Impact of low-level exposure to antibiotics on bile acid homeostasis in adults: Implication for human safety thresholds.

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.

Invisible enemies: evaluating human health threats of mosquito repellents through animal studies.

Mosquito-borne diseases continue to pose significant threats to human populations, especially in developing and underdeveloped regions, where access to effective preventive measures remains limited. Mosquito repellents represent a cornerstone in the arsenal against these diseases, providing a barrier against mosquito bites. Mosquito repellents come in various formulations, including topical ointments and commercial vaporizers, with varying compositions. Common constituents include deodorized kerosene (DOK) as a solvent, pyrethroids, amides, essential oils for fragrance, and synergists. Despite their widespread use, the toxicological profiles of these repellents remain inadequately understood, raising questions about their safety in prolonged or excessive exposure scenarios. However, while their efficacy in preventing mosquito-borne illnesses is well-established, concerns persist regarding their potential toxicity to humans and the environment. This review critically examines the existing literature on the toxicity of mosquito repellents, focusing on their adverse effects on human health and environmental sustainability. Through an extensive analysis of available research, this review aims to shed light on the potential health risks associated with mosquito repellents, such as dermatological irritation, respiratory complications, and allergic reactions in humans.

Pathophysiology and human cancer risk assessment of pharmaceutical-induced thymoma in carcinogenicity studies.

Thymoma, a tumor of thymic lymphocytes or thymic epithelial cells (TECs), is a common spontaneous tumor in Wistar Han rats, especially in females with up to 18% incidence in controls. In addition to sex, there are rat strain differences in background incidence of thymomas such as Sprague Dawley versus Wistar Han rats. Human thymomas are very rare and without clear differences in incidence between males and females. Immunomodulatory and anti-inflammatory pharmaceutical drug classes, including Janus kinase inhibitors, increase the incidence of benign thymoma in two-year rat carcinogenicity studies. Potential non-genotoxic mechanisms that might contribute to the pathogenesis of thymoma development in one sex (female) Wistar Han rats include: (1) hormonal differences, (2) high proliferation rate of TECs, (3) delayed physiologic thymic involution, and/or (4) significant level of immunosuppression at high doses of a pharmaceutical drug. Factors to consider in the human cancer risk assessment of pharmaceutical-induced thymoma are: the genotoxicity of the test article, sex and strain of rats, exposure safety margins, and pathophysiologic differences and similarities of thymoma between rats and humans. Totality of weight of evidence approach and available data suggest thymomas observed in carcinogenicity studies of pharmaceutical drugs are not relevant for human risk at clinically relevant therapeutic doses.

Mammalian toxicity of trifluoroacetate and assessment of human health risks due to environmental exposures.

While trifluoroacetic acid has limited technical uses, the highly water-soluble trifluoroacetate (TFA) is reported to be present in water bodies at low concentrations. Most of the TFA in the environment is discussed to arise from natural processes, but also with the contribution from decomposition of environmental chemicals. The presence of TFA may result in human exposures. For hazard and risk assessment, the mammalian toxicity of TFA and human exposures are reviewed to assess the margin of exposures (MoE). The potential of TFA to induce acute toxicity is very low and oral repeated dose studies in rats have identified the liver as the target organ with mild liver hypertrophy as the lead effect. Biomarker analyses indicate that TFA is a weak peroxisome proliferator in rats. TFA administered to rats did not induce adverse effects in an extended one-generation study and in a developmental toxicity study or induce genotoxic responses. Based on recent levels of TFA in water and diet, MoEs for human exposures to TFA are well above 100 and do not indicate health risks.

Comparative In vitro metabolism of purified mogrosides derived from monk fruit extracts.

