Effects of Micromachining on Anti-oxidant Elution from a Mechanically-Adaptive Polymer.

Intracortical microelectrodes (IMEs) can be used to restore motor and sensory function as a part of brain-computer interfaces in individuals with neuromusculoskeletal disorders. However, the neuroinflammatory response to IMEs can result in their premature failure, leading to reduced therapeutic efficacy. Mechanically-adaptive, resveratrol-eluting (MARE) neural probes target two mechanisms believed to contribute to the neuroinflammatory response by reducing the mechanical mismatch between the brain tissue and device, as well as locally delivering an antioxidant therapeutic. To create the mechanically-adaptive substrate, a dispersion, casting, and evaporation method is used, followed by a microfabrication process to integrate functional recording electrodes on the material. Resveratrol release experiments were completed to generate a resveratrol release profile and demonstrated that the MARE probes are capable of long-term controlled release. Additionally, our results showed that resveratrol can be degraded by laser-micromachining, an important consideration for future device fabrication. Finally, the electrodes were shown to have a suitable impedance for single-unit neural recording and could record single units in vivo.

Flexible multifunctional titania nanotube array platform for biological interfacing.

Abstract: The current work presents a novel flexible multifunctional platform for biological interface applications. The use of titania nanotube arrays (TNAs) as a multifunctional material is explored for soft-tissue interface applications. In vitro biocompatibility of TNAs to brain-derived cells was first examined by culturing microglia cells-the resident immune cells of the central nervous system on the surface of TNAs. The release profile of an anti-inflammatory drug, dexamethasone from TNAs-on-polyimide substrates, was then evaluated under different bending modes. Flexible TNAs-on-polyimide sustained a linear release of anti-inflammatory dexamethasone up to ~11 days under different bending conditions. Finally, microfabrication processes for patterning and transferring TNA microsegments were developed to facilitate structural stability during device flexing and to expand the set of compatible polymer substrates. The techniques developed in this study can be applied to integrate TNAs or other similar nanoporous inorganic films onto various polymer substrates. Impact statement: Titania nanotube arrays (TNAs) are highly tunable and biocompatible structures that lend themselves to multifunctional implementation in implanted devices. A particularly important aspect of titania nanotubes is their ability to serve as nano-reservoirs for drugs or other therapeutic agents that slowly release after implantation. To date, TNAs have been used to promote integration with rigid, dense tissues for dental and orthopedic applications. This work aims to expand the implant applications that can benefit from TNAs by integrating them onto soft polymer substrates, thereby promoting compatibility with soft tissues. The successful direct growth and integration of TNAs on polymer substrates mark a critical step toward developing mechanically compliant implantable systems with drug delivery from nanostructured inorganic functional materials. Diffusion-driven release kinetics and the high drug-loading efficiency of TNAs offer tremendous potential for sustained drug delivery for scientific investigations, to treat injury and disease, and to promote device integration with biological tissues. This work opens new opportunities for developing novel and more effective implanted devices that can significantly improve patient outcomes and quality of life. Supplementary information: The online version contains supplementary material available at 10.1557/s43577-023-00628-y.

In Vivo Characterization of Intracortical Probes with Focused Ion Beam-Etched Nanopatterned Topographies.

(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n = 6) or smooth control (n = 6) probes, and their recording performance was evaluated over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated an increased impedance and noise floor compared to controls. However, the recording performances of the nanopatterned and smooth probes were similar, with active electrode yields for control probes and nanopatterned probes being approximately 50% and 45%, respectively, by 4 weeks post-implantation. Gene expression analysis showed one gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: this study provides a foundation for investigating novel nanoscale topographies on neural probes.

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices.

Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.

Biomechanical characterization of isolated epineurial and perineurial membranes of rabbit sciatic nerve.

