Surveillance for SARS-CoV-2 in Norway Rats (Rattus norvegicus) from Southern Ontario

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from wildlife has raised concerns about spillover from humans to animals, the establishment of novel wildlife reservoirs, and the potential for future outbreaks caused by variants of wildlife origin. Norway rats (Rattus norvegicus) are abundant in urban areas and live in close proximity to humans, providing the opportunity for spillover of SARS-CoV-2. Evidence of SARS-CoV-2 infection and exposure has been reported in Norway rats. We investigated SARS-CoV-2 infection and exposure in Norway rats from Southern Ontario, Canada. From October 2019 to June 2021, 224 rats were submitted by collaborating pest control companies. The majority of samples were collected in Windsor (79.9%;n = 179), Hamilton (13.8%;n = 31), and the Greater Toronto Area (5.8%;n = 13). Overall, 50.0% (n = 112) were female and most rats were sexually mature (55.8%;n = 125). Notably, 202 samples were collected prior to the emergence of variants of concern (VOC) and 22 were collected while the Alpha variant (B.1.1.7) was the predominant circulating VOC in humans. Nasal turbinate (n = 164) and small intestinal (n = 213) tissue samples were analyzed for SARS-CoV-2 RNA by RT-PCR. Thoracic cavity fluid samples (n = 213) were tested for neutralizing antibodies using a surrogate virus neutralization test (sVNT) (GenScript cPass);confirmatory plaque reduction neutralization test (PRNT) was conducted on presumptive positive samples. We did not detect SARS-CoV-2 RNA in any samples tested. Two out of eleven samples positive on sVNT had neutralizing antibodies confirmed positive by PRNT (1 : 40 and 1 : 320 PRNT70);both were collected prior to the emergence of VOC. It is imperative that efforts to control and monitor SARS-CoV-2 include surveillance of rats and other relevant wildlife species as novel variants continue to emerge.

Special Issue: Mutagenic factors in the environment impacting human and animal health. (Special Issue: Mutagenic factors in the environment impacting human and animal health.)

This special issue includes 15 articles that discuss the mutagenic effect of tobacco smoke on male fertility;environmental and occupational exposure of metals and female reproductive health;free radical biology in neurological manifestations;paternal factors in recurrent pregnancy loss;mechanical dependency of the SARS-CoV-2 virus and the renin-angiotensin-aldosterone (RAAS) axis;a perspective review on medicinal plant resources for their antimutagenic potentials;asystematic review and meta-analysis of the impacts of glyphosate on the reproductive hormones;impact of ginseng on neurotoxicity induced by cisplatin in rats.

SARS-CoV-2 Exposure in Norway Rats (Rattus norvegicus) from New York City.

Millions of Norway rats (Rattus norvegicus) inhabit New York City (NYC), presenting the potential for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans to rats. We evaluated SARS-CoV-2 exposure among 79 rats captured from NYC during the fall of 2021. Our results showed that 13 of the 79 rats (16.5%) tested IgG- or IgM-positive, and partial SARS-CoV-2 genomes were recovered from all 4 rats that were qRT-PCR (reverse transcription-quantitative PCR)-positive. Genomic analyses suggest these viruses were associated with genetic lineage B, which was predominant in NYC in the spring of 2020 during the early pandemic period. To further investigate rat susceptibility to SARS-CoV-2 variants, we conducted a virus challenge study and showed that Alpha, Delta, and Omicron variants can cause infections in wild-type Sprague Dawley (SD) rats, including high replication levels in the upper and lower respiratory tracts and induction of both innate and adaptive immune responses. Additionally, the Delta variant resulted in the highest infectivity. In summary, our results indicate that rats are susceptible to infection with Alpha, Delta, and Omicron variants, and wild Norway rats in the NYC municipal sewer systems have been exposed to SARS-CoV-2. Our findings highlight the need for further monitoring of SARS-CoV-2 in urban rat populations and for evaluating the potential risk of secondary zoonotic transmission from these rat populations back to humans. IMPORTANCE The host tropism expansion of SARS-CoV-2 raises concern for the potential risk of reverse-zoonotic transmission of emerging variants into rodent species, including wild rat species. In this study, we present both genetic and serological evidence for SARS-CoV-2 exposure to the New York City wild rat population, and these viruses may be linked to the viruses that were circulating during the early stages of the pandemic. We also demonstrated that rats are susceptible to additional variants (i.e., Alpha, Delta, and Omicron) that have been predominant in humans and that susceptibility to infection varies by variant. Our findings highlight the reverse zoonosis of SARS-CoV-2 to urban rats and the need for further monitoring of SARS-CoV-2 in rat populations for potential secondary zoonotic transmission to humans.

