15,196 research outputs found

    Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

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    Background &amp; Aims: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes. Methods: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from four countries. Standardised immune assays were performed pre and post three vaccine doses (V1-3). Results: In the total cohort, there were incremental increases in antibody titres after each vaccine dose (p &lt;0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titres decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titres than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against nine Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5/122 (4%) were severe. Of the severe cases, 4/5 (80%) occurred in LTRs and 2/5 (40%) had no serological response post-V2. Conclusion: After three COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, LTRs have sustained no/low antibody titres and appear most vulnerable to severe disease. Impact and implications: Standardised assessments of the immune response to different COVID-19 vaccines in patients with liver disease are lacking. We performed antibody and T-cell assays at multiple timepoints following up to three vaccine doses in a large cohort of patients with a range of liver conditions. Overall, the three most widely available vaccine platforms were immunogenic and appeared to protect against severe breakthrough COVID-19. This will provide reassurance to patients with chronic liver disease who were deemed at high risk of severe COVID-19 during the pre-vaccination era, however, liver transplant recipients had the lowest antibody titres and remained vulnerable to severe breakthrough infection. We also characterise the immune response to multiple SARS-CoV-2 variants and describe the interaction between disease type, severity, and vaccine platform. These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease.</p

    Fecal carriage and genetic characteristics of carbapenem-resistant enterobacterales among adults from four provinces of China

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    Carbapenem-resistant Enterobacterales (CRE) is a global concern. This study investigated the prevalence of fecal colonization carriage and clonal dissemination of CRE among population in four provinces of China. A total of 685 stool samples were collected from four provinces in China. Among these samples, 141 and 544 were obtained from healthy and hospitalized individuals, respectively. The overall fecal carriage rate was 9.6% (65/685) with 4.26% (95% CI: 0.9–7.6) in healthy individuals and 10.84% (95% CI: 8.2–13.5) in hospitalized patients. The highest prevalence was in Henan province (18.35%, 95% CI: 9%–18.7%). Sixty-six CRE isolates were identified in Escherichia coli (56.06%, 37/66), Klebsiella (15.15%, 10/66), Citrobacter (13.63%, 9/66), Enterobacter (12.12%, 8/66), and Atlantibacter (1.51%, 1/66). All CRE strains carried carbapenemase genes and multiple antibiotics resistance genes, blaNDM−5 (77.27%, 51/66) was the most common carbapenemase gene, followed by blaNDM−1 (19.69%, 13/66). Antibiotic resistance genes, including blaIMP−4, and the colistin colistin resistance (mcr-1) gene were also identified. All CRE isolates belonged to different sequence types (STs). ST206 (36.84%, 14/38) in E. coli and ST2270 (60%, 6/10) in Klebsiella were significantly dominant clones. The results indicated the prevalence of CRE fecal carriage among adults of China, mostly blaNDM-producing E coli, which pose significant challenges for clinical management. Screening for CRE colonization is necessary to control infection

    Exploring Host Factors of the Human Metabolism as Promising Targets for Dengue Treatment

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    The absence of specific therapy and the challenges posed by currently available palliative drugs, such as paracetamol, underscore the urgent need for targeting medications against dengue. Extensive research in the field of antiviral therapies has primarily focused on investigating viral proteins as potential targets. However, despite these efforts, finding an effective therapy for dengue fever remains a daunting task. Importantly, like all viruses, Dengue virus relies on human host proteins to enable infection. Recognizing this fact has prompted the consideration of host factors as viable targets for intervention strategies to combat the infection. This chapter aims to provide an overview of host-virus interactions during Dengue virus infection, emphasizing the importance of metabolic pathways, as well as molecular and cellular processes such as lipid metabolism, autophagy, apoptosis, and the immune system, which are critical for virus propagation. The main goal here is to expand the list of human factors that could serve as potential drug targets. Additionally, molecules that interact with these factors are explored for their therapeutic potential. This comprehensive exploration of host-virus interactions lays the groundwork for more effective dengue treatments. The molecules highlighted here hold promise as antiviral agents, and their inclusion in repurposing research could expedite the development of therapies for dengue fever

    Neuroimmunopathology in Toxoplasmic Encephalitis

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    Toxoplasma gondii is a zoonotic protozoan parasite that causes mortality because of significant neuropathology. It is widespread in neonatal infections. Although the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) has been studied for many years, it is still not completely understood, showing the disease’s severity. The urge to write this chapter comes at this stage. The sections covered in this chapter show the pathogenesis that has been established and characterized so far. The involvement of astrocytes and microglia in the development of neuropathology, which begins with tachyzoites crossing the blood-brain barrier during acute infection, has been explored. The molecular mechanism between schizophrenia and TE has been thoroughly proven. Uncovering the molecular pathogenesis of TE is critical for both understanding neuropathology and elucidating the link between neuropsychiatric diseases. Each part covered here is expected to contribute to developing novel therapeutic agents for the treatment and maybe prevention of neuropathology. The pathogenesis of the steady progression of encephalitis has been meticulously revealed. Thus, this chapter will offer significant insight into developing novel treatments for all organisms suffering from this disease

    Burkholderia pseudomallei in soil and natural water bodies in rural Sri Lanka: A hidden threat to public health

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    Burkholderia pseudomallei is the causative agent of the potentially fatal infection, melioidosis. This study provides the first evidence for the presence of B. pseudomallei in soil and water in Sri Lanka. Targeted sampling of soil and natural water sources was done between November 2019 and October 2020 over eight field visits encompassing the neighborhood of 28 culture and/or antibody-positive melioidosis patients in northwestern, western and southern Sri Lanka. A total of eight environmental isolates of B. pseudomallei (BPs-env1 to BPs-env8) were cultured from 116 soil and 117 natural water samples collected from 72 locations. The presence of B. pseudomallei in soil and natural water in these areas poses a risk of melioidosis for populations cultivating crops in such soils and using untreated water from these sources for drinking, bathing, and other domestic purposes. Identifying sites positive for B. pseudomallei may help to mitigate risk by raising public awareness of contaminated environmental sources and allowing soil and water remediation

