Search Results (876)

Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates the treatment of skin and soft tissue infections (SSTI). It was previously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator complements peptide-derived immunostimulant-02 (CPDI-02; formerly EP67) and increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC, then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6 or 24 h post-challenge. Abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in subcutaneous abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity in male and female CD-1 mice was determined by IM dose escalation and repeat IM dosing. Results: Repeat IM treatment starting at 6 h post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolution, whereas repeat treatment by a topical, SQ, or IV route had no effect. Repeat treatment starting at 24 h post-challenge was ineffective by the current routes. Single IM treatment starting at 6 h post-challenge was as effective as repeat IM treatment, increased systemic exposure to CPDI-02, and, in subcutaneous abscesses, initially decreased IL-1β and increased MP. CPDI-02 was tolerated between 130 and 170 mg/kg after IM dose escalation and between 65 and 130 mg/kg after repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA and/or other pathogens controlled by activated MP. Full article

Cyanobacteria, also known as blue-green algae, are a diverse phylum of photosynthetic, Gram-negative bacteria and one of the largest microbial taxa. These organisms produce cyanotoxins, which are secondary metabolites that can have significant impacts on both human health and the environment. While toxins like Microcystins and Cylindrospermopsins are well-documented and have been extensively studied, other cyanotoxins, including those produced by Lyngbya and Nostoc, remain underexplored. These lesser-known toxins can cause various health issues in humans, including neurotoxicity, hepatotoxicity, and dermatotoxicity, each through distinct mechanisms. Moreover, recent studies have shown that cyanobacteria can be aerosolized and transmitted through the air over long distances, providing an additional route for human exposure to their harmful effects. However, it remains an area that requires much more investigation to accurately assess the health risks and develop appropriate public health guidelines. In addition to direct exposure to toxins, cyanobacteria can lead to harmful algal blooms, which pose further risks to human and wildlife health, and are a global concern. There is limited knowledge about these lesser-known cyanotoxins, highlighting the need for further research to understand their clinical manifestations and improve society’s preparedness for the associated health risks. This work aims to review the existing literature on these underexplored cyanotoxins, which are associated with human intoxication, elucidate their clinical relevance, address significant challenges in cyanobacterial research, and provide guidance on mitigating their adverse effects. Full article

This study explores the surface chemistry and electrical responses of ultra-high-sensitivity SnO₂ MEMS arrays to enable a novel sequential detection methodology for detecting nitrogen dioxide (NO₂) and ethanol (C₂H₅OH) as a route to achieve selective gas sensing in electronic nose (E-nose) applications. Utilizing tin oxide (SnO₂) thin films deposited via atomic layer deposition (ALD), the array achieves the lowest reported detection limits of 8 parts per billion (ppb) for NO₂. The research delves into the detection mechanisms of NO₂ and C₂H₅OH, both individually and in subsequent exposures, assessing the sensor’s dynamic response across various operating temperatures. It demonstrates rapid response and recovery times, with averages of 48 s and 277 s for NO₂ and 40 and 48 for C₂H₅OH. Understanding the role of individual gases on the SnO₂ surface chemistry is paramount in discerning subsequent gas exposure behavior. The oxidizing behavior of C₂H₅OH following NO₂ exposure is attributed to interactions between NO₂ and oxygen vacancies on the SnO₂ surface, which leads to the formation of nitrate or nitrite species. These species subsequently influence interactions with C₂H₅OH, inducing oxidizing properties, and need to be carefully considered. Principal component analysis (PCA) was used to further improve the sensor’s capability to precisely identify and quantify gas mixtures, improving its applicability for real-time monitoring in complex scenarios. Full article

Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new member of the coronavirus family. While respiratory transmission is the main route, concerns have arisen regarding possible vertical transmission, which refers to the transmission of the virus from mother to fetus through the dissemination of viral particles in the amniotic fluid. Fetal viral infection via the placenta can affect the formation of the auditory system and lead to congenital hearing disorders. The aim of this research was to investigate the effects of vertical exposure to COVID-19 on the auditory system of newborns. Methodology: The study included a study group (SG) and a control group (CG). Selected during neonatal hearing screening, the SG consisted of 23 infants up to 1 year old whose mothers had been infected with SARS-CoV-2. The CG consisted of 15 infants whose mothers became pregnant after the end of the pandemic, had tested negative for COVID-19, and had no respiratory symptoms during pregnancy. The assessments for both groups were brainstem auditory evoked potentials (BAEPs), tympanometry, transient evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs). The research was divided into two studies, one cross-sectional and the other longitudinal. Results: All participants exhibited absolute latencies within the normal range for waves I, III, and V, although in the SG, there was a statistically significant increase in the latency of wave I in the left ear. In terms of OAEs, in the SG, there appeared to be a tendency for TEOAEs to be absent at high frequencies. Over several months, there was a general decrease in the amplitude of high-frequency responses in both TEOAEs and DPOAEs. Conclusion: No evidence was found that vertical exposure to COVID-19 causes hearing loss, although there were signs of possible deterioration in hair cell functioning. Full article

The increasing use of Cannabis sativa products for medicinal, dietary, and recreational purposes has raised concerns about mycotoxin contamination in cannabis and hemp. Mycotoxins persist in these products’ post-processing, posing health risks via multiple exposure routes. This study investigated cytotoxic and genotoxic interactions between cannabidiol (CBD) and the mycotoxin citrinin (CIT) using human cell models: SH-SY5Y, HepG2, HEK293, and peripheral blood lymphocytes. IC₅₀ values and membrane disruption were initially assessed, followed by an evaluation of genotoxicity in lymphocytes using the Comet Assay and Cytokinesis Blocked Micronucleus Cytome Assay. Obtained findings demonstrate that cell-type sensitivity varied across treatments, with combined CBD and CIT exposure exhibiting distinct interactions. Lactate dehydrogenase (LDH) release remained minimal, suggesting cytotoxicity did not stem from membrane disruption but likely involved intracellular pathways. In lymphocytes, CBD alone produced negligible cyto/genotoxic effects and weak antiproliferative responses, whereas CIT displayed clear toxic impacts. DNA damage indicates that CIT may induce genome instability through indirect mechanisms rather than direct DNA interaction, with evidence of potential aneuploidic effects from the CBMN Cyt Assay. Combined exposure led to a reduction in CIT-induced DNA and cytogenetic damage, suggesting CIT’s potential interference with the beneficial properties of CBD. These results provide a foundation for further toxicological assessments and highlight the necessity of standardized mycotoxin monitoring in cannabis-derived products. Full article

In this study, Streptococcus mutans bacteria were tested on nickel–titanium archwires in the presence of silver nanoparticles (AgNPs) as coatings. As a growth control, a well containing the BHI broth and bacterial suspension without silver nanoparticles was inoculated. The test was carried out in triplicate. The NiTi archwires in the presence of artificial saliva were incubated at different exposure times between 0–24 h and 15–30 days, respectively. The archwires were then put in contact with S. mutans to evaluate the AgNPs bactericidal effect. The characterization of AgNPs with NiTi archwires was conducted using scanning electron microscopy (SEM), X-ray energy dispersive analysis (EDS), fast fourier transform (FFT), power spectral density (PSD), surface geometry analysis, metal relation analysis, and control process analysis. The results indicate that the bioelectric signal and chemical interaction of NiTi and Ag nanoparticles have an antibacterial effect. In this context, the high wavelength of 17.06 mm and the wave amplitude of 15.66 GL are representative of the light scattering and humidity of the system in which the bacteria and silver nanoparticles interact. The sizes of the Ag nanoparticles in the archwires were less than 150 nm. Under microaerophile conditions, the solution’s pH and temperature were 7.0 at 37 °C, respectively. The NiTi archwires AgNPs functionality and relation to the minimum inhibitory concentration, dominant wavelength in power spectral density, and fast fourier transform analyses were investigated. The analysis was of the interaction between the high and low frequencies of the AgNPs-NiTi archwires and the S. mutans bacteria. This approach opens up a new route for the assessment and management of bacterial growth in various fluids by utilizing alternative biologically acceptable materials. Full article

