Indirect Formation of Peptide Bonds as a Prelude to Ribosomal Transpeptidation.

The catalytic competency of the ribosome in extant protein biosynthesis is thought to arise primarily from two sources: an ability to precisely juxtapose the termini of two key substrates─3'-aminoacyl and -acyl-aminoacyl tRNAs─and an ability to ease direct transpeptidation by their desolvation and encapsulation. In the absence of ribosomal, or enzymatic, protection, however, these activated alkyl esters undergo efficient hydrolysis, while significant entropic barriers serve to hamper their intermolecular cross-aminolysis in bulk water. Given that the spontaneous emergence of a catalyst of comparable size and sophistication to the ribosome in a prebiotic RNA world would appear implausible, it is thus natural to ask how appreciable peptide formation could have occurred with such substrates in bulk water without the aid of advanced ribozymatic catalysis.

Number of Doses of Systemic Antibiotic Prophylaxis May Be Reduced in Cemented Primary Knee Arthroplasty Irrespective of Use of Antibiotic in the Cement: A Multiregistry-Based Meta-Analysis.

Background: The use of systemic antibiotic prophylaxis (SAP) and antibiotic-loaded bone cement (ALBC) is the accepted practice to reduce the risk of periprosthetic joint infection (PJI) in primary total knee arthroplasty (pTKA). However, practice varies internationally. This study's primary aim was to compare the risk of PJI revision after pTKA with ALBC + SAP vs.

Sex-based differences in risk of revision for infection after hip, knee, shoulder, and ankle arthroplasty in osteoarthritis patients: a multinational registry study of 4,800,000 implants.

Background And Purpose:  We aimed to determine sex differences for periprosthetic joint infections after primary arthroplasty of the hip, knee, ankle, and shoulder in osteoarthritis patients in an international perspective.

Methods:  This is a multinational combined arthroplasty registry study. Each arthroplasty registry performed Cox-regression analysis of their data and reported the crude and adjusted hazard ratios (HR) with an a priori designed data form.

Meeting Men Where they are: Motivators and Barriers to Accessing Health Services through a Men's Mobile Wellness Clinic, October 2019 to March 2020, Blantyre, Malawi.

Background: In Malawi approximately, 88.3% people living with HIV are aware of their HIV status. Significant gaps are among men aged 15-34 years; only 72% know their HIV status.

Understanding the epidemiology of iNTS disease in Africa in preparation for future iNTS- vaccine studies in endemic countries: Seroepidemiology in Africa of iNTS (SAiNTS) Study Protocol: Malawi site [Version 9.0].

Background: Non-typhoidal Salmonella (NTS) are a major cause of bloodstream infections amongst children in sub-Saharan Africa. A clear understanding of the seroepidemiology and correlates of protection for invasive NTS (iNTS) in relation to key risk factors (malaria, anaemia, malnutrition) in children in Africa is needed to inform strategies for disease control including vaccine implementation.

Methodology: The SAiNTS study is a prospective community cohort study with paired serology samples from 2500 Malawian children 0-5 years at baseline and three months to measure age-stratified acquisition of lipopolysaccharide (LPS) O-antigen antibody (IgG) and serum bactericidal activity to the main serovars causing iNTS ( Typhimurium and .

Diagnosing sucrase-isomaltase deficiency: a comparison of a C-sucrose breath test and a duodenal enzyme assay.

Background: Reduced activity of the sucrase-isomaltase (SI) enzyme can cause gastrointestinal symptoms. Biochemical measurement of SI activity in small intestinal biopsies is presently considered the gold standard for the diagnosis of SI deficiency, but this invasive test is not suitable as a routine diagnostic tool.

Aim: To evaluate a C-sucrose-breath test (CSBT) as a diagnostic tool for SI deficiency in an adult population.

Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement.

Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient.

Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement.

Design, Setting, And Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US.

How good are surgeons at disclosing periprosthetic joint infection at the time of revision, based on pre- and intra-operative assessment? A study on 16,922 primary total hip arthroplasties reported to the Norwegian Arthroplasty Register.

Background And Purpose: Revision due to infection, as reported to the Norwegian Arthroplasty Register (NAR), is a surrogate endpoint to periprosthetic joint infection (PJI). We aimed to find the accuracy of the reported causes of revision after primary total hip arthroplasty (THA) compared with PJI to see how good surgeons were at disclosing infection, based on pre- and intraoperative assessment.

Patients And Methods: We investigated the reasons for revision potentially caused by PJI following primary THA: infection, aseptic loosening, prolonged wound drainage, and pain only, reported to the NAR from surgeons in the region of Western Norway during the period 2010-2020.

Risk factors for fracture-related infection after ankle fracture surgery.

Introduction: Ankle fracture surgery comes with a risk of fracture-related infection (FRI). Identifying risk factors are important in preoperative planning, in management of patients, and for information to the individual patient about their risk of complications. In addition, modifiable factors can be addressed prior to surgery.

Characterization of Enzyme-Linked Immunosorbent Assay (ELISA) for Quantification of Antibodies against Typhimurium and Enteritidis O-Antigens in Human Sera.

Nontyphoidal Salmonella (NTS) is a leading cause of morbidity and mortality caused by enteric pathogens worldwide in both children and adults, and vaccines are not yet available. The measurement of antigen-specific antibodies in the sera of vaccinated or convalescent individuals is crucial to understand the incidence of disease and the immunogenicity of vaccine candidates. A solid and standardized assay used to determine the level of specific anti-antigens IgG is therefore of paramount importance.

