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Topic Review
Syndecan-4
Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta’s spike protein shift the protein towards a net positive electrostatic potential. Compared to the wild-type spike, the Delta one shows a higher affinity towards heparan sulfate proteoglycans than ACE2. Cellular studies showed that syndecan-4, the syndecan isoform abundant in the lung, enhances the transmission of the Delta variant by attaching its mutated spike glycoprotein and facilitating its cellular entry. In addition to the attachment to the polyanionic heparan sulfate chains, the Delta spike’s molecular interactions with syndecan-4 also involve syndecan-4’s cell-binding domain that mediates cell-to-cell adhesion. Exogenously added heparin or syndecan-4 knockdown efficiently blocks the Delta variant’s cellular entry. A profound understanding of syndecan-4-mediated endocytosis enables the development of molecularly targeted yet simple strategies to reduce the Delta variant’s spread.
  • 1.0K
  • 20 Jan 2022
Topic Review
Combination Antibody Therapy against Pseudomonas aeruginosa Infections
Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This entry highlights potential targets secreted by P. aeruginosa that future polyclonal antibodies may directed against in order to develop more efficacious treatments against these infections. 
  • 1.0K
  • 06 Jan 2022
Topic Review
Virion Structure of SARS-CoV-2 and Viral Inflammation
COVID-19 is an epidemic infection created by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). SARS-CoV-2 has a single-stranded, positive-sense RNA genome with 29,891 nucleotides and 38% G + C content, encoding 9860 amino acids. Human coronaviral inflammation induces the clinical symptoms of fever, cough, and shortness of breath.
  • 1.0K
  • 25 Nov 2022
Topic Review
COVID-19 Vaccine Approved for Public Use
Coronavirus disease 2019 (COVID-19) outbreak was first reported in Wuhan, China in December 2019, and was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel pleomorphic, positive-stranded RNA virus belonging to the Coronaviridae family. Quickly, it has become a global pandemic, infecting more than 176 million people and causing the death of more than 3.8 million individuals, that we are yet to recover from. Thus, an ongoing quest is being carried out for prophylaxis/therapy to prevent the transition from infection into serious forms of COVID-19.
  • 1.0K
  • 30 Nov 2021
Topic Review
Host Susceptibility of SARS-CoV-2
The COVID-19 pandemic has caused the death of approximately 6 million people, with a case fatality rate which may be as high as 20% in those over 80 years old. Vaccines have proved to be extremely effective in reducing the damage and hospitalisation caused by this infection, although some patients still need supportive care. As the SARS-CoV-2 virus has continued to evolve, the potential for the virus to escape vaccine and exposure induced immunity remains a threat. In this situation, as at the start of the pandemic when no such vaccines were available, it is important that there exist therapeutics for the treatment of severely ill patients. In addition, comparison with other agents demonstrates that this drug is the most potent of the immune modulators in reducing COVID-19 mortality. As a result, it is now strongly recommended for the treatment of COVID-19 by the WHO.
  • 1.0K
  • 01 Jul 2022
Topic Review
COVID-19 in the Brain and Nervous System
COVID-19 can spread throughout the central nervous system, impacting the brain and spinal cord, and neurological symptoms could explain this in people infected with long-term infection.
  • 1.0K
  • 29 Jul 2022
Topic Review
Vaccines for Bovine Mycoplasmoses
Two of the most important diseases of cattle are caused by mycoplasmas. Mycoplasma bovis is a world-wide bovine pathogen that can cause pneumonia, mastitis and arthritis. Due to its increasing resistance to antimicrobial therapy, vaccination is the principal focus of the control of infection, but effective vaccines are currently lacking. Despite being eradicated from most parts of the world, Mycoplasma mycoides subsp. mycoides, the cause of contagious bovine pleuropneumonia (CBPP), continues to plague sub-Saharan Africa. Numerous new experimental vaccines have been developed over the last 20 years to improve on protection afforded by the T1/44, a live vaccine in continuous use in Africa for over 60 years, but none so far have succeeded; indeed, many have exacerbated the disease.
