Clostridioides difficile hypervirulent strain ST1 isolated from clinical stool specimens obtained from three Provinces in South Africa.

Objectives: Clostridioides difficile infection is a serious healthcare-associated infection linked to antimicrobial use. The severity of the disease can be associated with hypervirulent ribotypes such as RT027. The study aimed to investigate the molecular epidemiology and genomic characteristics of C.

Molecular epidemiology of carbapenemase-producing Klebsiella pneumoniae in Gauteng South Africa.

Klebsiella pneumoniae multidrug-resistant (MDR) high-risk clones drive the spread of antimicrobial resistance (AMR) associated infections, resulting in limited therapeutic options. This study described the genomic characteristics of K. pneumoniae MDR high-risk clones in Gauteng, South Africa.

Klebsiella pneumoniae with carbapenemases: high prevalence of sequence type 307 with bla in South African community hospitals.

This study investigated the molecular characteristics of urinary carbapenemase-producing Klebsiella pneumoniae isolates (n = 194) in Gauteng, South Africa, using simple, cost-effective PCR methodologies. Extensively drug resistant (XDR) ST307 with bla on IncX3 plasmids was endemic in Gauteng community hospitals leaving limited options for treating in- and outpatient urinary tract infections. High-level ceftazidime/avibactam resistance was detected among isolates harbouring bla including bla.

Anti-TNF therapy impairs both short- and long-term IgG responses after repeated vaccination.

Background: Recently, it has been questioned whether vaccination of patients with inflammatory (auto)immune diseases under anti-tumor necrosis factor (TNF) treatment leads to impaired vaccine-induced immune responses and protection against breakthrough infections. However, the effects of TNF blockade on short- and long-term immune responses after repeated vaccination remain unclear. Vaccination studies have shown that initial short-term IgG antibodies (Abs) carry highly galactosylated and sialylated Fc glycans, whilst long-term IgG Abs have low levels of galactosylation and sialylation and are most likely generated by long-lived plasma cells (PCs) derived primarily from the germinal center (GC) response.

How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms.

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but the mechanisms underlying this link are poorly understood. Associative learning encompasses key mechanisms through which individuals learn to link important environmental inputs to emotional and behavioral responses. ACEs may impact the normative maturation of associative learning processes, resulting in their enduring maladaptive expression manifesting in psychopathology.

RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-,-diisopropyltryptamine.

Results from randomized clinical trials of psilocybin in depressive disorders highlight the therapeutic potential of serotonergic psychedelic compounds in mental health disorders. The synthetic 5-hydroxytryptamine 2A receptor agonist 4-hydroxy-,-diisopropyltryptamine (4-OH-DiPT) is structurally similar to psilocin but is reported to have a shorter duration (2-3 h) of psychedelic effects, suggesting the potential for psilocybin-like therapeutic activity with reduced clinical resource burden. Here, we describe the preclinical and translational characterization of RE104, a 4-OH-DiPT prodrug comprising a glutarate moiety designed to cleave rapidly in situ and thus provide reasonable bioavailability of the active drug.

Quantitation of propofol metabolites by LC-MS/MS demonstrating long detection window for urine drug monitoring.

Introduction: Chromatographic methods for analysis of propofol and its metabolites have been widely used in pharmacokinetic studies of propofol distribution, metabolism, and clearance. Application of chromatographic methods is also needed in clinical and forensic laboratories for detecting and monitoring propofol misuse.

Objective: We report a method for sensitive analysis of propofol, propofol 1-glucuronide (PG), 4-hydroxypropofol 1-glucuronide (1-QG), 4-hydroxypropofol 4-glucuronide (4-QG) and 4-hydroxypropofol 4-sulfate (4-QS) in urine by LC-MS/MS analysis.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients.

Genomic epidemiology and molecular characteristics of bla-positive carbapenem-resistant Pseudomonas aeruginosa belonging to international high-risk clone ST773 in the Gauteng region, South Africa.

Purpose: The emergence of carbapenem-resistant P. aeruginosa (CRPA) harbouring acquired carbapenemase genes (bla, bla and bla) has become a global public health threat. Three CRPA isolates included in the study had an extensively drug-resistant phenotype with susceptibility to colistin only and were positive for the bla gene.

