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The growing use of aptamers as target recognition elements in label-free biosensing necessitates corresponding transducers that can be used in relevant environments. While popular in many fields, capacitive sensors have seen relatively little, but growing use in conjunction with aptamers for sensing diverse targets. Few reports have shown physiologically relevant sensitivity in laboratory conditions and a cohesive picture on how target capture modifies the measured capacitance has been lacking. In this review, we assess the current state of the field in three areas: small molecule, protein, and cell sensing. We critically analyze the proposed hypotheses on how aptamer-target capture modifies the capacitance, as many mechanistic postulations appear to conflict between published works. As the field matures, we encourage future works to investigate individual aptamer-target interactions and to interrogate the physical mechanisms leading to measured changes in capacitance. To this point, we provide recommendations on best practices for developing aptasensors with a particular focus on considerations for biosensing in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: In Snohomish County, WA, the time from obtaining a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and initiating contact tracing is 4-6 days. We tested whether emergency department (ED)-based contact tracing reduces time to initiation and completion of contact tracing investigations., Methods: All eligible coronavirus disease 2019 (COVID-19)-positive patients were offered enrollment in this prospective case-control study. Contact tracers were present in the ED from 7 AM to 2 AM for 60 consecutive days. Tracers conducted interviews using the Washington State Department of Health's extended COVID-19 reporting form, which is also used by the Snohomish Health District (SHD)., Results: Eighty-one eligible SARS-CoV-2 positive patients were identified and 71 (88%) consented for the study. The mean time between positive COVID-19 test result and initiation of contact tracing investigation was 111 minutes with a median of 32 minutes (range: 1-1,203 minutes). The mean time from positive test result and completion of ED-based contact tracing investigation was 244 minutes with a median of 132 minutes (range: 23-1,233 minutes). In 100% of the enrolled cases, contact tracing was completed within 24 hours of a positive COVID-19 test result. For comparison, during this same period, SHD was able to complete contact tracing in 64% of positive cases within 24 hours of notification of a positive test result (P < 0.001). In the ED, each case identified a mean of 2.8 contacts as compared to 1.4 contacts identified by SHD-interviewed cases. There was no statistically significant difference between the percentage of contacts reached through ED contact tracing (82%) when compared to the usual practice (78%) (P = 0.16)., Conclusion: When contact tracing investigations occur at the point of diagnoses, the time to initiation and completion are reduced, there is higher enrollment, and more contacts are identified.

Methods for patterning neurons in vitro have gradually improved and are used to investigate questions that are difficult to address in or ex vivo . Though these techniques guide axons between groups of neurons, multiscale control of neuronal connectivity, from circuits to synapses, is yet to be achieved in vitro. As studying neuronal circuits with synaptic resolution in vivo poses significant challenges, we present an in vitro alternative to validate biophysical and computational models. In this work we use a combination of electron beam lithography and photolithography to create polydimethylsiloxane (PDMS) structures with features ranging from 150 nm to a few millimeters. Leveraging the difference between average axon and dendritic spine diameters, we restrict axon growth while allowing spines to pass through nanochannels to guide synapse formation between small groups of neurons (i.e., nodes). We show this technique can be used to generate large numbers of isolated feed-forward circuits where connections between nodes are restricted to regions connected by nanochannels. Using a genetically encoded calcium indicator in combination with fluorescently tagged postsynaptic protein, PSD-95, we demonstrate functional synapses can form in this region.

Bottom-up neuroscience, which consists of building and studying controlled networks of neurons in vitro , is a promising method to investigate information processing at the neuronal level. However, in vitro studies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with well-defined connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs), suggesting the formation of functional connections between the neurons of a circuit. Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.

Patient safety events are common in healthcare. We can learn from other safety-critical industries that further incidents are most likely to be prevented where lessons are learned at the system level rather than looking to attribute blame for errors to individuals. Progress has been made over the last 20 years and relies on a positive safety culture (or just culture) where staff trust organisations to investigate safety events for learning rather than blame. Systems-based investigation models, such as the Systems Engineering Initiative for Patient Safety (SEIPS), help investigators to consider the full range of contributory factors across a system and to identify important findings. Considering the hierarchy of controls, recommendations should be targeted at system changes which are more likely to produce sustained safety improvements, rather than at individual behaviours or training, which are less likely to influence future safety. Systems-based safety investigations can positively influence safety culture in organisations., (© Royal College of Physicians 2021. All rights reserved.)