Mogrosides are the primary components responsible for the sweet taste of Monk fruit which is derived from Siraitia grosvenorii (Swingle), a herbaceous plant native to southern China. Many mogrosides have been identified from Monk fruit extract, but the major sweetness component of Monk fruit by mass is mogroside V, comprising up to 0.5% of the dried fruit weight. Recent pharmacokinetic studies indicate that the parent mogrosides undergo minimal systemic absorption following ingestion and hydrolysis by digestive enzymes and/or intestinal flora and are excreted as mogrol (i.e., the aglycone) and its mono- and diglucosides. The objective of this study was to demonstrate whether individual mogrosides, are metabolized to a common and terminal deglycosylated metabolite, mogrol. An in vitro assay was conducted with pooled human male and female intestinal fecal homogenates (HFH) using mogrosides IIIe, mogroside V, siamenoside I, and isomogroside V at two concentrations over a 48 h period. The results show that various mogrosides that differ in the linkages and number of glucose units attached to a common cucurbitane backbone, share a common metabolic fate, and are metabolized within 24 h to mogrol. Aside from an apparent difference in the initial rate of deglycosylation between mogrosides at higher concentrations, no apparent difference in the rate of deglycosylation was observed between the male and female HFH. Given the similar structures of these mogrosides and a shared metabolic fate to mogrol, the study provides support for a reasonably conservative approach to assess safety based on bridging safety data from an individual mogroside (i.e., Mogroside V) to other mogrosides, and the establishment of a group Acceptable Daily Intake (ADI), rather than individual ADI's for mogrosides.

A Study on the Application of LSTM to Judge Bike Accidents for Inflating Wearable Airbags.

The traffic accident occurrence rate is increasing relative to the increase in the number of people using personal mobility device (PM). This paper proposes an airbag system with a more efficient algorithm to decide the deployment of a wearable bike airbag in case of an accident. The existing wearable airbags are operated by judging the accident situations using the thresholds of sensors. However, in this case, the judgment accuracy can drop against various motions. This study used the long short-term memory (LSTM) model using the sensor values of the inertial measurement unit (IMU) as input values to judge accident occurrences, which obtains data in real time from the three acceleration-axis and three angular velocity-axis sensors on the driver motion states and judges whether or not an accident has occurred using the obtained data. The existing neural network (NN) or convolutional neural network (CNN) model judges only the input data. This study confirmed that this model has a higher judgment accuracy than the existing NN or CNN by giving strong points even in "past information" through LSTM by regarding the driver motion as time-series data.

Weight of evidence and human relevance evaluation of the benfluralin mode of action in rodents (Part I): Liver carcinogenesis.

Benfluralin, an herbicide of the dinitroaniline class used in weed control, was first registered in the United States in 1970. Increased incidence of liver tumors was observed in the 2 year dietary carcinogenicity studies. A review of the toxicology database provides evidence that the mode of action (MOA) of benfluralin responsible for hepatocellular adenoma and carcinoma in rodents depends on activation of the constitutive androstane (CAR)/pregnane X (PXR) receptors, that triggers enzyme induction and altered gene expression leading to hepatocyte proliferation. After prolonged exposures at high dose levels, altered hepatic foci and liver tumors are observed. This hepatocarcinogenic MOA has been described in rodents following long-term dietary exposures to other CAR/PXR activator chemicals, such as phenobarbital, and is generally considered as non-relevant in humans due to differences between human and rodent responses. We analyzed the existing and newly acquired toxicology data to establish that the hepatocarcinogenic MOA of benfluralin in rodents includes the same key events previously described in the rodent MOA of phenobarbital. A weight of evidence approach was taken to establish temporal and dose-related concordance of the causal key events supporting the conclusion that rodent liver carcinogenicity of benfluralin is unlikely to be relevant for human cancer risk.

Investigation of Brassica juncea, Forsythia suspensa, and Inula britannica: phytochemical properties, antiviral effects, and safety.

