Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity

The rapid rise of multi-drug-resistant bacteria is a global healthcare crisis, and new antibiotics are urgently required, especially those with modes of action that have low-resistance potential. One promising lead is the liposaccharide antibiotic moenomycin that inhibits bacterial glycosyltransferases, which are essential for peptidoglycan polymerization, while displaying a low rate of resistance. Unfortunately, the lipophilicity of moenomycin leads to unfavourable pharmacokinetic properties that render it unsuitable for systemic administration. In this study, we show that using moenomycin and other glycosyltransferase inhibitors as templates, we were able to synthesize compound libraries based on novel pyranose scaffold chemistry, with moenomycin-like activity, but with improved drug-like properties. The novel compounds exhibit in vitro inhibition comparable to moenomycin, with low toxicity and good efficacy in several in vivo models of infection. This approach based on non-planar carbohydrate scaffolds provides a new opportunity to develop new antibiotics with low propensity for resistance induction

A Study on Effect of Employee Diversity on Organizational Performance

Purpose: The purpose of this study is to investigate the effect of employee diversity on organizational performance.   Theoretical framework: The study is based on the diversity-performance relationship theory, which suggests that a diverse workforce can lead to improved organizational performance.   Design/methodology/approach: The study employs a quantitative research design and utilizes survey data collected from employees and managers in multiple organizations. The data is analyzed using statistical methods to examine the relationship between employee diversity and organizational performance.   Findings: The findings indicate that organizations with a diverse workforce tend to have higher levels of organizational performance, as measured by factors such as productivity, innovation, and employee satisfaction.   Research, practical and social implications: The study has important implications for organizations, as it suggests that actively promoting diversity can lead to improved performance. Additionally, the findings have implications for society, as they suggest that promoting diversity in the workforce can lead to improved outcomes for organizations and their stakeholders.   Originality/value: This study adds to the existing literature by providing new evidence on the relationship between employee diversity and organizational performance, using a large and diverse sample of organizations

Social media in advancing equity and collaboration in rheumatology:the CORDIALITY review

Social media has transformed communication in academia and medicine, offering stakeholders innovative avenues for knowledge exchange and collaboration. The CORDIALITY review (soCial media fOR aDvancing equIty And coLlaboration In rheumaTologY) examines the impact of social media on education and information dissemination, patient education and empowerment, networking and mentorship, and research collaboration within rheumatology, when effectively used. In this narrative review, we consider the opportunities as well as the challenges related to each of these facets of social media use. With a focus on inequities faced globally, we give particular consideration to disparities by gender as they relate to the rheumatology workforce, and issues pertaining to lower-income and middle-income countries such as limitations of digital access and digital literacy. To maximise the potential of social media in rheumatology, we propose a strategic framework that encourages innovation, responsible practices and support from rheumatology organisations.</p

COVID-19 vaccination-related delayed adverse events among people with rheumatoid arthritis: results from the international COVAD survey

This study aimed to assess COVID-19 vaccination-related AEs in patients with rheumatoid arthritis (RA), in the COVID-19 Vaccination in Autoimmune Diseases (COVAD)-2 study. An online international cross-sectional survey captured self-reported data on COVID-19 vaccination-related adverse events (AEs) in people with RA, autoimmune diseases (AIDs; rheumatic [r] and non-rheumatic [nr]) and healthy controls (HCs). The survey was circulated by the COVAD study group, comprising 157 collaborators across 106 countries, from February to June 2022. Delayed AEs among RA were compared with other rAIDs, nrAIDs and HCs using multivariable binary regression. A total of 7203 participants were included (1423 [19.7%] RA, 2620 [36.4%] rAIDs, 426 [5.9%] nrAIDs, 2734 [38%] HCs), with 75% female. Compared to HCs, individuals with RA reported higher overall major AEs [OR 1.3 (1.0-1.7)], and an increased number of several minor AEs. Compared to nrAIDs, people with RA had several increased reported minor AEs including myalgia and joint pain. People with active RA had increased major AEs [OR 1.8 (1.1-3.0)] and hospitalisation [OR 4.1 (1.3 - 13.3)] compared to inactive RA. RA patients without autoimmune comorbidities had significantly fewer major and minor AEs than those with other rAIDs. A decreased incidence of hospitalisation was seen in patients taking methotrexate or TNF inhibitors compared to patients not taking these medications. COVID-19 vaccination is associated with minimal to no risks of delayed AEs in patients with RA compared to HCs, and fewer compared to other rAIDs. Active RA and presence of co-existing rAIDs were associated with an increased risk of delayed AEs

A checklist for translating and adapting questionnaires (CTAQ) in healthcare research: insights from a Delphi method approach

