Surface-Grafted Biocompatible Polymer Conductors for Stable and Compliant Electrodes for Brain Interfaces.

Durable and conductive interfaces that enable chronic and high-resolution recording of neural activity are essential for understanding and treating neurodegenerative disorders. These chronic implants require long-term stability and small contact areas. Consequently, they are often coated with a blend of conductive polymers and are crosslinked to enhance durability despite the potentially deleterious effect of crosslinking on the mechanical and electrical properties. Here the grafting of the poly(3,4 ethylenedioxythiophene) scaffold, poly(styrenesulfonate)-b-poly(poly(ethylene glycol) methyl ether methacrylate block copolymer brush to gold, in a controlled and tunable manner, by surface-initiated atom-transfer radical polymerization (SI-ATRP) is described. This "block-brush" provides high volumetric capacitance (120 F cm─3), strong adhesion to the metal (4 h ultrasonication), improved surface hydrophilicity, and stability against 10 000 charge-discharge voltage sweeps on a multiarray neural electrode. In addition, the block-brush film showed 33% improved stability against current pulsing. This approach can open numerous avenues for exploring specialized polymer brushes for bioelectronics research and application.

Molecular dynamics investigation of the influenza hemagglutinin conformational changes in acidic pH.

The surface protein hemagglutinin (HA) of the influenza virus plays a pivotal role in facilitating viral infection by binding to sialic acid receptors on host cells. Its conformational state is pH-sensitive, impacting its receptor-binding ability and evasion of the host immune response. In this study, we conducted extensive equilibrium microsecond-level all-atom molecular dynamics (MD) simulations of the HA protein to explore the influence of low pH on its conformational dynamics. Specifically, we investigated the impact of protonation on conserved histidine residues (His106 2 ) located in the hinge region of HA2. Our analysis encompassed comparisons between non-protonated (NP), partially protonated (1P, 2P), and fully-protonated (3P) conditions. Our findings reveal substantial pH-dependent conformational alterations in the HA protein, affecting its receptor-binding capability and immune evasion potential. Notably, the non-protonated form exhibits greater stability compared to protonated states. Conformational shifts in the central helices of HA2 involve outward movement, counterclockwise rotation of protonated helices, and fusion peptide release in protonated systems. Disruption of hydrogen bonds between the fusion peptide and central helices of HA2 drives this release. Moreover, HA1 separation is more likely in the fully-protonated system (3P) compared to non-protonated systems (NP), underscoring the influence of protonation. These insights shed light on influenza virus infection mechanisms and may inform the development of novel antiviral drugs targeting HA protein and pH-responsive drug delivery systems for influenza.

Systematic Review of Utilized Ports in Laparoscopic Cholecystectomy: Pushing the Boundaries.

Introduction: Surgical procedures have undergone a paradigm shift in the last 3 decades, with minimally invasive surgery becoming standard of care for a number of surgeries, including the treatment of benign gallbladder diseases. By providing a thorough and impartial summary of the earlier published systematic reviews, the current systematic review is the first to present comparison results. This review illustrates the data of intraoperative and postoperative results of each laparoscopic cholecystectomy technique. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was meticulously followed to conduct the present systematic review. MEDLINE (via PubMed), Cochrane Database of Systematic Reviews, and Web of Science were searched for eligible publications, and a total of 14 systematic reviews were included. A newly developed extraction table was utilized to obtain the predefined parameters from eligible systematic reviews, including operative time, conversion rate, estimated blood loss, bile leak, length of hospital stay, postoperative pain, and cosmetic results. All statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS) software, version 26.0. The analysis of dichotomous results was summarized using relative risks and 95% confidence intervals (95% CI), and continuous results were summarized using mean differences and 95% CIs. The proportions were compared using a single proportion z-test. Results: The analysis of our primary and secondary outcomes revealed a statistically significant improvement in aesthetic results after single-incision laparoscopic cholecystectomy (SILC) in comparison to the multiport approach of laparoscopic cholecystectomy. This, however, is accompanied by extended operative timing and subsequently, prolonged exposure to anesthesia. Conclusion: Patients should be carefully selected for SILC to minimize technical difficulties and prevent complications both intraoperatively and shortly after the procedure. This trial is registered with CRD42023392037.

Conductive block copolymer elastomers and psychophysical thresholding for accurate haptic effects.