Mental Health First Aid as a tool for improving mental health and well-being.

Background: The prevalence of mental health problems is high, and they have a wide-ranging and deleterious effect on many sectors in society. As well as the impact on individuals and families, mental health problems in the workplace negatively affect productivity. One of the factors that may exacerbate the impact of mental health problems is a lack of 'mental health literacy' in the general population.

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania.

Background And Purpose: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA).

Patients And Methods: This observational study is based on 2,971,357 primary TKAs reported in 2010-2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA.

Kinetics and Mechanism of Azole n-π*-Catalyzed Amine Acylation.

Azole anions are highly competent in the activation of weak acyl donors, but, unlike neutral (aprotic) Lewis bases, are not yet widely applied as acylation catalysts. Using a combination of and stopped-flow H/F NMR spectroscopy, kinetics, isotopic labeling, H DOSY, and electronic structure calculations, we have investigated azole-catalyzed aminolysis of -fluorophenyl acetate. The global kinetics have been elucidated under four sets of conditions, and the key elementary steps underpinning catalysis deconvoluted using a range of intermediates and transition state probes.

No difference in risk of revision due to infection between clindamycin and cephalosporins as antibiotic prophylaxis in cemented primary total knee replacements: a report from the Norwegian Arthroplasty Register 2005-2020.

Background And Purpose: Systemic antibiotic prophylaxis with clindamycin, which is often used in penicillin- or cephalosporin-allergic patients', has been associated with a higher risk of surgical revision for deep prosthetic joint infection (PJI) than cloxacillin in primary total knee replacement (TKR). We aimed to investigate whether clindamycin increases the risk of surgical revisions due to PJI compared with cephalosporins in primary cemented TKR.

Patients And Methods: Data from 59,081 TKRs in the Norwegian Arthroplasty Register (NAR) 2005-2020 was included.

Diet-microbiota interaction in irritable bowel syndrome: looking beyond the low-FODMAP approach.

Background: Diet is one of the main modulators of the gut microbiota, and dietary patterns are decisive for gut-microbiota-related diseases, including irritable bowel syndrome (IBS). The low-FODMAP diet (LFD) is commonly used to treat IBS, but its long-term effects on microbiota, symptoms and quality of life (QoL) are unclear. Alternative dietary strategies promoting beneficial gut microbiota, combined with reduced symptoms and improved QoL, are therefore of interest.

Increasing risk of revision due to infection after primary total hip arthroplasty: results from the Nordic Arthroplasty Register Association.

Background And Purpose: The incidence of periprosthetic joint infection after total hip arthroplasty (THA) may be increasing. We performed time-trend analyses of risk, rates, and timing of revision due to infection after primary THAs in the Nordic countries from the period 2004-2018.

Patients And Methods: 569,463 primary THAs reported to the Nordic Arthroplasty Register Association from 2004 to 2018 were studied.

What is the Source of Infections Causing Invasive Nontyphoidal Disease?

Invasive nontyphoidal (iNTS) disease is a clinical condition distinct from gastroenteritis. With an overall case-fatality rate of 14.5%, iNTS remains a major cause of morbidity and mortality, particularly in sub-Saharan Africa.

Fracture-related infection: Prevalence and application of the new consensus definition in a cohort of 1004 surgically treated ankle fractures.

Background: Surgical treatment of ankle fractures comes with a substantial risk of complications, including infection. An unambiguously definition of fracture-related infections (FRI) has been missing. Recently, FRI has been defined by a consensus group with a diagnostic algorithm containing suggestive and confirmatory criteria.

Development and Characterization of a Luminescence-Based High-Throughput Serum Bactericidal Assay (L-SBA) to Assess Bactericidal Activity of Human Sera against Nontyphoidal .

Typhimurium and Enteritidis are leading causative agents of invasive nontyphoidal (iNTS) disease, which represents one of the major causes of death and morbidity in sub-Saharan Africa, still partially underestimated. Large sero-epidemiological studies are necessary to unravel the burden of disease and guide the introduction of vaccines that are not yet available. Even if no correlate of protection has been determined so far for iNTS, the evaluation of complement-mediated functionality of antibodies generated towards natural infection or elicited upon vaccination may represent a big step towards this achievement.

"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.

Introduction: Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.

Evidence for the role of Rab11-positive recycling endosomes as intermediates in coronavirus egress from epithelial cells.

After their assembly by budding into the lumen of the intermediate compartment (IC) at the endoplasmic reticulum (ER)-Golgi interface, coronaviruses (CoVs) are released from their host cells following a pathway that remains poorly understood. The traditional view that CoV exit occurs via the constitutive secretory route has recently been questioned by studies suggesting that this process involves unconventional secretion. Here, using the avian infectious bronchitis virus (IBV) as a well-established model virus, we have applied confocal microscopy to investigate the pathway of CoV egress from epithelial Vero cells.

Mechanistic analysis by NMR spectroscopy: A users guide.

A 'principles and practice' tutorial-style review of the application of solution-phase NMR in the analysis of the mechanisms of homogeneous organic and organometallic reactions and processes. This review of 345 references summarises why solution-phase NMR spectroscopy is uniquely effective in such studies, allowing non-destructive, quantitative analysis of a wide range of nuclei common to organic and organometallic reactions, providing exquisite structural detail, and using instrumentation that is routinely available in most chemistry research facilities. The review is in two parts.