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BACKGROUND: Various countries have instituted risk governance measures to control and minimize the risks of chemicals at the national and international levels. Activities typically include risk assessment based on a) hazard and exposure assessments; b) setting limits on the production, use, and emissions of chemicals; c) enforcement of regulations; and d) monitoring the effectiveness of the measures taken. These steps largely depend on chemical analysis and access to pure chemical reference standards. However, except for specific highly regulated categories of chemicals, such reference standards often are not commercially available. This raises a critical question: Given the widespread lack of reference standards, is the current approach to governing chemicals adequate to protect humans and the environment from harm? If not, what measures could be taken to improve the situation? OBJECTIVE: We outline how current chemical risk governance is hampered by the widespread lack of reference standards to produce the required scientific evidence. We also provide a list of recommendations for controlling chemical risks in the absence of reference standards. DISCUSSION: We use per- and polyfluoroalkyl substances (PFASs), specifically the chemical C6O4 [perfluoro ([5-methoxy-1,3-dioxolan-4-yl]oxy) acetic acid], to illustrate how companies that produce chemicals can prevent access to reference standards. We argue that the very limited availability of reference standards undermines the ability of scientists to produce independent scientific evidence needed for chemical risk governance and, thereby, prevents society from protecting people and the environment against chemical pollution and its harms. Possible ways to improve the situation include a) guaranteeing access to chemical reference standards by creating a reference standards repository, b) redefining the level of confidence sufficient for regulatory action, c) providing alternative options for chemical identification and quantification when reference standards are not available, and d) considering, when no reference standards are available, regulation of chemicals by class rather than individually. https://doi.org/10.1289/EHP12331, Introduction Risk governance describes ways that society tries to minimize exposures to chemicals, with the goal of protecting human health and the environment. It includes governmental actions-regulations, directives, limit values, [...]

Author(s): Guilherme Sawczyn (corresponding author) [1]; Caio Brambilla [1]; Gilberto Jose Rodrigues [1]; Maykon William Aparecido Pires Pereira [1]; Leonardo Cardili [2]; Paulo Afonso de Carvalho [1]; Fabio Pescarmona Gallucci [...], Purpose: This study aims to assess the impact of unclassified renal cell carcinoma (uRCC) on clinical, pathological, and oncological outcomes compared with clear cell renal cell carcinoma (ccRCC). Materials and Methods: We analyzed the data of 48 uRCC and 688 ccRCC cases, collected from a histopathological database at a single center from July 2011 to August 2019. uRCC cases were confirmed according to the 2016 World Health Organization classification. Baseline characteristics, clinical findings, and oncological outcomes were compared between the groups. Results: Patients with uRCC exhibited the same clinical symptoms as ccRCC patients, a higher prevalence of lymphadenopathy (31.2 vs. 15.8, P < 0.01), and greater sarcomatoid/rhabdoid differentiation on histology (12.5 vs. 5, P = 0.03) compared to ccRCC patients. Although there was no difference regarding overall metastasis at initial diagnosis, distant lymphadenopathy (16.7 vs. 7.8, P = 0.04) and liver metastasis (8.9 vs. 2.8, P = 0.04) were more common in the uRCC group. The two groups had similar high-grade (HG) frequency on histology (62.5 for uRCC vs. 53.7 for ccRCC, P = 0.23). The estimated recurrence-free survival at 48 months was 94.3 for uRCC, 92.5 for low-grade (LG) ccRCC (P = 0.91), and 66.5 for HG ccRCC (P < 0.01). The estimated overall survival at 48 months was 66.1 for uRCC, 87.4 for LG ccRCC (P = 0.75), and 63.4 for HG ccRCC (P < 0.01). Conclusion: Our study demonstrates that uRCC has significantly higher rates of lymphadenopathy, sarcomatoid differentiation, and liver metastasis compared to ccRCC. Despite these differences, uRCC presents with similar clinical symptoms and histological grade as ccRCC. Furthermore, uRCC exhibits a recurrence rate comparable to LG ccRCC and an overall survival rate similar to HG ccRCC.

