Evaluation of surface water quality in basins of the Chilean Altiplano-Puna and implications for water treatment and monitoring.

Water quality characterization and assessment are key to protecting human health and ecosystems, especially in arid areas such as northern Chile, where water resources are scarce and rich in pollutants. The objective of this study was to review and assess available official water quality data in the Chilean Altiplano-Puna basins for a 10-year period (2008-2018), including water treatment systems. Within the 43,600 km2 of Chilean Altiplano-Puna territory, only 16 official water quality monitoring stations had up-to-date data, and the sampling frequency was less than 3 per year. Most of the water samples collected at the evaluated stations exceeded the drinking and irrigation water Chilean standards for arsenic, boron, and electrical conductivity. Moreover, the characteristics of the Altiplano-Puna affect water quality inside and beyond the area, limiting water usage throughout the Altiplano-Puna basins. Drinking water treatment plants exist in urban and rural settlements; however, the drinking water supply in rural locations is limited due to the lack of adequate treatment and continuity of service. Wastewater treatment plants operate in some urban locations but rarely exist in rural locations. Limited data impede the proper assessment of water quality and thus the evaluation of the need for treatment systems. As such, the implementation of public policies that prioritize water with appropriate quantity and quality for local communities and ecosystems is imperative.

Could Commercial Formulations Replace Individualized Prescription in Pediatric Home Parenteral Nutrition?

OBJECTIVES: Standard parenteral nutrition (PN) solutions are safe and can meet the nutritional requirements of a significant number of pediatric patients. However, they may not always be adequate for those on long term PN. We aimed to compare the composition of individually tailored prescriptions in a pediatric population on home PN with that of available commercial PN formulations. METHODS: Retrospective analysis of the individual prescriptions of metabolically stable pediatric patients on home PN over a 1-year period (March 2019 to March 2020). These were compared with commercially available solutions with electrolytes, and replacement was considered adequate if three successive criteria were met: non-protein calorie to volume ratio (maximum variation 15%); non-protein calorie to nitrogen ratio (NPC:N) (maximum variation either 20% for long term use or 35% for possible short term use); electrolyte concentration (maximum increase 20%). RESULTS: Twenty-four patients were included (67% male; median age 7.5 years). The most common diagnosis was short bowel syndrome (58%). Replacement with a standard formulation was considered appropriate for possible short term use (maximum variation of 35% in NPC:N) in 16 (67%) patients and for long term use (maximum variation of 20% in NPC:N), the number of patients decreased to 10 (42%). CONCLUSIONS: Standard PN solutions can be adequate for a significant proportion of pediatric patients on home PN. Their use in the short term may also be appropriate in holiday periods or in settings of limited resources or restricted access to hospital facilities, such as those imposed by the COVID-19 pandemic.

Increased antioxidant response in medium-chain acyl-CoA dehydrogenase deficiency: does lipoic acid have a protective role?

BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is the most frequent fatty acid oxidation (FAO) defect in humans. MCAD-deficient fibroblasts are more resistant to oxidative stress-induced cell death than other FAO defects and healthy controls. METHODS: Herein we investigate the antioxidant response and mitochondrial function in fibroblasts from MCAD-deficient patients (c.985 A>G/c.985 A>G) and healthy controls. RESULTS: MCAD-deficient fibroblasts showed increased level of mitochondrial superoxide, while lipids were less oxidatively damaged, and higher amount of manganese superoxide dismutase were detected compared to healthy controls, showing forceful antioxidant system in MCADD. We showed increased maximal respiration and reserve capacity in MCAD-deficient fibroblasts compared to controls, indicating more capacity through the tricarboxylic acid (TCA) cycle and subsequently respiratory chain. This led us to study the pyruvate dehydrogenase complex (PDC), the key enzyme in the glycolysis releasing acetyl-CoA to the TCA cycle. MCAD-deficient fibroblasts displayed not only significantly increased PDC but also increased lipoylated PDC protein levels compared to healthy controls. CONCLUSIONS: Based on these findings, we raise the interesting hypothesis that increased PDC-bound lipoic acid, synthesized from accumulated octanoic acid in MCADD, may affect the cellular antioxidant pool in MCADD.