Nanopore sensing of single nucleotides has emerged as a promising single-molecule technology for DNA sequencing and proteomics. Despite the conceptual simplicity of nanopores, adoption of this technology for practical applications has been limited by a lack of pore size adjustability and an inability to perform long-term recordings in complex solutions. Here we introduce a method for fast and precise on-demand formation of a nanopore with controllable size between 2 and 20 nm through force-controlled adjustment of the nanospace formed between the opening of a microfluidic device (made of silicon nitride) and a soft polymeric substrate. The introduced nanopore system enables stable measurements at arbitrary locations. By accurately positioning the nanopore in the proximity of single neurons and continuously recording single-molecule translations over several hours, we have demonstrated this is a powerful approach for single-cell proteomics and secretomics.

Sulfated glycosaminoglycans (sGAGs) are vital molecules of the extracellular matrix (ECM) of the nervous system known to regulate proliferation, migration, and differentiation of neurons mainly through binding relevant growth factors. Alginate sulfate (AlgSulf) mimics sGAGs and binds growth factors such as basic fibroblast growth factor (FGF-2). Here, thin films of biotinylated AlgSulf (b-AlgSulf n ) are engineered with sulfation degrees (DS = 0.0 and 2.7) and the effect of polysaccharide concentration on FGF-2 and nerve growth factor (β-NGF) binding and subsequent primary neural viability and neurite outgrowth is assessed. An increase in b-AlgSulf n concentration results in higher FGF-2 and β-NGF binding as demonstrated by greater frequency and dissipation shifts measured with quartz crystal microbalance with dissipation monitoring (QCM-D). Primary neurons seeded on the 2D b-AlgSulf n films maintain high viability comparable to positive controls grown on poly-d-lysine. Neurons grown in 3D AlgSulf hydrogels (DS = 0.8) exhibit a significantly higher viability, neurite numbers and mean branch length compared to neurons grown in nonsulfated controls. Finally, a first step is made toward constructing 3D neuronal networks by controllably patterning neurons encapsulated in AlgSulf into an alginate carrier. The substrates and neural networks developed in the current study can be used in basic and applied neural applications., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Symptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models., Design: Led by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi., Results: Consensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework., Conclusions: The Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Theoretical and in vivo neuroscience research suggests that functional information transfer within neuronal networks is influenced by circuit architecture. Due to the dynamic complexities of the brain, it remains a challenge to test the correlation between structure and function of a defined network. Engineering controlled neuronal networks in vitro offers a way to test structural motifs; however, no method has achieved small, multi-node networks with stable, unidirectional connections. Here, we screened ten different microchannel architectures within polydimethylsiloxane (PDMS) devices to test their potential for axonal guidance. The most successful design had a 92% probability of achieving strictly unidirectional connections between nodes. Networks built from this design were cultured on multielectrode arrays and recorded on days in vitro 9, 12, 15 and 18 to investigate spontaneous and evoked bursting activity. Transfer entropy between subsequent nodes showed up to 100 times more directional flow of information compared to the control. Additionally, directed networks produced a greater amount of information flow, reinforcing the importance of directional connections in the brain being critical for reliable communication. By controlling the parameters of network formation, we minimized response variability and achieved functional, directional networks. The technique provides us with a tool to probe the spatio-temporal effects of different network motifs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In an effort to increase the efficacy of topical medications for treating onychomycosis, several new nail penetration enhancers were recently developed. In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail is demonstrated by the use of a selection of in vitro nail penetration assays. These assays included the bovine hoof, TurChub zone of inhibition, and infected-nail models., (Copyright © 2017 American Society for Microbiology.)

Background and Aims: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients., Methods: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls., Results: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1)., Conclusions: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The aim of this study was to use in vitro nail models to investigate the potential of a novel base formulation (Recura) containing either fluconazole or miconazole for the treatment of onychomycosis in comparison to two commercial comparators (Jublia and a Penlac generic). Initially, a modified Franz cell was used, where sections of human nail served as the barrier through which drug penetrated into an agar-filled chamber infected with dermatophytes. A second study was performed using a novel infected nail model where dermatophytes grew into human nail and adenosine triphosphate levels were used as biological marker for antimicrobial activity. The novel enhancing system Recura increased the permeation of both existing drugs through human nail sections mounted in a modified Franz cell. Furthermore, the infected nail model also confirmed that the system also enhanced the permeation through infected nail resulting in a decrease in adenosine triphosphate levels superior (P ≤ 0.05) to Penlac generic and equivalent (P > 0.05) to the commercial comparator Jublia. This study demonstrated that with the use of a novel permeation-enhancing formulation base, Recura enhances delivery of miconazole and fluconazole when applied ungually such that the efficacy was equivalent or superior to commercial comparators. Such a topically applied system has the possibility of overcoming the systemic side effects of antifungals when taken orally.