Design of interface devices for effective, long-term integration into neural tissue is dependent on the biomechanical properties of the nerve membranes. Within the peripheral nerve, the two relevant connective tissue layers for interfacing are the epineurium and perineurium. Previous work has reported the forces needed to penetrate the whole nerve, but the mechanical differences between epineurium and perineurium were not reported. Design of intraneural electrodes that place electrodes within the nerve requires knowledge of the mechanics of individual tissues. This study quantified the Young's moduli and ultimate strains of the perineurium and the epineurium separately. We also measured the forces necessary to penetrate each tissue in isolation. We used a custom-built microtensile testing device to measure the Young's modulus values. The measured Young's moduli of the epineurium and the perineurium was 0.4 ± 0.1 MPa and 3.0 ± 0.3 MPa, respectively. We also measured the force required for blunt and sharp stainless steel, 100 µm diameter probes to be inserted into isolated epineurial tissue and perineurial tissue at 2 mm/s. These data provide additional guidelines for selection of materials for long-term implants that best match the tissue properties. The results will guide neural interface design such that electrodes can be placed through either the epineurium alone or both the epineurium and perineurium.

Progression of cardiac structure and function in people with human immunodeficiency virus.

OBJECTIVE: People living with HIV (PLWH) are at increased risk for cardiac dysfunction. It is unknown how their global longitudinal cardiac function, cardiac structure, and other indices of function progress over time. We aimed to characterize the longitudinal trend in cardiac structure and function in PLWH. DESIGN: Retrospective study of PLWH with clinically obtained echocardiograms at an academic medical center. METHODS: We reviewed archived transthoracic echocardiograms (TTEs) performed between 2001 and 2012 on PLWH. The primary outcome measures were progression of global longitudinal strain (GLS, left and right ventricles), LV mass, E/e' ratio, LV end-systolic, and -diastolic volumes using hierarchical mixed model analysis as a function of CD4+ T cell count and HIV RNA suppression. Models were adjusted for clinical and demographic characteristics. RESULTS: We analyzed 469 TTEs from 150 individuals (median age 46 years, 58% male). Median CD4+ T cell counts at nadir and proximal to first echocardiogram were 85 and 222 cells/mm3 , respectively. Over a median of 5 years, LV mass index increased regardless of nadir or proximal CD4+ T cell count or viral suppression status. PLWH with viral suppression at baseline had more normal GLS throughout the follow-up period. There were no significant trends in LV end-systolic volume index or E/e'. CONCLUSIONS: In PLWH, HIV viral suppression is associated with early gains in echocardiographic indices of cardiac function that persist for up to >5 years. HIV disease control impacts routine echocardiographic measures with known impacts on long-term prognosis.

Directed stimulation with interfascicular interfaces for peripheral nerve stimulation.

Objective.Computational models have shown that directional electrical contacts placed within the epineurium, between the fascicles, and not penetrating the perineurium, can achieve selectivity levels similar to point source contacts placed within the fascicle. The objective of this study is to test, in a murine model, the hypothesis that directed interfascicular contacts are selective.Approach.Multiple interfascicular electrodes with directional contacts, exposed on a single face, were implanted in the sciatic nerves of 32 rabbits. Fine-wire intramuscular wire electrodes were implanted to measure electromyographic (EMG) activity from medial and lateral gastrocnemius, soleus, and tibialis anterior muscles.Main results.The recruitment data demonstrated that directed interfascicular interfaces, which do not penetrate the perineurium, selectively activate different axon populations.Significance.Interfascicular interfaces that are inside the nerve, but do not penetrate the perineurium are an alternative to intrafascicular interfaces and may offer additional selectivity compared to extraneural approaches.

Irreversible, Self-Aligned Microfluidic Packaging for Chronic Implant Applications.