BACKGROUND: General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety of three herbs used in traditional Korean medicine. METHODS: Extracts of three medicinal herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) were prepared using ethanol or water. The total phenolic, flavonoid, and saponin content, condensed tannin content, and reducing sugar content of the herb extracts were determined via phytochemical screening. Tandem mass analysis was performed using an ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-Q/Orbitrap instrument. Virus titrations were determined via tissue culture infective dose (TCID50) and cytotoxicity assays. Hemolysis and hepatotoxicity were measured to determine safety. RESULTS: Among the three medicinal herbs, F. suspensa showed the highest concentration of phenolic compounds, flavonoids, and saponins. The number of phytochemical compounds detected via tandem mass analysis of B. juncea, F. suspensa, and I. britannica was 5 (including sinigrin, m/z [M-H] = 358.02), 14 (including forsythoside A, m/z [M-H] = 623.19), and 18 (including chlorogenic acid, m/z [M-H] = 353.20), respectively. The antiviral effects of the B. juncea extracts (ethanol and water) and I. britannica extract (ethanol) were further investigated. The ethanol extract of B. juncea showed a 3 Log TCID50/25 µL virus titration reduction and the water extract showed a selectivity index of 13.668 against infected influenza H1N1 virus A/NWS/33. The B. juncea extracts did not show hemolysis activities and hepatotoxicity (< 20%). The ethanol extract of I. britannica showed the most effective virus titration decrease, whereas its hemolytic and hepatotoxicity values were the most significantly different compared to the control. Despite the high concentration of phytochemicals detected in F. suspensa, the extract showed approximately 1 Log TCID50/25 µL at the highest concentration. CONCLUSION: B. juncea may show antiviral effects against H1N1 in a host. In addition, B. juncea may also show decreased disadvantages compared to other antiviral agents.

Differences in Spatiotemporal Patterns of Vehicle Collisions with Wildlife and Livestock.

Road ecology research has tended to focus on wildlife-vehicle collisions (WVCs) while omitting or failing to differentiate domestic (i.e., livestock) animal-vehicle collisions (DAVCs). This has limited our understanding of where, when, and how frequently DAVCs occur, and whether these patterns differ from those for WVCs. We used a 10-year collision data set for the U.S. state of Montana to compare temporal and spatial patterns of DAVCs versus WVCs at multiple scales. WVCs exhibited two diel peaks (dawn and dusk) versus only one prominent peak (late evening/early night) for DAVCs. Seasonal patterns of WVCs and DAVCs were broadly similar, but DAVCs exhibited a more pronounced late-fall peak. At the county scale, DAVCs were overrepresented relative to WVCs in most of eastern Montana and underrepresented in most of western Montana. WVC and DAVC hotpots did not show strong overlap at the 1-mile road segment scale. Our results suggest that DAVCs warrant greater attention, and they may represent a high priority for management and mitigation measures in some areas because (1) they can be locally common even when regionally rare, (2) they are more dangerous to motorists on a per-collision basis than WVCs, and (3) they can present a legal liability for livestock owners. Mitigation measures for DAVCs may differ from those for WVCs and require further development and testing. Future data collection efforts should include information not only on the location and timing of animal-vehicle collisions, but also on the species of animals killed.

Temperature elevation in the human brain and skin with thermoregulation during exposure to RF energy.

BACKGROUND: Two international guidelines/standards for human protection from electromagnetic fields define the specific absorption rate (SAR) averaged over 10 g of tissue as a metric for protection against localized radio frequency field exposure due to portable devices operating below 3-10 GHz. Temperature elevation is suggested to be a dominant effect for exposure at frequencies higher than 100 kHz. No previous studies have evaluated temperature elevation in the human head for local exposure considering thermoregulation. This study aims to discuss the temperature elevation in a human head model considering vasodilation, to discuss the conservativeness of the current limit. METHODS: This study computes the temperature elevations in an anatomical human head model exposed to radiation from a dipole antenna and truncated plane waves at 300 MHz-10GHz. The SARs in the human model are first computed using a finite-difference time-domain method. The temperature elevation is calculated by solving the bioheat transfer equation by considering the thermoregulation that simulates the vasodilation. RESULTS: The maximum temperature elevation in the brain appeared around its periphery. At exposures with higher intensity, the temperature elevation became larger and reached around 40 °C at the peak SAR of 100 W/kg, and became lower at higher frequencies. The temperature elevation in the brain at the current limit of 10 W/kg is at most 0.93 °C. The effect of vasodilation became notable for tissue temperature elevations higher than 1-2 °C and for an SAR of 10 W/kg. The temperature at the periphery was below the basal brain temperature (37 °C). CONCLUSIONS: The temperature elevation under the current guideline for occupational exposure is within the ranges of brain temperature variability for environmental changes in daily life. The effect of vasodilation is significant, especially at higher frequencies where skin temperature elevation is dominant.

