Search Results (9)

Background/Objectives: Leishmaniasis is a neglected tropical disease caused by a protozoan parasite of Leishmania. This study aimed to evaluate the in vitro efficacy and toxicity of a previously developed amphotericin gel as a possible treatment for cutaneous leishmaniasis. Methods: First, quality control of the AmB-gel was carried out, including microbiological stability. The permeated and retained drug was tested on healthy and lacerated human skin. Tolerance to the AmB-gel was tested in vitro using HaCaT, RAW 264.7, and J774 cell lines and by an irritation test (HET-CAM). Promastigotes and amastigotes of various Leishmania species were tested, and the microscopic morphology of promastigotes exposed to the formulation was analyzed. Computational analysis was performed on the drug, polymer, and ergosterol in the promastigote. Results: The AmB-gel presented appropriate characteristics for topical use, including no microbial contamination after storage. The amount of drug retained on the intact and injured skin was 1180.00 ± 13.54 µg/g/cm² and 750.18 ± 5.43 µg/g/cm², respectively. The AmB-gel did not cause significant signs of toxicity. The IC₅₀ of the AmB-gel for promastigotes was less than 1 µg/mL for the four species examined, i.e., Leishmania infantum, Leishmania tropica, Leishmania major, and Leishmania braziliensis, and less than 2 µg/mL for amastigotes of Leishmania infantum and Leishmania tropica. The AmB-gel caused notable effects on the surface of promastigotes. Computational analysis revealed primarily hydrophobic and van der Waals interactions between AmB and Pluronic^® F127 and ergosterol. Conclusions: Based on the drug retention content and IC₅₀ values observed for both parasite stages, the AmB-gel may be a promising candidate for in vivo studies in patients with cutaneous leishmaniasis. Full article

Mindfulness-Based Stress Reduction (MBSR) has not yet been evaluated for people with cerebral palsy (CP). The aims of this randomised control trial were to investigate whether a modified telehealth MBSR program could improve mindfulness and reduce depression, anxiety, and emotion regulation difficulties among adults with CP with elevated anxiety and/or emotional regulation difficulties. Participants (n = 31) with elevated anxiety and/or emotion regulation difficulties and no/mild intellectual impairment were randomised to a modified telehealth MBSR program (90 min weekly, 9 weeks) group or a wait-list group. Measurements were collected prior to (T1), after (T2), and 8 weeks post-intervention (T3). The primary outcome was the mean between-group difference in the change in Cognitive and Affective Mindfulness Scale-R (CAMS-R) scores in T1–T2. The secondary outcomes included mean within-group differences over time for the CAMS-R total scores, Depression Anxiety and Stress Scale—21 subscales, and Difficulties in Emotion Regulation Scale (DERS) total t-score. We found no statistically significant between-group difference in mean change in mindfulness scores for T1–T2 (primary outcome). Secondary outcomes: The MBSR intervention group had improved CAMS-R scores with respect to T1–T2 and T1–T3; improved mean scores for Depression and Stress subscales for T1–T2; and improved DERS t-scores for T1–T2 and T1–T3. In conclusion, this study found no significant between-group difference for the primary outcome of mindfulness. The MBSR program was successfully modified for adults with CP and was effective in improving depression, stress, and emotion regulation. ACTRN12621000960853 Full article

Although individual rare disorders are uncommon, it is estimated that, together, 6000+ known rare diseases affect more than 30 million people in Europe, and present a substantial public health burden. Together with the psychosocial burden on affected families, rare disorders frequently, if untreated, result in a low quality of life, disability and even premature death. Newborn screening (NBS) has the potential to detect a number of rare conditions in asymptomatic children, providing the possibility of early treatment and a significantly improved long-term outcome. Despite these clear benefits, the availability and conduct of NBS programmes varies considerably across Europe and, with the increasing potential of genomic testing, it is likely that these differences may become even more pronounced. To help improve the equity of provision of NBS and ensure that all children can be offered high-quality screening regardless of race, nationality and socio-economic status, a technical meeting, endorsed by the Slovenian Presidency of the Council of the European Union, was held in October 2021. In this article, we present experiences from individual EU countries, stakeholder initiatives and the meeting’s final conclusions, which can help countries attempting to establish new NBS programmes or expand existing provision. Full article

