Highly Diastereoselective Access to Densely Functionalized Piperidine Cores of Influenza Endonuclease Inhibitors via a Metal-Free S1 Approach.

A novel, highly diastereoselective, and metal-free synthesis of multisubstituted piperidines via an S1 approach is reported in this study. The method allows for the preparation of highly functionalized compounds with exceptional diastereomeric selectivities and consistently reproducible yields. These compounds are of significant interest due to their remarkable biological activities toward influenza endonuclease.

Molecular epidemiology of human herpesvirus 8 in patients with HHV-8-related diseases in Ireland.

Human Herpesvirus 8 (HHV-8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV-8 in an Irish population. This retrospective study included 30 patients who had HHV-8 DNA detected in plasma.

Multiple introductions of monkeypox virus to Ireland during the international mpox outbreak, May 2022 to October 2023.

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.

Mtb-Selective 5-Aminomethyl Oxazolidinone Prodrugs: Robust Potency and Potential Liabilities.

Linezolid is a drug with proven human antitubercular activity whose use is limited to highly drug-resistant patients because of its toxicity. This toxicity is related to its mechanism of action─linezolid inhibits protein synthesis in both bacteria and eukaryotic mitochondria. A highly selective and potent series of oxazolidinones, bearing a 5-aminomethyl moiety (in place of the typical 5-acetamidomethyl moiety of linezolid), was identified.

Disease-Modifying Treatments for Multiple Sclerosis Affect Measures of Cellular Immune Responses to EBNA-1 Peptides.

Background And Objectives: Epstein-Barr virus (EBV) has been strongly implicated in the pathogenesis of multiple sclerosis (MS). Despite this, there are no routinely used tests to measure cellular response to EBV. In this study, we analyzed the cellular response to EBV nuclear antigen-1 (EBNA-1) in people with MS (pwMS) using a whole blood assay.

DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in .

Natural products provide a rich source of potential antimicrobials for treating infectious diseases for which drug resistance has emerged. Foremost among these diseases is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of , revealed that it is a bactericidal genotoxin that induces a DNA damage response in () and inhibits growth by blocking the replicative DNA polymerase, DnaE1.

SARS-CoV-2 Antibody Testing in Health Care Workers: A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5,788 health care worker (HCW) serum samples by using two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) and Roche anti-SARS-CoV-2 anti-nucleocapsid total antibody) and a subset of samples (all Abbott assay positive or grayzone,  = 485) on Wantai SARS-CoV-2 anti-spike antibody enzyme-linked immunosorbent assay (ELISA).

SARS-CoV-2 anti-nucleocapsid assay performance in healthcare workers at baseline and 6 months.

Introduction: Serological SARS-CoV-2 assays have an important role in guiding the pandemic response. This research aimed to compare the performance of 2 antinucleocapsid assays.

Methods: Serum from 49 HCWs was analysed at baseline and 6 months using the Abbott diagnostics SARS-CoV-2 IgG assay and the Roche Diagnostics Elecsys Anti-SARS-CoV-2 total antibody assay.

Seroprevalence of human herpesvirus 8 in Ireland among blood donors, men who have sex with men, and heterosexual genitourinary medicine and infectious diseases clinic attendees.

Human herpesvirus 8 (HHV-8) seroprevalence varies geographically and between subpopulations. High seroprevalence rates have been ascribed to men who have sex with men (MSM), African migrants, and HIV-infected individuals. The objective of this study was to determine the seroprevalence of HHV-8 in an Irish population, including specific risk groups.

Opt-out screening for HIV, hepatitis B and hepatitis C: observational study of screening acceptance, yield and treatment outcomes.

Background: We initiated an emergency department (ED) opt-out screening programme for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) at our hospital in Dublin, Ireland. The objective of this study was to determine screening acceptance, yield and the impact on follow-up care.

Methods: From July 2015 through June 2018, ED patients who underwent phlebotomy and could consent to testing were tested for HIV, HBV and HCV using an opt-out approach.

The Fungal PCR Initiative's evaluation of in-house and commercial Pneumocystis jirovecii qPCR assays: Toward a standard for a diagnostics assay.

