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Pediatricians should be familiar with principles of medical toxicology given that intentional and unintentional ingestions are commonly encountered in different medical settings. Most exploratory ingestions are well tolerated and do not cause significant health effects, but a few noteworthy exceptions can lead to serious illness and death. This article reviews common medications and household products likely to cause significant toxicity in pediatric patients, even in small, exploratory ingestions. Increasing cannabis exposures among children and adolescents are also reviewed. Additionally, indications for gastric decontamination with activated charcoal are reviewed. Finally, poisoning prevention strategies are reviewed. [ Pediatr Ann . 2023;52(4):e139-e145.] .

Streptomyces species produce a wide variety of specialized metabolites, some of which are used for communication or competition for resources in their natural environments. In addition, many natural products used in medicine and industry are derived from Streptomyces , and there has been interest in their capacity to produce volatile organic compounds (VOCs) for different industrial and agricultural applications. Recently, a machine-learning workflow called MSHub/GNPS was developed, which enables auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data, molecular networking, and library search capabilities, but it has not been applied to Streptomyces volatilomes. In this study, 131 Streptomyces isolates from the island of Newfoundland were phylogenetically typed, and 37 were selected based on their phylogeny and growth characteristics for VOC analysis using both a user-guided (conventional) and an MSHub/GNPS-based approach. More VOCs were annotated by MSHub/GNPS than by the conventional method. The number of unknown VOCs detected by the two methods was higher than those annotated, suggesting that many novel compounds remain to be identified. The molecular network generated by GNPS can be used to guide the annotation of such unknown VOCs in future studies. However, the number of overlapping VOCs annotated by the two methods is relatively small, suggesting that a combination of analysis methods might be required for robust volatilome analysis. More than half of the VOCs annotated with high confidence by the two approaches are plant-associated, many with reported bioactivities such as insect behavior modulation. Details regarding the properties and reported functions of such VOCs are described. IMPORTANCE This study represents the first detailed analysis of Streptomyces volatilomes using MSHub/GNPS, which in combination with a routinely used conventional method led to many annotations. More VOCs could be annotated using MSHub/GNPS as compared to the conventional method, many of which have known antimicrobial, anticancer, and insect behavior-modulating activities. The identification of numerous plant-associated VOCs by both approaches in the current study suggests that their production could be a more widespread phenomenon by members of the genus, highlighting opportunities for their large-scale production using Streptomyces. Plant-associated VOCs with antimicrobial activities, such as 1-octen-3-ol, octanol, and phenylethyl alcohol, have potential applications as fumigants. Furthermore, many of the annotated VOCs are reported to influence insect behavior, alluding to a possible explanation for their production based on the functions of other recently described Streptomyces VOCs in dispersal and nutrient acquisition.

Burn induction methodologies are inconsistently described in rat models. A uniform burn wound model, which represents the clinical scenario, is necessary to perform reproducible burn research. The present protocol describes a simple and reproducible method to create ~20% total body surface area (TBSA) full-thickness burns in rats. Here, a 22.89 cm 2 (5.4 cm diameter) copper rod heated at 97 °C in a water bath was applied to the rat skin surface to induce the burn injury. A copper rod with a high thermal conductivity was able to dissipate the heat deeper in the skin tissue to create a full-thickness burn. Histology analysis shows attenuated epidermis with coagulative damage to the full-thickness extent of the dermis and the subcutaneous tissue. Additionally, this model is representative of the clinical situations observed in hospitalized burn patients following burn injury such as immune dysregulation and bacterial infections. The model can recapitulate the systemic bacterial infection by both Gram-positive and Gram-negative bacteria. In conclusion, this paper presents an easy-to-learn and robust rat burn model that mimics the clinical situations, including immune dysregulation and bacterial infections, which is of considerable utility for the development of new topical antibiotic drugs for burn wound and infections.

Introduction: Sodium nitrite is an oxidizing agent capable of producing profound methemoglobinemia. Large quantities of sodium nitrite can be purchased online, and recent literature has identified several cases of intentional self-poisoning, including multiple cases of mortality. This has raised concern that intentional sodium nitrite poisoning and resultant severe methemoglobinemia may be increasing in incidence and could represent a substantial public health threat., Materials and Methods: This study used data obtained from the National Poison Data System (NPDS) to evaluate the incidence and mortality rate of intentional sodium nitrite poisoning of suicidal intent reported to US poison centers over a five-year period. Patient demographics, exposure characteristics, treatments administered, and patient outcomes were analyzed. Temporal patterns in exposure were also investigated., Results: Forty-seven cases were identified in the NPDS database, of which three were excluded due to lack of outcome data. Median patient age was 23 years, 52% of patients were female and 86% of exposures occurred at the patient's residence. Serious outcomes were observed in 84% of cases, 77% of patients included were treated with methylene blue and 30% of patients died. No intentional sodium nitrite exposures were reported in the first two years studied, but we observed an increase in the incidence of exposures reported through the remainder of the investigation period., Discussion/conclusions: The incidence of intentional self-poisoning with sodium nitrite has been increasing since 2017. Many of these exposures result in toxicity requiring antidotal therapy, and a high mortality rate was observed. Recent literature indicates that this trend may be the result of ready access to this poison through online vendors combined with recommendations shared in online communities that sodium nitrite be used as an effective method of suicide. Further study is needed to better characterize this phenomenon and develop public health interventions to prevent future morbidity and mortality.

