Removing critical gaps in chemical test methods by developing new assays for the identification of thyroid hormone system-disrupting chemicals—the athena project

The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood–brain and blood–placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation

Intervention use and symptom change with unguided internet-based cognitive behavioral therapy for depression during the COVID-19 pandemic: log data analysis of a convenience sample

Background: Internet- and mobile-based interventions are most efficacious in the treatment of depression when they involve some form of guidance, but providing guidance requires resources such as trained personnel, who might not always be available (eg, during lockdowns to contain the COVID-19 pandemic). Objective: The current analysis focuses on changes in symptoms of depression in a guided sample of patients with depression who registered for an internet-based intervention, the iFightDepression tool, as well as the extent of intervention use, compared to an unguided sample. The objective is to further understand the effects of guidance and adherence on the intervention’s potential to induce symptom change. Methods: Log data from two convenience samples in German routine care were used to assess symptom change after 6-9 weeks of intervention as well as minimal dose (finishing at least two workshops). A linear regression model with changes in Patient Health Questionnaire (PHQ-9) score as a dependent variable and guidance and minimal dose as well as their interaction as independent variables was specified. Results: Data from 1423 people with symptoms of depression (n=940 unguided, 66.1%) were included in the current analysis. In the linear regression model predicting symptom change, a significant interaction of guidance and minimal dose revealed a specifically greater improvement for patients who received guidance and also worked with the intervention content (β=–1.75, t=–2.37, P=.02), while there was little difference in symptom change due to guidance in the group that did not use the intervention. In this model, the main effect of guidance was only marginally significant (β=–.53, t=–1.78, P=.08). Conclusions: Guidance in internet-based interventions for depression is not only an important factor to facilitate adherence, but also seems to further improve results for patients adhering to the intervention compared to those who do the same but without guidance

How are guide profession and routine care setting related to adherence and symptom change in iCBT for depression? - an explorative log-data analysis

Background: While the antidepressant efficacy of guided digital interventions has been proven in randomized controlled trials, findings from routine care are less clear. Low adherence rates are common and limit the potential effectiveness. Adherence has been linked to sociodemographic variables and the amount of guidance, but the role of the guide's profession and their work setting has not yet been studied for routine care. Methods: Routinely collected log data from a digital intervention for depressed patients (iFightDepression tool) were analyzed in an exploratory manner. The sample is a convenience sample from routine care, where guidance is provided by general practitioners (GP), certified psychotherapists (PT) or medical doctors specialized in mental health. Log data from 2184 patients were analyzed and five usage parameters were extracted to measure adherence (first-to-last login, time on tool, number of sessions, workshops completed and minimal dose). Multiple logistic regression was used to analyze relations between the guide's profession and clinical context as well as other covariates and adherence and symptom change on a brief depression questionnaire (PHQ-9). Results: The analyses showed a significant relation of guide profession and adherence. Guidance by PT was associated to the highest adherence scores (reference category). The odds ratios (ORs) of scoring above the median in each usage parameter for patients guided by GPs were 0.50–0.63 (all ps < 0.002) and 0.61–0.80 (p = .002–0.197) for MH. Higher age, initial PHQ-9 score and self-reported diagnosis of depression were also significantly associated with higher adherence scores. In a subsample providing enough data on the PHQ-9 (n = 347), no association of guide profession with symptom reduction was found. Instead, a greater reduction was observed for patients with a higher baseline PHQ-9 (β = −0. 39, t(341.75) = −8.814, p < .001) and for those who had achieved minimal dose (β = −2.42, t(340.34) = −4.174, P < .001) and those who had achieved minimal dose and scored high on time on tool (β = 0.22, t(341.75) = 1.965, P = .050). Conclusion: Being guided by PT was associated with the highest adherence. The lowest adherence was observed in patients who were guided by GP. While no association of guide profession and symptom reduction was found in a subsample, greater adherence was associated with symptom reduction

Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay

Early neurodevelopmental processes are strictly dependent on spatial and temporally modulated of thyroid hormone (TH) availability and action. Thyroid hormone transmembrane transporters (THTMT) are critical for regulating the local concentrations of TH, namely thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3), in the brain. Monocarboxylate transporter 8 (MCT8) is one of the most prominent THTMT. Genetically induced deficiencies in expression, function or localization of MCT8 are associated with irreversible and severe neurodevelopmental adversities. Due to the importance of MCT8 in brain development, studies addressing chemical interferences of MCT8 facilitated T3 uptake are a crucial step to identify TH system disrupting chemicals with this specific mode of action. Recently a non-radioactive in vitro assay has been developed to rapidly screen for endocrine disrupting chemicals (EDCs) acting upon MCT8 mediated transport. This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 31 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors.</p

