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Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl− cotransporter KCC2, dysrupting Cl−homeostasis, and hence the strength of GABAA- and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions.

Background: The objective of this study was to compare conventional versus digital impressions for Full-Arch maxillary rehabilitations. Methods: Patients selected for this study were treated with full-arch screw-retained rehabilitations supported by six immediately loaded dental implants. Patients have been scheduled randomly into control (conventional impression group, CIG) and test (digital impression group, DIG) groups respectively for a fully conventional workflow and a fully digital workflow. In both groups, within 24 h, temporary prostheses were delivered. Four months after the implant positioning, the two groups dealt with the fabrication of definitive restorations: conventional pick-up was performed in the control group, and definitive digital impressions were carried out in the test group. The time involved following these two procedures was recorded. Patients underwent intraoral digital radiographs to evaluate the accuracy of the framework-implant connection, check for the presence of voids at the bar-implant connection and measure bone level. Criteria used to assess success at the prosthetic level were the occurrence of prosthetic maintenance, the absence of fractures of the acrylic resin superstructure and voids. Results: A total of 50 patients received immediately loaded prostheses supported by six implants (total 300 implants). A fixture and prosthetic survival rate of 100% was observed. All digital X-ray examinations revealed a bar-implant connection accuracy and no voids. Differences that were not statistically significant (p > 0.05) in marginal bone loss were found between control and test groups. Significantly less time was spent to perform digital impression procedure (p < 0.05). Conclusions: Clinical and radiological results of the test group advocate a satisfactory accuracy and predictability of the intraoral scanner (IOS) to be a reliable alternative in clinical practice for implant full-arch rehabilitations and suggest fabrication of definitive restorations with a successful marginal fit precision.

The hypothesis was tested that isoprenoids and phenylpropanoids play a prominent role in countering photooxidative stress, following the depletion of antioxidant enzyme activity in plants exposed to severe drought stress under high solar irradiance and high temperatures. Platanus × acerifolia, a high isoprene-emitting species, was drought-stressed during summer (WS) and compared with unstressed controls (WW). Water relations and photosynthetic parameters were measured under mild, moderate, and severe drought stress conditions. Volatile and nonvolatile isoprenoids, antioxidant enzymes, and phenylpropanoids were measured with the same time course, but in four different periods of the day. Drought severely inhibited photosynthesis, whereas it did not markedly affect the photochemical machinery. Isoprene emission and zeaxanthin concentration were higher in WS than in WW leaves, particularly at mild and moderate stresses, and during the hottest hours of the day. The activities of catalase and ascorbate peroxidase steeply declined during the day, while the activity of guaiacol peroxidase and the concentration of quercetin increased during the day, peaking in the hottest hours in both WW and WS plants. Our experiment reveals a sequence of antioxidants that were used daily by plants to orchestrate defense against oxidative stress induced by drought and associated high light and high temperature. Secondary metabolites seem valuable complements of antioxidant enzymes to counter oxidative stress during the hottest daily hours.

Mediterranean plants biosynthesize high amounts of polyphenols, which are important health-promoting compounds. Leaf polyphenolic composition changes according to environmental conditions. Therefore, it is crucial to know the temporal variation in their production. This study aimed to: i) evaluate the monthly and daily changes in polyphenols of Phyllirea latifolia, Cistus incanus, and Pistacia lentiscus to identify their best harvesting moment, ii) verify the possible correlations between phenolic production and temperature and irradiation, iii) evaluate their antioxidant capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical (OH)scavenging assays. The extracts of leaves harvested at 8:00, 13:00 and 18:00, in May, July, and October for two years were analysed by HPLC-DAD. Both “month” and “time of the day” affected the polyphenolic content in all species. July at 13:00 was the best harvesting moment for all polyphenolic classes of P. latifolia and only for some classes of C. incanus and P. lentiscus. Environmental parameters positively correlated with the polyphenols of C. incanus and P. latifolia, while the antioxidant capacity only varied in this last species, reaching the highest value in July. Results of the study allow to determine the balsamic time for each species. Moreover, the relationship between polyphenols and environmental data can be useful for the cultivation of these plants under controlled conditions.

