Silica nanoparticles-induced cytotoxicity and genotoxicity in A549 cell lines.

Among the myriad of nanoparticles, silica nanoparticles (SiO2NPs) have gained significant attention since they are extensively produced and used across several kinds of industries. Because of its widespread usage, there has been increasing concern about the potential health effects. This study aims to evaluate the effects of SiO2NPs on Interleukin-6 (IL-6) gene expression in human lung epithelial cell lines (A549). In this study, A549 cells were exposed to SiO2NPs at concentrations of 0, 1, 10, 50, 100, and 200 µg/mL for 24 and 48 h. The IL-6 gene expression was assessed using Real-Time RT-PCR. Additionally, the impact of SiO2NPs on the viability of A549 cells was determined by MTT assay. Statistical analysis was performed using GraphPad Prism software 8.0. MTT assay results indicated a concentration-dependent impact on cell survival. After 24 h, survival decreased from 80 to 68% (1-100 µg/mL), rising to 77% at higher concentrations. After 48 h, survival dropped from 97 to 80%, decreasing to 90% at higher concentrations. RT-PCR showed a dose-response relationship in cellular toxicity up to 10 µg/mL. At higher concentrations, there was increased IL-6 gene expression, mitigating SiO2NP-induced cytotoxic effects. The study shows that the viability and proliferation of A549 cells are impacted by different SiO2NPs concentrations. There may be a potential correlation between IL-6 gene expression reduction and a mechanism linked to cellular toxicity. However, at higher concentrations, an unknown mechanism increases IL-6 gene expression, reducing SiO2NPs' cytotoxic effects. These effects are concentration-dependent and not influenced by exposure times. Further investigation is recommended to determine this mechanism's nature and implications, particularly in cancer research.

Snake eyes: Characterization of topical ocular exposures from rattlesnakes in Arizona.

Patients occasionally present with reports of ocular exposure to fluids from rattlesnakes, claiming or suspecting the substance to be venom. This study set out to evaluate and characterize reported cases of suspected venom-induced ophthalmia in humans. A retrospective review of rattlesnake exposures reported to the Arizona Poison and Drug Information Center over a 24-year period was conducted for ocular exposures. Recorded information included patient demographics, clinical course, laboratory results, and treatments. Documentation regarding interactions between patients and snakes was reviewed by Arizona Poison and Drug Information Center herpetologists to evaluate what substance was expelled from the snake resulting in ocular exposure. Our review of rattlesnake encounters found a total of 26 ocular exposure cases. Patient demographics were largely intentional interactions and involved the male sex. Symptoms ranged from asymptomatic to minor effects with 46.2% managed from home and treated with fluid irrigation. A review of cases by herpetologists concluded the exposure patients commonly experienced was to snake musk. Kinematics of venom expulsion by rattlesnakes conclude the venom gland must be compressed, fangs erected to ≥60o, and fang sheath compressed against the roof of the mouth for venom expulsion. Evidence suggests the chance of venom "spitting" by rattlesnakes is close to zero. Rattlesnakes are documented to forcefully expel airborne malodorous "musk" defensively. An important distinction to remember is musk has a foul odor and is usually colorless, while venom is comparatively odorless and yellow. Rattlesnake venom-induced ophthalmia is a rare event as venom expulsion requires the kinematics of feeding or defensive bites. If the rattlesnake is not in the process of biting or otherwise contacting some other object with its mouth, it is more biologically plausible patients are being exposed to snake musk as a deterrent. Whether it's venom or musk, topical exposure to the eyes should prompt immediate irrigation.

Static magnetic field reduces cisplatin resistance via increasing apoptosis pathways and genotoxicity in cancer cell lines.

