Sibutramine treatment in obesity: initial eating behaviour in relation to weight loss results and changes in mood.

The aim of the study was to study the role of initial eating behaviour for subsequent weight loss in treatment with sibutramine (Reductil, Meridia) an anti-obesity drug enhancing satiety, and also to assess changes in mood during the treatment. The participants were 36 obese patients with a mean BMI of 39 kg m(-2). Eating behaviour was assessed with the three factor eating questionnaire (TFEQ), and depressive features with the comprehensive psychopathological rating scale (CPRS). Sibutramine (15 mg) was administered daily. The TFEQ restraint scale was negatively related to 6 months weight loss. In particular, strategic dieting behaviour and a more controlled attitude towards self-regulation were negatively related to weight loss. A positive non-placebo controlled change in mood was found already after 2 months treatment. The changes in mood were not related to the weight loss. Patients with more unrestrained eating seem to have reduced their amount of food intake more radically with enhanced satiety, manifested by greater weight loss. Physiologically enhanced satiety could have the greatest weight loss effect for patients whose eating is more governed by hunger drives and appetite rather that by conscious efforts and cognitive control.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343     

Autosomal dominant cone-rod dystrophy due to a missense mutation (R838C) in the guanylate cyclase 2D gene (GUCY2D) with preserved rod function in one branch of the family

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disorder of photoreceptors. Mutations in several genes encoding different proteins of the visual cascade are described. The inheritance of two intragenic markers within the interstitial retinol binding protein (IRBP) gene was established in 45 Spanish families with a history of ARRP. Homozygosity mapping and cosegregation analyses were positive in 19 families. Only one heterozygous T-C transition at position 3024 (exon 1) was detected in one consanguineous family. This variant was identified as a rare polymorphism and was present in 5% of the chromosomes analyzed.     

Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer’s Disease Risk

Background: The interaction of aging-related, genetic, and environmental factors is thought to contribute to the etiology of late-onset, sporadic Alzheimer’s disease (AD). We previously reported that serum levels of p,p′-dichlorodiphenyldichloroethylene (DDE), a long-lasting metabolite of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT), were significantly elevated in patients with AD and associated with the risk of AD diagnosis. However, the mechanism by which DDT may contribute to AD pathogenesis is unknown.Objectives: This study sought to assess effects of DDT exposure on the amyloid pathway in multiple in vitro and in vivo models.Methods: Cultured cells (SH-SY5Y and primary neurons), transgenic flies overexpressing amyloid beta (Aβ), and C57BL/6J and 3xTG-AD mice were treated with DDT to assess impacts on the amyloid pathway. Real time quantitative polymerase chain reaction, multiplex assay, western immunoblotting and immunohistochemical methods were used to assess the effects of DDT on amyloid precursor protein (APP) and other contributors to amyloid processing and deposition.Results: Exposure to DDT revealed significantly higher APP mRNA and protein levels in immortalized and primary neurons, as well as in wild-type and AD-models. This was accompanied by higher levels of secreted Aβ in SH-SY5Y cells, an effect abolished by the sodium channel antagonist tetrodotoxin. Transgenic flies and 3xTG-AD mice had more Aβ pathology following DDT exposure. Furthermore, loss of the synaptic markers synaptophysin and PSD95 were observed in the cortex of the brains of 3xTG-AD mice.Discussion: Sporadic Alzheimer’s disease risk involves contributions from genetic and environmental factors. Here, we used multiple model systems, including primary neurons, transgenic flies, and mice to demonstrate the effects of DDT on APP and its pathological product Aβ. These data, combined with our previous epidemiological findings, provide a mechanistic framework by which DDT exposure may contribute to increased risk of AD by impacting the amyloid pathway. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10576","term_id":"372009961","term_text":"EHP10576"}}EHP10576     

Differential Effects of Obesity,Hyperlipidaemia, Dietary Intake and Physical Inactivity on Type I versus Type IV Allergies

Background: Alongside metabolic diseases (esp. obesity), allergic disorders are becoming increasingly prevalent. Since both obesity and allergies are highly impacted by environmental determinants, with this study we assessed the potential link between metabolic implications and two distinct types of allergies. Methods: Using cross-sectional data from the German FoCus cohort, n = 385 allergy cases, either hay fever (=type I allergy, n = 183) or contact allergy (=type IV allergy, n = 202) were compared to age- and sex-matched healthy control subjects (1:1 ratio, in total n = 770) regarding their metabolic phenotype, diet, physical activity, sleep, gut microbial composition, and serum metabolite profile using suitable BMI-adjusted models. Results: Obesity and metabolic alterations were found significantly more prevalent in subjects with allergies. In fact, this relation was more pronounced in contact allergy than hay fever. Subsequent BMI-adjusted analysis reveals particular importance of co-occurring hyperlipidaemia for both allergy types. For contact allergy, we revealed a strong association to the dietary intake of poly-unsaturated fatty acids, particularly α-linolenic acid, as well as the enrichment of the corresponding metabolic pathway. For hay fever, there were no major associations to the diet but to a lower physical activity level, shorter duration of sleep, and an altered gut microbial composition. Finally, genetic predisposition for hyperlipidaemia was associated to both contact allergy and hay fever. Conclusions: Reflected by higher allergy prevalence, our findings indicate an impaired immune response in obesity and hyperlipidaemia, which is differentially regulated in type I and type IV allergies by an unfavourable lifestyle constellation and subsequent microbial and metabolic dysfunctions.