Quantitative real-time PCR (qPCR) is increasingly used to detect Pneumocystis jirovecii for the diagnosis of Pneumocystis pneumonia (PCP), but there are differences in the nucleic acids targeted, DNA only versus whole nucleic acid (WNA), and also the target genes for amplification. Through the Fungal PCR Initiative, a working group of the International Society for Human and Animal Mycology, a multicenter and monocenter evaluation of PCP qPCR assays was performed. For the multicenter study, 16 reference laboratories from eight different countries, performing 20 assays analyzed a panel consisting of two negative and three PCP positive samples.

Prevalence, Macrolide Resistance, and Fluoroquinolone Resistance in Mycoplasma genitalium in Men Who Have Sex With Men Attending an Sexually Transmitted Disease Clinic in Dublin, Ireland in 2017-2018.

This is the first prevalence study of Mycoplasma genitalium and antimicrobial resistance study in Ireland. In urine samples from men who have sex with men (n = 400) attending a sexually transmitted disease clinic in Dublin, the prevalence of M. genitalium was 3% (12 of 400 specimens; 95% confidence interval, 1.

Multidrug-resistant isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018.

We describe a multidrug-resistant urethritis case with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Ireland, August 2018. Whole-genome sequencing showed that the isolate IR72 belongs to the internationally spreading multidrug-resistant ceftriaxone-resistant FC428 clade, initially described in Japan in 2015. IR72 was assigned MSLT ST1903, NG-MAST ST17842 and NG-STAR type 1133, including the ceftriaxone resistance-mediating 60.

Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey.

Background: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries.

A European multi-centre External Quality Assessment (EQA) study on phenotypic and genotypic methods used for Herpes Simplex Virus (HSV) drug resistance testing.

Background: Herpes Simplex Virus (HSV) drug resistance is a significant public health concern among immunocompromised individuals. Phenotypic assays are considered the gold standard method for detecting HSV drug resistance. However, plaque reduction assays (PRAs) are technically demanding, often with long turnaround times of up to four weeks.

Fourteen Draft Genome Sequences for the First Reported Cases of Azithromycin-Resistant in Ireland.

Here, we report the draft genome assemblies of 14 azithromycin-resistant clinical isolates, representing the first such strains identified in Ireland. Among these isolates are the first reported highly resistant strains (MIC >256 mg/liter), which both belonged to the ST1580 sequence type.

Development of chronic hepatitis B infection in a hepatitis B vaccine responder.

The Hepatitis B vaccine is highly effective for the prevention of hepatitis B (HBV) infection. We report the development of chronic HBV infection (Genotype F) in a vaccinated immunocompetent individual with an anti-HBsAb of 35 mIU/mL post completion of vaccine series. HBV vaccine is based on recombinant proteins of genotype-A and D (predominant genotypes in Europe).

WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014.

Objectives: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms.

Methods: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS.

Opt-Out Panel Testing for HIV, Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study.

Objectives: Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.

Methods: An opt-out ED blood borne virus screening programme was piloted from March 2014 to January 2015.

Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine.

In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP+HS IC50=0.67 nM), and selective compound (hERG IC50=19 μM) with favorable rodent pharmacokinetics (F=100%, t1/2=7h) is described.

The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis.

Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody.

How to use central venous catheter tip cultures.

Central venous catheter (CVC) tip cultures are useful in the assessment of a patient with a potential catheter-related bloodstream infection (CRBSI). However, these results can be misleading particularly in the absence of concomitant peripheral and central line blood cultures. Catheter tip cultures should not be submitted to the laboratory unless CRBSI is suspected as the predictive value of culture results depends on the pretest probability of CRBSI.

Molecular analysis of OXA-48-carrying conjugative IncL/M-like plasmids in clinical isolates of Klebsiella pneumoniae in Ireland.

This study characterized an IncL/M-like plasmid containing a bla(OXA-48)-encoding gene from a clinical isolate of Klebsiella pneumoniae, denoted as E71T. Investigation of this plasmid sequence identified unique regions of interest along with conserved regions detected in eight other clinical carbapenem-resistant isolates. A 63-kb plasmid (pE71T) from K.