Packaging is an often overlooked component in microfluidic devices for biomedical implant applications. Robust and reliable connectors to interface microscale and macroscale features are especially critical for chronic implant applications. Existing microfluidic packaging methods are incompatible with emerging polymeric materials designed to enhance device integration with the surrounding tissue. A microfluidic connector scheme was developed to promote compatibility with novel materials and implant applications. The connectors and an adhesive wax were printed on a scaffold via additive manufacturing processes. The low-temperature packaging process entailed bonding the connector to a polymer nanocomposite-based intracortical microfluidic probe using an adhesive wax. The robustness of the packaging was assessed by measuring the tensile and shear bond strengths of the connector-adhesive wax-polymer film interface. After soak testing for 4 weeks, the bond strength continued to exceed the force required to infuse fluids through the microfluidic channel. Further, the shear bond strength exceeded typical probe insertion forces by at least 10-fold. These results support the use of the connector and thermal bonding method as a viable option for chronic implant applications.

Mechanically adaptive implants fabricated with poly(2-hydroxyethyl methacrylate)-based negative photoresists.

Neural implants that are based on mechanically adaptive polymers (MAPs) and soften upon insertion into the body have previously been demonstrated to elicit a reduced chronic tissue response than more rigid devices fabricated from silicon or metals, but their processability has been limited. Here we report a negative photoresist approach towards physiologically responsive MAPs. We exploited this framework to create cross-linked terpolymers of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate and 2-ethylhexyl methacrylate by photolithographic processes. Our systematic investigation of this platform afforded an optimized composition that exhibits a storage modulus E' of 1.8 GPa in the dry state. Upon exposure to simulated physiological conditions the material swells slightly (21% w/w) leading to a reduction of E' to 2 MPa. The large modulus change is mainly caused by plasticization, which shifts the glass transition from above to below 37 °C. Single shank probes fabricated by photolithography could readily be implanted into a brain-mimicking gel without buckling and viability studies with microglial cells show that the materials display excellent biocompatibility.

The burden of non-cardiac comorbidities and association with clinical outcomes in an acute heart failure trial - insights from ASCEND-HF.

AIMS: Non-cardiac comorbidities are highly prevalent in patients with heart failure (HF). Our objective was to define the association between non-cardiac comorbidity burden and clinical outcomes, costs of care, and length of stay within a large randomized trial of acute HF patients. METHODS AND RESULTS: Patients with complete medical history for the following comorbidities were included: diabetes mellitus, chronic obstructive pulmonary disease, chronic liver disease, history of cancer within the last 5 years, chronic renal disease (baseline serum creatinine >3.0 mg/mL), current smoking, alcohol abuse, depression, anaemia, peripheral arterial disease, and cerebrovascular disease. Patients were classified by overall burden of non-cardiac comorbidities (0, 1, 2, 3, and 4+). Hierarchical generalized linear models were used to assess associations between comorbidity burden and 30-day all-cause death or HF hospitalization and 180-day all-cause death in addition to costs of care and length of stay. A total of 6945 patients were included in the final analysis. Mean comorbidity number was 2.2 (± 1.34). Patients with 4+ comorbidities had higher rates of 30-day all-cause death/HF hospitalization as compared with patients with no comorbidities [odds ratio (OR) 3.32, 95% confidence interval (CI) 1.61-6.84; P < 0.01]. Similar results were seen with respect to 180-day death (OR 2.13, 95% CI 1.33-3.43; P < 0.01). Higher comorbidity burden was associated with higher 180-day costs of care and length of stay. CONCLUSIONS: Higher comorbidity burden is associated with poor clinical outcomes, higher costs of care, and extended length of stay. Further studies are needed to define the impact of comorbidity management programmes on outcomes for HF patients.

Implications of Abnormal Exercise Electrocardiography With Normal Stress Echocardiography.

