Brunkara4913

Emerging and re-emerging viral diseases pose continuous public health threats, and effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, and prevention with vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide effective treatments. This lack of preparedness has been due, in large part, to a lack of investment in developing a diverse portfolio of antiviral agents, particularly those ready to combat viruses of pandemic potential. Here, we focus on a drug target called macrodomain that is critical for the replication and pathogenesis of alphaviruses and coronaviruses. Some mutations in alphavirus and coronaviral macrodomains are not tolerated for virus replication. In addition, the coronavirus macrodomain suppresses host interferon responses. Therefore, macrodomain inhibitors have the potential to block virus replication and restore the host's protective interferon response. Viral macrodomains offer an attractive antiviral target for developing direct acting antivirals because they are highly conserved and have a structurally well-defined (druggable) binding pocket. Given that this target is distinct from the existing RNA polymerase and protease targets, a macrodomain inhibitor may complement current approaches, pre-empt the threat of resistance and offer opportunities to develop combination therapies for combating COVID-19 and future viral threats.Mice are valuable models extensively used to test vaccine candidates against Chlamydia abortus and to clarify immunopathological mechanisms of the bacteria. As this pathogen has the ability to reactivate during pregnancy, it is important to deepen the knowledge and understanding of some of the effects of female hormones on immunity and vaccination. This study is aimed at describing the role of sex hormones in the pathology of OEA during chlamydial clearance using ovariectomised mice and also gaining an understanding of how 17β-oestradiol or progesterone may impact the effectiveness of vaccination. Animals were treated with sex hormones and infected with C. abortus, and the kinetics of infection and immune response were analysed by means of bacterial isolation, histopathology, and immunohistochemistry. check details In a second phase of the study, protection conferred by an experimental vaccine after hormone treatment was assessed. Oestradiol showed a stimulatory effect on the immune response during infection, with a more efficient recruitment of macrophages and T-cells at the infection site. Furthermore, after vaccination, oestradiol-treated animals showed a stronger protection against infection, indicating that this hormone has a positive effect, stimulating a specific memory response to the pathogen.Leishmaniasis is a protozoal vector-borne disease that affects both humans and animals. In the Mediterranean Basin, the primary reservoir hosts of Leishmania spp. are mainly rodents and canids. Lipidomic approaches have allowed scientists to establish Leishmania spp. lipid profiles for the identification of cell stage specific biomarkers, drug mechanisms of action, and host immune response. Using an in silico approach of global network interaction between genes involved in fatty acid (FA) synthesis followed by the GC-MS approach, we were able to characterize the fatty acid profiles of L. major derived from human and rodent hosts. Our results revealed that the lipid profile of L. major showed similarities and differences with those already reported for other Leishmania species. Phospholipids are the predominant lipid class. FA composition of rodent parasites was characterized by a lower abundance of the precursor C182(n-6). One of the rodent clones, which also expressed the lowest lipid abundance in PL and TAG, was the least sensitive clone to the miltefosine drug and has the lowest infection efficiency. Our findings suggest that the lipid composition variation may explain the response of the parasite toward treatment and their ability to infect their host.SCUBA divers are predisposed to otitis externa caused by Pseudomonas aeruginosa, which is becoming increasingly multi-drug resistant (MDR). The present work assessed the antibiotic resistance profiles of P. aeruginosa obtained from SCUBA divers and their environment in Sodwana Bay, South Africa. Bacterial isolates from a total of 137 random water and ear swab samples were identified using biochemical and molecular methods. P. aeruginosa strains were further evaluated for antibiotic susceptibility using the Kirby-Bauer assay. Double disk synergy test (DDST) to confirm metallo-β-lactamase (MBL) production and PCR amplification of specific antibiotic resistance genes was performed. All (100%) 22 P. aeruginosa isolates recovered were resistant to 6 of the β-lactams tested including imipenem but exhibited susceptibility to trimethoprim-sulfamethoxazole. MBL production was observed in 77% of isolates while the most prevalent extended-spectrum β-lactamase (ESBL) genes present included blaAmpC (86.9%) followed by blaTEM (82.6%). Sulfonamide resistance was largely encoded by sul1 (63.6%) and sul2 (77.3%) genes with a high abundance of class 1 integrons (77.3%) of which 18.2% carried both Intl1 and Intl2. P. aeruginosa found in Sodwana Bay exhibits multi-drug resistance (MDRce) to several pharmaceutically important drugs with the potential to transfer antibiotic resistance to other bacteria if the judicious use of antibiotics for their treatment is not practiced.Filth flies, cockroaches, and dung beetles have been close neighbors with humans and animals throughout our joint