Peptides extracted from edible mushroom: Lentinus squarrosulus induces apoptosis in human lung cancer cells.

CONTEXT: Lentinus squarrosulus Mont. (Polyporaceae) is an interesting source of diverse bioactive compounds. OBJECTIVE: This is the first study of the anticancer activity and underlying mechanism of peptides extracted from Lentinus squarrosuls. MATERIALS AND METHODS: Peptides were isolated from the aqueous extract of L. squarrosulus by employing solid ammonium sulphate precipitation. They were further purified by ion-exchange chromatography on diethylaminoethanol (DEAE)-cellulose and gel filtration chromatography on Sephadex G25. Anticancer activity was investigated in human lung cancer H460, H292 and H23 cells cultured with 0-40 µg/mL of peptide extracts for 24 h. Cell viability and mode of cell death were evaluated by MTT and nuclear staining assay, respectively. Western blotting was used to investigate the alteration of apoptosis-regulating proteins in lung cancer cells treated with peptide extracts (0-20 µg/mL) for 24 h. RESULTS: The cytotoxicity of partially-purified peptide extracts from L. squarrosulus was indicated with IC50 of ∼26.84 ± 2.84, 2.80 ± 2.14 and 18.84 ± 0.30 µg/mL in lung cancer H460, H292 and H23 cells, respectively. The extracts at 20 µg/mL induced apoptosis through the reduction of anti-apoptotic Bcl-2 protein (∼0.5-fold reduction) and up-regulation of BAX (∼4.5-fold induction), a pro-apoptotic protein. Furthermore, L. squarrosulus peptide extracts (20 µg/mL) also decreased the cellular level of death receptor inhibitor c-FLIP (∼0.6-fold reduction). CONCLUSIONS AND DISCUSSION: This study provides the novel anticancer activity and mechanism of L. squarrosulus peptide extracts, which encourage further investigation and development of the extracts for anticancer use.

Role of chronic toxicology studies in revealing new toxicities.

Chronic (>3 months) preclinical toxicology studies are conducted to support the safe conduct of clinical trials exceeding 3 months in duration. We have conducted a review of 32 chronic toxicology studies in non-rodents (22 studies in dogs and 10 in non-human primates) and 27 chronic toxicology studies in rats dosed with Merck compounds to determine the frequency at which additional target organ toxicities are observed in chronic toxicology studies as compared to subchronic studies of 3 months in duration. Our review shows that majority of the findings are observed in the subchronic studies since additional target organs were not observed in 24 chronic non rodent studies and in 21 chronic rodent studies. However, 6 studies in non rodents and 6 studies in rodents yielded new findings that were not seen in studies of 3-month or shorter duration. For 3 compounds the new safety findings did contribute to termination of clinical development plans. Although the incidence of compound termination associated with chronic toxicology study observations is low (∼10%), the observations made in these studies can be important for evaluating human safety risk.

