Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical ...extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required.
Neuralink is a neurotechnology company founded by Elon Musk in 2016, which has been quietly developing revolutionary technology allowing for ultra-high precision bidirectional communication between ...external devices and the brain. In this paper, we explore the multifaceted ethical considerations surrounding neural interfaces, analyzing potential societal impacts, risks, and call for a need for responsible innovation. Despite the technological, medical, medicolegal, and ethical challenges ahead, neural interface technology remains extremely promising and has the potential to create a new era of medicine.
The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites
. Here we created a ...single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1
HOXA9
MLLT3
MECOM
HLF
SPINK2
distinguishes HSCs from progenitors throughout gestation. In addition to the aorta-gonad-mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks. A comparison of HSCs at different maturation stages revealed the establishment of HSC transcription factor machinery after the emergence of HSCs, whereas their surface phenotype evolved throughout development. The HSC transition to the liver marked a molecular shift evidenced by suppression of surface antigens reflecting nascent HSC identity, and acquisition of the HSC maturity markers CD133 (encoded by PROM1) and HLA-DR. HSC origin was tracked to ALDH1A1
KCNK17
haemogenic endothelial cells, which arose from an IL33
ALDH1A1
arterial endothelial subset termed pre-haemogenic endothelial cells. Using spatial transcriptomics and immunofluorescence, we visualized this process in ventrally located intra-aortic haematopoietic clusters. The in vivo map of human HSC ontogeny validated the generation of aorta-gonad-mesonephros-like definitive haematopoietic stem and progenitor cells from human pluripotent stem cells, and serves as a guide to improve their maturation to functional HSCs.
To determine the relationship between consecutive esotropia (ET) and passive duction force (PDF) in patients with intermittent exotropia (XT).
The study enrolled 70 patients in whom PDF was measured ...under general anesthesia prior to XT surgery. The preferred eye for fixation (PE) and the nonpreferred eye for fixation (NPE) were determined using a cover-uncover test. The patients were subdivided into two groups according to the angle of deviation at 1 month postoperation: (1) consecutive ET (CET group), >10 prism diopters (PD) of ET; and (2) non-CET (NCET group), ≤10 ET or residual exodeviation. The relative PDF of the medial rectus muscle (MRM) was obtained by subtracting the ipsilateral PDF of the lateral rectus muscle (LRM) from the PDF of the MRM.
The PDFs for the LRM in the PE in the CET and NCET groups were 47.28 g and 58.59 g, respectively (p = 0.147), and 56.18 g and 46.59 g for the MRM (p = 0.11), and in the NPE were 59.84 g and 55.25 g, respectively, for the LRM (p = 0.993), and 49.12 g and 50.53 g, respectively, for the MRM (p = 0.81). However, in the PE, the PDF in the MRM was larger in the CET group than in the NCET group (p = 0.045), which was positively associated with the postoperatively overcorrected angle of deviation (p = 0.017).
An increased relative PDF in the MRM in the PE was a risk factor for consecutive ET after XT surgery. Quantitative evaluation of the PDF could be considered when planning strabismus surgery to achieve the desired surgical outcome.
Biosensors based on the localized surface plasmon resonance (LSPR) of individual metallic nanoparticles promise to deliver modular, low-cost sensing with high-detection thresholds. However, they ...continue to suffer from relatively low sensitivity and figures of merit (FOMs). Herein we introduce the idea of sensitivity enhancement of LSPR sensors through engineering of the material dispersion function. Employing dispersion and shape engineering of chiral nanoparticles leads to remarkable refractive index sensitivities (1,091 nm RIU(-1) at λ=921 nm) and FOMs (>2,800 RIU(-1)). A key feature is that the polarization-dependent extinction of the nanoparticles is now characterized by rich spectral features, including bipolar peaks and nulls, suitable for tracking refractive index changes. This sensing modality offers strong optical contrast even in the presence of highly absorbing media, an important consideration for use in complex biological media with limited transmission. The technique is sensitive to surface-specific binding events which we demonstrate through biotin-avidin surface coupling.
Three main research groups, on 3 continents, have so far reported their initial results regarding gene therapy for the treatment of Leber's hereditary optic neuropathy (LHON),1-3 which is the first ...described and the most common condition associated with mitochondrial mutations.4 In this issue of the Journal, Lam et al report the results of a Phase 1, single-institution, open-label clinical trial, aiming to assess the dose-dependent safety and efficacy of unilateral intravitreal injection of low, medium, high, or higher dose of AAV2 (Y444,500,730F)-P1ND4v2) in 28 patients with G11778A LHON.1 Patients were divided into 3 groups: chronic bilateral (onset of visual loss of ≥12 months in 1 eye and ≥6 months in the more recently affected eye); acute bilateral (visual loss in both eyes of ≤12 months); and acute unilateral (with only mildly impaired vision in the fellow eye). According to the prespecified criterion of visual acuity change from baseline (best-correct visual acuity change of 15 letters or more on the Early Treatment Diabetic Retinopathy Study ETDRS chart), some patients improved their vision across the 3 groups, that is, not only in the study eye or the fellow eye of the gene therapy participants, but also in eyes of the natural history patients.5 There was no apparent relationship between the injected dose and visual acuity improvement. The low number of included patients provided limited power to robustly evaluate the efficacy of this gene therapy on visual function; as the authors state, “if there is an efficacy effect, it is likely small and not related to the investigational product dose.”
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