The sulfur cycle below the sulfate-methane transition of marine sediments

The study of sulfate reduction below the sulfate-methane transition (SMT) in marine sediments requires strict precautions to avoid sulfate contamination from seawater sulfate or from sulfide oxidation during handling. We experimented with different methods of sampling porewater sulfate and found that modifications to our sampling procedure reduced the measured sulfate concentrations from hundreds of micromolar to ten micromolar or less. We here recommend some key modifications to porewater sampling to avoid contamination or oxidation artifacts, for example when measuring very low sulfate concentrations below the SMT of marine sediments. At three sites in Aarhus Bay, the sulfate concentrations below the SMT remained around ten micromolar. The calculated free energy change, ΔGr, available for sulfate reduction by such low concentrations is between −17.9 and −11.9 kJ mol−1 sulfate. This is near or below the energy yields that have previously been calculated for microbial sulfate reduction in marine sediments. The three sites are characterized by measurable and very different sulfate reduction rates depending on the depth and sediment age of the SMT. Our data show that sulfate is being consumed below the SMT in spite of the low sulfate concentrations. As sulfate is not drawn down to even lower concentrations, it must be continually regenerated below the SMT, most likely by Fe(III)-driven sulfide oxidation concurrent with the sulfate reduction. We conclude that the low sub-SMT sulfate concentrations are in steady state between reduction and production and are thermodynamically controlled by the minimum ΔGr requirements by sulfate reducing bacteria while sulfate reduction rates are controlled by the rate of sulfide oxidation. This study deals with the general sampling of uncontaminated pore water and hints to a systemic problem with low levels of contamination in porewater induced by coring and pore water extraction. Below the SMT, this contamination could be detected but above the SMT it goes unnoticed. Low levels of contamination as observed in this study may affect other low concentration or redox-sensitive elements in pore water

Padrão espacial da tuberculose em um município prioritário no estado do Mato Grosso - Brasil

Objetivo: analisar as características das pessoas acometidas por tuberculose e a distribuição espacial dos casos notificados, do abandono do tratamento, bem como de unidades de saúde em um município prioritário no Mato Grosso. Método: estudo ecológico com os casos de tuberculose notificados no período de 2011 a 2020 no município de Barra do Garças-MT. Os dados foram obtidos pelo Sistema de Informação de Agravos de Notificação, sendo investigadas as variáveis sociodemográficas e clínico-operacionais da tuberculose. Foi calculada a taxa de incidência dos casos por ano. Após realizou-se a distribuição espacial, de acordo com os bairros do município, do número de casos e de abandono do tratamento, bem como de unidades de saúde pertencentes a atenção básica. Resultados: Foram notificados 337 casos com predomínio do sexo masculino (n=230;68,25%), pessoas indígenas (n=120;35,61%), idade entre 15 e 59 anos (n=242;71,81%) e com 1 a 8 anos de estudo (n=159;46,88%). Quanto aos dados clínico-operacionais a maioria eram casos novos (n=269;79,82%), que não realizaram cultura de escarro (n=305;90,50%), sendo que 41,25% (n=139) não realizaram o tratamento diretamente observado (n=110;57,29%) e apenas 56,97% (n=192) evoluíram para cura. A incidência média anual foi de 54,62 casos por 100.000/habitantes. Os bairros Santo Antônio e Centro apresentaram maior número de notificados e abandono do tratamento. A presença de unidades de estratégia de saúde da família e policlínicas não foram determinantes para ocorrência dos fenômenos investigados. Conclusão: identificou o perfil das pessoas mais afetadas, bem como as áreas críticas em relação ao número de casos e abandono do tratamento

Polysaccharides from pinhão seeds of Araucaria angustifolia : Extraction, isolation and structural characterization

Araucaria angustifolia is one of the main conifer species with great economic importance. Its seeds, known as pinhão, play a fundamental role in ecosystem conservation and have promising potential for application in the food/nutraceutical industry. This study aimed to elucidate the fine chemical structure of polysaccharides, showing for the first time the composition of non-starch polysaccharides present in the pinhão seeds. For this, the seeds were submitted to sequential extractions giving rise to the water polysaccharide (PW), and alkaline polysaccharides (PA2M), and (PA4M) fractions, obtained after aqueous, 2 mol L-1 and 4 mol L-1 NaOH extraction, respectively. The polysaccharides isolated showed the presence of glucose (between 96.8% and 76.3%) indicating starch as the main component of all fractions. Moreover, after enzymatic treatment, the PA4M-A fraction was obtained showing mostly arabinose in its monosaccharide composition. In this way, the chemical structure of PA4M-A was investigated by 1D 1H, 13C NMR and 2D 1H–13C HSQC, 1H–1H COSY and 1H–13C HMBC NMR spectroscopy, which demonstrated the presence of arabinans composed with a backbone of (1→5)-linked-α-L-arabinofuranosyl units substituted in O-2 and/or O-3 position by α-L-Araf-(1→ or α-L-Araf-(1→3)-α-L-Araf-(1→ side chains. The structural elucidation of the arabinans presents in the pinhão cell wall contributes to the knowledge of the molecular structure of the A.angustifolia seeds.</p