Safety of medicinal and edible herbs from fruit sources for human consumption: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal and edible herbs from fruit sources have been increasingly used in traditional Chinese medicine dietotherapy. There are no restrictions on who could consume the medicinal and edible fruits or on the dosage of consumption. However, their safety for human consumption has yet to be established. AIM OF THE STUDY: This systematic review aimed to assess the safety of human consumption of 30 medicinal and edible fruits. MATERIALS AND METHODS: Seven English and Chinese databases were searched up to May 31, 2023, to collect AE reports following human consumption of medicinal and edible fruits. Eligible reports should include details on the occurrence, symptoms, treatments, and outcomes of AEs. AEs that were life-threatening or caused death, permanent or severe disability/functional loss, or congenital abnormality/birth defects were classified as serious AEs (SAEs). The causality between the consumption of fruits and AEs was graded as one of four ranks: "certain", "probable", "possible", or "unlikely". RESULTS: Thirty AE reports related to the consumption of medicinal and edible fruits were included, involving 12 species of fruits: Crataegi fructus, Gardeniae fructus, Mori fructus, Hippophae fructus, Cannabis fructus, Siraitiae fructus, Perillae fructus, Rubi fructus, Longan arillus, Anisi stellati fructus, Zanthoxyli pericarpium, and Lycii fructus. No AE reports were found for the remaining 18 species. A total of 97 AEs, featuring predominantly gastrointestinal symptoms, followed by allergic reactions and neuropsychiatric symptoms, were recorded. Thirty SAEs were noted, with Zanthoxyli pericarpium accounting for the most (14 cases), followed by Perillae fructus (7 cases), Anisi stellati fructus (6 cases), and Gardeniae fructus, Rubi fructus, and Mori fructus (1 case each). Mori fructus was associated with one death. All AEs were concordant with a causality to fruit consumption, judged to be "certain" for 37 cases, "probable" for 53 cases, and "possible" for 7 cases. CONCLUSIONS: Our findings suggest that among medicinal and edible fruits, 12 species have AE reports with a causality ranging from "possible" to "definite". SAEs were not scarce. Most AEs may be associated with an excessive dose, prolonged consumption, or usage among infants or young children. No AE reports were found for the remaining 18 species.

COVID-19, new challenges to human safety: a global review.

In the context of sustainable human development, human safety has gradually shifted from traditional state and political conflict to social conflict and horizontal inequality, and the pandemic has exacerbated this variation risk. This narrative review includes literature from 40 countries on five continents since 2020, explored and tidy up the impacts of pandemics on human safety based on three perspectives: personal safety, family safety and social safety, refined the macroscopic concept of human safety. The comprehensibility of the global review conclusions is enhanced by combining it with Maslow's hierarchy of needs. Finally, some novel and comparative results are included to broaden the understanding of the impact of the pandemic, and help policymaker better understand human safety changes from a new perspective.

Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma.

In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages.

Nonionizing Electromagnetic Irradiations; Biological Interactions, Human Safety.

Human is usually exposed to environmental radiation from natural and man-made sources. Therefore, it is important to investigate the effects of exposure to environmental radiation, partly related to understanding and protecting against the risk of exposure to environmental radiation with beneficial and adverse impacts on human life. The rapid development of technologies causes a dramatic enhancement of radiation in the human environment. In this study, we address the biological effects caused by different fractions of non-ionizing electromagnetic irradiation to humans and describe possible approaches for minimizing adverse health effects initiated by radiation. The main focus was on biological mechanisms initiated by irradiation and represented protection, and safety approaches to prevent health disorders.

Challenges and opportunities for overcoming dog use in agrochemical evaluation and registration.

Progress in developing new tools, assays, and approaches to assess human hazard and health risk provides an opportunity to re-evaluate the necessity of dog studies for the safety evaluation of agrochemicals. A workshop was held where partic­ipants discussed the strengths and limitations of past use of dogs for pesticide evaluations and registrations. Opportunities were identified to support alternative approaches to answer human safety questions without performing the required 90-day dog study. Development of a decision tree for determining when the dog study might not be necessary to inform pesticide safety and risk assessment was proposed. Such a process will require global regulatory authority participation to lead to its acceptance. The identification of unique effects in dogs that are not identified in rodents will need further evaluation and determination of their relevance to humans. The establishment of in vitro and in silico approaches that can provide critical data on relative species sensitivity and human relevance will be an important tool to advance the decision process. Promising novel tools including in vitro comparative metabolism studies, in silico models, and high-throughput assays able to identify metabolites and mechanisms of action leading to development of adverse outcome pathways will need further development. To replace or eliminate the 90-day dog study, a collaborative, multidisciplinary, international effort that transcends organi­zations and regulatory agencies will be needed in order to develop guidance on when the study would not be necessary for human safety and risk assessment.

