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The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 ( p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores ( p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer's test scores ( p < 0.001), whereas Group 2 did not ( p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.

Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups were compared. It is worth noting that the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs. 6.1 ± 1.3 IVTs; p = 0.0004). Therefore, TALF used as an adjuvant to RBZ reduces the need for RBZ-IVT retreatment with optimal visual and anatomic results.

Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA-loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled on the ocular surface. To evaluate the safety, tolerability, and biological activity of TALF, an animal study and a phase I clinical assay were performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biological activity of the formulation. No inflammation, lens opacity, swelling, or increase in intraocular pressure were recorded after the instillation of TALF in any of the animal or clinical studies. Mainly, mild and transient adverse events such as dry eye and burning were reported. TALF significantly improves visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biological activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroid IVTs and their associated hazards.

Pain has a major impact on health and quality of life. Since the level of knowledge of painful conditions can influence how these are addressed and managed, assessing this knowledge in patients becomes crucial. As a result, it is necessary to have culturally adapted and validated instruments that specifically measure patients' knowledge of chronic pain management. The objective of this study was to carry out the Spanish cultural adaptation and the validation of the outcome Knowledge: Pain M anagement of the Nursing Outcomes Classification (NOC) in patients with chronic pain, defined as extent of understanding conveyed about causes, symptoms, and treatment of pain. A three-stage study was designed: 1) translation and cultural adaptation through an expert panel, 2) content validation, 3) clinical validation. This study provides nurses with a Spanish version of this scale adapted to their context, as well as a set of structured indicators to measure patients' knowledge about chronic pain. The results indicated that the culturally adapted Spanish version of the outcome Knowledge: Pain M anagement had a high level of content validity (CVI = 0.92), with 27 indicators being distributed between two factors. This version has been shown to be reliable in terms of inter-observer agreement (κ = 0.79) and internal consistency (α = 0.95). In conclusion, Knowledge: Pain M anagement has been shown to be reliable and valid to measure knowledge of chronic pain.

As wireless sensor networks are usually deployed in unattended areas, security policies cannot be updated in a timely fashion upon identification of new attacks. This gives enough time for attackers to cause significant damage. Thus, it is of great importance to provide protection from unknown attacks. However, existing solutions are mostly concentrated on known attacks. On the other hand, mobility can make the sensor network more resilient to failures, reactive to events, and able to support disparate missions with a common set of sensors, yet the problem of security becomes more complicated. In order to address the issue of security in networks with mobile nodes, we propose a machine learning solution for anomaly detection along with the feature extraction process that tries to detect temporal and spatial inconsistencies in the sequences of sensed values and the routing paths used to forward these values to the base station. We also propose a special way to treat mobile nodes, which is the main novelty of this work. The data produced in the presence of an attacker are treated as outliers, and detected using clustering techniques. These techniques are further coupled with a reputation system, in this way isolating compromised nodes in timely fashion. The proposal exhibits good performances at detecting and confining previously unseen attacks, including the cases when mobile nodes are compromised.

The improvement of odometry systems in collaborative robotics remains an important challenge for several applications. Social odometry is a social technique which confers the robots the possibility to learn from the others. This paper analyzes social odometry and proposes and follows a methodology to improve its behavior based on cooperative reputation systems. We also provide a reference implementation that allows us to compare the performance of the proposed solution in highly dynamic environments with the performance of standard social odometry techniques. Simulation results quantitatively show the benefits of this collaborative approach that allows us to achieve better performances than social odometry.

The reliable operation of modern infrastructures depends on computerized systems and Supervisory Control and Data Acquisition (SCADA) systems, which are also based on the data obtained from sensor networks. The inherent limitations of the sensor devices make them extremely vulnerable to cyberwarfare/cyberterrorism attacks. In this paper, we propose a reputation system enhanced with distributed agents, based on unsupervised learning algorithms (self-organizing maps), in order to achieve fault tolerance and enhanced resistance to previously unknown attacks. This approach has been extensively simulated and compared with previous proposals.

Security in wireless sensor networks is difficult to achieve because of the resource limitations of the sensor nodes. We propose a trust-based decision framework for wireless sensor networks coupled with a non-deterministic routing protocol. Both provide a mechanism to effectively detect and confine common attacks, and, unlike previous approaches, allow bad reputation feedback to the network. This approach has been extensively simulated, obtaining good results, even for unrealistically complex attack scenarios.