Importance: Patients with abnormal (positive) exercise electrocardiography, but normal stress echocardiography (+ECG/-Echo) are commonly encountered in clinical practice; however, the prognostic significance of this discordant result is unclear. Objective: To determine whether patients with +ECG/-Echo have a higher rate of adverse clinical events and a poorer prognosis than patients with negative exercise ECG and normal stress Echo imaging (-ECG/-Echo). Design, Setting, and Participants: Between January 1, 2000, and February 28, 2014, a total of 47 944 consecutive patients without known coronary artery disease who underwent exercise stress Echo at Duke University Medical Center were evaluated for inclusion in this observational cohort study. Data analysis was conducted from January 1, 2000, to December 31, 2016. Interventions/Exposures: Patients were categorized as having -ECG/-Echo, +ECG/-Echo, or +Echo (-ECG/+Echo and +ECG/+Echo). Main Outcomes and Measures: The primary outcome was a composite end point of death, myocardial infarction, hospitalization for unstable angina, and coronary revascularization. Secondary outcomes included individual adverse events and downstream testing. Results: After excluding submaximal tests and nondiagnostic ECG or stress imaging results, 15 077 patients (mean [SD] age, 52 [13] years; 6228 [41.3%] men) were classified by stress test results. Of these, 12 893 patients (85.5%) had -ECG/-Echo, 1286 patients (8.5%) had +ECG/-Echo, and 898 patients (6.0%) had +Echo. Through a median follow-up of 7.3 (interquartile range, 4.4-10.0) years, the composite end point occurred in 794 patients with -ECG/-Echo (8.5%), 142 patients with +ECG/-Echo (14.6%), and 297 patients with +Echo (37.4%). Death occurred in 425 patients with -ECG/-Echo (4.8%), 50 patients with +ECG/-Echo (5.9%), and 70 patients with +Echo (11.2%). Myocardial infarction occurred in 195 patients with -ECG/-Echo (2.2%), 31 patients with +ECG/-Echo (3.6%), and 59 patients with +Echo (8.7%). The addition of stress ECG findings to clinical and exercise data yielded incremental prognostic value. Patients with -ECG/-Echo imaging results had the least downstream testing (2.3%), followed by +ECG/-Echo (12.8%), and +Echo (33.6%) (P < .001). Conclusions and Relevance: The presence of +ECG results with normal stress Echo imaging may identify a population of patients who are at slightly increased risk for adverse cardiac events, which was not previously recognized. Further study is needed to determine whether these patients will benefit from intensification of medical management.

Global Longitudinal Strain and Immune Status in Patients Living With Human Immunodeficiency Virus.

Improvement in survival in patients living with human immunodeficiency virus (PLHIV) has led to increased prevalence of cardiovascular disease. Whether HIV-associated immune dysfunction is associated with preclinical left ventricular (LV) dysfunction despite normal LV ejection fraction (LVEF) is unclear. Accordingly, we investigated the relation of immune status and LV function in PLHIV. Global longitudinal strain (GLS) analyses were performed retrospectively on all echocardiograms for PLHIV who had available HIV-1 RNA viral load, nadir, and proximal CD4 cell count data at Duke University Medical Center between 2001 and 2012. The relation between HIV-1 RNA viral load, nadir, and proximal CD4 count and GLS as a continuous dependent variable was assessed with unadjusted and adjusted linear regression. GLS was calculated for 253 PLHIV. Median GLS in our cohort was - 15.1% with interquartile range from (-16.7 to -13.6). All participants had an LVEF ≥50%. In adjusted analyses, proximal CD4 <500 cells/mm3 and nadir CD4 <250 cells/mm3 were significantly inversely correlated with GLS (p = 0.01 and p = 0.004, respectively). In PLHIV, patient with plasma HIV RNA <400 copies/ml at baseline had a trend toward significantly more negative values of GLS compared with those patients without viral suppression at baseline (p = 0.08). In conclusion, this study is the first to demonstrate such a high prevalence of abnormal GLS in PLHIV, and the first to identify that proximal and nadir CD4 cell count are independently associated with GLS despite normal LVEF.

Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score.

