A poisonous cocktail: interplay of cereulide toxin and its structural isomers in emetic Bacillus cereus.

Food intoxications evoked by emetic Bacillus cereus strains constitute a serious threat to public health, leading to emesis and severe organ failure. The emetic peptide toxin cereulide, assembled by the non-ribosomal peptide synthetase CesNRPS, cannot be eradicated from contaminated food by usual hygienic measures due to its molecular size and structural stability. Next to cereulide, diverse chemical variants have been described recently that are produced concurrently with cereulide by CesNRPS. However, the contribution of these isocereulides to the actual toxicity of emetic B. cereus, which produces a cocktail of these toxins in a certain ratio, is still elusive. Since cereulide isoforms have already been detected in food remnants from foodborne outbreaks, we aimed to gain insights into the composition of isocereulides and their impact on the overall toxicity of emetic B. cereus. The amounts and ratios of cereulide and isocereulides were determined in B. cereus grown under standard laboratory conditions and in a contaminated sample of fried rice balls responsible for one of the most severe food outbreaks caused by emetic B. cereus in recent years. The ratios of variants were determined as robust, produced either under laboratory or natural, food-poisoning conditions. Examination of their actual toxicity in human epithelial HEp2-cells revealed that isocereulides A-N, although accounting for only 10% of the total cereulide toxins, were responsible for about 40% of the total cytotoxicity. An this despite the fact that some of the isocereulides were less cytotoxic than cereulide when tested individually for cytotoxicity. To estimate the additive, synergistic or antagonistic effects of the single variants, each cereulide variant was mixed with cereulide in a 1:9 and 1:1 binary blend, respectively, and tested on human cells. The results showed additive and synergistic impacts of single variants, highlighting the importance of including not only cereulide but also the isocereulides in routine food and clinical diagnostics to achieve a realistic toxicity evaluation of emetic B. cereus in contaminated food as well as in patient samples linked to foodborne outbreaks. Since the individual isoforms confer different cell toxicity both alone and in association with cereulide, further investigations are needed to fully understand their cocktail effect.

Foliar application protected vegetable against poisonous element cadmium and mitigated human health risks.

Foliar application has been reported as an effective method to facilitate plant growth and mitigate cadmium (Cd) accumulation. However, the application of foliar fertilizers on plant production, Cd uptake and health risks of Solanaceae family remains unknown. In this study, four foliar fertilizers were applied to investigate their effects on the production, Cd accumulation and human health risk assessment of two varieties of pepper (Capsicum annuum L.) and eggplant (Solanum melongena L.), respectively. Compared with CK, the foliar application increased vegetable production to 104.16 %-123.70 % in peppers, and 100.83 %-105.17 % in eggplants, accordingly. The application of foliar fertilizers largely decreased Cd TF (transportation factor) by up to 23.32 % in JY, 18.37 % in GJ of pepper varieties, and up to 14.47 % in ZL, 15.24 % in HGR of eggplant varieties. Moreover, Cd BAF (bioaccumulation factor) also declined to different extents after the application of foliar fertilizers. As for human health risk assessments, foliar application diminished the hazard index (HI) and carcinogenic risk (CR) of both pepper and eggplant varieties. The results concluded that the application of composed foliar fertilizers was most effective, and could be a promising alternative for the improvement of vegetable production and mitigation of vegetable Cd accumulation and human health risks as well. The results further highlighted the understanding of foliar fertilizer application on vegetable production and health risks, which benefited better vegetable safe production and further guaranteed human health.

Hexahydrocannabinol poisoning reported to French poison centres.