The optimal management of cattle nutrition promotes animal health and welfare, increases livestock farms’ productivity and competitiveness, and enhances environmental sustainability practices. Animal feeding operations play a crucial role as many factors can drive the theoretical ration formulated by nutritionists far from the one the animals ingest. Precision feeding technologies (e.g., NIR sensors on the milling cutter of the chopper-mixer wagon; computer vision systems installed in the mixing tank) may allow for accurate and real-time analysis of the chemical and physical properties of total mixed ration (TMR) ingredients, reducing errors during its preparation and distribution. This work compares the physical quality and the length of the fibre of the TMR resulting from the chopping-mixing process of a conventional mixing wagon, one machine-learning-assisted mixing wagon and an automatic feeding system under actual operating conditions. Between October 2021 and November 2022, TMR sampling occurred on four dairy farms and one fattening bulls farm in Northern Italy, specifically in the Brescia, Cremona, and Mantua districts. TMR samples underwent particle size analysis using the Penn State Particle Separator (PSPS) method and, once in the laboratory, moisture analysis and fibre length measurement. Concerning TMR particle size analysis, the PSPS method revealed that the machine learning-assisted mixing wagon provided TMR with physical features comparable to that from ordinarily run mixing wagons. At the same time, the automatic feeding system resulted in TMR with finer particle size, following the farmers’ choice not to use long-stemmed forages. Regarding fibre length, only the TMR resulting from the operator-based mixing wagon aligned with the targeted fibre length of 5 cm, while the AFS and the ML-assisted mixing resulted in higher fibre lengths. Overall, the use of computer vision (CV) systems is helpful for the consistency of the TMR and represents a valuable solution for animal farming, particularly when employing low- or inexperienced operators. Further studies are, however, needed to improve the training of the with elements that can replicate the operator experience.

Abstract Stochiometric issues, encompassing both the quantity and heterogeneity of extracellular vesicles (EVs) derived from tumour or other tissues in blood, pose important challenges across various stages of biomarker discovery and detection, affecting the integrity of data, introducing losses and artifacts during blood processing, EV purification and analysis. These challenges shape the diagnostic utility of EVs especially within the framework of established and emerging methodologies. By addressing these challenges, we aim to delineate crucial parameters and requirements for tumour‐specific EV detection, or more precisely, for tumour identification via EV based assays. Our endeavour involves a comprehensive examination of the layers that mask or confound the traceability of EV markers such as nucleic acids and proteins, and focus on ‘low prevalence—low concentration’ scenario. Finally, we evaluate the advantages versus limitations of single‐particle analysers over more conventional bulk assays, suggesting that the combined use of both to capture and interpret the EV signals, in particular the EV surface displayed proteins, may ultimately provide quantitative information on their absolute abundance and distribution.

Aim To identify sleep abnormalities in individuals at clinical high risk for psychosis (CHR-P) or with schizophrenia spectrum disorders (SSDs) compared with healthy controls (HCs) using wrist actigraphy, and to assess potential differences in the direction of effect with self-reported assessments of sleep.Methods We conducted a systematic review of observational studies, with the search last updated on 29 April 2024. Primary outcome was total sleep time (TST), with secondary outcomes including time in bed (TIB), sleep latency, sleep efficiency, wake after sleep onset, nighttime awakenings and self-reported sleep quality. Random-effects pairwise meta-analyses were used to summarise the effects of each outcome.Results Nineteen studies were included, with 18 contributing to the meta-analyses (202 CHR-P, 584 SSD, 582 HC). TST results were inconclusive for CHR-P (MD −4.88 min (95% CI −20.57 to 10.81)), while SSD participants showed an increase in TST compared with HC (MD 106.13 min (86.02 to 124.24)). Factors such as antipsychotic medications (pseudo-R²=88.14%), age (38.89%) and gender (26.29%) partially explained the heterogeneity between subgroups. Additionally, CHR-P individuals exhibited reduced sleep efficiency (MD −2.04% (−3.55 to 0.53)), whereas SSD participants had increased TIB (MD 121.58 min (88.16 to 155.00)) and sleep latency (MD 13.05 min (2.11 to 24.00)). The risk-of-bias assessment ranged from some concerns to high risk.Conclusions Our analyses identified sleep abnormalities in CHR-P and SSD compared with placebo. However, observed heterogeneity and potential biases across studies may limit the interpretability of findings. These limitations underscore the need for standardised guidelines and more precise participant stratification.

Com a redução de alunos decorrente das condições macroeconômicas, as instituições Comunitárias de Ensino Superior (ICES) têm empreendido esforços para manterem seu equilíbrio econômico-financeiro. O presente estudo teve como objetivo identificar a forma como ICES participantes do Consórcio das Universidades Comunitárias Gaúchas (COMUNG) realizam sua gestão financeira de curto prazo frente ao novo cenário na educação superior. Para isso, realizaram-se entrevistas semiestruturadas com nove gestores financeiros das respectivas ICES. Realizou-se um estudo de caso múltiplo, configurando-se em uma pesquisa qualitativa, de delineamento descritivo e exploratório. Os dados foram tratados por meio da análise de conteúdo e divididos em três dimensões de pesquisa: planejamento financeiro, gestão do capital de giro e inadimplência. Verificou-se que o conjunto pesquisado é composto por instituições de alta complexidade de gestão, resultante das particularidades desse tipo de organização, com planejamento financeiro com alto grau de detalhamento de informações. Quanto à gestão do capital de giro, constatou-se que ocorre de forma criteriosa, com precisão e segurança nos processos financeiros. Em alguns casos, percebe-se a ocorrência da preponderância de aspectos políticos em detrimento de aspectos financeiros nas decisões tomadas, o que é atribuído ao caráter comunitário e de priorização da qualidade acadêmica.