Evaluation of the toxicological effects of favipiravir (T-705) on liver and kidney in rats: biochemical and histopathological approach.

Favipiravir is a selective RNA polymerase inhibitor and a broad-spectrum antiviral drug, an important agent used in viral infections, including Ebola, Lassa, and COVID-19. This study aims to evaluate the potential toxicological effects of favipiravir administration on rats' liver and kidney tissues. Favipiravir was applied for five and ten days in the present study. During this period, it was aimed to determine possible toxic effects on the liver and kidney. For this purpose, the impact of favipiravir on liver and kidney tissues were examined using histopathologic and biochemical methods. The present study showed that favipiravir administration led to an elevation in the liver and kidney serum enzymes and oxidative and histopathologic damages. Favipiravir administration caused apoptotic cell death (Caspase-3 and Bcl-2), inflammation (NF-κB and IL-6), and a decrease in renal reabsorption (AQP2) levels. In the evaluation of the findings obtained in this study, it was determined that the favipiravir or metabolites caused liver and kidney damages.

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats.

Budesonide (BUD), a glucocorticoids drug, inhibits all steps in the inflammatory response. It can reduce and treat inflammation and other symptoms associated with acute lung injury such as COVID-19. Loading BUD into bilosomes could boost its therapeutic activity, and lessen its frequent administration and side effects. Different bilosomal formulations were prepared where the independent variables were lipid type (Cholesterol, Phospholipon 80H, L-alpha phosphatidylcholine, and Lipoid S45), bile salt type (Na cholate and Na deoxycholate), and drug concentration (10, 20 mg). The measured responses were: vesicle size, entrapment efficiency, and release efficiency. One optimum formulation (composed of cholesterol, Na cholate, and 10 mg of BUD) was selected and investigated for its anti-inflammatory efficacy in vivo using Wistar albino male rats. Randomly allocated rats were distributed into four groups: The first: normal control group and received intranasal saline, the second one acted as the acute lung injury model received intranasal single dose of 2 mg/kg potassium dichromate (PD). Whereas the third and fourth groups received the market product (Pulmicort® nebulising suspension 0.5 mg/ml) and the optimized formulation (0.5 mg/kg; intranasal) for 7 days after PD instillation, respectively. Results showed that the optimized formulation decreased the pro-inflammatory cytokines TNF-α, and TGF-ß contents as well as reduced PKC content in lung. These findings suggest the potentiality of BUD-loaded bilosomes for the treatment of acute lung injury with the ability of inhibiting the pro-inflammatory cytokines induced COVID-19.

Repeat-Dose Toxicity of Candidate Omicron COVID-19 Vaccine in Sprague-Dawley Rats

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Hypoxia modeling techniques: A review.

