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Abstract Parkinson’s Disease (PD) exhibits heterogeneous cognitive deficits that may represent different cognitive phenotypes. While previous studies have described them in a “macro” manner, only one study has applied Network Analysis (NA) in PD. NA represents a model to explore relationships between cognitive abilities, aiding in understanding cognitive phenotypes. This study aims to verify whether the cognitive system undergoes reorganization in PD with Mild Cognitive Impairment (PD-MCI) patients. To explore this, a Level II cognitive assessment was administered to 275 PD patients, who were classified into two diagnostic categories: PD-Cognitive Unimpaired (CU) (n = 171) and PD-MCI (n = 104). NA was applied to construct Gaussian Graphical Models for each diagnostic group, where nodes represent cognitive tests and demographic factors, and edges represent their interconnections. The NA revealed substantial differences between the cognitive networks of PD-CU and PD-MCI patients. Specifically, the network of PD-MCI patients appears less sparse, with some weakened relationships between nodes. Overall, the results support the presence of a cognitive reorganization in PD-MCI patients, potentially indicating a functional compensation mechanism. In conclusion, this study enhances the understanding of the cognitive mechanisms underlying cognitive decline in patients with PD.

Abstract A major goal in synthetic development is to build gene regulatory circuits that control patterning. In natural development, an interplay between mechanical and chemical communication shapes the dynamics of multicellular gene regulatory circuits. For synthetic circuits, how non-genetic properties of the growth environment impact circuit behavior remains poorly explored. Here, we first describe an occurrence of mechano-chemical coupling in synthetic Notch (synNotch) patterning circuits: high cell density decreases synNotch-gated gene expression in different cellular systems in vitro. We then construct, both in vitro and in silico, a synNotch-based signal propagation circuit whose outcome can be regulated by cell density. Spatial and temporal patterning outcomes of this circuit can be predicted and controlled via modulation of cell proliferation, initial cell density, and/or spatial distribution of cell density. Our work demonstrates that synthetic patterning circuit outcome can be controlled via cellular growth, providing a means for programming multicellular circuit patterning outcomes.

Abstract Background Opicapone is a third-generation catechol-O-methyl-transferase inhibitor currently used for the treatment of motor fluctuations in Parkinson’s disease. Its benefit and safety have been established by clinical trials; however, data about its use in a real-life context, and particularly in an Italian population of patients with Parkinson’s disease, are missing. Objectives We aimed to gather data about the real-life tolerability/safety of opicapone when used for the treatment of Parkinson’s disease-related motor fluctuations. Methods We enrolled 152 consecutive patients with Parkinson’s disease and followed them for 2 years after opicapone introduction. We obtained baseline clinical and demographical information, including disease duration, stage, phenotype, as well as axial and non-motor symptoms. We collected the reasons for any treatment interruption and adverse events emerging after opicapone introduction. Results Eighty-nine (58%) patients reported adverse events and 46 (30%) patients discontinued the treatment. Adverse events occurred less frequently in “earlier” patients accordingly to the disease course and l-Dopa treatment pathway; a motor fluctuation duration ≥12 months and Hoehn and Yahr scale score ≥2.5 were the main predictors of therapy withdrawal. Conclusions This study confirms the good tolerability/safety profile of opicapone in a real-life setting and provides country-specific data for Italian patients with Parkinson’s disease.

In the microalgae harvesting process, which includes a step for dewatering the algal suspension, directly reusing extracted water in situ would decrease the freshwater footprint of cultivation systems. Among various algae harvesting techniques, membrane-based filtration has shown numerous advantages. This study evaluated the reuse of permeate streams derived from Scenedesmus obliquus (S. obliquus) biomass filtration under bench-scale and pilot-scale conditions. In particular, this study identified a series of challenges and mechanisms that influence the water reuse potential and the robustness of the membrane harvesting system. In a preliminary phase of this investigation, the health status of the initial biomass was found to have important implications for the harvesting performance and quality of the permeate stream to be reused; healthy biomass ensured better dewatering performance (i.e., higher water fluxes) and higher quality of the permeate water streams. A series of bench-scale filtration experiments with different combinations of cross-flow velocity and pressure values were performed to identify the operative conditions that would maximize water productivity. The selected conditions, 2.4 m·s−1 and 1.4 bar (1 bar = 105 Pa), respectively, were then applied to drive pilot-scale microfiltration tests to reuse the collected permeate as a new cultivation medium for S. obliquus growth in a pilot-scale photobioreactor. The investigation revealed key differences between the behavior of the membrane systems at the two scales (bench and pilot). It indicated the potential for beneficial reuse of the permeate stream as the pilot-scale experiments ensured high harvesting performance and growth rates of biomass in permeate water that were highly similar to those recorded in the ideal cultivation medium. Finally, different nutrient reintegration protocols were investigated, revealing that both macro- and micro-nutrient levels are critical for the success of the reuse approach.