Cisplatin is a chemotherapy drug widely used in cancer treatment. Alongside its clinical benefits, however, it may inflict intolerable toxicity and other adverse effects on healthy tissues. Due to the limitation of administering a high dose of cisplatin as well as cancer drug resistance, it is necessary to utilize new methods optimizing treatment modalities through both higher therapeutic efficacy and reduced administered doses of radiation and drugs. In this study, sensitive (A2780) and resistant (A2780CP) ovarian carcinoma cells underwent treatment with cisplatin + static magnetic field (SMF). First, the levels of genotoxicity after treatment were evaluated by Comet assay. Then, cell cycle analysis and apoptosis assay were conducted by a flow cytometer. Lastly, the expression levels of genes involved in apoptosis and cellular drug uptake were investigated by PCR. After treating different groups of cells for 24, 48, and 96 h, the co-treatment of SMF and cisplatin as a combination managed to increase the amount of DNA damage in both sensitive and resistant cell lines. A considerable increase in mortality of cells was also observed mostly in the form of apoptosis, which was caused by inhibition of the cell cycle. The combination also increased the expression levels of apoptotic genes, namely P53 and P21; however, it did not have much effect on the expression levels of BCL2. Besides, the levels of CTR1 gene expression increased significantly in the groups receiving the aforementioned combination. Our study suggests that the combination of cisplatin + SMF might have clinical potential which needs further investigations through future studies.

High inflammatory cytokines gene expression can be detected in workers with prolonged exposure to silver and silica nanoparticles in industries.

Occupational health must be strictly considered in industries particularly in nanoparticle factories where workers were exposed to different types of chemicals. We measured the serum levels of inflammatory cytokines in workers who developed skin lesions after exposure to silver and silica nanoparticles. Using a questionnaire in this cross-sectional study, we identified 110 workers in nanoparticle industries who were exposed to silver and silica nanoparticles. We also included 40 healthy subjects as controls from the administrative department of the same factories who were not exposed to nanoparticles. Peripheral blood samples used to measure the mRNA levels of inflammatory cytokines by qRT-PCR. In comparison with the control group, the workers who developed skin lesions had significantly higher levels of interleukin IL4, IL6, IL8, and TNF-α, particularly after two or three decades of exposure to silver and silica nanoparticles. Participants who were exposed to silver had higher levels of IL6 and IL8 compared with those who were exposed to silica. Necessary measures must be considered to protect workers in nanoparticle industries against the potential toxic effects of these compounds. Our network pharmacology study suggests corresponding biochemical pathways for these disorders.

Inhalation of multi-wall carbon nanotubes changes the expression of apoptosis and cancer genes in rat brain and lungs.

One of the important issues in urban areas is air pollution which causes respiratory disorders. A significant association between exposure to inhaled particulate matter (PM), mainly ultrafine particles, and increased neurological and pulmonary morbidity and mortality was observed in some research. This study aimed to demonstrate the relation between multi-wall carbon nanotubes (MWCNTs) inhalation and the carcinogenic effect of these materials in the brain and lungs. For this purpose, we investigated gene expression in rat brain and lung tissues induced by exposure to MWCNTs. Rats were exposed to MWCNTs in diameters of 10 and 100 nm (pure and impure) at a concentration of 5 mg/m3. Exposure was done through a whole-body exposure chamber for 5 h/day, 5 days/week for 14 days. After exposure, both brain and lung tissues were isolated to evaluate certain gene expressions including Bax, Bcl2, Rac1, Tp53, Mmp12, and Arc. The results showed that exposure to impure and pure MWCNTs (10 and 100 nm) at a concentration of 5 mg/m3 causes up-regulation or down-regulation of some of these genes. The results suggest that impure and pure MWCNTs (10 and 100 nm) can increase the risk of central nervous system disorders such as Alzheimer's disease and increase the risk of carcinogenesis in the lung tissues of rats exposed to MWCNTs (Tab. 2, Fig. 2, Ref. 64). Text in PDF www.elis.sk Keywords: multi-wall carbon nanotube, inhalation, gene expression, carcinogenicity, brain, lung.