Hypoxia is the main cause and effect of a large number of diseases, including the most recent one facing the world, the coronavirus disease (COVID-19). Hypoxia is divided into short-term, long-term, and periodic, it can be the result of diseases, climate change, or living and traveling in the high mountain regions of the world. Since each type of hypoxia can be a cause and a consequence of various physiological changes, the methods for modeling these hypoxias are also different. There are many techniques for modeling hypoxia under experimental conditions. The most common animal for modeling hypoxia is a rat. Hypoxia models (hypoxia simulations) in rats are a tool to study the effect of various conditions on the oxygen supply of the body. These models can provide a necessary information to understand hypoxia and also provide effective treatment, highlighting the importance of various reactions of the body to hypoxia. The main parameters when choosing a model should be reproducibility and the goal that the scientist wants to achieve. Hypoxia in rats can be reproduced both ways exogenously and endogenously. The reason for writing this review was the aim to systematize the models of rats available in the literature in order to facilitate their selection by scientists. The relative strengths and limitations of each model need to be identified and understood in order to evaluate the information obtained from these models and extrapolate these results to humans to develop the necessary generalizations. Despite these problems, animal models have been and remain vital to understanding the mechanisms involved in the development and progression of hypoxia. The eligibility criteria for the selected studies was a comprehensive review of the methods and results obtained from the studies. This made it possible to make generalizations and give recommendations on the application of these methods. The review will assist scientists in choosing an appropriate hypoxia simulation method, as well as assist in interpreting the results obtained with these methods.

An Old Mobbing Story and Covid-19

Innovative medical education greatly relies on lifelong learning with universal standards in research, for generating novel knowledge for improvement maximum patient care. The other side of innovative medical education relies on success of development of novel ideas, perspective;skill building, future career objectives. Leaders have curious roles in the research assistant education. In the current century, both technology and education raced forward in many countries. Mobbing and bullying is an important problem in all fields, every sphere of life in workplaces. Unethical behavior must not take place in universities because universities are the centers of learning, and best academic teaching in ethical standards. Bullying may damage every individual in every academic degree and effect academic performance. In this paper I will discuss a mobbing case which is done to a young academician in many years ago, which is not most frequently observed type. However, such bullying behaviors may increase due to COVID-19 pandemic. Because COVID-19 pandemic may cause various problems in social groups difficulties, anxiety, and economic challenges, problems. Nowadays everybody is experiencing worry, uncertainty, anxiety, fear of economic problems, fear of dying. COVID-19 pandemic has created some unexpected problems to everybody however, academic researchers have additional worries and fears such as;the expiration time of chemicals, problems on chemicals are not imported from abroad on time also difficulties of knockout or transgenic experimental animals cannot be imported from abroad on time, and all these problems cause fear of unsuccessful experimental results, spending extra time. All these anxieties may cause arouse increasing unstable friendships and mobbing possibilities. The COVID-19 disease takes our future and experimental plans to waste basket and change everything including friendship.

Analysis of intermediate hosts and susceptible animals of SARS-CoV-2 by computational methods

COVID-19, a disease caused by SARS-CoV-2 that produces major symptoms of pneumonia, has been a disaster worldwide. The traceability of SARSCoV- 2 and the discovery of susceptible animal species is crucial to halt viral transmission and explore the mechanism of cross-species transmission. We selected 82 representative ACE2 sequences from the 1000 sequences with the closest homology to the hACE2 protein. All selected ACE2 proteins were subjected to homology modeling. Potential natural and intermediate hosts, as well as animal species susceptible to SARS-CoV-2, were analyzed systematically by calculation of the binding free energy of ACE2 protein to the RBD of SARSCoV- 2. Primates, some wild Felidae, civets, goats, spotted hyenas and golden hamsters are susceptible to SARS-CoV-2 and may be potential intermediate hosts, whereas pangolins, birds and reptiles are unlikely to be intermediate hosts. Mice, rats and guinea pig are not susceptible to SARS-CoV-2. Given their possible susceptibility, non-human primates, goats and golden hamsters could potentially be used as experimental models to examine SARS-CoV-2 infection without transgenesis. Herein, possible candidates for the natural and intermediate hosts of SARS-CoV-2 are suggested, to provide guidance for subsequent studies.

Risk Factors and Mechanisms of Cardiovascular Diseases in Posttraumatic Stress Disorder Model in Wistar Rats as Dependent on Stress Resistance and Age.

