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The BONEBRIDGE is a partially implantable, transcutaneous bone conduction device that can be used to treat conductive or mixed mild-to-moderate hearing loss in patients who do not attain sufficient improvement from conventional hearing aids. The following case report describes sequential bilateral BONEBRIDGE implantation in a 25-year-old patient with achondroplasia and bilateral mixed-hearing loss with a significant sensorineural component in the setting of chronic suppurative otitis media. Although the patient did not meet the approved BONEBRIDGE criteria, implantation was successful with improvements in audiological outcomes and self-reported quality of life. There were no reported complications at 5-years post-implantation.

Karol P Steckiewicz,1 Piotr Cieciórski,2 Ewelina Barcińska,1 Maciej Jaśkiewicz,3 Magdalena Narajczyk,4 Marta Bauer,3 Wojciech Kamysz,3 Elżbieta Megiel,2 Iwona Inkielewicz-Stepniak1 1Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland; 2Faculty of Chemistry, University of Warsaw, Warsaw, Poland; 3Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland; 4Laboratory of Electron Microscopy, Faculty of Biology, University of Gdansk, Gdansk, PolandCorrespondence: Iwona Inkielewicz-Stepniak Tel +48 58 349 1516Fax +48 58 349 1517Email iinkiel@gumed.edu.plPurpose: Periodontal disease (PD), defined as oral inflammation caused by dental plaque, is an emerging problem. PD may lead to tooth loss, and treatment options are limited. In this study, we designed, synthesized, and characterized silver nanoparticles (AgNPs) conjugated with chlorhexidine (AgNPs-CHL) or metronidazole (AgNPs-PEG-MET) to determine whether they can be used to treat PDs.Materials and Methods: AgNPs were synthesized and characterized by transmission electron microscopy, UV-vis spectrometry, thermogravimetric analyses, and dynamic light scattering. We determined the safety and the antimicrobial and anti-inflammatory properties of synthesized AgNPs in an in vitro model of periodontitis. Antimicrobial properties were determined by measuring the minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) on reference strains of bacteria and fungi. Human gingival fibroblast (HGF-1), murine macrophage (RAW264.7) and human foetal osteoblast (hFOB1.19) cells were used in the study. Lipopolysaccharide (LPS) was used to induce inflammation. Cytokine levels were measured using an enzyme-linked immunosorbent assay; metalloproteinase expression was measured using Western blotting.Results: The synthesized AgNPs were spherical and narrow-dispersed with an average diameter of 13.4 nm ±  3.0 nm in the case of AgNPs-CHL and 3.72 nm ±  0.72 nm in the case of AgNPs-PEG-MET. Both types of AgNPs were active against bacteria and fungi. AgNPs-CHL proved to be a more potent antimicrobial agent, although they were more cytotoxic than AgNPs-PEG-MET; however, both demonstrated beneficial properties in nontoxic concentrations. AgNPs-CHL and AgNPs-PEG-MET decreased the production of proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. Both agents also decreased the levels of metalloproteinases MMP3 and MMP8, which may indicate that they will inhibit tissue degradation.Conclusion: AgNPs-CHL and AgNPs-PEG-MET may be possible therapeutic options for PD, as they have antibacterial and anti-inflammatory properties. However, to fully understand the potential of AgNPs, our in vitro findings must be evaluated in an in vivo model.Keywords: drug delivery platforms, gingival fibroblast, macrophages, osteoblasts, periodontal disease, periodontitis

An in-depth study of the second order Volterra kernel of light emitting diodes (LEDs) is provided, with a special focus on compensation of dynamic nonlinear distortion generated by the LED when used as a communications signal transmitter. It is shown that from the factorization of the kernel in the frequency domain follows a simplified time-domain model for LED nonlinearity, consisting of three operations: two linear filtrations and squaring. Next, using the p th inverse theory, the corresponding block structures of nonlinear pre- and postdistorters are derived. As it turns out, they exhibit linear computational complexity. It is shown that the model coefficients defining the kernel may be estimated up to the Nyquist frequency. Numerical results indicate that pre- and postdistortion achieve the same performance with respect to receiver signal to noise power ratio (SNR) and have a considerable advantage over linear equalizers. However, in a practical scenario, the predistortion increases the peak to average power ratio of the transmitted signal (unless it is not high already), possibly leading to performance inferior to postdistortion. Finally, it is shown that the simplified equalizer based on the LED model has roughly identical performance to the regular, quadratic Volterra equalizer.

