Antibiotic resistance and nanotechnology: A narrative review.

The rise of antibiotic resistance poses a significant threat to public health worldwide, leading researchers to explore novel solutions to combat this growing problem. Nanotechnology, which involves manipulating materials at the nanoscale, has emerged as a promising avenue for developing novel strategies to combat antibiotic resistance. This cutting-edge technology has gained momentum in the medical field by offering a new approach to combating infectious diseases. Nanomaterial-based therapies hold significant potential in treating difficult bacterial infections by circumventing established drug resistance mechanisms. Moreover, their small size and unique physical properties enable them to effectively target biofilms, which are commonly linked to resistance development. By leveraging these advantages, nanomaterials present a viable solution to enhance the effectiveness of existing antibiotics or even create entirely new antibacterial mechanisms. This review article explores the current landscape of antibiotic resistance and underscores the pivotal role that nanotechnology plays in augmenting the efficacy of traditional antibiotics. Furthermore, it addresses the challenges and opportunities within the realm of nanotechnology for combating antibiotic resistance, while also outlining future research directions in this critical area. Overall, this comprehensive review articulates the potential of nanotechnology in addressing the urgent public health concern of antibiotic resistance, highlighting its transformative capabilities in healthcare.

Clinical characteristics of hospitalized patients with Nocardia genus detection by metagenomic next generation sequencing in a tertiary hospital from southern China.

OBJECTIVE: As an opportunistic pathogen, Nocardia often occurring in the immunocompromised hosts. As the unspecifc clinical presentation and low identification rate of the culture dependent methods, Nocardia infection may be under-diagnosis. Recent study have reported physicians could benefit from metagenomic next-generation sequencing (mNGS) in Nocardia diagnosis. Herein, we present patients with a positive detection of nocardiosis in mNGS, aiming to provide useful information for an differential diagnosis and patients management. METHODS: A total of 3756 samples detected for mNGS from March 2019 to April 2022 at the Fifth Affifiliated Hospital of Sun Yat-sen University, were screened. Clinical records, laboratory finding, CT images and mNGS results were reviewed for 19 patients who were positive for Nocardia genus. RESULTS: Samples from low respiratory tract obtained by bronchoscope took the major part of the positive (15/19). 12 of 19 cases were diagnosis as Nocardiosis Disease (ND) and over half of the ND individuals (7/12) were geriatric. Nearly all of them (10/12) were immunocompetent and 2 patients in ND group were impressively asymptomatic. Cough was the most common symptom. Nocardia cyriacigeorgica (4/12) was more frequently occurring in ND, followed by Nocardia abscessus (3/12). There are 3 individuals detected more than one kind of Nocardia species (Supplementary table 1). Except one with renal failure and one allergic to sulfamethoxazole, all of them received co-sulfonamide treatment and relieved eventually. CONCLUSION: Our study deciphered the clinical features of patients with positive nocardiosis detected by mNGS. Greater attention should be paid to the ND that occurred in the immunocompetent host and the geriatric. Due to the difficulties in establishing diagnosis of Nocardiosis disease, mNGS should play a much more essential role for a better assessment in those intractable cases. Co-sulfonamide treatment should still be the first choice of Nocardiosis disease.

Prevalence of gram-negative bacteria and their antibiotic resistance in neonatal sepsis in Iran: a systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis, particularly gram-negative (GN) bacteria-induced, is a significant cause of morbidity and mortality in newborns. Healthcare professionals find this issue challenging because of antibiotic resistance. This study aims to combine findings to identify the prevalence of GN bacteria and their antibiotic resistance in Iranian neonates with sepsis. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed through international databases, including (PubMed/MEDLINE, EMBASE, Scopus, and Web of Science), Iranian local databases (Magiran, Iranmedex, Irandoc, Scimed, and SID), and the first 100 records of Google Scholar. Analytical cross-sectional study checklist from the Joanna Briggs Institute (JBI) was used for the quality assessment of included studies. Comprehensive Meta-Analysis Software Version 2 was used to conduct the meta-analysis. The between-study heterogeneity was investigated by I2 statistics. RESULTS: The prevalence of GN bacteria was estimated to be 53.6% [95% CI: 45.9- 61.1: P = 0.362] in Iranian neonates with sepsis, based on 31 studies with a sample size of 104,566. klebsiella pneumoniae (K.pneumonia) (23.2% [95% CI: 17.5-30.0, P < 0.001]) followed by Escherichia coli (E.coli) (13.5% [95% CI: 9.4-18.9, P < 0.001]) were more prevalent among GN bacteria. The highest resistance in K.pneumoniae was observed in Cefixime (80.6%, [95% CI: 56.3-93.1, P = 0.018]). E.coli showed greater resistance to Ampicillin (61.8%, [95% CI: 44.2-76.5, P = 0.188]. The prevalence of GN bacteria in Iranian neonates with sepsis has a decreasing trend based on the year, as shown by a meta-regression model (P < 0.0004). CONCLUSION: GN pathogens, particularly K.pneumoniae, and E.coli, are the leading cause of neonatal sepsis in Iran. GN bacteria showed the highest resistance to Third-generation cephalosporin and Aminoglycosides.