    Life in plastic, it’s fantastic! How Leishmania exploit genome instability to shape gene expression

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    Leishmania are kinetoplastid pathogens that cause leishmaniasis, a debilitating and potentially life-threatening infection if untreated. Unusually, Leishmania regulate their gene expression largely post-transcriptionally due to the arrangement of their coding genes into polycistronic transcription units that may contain 100s of functionally unrelated genes. Yet, Leishmania are capable of rapid and responsive changes in gene expression to challenging environments, often instead correlating with dynamic changes in their genome composition, ranging from chromosome and gene copy number variations to the generation of extrachromosomal DNA and the accumulation of point mutations. Typically, such events indicate genome instability in other eukaryotes, coinciding with genetic abnormalities, but for Leishmania, exploiting these products of genome instability can provide selectable substrates to catalyse necessary gene expression changes by modifying gene copy number. Unorthodox DNA replication, DNA repair, replication stress factors and DNA repeats are recognised in Leishmania as contributors to this intrinsic instability, but how Leishmania regulate genome plasticity to enhance fitness whilst limiting toxic under- or over-expression of co-amplified and co-transcribed genes is unclear. Herein, we focus on fresh, and detailed insights that improve our understanding of genome plasticity in Leishmania. Furthermore, we discuss emerging models and factors that potentially circumvent regulatory issues arising from polycistronic transcription. Lastly, we highlight key gaps in our understanding of Leishmania genome plasticity and discuss future studies to define, in higher resolution, these complex regulatory interactions

    Proton pump inhibitors may enhance the risk of digestive diseases by regulating intestinal microbiota

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    Proton pump inhibitors (PPIs) are the most used acid-inhibitory drugs, with a wide range of applications in the treatment of various digestive diseases. However, recently, there has been a growing number of digestive complications linked to PPIs, and several studies have indicated that the intestinal flora play an important role in these complications. Therefore, developing a greater understanding of the role of the gut microbiota in PPI-related digestive diseases is essential. Here, we summarize the current research on the correlation between PPI-related digestive disorders and intestinal flora and establish the altered strains and possible pathogenic mechanisms of the different diseases. We aimed to provide a theoretical basis and reference for the future treatment and prevention of PPI-related digestive complications based on the regulation of the intestinal microbiota

    Risk of admission to intensive care units due to Covid-19: comparative analysis between European countries

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    The Covid-19 epidemic has posed an unprecedented challenge to the European healthcare system, which has had to cope with a much higher than usual demand for hospitalization. This work is devoted to the construction and comparison of risk indicators of admission to intensive care units (ICU) for Covid-19 for eight European countries. (...

    National Koala Disease Risk Analysis Report V 1.2

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    The Koala Disease Risk Analysis (KDRA) identifies the knowledge base, information gaps, risk assessments and critical control points for koala disease hazards. The national focus of the KDRA provides a clear, evidence-based assessment of koala disease which will be of value in evaluating disease risk at all regional levels and for koalas in all management situations (captive, rehabilitation and free-ranging). The KDRA is a key guiding document for actions to achieve a vision of “sustainable, resilient and healthy populations of koalas, living in positive welfare within healthy ecosystems across their range

    In Vitro Assessment of Biofilm Production, Antibacterial Resistance of Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. Obtained from Tonsillar Crypts of Healthy Adults

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    Publisher Copyright: © 2023 by the authors.Background and Objective: Tonsillar crypts can be considered a reservoir for a variety of bacterial species. Some bacterial species can be considered part of the normal oropharyngeal microbiota. The roles of other pathogens, for example, the so-called non-oral and respiratory pathogens Staphylococcus aureus, Klebsiella, Pseudomonas, and Acinetobacter spp., which have strong virulence factors, biofilm production capacity, and the ability to initiate infectious diseases, are unclear. The purpose of this study was to detect the presence of S. aureus, K. pneumoniae, P. aeruginosa, and Acinetobacter spp. within the tonsillar crypts of healthy individuals, and to analyze the pathogens’ biofilm production and antibacterial resistances. Results: Only common oropharyngeal microbiota were cultivated from 37 participant samples (40.7%). The most commonly isolated pathogenic bacterium was S. aureus, which was isolated in 41 (45%) participant samples. K. pneumoniae was isolated in seven (7.7%) samples, Acinetobacter spp. were isolated in five (5.5%) samples, and P. aeruginosa was isolated in two (2.2%) samples. Biofilm producers predominated among the pathogenic bacteria; 51 strains were biofilm producers, and among them, 31 strains were moderate or strong biofilm producers. The tested S. aureus, K. pneumoniae, P. aeruginosa, and Acinetobacter spp. strains were sensitive to commonly used antibiotics (amoxicillin–clavulanic acid, clindamycin, or ciprofloxacin). One of the isolated S. aureus strains was MRSA. Conclusions: Biofilm is a commonly observed feature that seems to be a naturally existing form of pathogenic bacteria colonizing human tissue. S. aureus, K. pneumoniae, P. aeruginosa, and Acinetobacter spp. occasionally occur in the tonsillar crypts of healthy individuals, and, therefore, it is most likely that S. aureus, K. pneumoniae, P. aeruginosa, and Acinetobacter spp. in opportunistic tonsillar infections originate from the tonsillar crypt microbiota.publishersversionPeer reviewe