Wastewater Treatment Lagoons: Local Pathways of Perfluoroalkyl Acids and Brominated Flame Retardants to the Arctic Environment.

Concentrations of perfluoroalkyl acids (PFAAs), polybrominated diphenyl ethers (PBDEs), and "novel" brominated flame retardants (NBFRs) were determined in lagoons processing wastewater from two high-Arctic and two sub-Arctic of Canada communities to assess the importance of local anthropogenic sources. ∑PFAAs in influent and effluent of the Arctic lagoons were within the lower end of the range of concentrations previously observed in Canadian temperate wastewater treatment plants (WWTPs). In comparison, influent and effluent concentrations of ∑PBDEs and NBFRs were significantly greater (p < 0.05) in high-Arctic lagoons compared to sub-Arctic and temperate plants. The surprisingly elevated concentrations of PBDEs and NBFRs in high-Arctic lagoons were probably related to high organic matter found in Arctic wastewater due to lower consumption of potable water leading to less dilution compared to temperate regions. Although PFAAs also sorb to solids, the wastewater samples were filtered prior to analysis of PFAAs (but not PBDEs and NBFRs), which likely reduced the impacts of solids on the results for PFAAs. Based on an extrapolation of per capita mass effluent loadings of the four Arctic lagoons, mass loadings to the Arctic of Canada via WWTP effluent were estimated as 1405 g/year and 549 g/year for ∑PFAAs and ∑PBDEs, respectively.

Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.

AIMS: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes. MATERIALS AND METHODS: Tissue-specific uptake of metformin was assessed in mice by PET/CT imaging after injection of [11 C]-metformin. Human brown adipose tissue was obtained from elective neck surgery and metformin transporter expression levels in human and murine BAT were determined by qPCR. Oxygen consumption in metformin-treated human brown adipocyte cell models was assessed by Seahorse XF technology. RESULTS: Injected [11 C]-metformin showed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was similar to hepatic exposure. Non-specific inhibition of the organic cation transporter (OCT) protein by cimetidine administration eliminated BAT exposure to metformin, demonstrating OCT-mediated uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose-dependent manner. CONCLUSION: These results support BAT as a putative metformin target.

Secondary coenzyme Q10 deficiency and oxidative stress in cultured fibroblasts from patients with riboflavin responsive multiple Acyl-CoA dehydrogenation deficiency.

Coenzyme Q10 (CoQ10) is essential for the energy production of the cells and as an electron transporter in the mitochondrial respiratory chain. CoQ10 links the mitochondrial fatty acid ß-oxidation to the respiratory chain by accepting electrons from electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). Recently, it was shown that a group of patients with the riboflavin responsive form of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) carrying inherited amino acid variations in ETF-QO also had secondary CoQ10 deficiency with beneficial effects of CoQ10 treatment, thus adding RR-MADD to an increasing number of diseases involving secondary CoQ10 deficiency. In this study, we show that moderately decreased CoQ10 levels in fibroblasts from six unrelated RR-MADD patients were associated with increased levels of mitochondrial reactive oxygen species (ROS). Treatment with CoQ10, but not with riboflavin, could normalize the CoQ10 level and decrease the level of ROS in the patient cells. Additionally, riboflavin-depleted control fibroblasts showed moderate CoQ10 deficiency, but not increased mitochondrial ROS, indicating that variant ETF-QO proteins and not CoQ10 deficiency are the causes of mitochondrial ROS production in the patient cells. Accordingly, the corresponding variant Rhodobacter sphaeroides ETF-QO proteins, when overexpressed in vitro, bind a CoQ10 pseudosubstrate, Q10Br, less tightly than the wild-type ETF-QO protein, suggesting that molecular oxygen can get access to the electrons in the misfolded ETF-QO protein, thereby generating superoxide and oxidative stress, which can be reversed by CoQ10 treatment.

Occurrence and Fate of Trace Contaminants during Aerobic and Anaerobic Sludge Digestion and Dewatering.