Antibiotic Management of Patients with Hematologic Malignancies: From Prophylaxis to Unusual Infections.

PURPOSE OF REVIEW: Patients with hematological malignancies are recognized for their high susceptibility and increased risk of developing infections associated with immunosuppression that can be caused by the infection itself or by the treatments that condition a decrease in the humoral and T lymphocyte response, so this review attempts to gather the main bacterial, viral, parasitic, and fungal agents that affect them and give recommendations for their approach and diagnosis. RECENT FINDINGS: In recent years, with the discovery and use of new therapies including immunological and targeted treatments, it has been possible to improve the survival and response of patients with hematological malignancies; however, antimicrobial resistance has also increased; we have faced new and unknown microorganisms, such as the SARS-CoV-2 that caused the COVID-19 pandemic in the past year, and therefore, new risks and more severe infections are presented. We present a review of the different circumstances where hematological malignancies increased the risk of infections and which microorganisms affect these patients, their characteristics, and the suggested prophylaxis.

Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases.

Taurine haloamines, N-chlorotaurine (NCT, TauCl), and N-bromotaurine (NBT, TauBr) are formed by a reaction between taurine and hypohalous acids, HOCl and HOBr, respectively. The major source of endogenous taurine haloamines is neutrophils. Both NCT and NBT share strong anti-inflammatory and microbicidal activities supported by an absence of microbial resistance. In the light of these properties, a number of clinical studies have been performed to document their effectiveness in treatment of bacterial, fungal, and viral infections. The administration of NCT and NBT has been limited to topical application, as they are decomposed upon systemic delivery. This review summarizes current knowledge concerning the therapeutic use of NCT and NBT mainly in various skin disorders such as non-healing wounds, acne vulgaris, herpes zoster, and psoriasis. Moreover, the beneficial effect of NCT inhalation in early stages of COVID-19 and other viral respiratory infections is discussed. And finally, we would like to suggest that NCT might be used to inhibit the development of the cytokine storm through its capacity to suppress the production of IL-6.

Estimating the incidence rate ratio of common cold among patients with non-apnea sleep disorders: a retrospective cohort study.

The purpose was to explore the potential effects of nonapnea sleep disorders (NSDs) and hypnotic use on the incidence of common cold. This study adapted population-based retrospective cohort study designed. We used the data from the Taiwan National Health Insurance Research Database between 1998 and 2011. In total, 59,476 patients with NSDs were included in the study cohort, and the reference cohort comprised 59,476 propensity score-matched patients. We conducted a Poisson regression analysis to assess the incidence of common cold. The overall incidence of common cold was significantly higher than that in the reference cohort. Compared with the patients of the reference cohort without hypnotic use, those of the NSDs cohort with benzodiazepines and zolpidem use had higher incidence of common cold. In conclusion, study cohort had a higher incidence of developing common cold, and particularly pronounced in NSDs with hypnotic use.

A knowledge-based self-pre-diagnosis system to predict Covid-19 in smartphone users using personal data and observed symptoms.