The effect of subacute co-exposure to carbon tetrachloride and diclofenac on the liver of male wistar rats.

Carbon tetrachloride (CCl4) is a potent liver toxin. Diclofenac (Dic), leading adverse effects on the liver, is used among the employees of the industries that use CCl4. The increased use of CCl4 and Dic in industrial workers has prompted us to investigate their synergistic effect on the liver using male Wistar rats as a model. Male Wistar rats were divided into seven groups (n = 6), and the exposure was by intraperitoneal injection for 14 days as follows. Group 1: Control, 2: Olive oil, 3: CCl4 (0.8 mL/kg/day (3 times per week)), 4: Normal saline, 5: Dic (1.5 mg/kg/day per day), 6: Olive oil with normal saline, 7: CCl4 (0.8 mL/kg/day (3 times per week)) and Dic (1.5 mg/kg/day daily). At the end of day 14, the heart blood was collected to measure the liver enzymes, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), blood alkaline phosphatase (ALP), albumin (ALB), direct bilirubin, and total bilirubin. A pathologist examined the liver tissue. Prism software was used to analyze data using ANOVA and Tukey statistical tests. ALT, AST, ALP, and Total Bilirubin enzymes were increased significantly in the co-administered CCl4 and Dic group, while the ALB levels decreased (p < 0.05). The histological findings reported liver necrosis, focal hemorrhage, adipose tissue change, and lymphocytic portal hepatitis. In conclusion, using Dic while exposed to CCl4 may exacerbate hepatotoxicity in rats. Therefore, it is suggested that more severe restrictions and safety regulations be placed on using CCl4 in the industry, and caution is advised to these industry workers to use Diclofenac.

Medically important snakes and snakebite envenoming in Iran.

Snakebite is a relatively common health condition in Iran with a diverse snake fauna, especially in tropical southern and mountainous western areas of the country with a plethora of snake species. The list of medically important snakes, circumstances and effects of their bite, and necessary medical care require critical appraisal and should be updated regularly. This study aims to review and map the distributions of medically important snake species of Iran, re-evaluate their taxonomy, review their venomics, describe the clinical effects of envenoming, and discuss medical management and treatment, including the use of antivenom. Nearly 350 published articles and 26 textbooks with information on venomous and mildly venomous snake species and snakebites of Iran, were reviewed, many in Persian (Farsi) language, making them relatively inaccessible to an international readership. This has resulted in a revised updated list of Iran's medically important snake species, with taxonomic revisions of some, compilation of their morphological features, remapping of their geographical distributions, and description of species-specific clinical effects of envenoming. Moreover, the antivenom manufactured in Iran is discussed, together with treatment protocols that have been developed for the hospital management of envenomed patients.

The role of decision tree and machine learning models for outcome prediction of bupropion exposure: A nationwide analysis of more than 14 000 patients in the United States.

Bupropion is widely used for the treatment of major depressive disorder and for smoking cessation assistance. Unfortunately, there are no practical systems to assist clinicians or poison centres in predicting outcomes based on clinical features. Hence, the purpose of this study was to use a decision tree approach to inform early diagnosis of outcomes secondary to bupropion overdose. This study utilized a dataset from the National Poison Data System, a 6-year retrospective cohort study on toxic exposures and patient outcomes. A machine learning algorithm (decision tree) was applied to the dataset using the sci-kit-learn library in Python. Shapley Additive exPlanations (SHAP) were used as an explainable method. Comparative analysis was performed using random forest (RF), Gradient Boosting classification, eXtreme Gradient Boosting, Light Gradient Boosting (LGM) and voting ensembling. ROC curve and precision-recall curve were used to analyse the performance of each model. LGM and RF demonstrated the highest performance to predict outcome of bupropion exposure. Multiple seizures, conduction disturbance, intentional exposure, and confusion were the most influential factors to predict the outcome of bupropion exposure. Coma and seizure, including single, multiple and status, were the most important factors to predict major outcomes.