INTRODUCTION: Hexahydrocannabinol is a hexahydro derivative of cannabinol. Poisoning with hexahydrocannabinol was first observed in Europe in May 2022. METHOD: This is a retrospective observational study of cases of self-reported hexahydrocannabinol exposure reported to French poison centres between 1 January 2022 and 31 May 2023. RESULTS: There were 37 cases, including 19 in May 2023. The median age of the patients was 36 (interquartile range 28-43) years, and most were men. Eight patients had a history of substance use disorder. The route of exposure was ingestion in 24, inhalation (smoking or vaping) in 10, inhalation and ingestion in two and sublingual in one. Clinical features were neurological (85 per cent), cardiovascular (61 per cent), gastrointestinal (33 per cent), psychiatric (27 per cent) and ocular (21 per cent). Fifty-nine per cent of the patients were hospitalized. In four patients, the Poisoning Severity Score was 0 (asymptomatic); in 15 patients, the Score was 1 (minor); in 16, the Score was 2 (moderate); and in two cases, the Score was 3 (severe). In 70 per cent of patients, the outcome was known, and all recovered. Testing of biological samples was only undertaken in six cases. Five patients had positive blood or urine tests for hexahydrocannabinol; in two patients, tetrahydrocannabinol and metabolites were also detected. In addition, there was an additional patient in whom Δ8- and Δ9-tetrahydrocannabinol was detected in the substances used. DISCUSSION: Clinical effects reported in this series included neuropsychiatric and somatic effects. Whilst these cases related to self-reported hexahydrocannabinol use, it is likely that tetrahydrocannabinol use also contributed to the effects in a substantial proportion of cases. This study has some limitations, such as the lack of available information due to the retrospective nature of the study. As a result, it probably overestimates the number of moderate and severe cases due to under-reporting of cases of little or no severity. Analysis of the patient's blood and urine was performed only in six patients, so we cannot be certain that the products consumed by the other patients were hexahydrocannabinol. CONCLUSION: The clinical effects attributed to hexahydrocannabinol were neurological, cardiovascular, gastrointestinal, psychiatric and ocular predominantly and were sometimes serious.

Public health risk due to contamination of Solanum nigrum in frozen green beans - collaboration effort between a poison centre, a hospital and health authorities.

INTRODUCTION: We describe a rare food contamination of organically grown frozen green beans with Solanum nigrum, also called black night shade, which were widely available in supermarkets in the Netherlands. CASE SERIES: To our knowledge, only three adults and one child were referred to the emergency department for observation after eating the contaminated green beans. Only minor symptoms were seen during observation. The remainder of the frozen green beans were obtained from the patients and sent for analysis within one day. Within two and a half days after the first case, a public safety warning and recall were launched. DISCUSSION: Due to an increase in popularity of organic food, more incidents involving toxic weed contaminants like the one we describe in this report could happen when quality control in organic agriculture is insufficient. In this event, the critical control point obtained from the hazard analysis was insufficiently managed by the producer. CONCLUSION: This report demonstrates the efficient collaboration between the Dutch Poisons Information Centre, treating physicians at the hospital and the Netherlands Food and Consumer Product Safety Authority in case of a possible public safety issue. Because of quick acting and collaboration between the involved parties, the product was quickly withdrawn from the market.

Fomepizole use reported to United States Poison Centers from 2010 to 2021.

BACKGROUND: The diagnosis of toxic alcohol poisoning is often based on clinical presentation and nonspecific surrogate laboratory studies due to limited testing availability. Fomepizole is the recommended antidote and often administered empirically. The objective of this study is to identify substances that mimic toxic alcohols and compare key clinical factors between toxic alcohol and non-toxic alcohol exposures when fomepizole was administered. METHODS: This study was a retrospective evaluation using the National Poison Data System from January 1, 2010 through December 31, 2021. Exposures were included if fomepizole was administered. Toxic alcohol exposures had ethylene glycol or methanol as a coded substance. For exposures not coded as a toxic alcohol, the first substance was described. Paracetamol (acetaminophen) exposures from 2020 and 2021 were excluded. RESULTS: Fomepizole was reportedly used 25,110 times over 12 years. Use increased from 1,955 in 2010 to 2,710 in 2021. Most administrations were for reported toxic alcohol poisoning (60 percent) but use in reported non-toxic alcohol poisoning was greater starting in 2020. Toxic alcohol exposures were older (43.3 versus 39.8 years; P < 0.001) and more likely male (65.7 percent versus 58.2 percent). Level of care was mostly a critical care unit (67.7 percent), which was less common in toxic alcohol (63.3 percent) than non-toxic alcohol exposures (74.2 percent). The most common non-toxic alcohol substances were ethanol (24.9 percent) or an unknown drug (17.5 percent). Acidosis, increased creatinine concentration, anion gap, and osmolal gap, and kidney failure were coded in a lower proportion of toxic alcohol exposures than non-toxic alcohol exposures (P < 0.001). DISCUSSION: The inability to provide rapid clinical confirmation of toxic alcohol poisoning results in the empiric administration of fomepizole to many patients who will ultimately have other diagnoses. Although fomepizole is relative well tolerated we estimated that this practice costs between $1.5 to $2.5 million. The major limitations of this work include the biases associated with retrospective record review, and the inability to confirm the exposures which may have resulted in allocation error. CONCLUSION: Most fomepizole use was for a presumed toxic alcohol. This recently shifted to greater use in likely non-toxic alcohol poisoning. Key difference between the groups suggest fomepizole administration was likely due to the difficulty in diagnosis of toxic alcohol poisoning along with the efficacy and safety of fomepizole. Increased toxic alcohol laboratory testing availability could improve timely diagnosis, reserving fomepizole use for toxic alcohol poisoning.