Two-Year Outcomes of Novel Dual-Mobility Implant in Primary Total Hip Arthroplasty.

Introduction: Dual-mobility (DM) implants for total hip arthroplasty (THA) have gained popularity due to their potential to reduce hip instability and dislocation events that may lead to revision surgery. These implants consist of a femoral head articulated within a polyethylene liner, which articulates within an outer acetabular shell, creating a dual-bearing surface. Our study aimed to report our observations on the survivorship of a novel DM implant for primary total hip arthroplasty at two years.

The B Cell Response and Formation of Allergenic and Anti-Allergenic Antibodies in Food Allergy.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc -glycosylation patterns that can affect the allergic reaction to food in multiple ways.

Population structure of Salmonella enterica Typhi in Harare, Zimbabwe (2012-19) before typhoid conjugate vaccine roll-out: a genomic epidemiology study.

Background: The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme.

Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Typhi genomes.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).

Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.

Implementing strabismus-specific psychosocial questionnaires in everyday clinical practice: mental health and quality of life in the context of strabismus surgery.

Background: Strabismus can have a great negative impact on the quality of life and the well-being of affected patients. In the past, these aspects were often neglected and, compared with somatic functioning, placed in the background. The aim of our study is to elicit factors influencing satisfaction with strabismus surgery, quality of life and expectations of surgery in order to better predict who will benefit the most and who may need further support.

Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum.

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins.

mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine.

Background: The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.

Objective: However, the impact of these new vaccine formats with unclear effects on the long-term Ab response - including isotype, subclass, and their type of Fc glycosylation - is less explored.

Faecal carriage of ESBL producing and colistin resistant in avian species over a 2-year period (2017-2019) in Zimbabwe.

Introduction: Extended spectrum beta-lactamase (ESBL) producing have become widespread among food producing animals. These strains serve as a reservoir of antibiotic resistance genes (ARGs) and act as a possible source of infection to humans as transmission can occur by direct or indirect contact.

Methods: This study investigated the faecal carriage of ESBL producing and colistin resistant in poultry over a 2-year period (2017-2019) from Zimbabwe.

Decomposing Neural Representational Patterns of Discriminatory and Hedonic Information during Somatosensory Stimulation.

The ability to interrogate specific representations in the brain, determining how, and where, difference sources of information are instantiated can provide invaluable insight into neural functioning. Pattern component modeling (PCM) is a recent analytic technique for human neuroimaging that allows the decomposition of representational patterns in brain into contributing subcomponents. In the current study, we present a novel PCM variant that tracks the contribution of prespecified representational patterns to brain representation across areas, thus allowing hypothesis-guided employment of the technique.

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylated IgG1 in naive but not in antigen-experienced vaccinees.

Background: Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses.

Risk assessment of SARS-CoV-2 transmission in hospitality employees in a highly frequented tourist area.

Right from the start of the COVID pandemic in January 2020, the entire tourism sector was put under immense pressure because of its assumed role in SARS-CoV-2 transmission and infection dynamics. Based on reports of single superspreading events in the early days of the pandemic, the hotel industry appeared in a bad light that impaired a strategic risk-assessment of existing transmission risks between tourists and employees. We prospectively analysed samples of 679 employees of 21 hotels and restaurants from July 2020 to December 2020, a time during which more than 1.

Multiclonal human origin and global expansion of an endemic bacterial pathogen of livestock.

Most new pathogens of humans and animals arise via switching events from distinct host species. However, our understanding of the evolutionary and ecological drivers of successful host adaptation, expansion, and dissemination are limited. is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide.

Influence of nutrients and metabolites on the differentiation of plasma cells and implications for autoimmunity.

The modulation of inflammatory (auto)immune reactions by nutrients and gut bacterial metabolites is of great interest for potential preventive and therapeutic strategies. B cell-derived plasma cells are major players in inflammatory (auto)immune responses and can exhibit pro- or anti-inflammatory effects through (auto)antibody-dependent and -independent functions. Emerging evidence indicates a key role of nutrients and microbial metabolites in regulating the differentiation of plasma cells as well as their differentiation to pro- or anti-inflammatory phenotypes.