histories. However, these insects can also serve as vectors for many zoonotic enteric parasites (ZEPs). Zoonoses by ZEPs remain a paramount public health threat due to our close contact with animals, combined with poor water, sanitation, and hygiene access, services, and behaviors in many global regions. Our objective in this systematic review was to determine which ZEPs have been documented in these vectors, to identify risk factors associated with their transmission, and to provide effectual One Health recommendations for curbing their spread. Using PRISMA guidelines, a total of 85 articles published from 1926 to 2021 were reviewed and included in this study. Qualitative analysis revealed that the most common parasites associated with these insects included, but were not limited to Ascaris spp., Trichuris spp., Entamoeba spp., and Cryptosporidium spp. Additionally, prominent risk factors discovered in the review, such as poor household and community WASH services, unsafe food handling, and exposure to domestic animals and wildlife, significantly increase parasitic transmission and zoonoses. The risk of insect vector transmission in our shared environments makes it critically important to implement a One Health approach in reducing ZEP transmission.Lyme disease is the most important vector-borne disease in the United States and is increasing in incidence and geographic range. In the Pacific west, the western black-legged tick, Ixodes pacificus Cooley and Kohls, 1943 is an important vector of the causative agent of Lyme disease, the spirochete, Borrelia burgdorferi. Ixodes pacificus life cycle is expected to be more than a year long, and all three stages (larva, nymph, and adult) overlap in spring. The optimal habitat consists of forest cover, cooler temperatures, and annual precipitation in the range of 200-500 mm. Therefore, the coastal areas of California, Oregon, and Washington are well suited for these ticks. Immature stages commonly parasitize Western fence lizards (Sceloporus occidentalis) and gray squirrels (Sciurus griseus), while adults often feed on deer mice (Peromyscus maniculatus) and black-tailed deer (Odocoileus h. columbianus). Ixodes pacificus carry several pathogens of human significance, such as Borrelia burgdorferi, Bartonella, and Rickettsiales. These pathogens are maintained in the environment by many hosts, including small mammals, birds, livestock, and domestic animals. Although a great deal of work has been carried out on Ixodes ticks and the pathogens they transmit, understanding I. pacificus ecology outside California still lags. Additionally, the dynamic vector-host-pathogen system means that new factors will continue to arise and shift the epidemiological patterns within specific areas. Here, we review the ecology of I. pacificus and the pathogens this tick is known to carry to identify gaps in our knowledge.Gurltia paralysans, a metastrongyloid nematode, parasitizes in meningeal vessels in the thoracolumbar spinal cord of cats in South America and causes progressive paraparesis. Recently, the first report outside of South America described gurltiosis in a cat in Spain. As this parasitic disease has so far been largely neglected, especially outside of South America, the aim of the present case study was to add knowledge to the histologic and immunohistochemical characterization of central nervous lesions. To this purpose, formalin-fixed and paraffin-embedded (FFPE) tissue samples from the spinal cord and brain of five cats affected by clinical signs caused by Gurltia paralysans and of three control cats without CNS lesions were histopathologically examined using hematoxylin and eosin stain (HE), Elastica van Gieson stain, as well as periodic acid-Schiff (PAS) reaction. Moreover, immuno- histochemistry for alpha smooth muscle actin and Factor VIII-related antigen were performed to characterize vascular lesions. Lesions were consistent with previous descriptions and were mainly located in the spinal cord and consisted of chronic suppurative or lymphoplasmahistiocytic meningi tis as well as suppurative vasculitis, congestion and varicosis of meningeal veins. In view of the recent detection of this parasite in Europe and the increasing inner-European transport of rescued domestic cats, veterinarians in Europe should be aware of the clinical and pathomorphological presentation of this disease.Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by Mycobacterium tuberculosis (Mtb) disease before the activation of antigen-specific T cells. Additionally, the potential link and synergistic function between diabetes mellitus (DM) and tuberculosis (TB) has been recognized for a long time. However, the role of MAIT cells in latent TB (LTB) DM or pre-DM (PDM) and non-DM (NDM) comorbidities is not known. Hence, we examined the frequencies (represented as geometric means, GM) of unstimulated (UNS), mycobacterial (purified protein derivative (PPD) and whole-cell lysate (WCL)), and positive control (phorbol myristate acetate (P)/ionomycin (I)) antigen stimulated MAIT cells expressing Th1 (IFNγ, TNFα, and IL-2), Th17 (IL-17A, IL-17F, and IL-22), and cytotoxic (perforin (PFN), granzyme (GZE B), and granulysin (GNLSN)) markers in LTB comorbidities by uniform manifold approximation (UMAP) and flow cytometry. We also performed a correlation analysis of Thifferent Th1 cytokines and cytotoxic marker population clusters and increased Th1 and Th17 (IL-17A, IL-22) cytokines and diminished cytotoxic markers expressing MAIT cells are associated with LTB-PDM and DM comorbidities.