The article focuses on the pathogenetic mechanisms of posttraumatic stress disorder (PTSD), which is associated with psychological stress because of the coronavirus pandemic. The molecular mechanisms responsible for disease susceptibility in some individuals and stress resistance in others are amongst crucial research interests of experimental and clinical medicine. Priority data were obtained to indicate that distortions of synthesis and metabolism and, most significantly, a switch between two energy transport forms, glucose and lipids, underlie myocardial dysfunction in young and old stress-sensitive Wistar rats in a PTSD model. Histochemistry and polarization microscopy showed energy deficit in cardiomyocytes and signs of ischemic and hypoxic areas emerging in the myocardium as a result of an accumulation of NADH and NADPH, which initiate excessive production of reactive oxygen species.

Transcutaneous auricular vagal nerve stimulation releases extrapineal melatonin and reduces thermal hypersensitivity in Zucker diabetic fatty rats.

Type 2 diabetes (T2D) is the most common comorbidity of COVID-19, and both are related to the lack of circulating melatonin. In addition, chronic pain is a common sequela of both COVID-19 and T2D. Using a neuropathic pain model produced by sciatic nerve chronic constriction injury in Zucker diabetic fatty rats, a verified preclinical genetic T2D neuropathy animal model, this study aimed to show that transcutaneous auricular vagal nerve stimulation (taVNS) could elevate plasma melatonin concentration, upregulate the expression of melatonin receptors (MTRs) in the amygdala, and relieve peripheral neuropathic pain. Furthermore, taVNS would restore melatonin levels and relieve pain even in pinealectomized rats. On the contrary, intraperitoneally injected luzindole, a melatonin receptor antagonist, would attenuate the antinociceptive effects of taVNS. In conclusion, the mechanism of the therapeutic effect of taVNS on chronic pain involves the release of extrapineal melatonin and the positive regulation of the expression of central MTRs. This beneficial efficacy should be considered during COVID-19 rehabilitation in individuals with diabetes.

Clinical practice of rapid antigen tests for SARS-CoV-2 Omicron variant: A single-center study in China.

Responding to the fast-spreading SARS-CoV-2 Omicron variant, to improve screening efficiency, rapid antigen tests (RATs) were first added as a supplementary detection method in China in mid-March, 2022. What and how big a role RATs should play need to be supported by clinical data. Here, RAT performance and relevant factors in comparison with nucleic acid amplification tests (NAATs) were assessed in Omicron-infected inpatients. From the NAAT results, nasopharyngeal swabs (NPs) performed better than oropharyngeal swabs (OPs). RATs tested on NAAT positive NPs performed better than those with OP-positive samples. The RAT positivity rate was strongly associated with high levels of N and OFR1ab genes, especially in NPs where patients also had significantly longer hospital stays and shorter days from symptom onset to RAT testing. Self-performed RATs had a detection accuracy that was comparable to professionally performed RATs when the subjects were well guided. The antigen negative rate of the studied patients was 100% at discharge. These findings suggest that, in addition to a supplementary detection role, RATs can be an important strategy for evaluating the disease progression of Omicron-infected inpatients. This study provides important clinical data to support better rules regarding RATs under China's COVID-19 prevention and control policy.

Impact of Clarified Apple Juices with Different Processing Methods on Gut Microbiota and Metabolomics of Rats.

The consumption of processed foods has increased compared to that of fresh foods in recent years, especially due to the coronavirus disease 2019 pandemic. Here, we evaluated the health effects of clarified apple juices (CAJs, devoid of pectin and additives) processed to different degrees, including not-from-concentrate (NFC) and from-concentrate (FC) CAJs. A 56-day experiment including a juice-switch after 28 days was designed. An integrated analysis of 16S rRNA sequencing and untargeted metabolomics of cecal content were performed. In addition, differences in the CAJs tested with respect to nutritional indices and composition of small-molecule compounds were analyzed. The NFC CAJ, which showed a higher phenolic content resulting from the lower processing degree, could improve microbiota diversity and influence its structure. It also reduced bile acid and bilirubin contents, as well as inhibited the microbial metabolism of tryptophan in the gut. However, we found that these effects diminished with time by performing experiment extension and undertaking juice-switching. Our study provides evidence regarding the health effects of processed foods that can potentially be applied to public health policy decision making. We believe that NFC juices with a lower processing degree could potentially be healthier than FC juice.