Digestion of municipal wastewater biosolids is a necessary prerequisite to their beneficial use in land application, in order to protect public health and the receiving environment. In this study, 13 pharmaceuticals and personal care products (PPCPs), 11 musks, and 17 polybrominated diphenyl ethers were analyzed in 84 samples including primary sludge, waste activated sludge, digested biosolids, dewatered biosolids, and dewatering centrate or filtrate collected from five wastewater treatment plants with aerobic or anaerobic digestion. Aerobic digestion processes were sampled during both warm and cold temperatures to analyze seasonal differences. Among the studied compounds, triclosan, triclocarban, galaxolide, and BDE-209 were the substances most frequently detected under different treatment processes at levels up to 30,000 ng/g dry weight. Comparing aerobic and anaerobic digestion, it was observed that the levels of certain PPCPs and musks were significantly higher in anaerobically digested biosolids, relative to the residues from aerobic digestion. Therefore, aerobic digestion has the potential advantage of reducing levels of PPCPs and musks. On the other hand, anaerobic digestion has the advantage of recovering energy from the biosolids in the form of combustible gases while retaining the nutrient and soil conditioning value of this resource.

Laryngeal Foreign Body Aspiration in Infancy: A Diagnostic Challenge.

Foreign body aspiration (FBA) is a significant cause of accidental death among children, with laryngeal FBA being relatively rare but potentially fatal due to airway obstruction. This report highlights a case of laryngeal FBA in an 11-month-old child, initially misdiagnosed as viral croup. Otolaryngological evaluation, particularly in the case of laryngeal FBA, may facilitate management. An 11-month-old male was brought to the emergency department, presenting with inspiratory stridor following a choking episode. A chest radiograph and CT scan of the chest were read as normal. He was suspected of having croup and treated with dexamethasone and racemic nebulized epinephrine, which led to temporary clinical improvement.  The child returned with persistent stridor to the emergency department eight days after his initial visit, prompting an otolaryngological consultation. Flexible laryngoscopy ultimately identified a star-shaped sequin lodged in the glottis. The foreign body was successfully removed via direct laryngoscopy and bronchoscopy (DLB). Following the removal, the patient demonstrated significant improvement and eventually made a full recovery. This case emphasizes the difficulty in diagnosing laryngeal FBA due to its non-specific symptoms and the limitations of imaging techniques. The importance of a thorough clinical history, physical examination, and proper imaging combined with a high index of suspicion is crucial for early diagnosis and treatment. Additionally, the report discusses the potential for severe complications if diagnosis and treatment are delayed, highlighting the need for awareness and prompt intervention in suspected laryngeal FBA cases.

Perceived impact of pediatric palliative care: caregiver's perspective.

BACKGROUND: Caregivers of children with complex chronic diseases (CCD) or life-limiting conditions (LLC) experience heightened strain. Understanding their concerns is essential for effective support, particularly in pediatric palliative care (PPC) where compassionate support is crucial. Amid substantial growth in PPC services in Portugal, assessing the effectiveness of care in addressing these concerns and adapting to the evolving needs of parents is imperative. The aim of this study was to perceive the impact of PPC from the caregivers' perspective. METHODS: Participants consisted of children with CDD or LLC and their caregivers followed by the PPC team. Institutionalized children were excluded. Our mixed-methods study involved analyzing sociodemographic characteristics and assessing caregiver and child well-being using quantitative data and explored caregiver concerns and the impact of PPC through qualitative data obtained from semi-structured interviews. RESULTS: We included 43 children and caregivers. Caregivers (90.6% mothers; mean age 40) often experience fatigue (90.7%) although they rarely feel exhausted (67.4%). Sleep disturbances (58.1%) are the children's most frequent perceived symptom. Seven categories emerge from caregivers' concerns. Among the five categories arising from caregivers' perceived impact of PPC integration, 95.3% prioritize enhanced contact with healthcare professionals. Increased support to facilitate caregiver rest and early referral emerges as primary suggestions for improving PPC. CONCLUSIONS: The PPC appears to be effective in alleviating parents' primary concerns, highlighting the crucial importance of early referral. Implementing strategies to provide respite for caregivers and closer monitoring of these children becomes a priority to improve the quality of life for this inherently intertwined dyad, the child-family unit.