[Development of an analytical system for dried blood spots for forensic toxicology: a case study of five common drugs and poisons].

Dried blood spot (DBS) technology is a simple and convenient method for collecting, transporting, and storing blood samples on filter paper, and has numerous applications in the clinical, research, and public health settings. This technique is gaining popularity in the field of forensic science because it facilitates the rapid analysis of prohibited drugs in blood samples and offers significant advantages in toxicology scenarios such as drinking-driving screening, drug abuse detection, and doping detection. However, the lack of a standardized system and the fact that its stability and reliability have not been thoroughly researched and demonstrated limit its application in judicial practice in China. DBS samples can be prepared, stored, and analyzed in various ways, all of which may significantly affect the results. In this study, we developed a method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) that focuses on the preparation, pretreatment, analysis, and storage of DBS samples. A thorough investigation was conducted to examine the optimal preparation conditions, including the blood spot matrix, drying technique, and preprocessing parameters, such as the solvent and extraction method. Moreover, the analytical conditions, such as the mobile phase system and elution gradient, were established to facilitate the quantitative detection of methamphetamine, lidocaine, ketamine, fentanyl, and diazepam in both DBS and whole-blood samples. The impact of storage conditions, such as the temperature, humidity, and sealing, on the analytical results of the DBS and whole-blood samples was also examined. The results showed a strong linear relationship for lidocaine and fentanyl within the range of 0.5-100 ng/mL. Similarly, methamphetamine, ketamine, and diazepam exhibited good linearity within the range of 2-100 ng/mL. The coefficients of determination (r2) ranged from 0.9983 to 0.9997, and the limits of detection ranged from 0.2 to 0.5 ng/mL, indicating a high degree of correlation and sensitivity. Stability tests demonstrated that the five target substances remained stable in the DBS for 60 days, with the measured contents deviating from the nominal values by 15%. Moreover, the measurement results of the DBS samples were highly similar to those of the whole-blood samples, with mean percentage differences of 4.44%, 3.50%, 7.66%, 5.10%, and 5.25% for fentanyl, diazepam, ketamine, lidocaine, and methamphetamine, respectively. Throughout the 60-day storage period, the maintenance of temperatures of -20 and 4 ℃, as well as sealing and dry storage, was not necessary. Room temperature was the most practical storage environment for the DBS samples. The results for each target showed very small concentration differences between the whole-blood and DBS samples, indicating that the DBS samples were suitable for drug and poison analysis in blood. Furthermore, the DBSs exhibited high quantitative consistency with the whole-blood samples, rendering them suitable matrices for preserving blood samples. Because DBS samples are easy to handle and store, they can realize the lightweight preservation of blood samples and provide a novel solution for the analysis and preservation of blood samples in public security practice. We recommend conducting comprehensive validations before utilizing DBS for analysis, particularly in terms of quantification, to ensure the judicial reliability of the results.

Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin.

The poison dart toxin batrachotoxin is exceptional for its high potency and toxicity, and for its multifaceted modification of the function of voltage-gated sodium channels. By using cryogenic electron microscopy, we identify two homologous, but nonidentical receptor sites that simultaneously bind two molecules of toxin, one at the interface between Domains I and IV, and the other at the interface between Domains III and IV of the cardiac sodium channel. Together, these two bound toxin molecules stabilize α/π helical conformation in the S6 segments that gate the pore, and one of the bound BTX-B molecules interacts with the crucial Lys1421 residue that is essential for sodium conductance and selectivity via an apparent water-bridged hydrogen bond. Overall, our structure provides insight into batrachotoxin's potency, efficacy, and multifaceted functional effects on voltage-gated sodium channels via a dual receptor site mechanism.

Glucagon-Like Peptide-1 Receptor Agonist Cases Reported to United States Poison Centers, 2017-2022.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS: We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS: There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS: Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications.

