Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition.

3,3',5.5'-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures at 0.75 h post fertilization (hpf) and showed that TBBPA induced developmental delays during maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 µM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Immunostaining and in vitro experiments showed inhibition of histone H3 lysine 27 acetylation (H3K27Ac) as well as its catalyzing enzyme, p300. Finally, co-exposure with a p300 activator showed partial mitigation of effects, demonstrating that inhibition of histone acetylation drives TBBPA-induced developmental delays.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Exploring the Structurally Conserved Regions and Functional Significance in Bacterial N-Terminal Nucleophile (Ntn) Amide-Hydrolases.

The initial adoption of penicillin as an antibiotic marked the start of exploring other compounds essential for pharmaceuticals, yet resistance to penicillins and their side effects has compromised their efficacy. The N-terminal nucleophile (Ntn) amide-hydrolases S45 family plays a key role in catalyzing amide bond hydrolysis in various compounds, including antibiotics like penicillin and cephalosporin. This study comprehensively analyzes the structural and functional traits of the bacterial N-terminal nucleophile (Ntn) amide-hydrolases S45 family, covering penicillin G acylases, cephalosporin acylases, and D-succinylase. Utilizing structural bioinformatics tools and sequence analysis, the investigation delineates structurally conserved regions (SCRs) and substrate binding site variations among these enzymes. Notably, sixteen SCRs crucial for substrate interaction are identified solely through sequence analysis, emphasizing the significance of sequence data in characterizing functionally relevant regions. These findings introduce a novel approach for identifying targets to enhance the biocatalytic properties of N-terminal nucleophile (Ntn) amide-hydrolases, while facilitating the development of more accurate three-dimensional models, particularly for enzymes lacking structural data. Overall, this research advances our understanding of structure-function relationships in bacterial N-terminal nucleophile (Ntn) amide-hydrolases, providing insights into strategies for optimizing their enzymatic capabilities.

Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition.

3,3',5.5'-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40µM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 µM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 µM. Embryos exposed to sublethal TBBPA concentrations from 0.75-6 hpf and raised in clean water to 120 hpf showed altered larval photomotor response (LPR), suggesting a compromised developmental health. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 µM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we immunostained embryos with an H3K27Ac antibody and demonstrated reduced acetylation in TBBPA-exposed embryos. Leveraging in silico molecular docking studies and in vitro assays, we also showed that TBBPA potentially binds to P300- a protein that catalyzes acetylation- and inhibits P300 activity. Finally, we co-exposed embryos to 20 µM TBBPA and 50 µM n-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTPB co or pre-exposures significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.

Thyroid Leiomyoma: Case Report.

37-year-old Colombian male with mass in the anterior region of the neck. Initial ultrasonography and computed tomography (CT) scan showed a large solid mass (67 × 20.7 mm), dependent on the thyroid isthmus. Total thyroidectomy (TT) was performed. The latest pathological and immunohistochemical findings showed a mesenchymal neoplasm compatible with primary thyroid leiomyoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04356-2.

Detection and mapping of the seasonal distribution of water hyacinth (Eichhornia crassipes) and valorization as a biosorbent of Pb(II) in water.

In the present research, the presence of water hyacinth (Eichhornia crassipes) on the surface of the San Jose Dam located in the city of San Luis Potosi, S.L.P, Mexico, was monitored and mapped. The monitoring was conducted for 2 years (2018-2020) with remote sensing data from OLI Landsat 8 sensors, based on the normalized difference vegetation index (NDVI). The results demonstrated the capability and accuracy of this method, where it was observed that the aboveground cover area, proliferation, and distribution of water hyacinth are influenced by climatic and anthropogenic factors during the four seasons of the year. As part of a sustainable environmental control of this invasive species, the use of water hyacinth (WH) root (RO), stem (ST), and leaf (LE) components as adsorbent material for Pb(II) present in aqueous solution was proposed. The maximum adsorption capacity was observed at pH 5 and 25 °C and was 107.3, 136.8, and 120.8 mg g-1 for RO, ST, and LE, respectively. The physicochemical characterization of WH consisted of scanning electron microscopy (SEM), N2 physisorption, infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), charge distribution, and zero charge point (pHPZC). Due to the chemical nature of WH, several Pb(II) adsorption mechanisms were proposed such as electrostatic attractions, ion exchange, microprecipitation, and π-cation.

Binary fluoride and As(V) adsorption in water using pleco fish bone chars.

