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.

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.

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.

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.

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.

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.

Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction. Here, we evaluated patients' symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls. We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being. This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels. Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.

Chylothorax in the neonate-A stepwise approach algorithm.

BACKGROUND: Chylothorax in neonates results from leakage of lymph from thoracic lymphatic ducts and is mainly congenital or posttraumatic. The clinical course of the effusion is heterogeneous, and consensus on treatment, timing, and modalities of measures has not yet been established. This review aims to present, along with levels of evidence and recommendation grades, all current therapeutic possibilities for the treatment of chylothorax in neonates. METHODS: An extensive search of publications between 1970 and 2020 was performed in the PubMed, Cochrane Database of Systematic Reviews, and UpToDate databases. A stepwise approach algorithm was proposed for both congenital and traumatic conditions to guide the clinician in a rational and systematic way for approaching the treatment of neonates with chylothorax. DISCUSSION AND CONCLUSION: The treatment strategy for neonatal chylothorax generally involves supportive care and includes drainage and procedures to reduce chyle flow. A stepwise approach starting with the least invasive method is advocated. Progression in the invasiveness of treatment options is determined by the response to previous treatments. A practical stepwise approach algorithm is proposed for both, congenital and traumatic chylothoraces.

Comunidades profesionales de aprendizaje en educación parvularia en chile / Professional learning communities in early childhood in chile / Communautes dapprentissage professionnel en education prescolaire au chili / Comunidades profissionais de aprendizagem em educação pré-escolar no chile

Resumen Una alternativa de desarrollo profesional docente son las comunidades profesionales de aprendizaje (CPA), espacio formativo altamente valorizado y respaldado por creciente evidencia. Un ámbito escasamente abordado son los factores contextuales e institucionales asociados a las CPA. Para indagar en ellos se analizaron dos CPA compuestas por educadoras de párvulos. Mediante un estudio de caso, se entrevistaron, grupal e individualmente, educadoras y representantes institucionales. Los hallazgos destacan la gestión, coordinación de procesos, visión y planeamiento estratégico como aspectos relevantes, junto a procesos reflexivos que acompañan la evolución de las CPA. Se discuten las convergencias y divergencias de ambos casos, así como las implicancias teóricas y prácticas.

Abstract An alternative for teacher professional development is Professional Learning Communities (PLC), a space highly valued and supported by evidence. An area rarely addressed are the contextual and institutional factors associated with PLCs. In order to investigate them, two PLCs composed of early childhood teachers were analyzed. Through a case study, teachers and institutional representatives were interviewed, as a group and individually. The findings highlight management, process coordination, vision and strategic planning as relevant aspects, along with reflective processes that accompany the evolution of PLCs. The convergences and divergences of both cases are discussed, as well as the theoretical and practical implications.

Resumo Uma alternativa de desenvolvimento docente são as comunidades profissionais de aprendizagem (CPA), espaço de formação altamente valorizado e respaldado por crescente evidência. Um âmbito pouco abordado são os fatores contextuais e institucionais associados às CPA. Para conhecê-los melhor foram analisadas duas CPA compostas por educadoras de pré-escolares. Por meio de um estudo de caso foram entrevistados, em grupo e individualmente, educadoras e representantes de instituições. Os achados destacam a gestão, coordenação de processos, visão e planejamento estratégico como aspectos relevantes, além dos processos de reflexão que acompanham a evolução das CPA. São discutidas as convergências e as divergências de ambos os casos, bem como as implicações teóricas y práticas.

Résumé Communautés d'apprentissage professionnel (CAP) sont une alternative pour le développement professionnel des enseignants; un espace de formation très apprécié et attesté par un nombre croissant d'indices. Les facteurs contextuels et institutionnels associés aux CAP sont rarement abordés. Afin de mieux les connaître, deux CAP d'enseignants de maternelle ont été analysés. Grâce à une étude de cas, des éducateurs et des gestionnaires ont été interrogés, en groupe et individuellement. Les résultats mettent en évidence la pertinence de la gestion, de la coordination des procédés, de la vision et de la planification stratégique outre celle des processus de réflexion qui accompagnent l'évolution des CAP. Les convergences et divergences des deux cas sont discutées, ainsi que les implications théoriques et pratiques.

A recurrent de novo HSPD1 variant is associated with hypomyelinating leukodystrophy.

Standardization of the use of next-generation sequencing for the diagnosis of rare neurological disorders has made it possible to detect potential disease-causing genetic variations, including de novo variants. However, the lack of a clear pathogenic relevance of gene variants poses a critical limitation for translating this genetic information into clinical practice, increasing the necessity to perform functional assays. Genetic screening is currently recommended in the guidelines for diagnosis of hypomyelinating leukodystrophies (HLDs). HLDs represent a group of rare heterogeneous disorders that interfere with the myelination of the neurons in the central nervous system. One of the HLD-related genes is HSPD1, encoding the mitochondrial chaperone heat shock protein 60 (HSP60), which functions as folding machinery for the mitochondrial proteins imported into the mitochondrial matrix space. Disease-causing HSPD1 variants have been associated with an autosomal recessive form of fatal hypomyelinating leukodystrophy (HLD4, MitCHAP60 disease; MIM #612233) and an autosomal dominant form of spastic paraplegia, type 13 (SPG13; MIM #605280). In 2018, a de novo HSPD1 variant was reported in a patient with HLD. Here, we present another case carrying the same heterozygous de novo variation in the HSPD1 gene (c.139T > G, p.Leu47Val) associated with an HLD phenotype. Our molecular studies show that the variant HSP60 protein is stably present in the patient's fibroblasts, and functional assays demonstrate that the variant protein lacks in vivo function, thus confirming its disease association. We conclude that de novo variations of the HSPD1 gene should be considered as potentially disease-causing in the diagnosis and pathogenesis of the HLDs.