Abstract Background Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. Main body Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ (“A”), tau (“T”), and neurodegeneration (“N”), by incorporating a novel inflammatory component (“I”). Conclusions The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.

Abstract Background Globally, non-fatal overdose (NFOD) rates consequent to drug use, typically opioids, continue increasing at a startling rate. Existing quantitative research has revealed myriad factors and characteristics linked to experiencing NFOD, but it is critically important to explore the lived context underlying these associations. In this qualitative study, we sought to understand the experiences of NFOD among people who use drugs in a Scottish region in order to: enhance public policy responses; inform potential intervention development to mitigate risk; and contribute to the literature documenting the lived experience of NFOD. Methods From June to July 2021, two peer researchers conducted face-to-face semi-structured interviews with people who use drugs who had experienced recent NFOD attending harm reduction services in Tayside, Scotland. These were transcribed verbatim and evaluated using thematic analysis with an inductive approach which had an experiential and essentialist orientation. Results Twenty people were interviewed across two sites. Of those, 15 (75%) were male and mean age was 38.2 (7.7) years. All had experienced at least one NFOD in the prior six months, and all reported polydrug use. Five themes were identified, within which 12 subthemes were situated. The themes were: social context; personal risk-taking triggers; planned and impulsive consumption; risk perception; and overdose reversal. The results spoke to the environmental, behavioural, cognitive, economic, and marketplace, factors which influence the context of NFOD in the region. Conclusions A complex interplay of behavioural, psychological, and situational factors were found to impact the likelihood of experiencing NFOD. Structural inequities which policy professionals and civic leaders should seek to remedy were identified, while service providers may seek to reconfigure healthcare provision for people who use drugs to account for the interpersonal, psychological, and social factors identified, which appear to precipitate NFOD. Trial registration Not applicable.

Abstract Pharmacological treatments in Parkinson’s disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease’s progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.

Abstract Background and aims Psychological and social status, and environmental context, may mediate the likelihood of experiencing overdose subsequent to illicit drug use. The aim of this systematic review was to identify and synthesise psychosocial factors associated with overdose among people who use drugs. Methods This review was registered on Prospero (CRD42021242495). Systematic record searches were undertaken in databases of peer-reviewed literature (Medline, Embase, PsycINFO, and Cinahl) and grey literature sources (Google Scholar) for work published up to and including 14 February 2023. Reference lists of selected full-text papers were searched for additional records. Studies were eligible if they included people who use drugs with a focus on relationships between psychosocial factors and overdose subsequent to illicit drug use. Results were tabulated and narratively synthesised. Results Twenty-six studies were included in the review, with 150,625 participants: of those 3,383–4072 (3%) experienced overdose. Twenty-one (81%) studies were conducted in North America and 23 (89%) reported polydrug use. Psychosocial factors associated with risk of overdose (n = 103) were identified and thematically organised into ten groups. These were: income; housing instability; incarceration; traumatic experiences; overdose risk perception and past experience; healthcare experiences; perception of own drug use and injecting skills; injecting setting; conditions with physical environment; and social network traits. Conclusions Global rates of overdose continue to increase, and many guidelines recommend psychosocial interventions for dependent drug use. The factors identified here provide useful targets for practitioners to focus on at the individual level, but many identified will require wider policy changes to affect positive change. Future research should seek to develop and trial interventions targeting factors identified, whilst advocacy for key policy reforms to reduce harm must continue.