Decision tree algorithm can determine the outcome of repeated supratherapeutic ingestion (RSTI) exposure to acetaminophen: review of 4500 national poison data system cases.

This study is aimed at establishing the outcome of RSTI exposure to acetaminophen based on a decision tree algorithm for the first time. This study used the National Poison Data System (NPDS) to conduct a six-year retrospective cohort analysis, which included 4522 individuals. The patients had a mean age of 26.75 ± 16.3 years (1-89). 3160 patients (70%) were females. Most patients had intentional exposure to acetaminophen. Almost all the patients had acetaminophen exposure via ingestion. In addition, 400 (8.8%) experienced major outcomes, 1500 (33.2%) experienced moderate outcomes, and 2622 (58%) of the patients experienced mild ones. The decision tree model performed well in the training and test groups. In the test group, the accuracy was 0.813, precision of 0.827, recall being 0.798, specificity 0.898, and an F1 score 0.80. In the training group, accuracy was 0.831, recall was 0.825, precision was 0.837, specificity was 0.90, and F1 score was 0.829. Our results showed that serum liver enzymes being present at elevated levels (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) greater than 1000 U/L followed by ALT, AST between 100 and 1000 U/L), prothrombin time (PT) prolongation, bilirubin increase, renal failure, confusion, age, hypotension, other coagulopathy (such as partial thromboplastin time (PTT) prolongation), acidosis, and electrolyte abnormality were the effective factors in determining the outcomes in these patients. The decision tree algorithm is a dependable method for establishing the prognosis of patients who have been exposed to RSTI acetaminophen and can be used throughout the patients' hospitalization period.

Design and Evaluation of a Novel Anti-microbial Peptide from Cathelicidin-2: Selectively Active Against Acinetobacter baumannii.

Background: Infections caused by pathogenic microorganisms have increased the need for hospital care and have thus represented a public health problem and a significant financial burden. Classical treatments consisting of traditional antibiotics face several challenges today. Anti-microbial peptides (AMPs) are a conserved characteristic of the innate immune response among different animal species to defend against pathogenic microorganisms. Objectives: In this study, a new peptide sequence (mCHTL131-140) was designed using the in silico approach. Methods: Cathelicidin-2 (UniprotID: Q2IAL7) was used as a potential antimicrobial protein, and a novel 10 - 12 amino acids sequence AMP was designed using bioinformatics tools and the AMP databases. Then, the anti-bacterial, anti-biofilm, and anti-fungal properties of the peptide, as well as its hemolytic activity and cytotoxicity towards human fibroblast (HDF) cells, were investigated in vitro. Results: Online bioinformatics tools indicated that the peptide sequence could have anti-bacterial, anti-viral, anti-fungal, and anti-biofilm properties with little hemolytic properties. The experimental tests confirmed that mCHTL131-140 exhibited the best anti-bacterial properties against Acinetobacter baumannii and had fair anti-fungal properties. Besides, it did not cause red blood cell lysis and showed no cytotoxicity towards HDF cells. Conclusions: In general, the designed peptide can be considered a promising AMP to control hospital-acquired infections by A. baumannii.

How much natural ventilation rate can suppress COVID-19 transmission in occupancy zones?

Background: Previous research has emphasized the importance of efficient ventilation in suppressing COVID-19 transmission in indoor spaces, yet suitable ventilation rates have not been suggested. Materials and Methods: This study investigated the impacts of mechanical, natural, single-sided, cross-ventilation, and three mask types (homemade, surgical, N95) on COVID-19 spread across eight common indoor settings. Viral exposure was quantified using a mass balance calculation of inhaled viral particles, accounting for initial viral load, removal via ventilation, and mask filtration efficiency. Results: Results demonstrated that natural cross-ventilation significantly reduced viral load, decreasing from 10,000 to 0 viruses over 15 minutes in a 100 m2 space by providing ~1325 m3/h of outdoor air via two 0.6 m2 openings at 1.5 m/s wind speed. In contrast, single-sided ventilation only halved viral load at best. Conclusion: Natural cross-ventilation with masks effectively suppressed airborne viruses, lowering potential infections and disease transmission. The study recommends suitable ventilation rates to reduce COVID-19 infection risks in indoor spaces.