Covid-19 is an acute respiratory infection and presents various clinical features ranging from no symptoms to severe pneumonia and death. Medical expert systems, especially in diagnosis and monitoring stages, can give positive consequences in the struggle against Covid-19. In this study, a rule-based expert system is designed as a predictive tool in self-pre-diagnosis of Covid-19. The potential users are smartphone users, healthcare experts and government health authorities. The system does not only share the data gathered from the users with experts, but also analyzes the symptom data as a diagnostic assistant to predict possible Covid-19 risk. To do this, a user needs to fill out a patient examination card that conducts an online Covid-19 diagnostic test, to receive an unconfirmed online test prediction result and a set of precautionary and supportive action suggestions. The system was tested for 169 positive cases. The results produced by the system were compared with the real PCR test results for the same cases. For patients with certain symptomatic findings, there was no significant difference found between the results of the system and the confirmed test results with PCR test. Furthermore, a set of suitable suggestions produced by the system were compared with the written suggestions of a collaborated health expert. The suggestions deduced and the written suggestions of the health expert were similar and the system suggestions in line with suggestions of the expert. The system can be suitable for diagnosing and monitoring of positive cases in the areas other than clinics and hospitals during the Covid-19 pandemic. The results of the case studies are promising, and it demonstrates the applicability, effectiveness, and efficiency of the proposed approach in all communities.

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID-19 patients.

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID-19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID-19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse-transcriptase polymerase chain reactions virologically confirmed COVID-19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6-22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56-10.63, p < .001]), gender (aHR for male: 2.97 [1.47-5.99, p = .002]), chronic pulmonary disease (aHR: 4.84 [2.32-10.07, p < .001]), obesity (aHR: 3.32 [1.70-6.52, p < .001]), and diabetes (aHR: 1.98 [1.01-3.89, p = .048]). The median nasopharyngeal viral load at admission was 6.4 log10 copies/ml and was associated with mortality regardless of clinical risk factors. Viral load decreased with time elapsed since symptoms onset. Our study confirmed that mortality was associated with clinical characteristics at admission. The viral load at admission was significantly lower in patients admitted late after the onset of symptoms in both dead and alive patients. Our results could improve earlier identification of patients with increased risk of mortality and adapted management.

Antibody detection by agglutination-PCR (ADAP) enables early diagnosis of HIV infection by oral fluid analysis.

Oral fluid (OF) is a highly effective substrate for population-based HIV screening efforts, as it is noninfectious and significantly easier to collect than blood. However, anti-HIV antibodies are found at far lower concentrations in OF compared with blood, leading to poor sensitivity and a longer period of time from infection to detection threshold. Thus, despite its inherent advantages in sample collection, OF is not widely used for population screening. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. This assay is 1,000-10,000 times more analytically sensitive than clinical enzyme-linked immunoassays (EIAs), displaying both 100% clinical sensitivity and 100% specificity for detecting HIV antibodies within OF samples. We show that the enhanced analytical sensitivity enables this assay to correctly identify HIV-infected individuals otherwise missed by current OF assays. We envision that the attributes of this improved HIV OF assay can increase testing rates of at-risk individuals while enabling diagnosis and treatment at an earlier time point.

Fungal recognition by mammalian fibrinogen-related proteins.

Fungi are ubiquitous eukaryotic micro-organisms present in virtually all environmental habitats. Although rarely pathogenic to the healthy population, many fungal species are capable of causing human disease in immunocompromised individuals. Thus, fungal infections remain a significant cause of morbidity and mortality, with rising prevalence accompanying the worldwide increase in immunosuppression-based therapies. Therefore, better understanding of the mutual interactions between the protective host mechanisms and the invading fungi remains of critical importance. The innate immune system constitutes the first line of defence against exogenous insults. The innate antifungal immunity is mediated through recognition of specific pathogen-associated molecular patterns (PAMPs) by a broad panel of host pattern recognition receptors (PRRs), responsible for mounting adequate protective responses. In this review, we describe fungal PAMPs as well as a selection of PRRs able to recognize them. We focus on the members of the fibrinogen-related domain (FReD) protein family that have been shown to recognize fungi-derived molecules: ficolins, fibrinogen C domain containing 1 (FIBCD1) and tenascin-C. We describe their structure, their binding targets and their established as well as putative biological functions related to fungal recognition and immunity.

Contactless Vital Signs Measurement System Using RGB-Thermal Image Sensors and Its Clinical Screening Test on Patients with Seasonal Influenza.

Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.

MF59 adjuvant enhances the immunogenicity and protective immunity of the OmpK/Omp22 fusion protein from Acineterbacter baumannii through intratracheal inoculation in mice.