The aim of this in vitro study was to compare the quality of digital workflows generated by different scanners (Intra-oral digital scanners (I.O.S.s)) focusing on marginal fit analysis. A customized chrome-cobalt (Cr-Co) implant abutment simulating a maxillary right first molar was fixed in hemi-maxillary stone model and scanned by eight different I.O.S.s: Omnicam® (Denstply Sirona, Verona, Italy) CS3500®, CS3600®, (Carestream Dental, Atlanta, GA, USA), True Definition Scanner® (3M, St. Paul, MN, USA), DWIO® (Dental Wings, Montreal, Quebec, Canada), PlanScan® (Planmeca Oy, Helsinki, Finland), 3D PROGRESS Plus® (MHT, Verona, Italy), TRIOS 3® (3Shape, Copenhagen, Denmark). Nine scans were performed by each tested I.O.S. and 72 copings were designed using a dental computer-assisted-design/computer-assisted-manufacturing (CAD/CAM) software (exocad GmbH, Darmstadt, Germany). According to CAD data, zirconium dioxide (ZrO2) copings were digitally milled (Roland DWX-50, Irvine, CA, USA). Scanning electron microscope (SEM) direct vision allowed for marginal gap measurements in eight points for each specimen. Descriptive analysis was performed using mean, standard deviation, and median, while the Kruskal–Wallis test was performed to determine whether the marginal discrepancies were significantly different between each group (significance level p < 0.05). The overall mean marginal gap value and standard deviation were 53.45 ± 30.52 μm. The minimum mean value (40.04 ± 18.90 μm) was recorded by PlanScan®, then 3D PROGRESS Plus® (40.20 ± 21.91 μm), True Definition Scanner® (40.82 ± 26.19 μm), CS3500® (54.82 ± 28.86 μm) CS3600® (59,67 ± 28.72 μm), Omnicam® (61.57 ± 38.59 μm), DWIO® (62.49 ± 31.54 μm), while the maximum mean value (67.95 ± 30.41 μm) was recorded by TRIOS 3®. The Kruskal–Wallis tests revealed a statistically significant difference (p-value < 0.5) in the mean marginal gaps between copings produced by 3D PROGRESS Plus®, PlanScan, True Definition Scanner, and the other evaluated I.O.S.s. The use of an I.O.S. for digital impressions may be a viable alternative to analog techniques. Although in this in vitro study PlanScan®, 3D PROGRESS Plus® and True Definition Scanner® may have showed the best performances, all I.O.S.s tested could provide clinically encouraging results especially in terms of marginal accuracy, since mean marginal gap values were all within the clinically acceptable threshold of 120 μm.

Treatment of pain with morphine leads to paradoxical hyperalgesia. The authors provide evidence that morphine-induced hyperalgesia is a result of downregulation of the chloride transporter KCC2 in spinal lamina I neurons. Microglial expression of P2X4 receptors and release of BDNF may underlie this change in neuronal chloride homeostasis and morphine-induced hyperalgesia. A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K + -Cl − co-transporter KCC2, impairing Cl − homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor–dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signaling preserved Cl − homeostasis and reversed the hyperalgesia. Gene-targeted mice in which Bdnf was deleted from microglia did not develop hyperalgesia to morphine. However, neither morphine antinociception nor tolerance was affected in these mice. Our findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalgesia without affecting morphine analgesia.

In recent years, the proliferation of unmanned aerial vehicles (UAVs) has increased dramatically. UAVs can accomplish complex or dangerous tasks in a reliable and cost-effective way but are still limited by power consumption problems, which pose serious constraints on the flight duration and completion of energy-demanding tasks. The possibility of providing UAVs with advanced decision-making capabilities in an energy-effective way would be extremely beneficial. In this paper, we propose a practical solution to this problem that exploits deep learning on the edge. The developed system integrates an OpenMV microcontroller into a DJI Tello Micro Aerial Vehicle (MAV). The microcontroller hosts a set of machine learning-enabled inference tools that cooperate to control the navigation of the drone and complete a given mission objective. The goal of this approach is to leverage the new opportunistic features of TinyML through OpenMV including offline inference, low latency, energy efficiency, and data security. The approach is successfully validated on a practical application consisting of the onboard detection of people wearing protection masks in a crowded environment.