ABSTRACT Objectives: to construct and validate the content of a checklist for the management of totally implanted catheters in hospitalized children and adolescents. Methods: methodological research conducted from October 2021 to December 2022 in two stages: development of the instrument with care guidelines and content validation of the checklist. The instrument, containing 23 items presented in Likert format, was evaluated online by specialists in two rounds. The Content Validity Index was applied, considering indices above 0.8 as valid. Results: the final checklist included four domains and 22 checklist items, validated with a Content Validity Index of 0.98. The overall evaluation of the instrument presented a global score of 9.9. Conclusions: the validation and application of instruments that standardize procedures, in addition to supporting professionals, promote autonomy and quality of care for children and adolescents using this device.

Resumo O número de Indicações Geográficas (IG) reconhecidas por entidades governamentais ou privadas em países com economias emergentes tem aumentado muito. Este aumento é acompanhado por evidências de que proporção significativa de IGs não atinge os objetivos de contribuir para o desenvolvimento regional e local. Para que as IGs se tornem ativas no mercado, é necessário que as necessidades e expectativas dos grupos de partes interessadas, stakeholders, tenham suas necessidades e expectativas atendidas. Este artigo realiza revisão sistemática da literatura (RSL) para identificar os fatores que a pesquisa acadêmica aponta como causas do não desenvolvimento das IGs e os analisa sob a perspectiva da Teoria do Engajamento de Stakeholders. Realizamos análise de conteúdo de 29 artigos publicados entre 2017 e 2022 sobre fatores que limitam o desenvolvimento das IGs. A RSL identifica 13 fatores agrupados em três categorias como causas. A investigação contribui para a literatura sobre o desenvolvimento das IGs identificando fatores que limitam o seu desenvolvimento e analisando esses fatores na perspectiva do envolvimento dos stakeholders. Fornece uma base conceptual para diagnosticar as razões para o não envolvimento dos stakeholders nas IGs.

Abstract The rising demand for sustainable wastewater management and high-value resource recovery is pressing industries involved in, e.g., textiles, metals, and food production, to adopt energy-efficient and flexible liquid separation methods. The current techniques often fall short in achieving zero liquid discharge and enhancing socio-economic growth sustainably. Osmotic membrane distillation (OMD) has emerged as a low-temperature separation process designed to concentrate valuable elements and substances in dilute feed streams. The efficacy of OMD hinges on the solvent’s migration from the feed to the draw stream through a hydrophobic membrane, driven by the vapor pressure difference induced by both temperature and concentration gradients. However, the intricate interplay of heat and mass processes steering this mechanism is not yet fully comprehended or accurately modeled. In this research, we conducted a combined theoretical and experimental study to explore the capabilities and thermodynamic limitations of OMD. Under diverse operating conditions, the experimental campaign aimed to corroborate our theoretical assertions. We derived a novel equation to govern water flux based on foundational principles and introduced a streamlined version for more straightforward application. Our findings spotlight complex transport-limiting and self-adjusting mechanisms linked with temperature and concentration polarization phenomena. Compared with traditional methods like membrane distillation and osmotic dilution, which are driven by solely temperature or concentration gradients, OMD may provide improved and flexible performance in target applications. For instance, we show that OMD—if properly optimized—can achieve water vapor fluxes 50% higher than osmotic dilution. Notably, OMD operation at reduced feed temperatures can lead to energy savings ranging between 5 and 95%, owing to the use of highly concentrated draw solutions. This study underscores the potential of OMD in real-world applications, such as concentrating lithium in wastewater streams. By enhancing our fundamental understanding of OMD’s potential and constraints, we aim to broaden its adoption as a pivotal liquid separation tool, with focus on sustainable resource recovery.

The Norwegian Transparency Act imposes on businesses to respect human rights and ensure decent working conditions, as well as a duty to carry out due diligence in accordance with the OECD Guidelines for Multinational Enterprises. Countries adhering to the Guidelines are required to set up National Contact Points (NCPs), which are tasked with furthering the effectiveness of the Guidelines and to offer a grievance mechanism to resolve cases relating to non-observance of the Guidelines. Since the fundamental human rights and decent working conditions referred to by the Transparency Act are expansive concepts directly deriving from international standards, the evolution of the Guidelines through the concrete interpretation by the NCPs plays a role in the implementation of the Act itself. This contribution examines the implementation by NCPs of some of the core elements of the Guidelines, including which are the relevant stakeholders whose interests are protected in concrete cases, the responsibility of companies for their direct and indirect suppliers, and the coverage of the Guidelines also of minority shareholders and financial investors, which have no direct control of the actions of a business entity. The NCPsʼ implementation of international standards might thus have an impact on the general categories of domestic legislation and will thus affect—even if indirectly—the general understanding of respect for sustainability standards in domestic systems.

