Multidrug-resistant organisms in patients from Ukraine in the Netherlands,March to August 2022

Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-β-lactamase (NDM) genes. Professionals should be aware of an increase in such MDRO associated with migration and medical evacuation of people from Ukraine.     

Biomechanical Behavior of Narrow Dental Implants Made with Aluminum- and Vanadium-Free Alloys: A Finite Element Analysis

Titanium (Ti) alloys used for narrow dental implants usually contain aluminum (Al) and vanadium (V) for improved resistance. However, those elements are linked to possible cytotoxic effects. Thus, this study evaluated the biomechanical behavior of narrow dental implants made with Al- and V-free Ti alloys by the finite element method. A virtual model of a partially edentulous maxilla received single implants (diameter: 2.7 and 2.9 mm; length: 10 mm) at the upper lateral incisor area, with respective abutments and porcelain-fused-to-metal crowns. Simulations were performed for each implant diameter and the following eight alloys (and elastic moduli): (1) Ti–6Al–4V (control; 110 GPa), (2) Ti–35Nb–5Sn–6Mo–3Zr (85 GPa), (3) Ti–13Nb–13Zr (77 GPa), (4) Ti–15Zr (113 GPa), (5) Ti–8Fe–5Ta (120 GPa), (6) Ti–26.88Fe–4Ta (175 GPa), (7) TNTZ–2Fe–0.4O (107 GPa), and (8) TNTZ–2Fe–0.7O (109 GPa). The implants received a labially directed total static load of 100 N at a 45° angle relative to their long axis. Parameters for analysis included the maximum and minimum principal stresses for bone, and von Mises equivalent stress for implants and abutments. Ti–26.88Fe–4Ta reaches the lowest maximum (57 MPa) and minimum (125 MPa) principal stress values, whereas Ti–35Nb–5Sn–6Mo–3Zr (183 MPa) and Ti–13Nb–13Zr (191 MPa) models result in the highest principal stresses (the 2.7 mm model surpasses the threshold for bone overload). Implant diameters affect von Mises stresses more than the constituent alloys. It can be concluded that the narrow implants made of the Ti–26.88Fe–4Ta alloy have the most favorable biomechanical behavior, mostly by mitigating stress on peri-implant bone.     

In Vitro Diagnostic Assay to Detect SARS-CoV-2-Neutralizing Antibody in Patient Sera Using Engineered ACE-2 Mini-Protein

The recent development and mass administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines allowed for disease control, reducing hospitalizations and mortality. Most of these vaccines target the SARS-CoV-2 Spike (S) protein antigens, culminating with the production of neutralizing antibodies (NAbs) that disrupt the attachment of the virus to ACE2 receptors on the host cells. However, several studies demonstrated that the NAbs typically rise within a few weeks after vaccination but quickly reduce months later. Thus, multiple booster administration is recommended, leading to vaccination hesitancy in many populations. Detecting serum anti-SARS-CoV-2 NAbs can instruct patients and healthcare providers on correct booster strategies. Several in vitro diagnostics kits are available; however, their high cost impairs the mass NAbs diagnostic testing. Recently, we engineered an ACE2 mimetic that interacts with the Receptor Binding Domain (RBD) of the SARS-2 S protein. Here we present the use of this engineered mini-protein (p-deface2 mut) to develop a detection assay to measure NAbs in patient sera using a competitive ELISA assay. Serum samples from twenty-one patients were tested. Nine samples (42.8%) tested positive, and twelve (57.1%) tested negative for neutralizing sera. The data correlated with the result from the standard commercial assay that uses human ACE2 protein. This confirmed that p-deface2 mut could replace human ACE2 in ELISA assays. Using bacterially expressed p-deface2 mut protein is cost-effective and may allow mass SARS-CoV-2 NAbs detection, especially in low-income countries where economical diagnostic testing is crucial. Such information will help providers decide when a booster is required, reducing risks of reinfection and preventing the administration before it is medically necessary.     

Nanomechanical and Vibrational Signature of Chikungunya Viral Particles

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV′s ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus’ behavior upon mechanical disruptions besides its molecular composition.     