Cytotoxic Activity and Phytochemical Analysis of Artemisia haussknechtii Boiss.

Cytotoxic activity of crude extract and fractions (petroleum ether, dichloromethane, and n-butanol) of Artemisia haussknechtii aerial parts was investigated by MTT assay. Dichloromethane fraction showed the highest cytotoxic effect on MCF-7 cell line (IC50 = 297.17 ± 7.99 µg/mL). Phytochemical analysis of the most effective fraction was carried out using normal phase column chromatography (CC) to get eight sub-fractions (A-H). Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) were used for further purification. Four known compounds with cytotoxic effects on cancer cell lines were isolated from the most active fraction, including 5-Hydroxy-3',4',6,7-tetramethoxyflavone (eupatilin 7-methyl ether), 5-hydroxy 3,3',4',6,7-pentamethoxy-flavone (artemetin), 6-methoxy-7-hydroxycoumarin (scopoletin), and methyl caffeate. Structure elucidation of isolated compounds was done using spectroscopic techniques, including ESIMS and 1D-NMR (1H and 13C). Cytotoxic activity of A. haussknechtii is probably due to coumarin and flavonoid compounds.

Utility of support vector machine and decision tree to identify the prognosis of metformin poisoning in the United States: analysis of National Poisoning Data System.

BACKGROUND: With diabetes incidence growing globally and metformin still being the first-line for its treatment, metformin's toxicity and overdose have been increasing. Hence, its mortality rate is increasing. For the first time, we aimed to study the efficacy of machine learning algorithms in predicting the outcome of metformin poisoning using two well-known classification methods, including support vector machine (SVM) and decision tree (DT). METHODS: This study is a retrospective cohort study of National Poison Data System (NPDS) data, the largest data repository of poisoning cases in the United States. The SVM and DT algorithms were developed using training and test datasets. We also used precision-recall and ROC curves and Area Under the Curve value (AUC) for model evaluation. RESULTS: Our model showed that acidosis, hypoglycemia, electrolyte abnormality, hypotension, elevated anion gap, elevated creatinine, tachycardia, and renal failure are the most important determinants in terms of outcome prediction of metformin poisoning. The average negative predictive value for the decision tree and SVM models was 92.30 and 93.30. The AUC of the ROC curve of the decision tree for major, minor, and moderate outcomes was 0.92, 0.92, and 0.89, respectively. While this figure of SVM model for major, minor, and moderate outcomes was 0.98, 0.90, and 0.82, respectively. CONCLUSIONS: In order to predict the prognosis of metformin poisoning, machine learning algorithms might help clinicians in the management and follow-up of metformin poisoning cases.

The Complexity of Response to the Proliferation Agonist and Antagonist Agents, in the Breast Cancer Cell Lines with Various Receptors.

Breast cancer is a heterogeneous disease in which many factors and receptors are effective in the disease process and response to treatment. Currently, estrogen, progesterone, and HER2 receptors are among the most important factors in choosing a treatment regimen. Other metabolic factors that may affect the treatment outcome include diabetes and hyperinsulinemia. In order to evaluate the role and complexity of cross-talk between different pathways initiating from various receptors, value the most common drugs in the treatment of breast cancer are investigated on different cell lines in this manuscript at the cell culture level. The result of different doses of Tamoxifen and estradiol on the cells with various levels of the estrogenic, progesterone, and HER2 receptors is examined alone, or in combinations, and the presence or absence of insulin. The effects of these variables on the cells' growth pattern and survival in various breast cancer cells are investigated using cell counting, colony counting, and MTT assays. Our results have further confirmed the complexity of deciding on the outcome of treatment for breast cancer with such a wide variability in the kind of receptors and biochemical agents present in the body of a cancer patient.