Abstract Alzheimer's disease (AD) is an age‐related neurodegenerative pathology. Brain‐derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid‐β and inflammatory cytokines. However, the impact of peripheral EVs (pEVs) in AD pathogenesis remains poorly investigated. The objective of our study was to compare the passage of pEVs from adults, cognitively healthy elderly, and AD patients through the blood‐brain barrier (BBB), to evaluate their uptake in the brain and to assess their impact on the microglia activity using in vitro and in vivo models. To this end, pEVs were enriched, characterized, and fluorescently labelled. The passage of pEVs through the endothelial bEnd.3 cells was studied in a Transwell device with either neuronal or microglia cells seeded at the bottom of the well. Following the internalization of pEVs from AD patients, microglia adopted an amoeboid morphology and released a heightened level of pro‐inflammatory cytokine IL‐6. To further assess their in vivo transport across the BBB, pEVs were injected into the blood circulation of 2‐days post‐fertilization Tg(flk1:EGFP) zebrafish. The biodistribution of pEVs was monitored at 1 and 24 h post‐injection using confocal microscopy. We demonstrated that pEVs traverse the BBB by transcytosis and subsequently diffuse progressively into the brain. pEVs were then internalized by neuronal and radial glial cells as seen in Tg(huc:EGFP) and Tg(gfap:EGFP) zebrafish, respectively. Additional experiments were performed with the intrahippocampal injection of pEVs in the mouse, indicating their spreading throughout the brain and their uptake by neuronal and glial cells. These findings contribute to novel insights into the fate of pEVs following their passage through the BBB in vitro and in vivo, and demonstrate for the first time that pEVs from AD patients affect microglia activity. This suggests a potential mechanism through which peripheral tissue cues may contribute to AD pathogenesis.

Multiple sclerosis (MS) is the most common cause of disability in young adults due to several motor, sensory, and cognitive symptoms. However, little is still known about the impact of psychological, cognitive, and social-support variables on subjective disability. This study is aimed at exploring the role of clinical, psychological, cognitive, and social-support variables in predicting disability levels as perceived by persons with multiple sclerosis (pwMS). The World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the Expanded Disability Status Scale (EDSS) were used as subjective and objective measures of disability, respectively. State-Trait Anxiety Inventory and Beck Depression Inventory-II assessed symptoms of anxiety and depression; 19-item Medical Outcome Study–Social Support Survey assessed social support; and Rao’s Brief Repeatable Battery assessed cognitive functioning. A multivariable regression analysis was applied using the WHODAS 2.0 as an outcome. One hundred and fifty-one pwMS (93 females, mean age 51.6, standard deviation (SD) 5.8) were enrolled. EDSS (β=7.190; p

IntroductionParkinson’s Disease is the second most common neurodegenerative disease in the world. It affects mainly people over 65 and the incidence increases with age. It is characterized by motor and non-motor symptoms and several clinical manifestations. The most evident symptom that affects all patients with Parkinson’s Disease is the impairment of motor control, including bradykinesia, tremor, joint rigidity, and postural instability. In the literature, it has been evaluated with muscle synergies, a well-known method for evaluating motor control at the muscular level. However, few studies are available and there is still a major gap to fill to exploit the potential of the method for assessing motor control in Parkinson’s Disease, both in the understanding of physiopathology and clinical practice.MethodsIn the light of understanding and fostering future developments for the field, in this review we initially screened 212 papers on Scopus and Web of Science and selected 15 of them to summarize the main features of investigations that employed muscle synergies to analyze patients with Parkinson’s Disease. We detailed the features of the screened papers by reporting the clinical findings, a detailed report of EMG processing choices and synergy-based results.ResultsWe found that synergistic control is in general altered in patients with Parkinson’s Disease, but it can improve if patients are subjected to pharmacological and rehabilitation therapies. Moreover, a further understanding of synergistic control in Parkinson’s patients is needed.DiscussionWe discuss the future developments in the field with a detailed assessment of the topic on the view of physicians, including the most promising lines of research for clinical practice and from the perspective of engineers, for methodological application of synergistic approaches.