A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water

AbstractGlcNAc2 is the core disaccharide fragment present in N‐glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N‐glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc2 by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl‐β‐glycoside of GlcNAc2 in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers‐shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono‐ and disaccharides. Molecular modelling calculations supported by NOE data provided a three‐dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor

Doping of inorganic materials in microreactors – preparation of Zn doped Fe₃O₄ nanoparticles

Microreactor systems are now used more and more for the continuous production of metal nanoparticles and metal oxide nanoparticles owing to the controllability of the particle size, an important property in many applications. Here, for the first time, we used microreactors to prepare metal oxide nanoparticles with controlled and varying metal stoichiometry. We prepared and characterised Zn-substituted Fe₃O₄ nanoparticles with linear increase of Zn content (ZnxFe₃−xO₄ with 0 ≤ x ≤ 0.48), which causes linear increases in properties such as the saturation magnetization, relative to pure Fe₃O₄. The methodology is simple and low cost and has great potential to be adapted to the targeted doping of a vast array of other inorganic materials, allowing greater control on the chemical stoichiometry for nanoparticles prepared in microreactors

Surgical treatment of symptomatic degenerative lumbar spondylolisthesis by decompression and instrumented fusion

Degenerative spondylolisthesis is characterized by the slippage of one vertebral body over the one below, with association of intervertebral disc degeneration and degenerative arthritis of the facet joints, which cause spinal stenosis. The aim of this study was to evaluate the clinical and radiographic results of 22 patients with symptomatic degenerative spondylolisthesis, operated on by decompressive laminectomy and instrumented posterolateral fusion associated with interbody fusion (PLIF). Mean age at surgery was 64 years (range, 57\u201372). Clinical results were evaluated on a questionnaire at the last follow-up visit concerning postoperative low back and leg pain, restriction of daily life activities, and resumption of sports activity. Lumbar spine radiographs were used to evaluate the status of fixation devices, the reduction of the spondylolisthesis, the lumbar sagittal balance and the presence of spinal fusion. No intraoperative or postoperative complications were encountered. There were no superficial or deep infections, fixation device loosening, or hardware removal. Mean follow-up time was 4 years (range, 3\u20136 years). Clinical outcome was excellent or good in 19 patients and fair in 3 patients. Preoperatively, mean forward vertebral slipping on neutral lateral radiographs was 5 mm, while postoperatively it decreased to 3 mm. Preoperatively, mean sagittal motion was 3 mm and angular motion was 8\ub0, while postoperatively these values decreased to 1 mm and 1\ub0, respectively. This study demonstrated that spinal decompression followed by transpedicular instrumentation associated with PLIF technique is a valid surgical option for the treatment of degenerative spondylolisthesis with symptomatic spinal stenosis. Clinical outcome, intended as relief of pain and resumption of activity, was improved significantly and fusion rate was high

Alternative Chelator for 89Zr Radiopharmaceuticals: Radiolabeling and Evaluation of 3,4,3-(LI-1,2-HOPO)

Zirconium-89 is an effective radionuclide for antibody-based positron emission tomography (PET) imaging because its physical half-life (78.41 h) matches the biological half-life of IgG antibodies. Desferrioxamine (DFO) is currently the preferred chelator for 89Zr4+; however, accumulation of 89Zr in the bones of mice suggests that 89Zr4+ is released from DFO in vivo. An improved chelator for 89Zr4+ could eliminate the release of osteophilic 89Zr4+ and lead to a safer PET tracer with reduced background radiation dose. Herein, we present an octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO) as a potentially superior alternative to DFO. The HOPO ligand formed a 1:1 Zr-HOPO complex that was evaluated experimentally and theoretically. The stability of 89Zr-HOPO matched or surpassed that of 89Zr-DFO in every experiment. In healthy mice, 89Zr-HOPO cleared the body rapidly with no signs of demetalation. Ultimately, HOPO has the potential to replace DFO as the chelator of choice for 89Zr-based PET imaging agents

The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18Rα (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons

Large Direct Repeats Flank Genomic Rearrangements between a New Clinical Isolate of Francisella tularensis subsp. tularensis A1 and Schu S4

Francisella tularensis subspecies tularensis consists of two separate populations A1 and A2. This report describes the complete genome sequence of NE061598, an F. tularensis subspecies tularensis A1 isolated in 1998 from a human with clinical disease in Nebraska, United States of America. The genome sequence was compared to Schu S4, an F. tularensis subspecies tularensis A1a strain originally isolated in Ohio in 1941. It was determined that there were 25 nucleotide polymorphisms (22 SNPs and 3 indels) between Schu S4 and NE061598; two of these polymorphisms were in potential virulence loci. Pulsed-field gel electrophoresis analysis demonstrated that NE061598 was an A1a genotype. Other differences included repeat sequences (n = 11 separate loci), four of which were contained in coding sequences, and an inversion and rearrangement probably mediated by insertion sequences and the previously identified direct repeats I, II, and III. Five new variable-number tandem repeats were identified; three of these five were unique in NE061598 compared to Schu S4. Importantly, there was no gene loss or gain identified between NE061598 and Schu S4. Interpretation of these data suggests there is significant sequence conservation and chromosomal synteny within the A1 population. Further studies are needed to determine the biological properties driving the selective pressure that maintains the chromosomal structure of this monomorphic pathogen