  • 1.0K
  • 23 Jun 2021
Topic Review
Importance and Reality of TDM for Antibiotics
Under the Japanese health insurance system, medicines undergoing therapeutic drug monitoring (TDM) can be billed for medical fees if they meet the specified requirements. In Japan, TDM of vancomycin, teicoplanin, aminoglycosides, and voriconazole, which are used for the treatment of infectious diseases, is common practice. This means the levels of antibiotics are measured in-house using chromatography or other methods. In some facilities, the blood and/or tissue concentrations of other non-TDM drugs are measured by HPLC and are applied to treatment, which is necessary for personalized medicine.
  • 1.0K
  • 07 Apr 2022
Topic Review
Efficacy and Effectiveness of SARS-CoV-2 Vaccines
The major determinants of vaccine acceptance are vaccine safety and efficacy. Most COVID-19 vaccines have mild side effects, such as pain at the site of injection, tiredness, headache, fever, or shivering for 1–2 days after vaccination. Very rare side effects include allergic reactions and blood clotting problems, the latter affecting a small number of people who had the Oxford/AstraZeneca vaccine. Vaccine efficacy is defined as the degree to which a vaccine prevents disease, and possibly, also its transmission under ideal and controlled circumstances; this is determined by comparing a vaccinated group with a placebo group in a randomized controlled trial (RCT). Vaccine effectiveness also refers to how well the vaccine performs in the real world based on observational studies.
  • 1.0K
  • 04 Mar 2022
Topic Review
The Pathophysiology of COVID-19 and T2DM Coagulopathy
Chronic inflammation and endothelium dysfunction are present in diabetic patients. COVID-19 has a high mortality rate in association with diabetes, partially due to the development of thromboembolic events in the context of coronavirus infection. Chronic inflammation, present in DM, enhances the synthesis of several cytokines. This chronic inflammatory state is preceded by a subclinical inflammatory response, represented by elevated IL-1β and IL-6 before the onset of type 2 diabetes mellitus (T2DM). Endothelial dysfunction is also a consequence of Diabetes mellitus (DM) and leads to micro- and macroangiopathy, and concomitantly to hypercoagulability.
  • 1.0K
  • 03 Apr 2023
Topic Review
Malaria Treatment
Malaria is a severe disease caused by parasites of the genus Plasmodium, which is transmitted to humans by a bite of an infected female mosquito of the species Anopheles. Malaria remains the leading cause of mortality around the world, and early diagnosis and fast-acting treatment prevent unwanted outcomes. It is the most common disease in Africa and some countries of Asia, while in the developed world malaria occurs as imported from endemic areas. 
  • 1.0K
  • 10 Jan 2022
Topic Review
The Impact of Coinfection on the COVID-19 Infection
Patients with viral illness are at higher risk of secondary infections—whether bacterial, viral, or parasitic—that usually lead to a worse prognosis. In the setting of Corona Virus Disease 2019 (COVID-19), the Severe Acute Respiratory Syndrome Coronavirus-type 2 (SARS-CoV-2) infection may be preceded by a prior microbial infection or has a concurrent or superinfection. Previous reports documented a significantly higher risk of microbial coinfection in SARS-CoV-2-positive patients. Initial results from the United States (U.S.) and Europe found a significantly higher risk of mortality and severe illness among hospitalized patients with SARS-CoV-2 and bacterial coinfection. However, later studies found contradictory results concerning the impact of coinfection on the outcomes of COVID-19. 