The Zika virus (ZIKV) epidemic elicited a rapid commitment to the development of animal models for ZIKV research. Non-human primates (NHPs) and mice have made significant contributions to this research, but NHPs are expensive, have a long gestation period, and are available only in small numbers; non-genetically modified mice are resistant to infection. To address these deficiencies, we have established the laboratory opossum, Monodelphis domestica, as a small animal model that complements the mouse and monkey models. We developed and validated an indirect ELISA for measuring antibodies to ZIKV in opossums, as well as an immunohistochemistry (IHC) method to detect ZIKV NS1 protein in tissue samples. Opossum pups inoculated intracerebrally as embryos, juveniles inoculated by several routes, and mothers that cannibalized inoculated pups became persistently infected with ZIKV. The virus spread to multiple organs and persisted for up to 38 weeks (the latest endpoint of the experiments). A robust humoral immune response was mounted, and high titers of antibodies also persisted for 38 weeks. The results establish M. domestica as a natural, non-genetically modified animal model in which ZIKV persists long-term after experimental exposure and as a unique animal model for research on the immune response to ZIKV. Full article

The American College of Obstetricians and Gynecologists provided updated guidance in 2021, recommending that reproductive health professionals should include discussion of environmental exposures with their patients. However, environmental health is seldom included in medical training, with endocrine-disrupting chemicals, such as phthalates—linked to adverse pregnancy outcomes—being among the least discussed. We developed a one-hour virtual educational intervention to train reproductive health professionals on the routes of phthalate exposure, potential associated health impacts, and suggestions on how to discuss exposure reduction with patients. The intervention was designed to include perspectives from patients, scientists, and clinicians. Using a pre/post/post design, we evaluated the impact of the intervention on reproductive health professionals’ phthalate-related reproductive health literacy via a validated environmental health literacy (EHL) scale, their confidence in discussing phthalates, and the frequency of discussions about phthalates with patients. All materials, including the study questionnaires and intervention materials, were administered virtually to reproductive health professionals (n = 203) currently seeing patients working in the United States. After completing the intervention, reproductive health professionals’ average EHL increased (pre-course: 22.3, post-course: 23.7, 2 months post-course: 24.0), as did their confidence in discussing phthalates with their patients (pre-course: 1% (2/203) reported being quite confident, post-course: 64% (131/203) reported being quite confident, and 2 months post course: 86% (174/203) reported being quite confident). Additionally, the reported frequency of discussions about phthalates with patients rose substantially (pre-course: 0% (0/203) reported usually discussing phthalates with patients, and 2 months post-course: 86% (175/203) reported usually discussing phthalates with patients): In line with the recommendations of the American College of Obstetricians and Gynecologists, this online phthalate educational intervention tool increased EHL among reproductive health professionals and shifted clinical care to include discussion about phthalates, a reproductive toxicant. Full article

Since the Industrial Revolution, underwater soundscapes have become more complex and contaminated due to increased cumulative human activities. Anthropogenic underwater sources have been growing in number, and shipping noise has become the primary source of chronic acoustic exposure. However, global data on current and historic noise levels is lacking. Here, using the Listening to the Deep-Ocean Environment network, we investigated the baseline shipping noise levels in thirteen observatories (eight stations from ONC Canada, four from the JAMSTEC network, and OBSEA in the Mediterranean Sea) and, in five of them, animal presence. Our main results show yearly noise variability in the studied locations that is not dominated by marine traffic but by natural and biological patterns. The halt in transportation due to COVID was insignificant when the data were recorded far from shipping routes. In order to better design a legislative framework for mitigating noise impacts, we highlight the importance of using tools that allow for long-term acoustic monitoring, automated detection of sounds, and big data handling and management. Full article