Active debris multi-removal mission concept based on hybrid propulsion

During the last 40 years, the mass of the artificial objects in orbit increased quite steadily at the rate of about 145 metric tons annually, leading to about 7000 metric tons. Most of the cross-sectional area and mass (97% in low Earth orbit) is concentrated in about 4500 intact abandoned objects plus a further 1000 operational spacecraft. Analyses have shown that the most effective mitigation strategy should focus on the disposal of objects with larger cross-sectional area and mass from densely populated orbits. Recent NASA results have shown that the worldwide adoption of mitigation measures in conjunction with active yearly removal of approximately 0.2–0.5% of the abandoned objects would stabilize the debris population. Targets would have typical masses between 500 and 1000 kg in the case of spacecraft, and of more than 1000 kg for rocket upper stages. In the case of Cosmos-3M second stages, more than one object is located nearly in the same orbital plane. This provides the opportunity of multi-removal missions, more suitable for yearly removal rate and cost reduction needs. This paper deals with the feasibility study of a mission for the active removal of large abandoned objects in low Earth orbit. In particular, a mission is studied in which the removal of two Cosmos-3M second stages, that are numerous in low Earth orbit, is considered. The removal system relies on a Chaser spacecraft which performs rendezvous maneuvers with the two targets. The first Cosmos-3M stage is captured and an autonomous de-orbiting kit, carried by the Chaser, is attached to it. The de-orbiting kit includes a Hybrid Propulsion Module, which is remotely ignited to perform stage disposal and controlled reentry after Chaser separation. Then, the second Cosmos-3M stage is captured and, in this case, the primary propulsion system of the Chaser is used for the disposal of the mated configuration. Critical mission aspects and related technologies are investigated at a preliminary level. In particular, an innovative electro-adhesive system for target capture, a mechanical system for the hard docking with the target and a hybrid propulsion system suitable for rendezvous, de-orbiting and controlled reentry operations are analyzed. This is performed on the basis of a preliminary mission profile, in which suitable rendezvous and disposal strategies have been considered and investigated by numerical analysis. A preliminary system mass budget is also performed, showing that the Chaser overall mass is about 1350 kg, including a primary propulsion system of about 300 kg and a de-orbiting kit with a mass of about 200 kg. This system is suitable to be launched with VEGA, actually the cheapest European space launcher

Economic analysis of remote monitoring in patients with implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators in the Trento area, Italy

Introduction: Remote monitoring (RM) technologies have the potential to improve patient care by increasing compliance, providing early indications of heart failure (HF), and potentially allowing for therapy optimization to prevent HF admissions. The aim of this retrospective study was to assess the clinical and economic consequences of RM vs. standard monitoring (SM) through in-office cardiology visits, in patients carrying a cardiac implantable electronic device (CIED). Methods: Clinical and resource consumption data were extracted from the Electrophysiology Registry of the Trento Cardiology Unit, which has been systemically collecting patient information from January 2011 to February 2022. From a clinical standpoint, survival analysis was conducted, and incidence of cardiovascular (CV) related hospitalizations was measured. From an economic standpoint, direct costs of RM and SM were collected to compare the cost per treated patient over a 2-year time horizon. Propensity score matching (PSM) was used to reduce the effect of confounding biases and the unbalance of patient characteristics at baseline. Results: In the enrollment period, N = 402 CIED patients met the inclusion criteria and were included in the analysis (N = 189 patients followed through SM; N = 213 patients followed through RM). After PSM, comparison was limited to N = 191 patients in each arm. After 2-years follow-up since CIED implantation, mortality rate for any cause was 1.6% in the RM group and 19.9% in the SM group (log-rank test, p < 0.0001). Also, a lower proportion of patients in the RM group (25.1%) were hospitalized for CV-related reasons, compared to the SM group (51.3%; p < 0.0001, two-sample test for proportions). Overall, the implementation of the RM program in the Trento territory was cost-saving in both payer and hospital perspectives. The investment required to fund RM (a fee for service in the payer perspective, and staffing costs for hospitals), was more than offset by the lower rate of hospitalizations for CV-related disease. RM adoption generated savings of −€4,771 and −€6,752 per patient in 2 years, in the payer and hospital perspective, respectively. Conclusion: RM of patients carrying CIED improves short-term (2-years) morbidity and mortality risks, compared to SM and reduces direct management costs for both hospitals and healthcare services