Research-Relevant Conditions and Pathology of Laboratory Mice, Rats, Gerbils, Guinea Pigs, Hamsters, Naked Mole Rats, and Rabbits.

Animals are valuable resources in biomedical research in investigations of biological processes, disease pathogenesis, therapeutic interventions, safety, toxicity, and carcinogenicity. Interpretation of data from animals requires knowledge not only of the processes or diseases (pathophysiology) under study but also recognition of spontaneous conditions and background lesions (pathology) that can influence or confound the study results. Species, strain/stock, sex, age, anatomy, physiology, spontaneous diseases (noninfectious and infectious), and neoplasia impact experimental results and interpretation as well as animal welfare. This review and the references selected aim to provide a pathology resource for researchers, pathologists, and veterinary personnel who strive to achieve research rigor and validity and must understand the spectrum of "normal" and expected conditions to accurately identify research-relevant experimental phenotypes as well as unusual illness, pathology, or other conditions that can compromise studies involving laboratory mice, rats, gerbils, guinea pigs, hamsters, naked mole rats, and rabbits.

Monitoring Urban Zoonotic Virus Activity: Are City Rats a Promising Surveillance Tool for Emerging Viruses?

Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens is important to estimate the risk of spillover to humans in cities. As brown rats (Rattus norvegicus) are ubiquitous in urban habitats, and are hosts of several zoonotic viruses, we conducted longitudinal sampling of brown rats in Vienna, Austria, a large population center in Central Europe. We investigated rat tissues for the presence of several zoonotic viruses, including flaviviruses, hantaviruses, coronaviruses, poxviruses, hepatitis E virus, encephalomyocarditis virus, and influenza A virus. Although we found no evidence of active infections (all were negative for viral nucleic acids) among 96 rats captured between 2016 and 2018, our study supports the findings of others, suggesting that monitoring urban rats may be an efficient way to estimate the activity of zoonotic viruses in urban environments.

Can Self-Administered Rapid Antigen Tests (RATs) Help Rural India? An Evaluation of the CoviSelf Kit as a Response to the 2019-2022 COVID-19 Pandemic.

This paper evaluates India's first officially approved self-administered rapid antigen test kit against COVID-19, a device called CoviSelf. The context is rural India. Rapid antigen tests (RATs) are currently popular in situations where vaccination rates are low, where sections of the community remain unvaccinated, where the COVID-19 pandemic continues to grow and where easy or timely access to RTPCR (reverse transcription-polymerase chain reaction) testing is not an option. Given that rural residents make up 66% of the Indian population, our evaluation focuses on the question of whether this self-administered RAT could help protect villagers and contain the Indian pandemic. CoviSelf has two components: the test and IT (information technology) parts. Using discourse analysis, a qualitative methodology, we evaluate the practicality of the kit on the basis of data in its instructional leaflet, reports about India's 'digital divide' and our published research on the constraints of daily life in Indian villages. This paper does not provide a scientific assessment of the effectiveness of CoviSelf in detecting infection. As social scientists, our contribution sits within the field of qualitative studies of medical and health problems. Self-administered RATs are cheap, quick and reasonably reliable. Hence, point-of-care testing at the doorsteps of villagers has much potential, but realising the benefits of innovative, diagnostic medical technologies requires a realistic understanding of the conditions in Indian villages and designing devices that work in rural situations. This paper forms part of a larger project regarding the COVID-19 pandemic in rural India. A follow-up study based on fieldwork is planned for 2022-2023.