Cytokine production by human B cells: role in health and autoimmune disease

B cells are classically considered solely as antibody-producing cells driving humoral immune responses to foreign antigens in infections and vaccinations as well as self-antigens in pathological settings such as autoimmunity. However, it has now become clear that B cells can also secrete a vast array of cytokines, which influence both pro- and anti-inflammatory immune responses. Indeed, similarly to T cells, there is significant heterogeneity in cytokine-driven responses by B cells, ranging from the production of pro-inflammatory effector cytokines such as IL-6, through to the release of immunosuppressive cytokines such as IL-10. In this review, focusing on human B cells, we summarize the key findings that have revealed that cytokine-producing B cell subsets have critical functions in healthy immune responses and contribute to the pathophysiology of autoimmune diseases.     

Short-term safety and efficacy of Preserflo™ Microshunt in glaucoma patients: a multicentre retrospective cohort study

Background/aimsTo evaluate 1-year success rates and safety profile of Preserflo™ Microshunt in glaucoma patients.MethodsRetrospective multicentre cohort study of 100 consecutive eyes (91 patients) from four tertiary-referral glaucoma centres. Four intraocular pressure (IOP) criteria were defined: A: IOP ≤ 21 mmHg+IOP reduction ≥20% from baseline; B: IOP ≤ 18 mmHg+IOP reduction ≥20%; C: IOP ≤ 15 mmHg+IOP reduction ≥25%; D: IOP≤12 mmHg+IOP reduction ≥30%. Success was defined as qualified or complete based on whether reached with or without medication. Primary outcome was success according to the above criteria. Secondary outcomes included: IOP, best-corrected visual acuity (BCVA), medication use, complications, postoperative interventions, and failure-associated factors.ResultsQualified and complete success rates (95% CI) at 12 months were 74%(66–83%) and 58%(49–69%) for criterion A, 72%(63–82%) and 57%(48–68%) for B, 52%(43–63%) and 47%(38–58%) for C, 29%(21–40%) and 26%(19–36%) for D. Overall median (interquartile range (IQR)) preoperative IOP decreased from 21.5(19–28) mmHg to 13(11–16) mmHg at 12 months. BCVA was not significantly different up to 12 months (p = 0.79). Preoperative median (IQR) number of medications decreased from 3 (2–3) to 0 (0–1) at 12 months. Twelve eyes underwent needling, five surgical revision and one device removal due to corneal oedema. There were no hypotony-related complications. Non-Caucasian ethnicity was the only risk factor consistently associated with increased failure.ConclusionsPreserflo™ Microshunt is a viable surgical option in glaucoma patients, with reasonable short-term success rates, decreased medications use, excellent safety profile, smooth postoperative care, and rapid learning curve. Success rates for the most stringent IOP cutoffs were modest, indicating that it may not be the optimal surgery when very low target IOP is required.Subject terms: Outcomes research, Optic nerve diseases     

Case report. Isolation of Cladosporium cladosporioides from cerebrospinal fluid

Cladosporium cladosporioides was isolated from three subsequent cerebrospinal fluid specimens and from a brain biopsy specimen of a human patient. Susceptibility testing of the isolate was performed against seven antifungal agents.     

GM-CSF secreted by murine adenocarcinoma cells modulates tumor progression and immune activity

During tumor development, growth factors may act in autocrine manner stimulating cell proliferation, or in paracrine manner affecting the microenvironment of the tumor and modulating the immune system. Murine mammary adenocarcinoma M3 tumor bearers develop lung metastases and leukocytosis during its evolution. Previously we described that M3 conditioned media enhanced metastasis incidence, when it was inoculated in tumor-operated mice. In the present study we determine that spleen cells from M3 tumor operated mice treated with M3 conditioned media, were able to transfer the capacity to enhance metastasis to other tumor operated mice. Spleen cells have immune suppressor activity that could be reversed by cyclophosfamide treatment. M3 tumor cells secrete GM-CSF, which is able to promote in vitro proliferation of M3 cells as well as spleen cells. This proliferation could be abrogated by the addition of anti-GM-CSF. We report that the GM-CSF secreted by M3 tumor cells had stimulatory activity on M3 tumor cell and lymphocyte proliferation.