To better understand cellular communication driving diverse behaviors, we need to uncover the molecular mechanisms of within-cell-type functional heterogeneity. While single-cell RNA sequencing (scRNAseq) has advanced our understanding of cell heterogeneity, linking individual cell phenotypes to transcriptomic data remains challenging. Here, we used a phenotypic cell sorting technique to ask whether phenotypically supervised scRNAseq analysis (pheno-scRNAseq) can provide more insight into heterogeneous cell behaviors than unsupervised scRNAseq. Using a simple 3D in vitro breast cancer (BRCA) model, we conducted pheno-scRNAseq on invasive and non-invasive cells and compared the results to phenotype-agnostic scRNAseq analysis. Pheno-scRNAseq identified unique and more selective differentially expressed genes than unsupervised scRNAseq analysis. Functional studies validated the utility of pheno-scRNAseq in understanding within-cell-type functional heterogeneity and revealed that migration phenotypes were coordinated with specific metabolic, proliferation, stress, and immune phenotypes. This approach lends new insight into the molecular systems underlying BRCA cell phenotypic heterogeneity., Competing Interests: The authors declare no competing interests., (© 2020 The Author(s).)

The Streptomyces produce a great diversity of specialized metabolites, including highly volatile compounds with potential biological activities. Volatile organic compounds (VOCs) produced by nine Streptomyces spp., some of which are of industrial importance, were collected and identified using gas chromatography-mass spectrometry (GC-MS). Biosynthetic gene clusters (BGCs) present in the genomes of the respective Streptomyces spp. were also predicted to match them with the VOCs detected. Overall, 33 specific VOCs were identified, of which the production of 16 has not been previously reported in the Streptomyces . Among chemical classes, the most abundant VOCs were terpenes, which is consistent with predicted biosynthetic capabilities. In addition, 27 of the identified VOCs were plant-associated, demonstrating that some Streptomyces spp. can also produce such molecules. It is possible that some of the VOCs detected in the current study have roles in the interaction of Streptomyces with plants and other higher organisms, which might provide opportunities for their application in agriculture or industry.

Redox modulators have been developed as an attractive approach to treat cancer. Herein, we report the synthesis, identification, and biological evaluation of a quinazolinedione reactive oxygen species (ROS) inducer, QD394, with significant cytotoxicity in pancreatic cancer cells. QD394 shows a transcriptomic profile remarkably similar to napabucasin, a cancer stemness inhibitor. Both small molecules inhibit STAT3 phosphorylation, increase cellular ROS, and decrease the GSH/GSSG ratio. Moreover, QD394 causes an iron- and ROS-dependent, GPX4 mediated cell death, suggesting ferroptosis as a major mechanism. Importantly, QD394 decreases the expression of LRPPRC and PNPT1, two proteins involved in mitochondrial RNA catabolic processes and both negatively correlated with the overall survival of pancreatic cancer patients. Pharmacokinetics-guided lead optimization resulted in the derivative QD394-Me, which showed improved plasma stability and reduced toxicity in mice compared to QD394. Overall, QD394 and QD394-Me represent novel ROS-inducing drug-like compounds warranting further development for the treatment of pancreatic cancer.

Female choice is an important driver of sexual selection, but can be costly, particularly when choosy females risk remaining unmated or experience delays to reproduction. Thus, females should reduce choosiness when mate encounter rates are low. We asked whether choosiness is affected by social context, which may provide reliable information about the local availability of mates. This has been demonstrated in the lab, but rarely under natural conditions. We studied western black widow spiders (Latrodectus hesperus) in the field, placing experimental final-instar immature females so they were either 'isolated' or 'clustered' near naturally occurring conspecifics (≥10 m or ≤1 m, respectively, from a microhabitat occupied by at least one other female). Upon maturity, females in both treatments were visited by similar numbers of males, but clustered females were visited by males earlier and in more rapid succession than isolated females, confirming that proximity to conspecifics reduces the risk of remaining unmated. As predicted, isolated females were less choosy in staged mating trials, neither rejecting males nor engaging in pre-copulatory cannibalism, in contrast to clustered females. These results demonstrate that exposure of females to natural variation in demography in the field can alter choosiness of adults. Thus, female behaviour in response to cues of local population density can affect the intensity of sexual selection on males in the wild.