Background and purpose: Peptides constitute an interesting starting point for drugs, although research on them is quite slowed by the fact that most of them are non-patentable. Given that carnosine, β-Ala-His dipeptide, was found useful in cancer treatment, we aimed to inspect whether its similar structures could also possess such activity. Experimental Approach: The interdisciplinary approach allows for the much more detailed analysis, hence our study presents computational analysis of potential targets and therapeutic activities of dipeptides with β-Ala or His at the N-end, synthesis and in vitro cytotoxicity and apoptosis tests against a chosen cancerous and non-cancerous cell line. Key Results: We preliminarily propose β-Ala-Ala, His-Val and His-Arg as most potent entities, in regard to carnosine, a known anticancer peptide. Conclusion and Implications: An interdisciplinary approach allows for a much more complex analysis and in silico tests should be a standard element of every toxicological report and we hope to popularize that concept worldwide. Peptides indeed possess activity against cancer, with little to no harm to non-cancerous cells, which is highly valuable.

The continuous development of low-cost Global Navigation Satellite Systems (GNSS) chipsets and advances in processing algorithms that address the limitations of such hardware enable the exploitation of this equipment in new fields of engineering and science. In this study, we verify whether recent low-cost antennas and receivers may be employed in precise geodetic applications, such as deformation monitoring at a local scale. We focus on the actual positioning performance and examine if the low-cost equipment may reach an accuracy level close to that of a high-grade one. The results reveal that with the optimal GNSS data processing strategy and state-of-the-art scientific software, the latest low-cost equipment might be considered a mature complement to high-grade receivers in engineering applications.The second goal of this research is to analyze the potential usability of low-cost GNSS receivers for weather monitoring. Multi-GNSS data from low-cost receivers are processed in Precise Point Positioning mode with ambiguity resolution to retrieve tropospheric estimates. Zenith tropospheric delays, integrated water vapor, and horizontal gradients restored from GNSS data of mass-market receivers are validated against those of the high-grade receivers and the fifth-generation reanalysis for the global climate and weather – ERA5 and regional CERRA reanalysis. A strong correspondence between GNSS-derived tropospheric parameters and these of the reanalysis is proved., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

We develop a method for dynamic displacement retrieval by combining asynchronous high-rate GNSS and accelerometer data and smoothing with the Rauch Tung Striebel (RTS) algorithm. It adopts relative GNSS positioning with observations of different sampling rates at rover and reference stations. We analyze the feasibility of downsampling GNSS data at reference stations and thus verify whether existing permanent GNSS networks collecting low-rate observations can serve as reference sites. The performance is assessed using a shake table for inducing displacement waveforms. We show that the combined solution enhances the displacement accuracy by half compared to the GNSS-only one. Further accuracy improvement is obtained by applying the RTS smoother. Consequently, it is reasonable to downsample high-rate GNSS data at the reference station even to a 2 s interval and preserve the displacement error below 1 mm. The results also highlight the impact of the satellite orbit and clock error on the performance of asynchronous GNSS data processing. Fortunately, a fusion of GNSS with accelerometer and RTS smoothing helps to mitigate the ephemeris error. With the assessment in the time-frequency domain, we show that the combined solution better recovers displacement waveforms than GNSS-only. For the former solution, the detected peak frequencies agree very well with those of the Linear Variable Differential Transformer, and the amplitude error does not exceed 0.5 mm. We conclude that the proposed approach based on asynchronous GNSS observations provides millimeter-level precision results and is better for reconciling dynamic displacements than a GNSS-only solution or simply by integrating accelerometer data., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

In this work, we demonstrated a convenient and reliable method to realize the vertical stack integration of the blue and yellow InGaN micro-LED arrays. The standard white and color-tunable micro-light sources can be achieved by adjusting the current densities injection of the micro-LEDs. The spectra cover violet, standard white, cyan, etc., showing an excellent color-tunable property. And the mixed standard white light can be separated into red-green-blue three primary colors through the color filters to realize full-color micro-LED display with a color gamut of 75% NTSC. Besides, the communication capability of the integrated micro-LED arrays as visible light communication (VLC) transmitters is demonstrated with a maximum total data rate of 2.35 Gbps in the wavelength division multiplexing (WDM) experimental set-up using orthogonal frequency division multiplexing modulation. In addition, a data rate of 250 Mbps is also realized with the standard white light using on-off keying (OOK) modulation. This integrated device shows great potential in full-color micro-LED display, color-tunable micro-light sources, and high-speed WDM VLC multifunctional applications.

