Search

Phthalates are environmental endocrine disruptors with thyroid-disrupting properties; however, the association between phthalate exposure and subclinical hypothyroidism (SCH) during pregnancy is unknown. We recruited a study population from a cohort of pregnant women in Beijing, China, and conducted the present pilot case-control study of 42 SCH cases and 84 non-SCH controls matched with age and body mass index (BMI). Serum levels of thyroid peroxidase antibody, free thyroxine (FT 4), thyroid-stimulating hormone (TSH), and urinary levels of ten phthalate metabolites during early pregnancy were measured. Urinary monoethyl phthalate (MEP) levels in SCH cases were observably higher than those in controls (p = 0.01). Conditional logistic regression analysis revealed that mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), MEP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and di-(2-ethylhexyl) phthalate (ΣDEHP) were significantly associated with a higher risk of SCH during early pregnancy (adjusted odds ratios = 1.89, 1.42, 1.81, and 1.92, respectively). Concomitantly, multiple linear regression analysis showed that MECPP, MEOHP, and ΣDEHP were positively associated with TSH and FT 4 × TSH in the entire study population. Bayesian kernel machine regression analysis and stratified analysis by BMI revealed upward tendencies in the serum levels of TSH and FT 4 × TSH. In summary, exposure to phthalates, especially DEHP, may be associated with a higher risk of SCH during early pregnancy, and a possible mechanism is the disruption of the hypothalamus-pituitary-thyroid axis. [Display omitted] • DEP exposure levels of SCH cases were observably higher than those of controls. • Phthalate exposure during early pregnancy may be related to a higher risk of SCH. • MECPP, MEOHP and ΣDEHP were positively associated with TSH and FT 4 × TSH. [ABSTRACT FROM AUTHOR]

Cinnabar, a mercury-containing mineral medicine, has long been widely used in pediatric prescriptions. The safety of cinnabar-containing prescriptions, particularly for children, is drawing increasing attention worldwide. However, whether cinnabar and these pediatric prescriptions have adverse effects on neurobehavior is unknown. Yi-Nian-Jin (YNJ), a classic pediatric prescription, contains 5.66% (w/w) cinnabar, along with other four herbs. YNJ is widely prescribed to promote digestion, eliminate phlegm, and prevent constipation in children (aged 0–6 years). In this study, we used YNJ as an example of cinnabar-containing pediatric prescriptions to determine mercury absorption, distribution, and accumulation and further investigate its potential neurotoxicity in juvenile rats. Low (67.9 mg/kg), middle (169.8 mg/kg), and high dose (339.6 mg/kg) of cinnabar, and low (1.2 g/kg), middle (3.0 g/kg), and high dose (6.0 g/kg) of YNJ were used in this study, corresponding to 3, 7.5, and 15 times the clinically equivalent dose, respectively. Juvenile rats were orally administered different doses of cinnabar or YNJ for 14 consecutive days. The mercury content in rat blood and tissues (brain, liver, and kidney) and serum biochemical changes on day 14 of consecutive administration and on day 14 after cessation were measured. Moreover, a series of behavioral assays (open field, elevated plus-maze, and Morris water maze assays) were performed after 14 consecutive days of administration. The mercury absorption, distribution, and accumulation of cinnabar and YNJ in juvenile rats were substantially different. Mercury in cinnabar was absorbed to a greater extent than that in YNJ, and the mercury content in cinnabar high-dose group (cinnabar-H) was approximately seven times higher than that in YNJ high-dose group (YNJ-H) on day 14 of administration. In contrast, compared with that of cinnabar, the mercury content in YNJ accumulated more in the tissues, especially in the brain and kidney. Repeated administration of cinnabar or YNJ did not affect liver function, renal function, learning, and memory in juvenile rats. However, repeated administration of YNJ at a high dose (6.0 g/kg) affected locomotor activity in juvenile rats. Repeated administration of cinnabar (339.6 mg/kg) or YNJ (>1.2 g/kg) induced anxiety-related behavior in juvenile rats. Mercury in YNJ exhibited lower absorption but higher accumulation in tissues than those of the mercury in cinnabar. Consecutive oral administration of cinnabar or YNJ had no impact on liver function, renal function, learning, and memory, but could cause motor dysfunction and anxiety in juvenile rats. [Display omitted] • A pilot study of cinnabar-containing pediatric prescription Yi-Nian-Jin (YNJ). • Mercury in YNJ exhibited lower absorption but higher accumulation in tissues than those of the mercury in cinnabar. • YNJ had no impact on the liver and renal function. • YNJ had no impact on the learning and memory. • Repeated administration of YNJ could affect locomotor activity and induce anxiety. [ABSTRACT FROM AUTHOR]

Measuring adenoma detection rates (ADRs) at the population level is challenging because pathology reports are often reported in an unstructured format; further, there is significant variation in reporting methods across institutions. Natural language processing (NLP) can be used to extract relevant information from text-based records. We aimed to develop and validate an NLP algorithm to identify colorectal adenomas that could be used to report ADR at the population level in Ontario, Canada. The sampling frame included pathology reports from all colonoscopies performed in Ontario in 2015 and 2016. Two random samples of 450 and 1000 reports were selected as the training and validation sets, respectively. Expert clinicians reviewed and classified reports as adenoma or other. The training set was used to develop an NLP algorithm (to identify adenomas) that was evaluated using the validation set. The NLP algorithm test characteristics were calculated using expert review as the reference. We used the algorithm to measure ADR for all endoscopists in Ontario in 2019. The 1450 pathology reports were derived from 62 laboratories, 266 pathologists, and 532 endoscopists. In the training set, the NLP algorithm for any adenoma had a sensitivity of 99.60% (95% confidence interval (CI), 97.77-99.99), specificity of 99.01% (95% CI, 96.49-99.88), positive predictive value of 99.19% (95% CI, 97.12-99.90), and F1 score of.99. Similar results were obtained for the validation set. The median ADR was 33% (interquartile range, 26%-40%). When we used a population-based sample from Ontario, our NLP algorithm was highly accurate and was used at the system level to measure ADR. [ABSTRACT FROM AUTHOR]