Perspective: Revisiting the Concepts of Prebiotic and Prebiotic Effect in Light of Scientific and Regulatory Progress - A Consensus Paper from the Global Prebiotic Association (GPA).

The term prebiotic has been used for almost three decades and has undergone numerous updates over the years. The scientific literature reveals that despite continuous efforts to establish a globally unified definition to guide jurisdictional regulations and product innovations, ambiguity continues to surround the terms prebiotic and prebiotic effect, leading to products that lack in full regulatory adherence being marketed worldwide. Thus, to reflect the current state of scientific research and knowledge and for the continuous advancement of the category, an update to the current prebiotic definition is warranted. This update includes removing the term selectivity, considering additional locations of action besides the gut, highlighting prebiotic performance benefits such as cognitive and athletic, and providing a clear standalone definition for prebiotic effect. The Global Prebiotic Association (GPA) is a leading information and industry hub committed to raising awareness about prebiotics, their emerging and well-established health benefits, and prebiotic product integrity and efficacy. In this position paper, GPA builds on previous prebiotic definitions to propose the following expanded definition for prebiotic: "a compound or ingredient that is utilized by the microbiota producing a health or performance benefit." In addition to prebiotic, GPA also defines prebiotic effect as: "a health or performance benefit that arises from alteration of the composition and/or activity of the microbiota, as a direct or indirect result of the utilization of a specific and well-defined compound or ingredient by microorganisms." With these two definitions, GPA aims to paint a clearer picture for the term prebiotic, and by incorporating an industry point of view, these updated definitions may be used alongside current scientific and regulatory perspectives to move the category forward. STATEMENT OF SIGNIFICANCE: The purpose of this paper is to revisit the concepts of prebiotic and prebiotic effect by providing a scientific-based industry perspective. The proposed definitions of prebiotic and prebiotic effect reflect the recent discoveries in metagenomics and prebiotic research after the International Scientific Association for Probiotics and Prebiotics' (ISAPP's) 2017 prebiotic definition and propose terminology changes that are timely and necessary. These changes aim to maintain the clarity and usefulness of the prebiotic definition to the scientific community, industry, healthcare providers, and consumers, while ensuring scientific validity, comprehensiveness, and justification of each part of the prebiotic definition, including abandoning the term selectivity and introducing concepts of performance benefits and prebiotic effect.

Senescence of skeletal stem cells and their contribution to age-related bone loss.

Human aging is linked to bone loss, resulting in bone fragility and an increased risk of fractures. This is primarily due to an age-related decline in the function of bone-forming osteoblastic cells and accelerated cellular senescence within the bone microenvironment. Here, we provide a detailed discussion of the hypothesis that age-related defective bone formation is caused by senescence of skeletal stem cells, as they are the main source of bone forming osteoblastic cells and influence the composition of bone microenvironment. Furthermore, this review discusses potential strategies to target cellular senescence as an emerging approach to treat age-related bone loss.

HSP60 chaperone deficiency disrupts the mitochondrial matrix proteome and dysregulates cholesterol synthesis.

OBJECTIVE: Mitochondrial proteostasis is critical for cellular function. The molecular chaperone HSP60 is essential for cell function and dysregulation of HSP60 expression has been implicated in cancer and diabetes. The few reported patients carrying HSP60 gene variants show neurodevelopmental delay and brain hypomyelination. Hsp60 interacts with more than 260 mitochondrial proteins but the mitochondrial proteins and functions affected by HSP60 deficiency are poorly characterized. METHODS: We studied two model systems for HSP60 deficiency: (1) engineered HEK cells carrying an inducible dominant negative HSP60 mutant protein, (2) zebrafish HSP60 knockout larvae. Both systems were analyzed by RNASeq, proteomics, and targeted metabolomics, and several functional assays relevant for the respective model. In addition, skin fibroblasts from patients with disease-associated HSP60 variants were analyzed by proteomics. RESULTS: We show that HSP60 deficiency leads to a differentially downregulated mitochondrial matrix proteome, transcriptional activation of stress responses, and dysregulated cholesterol biosynthesis. This leads to lipid accumulation in zebrafish knockout larvae. CONCLUSIONS: Our data provide a compendium of the effects of HSP60 deficiency on the mitochondrial matrix proteome. We show that HSP60 is a master regulator and modulator of mitochondrial functions and metabolic pathways. HSP60 dysfunction also affects cellular metabolism and disrupts the integrated stress response. The effect on cholesterol synthesis explains the effect of HSP60 dysfunction on myelination observed in patients carrying genetic variants of HSP60.