OBJECTIVES: This study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS). BACKGROUND: Current risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification. METHODS: A total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971). RESULTS: The mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort. CONCLUSIONS: The new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/).

Predictors and Changes in Cardiac Hemodynamics and Geometry With Transcatheter Aortic Valve Implantation.

The introduction of transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of patients with severe aortic stenosis (AS). However, despite the great clinical success of TAVI, less is known about the cardiac hemodynamics and structural changes to post-TAVI. We analyzed patients with AS who had a transthoracic echocardiography at most 6 months before index TAVI and follow-up transthoracic echocardiography 9 to 18 months later, performed at Duke University Medical Center from 2012 to 2014. A total of 152 TAVI patients with a median age of 81 years (median interquartile range 74 to 86) were included. TAVI resulted in the reduction of left ventricle (LV) mass index (g/m2), median (interquartile range) 130 (115 to 157) pre versus 106 (85 to 135) post, p <0.001; LV end-diastolic volume (ml) 127 (105 to 143) pre versus 120 (100 to 143) post, p = 0.013; and LV end-systolic volume (ml) 55 (38 to 77) pre versus 45 (40 to 65) post, p = 0.027. TAVI also significantly improved LV global longitudinal strain (%) -14.4 (-11.3, -15.5) pre versus -14.8 (-12.2, -16.6) post (p <0.001, respectively). Post-TAVI LV mass regression was predicted by baseline LV mass and LV global longitudinal strain whereas post-TAVI LV ejection fraction was predicted by baseline LV ejection fraction, LV mass, and post-TAVI paravalvular leak. In conclusion, TAVI results in significant cardiac hemodynamic, geometrical, and functional changes at approximately 1-year postprocedure for patients with AS. Better baseline myocardial structure and function leads to more reverse remodeling.

Electrically Conductive, Reduced Graphene Oxide Structures Fabricated by Inkjet Printing and Low Temperature Plasma Reduction.

Here, an environmentally-friendly and scalable process is reported to synthesize reduced graphene oxide (RGO) thin films for printed electronics applications. The films are produced by inkjet printing GO flakes dispersed binder-free in aqueous solutions followed by treatment with a nonthermal, radio-frequency (RF) plasma containing only argon (Ar) gas. The plasma process is found to heat the substrate to temperatures no greater than 138 °C, enabling RGO to be printed directly on a wide range of temperature-sensitive substrate materials including photo paper. Unlike other low-temperature methods such as electrochemical reduction, plasma reduction is friendly to moisture absorbent materials. Moreover, the plasma treatment can be performed on nonconducting substrates, eliminating the need for film transfer. From an applications perspective, the printed, plasma-reduced RGO exhibits excellent electrical, mechanical, and electrochemical properties. As a technology demonstrator, the working electrodes of hydrogen peroxide (H2O2) sensors fabricated from plasma-reduced GO show a sensitivity of 277 ± 80 µA mm-1 cm-2, which is comparable to RGO working electrodes made by electrochemical reduction.

A Mechanically-Adaptive Polymer Nanocomposite-Based Intracortical Probe and Package for Chronic Neural Recording.

Mechanical, materials, and biological causes of intracortical probe failure have hampered their utility in basic science and clinical applications. By anticipating causes of failure, we can design a system that will prevent the known causes of failure. The neural probe design was centered around a bio-inspired, mechanically-softening polymer nanocomposite. The polymer nanocomposite was functionalized with recording microelectrodes using a microfabrication process designed for chemical and thermal process compatibility. A custom package based upon a ribbon cable, printed circuit board, and a 3D-printed housing was designed to enable connection to external electronics. Probes were implanted into the primary motor cortex of Sprague-Dawley rats for 16 weeks, during which regular recording and electrochemical impedance spectroscopy measurement sessions took place. The implanted mechanically-softening probes had stable electrochemical impedance spectra across the 16 weeks and single units were recorded out to 16 weeks. The demonstration of chronic neural recording with the mechanically-softening probe suggests that probe architecture, custom package, and general design strategy are appropriate for long-term studies in rodents.