5, Atezolizumab induced high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). In the Abstract section, "However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy" now reads: "However, aglycosylated Atezolizumab is unstable and easy to form aggregates." 5, Atezolizumab induced extremely high titers of ADA in mice, in good agreement with what was observed in monkeys (100%) and cancer patients (41.5%). [Extracted from the article]

Previous direct C−H nitrogenation suffered from simple amidation/amination with limited atom-economy and is mostly limited to C(sp2)−H substrates. In this work, anthranil was designed as a novel bifunctional aminating reagent for both C(sp2)−H and C(sp3)−H bonds under rhodium(III) catalysis, thus affording a nucleophilic aniline tethered to an electrophilic carbonyl. A tridendate rhodium(III) complex has been isolated as the resting state of the catalyst, and DFT studies established the intermediacy of a nitrene species. [ABSTRACT FROM AUTHOR]

We report the case of a 59‐year‐old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C‐reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen‐B27 were unremarkable. Whole body bone scintigraphy via technetium 99m‐methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement. [ABSTRACT FROM AUTHOR]

Phthalates are a class of environmental endocrine disruptors. Previous studies have demonstrated that phthalate exposure can affect thyroid function; however, limited studies have assessed the associations between phthalate exposure and thyroid function, especially thyroid autoimmunity in pregnant women during the first trimester. We recruited participants from a cohort of pregnant women in Beijing, China, and collected urine samples to measure ten phthalate metabolites, serum samples to measure free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) during the first trimester. We included 325 pregnant women without thyroid diseases or dysfunction in this study. Associations between phthalate metabolites and thyroid function parameters were assessed with the Bayesian kernel machine regression (BKMR) model, multiple linear regression model, and restricted cubic spline. In the BKMR model analysis, compared to the 50th percentile, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels when phthalate metabolites were at or below the 40th percentile. Stratifying by body mass index, total urinary phthalate metabolites levels were negatively associated with serum TPOAb levels in normal weight women when phthalate metabolites were at or below the 45th percentile. However, total urinary phthalate metabolites levels were positively associated with serum TPOAb levels in underweight women when phthalate metabolites were at or below the 30th percentile. In restricted cubic spline analysis, L -shaped nonlinear associations of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), di-(2-ethylhexyl) phthalate (ΣDEHP), and inverted S-shaped nonlinear association of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with TPOAb were observed. In conclusion, our findings suggest that phthalate exposure may affect thyroid autoimmunity in underweight pregnant women during early pregnancy, and the potential effects of phthalate exposure on thyroid autoimmunity may be nonlinear. [Display omitted] • The joint effects of phthalate exposure were assessed using the BKMR model. • Urinary phthalate metabolites were mainly associated with serum TPOAb levels. • Phthalates may affect thyroid autoimmunity in underweight pregnant women. [ABSTRACT FROM AUTHOR]

Previous data suggested that activation of endocannabinoid receptor 1 (CB1) was necessary for the orexigenic effect of Ghrelin in rodents, but the information is limited in teleosts. To investigate the feeding regulation pathway of Ghrelin and CB1 in Siberian sturgeon (Acipenser baerii), this study first identified the Ghrelin (345 bp, complete coding sequence) and Ghrelin receptor (GHSR, 500 bp, partial coding sequence) sequences, and then detected their tissue distribution patterns, which showed that Ghrelin is mainly distribution in peripheral tissues, while GSHR is mainly in different brain divisions. Besides, the qPCR before and after feeding showed that the mRNA expressions of Ghrelin and GHSR were inhibited after feeding in telencephalon, diencephalon and mesencephalon. Subsequently, the food intake and appetite factor expressions were measured by i.c.v. co-injection of Ghrelin and GSHR antagonist. The results showed that Ghrelin promoted the food intake of Siberian sturgeon, which was reversed by its receptor antagonist. Besides, i.c.v. injection of Ghrelin decreased telencephalon CART expression while increased NPY expression in the three brain regions. In addition, to further explore the relationship of Ghrelin and CB1 signal regulating feeding, the co-injection of Ghrelin and CB1 antagonists was performed. The results showed that AM6545 (CB1 peripheral restricted antagonist) failed to affect the orexigenic effect of Ghrelin and the expression pattern of NPY mRNA in the telencephalon. While in the diencephalon, the increase of food intake and NPY mRNA expression induced by Ghrelin was completely reversed by Rimonabant (CB1 global antagonist). These results indicate Ghrelin-GSHR pathway promotes the food intake of Siberian sturgeon by inducing the expression of NPY in the diencephalon, and the stimulating effect will be reversed by cannabinoid receptor antagonism. This study provides a foundation for understanding the pathways Ghrelin and CB1 signals in appetite regulation of the teleost. • Ghrelin mainly distributed in the peripheral, while GSHR primarily expressed in the brain. • Ghrelin-GSHR pathway affects the appetite of Siberian sturgeon via CART and NPY, especially by NPY. • The orexigenic effect of ghrelin was mainly eliminated by global CB1 inhibitor. • Ghrelin induced food intake mainly by endocannabinoid signal to affect the NPY in the diencephalon. [ABSTRACT FROM AUTHOR]