Selective thyroid hormone receptor beta agonist, GC-1, is capable to reduce growth of colorectal tumor in syngeneic mouse models.

OBJECTIVE: The effect of thyroid hormone (TH) on cancers was proposed more than 100 years ago; however, conclusions are conflicting. THs are precisely regulated at tissue and cellular levels. It seems that this regulation is altered in cancers. Thyroid hormone receptor beta (TRß) has anti-proliferative and tumor-suppressive effects in many cancer cells. Therefore, we decided to investigate thyroid hormone receptor beta (THRB) expression and activation by the selective agonist, GC-1, on tumor growth in a syngeneic mouse model of colorectal cancer (CRC) and colon cell lines. METHODS: In vitro cell viability assay using MTT analysis, cell cycle analysis by PI staining, and FACS analysis were performed. In vivo tumor growth measurements were carried out by caliper and [18F] Fluoro-2-deoxy-2-D-glucose (FDG) - PET imaging. Gene expressions were determined using quantitative-PCR. RESULTS: Some concentrations of GC-1 had a marked negative effect on the cell viability of colorectal cell lines. Cell cycle analysis showed that the anti-proliferative effect of GC-1 may not result from cell cycle arrest or apoptosis. Tumor growth analysis in mice harboring colorectal tumor showed that GC-1 treatment for 8 d profoundly inhibited tumor growth and 18FDG uptake. THRB expression was decreased in mice tumor; however, it was upregulated following GC-1 administration. CONCLUSIONS: Our results showed that specific activation of TRß by GC-1 had negative effect on tumor growth and restored its gene expression in tumors of CRC mice model.

Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F(ab')2 antivenoms.

BACKGROUND: Rattlesnake envenomation may lead to a multitude of clinical effects, including a late onset hemorrhage. Laboratory values such as platelets and fibrinogen are commonly used to assess the risk of developing a life-threatening bleed. To date, no specific threshold has been identified that links a lab value to the risk of bleeding. This has led to widespread practice variability among clinicians managing snake bites. In assessing risk for patients, we apply the concept that the more abnormal the lab values are, the higher the risk probably is. Late onset coagulopathies pose a unique clinical challenge because they indicate the potential risk for a life-threatening hemorrhage, yet they have been identified after hospital discharge. There are currently two antivenom (AV) products on the US market to treat rattlesnake envenomations, a Fab product, CroFab® (BTG, UK) and a F (ab')2 product, Anavip® (Bioclon, Mexico). OBJECTIVE: This study intended to characterize the incidence and severity of late coagulopathies reported to a Regional Poison Center (RPC) and hypothesized that late coagulopathies occur at rates higher than previously reported in the literature. Additionally, we sought to compare rates of late coagulopathy between Fab and F (ab')2 AV. METHODS: The investigators performed an in-depth review of all suspected snakebite envenomations from 2018 to 2020 that presented to an Arizona healthcare facility in the RPC's catchment area between January 2018 through December of 2020. Patients were excluded from analysis if they did not receive any antivenom, had an incomplete medical record with the APDIC, were diagnosed as something other than a rattlesnake bite or had a known medical history that clouded the diagnosis or assessment of a rattlesnake envenomation. RESULTS: In total, 522 records were reviewed of which 283 patients met the inclusion criteria. There were 149 patients who received Fab AV and 134 who received F (ab')2. No significant baseline or demographic differences existed between the groups. 95 of the 283 patients developed a late onset coagulopathy. 39% of the late onset coagulopathies were delayed, 32% were recurrent and 29% were persistent. When comparing the two different AV products, delayed or recurrent coagulopathies occurred in 36% of Fab AV- and 10% of F (ab')2 treated patients. Persistent coagulopathies occurred in 17% of Fab AV- and 8% of F (ab')2 treated patients. Interestingly, there were zero cases of late hypofibrinogenemia in any of the 134 F (ab')2 treated patients compared to 26% of all Fab treated ones. The average onset of late coagulopathy post-bite was 8 days for Fab AV and 7 for F (ab')2. CONCLUSION: The results from this study suggest the total rate of late onset coagulopathies may be underestimated. Additionally, our results suggest the potential that F (ab')2 AV may be associated with fewer late onset coagulopathies, especially late onset hypofibrinogenemia.