Diosmin and hesperidin - the current state of knowledge

Diosmin is the 7-rutinoside of 3 ', 5,7-trihydroxy-4'-methoxyflavone (7-O-rutinoside of diosmetin), and hespheridine is the 7-rutinoside of 3', 5,7-trihydroxy-4'-methoxyflavanone (7 -O-rutinoside hesperetin). Diosmin, is a gray-yellow or pale-yellow, hygroscopic powder, whereas hesperidine is in the form of light-yellow spherocrystals. Diosmin was isolated from fruits of the Citrus genus (C. sinensis, C. limonia), now it is obtained semi-synthetically from natural hesperidin. These flavonoids have, among others: antimicrobial, anti-inflammatory, anti-diabetic, anti-cancer, analgesic, antioxidant and possibly anti-virus activity, that cause COVID-19. The metabolism of diosmin takes place initially in the small intestine and involves demethoxylation and hydrolysis. In contrast, oxidation and conjugation take place in the liver. There is no presence of diosmin and diosmetin in the urine, which are mainly eliminated in the form of glucuronic acid conjugates. The dominant metabolite detected in urine samples is m-hydroxy-phenylpropionic acid, excreted in conjugated form. Diosmin may reduce the aggregation of Red Blood Cells, and thus it is able to reduce blood viscosity. The LD50 of the mixture of 90% diosmin and 10% hesperidin for rats is over 3 g/kg. The tests did not reveal any mutagenic effects or effects on reproductive functions. It also does not pose a significant threat during breast feeding, as it poorly passes into breast milk.

The SARS-CoV-2 B.1.351 Variant Can Transmit in Rats But Not in Mice.

Previous studies have shown that B.1.351 and other variants have extended the host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to mice. Sustained transmission is a prerequisite for viral maintenance in a population. However, no evidence of natural transmission of SARS-CoV-2 in wild mice has been documented to date. Here, we evaluated the replication and contact transmission of the B.1.351 variant in mice and rats. The B.1.351 variant could infect and replicate efficiently in the airways of mice and rats. Furthermore, the B.1.351 variant could not be transmitted in BALB/c or C57BL/6 mice but could be transmitted with moderate efficiency in rats by direct contact. Additionally, the B.1.351 variant did not transmit from inoculated Syrian hamsters to BALB/c mice. Moreover, the mouse-adapted SARS-CoV-2 strain C57MA14 did not transmit in mice. In summary, the risk of B.1.351 variant transmission in mice is extremely low, but the transmission risk in rats should not be neglected. We should pay more attention to the potential natural transmission of SARS-CoV-2 variants in rats and their possible spillback to humans.

Use of personal protective equipment by healthcare workers exposed to COVID-19 infection at a tertiary care hospital in a lower middle-income country

Introduction: Data on PPE use and COVID-19 transmission in a healthcare setting is sparse. Method: This study is a retrospective descriptive study on PPE use and Covid-19 transmission in a hospital. Data collected during routine risk assessment was analyzed using SPSS_26 software.

Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats.

This study evaluates safety of FINLAY-FR-02, a vaccine candidate against SARS-CoV-2 based on the recombinant receptor binding domain conjugated to tetanus toxoid, in a preclinical, repeat-dose toxicity and local tolerance study. Sprague Dawley rats were randomly allocated to three experimental groups: control (receiving physiological saline solution); placebo (receiving all vaccine components except antigens) and vaccine group (receiving three doses of the vaccine candidate, 37.5 µg of RBD) administered intramuscularly in hind limbs at 24 h intervals during three days. We evaluated physiological condition, pain, food and water consumption, body temperature, dermal irritability, injection site temperature and inflammation, immunological response, blood chemistry, relative organ weight, histopathology and immunotoxicology. The product was well tolerated; no clinically relevant changes, pain, local effects or adverse systemic toxicological changes or deaths were observed. These preliminary results permitted the Cuban regulatory authorities to authorize clinical trials in humans.