Vehicular Ad-Hoc Networks (VANETs) play an essential role in the intelligent transportation era, furnishing users with essential roadway data to facilitate optimal route selection and mitigate the risk of accidents. However, the network exposure makes VANETs susceptible to cyber threats, making authentication crucial for ensuring security and integrity. Therefore, joining entity verification is essential to ensure the integrity and security of communication in VANETs. However, to authenticate the entities, authentication time should be minimized to guarantee fast and secure authentication procedures. We propose an authentication system for VANETs using blockchain and Kerberos for storing authentication messages in a blockchain ledger accessible to Trusted Authentication Servers (TASs) and Roadside Units (RSUs). We evaluate the system in three diverse network scenarios: suburban, urban with 1 TAS, and urban with 2 TASs. The findings reveal that this proposal is applicable in diverse network scenarios to fulfill the network requirements, including authentication, handover, and end-to-end delay, considering an additional TAS for an increasing number of vehicles. The system is also practicable in storing the authentication message in blockchain considering the gas values and memory size for all scenarios. Full article

The development of new organic nitrates is still relevant due to the clinical limitations of their use. Tetrahydrofurfuryl nitrate (NTHF) is a new organic nitrate obtained through a synthetic route of sugarcane. The aim of this research was to investigate the cardiovascular effects promoted by NTHF in rats. Isolated vascular smooth muscle cells (VSMC) were incubated with a specific probe and were analyzed in a flow cytometer to measure the NO concentration after NTHF treatment. Rat superior mesenteric rings were isolated and used for isometric tension recordings and the evaluation of the vasorelaxant activity induced by NTHF. For the in vivo study, polyethylene catheters were implanted into the abdominal aorta and inferior vena cava of the rats (weighing 250–300 g). NTHF increased NO levels in rat VSMCs. In anesthetized rats, NTHF induced hypotension and bradycardia after intravenous administration. These effects were attenuated after the administration of a sGC inhibitor, methylene blue. In the phenylephrine pre-contracted superior mesenteric artery of rats, NTHF (1 pM–10 μM) induced concentration-dependent vasodilatation in both the intact and removed endothelium. Furthermore, in the presence of NO° scavenging (C-PTIO and HDX) or ODQ, a sGC inhibitor, the vasorelaxation induced by NTHF was decreased. NTHF tolerance was evaluated in mesenteric artery rings previously exposed with isolated concentrations of the new organic nitrate. The vasorelaxant effect was not modified by exposure to nitrate. These results demonstrated that NTHF induced hypotension and bradycardia in vivo and a vasorelaxant effect with the participation of the NO-sGC-PKG pathway and triggering calcium-activated K⁺ channels without vascular tolerance induction. Full article

Objective: To establish and validate an LC-MS/MS method for the simultaneous determination of curcumin (CUR) as well as its glucuronide conjugate (COG) and sulfate conjugate (COS) in rat plasma. The method was employed to evaluate and compare the pharmacokinetic behaviors of curcumin following oral and intratracheal administration in rats. Methods: Rat plasma samples were separated by chromatography on a C18 column after protein precipitation with acetonitrile. Gradient elution with a mobile phase of 0.5 mM ammonium acetate in acetonitrile was utilized. Mass spectrometry detection incorporated an electrospray ionization (ESI) source, multiple reaction monitoring (MRM), and dual-mode (positive and negative) scanning for quantitative analysis. A total of 12 SD rats were randomly divided into two groups and were orally (20 mg/kg) or intratracheally (10 mg/kg) administrated curcumin, respectively. CUR, COG, and COS concentrations in plasma were measured to assess pharmacokinetic disparities. Results: The method demonstrated linearity within the ranges of 2–400 ng/mL for CUR and COS and 5–1000 ng/mL for COG. Intratracheal administration significantly elevated CUR plasma concentrations compared to oral administration. The exposure of COG was higher than COS following oral administration. Conversely, intratracheal administration resulted in markedly higher COS exposure, with no significant difference in COG exposure after dose normalization between oral and inhalation routes. Conclusions: The established LC-MS/MS method provides a reliable tool for the simultaneous measurement of CUR, COG, and COS in rat plasma, facilitating preclinical pharmacokinetic investigations. The study reveals distinct pharmacokinetic profiles for CUR following oral versus intratracheal administration, suggesting that inhalation may offer superior therapeutic efficacy. Full article