Study on the Vaccination of the Population of Romania against Monkeypox in Terms of Medical Security.

Although it has been shown in numerous studies that immunization of the population by vaccination is the most effective way to protect against smallpox or other polioviruses, the anti-vaccination public rhetoric recorded during the COVID-19 pandemic is likely to influence the populations acceptance of vaccination against newly emerging viruses. This fact influenced our decision to study the vaccination of the Romanian population against the virus that causes monkeypox, aiming to identify the degree of compliance regarding the decision related to vaccination acceptance/non-acceptance/hesitation, based on the survey of a representative sample of respondents. The study is based on an online questionnaire completed between 1 July and 31 July 2022 by 820 individuals, aged 18 years or above, with a permanent residency in Romania. The study was undertaken in order to observe the attitudes of the respondents regarding the acceptance, refusal, or hesitation of vaccination against monkeypox. The sociological data resulting from the application of the questionnaire on 820 people highlighted that 97.16% were vaccinated with the vaccines of the national mandatory scheme and 53.32% were vaccinated with the optional vaccines (rotavirus vaccine, anti-hepatitis A, meningococcal vaccine, etc.). Although 47.13% of respondents considered monkeypox to be a real problem facing humanity today, only 26.37% of those surveyed expressed their fear of becoming infected, and 29.30% were willing to immunize themselves against the virus by vaccination. Only 19.59% of respondents believed that the monkeypox disease will generate a new global pandemic, while 31.86% considered pandemics to be a human security issue, and 30.28% expressed their desire to accept a reduction in some rights and freedoms, in the short term, for the adoption of institutional measures to combat a possible pandemic caused by monkeypox. The study clearly highlights the fact that monkeypox is perceived as a threat to the health of the population, with relatively low acceptance of conspiracy theories regarding its origins/manifestation/consequences among respondents (between 21.7% and 28.9%). The vaccination of the population against monkeypox is strongly influenced by the validity of the results obtained over time, in the vaccination campaigns against the smallpox virus (vaccine found in the mandatory vaccination scheme in Romania until 1979). We believe that the negative public rhetoric regarding the COVID-19 vaccination is likely to negatively influence monkeypox vaccination. Although specialized studies and practical results showed that the immunization of the population through vaccination represents an important vector in the prevention/management of pandemic-type issues, we believe that a national pro-vaccination campaign, based on scientific evidence, can lead the population to accept vaccination when the epidemiological context requires it. We also believe that a culture of health security needs to be developed among citizens to raise awareness of the role of vaccines as an important vector in the field of population health.

Integrated modeling of 2D urban surface and 1D sewer hydrodynamic processes and flood risk assessment of people and vehicles.

In order to accurately simulate the whole urban flooding processes and assess the flood risks to people and vehicles in floodwaters, a 2D-surface and a 1D-sewer integrated hydrodynamic model was proposed in this study, with the module of flood risk assessment of people and vehicles being included. The proposed model was firstly validated by a dual-drainage laboratory experiment on the flood inundation process over a typical urban street, and the relative importance of model parameters and model uncertainties were evaluated using the GSA-GLUE method. Then the model was applied to simulate an actual urban flooding process that occurred in Glasgow, UK, with the influence of the sewer drainage system on flood inundation processes and hazard degree distributions of people and vehicles being comprehensively discussed. The following conclusions are drawn from this study: (i) The proposed model has a high degree of accuracy with the NSE values of key hydraulic variables greater than 0.8 and the GSA indicates that Manning roughness coefficients for surface and sewer flows, inlet weir and orifice discharge coefficients, are the most relevant parameters to influence the simulated results; (ii) vehicles are vulnerable to larger water depths while human stability is significantly influenced by higher flow velocities, with the overall flood risk of people being less than that of vehicles; and (iii) about 88.7% of the total inflow volume was drained to the sewer network, and the sewer drainage system greatly reduced the flood risks to people and vehicles except the local areas with large inundation water depths, where the sewer drainage increased the local flow velocity leading to higher flood risks especially for people.