Relation of Volume Overload to Clinical Outcomes in Acute Heart Failure (From ASCEND-HF).

We aimed to study whether jugular venous distension (JVD) and peripheral edema were associated with worse outcomes in patients with acute heart failure in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure trial. Of 7,141 patients in Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure, 7,135 had complete data on baseline JVD and peripheral edema status. Patients were grouped according to baseline examination findings: (1) no JVD or peripheral edema; (2) JVD only; (3) peripheral edema only; (4) JVD and peripheral edema. We used unadjusted and adjusted logistic or Cox regression analyses to assess associations between groups and the outcomes of index length of stay (LOS), in-hospital mortality, 30- and 180-day all-cause mortality. Patients with peripheral edema (Groups 3 and 4) had higher body mass index, NT-proBNP and BNP values, and more co-morbid disease, and reduced left ventricular ejection fraction compared with patients in Groups 1-2. The median (25th-75th) LOS for Groups 1-4 was 6 (4-9), 5 (4-8), 7 (4-11), and 6 days (4-10), respectively. For the 30-day and 180-day outcomes, adjusted analyses found no significant difference in risk for patients presenting with JVD only or peripheral edema only as compared with patients without evidence of JVD or peripheral edema (p >0.05 for all). The presence of both JVD and peripheral edema was associated with an adjusted 24% increase in risk for all-cause mortality at 30 days, but no risk difference at 180 days. In conclusion, in patients with heart failure presenting to the hospital with dyspnea, the presence of peripheral edema is associated with a longer hospital LOS, but no difference in short- and long-term clinical outcomes when compared with patients wihout peripheral edema. The combination of peripheral edema and JVD identifies the highest risk cohort for poor clinical outcomes.

Nano-Architectural Approaches for Improved Intracortical Interface Technologies.

Intracortical microelectrodes (IME) are neural devices that initially were designed to function as neuroscience tools to enable researchers to understand the nervous system. Over the years, technology that aids interfacing with the nervous system has allowed the ability to treat patients with a wide range of neurological injuries and diseases. Despite the substantial success that has been demonstrated using IME in neural interface applications, these implants eventually fail due to loss of quality recording signals. Recent strategies to improve interfacing with the nervous system have been inspired by methods that mimic the native tissue. This review focusses on one strategy in particular, nano-architecture, a term we introduce that encompasses the approach of roughening the surface of the implant. Various nano-architecture approaches have been hypothesized to improve the biocompatibility of IMEs, enhance the recording quality, and increase the longevity of the implant. This review will begin by introducing IME technology and discuss the challenges facing the clinical deployment of IME technology. The biological inspiration of nano-architecture approaches will be explained as well as leading fabrication methods used to create nano-architecture and their limitations. A review of the effects of nano-architecture surfaces on neural cells will be examined, depicting the various cellular responses to these modified surfaces in both in vitro and pre-clinical models. The proposed mechanism elucidating the ability of nano-architectures to influence cellular phenotype will be considered. Finally, the frontiers of next generation nano-architecture IMEs will be identified, with perspective given on the future impact of this interfacing approach.

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort.

OBJECTIVE: The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH). METHODS AND RESULTS: We reviewed archived transthoracic echocardiograms (TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15% with diabetes). Among those with usable images, LVH was detected in 174 of 473 persons (37%) according to LV mass criteria and in 99 of 322 persons (31%) according to American Society of Echocardiography LV mass index criteria. Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH with a CD4 count ≤ 200 cells/mm3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08-2.62), CD4 nadir ≤ 200 cells/mm3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4 nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with DD. CONCLUSIONS: Persons with a history of advanced human immunodeficiency virus-associated immune suppression are at higher risk of LVH and DD than infected persons with preserved immune function.