The present work studied individual and binary adsorption of fluorides and As(V) in water on pleco fish bone chars (BC), as well as the effect of BC mass variation on the adsorption capacity of fluoride and As(V) in water for human consumption. The results of individual adsorption indicated that the adsorption of fluoride and As(V) on BC depends on solution pH. The adsorption capacity of fluorides at an initial concentration of 30 mg L-1 increases approximately 3 times, from 5.9 to 15.3 mg g-1, when decreasing the pH of the solution from 9 to 5, however, for the case of As(V) an antagonistic effect is observed, the adsorption capacity increases 7 times when raising the pH from 5 to 9, from 18.4 to 132.1 µg g-1 at an initial As(V) concentration of 300 µg L-1. Besides, in the binary adsorption, BC showed a higher affinity to adsorb fluoride since its adsorption capacity decreased from 16.55 to 12.50 mg g-1 as the As(V) concentration increased from 0 to 800 µg L-1 in solution. In contrast, As(V) adsorption was severely affected, decreasing from 140.2 to 32.7 µg g-1 when the fluoride concentration in the solution increased from 0 to 100 mg L-1. On the other hand, in the adsorption of groundwater contaminated with fluoride and As(V), it was determined that increasing the mass of BC from 0.5 to 20 g increases the removal percentage, reaching 99.3 and 75.7% removal for fluoride and As(V), respectively, due to the fact that increasing the mass of the adsorbent leads to a larger area and a greater number of sites that allow the adsorption of these contaminants. The thermodynamic study revealed the spontaneity of fluoride and As(V) adsorption, better affinity for fluoride but higher adsorption rate of As(V) on BC. Characterization techniques such as XRD and EDS allowed identifying hydroxyapatite as the mineral phase of BC, which is responsible for the adsorption of BC. By studying the effect of solution pH on the adsorption capacities and the characterization of BC such as XRD, EDS and TGA, it was determined that the mechanisms of fluoride adsorption are by electrostatic attractions and ion exchange, and for As(V) it is by coprecipitation and ion exchange. It was concluded that BC from pleco fish could be an alternative for treating water contaminated by fluorides and As(V).

Neuroendocrine Tumor Metastases to the Breast: A Case Report and Review of the Literature.

Breast metastases from neuroendocrine neoplasms (NENs) are considered infrequent. We report a case of a patient with ileocecal neuroendocrine tumor (NET) metastases to both breasts, for whom the initial clinical presentation was chronic diarrhea. Breast metastasis was initially suspected by a 68-Gallium DOTANOC positron emission tomography (PET)/CT and was confirmed by histopathology. We also performed a literature review in which we identified 116 cases of NENs metastatic to the breast reported so far. Most cases occurred in older women, were caused by NETs, and had the gastrointestinal tract as the primary site.

"Measuring the Environmental Context of Child Growth in Burkina Faso".

Child growth failure, as indicated by low height-for-age z-scores (HAZ), is an important metric of health, social inequality, and food insecurity. Understanding the environmental pathways to this outcome can provide insight into how to prevent it. While other studies have examined the environmental determinants of HAZ, there is no agreed upon best-practices approach to measure the environmental context of this outcome. From this literature, we derive a large set of potential environmental predictors and specifications including temperature and precipitation levels, anomalies, and counts as well as vegetation anomalies and trends, which we include using linear, nonlinear, and interactive specifications. We compare these measures and specifications using four rounds of DHS survey data from Burkina Faso and a large set of fixed effects regression models, focusing on exposures from the time of conception through the second year of life and relying on joint hypothesis tests and goodness-of-fit measures to determine which approach best explains HAZ. Our analysis reveals that nonlinear and interactive transformations of climate anomalies, as opposed to climate levels or vegetation indices, provide the best explanation of child growth failure. These results underline the complex and nonlinear pathways through which climate change affects child health and should motivate climate-health researchers to more broadly adopt measures and specifications that capture these pathways.

A Study of the Interactions of Heavy Metals in Dairy Matrices Using Fourier Transform Infrared Spectroscopy, Chemometric, and In Silico Analysis.

Heavy metals are among the toxic substances longest recognized by man. Today, due to the myriad sources of exposure, such as contaminated water, food, or air, they have become a major public health problem. This work presents the effects manifested in the infrared spectrum behavior caused by the presence of Cd2+, Cr6+, and Pb2+ at different concentrations in three different matrices: water, casein, and milk; observing that the spectral modifications in the regions of different vibrational modes of nucleophilic groups such as -OH, COO- and NH2 depending on the nature of the metal and its concentration. These findings were correlated in-silico using optimized models in Gabedit software and structural optimization was performed with MOPAC 2016 showing stable structures between the metals and Gln, Hys, Glu, and Phe of casein. By applying chemometrics (Principal Component Analysis), it was possible to observe a good correlation between the experimental data and to discriminate between the type of metal, the matrix that contains it, and the concentration could be represented through linear models that showed adjustments with a value of r2 ≥ 0.95.