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Abstract Viral vectors and lipofection‐based gene therapies have dispersion‐dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close‐field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of “naked” plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near‐field conductivity (“conductivity‐clamping”–CC), increasing the efficiency of plasma membrane molecular translocation. This enables titratable gene delivery with unprecedently low charge transfer. The clinic‐ready bionics‐derived CC‐GET device achieved neurotrophin‐encoding miniplasmid DNA delivery to the cochlea to promote auditory nerve regeneration; validated in deafened guinea pig and cat models, leading to improved central auditory tuning with bionics‐based hearing. The performance of CC‐GET is evaluated in the brain, an organ problematic for pulsed electric field‐based plasmid DNA delivery, due to high required currents causing Joule‐heating and damaging electroporation. Here CC‐GET enables safe precision targeting of gene expression. In the guinea pig, reporter expression is enabled in physiologically critical brainstem regions, and in the striatum (globus pallidus region) delivery of a red‐shifted channelrhodopsin and a genetically‐encoded Ca2+ sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.

Abstract Purpose Non-invasive, beat-to-beat variations in physiological indices provide an opportunity for more accessible assessment of autonomic dysfunction. The potential association between the changes in these parameters and arterial stiffness in hypertension remains poorly understood. This systematic review aims to investigate the association between non-invasive indicators of autonomic function based on beat-to-beat cardiovascular signals with arterial stiffness in individuals with hypertension. Methods Four electronic databases were searched from inception to June 2022. Studies that investigated non-invasive parameters of arterial stiffness and autonomic function using beat-to-beat cardiovascular signals over a period of > 5min were included. Study quality was assessed using the STROBE criteria. Two authors screened the titles, abstracts, and full texts independently. Results Nineteen studies met the inclusion criteria. A comprehensive overview of experimental design for assessing autonomic function in terms of baroreflex sensitivity and beat-to-beat cardiovascular variabilities, as well as arterial stiffness, was presented. Alterations in non-invasive indicators of autonomic function, which included baroreflex sensitivity, beat-to-beat cardiovascular variabilities and hemodynamic changes in response to autonomic challenges, as well as arterial stiffness, were identified in individuals with hypertension. A mixed result was found in terms of the association between non-invasive quantitative autonomic indices and arterial stiffness in hypertensive individuals. Nine out of 12 studies which quantified baroreflex sensitivity revealed a significant association with arterial stiffness parameters. Three studies estimated beat-to-beat heart rate variability and only one study reported a significant relationship with arterial stiffness indices. Three out of five studies which studied beat-to-beat blood pressure variability showed a significant association with arterial structural changes. One study revealed that hemodynamic changes in response to autonomic challenges were significantly correlated with arterial stiffness parameters. Conclusions The current review demonstrated alteration in autonomic function, which encompasses both the sympathetic and parasympathetic modulation of sinus node function and vasomotor tone (derived from beat-to-beat cardiovascular signals) in hypertension, and a significant association between some of these parameters with arterial stiffness. By employing non-invasive measurements to monitor changes in autonomic function and arterial remodeling in individuals with hypertension, we would be able to enhance our ability to identify individuals at high risk of cardiovascular disease. Understanding the intricate relationships among these cardiovascular variability measures and arterial stiffness could contribute toward better individualized treatment for hypertension in the future. Systematic review registration: PROSPERO ID: CRD42022336703. Date of registration: 12/06/2022.

To achieve the accurate recognition of biomarkers or pathological characteristics within tissues or cells, in situ detection using biosensor technology offers crucial insights into the nature, stage, and progression of diseases, paving the way for enhanced precision in diagnostic approaches and treatment strategies. The implementation of needle-shaped biosensors (N-biosensors) presents a highly promising method for conducting in situ measurements of clinical biomarkers in various organs, such as in the brain or spinal cord. Previous studies have highlighted the excellent performance of different N-biosensor designs in detecting biomarkers from clinical samples in vitro. Recent preclinical in vivo studies have also shown significant progress in the clinical translation of N-biosensor technology for in situ biomarker detection, enabling highly accurate diagnoses for cancer, diabetes, and infectious diseases. This article begins with an overview of current state-of-the-art benchtop N-biosensor designs, discusses their preclinical applications for sensitive diagnoses, and concludes by exploring the challenges and potential avenues for next-generation N-biosensor technology.

Heart failure occurs when the heart cannot pump adequate blood to the body, which afflicts over 60 million people worldwide. Its treatment options include physiotherapy, medication, mechanical heart support, heart surgery, or heart transplantation. Ventricular assist devices have direct blood contact while passive ventricular constraint devices have only modest therapeutic efficacy. Current direct cardiac compression devices are either bulky, require noisy driving pneumatic sources, or are unable to mimic the natural heart motion. This study introduces a robotic cardiac compression device made of soft artificial muscle filaments that can simultaneously produce radial, axial, and torsional movements, potentially augmenting the pumping function of a failing heart. An empirical model is developed to describe the device motion and an artificial pericardium is employed to enable uniform force distribution to the heart and real‐time pressure sensing. The proposed device could deliver a stroke volume of 70 mL at 15 beats per minute, or a cardiac output of 1.05 L min−1, and achieve a peak instantaneous flow rate of 2.8 L min−1 and an output pressure of 50 mmHg. The new devices are highly customizable and experimentally validated with fresh porcine heart. They are expected to inspire future development of nonblood‐contacting cardiac assist devices.

Introduction This feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of medicine-induced harms in residential aged care.Methods and analysis Thirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents’ health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident’s medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists’ recommendations implemented at 4-week, 8-week and 12-week postbaseline period.Ethics and dissemination Ethical approval has been obtained from the University of South Australia’s Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder.Trial registration number ACTRN12623000506695.