Exposure to ammonia solution due to substance use: a retrospective study from the French poison centres database (2009-2018).

INTRODUCTION: Ammonia solution (ammonium hydroxide) is used to convert cocaine hydrochloride to freebase cocaine. Due to its causticity, unintentional exposure to ammonia in a substance use context can result in injury. The objective of this study was to describe the characteristics of unintentional oral and buccal ammonia solution exposure in a substance use context. METHODS: A retrospective study was conducted using the French poison centres database over a 10-year period (2009-2018). RESULTS: A total of 1,546 files were extracted, and 263 substance users were included. There was a significant increase in the number of these exposures between 2009 and 2018. Unintentional ingestion of ammonia solution was linked to product decanting in 89 per cent of cases. Substance use prior to the exposure and a festive context, such as free parties or teknivals, were identified in 25 per cent and 21 per cent of cases, respectively. Patients received a hospital examination in 87 per cent of cases. The severity of intoxication in substance users was graded as moderate (33 per cent) or severe (15 per cent) using the Poisoning Severity Score. DISCUSSION: The increased number of ammonia solution cases reported was consistent with an increase in the number of crack users in Europe in the same period. Ammonia solution exposure can suggest the possibility of substance use disorders. In such cases, patients can be referred to receive appropriate treatment and support. This study had some limitations, such as the lack of available information due to the retrospective nature of the study and the non-standardized questions asked by the poison centre during the medical phone interviews. CONCLUSION: Oral and buccal ammonia solution exposure in known substance users in France increased between 2009 and 2018. These users were mostly young men. A festive context and decanting were frequent. Patients were mainly referred to emergency departments to receive clinical examination and care. The potential severity of oral or buccal ammonia solution exposure in substance users requires increased vigilance among all healthcare professionals involved in the management of these intoxication cases.

Prediction the prognosis of the poisoned patients undergoing hemodialysis using machine learning algorithms.

BACKGROUND: Hemodialysis is a life-saving treatment used to eliminate toxins and metabolites from the body during poisoning. Despite its effectiveness, there needs to be more research on this method precisely, with most studies focusing on specific poisoning. This study aims to bridge the existing knowledge gap by developing a machine-learning prediction model for forecasting the prognosis of the poisoned patient undergoing hemodialysis. METHODS: Using a registry database from 2016 to 2022, this study conducted a retrospective cohort study at Loghman Hakim Hospital. First, the relief feature selection algorithm was used to identify the most important variables influencing the prognosis of poisoned patients undergoing hemodialysis. Second, four machine learning algorithms, including extreme gradient boosting (XGBoost), histgradient boosting (HGB), k-nearest neighbors (KNN), and adaptive boosting (AdaBoost), were trained to construct predictive models for predicting the prognosis of poisoned patients undergoing hemodialysis. Finally, the performance of paired feature selection and machine learning (ML) algorithm were evaluated to select the best models using five evaluation metrics including accuracy, sensitivity, specificity the area under the curve (AUC), and f1-score. RESULT: The study comprised 980 patients in total. The experimental results showed that ten variables had a significant influence on prognosis outcomes including age, intubation, acidity (PH), previous medical history, bicarbonate (HCO3), Glasgow coma scale (GCS), intensive care unit (ICU) admission, acute kidney injury, and potassium. Out of the four models evaluated, the HGB classifier stood out with superior results on the test dataset. It achieved an impressive mean classification accuracy of 94.8%, a mean specificity of 93.5 a mean sensitivity of 94%, a mean F-score of 89.2%, and a mean receiver operating characteristic (ROC) of 92%. CONCLUSION: ML-based predictive models can predict the prognosis of poisoned patients undergoing hemodialysis with high performance. The developed ML models demonstrate valuable potential for providing frontline clinicians with data-driven, evidence-based tools to guide time-sensitive prognosis evaluations and care decisions for poisoned patients in need of hemodialysis. Further large-scale multi-center studies are warranted to validate the efficacy of these models across diverse populations.

Assessing the frequency and types of errors involved in the use of a modified intravenous N-acetylcysteine protocol for acetaminophen overdose.