  • 1.0K
  • 27 May 2022
Topic Review
Loss of Homeostatic Microglia Signature in Prion Diseases
Prion diseases are neurodegenerative diseases that affect humans and animals. They are always fatal and, to date, no treatment exists. The hallmark of prion disease pathophysiology is the misfolding of an endogenous protein, the cellular prion protein (PrPC), into its disease-associated isoform PrPSc. Besides the aggregation and deposition of misfolded PrPSc, prion diseases are characterized by spongiform lesions and the activation of astrocytes and microglia. Microglia are the innate immune cells of the brain. Activated microglia and astrocytes represent a common pathological feature in neurodegenerative disorders. Microglia are dysregulated in neurodegenerative diseases. However, the loss of the microglia homeostatic signature might contribute to disease progression. 
  • 1.0K
  • 15 Mar 2023
Topic Review
Gut Microbiome and Adjuvant Treatment of COVID-19
High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed.
  • 1.0K
  • 23 Nov 2021
Topic Review
Bartonellosis
Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella. Bartonella species cause diseases such as Carrión's disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders.
  • 1.0K
  • 15 Nov 2022
Topic Review
Treatment for Pseudomonas aeruginosa Infections
Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium renowned for its resilience and adaptability across diverse environments, including clinical settings, where it emerges as a formidable pathogen. Notorious for causing nosocomial infections, P. aeruginosa presents a significant challenge due to its intrinsic and acquired resistance mechanisms.
  • 1.0K
  • 15 Nov 2023
Topic Review
The Potential of Probiotics
Probiotics, by definition, are live microorganisms, and should remain viable when they reach the intended site of action, which is typically the cecum and/or the colon.
  • 1.0K
  • 24 Nov 2021
Topic Review
ESAT-6 a Major Virulence Factor of Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) virulence relies on its ability to manipulate host macrophages, where it establishes intracellular niches to cross mucosal barriers and avoid pathogen destruction. First, Mtb subverts the endocytic pathway, preventing phagolysosome fusion and proteolytic digestion. Second, it activates innate immune responses to induce its transmigration into the lung parenchyma. There, infected macrophages attract more permissive cells, expanding intracellular niches. Mtb induces the adaptive responses that stimulate its containment and encourage a long life inside granulomas. Finally, the pathogen induces necrotic cell death in macrophages, granuloma destruction, and lung cavitation for transmission. Common to all these events is the major virulence factor: the “early secreted antigenic target of 6 kDa” (ESAT-6, also called EsxA). The loss or gain of mycobacterial virulence is closely linked to the ability of mycobacteria to produce and secrete ESAT-6, and the extension of virulence is correlated with the amount of protein secreted. ESAT-6 secretion from the bacilli requires both the expression of the esx-1 locus for the type VII secretion apparatus and the transcription of both the ESAT-6 gene (esxA) and the culture filtrate protein 10 (CFP-10) gene (esx-B) contained in the RD1 region of the genome. In addition, it requires the protein EspA, which is not encoded in the esx-1 locus but in the extended espACD operon adjacent to RD8. All species and strains deleted in the esx-1 locus, the internal RD1 region, or the esx-1 extended locus espACD exhibit an attenuated phenotype. Mutants with deletions on ESX-1 of Mtb are attenuated in virulence, translating into reduced survival of mycobacteria in cultured macrophages or in experimental animal models of TB. Curiously, the saprophyte species M. smegmatis (Ms) also encodes for an ESX-1 apparatus; however, it does not appear to confer Ms virulence capabilities, as demonstrated by its inability to survive in human macrophages or in amoeba in the environment. Predatory amoeba may have contributed to the evolutionary pressure that selected mycobacterial pathogens for intracellular survival. 
  • 999
  • 25 Jun 2023
Topic Review
Use of COVID-19 Boosters among Health Care Providers
While the World Health Organization (WHO) has de-escalated coronavirus disease 2019 (COVID-19) from a global health emergency, ongoing discussions persist as new viral variants. 
  • 999
  • 27 Feb 2024
Topic Review
Treatment of Invasive Candidiasis
Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used.
  • 998
  • 21 Jun 2022
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