The functional reasons for isoprene emission are still a matter of hot debate. It was hypothesized that isoprene biosynthesis evolved as an ancestral mechanism in plants adapted to high water availability, to cope with transient and recurrent oxidative stresses during their water-to-land transition. There is a tight association between isoprene emission and species hygrophily, suggesting that isoprene emission may be a favorable trait to cope with occasional exposure to stresses in mesic environments. The suite of morpho-anatomical traits does not allow a conservative water use in hygrophilic mesophytes challenged by the environmental pressures imposed or exacerbated by drought and heat stress. There is evidence that in stressed plants the biosynthesis of isoprene is uncoupled from photosynthesis. Because the biosynthesis of isoprene is costly, the great investment of carbon and energy into isoprene must have relevant functional reasons. Isoprene is effective in preserving the integrity of thylakoid membranes, not only through direct interaction with their lipid acyl chains, but also by up-regulating proteins associated with photosynthetic complexes and enhancing the biosynthesis of relevant membrane components, such as mono- and di-galactosyl-diacyl glycerols and unsaturated fatty acids. Isoprene may additionally protect photosynthetic membranes by scavenging reactive oxygen species. Here we explore the mode of actions and the potential significance of isoprene in the response of hygrophilic plants when challenged by severe stress conditions associated to rapid climate change in temperate climates, with special emphasis to the concomitant effect of drought and heat. We suggest that isoprene emission may be not a good estimate for its biosynthesis and concentration in severely droughted leaves, being the internal concentration of isoprene the important trait for stress protection.

Diabetes is a chronic and progressive disease associated with high blood glucose levels. Several co-morbidities arise from diabetes, the most common and severe one is diabetic neuropathy whose symptoms also include pain hypersensitivity. Currently, there are no effective therapies to counteract painful diabetic neuropathy or slow down the progression of the disease, and the underlying mechanisms are yet to be fully understood. Emerging data in recent decades have provided compelling evidence that the molecular and cellular mechanisms underlying chronic pain are different across the sexes. Interestingly, relevant differences have also been observed in the course and clinical presentation of painful diabetic neuropathy in humans. Here, we reviewed the current state of the art on sex differences in diabetic neuropathy, from animal models to clinical data. Comparing the output of both preclinical and clinical studies is necessary for properly orienting future choices in pain research, refining animal models, and interpreting clinical data. The identification of sex-specific mechanisms may help to develop more targeted therapies to counteract pain symptoms in diabetes.

Spinal disinhibition has been hypothesized to underlie pain hypersensitivity in neuropathic pain. Apparently contradictory mechanisms have been reported, raising questions on the best target to produce analgesia. Here, we show that nerve injury is associated with a reduction in the number of inhibitory synapses in the spinal dorsal horn. Paradoxically, this is accompanied by a BDNF-TrkB-mediated upregulation of synaptic GABA A Rs and by an α1-to-α2GABA A R subunit switch, providing a mechanistic rationale for the analgesic action of the α2,3GABA A R benzodiazepine-site ligand L838,417 after nerve injury. Yet, we demonstrate that impaired Cl -  extrusion underlies the failure of L838,417 to induce analgesia at high doses due to a resulting collapse in Cl -  gradient, dramatically limiting the benzodiazepine therapeutic window. In turn, enhancing KCC2 activity not only potentiated L838,417-induced analgesia, it rescued its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABA A R-subtypes and restoring Cl -  homeostasis. Disinhibition in the dorsal horn of the spinal cord may contribute to chronic pain. Here the authors show that, despite a paradoxical increase in α2/α3 subunits of the GABA A receptor in a neuropathic pain model, inhibition eventually fails due to KCC2 hypofunction.