BACKGROUND: Acetaminophen overdose is a leading cause of acute liver failure in developing countries. N-acetylcysteine (NAC) is a highly effective antidote for acetaminophen hepatotoxicity, typically initiated in the emergency department. Due to a known high rate of errors with the standard three-bag IV NAC protocol, in 2019, the Ontario Poison Center changed to a modified 3% IV NAC one-bag protocol. This study was undertaken to determine the frequency and types of errors associated with the use of this protocol. METHODS: Data were gathered via chart review of Ontario Poison Centre electronic medical record cases identified as receiving IV NAC for acetaminophen overdose between August 1 and September 30, 2022. 218 total charts were identified, and 188 were deemed eligible based on inclusion and exclusion criteria. RESULTS: Errors were identified in 25% of charts, consisting of dosing errors in 11.7%, stopping errors in 9.0%, initiation errors in 3.7%, and interruptions in therapy in 3.2%. Dosing errors were the most common type of error (44.4%), with overdoses occurring three times more than underdoses. Errors were identified at 39% of geographic locations in the charts reviewed, with similar frequency in Ontario, Manitoba, and Nunavut. Clinical outcomes were similar in charts with and without errors. INTERPRETATION: The rate of errors identified with this 3% IV NAC one-bag protocol is lower than reported for the standard three-bag protocol, but remains high due to dosing errors. Previously reported issues with prolonged interruptions in therapy with the standard three-bag protocol were low with the current 3% one-bag protocol. Although severe outcomes are rare, IV NAC overdose can be fatal. Identifying local factors in emergency departments that can contribute to administration errors (i.e., dose calculation, pump programming issues) can enhance the safety of this important antidote.

RéSUMé: CONTEXTE: La surdose d'acétaminophène est l'une des principales causes d'insuffisance hépatique aiguë dans les pays en développement. La N-acétylcystéine (NAC) est un antidote très efficace contre l'hépatotoxicité de l'acétaminophène, généralement initiée au service des urgences. En raison d'un taux élevé connu d'erreurs avec le protocole NAC standard à 3 sacs IV, en 2019, le Centre antipoison de l'Ontario a adopté un protocole NAC à 1 sac IV modifié à 3 %. Cette étude a été entreprise pour déterminer la fréquence et les types d'erreurs associées à l'utilisation de ce protocole. MéTHODES: Les données ont été recueillies au moyen d'un examen des dossiers médicaux électroniques du Centre antipoison de l'Ontario qui ont reçu une dose IV de NAC pour une surdose d'acétaminophène entre le 1 août et le 30 septembre 2022. 218 cartes au total ont été identifiées, et 188 ont été jugées admissibles en fonction de critères d'inclusion et d'exclusion. RéSULTATS: Des erreurs ont été relevées dans 25 % des dossiers, soit des erreurs de dosage dans 11,7 %, des erreurs d'arrêt dans 9,0 %, des erreurs d'initiation dans 3,7 % et des interruptions du traitement dans 3,2 %. Les erreurs de dosage étaient le type d'erreur le plus courant (44,4 %), les surdoses étant trois fois plus fréquentes que les sous-doses. Des erreurs ont été relevées à 39 % des emplacements géographiques dans les cartes examinées, avec une fréquence similaire en Ontario, au Manitoba et au Nunavut. Les résultats cliniques étaient similaires dans les tableaux avec et sans erreurs. INTERPRéTATION: Le taux d'erreurs identifiées avec ce protocole à un sac NAC IV à 3 % est inférieur à celui du protocole standard à 3 sacs, mais reste élevé en raison d'erreurs de dosage. Les problèmes précédemment rapportés avec les interruptions prolongées du traitement avec le protocole standard à 3 sacs étaient faibles avec le protocole actuel à 3% à un sac. Bien que les résultats graves soient rares, une surdose de NAC IV peut être fatale. L'identification de facteurs locaux dans les services d'urgence qui peuvent contribuer aux erreurs d'administration (c.-à-d. le calcul de la dose, les problèmes de programmation de la pompe) peut améliorer l'innocuité de cet antidote important.

Risk factors for deliberate self-poisoning among children and adolescents in The Netherlands.