Clinical, Economic, and Humanistic Impact of Short-Bowel Syndrome/Chronic Intestinal Failure in Portugal (PARENTERAL Study).

Introduction: This study aimed to assess the clinical, economic, and humanistic impact of short-bowel syndrome/chronic intestinal failure (SBS/CIF) in Portugal. Methods: This is a retrospective multicenter cohort chart review study, with a cross-sectional component for quality-of-life (QoL) evaluation. Inclusion criteria comprised patients with SBS/CIF, aged ≥1 year, with stable parenteral nutrition (PN). Data collection included patient chart review over a 12-month period and patient/caregiver self-report and SF-36/PedsQL™ questionnaires. Main endpoints comprised clinical and PN characterization, healthcare resource use (HRU), direct costs, and patient QoL. Results: Thirty-one patients were included (11 adults and 20 children). Patients' mean age (standard deviation [SD]) was 57.9 (14.3) years in adults and 7.5 (5.0) years in children, with a mean time since diagnosis of 10.2 (5.9) and 6.6 (4.2) years, respectively. PN was administered for a mean of 5.2 and 6.6 days/week in adults and children, respectively; home PN occurred in 81.8% of adults and 90.0% of children for a mean of 9.6 and 10.8 months/year, respectively. The mean annual number of hospitalizations was 1.9 and 2.0 which lasted for a mean of 34.0 and 29.4 days in adults and children, respectively. Twenty-one and forty hospitalization episodes were reported in adults and children, respectively, of which 71.4% and 85.0% were due to catheter-related complications. Mean annual direct costs per patient amounted to 47,857.53 EUR in adults and 74,734.50 EUR in children, with PN and hospitalizations as the main cost-drivers. QoL assessment showed a clinically significant impaired physical component in adults and a notable deterioration in the school functioning domain in children. Conclusion: In Portugal, SBS/CIF patient management is characterized by a substantial therapeutic burden and HRU, translating into high direct costs and a substantial impairment of the adults' physical function and children's school functioning.

Introdução: Este estudo teve como objetivo avaliar o impacto clínico, económico e social da síndrome do intestino curto/falência intestinal crónica (SIC/FIC) em Portugal. Métodos: Estudo de coorte retrospectivo e multicêntrico de revisão dos processos clínicos incluindo uma componente transversal para avaliação da qualidade de vida (QV). Os critérios de elegibilidade incluíram doentes com SIC/FIC, idade ≥1 ano, em nutrição parenteral (NP) e clinicamente estáveis. A recolha de dados incluiu a revisão dos processos clínicos ao longo de um período de 12 meses e a aplicação de questionários auto-administrados a doentes e cuidadores e de questionários de QV (SF-36/PedsQL™). Os indicadores principais foram a caracterização clínica e da NP, a utilização de recursos de saúde, custos diretos e QV dos doentes. Resultados: Foram incluídos 31 doentes (11 adultos e 20 crianças). A idade média (desvio padrão: DP) foi de 57.9 (14.3) anos nos adultos e de 7.5 (5.0) nas crianças com um tempo médio desde o diagnóstico de 10.2 (5.9) e 6.6 (4.2) anos, respetivamente. A NP foi administrada durante uma média de 5.2 e 6.6 dias por semana, em adultos e crianças respetivamente, em 81.8% e 90.0% dos adultos/crianças foi feita em casa durante uma média de 9.6 ou 10.8 meses por ano, respetivamente. O número médio anual de hospitalizações foi de 1.9 (1.6) e 2.0 (1.5) com uma duração média de 34.0 (47.4) e 29.4 (32.3) dias, em adultos e crianças, respetivamente. Foram reportados 21 e 40 episódios de hospitalização em adultos/crianças, dos quais 71.4% e 85.0% foram devido a complicações relacionadas ao uso de cateter. Os custos diretos anuais médios por doente ascenderam a 47,857.53 EUR nos adultos e a 74,734.50 EUR nas crianças, sendo que os maiores responsáveis foram a NP e as hospitalizações. A avaliação da QV mostrou um comprometimento clinicamente significativo da componente física nos adultos e uma deterioração relevante da dimensão escolar nas crianças. Conclusões: A gestão dos doentes com SIC/FIC em Portugal é caracterizada por uma sobrecarga substancial a nível terapêutico e de utilização de recursos de saúde, o que se traduz em elevados custos diretos e comprometimento substancial da componente física nos adultos e do desempenho escolar nas crianças.

GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells.

OBJECTIVE: Drugs targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) are emerging as treatments for type-2 diabetes and obesity. GIP acutely decreases serum markers of bone resorption and transiently increases bone formation markers in short-term clinical investigations. However, it is unknown whether GIP acts directly on bone cells to mediate these effects. Using a GIPR-specific antagonist, we aimed to assess whether GIP acts directly on primary human osteoclasts and osteoblasts. METHODS: Osteoclasts were differentiated from human CD14+ monocytes and osteoblasts from human bone. GIPR expression was determined using RNA-seq in primary human osteoclasts and in situ hybridization in human femoral bone. Osteoclastic resorptive activity was assessed using microscopy. GIPR signaling pathways in osteoclasts and osteoblasts were assessed using LANCE cAMP and AlphaLISA phosphorylation assays, intracellular calcium imaging and confocal microscopy. The bioenergetic profile of osteoclasts was evaluated using Seahorse XF-96. RESULTS: GIPR is robustly expressed in mature human osteoclasts. GIP inhibits osteoclastogenesis, delays bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways (Src, cAMP, Akt, p38, Akt, NFκB) to impair nuclear translocation of nuclear factor of activated T cells-1 (NFATc1) and nuclear factor-κB (NFκB). Osteoblasts also expressed GIPR, and GIP improved osteoblast survival. Decreased bone resorption and improved osteoblast survival were also observed after GIP treatment of osteoclast-osteoblast co-cultures. Antagonizing GIPR with GIP(3-30)NH2 abolished the effects of GIP on osteoclasts and osteoblasts. CONCLUSIONS: GIP inhibits bone resorption and improves survival of human osteoblasts, indicating that drugs targeting GIPR may impair bone resorption, whilst preserving bone formation.

Serial transverse enteroplasty (STEP): intermediate outcomes in children with short bowel syndrome.

Short bowel syndrome is the most common cause of intestinal failure in children. The treatment is based on a multidisciplinary approach involving pediatricians, pediatric surgeons, and nutritionists. Surgical procedures for intestinal lengthening may be decisive, having been revalued after the recent description of serial transverse enteroplasty (STEP). We reviewed the patients who underwent the STEP operation for short bowel syndrome in our hospital in order to evaluate medium-term outcome. Between April 2006 and December 2008, three children were submitted to STEP without postoperative complications directly related to the procedure. In two cases the autonomy for oral/enteric feeding was obtained within 3 and 7 months after surgery with sustained growth, persisting at 5 years of follow-up after STEP. One child remained dependent of parenteral nutrition and was submitted to intestinal transplantation 30 months after STEP. However, since STEP until transplantation, it was possible to increase enteric volume and decrease intestinal dilation and the frequency of occlusive episodes. STEP is an effective and safe technique for intestinal lengthening that may allow increased tolerance to oral/enteric feeding or at least alleviate some complications of short bowel syndrome.

Dreaming is not enough. Audiovisual methodologies, social inclusion, and new forms of youth biopolitical resistance.