Volcanic hazard assessment is generally based on past eruptive behavior, assuming that previous activity is representative of future activity. Hazard assessment can be supported by Artificial Intelligence (AI) techniques, such as machine learning, which are used for data exploration to identify features of interest in the data. Here, we applied a machine learning technique to automate the analysis of these datasets, handling intricate patterns that are not easily captured by explicit commands. Using the k-means clustering algorithm, we classified effusive eruptions of Mount Etna over the past 400 years based on key parameters, including lava volume, Mean Output Rate (MOR), and eruption duration. Our analysis identified six distinct eruption clusters, each characterized by unique eruption dynamics. Furthermore, spatial analysis revealed significant sectoral variations in eruption activity across Etna’s flanks. These findings, derived through unsupervised learning, offer new insights into Etna’s eruptive behavior and contribute to the development of hazard maps that are essential for long-term spatial planning and risk mitigation.

This paper presents the conceptual underpinnings organized by a group of designers and design researchers for the creation of the Ecotopias Socioenvironmental Design Laboratory at PUC-Rio University. It begins by discussing the anthropogenic crisis, which the planet is currently facing, and the consequent design crisis. It also presents the field of design for sustainability, its transversality and eco-logic possibilities. It situates the process of constructing scenarios in this field as a methodological option for opening the imaginative and anticipatory potential of art and design to confront the planetary environmental crises and regenerate ecologies of the mind, social relations, and the environment. It describes the methodological steps of the scenario-building process derived from the project Sustainable Everyday, and, finally, it distinguishes the concepts of utopia and ecotopia.

Environmental degradation and global social inequality require an education focused on transforming values and practices in today's world. Bamboo, both as a plant and a material, has mitigated the impacts of climate change. Combined with design within a bamboo productive chain, it also enhances the possibility of a pedagogical dimension for design students and the participation of local communities. This study aims to examine how social design can collaborate in education for sustainability, involving the researcher’s participant observation and co-creation, which resulted in the Take Akari Bamboo Lantern Workshop, held at the Unesp Campus in Bauru/SP. Results show that social design combined with bamboo helps in motivating people to internalize and carry out new practices due to the collaborative and collective ways of working collectively based on which it was held, and is capable of transforming scenarios and changing beliefs and values.

ABSTRACT Fatigue is one of the most prevalent symptoms in individuals with Chronic Obstructive Pulmonary Disease (COPD), but it is poorly evaluated. The Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) is one of the main instruments used to measure fatigue. However, this instrument has not yet been validated for the Brazilian population with COPD. This study aimed to investigate the validity of the FACIT-F fatigue scale in individuals with COPD. In a cross-sectional study, the impact of symptoms (COPD Assessment Test - CAT), dyspnea (modified Medical Research Council - MRC scale), functional capacity (six-minute step test - 6MST), exertional fatigue (Borg modified scale at the end of 6MST), and the FACIT-F scale to assess multidimensional fatigue were evaluated. Concurrent validity was assessed by associating the FACIT-F with the CAT, and convergent validity by associating it with the number of steps, perceived exertional fatigue, and dyspnea. Discriminant validity was assessed by comparing fatigue with the dyspnea severity strata. In total, 92 participants were studied (69.9±8.8 years, FEV1: 48.4% of predicted). The FACIT-F presented an average of 30.1±10.9 points, strong concurrent validity with the CAT (r=-0.80), strong convergent validity with dyspnea (r=−0.66), and low with exercise capacity (r=0.40) and fatigue on exertion (r=-0.44). FACIT-F was effective in discriminating groups with different intensities of dyspnea. Conclusion: The FACIT-F is a valid tool for assessing fatigue in the Brazilian population with COPD.

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration.

