Publications by authors named "Robert Sim"

Objective: To examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM).

Design: In a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG.

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  • The classical pathway of the complement system is initiated when C1q binds to target activators, including immune complexes, while factor H primarily regulates the alternative pathway but can also influence the classical pathway by competing for binding sites with C1q.
  • Both C1q and factor H can recognize and bind to foreign or altered-self materials, including fibrin clots, which can activate the classical complement pathway through mechanisms involving FXIIIa.
  • The study showed that fibrin clots do indeed activate the classical pathway, leading to complement activation, but factor H effectively downregulates this activation, highlighting the complex interplay between the complement and coagulation systems.
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  • The complement system plays a crucial role in the immune response to infections like SARS-CoV-2, with some evidence suggesting it can both harm (through cytokine storms) and protect against the virus.
  • This study specifically looked at the roles of two complement proteins, C1q and C4b-binding protein (C4BP), in preventing SARS-CoV-2 infection, focusing on their ability to bind to the virus's spike protein.
  • Results showed that C1q and C4BP not only reduced the virus's ability to enter cells but also decreased the expression of proinflammatory cytokines, suggesting they offer a protective effect during infection.
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  • The study examines how in utero adversities like hypoxia and malnutrition relate to the development of schizophrenia (SZ) by investigating specific proteins (l-ficolin and MASP-2) linked to the immune response in patients.
  • Results show that SZ patients had significantly higher levels of l-ficolin (about 40% increase) and a notable gender difference in MASP-2 levels, especially among female patients.
  • The study also notes that while there are increases in certain protein activities in SZ, there was no significant association with demographic factors like age, family history, or smoking habits.
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Context: Hysterosalpingography (HSG) using oil-soluble contrast medium (OSCM) improves pregnancy rates but results in severe and persistent iodine excess, potentially impacting the fetus and neonate.

Objective: To determine the incidence of thyroid dysfunction in newborns conceived within six months of OSCM HSG.

Design: Offspring study of a prospective cohort of women who underwent OSCM HSG.

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  • - Fusarium endophytes, particularly Fusarium verticillioides (or Gibberella moniliformis), damage cereal crops by detoxifying host defenses through a specific enzyme, (GIBMO)NAT1, which plays a crucial role in their pathogenicity and ability to produce mycotoxins.
  • - The study presents the detailed crystallographic structure of (GIBMO)NAT1, highlighting its unique monomeric arrangement, which facilitates access to the catalytic core through two distinct "tunnel-like" openings.
  • - Biochemical assays indicate varying substrate preferences among different NAT isoenzymes, suggesting they have evolved separately and that understanding (GIBMO)NAT1's structure and function
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Context: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates. However, OSCM has high iodine content and long half-life, leading to potential iodine excess.

Objective: This work aimed to determine the pattern of iodine excess after OSCM HSG and the effect on thyroid function.

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Objective: Hysterosalpingography (HSG) with oil-soluble contrast medium (OSCM) improves pregnancy rates in women with idiopathic infertility. However, OSCM has high iodine content and slow clearance resulting in potential iodine excess. If pregnancy occurs, this could impact fetal thyroid gland development and function.

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  • * The study focused on properdin's role against Influenza A virus (IAV), demonstrating that it interacts with certain viral proteins and influences immune responses in a subtype-specific manner.
  • * Properdin was shown to suppress H1N1 replication while promoting H3N2 replication, triggering different inflammatory responses in infected cells, thus highlighting its dual role during viral infections.
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  • - The complement system is a vital part of the immune system that helps fight off pathogens, operating through three main pathways: classical, alternative, and lectin.
  • - It has various roles in combating viruses, including opsonization, inducing phagocytosis, and forming a membrane attack complex, while also enhancing immune responses.
  • - However, many viruses have developed strategies to evade the complement system by producing inhibitors, which aids in their survival and makes them more prone to cause disease.
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  • C4b Binding Protein (C4BP) inhibits the complement system by binding to activated component C4b, working alongside factor I to prevent the formation of the C3-convertase, which is essential for immune response.
  • The study investigates C4BP's ability to interact with Influenza A Virus (IAV) subtypes H1N1 and H3N2, discovering that C4BP binds to various viral proteins and affects infection rates differently for each subtype.
  • C4BP decreases inflammatory responses for H1N1, acting as an entry inhibitor, while it enhances pro-inflammatory responses for H3N2, suggesting that C4BP has strain-dependent effects on IAV entry and replication independent of its
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Recent interest in the use of oil-soluble contrast media (OSCM) for hysterosalpingography (HSG) and other tubal flushing procedures is largely the result of publication of the large, multicentre, randomized controlled H2Oil trial in the New England Journal of Medicine in 2017, addressing the long-held suspicion that pregnancy rates following HSG with OSCM are higher than if a water-soluble contrast media (WSCM) is used. However, the findings of this trial have been compromised by the WSCM selected for comparison with OSCM. The chosen WSCM belongs to a superceded class of ionic media, with an iodine concentration, osmolality and viscosity all lying at the extreme end of the range for water-soluble radiographic contrast.