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.

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.

Portal Vein Thrombosis Secondary to Occult Polycythemia Vera.

Portal vein thrombosis (PVT) is an uncommon finding in patients without cirrhosis. The underlying x\aetiology is challenging and the condition has a wide differential diagnosis. We present a case of PVT in an anaemic patient with chronic iron and folic acid deficiency masking underlying polycythemia vera (PV). Only a careful review of the patient's clinical history allowed the identification of a short period of laboratory erythrocytosis, 6 months before the clinical onset of PVT, while the patient was on iron and folic acid supplementation. The finding raised clinical suspicion of PV previously masked by iron deficiency anaemia. Subsequent investigation confirmed the presence of the JAK2 V617F mutation and, ultimately, showed that the patient met all diagnostic criteria for PV. Myeloproliferative disorders (MPD) are associated with systemic prothrombotic states. PV is distinguished clinically from other MPD by the presence of increased red blood cell mass. Moreover, patients with abnormal haematocrit values in the pre-JAK2 V617F era may have had occult or latent PV. Diagnosis confirmation requires a combination of major and minor criteria to capture occasional cases of occult PV. This case emphasizes the importance of always considering MPD in the aetiological investigation of PVT, even in patients who apparently do not fulfil the diagnostic criteria. LEARNING POINTS: We describe a rare gastroenterological presentation of a haematological condition, which provided an unexpected diagnosis.Myeloproliferative disorders should always be considered in the investigation of portal vein thrombosis.

Occurrence and removal of triclosan in Canadian wastewater systems.

Triclosan (TCS) is an antimicrobial agent used in many personal care and cleaning products. It has been detected in most environmental compartments and the main entry pathway is wastewater effluents and biosolids. TCS was analyzed in 300 samples of raw influent, final effluent, and biosolids from 13 wastewater treatment plants (WWTPs) across Canada representing five types of typical wastewater treatment systems. TCS was almost always detected in influent (median 1480 ng/L), effluent (median 107 ng/L), and biosolids (median 8000 ng/g dry weight) samples. Removals of TCS from lagoons as well as secondary and advanced treatment facilities were significantly higher than primary treatment facilities (p < 0.001). TCS removal was strongly correlated with organic nitrogen removal. TCS removals at most lagoons and plants that use biological treatment were higher during summer compared with winter. However, no seasonal or temperature effects were observed at the two primary facilities, likely due to the absence of biological activity. Aerobically digested solids contained the lowest levels (median 555 ng/g) while anaerobically digested primary solids contained the highest levels of TCS (median 22,700 ng/g). The results of this large comprehensive study demonstrate that TCS is consistently present in wastewater and biosolids at relatively high concentrations and that removal from wastewater and levels in biosolids are strongly influenced by the wastewater and solids treatment types.

[Myalgic encephalomyelitis or chronic fatigue syndrome].

In this review, we discuss the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is characterised by extreme mental and physical fatigue with associated symptoms of pain, disturbed sleep, cognitive and autonomic dysfunction, as well as post-exertional malaise. This con-dition is often preceded by an infection, severe physiological and/or psychological strain. Over the last decades, research has demonstrated mitochondrial, neuroendocrine, immuno-logical, and metabolic perturbations in patients with ME/CFS, giving hope for the development of new biomarkers and new treatment modalities.

A Cell Model for HSP60 Deficiencies: Modeling Different Levels of Chaperonopathies Leading to Oxidative Stress and Mitochondrial Dysfunction.

Besides providing the majority of ATP production in cells, mitochondria are also involved in many other cellular functions and are central for cellular stress signaling. Mitochondrial dysfunction induces not only inherited mitochondrial disorders but also contributes to neurodegenerative diseases, cancer, diabetes, and metabolic syndrome. The HSP60/HSP10 molecular chaperone complex facilitates folding of mitochondrial proteins and is thus an important factor for many mitochondrial functions. To model different degrees of oxidative stress and mitochondrial dysfunction we here describe a HEK293 derived Flp-In cell system with stable insertion and tunable expression of HSP60 cDNA carrying a dominant negative mutation. When expressed the dominant negative HSP60 mutant is incorporated into endogenously encoded HSP60/HSP10 complexes and impairs chaperone activity of the HSP60/HSP10 complex in a dose dependent manner. Using this system, different levels of oxidative stress and mitochondrial dysfunction challenges can be generated depending on the induction level of the mutant HSP60 cDNA insert. Here we describe our system and pertinent analysis methodology for use in studies of mitochondrial chaperone deficiency and resulting effects of increased production of reactive oxygen species and mitochondrial dysfunction.