To assess the human impact on the water of Dayat Roumi Lake and to develop effective management strategies to protect and restore this vital ecosystem in the region, seasonal sampling was carried out at six stations distributed around the lake. During these sampling campaigns, 24 parameters were measured, including 20 trace elements. Results showed that measured levels of trace elements increased in the following order: Cd < Be < Tl < Co < Sb < Mo < Cu < Zn < Ni < V < Rb < Mn < As < Cr < Pb < Li < Ba < Se < Pd < Sr in the lake water and that these recorded values were lower than those recommended by the Moroccan standard and the World Health Organization, except for Pb and Se. Correlation analysis revealed two principal water-contamination sources: natural geological origins and anthropogenic inputs. In addition, the Water Quality Index WQI showed that the lake’s water quality is poor, and its use can be dangerous for human and animal health. Health risk assessment associated with prolonged exposure to trace elements in lake water revealed that the Hazard quotient HQ and Hazard index HI of certain elements, such as Tl, Sb, V, As, Cr, Pb, Li, and Se, are higher than 1 in adult and children, indicating a significant risk for people living near the lake. Children are particularly vulnerable, with higher levels of HQ and HI, and selenium poses a substantial risk to their health through ingestion and skin absorption. In both adults and children, the total risk of cancer due to metals is classified as follows: CI (Cr) > CI (Ni) > CI (As) > CI (Pb) > CI (Cd). The Cr presents the highest carcinogenic risk—by ingestion or dermal route—in both groups. The total risk for these five metals exceeds 1 × 10⁻⁴, indicating a danger for residents who drink or swim in the lake. Full article

Informal e-waste recycling can cause serious heavy metal(loid) pollution to nearby bodies of water, thereby increasing the risk of heavy metal exposure to local residents. This study investigates metal(loid) pollution levels in the Lianjiang River, which flows through Guiyu, an e-waste recycling town in Shantou, Guangdong. In 2009 and 2020, water samples from the Lianjiang River were taken, and the levels of 12 metal(loid)s (V, Cr, Mn, Sr, Ni, Cu, Zn, As, Se, Cd, Ba, and Pb) were measured by ICP-MS. In total, 380 valid questionnaires from Guiyu kindergarten children were selected to assess child health. Exposure health risks for children were calculated using two forms of exposure (dermal and inhalation) and statistical methods (multiple linear regression and Bayesian kernel machine regression—BKMR). The concentrations of Mn, Ni, Pb, and Cd in 2009 were significantly higher than those in 2020. The concentration of heavy metal(loid)s had been decreasing in 2020. The non-carcinogenic risk levels of the 12 metal(loid)s in both exposure routes were at an acceptable risk level. The average carcinogenic risk levels for As, Cr, Ni, Pb, and Cd exceeded the ILCRi <10–6 acceptable range. According to MLR, it was found that daily oral intake doses of Pb [β(95% CI): −0.949 (−1.596, −0.863), p < 0.001 and Se [β(95% CI): −0.911 (−1.888, −0.092), p = 0.031] were negatively associated with body mass index. A BKMR model was developed, through which the synergistic effects of co-exposure to 12 heavy metal(loid)s on growth and development indicators in children were analyzed. Concentrations of heavy metal(loid)s in rivers near e-waste recycling sites have been decreasing for 10 years. It was found that the growth and development of children are affected by the intake of heavy metal(loid)s in water. The reduction in heavy metal(loid) contamination in e-waste recycling areas needs to be continued, and concern about its impact on children’s health must remain. Full article

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity. Full article