Abstract The development of membranes and membrane-based separation processes should be accompanied by a standardization of the protocols applied for membrane characterization and for data analysis. Here, streamlined equations for the estimation of the water flux and of the observed salt permeability coefficient in pressure-driven processes deploying dense membranes are presented. Also, a protocol for the experimental characterization of the transport properties of dense membranes is presented and the results are validated against the proposed equations. The proposed water flux equation is algebraic, whereas the ordinary equation needs to be solved iteratively. Moreover, in contrast to the traditional expression for the solute transport coefficient, which requires estimation of the concentration polarization, the respective equation proposed in this study only requires bulk parameters. Dimensionless variables for water flux, driving pressure, and mass transfer are introduced, and a filtration efficiency is defined, a useful parameter in terms of process design.

BackgroundIndividuals with chronic obstructive pulmonary disease (COPD) exhibit reduced levels of physical activity, which are associated with poorer outcomes. The number of clinical trials aiming to promote behavioral changes to increase physical activity in this population has grown; therefore, these trials have yet to produce satisfactory results. An ecological model encompassing individual, social, environmental, and political factors represent a potentially more effective approach to promoting physical activity. While favorable urban environments can positively impact physical activity, specifically tailored environmental interventions for individuals with COPD could enhance their engagement in physical activity. Therefore, the aim of this randomized controlled trial (RCT) study was to analyze the effects of walking in a suggested environment and free walking on physical activity levels in individuals with COPD.MethodsThe environment on physical activity for chronic obstructive disease (EPCOT) is a randomized controlled clinical trial protocol approved by our institution's Ethics Committee and registered with The Brazilian Registry of Clinical Trials (ReBEC) (https://ensaiosclinicos.gov.br, number RBR-4tfwdhp). This protocol will involve 38 volunteers diagnosed with COPD recruited from the pulmonary physiotherapy and rehabilitation service. The volunteers were randomly divided into two walking groups: an experimental group (ERG) with guidance for walking in a suggested environment and an active control group (ACG) instructed to choose their own routes. The intervention consisted of eight consecutive weeks, with progressive walks carried out 3 to 5 times weekly. The primary outcome will be assessing participants' physical activity levels. Secondary outcomes will include exercise capacity, quality of life, dyspnea levels, motivation, anxiety, depression, and perceptions of the environment. All assessments will occur before and after the intervention period, aiming to fill a literature gap by investigating the impact of urban environments on COPD-related physical activity. The results may shed light on the importance of environmental factors in promoting physical activity among individuals with COPD, helping to develop more effective interventions.

Abstract Prolonged human-crewed missions on the Moon are foreseen as a gateway for Mars and asteroid colonisation in the next decades. Health risks related to long-time permanence in space have been partially investigated. Hazards due to airborne biological contaminants represent a relevant problem in space missions. A possible way to perform pathogens’ inactivation is by employing the shortest wavelength range of Solar ultraviolet radiation, the so-called germicidal range. On Earth, it is totally absorbed by the atmosphere and does not reach the surface. In space, such Ultraviolet solar component is present and effective germicidal irradiation for airborne pathogens’ inactivation can be achieved inside habitable outposts through a combination of highly reflective internal coating and optimised geometry of the air ducts. The Solar Ultraviolet Light Collector for Germicidal Irradiation on the Moon is a project whose aim is to collect Ultraviolet solar radiation and use it as a source to disinfect the re-circulating air of the human outposts. The most favourable positions where to place these collectors are over the peaks at the Moon’s poles, which have the peculiarity of being exposed to solar radiation most of the time. On August 2022, NASA communicated to have identified 13 candidate landing regions near the lunar South Pole for Artemis missions. Another advantage of the Moon is its low inclination to the ecliptic, which maintains the Sun’s apparent altitude inside a reduced angular range. For this reason, Ultraviolet solar radiation can be collected through a simplified Sun’s tracking collector or even a static collector and used to disinfect the recycled air. Fluid-dynamic and optical simulations have been performed to support the proposed idea. The expected inactivation rates for some airborne pathogens, either common or found on the International Space Station, are reported and compared with the proposed device efficiency. The results show that it is possible to use Ultraviolet solar radiation directly for air disinfection inside the lunar outposts and deliver a healthy living environment to the astronauts.