Steckiewicz KP, Cieciórski P, Barcińska E, et al. Int J Nanomedicine. 2022;17:495–517. Our authors have advised that the funding source number listed in the Acknowledgment section on page 513 was incorrect. The sentence should read from “This work was supported by PRELUDIUM grant 2017/27/N/NZ7/0267 from the Polish National Science Centre…” to “This work was supported by PRELUDIUM grant 2017/27/N/NZ7/02675 from the Polish National Science Centre…” The authors apologize for this oversight.

Background: Cancer, along with cardiovascular diseases, is globally defined as the leading cause of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelet aggregation is observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs for these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized, and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumor-associated angiogenesis. Results: The results of the analysis of data based on drugs with nanoparticles confirm their improved pharmaceutical and biological properties, which give promising antiplatelet, anticoagulant, and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a limited expansion of CGG repeats in the FMR1 gene. Degeneration of neurons in FXTAS cell models can be triggered by accumulation of polyglycine protein (FMRpolyG), a by-product of translation initiated upstream to the repeats. Specific aims of our work included testing if naphthyridine-based molecules could (i) block FMRpolyG synthesis by binding to CGG repeats in RNA, (ii) reverse pathological alterations in affected cells and (iii) preserve the content of FMRP, translated from the same FMR1 mRNA. We demonstrate that cyclic mismatch binding ligand CMBL4c binds to RNA structure formed by CGG repeats and attenuates translation of FMRpolyG and formation of nuclear inclusions in cells transfected with vectors expressing RNA with expanded CGG repeats. Moreover, our results indicate that CMBL4c delivery can reduce FMRpolyG-mediated cytotoxicity and apoptosis. Importantly, its therapeutic potential is also observed once the inclusions are already formed. We also show that CMBL4c-driven FMRpolyG loss is accompanied by partial FMRP reduction. As complete loss of FMRP induces FXS in children, future experiments should aim at evaluation of CMBL4c therapeutic intervention in differentiated tissues, in which FMRpolyG translation inhibition might outweigh adverse effects related to FMRP depletion.

The aim of this work is to review tacrine analogues from the last three years, which were not included in the latest review work, donepezil and galantamine hybrids from 2015 and rivastigmine derivatives from 2014. In this account, we summarize the efforts toward the development and characterization of non-toxic inhibitors of cholinesterases based on mentioned drugs with various interesting additional properties such as antioxidant, decreasing β-amyloid plaque aggregation, nitric oxide production, pro-inflammatory cytokines release, monoamine oxidase-B activity, cytotoxicity and oxidative stress in vitro and in animal model that classify these hybrids as potential multifunctional therapeutic agents for Alzheimer’s disease. Moreover, herein, we have described the cholinergic hypothesis, mechanisms of neurodegeneration and current pharmacotherapy of Alzheimer’s disease based on the restoration of cholinergic function through blocking enzymes that break down acetylcholine.

Muscular dystrophy is a group of heterogeneous diseases that cause progressive muscle weakness and atrophy. Many types of muscular dystrophy is distinguished involving Duchenne/Becker, myotonic, limb-girdle, congenital, or facioscapulohumeral muscular dystrophies. Different molecular techniques, including next-generation sequencing (NGS) were performed to identify the genetic cause of Polish patient with limb–girdle muscle weakness and atrophy. Homozygous pathogenic mutation c.550delA, (p.Thr184ArgfsTer36) in the CAPN3 gene as well as a heterozygous expansion of a CCTG repeat of the CNBP gene in this patient had been identified. Segregation analysis showed both maternal and paternal heterozygous carriers for CAPN3 mutation, and a maternally inherited CNBP expansion. Here, we report on the first patient who carried both a homozygous mutation in the CAPN3 and CCTG expansion in the CNBP gene, suggesting the co-occurrence of recessive limb-girdle muscular dystrophy 1 and myotonic dystrophy 2 (DM2) in a single patient. In general, this phenomenon is considered as uncommon, although is possible and, therefore, should be taken into consideration in those populations with a relatively high prevalence of DM2.