Pharmacy Calls for Prescription Clarification at an Academic Emergency Department.

BACKGROUND: Approximately two-thirds of patients discharged from an emergency department (ED) are prescribed at least one medication. Prescription clarification by outpatient pharmacies for ED patients can lead to delays for patients and added workload. OBJECTIVES: This study aims to describe prescriptions requiring clarification prior to being dispensed by an outpatient pharmacy for patients recently discharged from an ED. METHODS: This study was conducted at an urban, 61-bed academic ED. Prescription clarification forms were used to identify common causes for outpatient pharmacies to contact the ED to clarify prescriptions prior to dispensation. Clarification types were reviewed and classified. Descriptive statistics were used to present the classification types. RESULTS: There were 1278 documented calls to the ED for prescription clarification that were classified as clarification of directions for use (611, 47.7%), insurance or affordability issues (182, 14.2%), dose (172, 13.4%), medication availability (126, 9.8%), lost or missing prescription (93, 7.3%), patient allergy or adverse event (62, 4.8%), duplication in therapy (17, 1.3%), and clarification of medication ordered (17, 1.3%). When grouped into provider, system, or patient-related issues, provider issues were noted to be most frequent clarifications (862 clarifications, 67.3%), followed by system issues (325 clarifications, 25.4%), and finally, patient-related issues (93 clarifications, 7.3%). CONCLUSIONS: Clarification of directions for use, insurance or affordability issues, and clarification of the dose were the most common reasons that outpatient pharmacies contacted an ED regarding a prescription for a recently discharged patient.

Repurposing the drug, ivermectin, in COVID-19: toxicological points of view.

The global COVID-19 pandemic has affected the world's population by causing changes in behavior, such as social distancing, masking, restricting people's movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150-200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.

First report of a confirmed case of Montivipera latifii (Latifi's viper) envenoming and a literature review of envenoming by Montivipera species.

Latifi's viper (Montivipera latifii), also known as Lar Valley or Damavandi viper, is endemic to Iran. It has rarely been recorded, as it occurs in a highly-protected national park. In this first clinical report of a confirmed bite by this species, a teenage girl was bitten on the chin, causing rapidly-progressive swelling of the face and oropharyngeal mucosa. At a local hospital, a misleading history given by the patient's relatives of a wasp sting and inadequate inspection of the bite wound misled the physicians from making the correct diagnosis, resulting in a considerable delay in the administration of antivenom. This allowed the development of partial obstruction of the upper airway causing respiratory distress. After transfer to a tertiary hospital, attempts at endotracheal intubation failed, necessitating tracheostomy, but this was not implemented early enough to prevent her developing respiratory failure and losing consciousness. After she was stabilized, snakebite envenoming was diagnosed by a clinical toxicologist who observed two fang puncture marks on her chin. This was later confirmed when a snake, identified as M. latifii, was discovered at the room where the bite had occurred. Her facial swelling and ecchymosis, attributable to envenoming, were effectively controlled by high-dose antivenom therapy. However, she did not recover consciousness, remaining in a vegetative state. About three weeks after the bite, she died as an indirect result of hypoxic brain damage complicated by septicemia. Prompt diagnosis, relief of upper airway obstruction and timely antivenom therapy might have prevented this tragic fatal outcome.