Acinetobacter baumannii (A baumannii) is an emerging nosocomial pathogenic bacterium which leads to hospital infections. The increase in drug-resistant A baumannii strains makes it difficult to control by using common antibiotics. The development of effective vaccines is an alternative means to avoid A baumannii infections. In the present study, Balb/c mice were inoculated intratracheally with 30 µg of OmpK/Omp22 fusion protein alone or OmpK/Omp22 formulated with MF59 adjuvant. After two times of boosting at day 14 and 21, the antigen-specific antibody levels and the protective immunity against A baumannii challenge were evaluated. The results showed that the OmpK/Omp22 formulated with MF59 immunized mice produced much higher level of antigen-specific antibodies compared to mice immunized with OmpK/Omp22 alone (P < 0.01). Mice immunized with 30 µg of OmpK/Omp22 formulated with MF59 also provided more potent protection post-challenge, which showed lower bacterial loads in the blood and lung tissue, lower level of blood inflammatory cytokines and higher survival rate (83.3%) than mice immunized with OmpK/Omp22 alone (P < 0.001). In conclusion, this study demonstrated that OmpK/Omp22 fusion protein adjuvanted with MF59 induced superior immune response and better protection than OmpK/Omp22 alone through intratracheal inoculation in mice.

Association between MASP-2 gene polymorphism and risk of infection diseases: A meta-analysis.

BACKGROUND: The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. AIMS: To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. METHOD: Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. RESULTS: 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). CONCLUSION: This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms.

The role of P450 enzymes in malaria and other vector-borne infectious diseases.

Vector-borne infectious diseases are still an important global health problem. Malaria is the most important among them, mainly pediatric, life-threatening disease. Malaria and other vector-borne disorders caused by parasites, bacteria, and viruses have a strong impact on public health and significant economic costs. Most vector-borne diseases could be prevented by vector control, with attention to the ecological and biodiversity conservation aspects. Chemical control with pesticides and insecticides is widely used as a measure of prevention although increasing resistance to insecticides is a serious issue in vector control. Metabolic resistance is the most common mechanism and poses a big challenge. Insect enzyme systems, including monooxygenase CYP P450 enzymes, are employed by vectors mainly to metabolize insecticides thus causing resistance. The discovery and application of natural specific inhibitors/blockers of vector P450 enzymes as synergists for commonly used pesticides will contribute to the "greening" of insecticides. Besides vector CYPs, host CYP enzymes could also be exploited to fight against vector-borne diseases: using mostly their detoxifying properties and involvement in the immune response. Here, we review published research data on P450 enzymes from all players in vector-borne infections, that is, pathogens, vectors, and hosts, regarding the potential role of CYPs in disease. We discuss strategies on how to exploit cytochromes P450 in vector-borne disease control.

Lives of Skin Lesions in Monkeypox: Histomorphological, Immunohistochemical, and Clinical Correlations in a Small Case Series.

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.

Improvement of the software for modeling the dynamics of epidemics and developing a user-friendly interface.

The challenges humanity is facing due to the Covid-19 pandemic require timely and accurate forecasting of the dynamics of various epidemics to minimize the negative consequences for public health and the economy. One can use a variety of well-known and new mathematical models, taking into account a huge number of factors. However, complex models contain a large number of unknown parameters, the values of which must be determined using a limited number of observations, e.g., the daily datasets for the accumulated number of cases. Successful experience in modeling the COVID-19 pandemic has shown that it is possible to apply the simplest SIR model, which contains 4 unknown parameters. Application of the original algorithm of the model parameter identification for the first waves of the COVID-19 pandemic in China, South Korea, Austria, Italy, Germany, France, Spain has shown its high accuracy in predicting their duration and number of diseases. To simulate different epidemic waves and take into account the incompleteness of statistical data, the generalized SIR model and algorithms for determining the values of its parameters were proposed. The interference of the previous waves, changes in testing levels, quarantine or social behavior require constant monitoring of the epidemic dynamics and performing SIR simulations as often as possible with the use of a user-friendly interface. Such tool will allow predicting the dynamics of any epidemic using the data on the number of diseases over a limited period (e.g., 14 days). It will be possible to predict the daily number of new cases for the country as a whole or for its separate region, to estimate the number of carriers of the infection and the probability of facing such a carrier, as well as to estimate the number of deaths. Results of three SIR simulations of the COVID-19 epidemic wave in Japan in the summer of 2022 are presented and discussed. The predicted accumulated and daily numbers of cases agree with the results of observations, especially for the simulation based on the datasets corresponding to the period from July 3 to July 16, 2022. A user-friendly interface also has to ensure an opportunity to compare the epidemic dynamics in different countries/regions and in different years in order to estimate the impact of vaccination levels, quarantine restrictions, social behavior, etc. on the numbers of new infections, death, and mortality rates. As example, the comparison of the COVID-19 pandemic dynamics in Japan in the summer of 2020, 2021 and 2022 is presented. The high level of vaccinations achieved in the summer of 2022 did not save Japan from a powerful pandemic wave. The daily numbers of cases were about ten times higher than in the corresponding period of 2021. Nevertheless, the death per case ratio in 2022 was much lower than in 2020.

Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.

The coordinating role of nuclear factor erythroid-2-related factor 2 (Nrf2) in cellular function is undeniable. Evidence indicates that this transcription factor exerts massive regulatory functions in multiple signaling pathways concerning redox homeostasis and xenobiotics, macromolecules, and iron metabolism. Being the master regulator of antioxidant system, Nrf2 controls cellular fate, influencing cell proliferation, differentiation, apoptosis, resistance to therapy, and senescence processes, as well as infection disease success. Because Nrf2 is the key coordinator of cell defence mechanisms, dysregulation of its signaling has been associated with carcinogenic phenomena and infectious and age-related diseases. Deregulation of this cytoprotective system may also interfere with immune response. Oxidative burst, one of the main microbicidal mechanisms, could be impaired during the initial phagocytosis of pathogens, which could lead to the successful establishment of infection and promote susceptibility to infectious diseases. There is still a knowledge gap to fill regarding the molecular mechanisms by which Nrf2 orchestrates such complex networks involving multiple pathways. This review describes the role of Nrf2 in non-pathogenic and pathogenic cells.

Trends of the COVID-19 dynamics in 2022 and 2023 vs. the population age, testing and vaccination levels.

Introduction: The population, governments, and researchers show much less interest in the COVID-19 pandemic. However, many questions still need to be answered: why the much less vaccinated African continent has accumulated 15 times less deaths per capita than Europe? or why in 2023 the global value of the case fatality risk is almost twice higher than in 2022 and the UK figure is four times higher than the global one? Methods: The averaged daily numbers of cases DCC and death DDC per million, case fatality risks DDC/DCC were calculated for 34 countries and regions with the use of John Hopkins University (JHU) datasets. Possible linear and non-linear correlations with the averaged daily numbers of tests per thousand DTC, median age of population A, and percentages of vaccinations VC and boosters BC were investigated. Results: Strong correlations between age and DCC and DDC values were revealed. One-year increment in the median age yielded 39.8 increase in DCC values and 0.0799 DDC increase in 2022 (in 2023 these figures are 5.8 and 0.0263, respectively). With decreasing of testing level DTC, the case fatality risk can increase drastically. DCC and DDC values increase with increasing the percentages of fully vaccinated people and boosters, which definitely increase for greater A. After removing the influence of age, no correlations between vaccinations and DCC and DDC values were revealed. Discussion: The presented analysis demonstrates that age is a pivot factor of visible (registered) part of the COVID-19 pandemic dynamics. Much younger Africa has registered less numbers of cases and death per capita due to many unregistered asymptomatic patients. Of great concern is the fact that COVID-19 mortality in 2023 in the UK is still at least 4 times higher than the global value caused by seasonal flu.

Nanoemulsion and nanogel containing Artemisia dracunculus essential oil; larvicidal effect and antibacterial activity.

OBJECTIVE: Microbial infections and mosquito-borne diseases such as malaria, with 627 k deaths in 2020, are still major public health challenges. RESULTS: This study prepared nanoemulsion and nanogel containing Artemisia dracunculus essential oil. ATR-FTIR analysis (Attenuated Total Reflection-Fourier Transform InfraRed) confirmed the successful loading of the essential oil in nanoemulsion and nanogel. LC50 values (Lethal Concentration 50%) of nanogel and nanoemulsion against Anopheles stephensi larvae were obtained as 6.68 (2-19 µg/mL) and 13.53 (7-25 µg/mL). Besides, the growth of Staphylococcus aureus after treatment with 5000 µg/mL nanogel and nanoemulsion was reduced by ~ 70%. However, about 20% growth of Pseudomonas aeruginosa was reduced at this dose. Considering the proper efficacy of the nanogel as a larvicide and proper antibacterial effect against S. aureus, it could be considered for further investigations against other mosquitoes' larvae and gram-positive bacteria.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.