The eleventh Sustainable Development Goal, "make cities and human settlements inclusive, safe, resilient and sustainable," can only be truly answered when there are no individuals in our societies who feel forgotten by the various social institutions. Not in Education, Employment, or Training [NEET] are among those most affected by this social invisibility. Nevertheless, these young people are not alienated or lost. Far from it. Instead, some of them found in the arts registered in the community-music, dance, photography and graffiti-a possibility to resist the various social stigmas attached on them. This was the view on which we conducted our artistic and social intervention, based on the innovative "arts-based research" methodology and "youth-led participatory research," called "The Neighborhood is Ours II!," with young NEETs in the socially underprivileged Cerco neighborhood of Porto in Portugal in 2022. We propose a theoretical-empirical approach around a visual/narrative sociology-namely using digital cinema-which will be based on a short film about the life narrative of a young NEET, who has used artistic practices to establish himself in the city of Porto as a cultural mediator. Thus-through these processes of co-creation of knowledge (cine-making)- we aim to demonstrate how the use of the arts can be a key tool in promoting social inclusion and reducing/minimizing feelings of insecurity, but also act as a means of resistance to the daily adversities experienced by marginalized young people and, of course, demonstrate the ways in which the use of artistic practices plays a pivotal role in the development of sustainable and alternative professional, social futures and citizenship.

The psychiatric risk gene BRD1 modulates mitochondrial bioenergetics by transcriptional regulation.

Bromodomain containing 1 (BRD1) encodes an epigenetic regulator that controls the expression of genetic networks linked to mental illness. BRD1 is essential for normal brain development and its role in psychopathology has been demonstrated in genetic and preclinical studies. However, the neurobiology that bridges its molecular and neuropathological effects remains poorly explored. Here, using publicly available datasets, we find that BRD1 targets nuclear genes encoding mitochondrial proteins in cell lines and that modulation of BRD1 expression, irrespective of whether it is downregulation or upregulation of one or the other existing BRD1 isoforms (BRD1-L and BRD1-S), leads to distinct shifts in the expression profile of these genes. We further show that the expression of nuclear genes encoding mitochondrial proteins is negatively correlated with the expression of BRD1 mRNA during human brain development. In accordance, we identify the key gate-keeper of mitochondrial metabolism, Peroxisome proliferator-activated receptor (PPAR) among BRD1's co-transcription factors and provide evidence that BRD1 acts as a co-repressor of PPAR-mediated transcription. Lastly, when using quantitative PCR, mitochondria-targeted fluorescent probes, and the Seahorse XFe96 Analyzer, we demonstrate that modulation of BRD1 expression in cell lines alters mitochondrial physiology (mtDNA content and mitochondrial mass), metabolism (reducing power), and bioenergetics (among others, basal, maximal, and spare respiration) in an expression level- and isoform-dependent manner. Collectively, our data suggest that BRD1 is a transcriptional regulator of nuclear-encoded mitochondrial proteins and that disruption of BRD1's genomic actions alters mitochondrial functions. This may be the mechanism underlying the cellular and atrophic changes of neurons previously associated with BRD1 deficiency and suggests that mitochondrial dysfunction may be a possible link between genetic variation in BRD1 and psychopathology in humans.

Dechlorane plus and related compounds in peregrine falcon (Falco peregrinus) eggs from Canada and Spain.

Concentrations of Mirex, Dechlorane (Dec) Plus (DP), Dec 602, Dec 603, and Dec 604 were significantly higher in peregrine falcon (Falco peregrinus) eggs from Canada than Spain, with the former having the only measurable concentrations of the dechlorinated DP products, decachloropentacyclooctadecadiene (aCl10DP) and undecachloropentacyclooctadecadiene (aCl11DP). Large variations also occurred in the in ovo concentrations of the DP monoadduct, DPMA. This is the first study to report the accumulation and metabolism of DP by peregrines, both DP and dechloranes in European biota, as well as dechloranes in a terrestrial organism and one at the top of the food web. The geographical differences in the measured in ovo concentrations reflect local exposure of the adult peregrines on their breeding grounds, likely differences in diet of the adults, the production of DP on the Niagara River, and the greater use of Mirex and dechloranes as flame retardants in North America than Europe.