Purpose: Accurate translation and adaptation of survey questionnaires are essential for ensuring validity and reliability in cross-cultural healthcare research. Despite the global expansion of healthcare studies, standardized guidelines for the translation process are limited. Methods: To address this gap, we developed the Checklist for Translating and Adapting Questionnaires (CTAQ). A three-round Delphi survey was conducted to refine and validate the CTAQ. An international panel of experts in survey methodology, cross-cultural research, and healthcare participated in the study, providing iterative feedback to achieve consensus on checklist items. The development of the CTAQ involved: (i) drafting an initial checklist based on a comprehensive literature review and expert insights; (ii) rating the importance and relevance of each item using an 80% consensus threshold; and (iii) revising items through successive Delphi rounds until consensus was reached. Results: The finalized CTAQ comprises eight stages: defining the target audience and objectives; forming a translation team; forward and backward translation; comparing versions; reconciliation; pretesting and evaluation; final review and proofreading; and post-survey evaluation. This structured approach, informed by expert consensus, integrates best practices and addresses cultural nuances, thereby enhancing the accuracy and reliability of translated survey instruments. Conclusions: The CTAQ offers a systematic, consensus-based framework that enhances the linguistic and cultural accuracy of translated survey instruments in healthcare research. Practice implications: Adopting the CTAQ standardizes translation workflows and promotes the production of valid, reliable, and culturally appropriate questionnaires. This contributes to greater rigor and quality in international and cross-cultural healthcare studies

Doping and Transfer of High Mobility Graphene Bilayers for Room Temperature Mid-Wave Infrared Photodetectors

High-performance graphene-HgCdTe detector technology has been developed combining the best properties of both materials for mid-wave infrared (MWIR) detection and imaging. The graphene functions as a high mobility channel that whisks away carriers before they can recombine, further contributing to detection performance. Comprehensive modeling on the HgCdTe, graphene, and the HgCdTe-graphene interface has aided the design and development of this MWIR detector technology. Chemical doping of the bilayer graphene lattice has enabled p-type doping levels in graphene for high mobility implementation in high-performance MWIR HgCdTe detectors. Characterization techniques, including SIMS and XPS, confirm high boron doping concentrations. A spin-on doping (SOD) procedure is outlined that has provided a means of doping layers of graphene on native substrates, while subsequently allowing integration of the doped graphene layers with HgCdTe for final implementation in the MWIR photodetection devices. Successful integration of graphene into HgCdTe photodetectors can thus provide higher MWIR detector efficiency and performance compared to HgCdTe-only detectors. New earth observation measurement capabilities are further enabled by the room temperature operational capability of the graphene-enhanced HgCdTe detectors and arrays to benefit and advance space and terrestrial applications

Effect of carbapenem resistance on outcomes of bloodstream infection caused by Enterobacteriaceae in low-income and middle-income countries (PANORAMA): a multinational prospective cohort study

Background Low-income and middle-income countries (LMICs) are under-represented in reports on the burden of antimicrobial resistance. We aimed to quantify the clinical effect of carbapenem resistance on mortality and length of hospital stay among inpatients in LMICs with a bloodstream infection due to Enterobacteriaceae. Methods The PANORAMA study was a multinational prospective cohort study at tertiary hospitals in Bangladesh, Colombia, Egypt, Ghana, India, Lebanon, Nepal, Nigeria, Pakistan, and Vietnam, recruiting consecutively diagnosed patients with carbapenem-susceptible Enterobacteriaceae (CSE) and carbapenem-resistant Entero-bacteriaceae (CRE) bloodstream infections. We excluded patients who had previously been enrolled in the study and those not treated with curative intent at the time of bloodstream infection onset. There were no age restrictions. Central laboratories in India and the UK did confirmatory testing and molecular characterisation, including strain typing. We applied proportional subdistribution hazard models with inverse probability weighting to estimate the effect of carbapenem resistance on probability of discharge alive and in-hospital death, and multistate modelling for excess length of stay in hospital. All patients were included in the analysis. Findings Between Aug 1, 2014, and June 30, 2015, we recruited 297 patients from 16 sites in ten countries: 174 with CSE bloodstream infection and 123 with CRE bloodstream infection. Median age was 46 years (IQR 15–61). Crude mortality was 20% (35 of 174 patients) for patients with CSE bloodstream infection and 35% (43 of 123 patients) for patients with CRE bloodstream infection. Carbapenem resistance was associated with an increased length of hospital stay (3·7 days, 95% CI 0·3–6·9), increased probability of in-hospital mortality (adjusted subdistribution hazard ratio 1·75, 95% CI 1·04–2·94), and decreased probability of discharge alive (0·61, 0·45–0·83). Multilocus sequence typing showed various clades, with marginal overlap between strains in the CRE and CSE clades. Interpretation Carbapenem resistance is associated with increased length of hospital stay and mortality in patients with bloodstream infections in LMICs. These data will inform global estimates of the burden of antimicrobial resistance and reinforce the need for better strategies to prevent, diagnose, and treat CRE infections in LMICs

Magnetic and transport measurements on RAuAl (R=La, Ce, and Nd) compounds: Kondo-lattice behavior of CeAuAl

Magnetic susceptibility, electrical resistivity, and magnetoresistance measurements have been made on RAuAl (R=La, Ce, and Nd) compounds. These reveal that CeAuAl is an antiferromagnetic compound with a Neel temperature of ~3.8 K. Its resistivity shows a shallow minimum at ~20 K and a ln(T) behavior below this temperature. These features suggest a Kondo-lattice behavior in CeAuAl. The compound LaAuAl is metallic down to 2 K while NdAuAl is a ferromagnet with a Curie temperature of ~10 K. The susceptibility of CeAuAl deviates from Curie-Weiss behavior below 70 K and this has been analyzed in terms of crystal-field effects