Chloramphenicol (CHL) is a ribosome-targeting antibiotic that binds to the peptidyl transferase center (PTC) of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving the properties of this inhibitor, we explored ribosome binding and inhibitory properties of a semi-synthetic triphenylphosphonium analog of CHL—CAM-C4-TPP. Our data demonstrate that this compound exhibits a ~5-fold stronger affinity for the bacterial ribosome and higher potency as an in vitro protein synthesis inhibitor compared to CHL. The X-ray crystal structure of the Thermus thermophilus 70S ribosome in complex with CAM-C4-TPP reveals that, while its amphenicol moiety binds at the PTC in a fashion identical to CHL, the C4-TPP tail adopts an extended propeller-like conformation within the ribosome exit tunnel where it establishes multiple hydrophobic Van der Waals interactions with the rRNA. The synthesized compound represents a promising chemical scaffold for further development by medicinal chemists because it simultaneously targets the two key functional centers of the bacterial ribosome—PTC and peptide exit tunnel. Full article

Mixed Integer Linear Programming (MILP) optimization algorithms provide accurate and clear solutions for Microgrid and Distributed Energy Resources projects. Full-scale optimization approaches optimize all time-steps of data sets (e.g., 8760 time-step and higher resolutions), incurring extreme and unpredictable run-times, often prohibiting such approaches for effective Microgrid designs. To reduce run-times down-sampling approaches exist. Given that the literature evaluates the full-scale and down-sampling approaches only for limited numbers of case studies, there is a lack of a more comprehensive study involving multiple Microgrids. This paper closes this gap by comparing results and run-times of a full-scale 8760 h time-series MILP to a peak preserving day-type MILP for 13 real Microgrid projects. The day-type approach reduces the computational time between 85% and almost 100% (from 2 h computational time to less than 1 min). At the same time the day-type approach keeps the objective function (OF) differences below 1.5% for 77% of the Microgrids. The other cases show OF differences between 6% and 13%, which can be reduced to 1.5% or less by applying a two-stage hybrid approach that designs the Microgrid based on down-sampled data and then performs a full-scale dispatch algorithm. This two stage approach results in 20–99% run-time savings. Full article

This paper investigates the effect of selected strategies of distributed energy resources (DER) on an energy cost function that optimizes the distribution of distributed energy resources for a mid-rise apartment building. This is achieved through comparing parameter optimization results for both a high-level and low-level optimizer, respectively. The optimization process is carried out using the following approach: (1) a two-objective function is constructed with one objective function similar to that of the high-level optimizer (DER-CAM); (2) an evolutionary algorithm (EA) with modified selection capability is used to optimize the two-objective function problem in (1) for four selected cases of DER utilization that were previously optimized in DER-CAM; and (3) the optimization results of the low-level optimizer are compared with the outcome of DER-CAM optimization for the four selected cases. This is done to establish the capability of DER-CAM as an effective tool for optimal distributed energy resource allocation. Results obtained reveal the effect of load shifting and solar photovoltaic (PV) panels with power exporting capability on the optimization of the cost function. The Pareto-based MOEA approach has also proved to be effective in observing the interactions between objective function parameters. Mean inverted generational distance (MIGD) values obtained over 10 runs for each of the four cases that were considered show that a DER combination of PV panel, battery storage, heat pump, and load shifting outperforms the other strategies in 70% of the total simulation runs. Full article

The possibility of replacing the existing autonomous thermal power plants by Distributed Energy Resources (DER) based on renewable energy sources (RES), along with the appropriate energy storage technologies in order to deal with the major problems that autonomous islands usually face was investigated. A case study of a small Greek island, which is confronted by various energy and water shortages, was studied for assessing the feasibility of DER deployment. The main objectives investigated were cost minimization, CO₂ emissions minimization and DER reliability maximization. The DER-CAM (Distributed Energy Resources Customer Adoption Model) decision support tool was used for the multi-objective analysis conducted, which proposes a set of optimal solutions defining the appropriate Distributed Generation (DG) technologies, the capacities of storage and other technologies and the optimal dispatch of the DG system. A mutual beneficial solution, for all stakeholders, was proposed indicating the scope for developing such systems for all islands facing the same problems. Full article

Integrated community energy systems (ICESs) are emerging as a modern development to re-organize local energy systems allowing simultaneous integration of distributed energy resources (DERs) and engagement of local communities. Although local energy initiatives, such as ICESs are rapidly emerging due to community objectives, such as cost and emission reductions as well as resiliency, assessment and evaluation are still lacking on the value that these systems can provide both to the local communities as well as to the whole energy system. In this paper, we present a model-based framework to assess the value of ICESs for the local communities. The distributed energy resources-consumer adoption model (DER-CAM) based ICES model is used to assess the value of an ICES in the Netherlands. For the considered community size and local conditions, grid-connected ICESs are already beneficial to the alternative of solely being supplied from the grid both in terms of total energy costs and CO₂ emissions, whereas grid-defected systems, although performing very well in terms of CO₂ emission reduction, are still rather expensive. Full article