INTRODUCTION: In the past decade, the number of deliberate self-poisonings involving young people has increased strongly worldwide. This study aimed to gain insight into risk factors associated with deliberate self-poisonings among children and adolescents reported to the Dutch Poisons Information Center. METHODS: A study was performed between 1 February 2022 and 31 January 2023 involving those aged 8-17 years of age with deliberate self-poisoning. Data were collected on patient characteristics (age, gender, body mass index and living situation) and exposure characteristics (type of toxicant, way of acquiring toxicant and day of exposure). RESULTS: The Dutch Poisons Information Center was consulted about 1,424 deliberate self-poisonings among children and adolescents (10-17 years old). A high percentage of patients were female (85 percent), had a body mass index classified as overweight/obese (27 percent) and lived in a mental healthcare facility (13 percent). Patients mainly exposed themselves to pharmaceuticals, especially over-the-counter medications such as paracetamol (46 percent) and ibuprofen (15 percent). Young people living with parents/caregivers had higher odds of ingesting prescription pharmaceuticals or over-the-counter medication, while those living in a mental healthcare facility were more likely to ingest household products, personal care products or foreign bodies (predominantly batteries). DISCUSSION: This study sheds light on the pervasive issue of deliberate self-poisoning among children and adolescents, advocating for poisoning prevention strategies and promoting mental health of youth. Limitations include reliance on self-reported data from patients and the absence of clinical outcome data. CONCLUSIONS: Female gender, a high body mass index and living in a mental healthcare facility are associated with in increased risk of deliberate self-poisonings in children and adolescents (10-17 years old). Prevention of deliberate self-poisonings among youth could focus on restricting access to medication and other potentially hazardous non-pharmaceuticals, such as household products and batteries, as well as limiting the sales of over-the-counter medication, especially paracetamol, to this young population.

Oral potassium poisoning: a retrospective review of the National Poison Data System 2010-2021.

INTRODUCTION: Oral potassium poisoning can be life-threatening. The study aimed to describe patterns of oral potassium poisoning in adult and pediatric populations and characterize its clinical presentation and management as reported by United States poison centers. METHODS: This is a retrospective review of the National Poison Data System from 1 January 2010 through 30 June 2021. We descriptively analyzed cases involving single substance, oral potassium salts. In a second step, we requested a subset of case-specific narratives for cases that resulted in major outcome or death, as well as cases where patients received any of the following therapies: whole bowel irrigation, sodium bicarbonate, calcium, insulin or hemodialysis. We classified hyperkalemia by expected toxicity: mild (peak potassium concentration <6.5 mEq/L), moderate (peak potassium concentration 6.5 to <8 mEq/L) or severe (peak potassium concentration ≥ 8mEq/L). RESULTS: The National Poison Data System included 1,820 cases, 52.3 percent being adults. Among adult cases, 20% (n = 189) resulted in a moderate effect, major effect or death. Among pediatric cases aged <10 years, all exposures were unintentional. Analysis of 49 case narratives showed a median peak potassium concentration of 7.1 mEq/L (interquartile range 5.4-8.6) and a moderate correlation with the dose ingested (r = 0.66). Severe hyperkalemia was associated with QRS complex widening (P < 0.001), peaked T-waves (P = 0.001), and neurological symptoms (P = 0.04). Whole bowel irrigation was associated with mild hyperkalemia (P = 0.011), and hemodialysis was associated with severe hyperkalemia (P < 0.001). DISCUSSION: Analysis of data showed that therapy to promote intracellular shift of potassium is the mainstay of management of oral potassium poisoning, followed by hemodialysis. LIMITATIONS: Poison center data are susceptible to reporting bias. National Poison Data System data are affected by completeness and accuracy of reporting from health care providers and the lay public. CONCLUSIONS: Single substance, oral potassium poisoning, reported to United States poison centers, is mostly unintentional and rarely results in hyperkalemia.

When the antidote is the poison: Investigating the relationship between people's social media usage and loneliness when face-to-face communication is restricted.

When governments mandated lockdowns to limit the spread of the coronavirus, the resulting reduction of face-to-face communication threatened many people's psychological well-being by fostering feelings of loneliness. Given social media's eponymous social nature, we study the relationship between people's social media usage and their loneliness during these times of physical social restrictions. We contrast literature highlighting the social value of social media with a competing logic based on the "internet paradox," according to which increased social media usage may paradoxically be associated with increasing, not decreasing, levels of loneliness. As the extant literature provides opposing correlational insights into the general relationship of social media usage and loneliness, we offer competing hypotheses and offer novel longitudinal insights into the phenomenon of interest. In the empirical context of Germany's initial lockdown, our research uses survey panel data from February 2020 (before the lockdown) and April 2020 (during the lockdown) to contribute longitudinal evidence to the matter. We find that more usage of social media in the studied lockdown setting is indeed associated with more, not less loneliness. Thus, our results suggest a "social media paradox" when physical social restrictions are mandated and caution social media users and policy makers to not consider social media as a valuable alternative for social interaction. A post-hoc analysis suggests that more communication via richer digital media which are available during physical lockdowns (e.g., video chats) softens the "social media paradox". Conclusively, this research provides deeper insights into the social value of social interactions via digital media during lockdowns and contributes novel insights into the relationship between social media and loneliness during such times when physical social interaction is heavily restricted.

