY) model, the present study provides an assessment of 20 batoids and 16 shark species in the Strait of Sicily, sampled during a bottom trawl survey from 1995 to 2020. Overall, the outputs underline a progressively improving condition for shark and ray assemblages of both shelf and eurybathic zones. As for slope-dwelling species, a horseshoe-shaped dynamic, characterized by a progressive decrease in relative harvesting pressure and an increase in relative biomass followed by an increase in fishing pressure and decrease in biomass, was detected. The dynamics of the Elasmobranchii living in the Strait of Sicily appear to be affected by changes in the fishing patterns of trawlers, showing a shift from shallow water to bathyal fishing grounds and targeting deep-water red shrimp. In this context, it seems wise to limit the impact of deep-water fisheries on Elasmobranchii by reducing fishing efforts and implementing ad hoc management measures aimed at safeguarding these vulnerable species

Nurses’ behavior regarding pain treatment in an emergency department: A single-center observational study

Purpose: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting. Methods: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses’ approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia. Results: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia. Conclusion: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients’ pain more effectively and in a more timely manner