Mate-searching success is a critical precursor to mating, but there is a dearth of research on traits and tactics that confer a competitive advantage in finding potential mates. Theory and available empirical evidence suggest that males locate mates using mate-attraction signals produced by receptive females (personal information) and avoid inadvertently produced cues from rival males (social information) that indicate a female has probably already mated. Here, we show that western black widow males use both kinds of information to find females efficiently, parasitizing the searching effort of rivals in a way that guarantees competition over mating after reaching a female's web. This tactic may be adaptive because female receptivity is transient, and we show that (i) mate searching is risky (88% mortality) and (ii) a strongly male-biased operational sex ratio (from 1.2 : 1 to more than 10 : 1) makes competition inevitable. Males with access to rivals' silk trails moved at higher speeds than those with only personal information, and located females even when personal information was unreliable or absent. We show that following rivals can increase the potential for sexual selection on females as well as males and argue it may be more widespread in nature than is currently realized.

Chemical communication is common in spiders but few pheromones have been identified. Female widow spiders in the genus Latrodectus spin webs that disseminate an attractive sex pheromone, and a contact pheromone on the silk elicits courtship behavior by males. The methyl ester of N-3-methylbutanoyl-O-(S)-2-methylbutanoyl-L-serine is a contact pheromone of the Australian redback spider Latrodectus hasselti. We hypothesized that the contact pheromone of congeneric L. hesperus resembles that of L. hasselti. The silk of virgin L. hesperus females was extracted with methanol, and analyses by gas chromatography-mass spectrometry (GC/MS) provided evidence for the presence of N-3-methylbutanoyl-O-methylpropanoyl-L-serine methyl ester (MB-MP-S), a lower homologue of the L. hasselti contact pheromone. Behavioral responses of L. hesperus males to test stimuli were assayed on T-shaped rods with the end sections of the horizontal arm enveloped in filter paper. Males spent 40 % longer in contact with paper bearing female silk than with blank paper, and 39 % longer in contact with paper treated with silk extract than with solvent controls. Contact with silk and silk extract induced courtship behavior by 96 % and 80 % of males, respectively, indicating that there was a methanol-soluble courtship-eliciting contact pheromone on the silk. Males responded less strongly to synthetic MB-MP-S than to silk or silk extract. Paper impregnated with synthetic MB-MP-S (10 or 100 μg) induced courtship behavior in 3-16 % of males, and prompted males to stay 10-16 % longer than on control paper. Our data support the conclusion that MB-MP-S is part of a multi-component contact pheromone of L. hesperus.

Expression of the ErbB4 tyrosine kinase is elevated in colonic epithelial cells during inflammatory bowel disease, whereas ErbB4 overexpression in cultured colonocytes blocks TNF-induced apoptosis in a ligand-dependent manner. Together, these observations suggest that ErbB4 induction may be a protective response. However, the effects of ErbB4 signaling in the colonic epithelium in vivo are not known. Furthermore, previous work on ErbB4 used ligands shared with other receptors, raising the question of whether the observed responses are explicitly due to ErbB4. In this study, we used the ErbB4-specific ligand neuregulin-4 (NRG4) to activate ErbB4 and define its role in colonocyte biology. NRG4 treatment, either in cultured cells or in mice, blocked colonic epithelial apoptosis induced by TNF and IFN-γ. It was also protective in a murine experimental colitis model. NRG4 stimulated phosphorylation of ErbB4 but not other ErbB receptors, indicating that this is a specific response. Furthermore, in contrast to related ligands, NRG4 enhanced cell survival but not proliferation or migration, and stimulated phosphorylation of the anti-apoptotic mediator Akt but not ERK MAPK. Pharmacological inhibition of PI3K/Akt signaling reversed the anti-apoptotic effects of NRG4, confirming the role of this cascade in NRG4-induced cell survival. With regard to the potential clinical importance of this pathway, NRG4 expression was decreased in human inflammatory bowel disease samples and mouse models of colitis, suggesting that activation of ErbB4 is altered in disease. Thus, exogenous NRG4 may be beneficial for disorders in which epithelial apoptosis is part of the pathology.

Both gene methylation changes and genetic instability have been noted in offspring of male rodents exposed to radiation or chemicals, but few specific gene targets have been established. Previously, we identified the gene for ribosomal RNA, rDNA, as showing methylation change in sperm of mice treated with the preconceptional carcinogen, chromium(III) chloride. rDNA is a critical cell growth regulator. Here, we investigated the effects of paternal treatments on rDNA in offspring tissue. A total of 93 litters and 758 offspring were obtained, permitting rigorous mixed-effects models statistical analysis of the results. We show that the offspring of male mice treated with Cr(III) presented increased methylation in a promoter sequence of the rDNA gene, specifically in lung. Furthermore polymorphic variants of the multi-copy rDNA genes displayed altered frequencies indicative of structural changes, as a function of both tissue type and paternal treatments. Organismal effects also occurred: some groups of offspring of male mice treated with either Cr(III) or its vehicle, acidic saline, compared with those of untreated mice, had altered average body and liver weights and levels of serum glucose and leptin. Males treated directly with Cr(III) or acidic saline presented serum hormone changes consistent with a stress response. These results establish for the first time epigenetic and genetic instability effects in a gene of central physiological importance, in offspring of male mice exposed preconceptionally to chemicals, possibly related to a stress response in these males., (Copyright © 2012 Wiley Periodicals, Inc.)