Psilocybin Exposures Reported to U.S. Poison Centers: National Trends Over a Decade.

PURPOSE: We describe trends in psilocybin exposures among adolescents and young adults as reported to US poison centers over the past decade. METHODS: We queried the National Poison Data System for cases involving psilocybin during January 1, 2013-December 31, 2022. Persons aged 13-25 years were included. We examined exposures to psilocybin by demographics, clinical effects, level of care, and medical outcome. RESULTS: During the 10-year study period, 4,055 psilocybin-involved exposures were reported among adolescents and young adults, 2,667 (65.8%) being single substance exposures. Most single substance cases received medical attention (adolescents: 75.3% [n = 1,176], young adults: 72.1% [n = 797]). We did not find significant change in the number of cases during 2013-2018. Cases started increasing in 2019. In 2022, cases more than tripled among adolescents and more than doubled among young adults, compared to 2018 (p < .0001). DISCUSSION: Continued national surveillance is critical to determine the impact of psilocybin exposures on youth as it becomes increasingly available.

Nicotine and Cardiovascular Health: When Poison is Addictive - a WHF Policy Brief.

Nicotine is universally recognized as the primary addictive substance fuelling the continued use of tobacco products, which are responsible for over 8 million deaths annually. In recent years, the popularity of newer recreational nicotine products has surged drastically in many countries, raising health and safety concerns. For decades, the tobacco industry has promoted the myth that nicotine is as harmless as caffeine. Nonetheless, evidence shows that nicotine is far from innocuous, even on its own. In fact, numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems. Tobacco and recreational nicotine products are commercialized in various types and forms, delivering varying levels of nicotine along with other toxic compounds. These products deliver nicotine in profiles that can initiate and perpetuate addiction, especially in young populations. Notably, some electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) can deliver concentrations of nicotine that are comparable to those of traditional cigarettes. Despite being regularly advertised as such, ENDS and HTP have demonstrated limited effectiveness as tobacco cessation aids in real-world settings. Furthermore, ENDS have also been associated with an increased risk of cardiovascular disease. In contrast, nicotine replacement therapies (NRT) are proven to be safe and effective medications for tobacco cessation. NRTs are designed to release nicotine in a slow and controlled manner, thereby minimizing the potential for abuse. Moreover, the long-term safety of NRTs has been extensively studied and documented. The vast majority of tobacco and nicotine products available in the market currently contain nicotine derived from tobacco leaves. However, advancements in the chemical synthesis of nicotine have introduced an economically viable alternative source. The tobacco industry has been exploiting synthetic nicotine to circumvent existing tobacco control laws and regulations. The emergence of newer tobacco and recreational nicotine products, along with synthetic nicotine, pose a tangible threat to established tobacco control policies. Nicotine regulations need to be responsive to address these evolving challenges. As such, governments should regulate all tobacco and non-medical nicotine products through a global, comprehensive, and consistent approach in order to safeguard tobacco control progress in past decades.

New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis.

Gymnopilus orientispectabilis, also known as "big laughter mushroom," is a hallucinogenic poisonous mushroom that causes excessive laughter upon ingestion. From the fruiting bodies of G. orientispectabilis, eight lanostane-type triterpenoids (1-8), including seven novel compounds: gymnojunols A-G (2-8), were isolated. The chemical structures of these new compounds (2-8) were determined by analyzing their 1D and 2D NMR spectra and HR-EISMS, and their absolute configurations were unambiguously assigned by quantum chemical ECD calculations and a computational method coupled with a statistical procedure (DP4+). Upon evaluating autophagic activity, compounds 2, 6, and 7 increased LC3B-II levels in HeLa cells to a similar extent as bafilomycin, an autophagy inhibitor. In contrast, compound 8 decreased the levels of both LC3B-I and LC3B-II, and a similar effect was observed following treatment with rapamycin, an autophagy inducer. Our findings provide experimental evidence for new potential autophagy modulators in the hallucinogenic poisonous mushroom G. orientispectabilis.