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Iodine is a vital micronutrient and its importance in thyroid function is well established. However, abnormalities in iodine intake may also have other effects. In particular, iodine is taken up avidly by the ovary and endometrium.

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Assessment of tubal patency and therapeutic tubal flushing using Lipiodol, an oil-soluble contrast media (OSCM), has been shown to enhance fertility, resulting in increased interest in the use of Lipiodol. A modified hysterosalpingogram (HSG) technique, including a supplementary ultrasound with the contrast in situ, is recommended when using Lipiodol, taking into account both safety issues and technical challenges specific to Lipiodol.

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  • - The complement system is a key part of the innate immune defense that identifies pathogens, with factor H serving to regulate complement activation on host cells and locally at infection sites like the lungs.
  • - Factor H interacts with the influenza A virus (IAV), affecting its entry into cells and modulating the expression of matrix protein 1 (M1), with varying effects on inflammatory cytokines depending on the IAV subtype (H1N1 vs. H3N2).
  • - Both factor H and a similar protein (VCP) demonstrate different impacts on luciferase reporter activity in response to H1N1 and H3N2, highlighting factor H's role in modulating IAV infection and inflammatory responses outside of
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  • The complement system plays a key role in the immune response against tumors, but many cancer cells, including those from Glioblastoma multiforme (GBM), can evade destruction by this system.
  • Researchers identified that primary GBM cells secrete a protein called FHR5, which functions similarly to factor H in inhibiting immune attack.
  • The study showed that GBM-derived FHR5 not only prevents complement-mediated cell lysis but also assists in the breakdown of the complement component C3b, helping tumor cells to survive immune surveillance.
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  • Enterococcus faecalis is a major cause of bloodstream infections in critically ill patients, and the complement system helps the immune response target these bacteria.
  • In an experiment with mice, those treated with anti-Factor H antibodies showed a lower bacterial count in their blood and organs compared to controls, suggesting the treatment enhanced immune response.
  • The study found that E faecalis can evade the alternative pathway of the complement system by binding Factor H to its surface, effectively escaping phagocytosis while still being targeted by other pathways.
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  • * A recombinant form of conglutinin (rfBC) was found to bind to and inhibit the growth of BCG (a model organism for studying tuberculosis) in a dose-dependent manner, as well as suppress the uptake of BCG by human macrophage cells (THP-1).
  • * The study reveals that rfBC can inhibit mycobacterial uptake through two mechanisms: masking lipoarabinomannan to prevent receptor-mediated uptake and blocking interactions with iC3b,
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  • Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious conditions caused by factors like trauma or infection, leading to major inflammation and damage in lung tissues due to neutrophil activity.
  • Researchers found that a recombinant chemotaxis inhibitory protein (rCHIPS) from Staphylococcus aureus can effectively reduce the severity of ALI/ARDS in mice by decreasing lung inflammation and permeability after exposure to harmful substances.
  • Treatment with rCHIPS leads to reduced levels of inflammatory markers, less neutrophil and leukocyte recruitment, and improved lung health, indicating its potential as a therapeutic option for treating ALI/ARDS.
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  • Mycobacterium can enter macrophages, reduce complement activation, suppress macrophage death, and survive inside these immune cells.
  • The study indicates that properdin and TSR4+5 inhibit the intake of BCG by macrophages and alter inflammatory responses, enhancing pro-inflammatory signals initially before decreasing over time.
  • Findings highlight that properdin may play a role in preventing mycobacterial entry into macrophages, suggesting its potential importance in the immune response to tuberculosis.
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  • * The study identifies that human properdin binds to functionalized carbon nanotubes (CNTs) and enhances their uptake by immune cells, leading to increased inflammatory responses.
  • * Coating carbon nanotubes with recombinant TSR4+5 serves as a method to reduce unwanted complement activation, indicating potential therapeutic applications for these modified nanoparticles in inflammatory conditions.
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  • The study aimed to evaluate the activities of MASP-1 and MASP-2 proteins in the blood of patients with ischaemic stroke and explore the relationship between certain genetic polymorphisms and the disease.
  • A total of 250 patients and 300 healthy individuals were tested, revealing significantly higher MASP-1 and MASP-2 activities in stroke patients.
  • The research identified two specific genetic variations (rs3203210 and rs147270785) that are linked to ischaemic stroke risk, suggesting that these genetic factors may serve as protective markers in the population studied.
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