Electrotactile stimulus is a form of sensory substitution in which an electrical signal is perceived as a mechanical sensation. The electrotactile effect could, in principle, recapitulate a range of tactile experience by selective activation of nerve endings. However, the method has been plagued by inconsistency, galvanic reactions, pain and desensitization, and unwanted stimulation of nontactile nerves. Here, we describe how a soft conductive block copolymer, a stretchable layout, and concentric electrodes, along with psychophysical thresholding, can circumvent these shortcomings. These purpose-designed materials, device layouts, and calibration techniques make it possible to generate accurate and reproducible sensations across a cohort of 10 human participants and to do so at ultralow currents (≥6 microamperes) without pain or desensitization. This material, form factor, and psychophysical approach could be useful for haptic devices and as a tool for activation of the peripheral nervous system.

Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease.

Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with 68Ga-NOTA-GZP (where GZP is ß-Ala-Gly-Gly-Ile-Glu-Phe-Asp-CHO) to detect early intestinal inflammation in murine models of colitis. Methods: Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10-/- mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti-tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with 68Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. Results: Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD (P = 0.032).68Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10-/- mice with DSS-induced colitis compared with vehicle-treated IL-10-/- mice (SUVmean, 0.75 vs. 0.24; P < 0.001) and both vehicle- and DSS-treated wild-type mice (SUVmean, 0.26 and 0.37; P < 0.001). In the IL-10-/- DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor-α (SUVmean, 0.32; P < 0.001). There was a 4-fold increase in colonic uptake of 68Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUVmean, 0.23 vs. 0.08; P = 0.001). Conclusion: GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings.

Allysine-Targeted Molecular MRI Enables Early Prediction of Chemotherapy Response in Pancreatic Cancer.

Neoadjuvant therapy (NAT) is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis allysine residues are formed on collagen proteins by the action of lysyl oxidases (LOX). Here we report the application of an allysine-targeted molecular magnetic resonance imaging (MRI) probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of NAT with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, while no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes.

P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Cholesterol Dependence of the Conformational Changes in Metabotropic Glutamate Receptor 1.

Metabotropic glutamate receptors (mGluRs) are class C G protein-coupled receptors that function as obligate dimers in regulating neurotransmission and synaptic plasticity in the central nervous system. The mGluR1 subtype has been shown to be modulated by the membrane lipid environment, particularly cholesterol, though the molecular mechanisms remain elusive. In this study, we employed all-atom molecular dynamics simulations to investigate the effects of cholesterol on the conformational dynamics of the mGluR1 seven-transmembrane (7TM) domain in an inactive state model. Simulations were performed with three different cholesterol concentrations (0%, 10%, and 25%) in a palmitoyl-oleoyl phosphatidylcholine (POPC) lipid bilayer system. Our results demonstrate that cholesterol induces conformational changes in the mGluR1 dimer more significantly than in the individual protomers. Notably, cholesterol modulates the dynamics and conformations of the TM1 and TM2 helices at the dimer interface. Interestingly, an intermediate cholesterol concentration of 10% elicits more pronounced conformational changes compared to both cholesterol-depleted (0%) and cholesterol-enriched (25%) systems. Specific electrostatic interaction unique to the 10% cholesterol system further corroborate these conformational differences. Given the high sequence conservation of the 7TM domains across mGluR subtypes, the cholesterol-dependent effects observed in mGluR1 are likely applicable to other members of this receptor family. Our findings provide atomistic insights into how cholesterol modulates the conformational landscape of mGluRs, which could impact their function and signaling mechanisms.

Lipid-dependent conformational dynamics of bacterial ATP-binding cassette transporter Sav1866.

Sav1866, a bacterial ATP-binding cassette (ABC) exporter, plays a crucial role in cellular processes by facilitating the efflux of a diverse range of substrates, including drugs, chemotherapeutic agents, peptides, and lipids. This efflux activity significantly impacts the effectiveness of various therapies against bacterial infections. In our recent investigation, we focused on understanding the conformational dynamics of Sav1866 within different lipid environments. Specifically, we explored its behavior in environments composed of DMPC and POPE lipids, which exhibit crucial distinctions not only in their headgroup polarity but also in the length and saturation of their hydrophobic tails. Our extensive set of equilibrium microsecond-level all-atom molecular dynamics (MD) simulations revealed significant distinctions in transporter behavior influenced by these lipid compositions. We observed a rapid transition to an occluded-inward-facing (IF-occ) conformation in POPE environments, contrasting with a channel-like behavior in DMPC environments, deviating from the expected alternating access mechanism (AAM). These findings underscore the significant impact of lipid compositions on ABC transporter function, offering new perspectives on membrane transport mechanisms.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 µg mL-1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 µg mL-1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.

An electroencephalogram microdisplay to visualize neuronal activity on the brain surface.

Functional mapping during brain surgery is applied to define brain areas that control critical functions and cannot be removed. Currently, these procedures rely on verbal interactions between the neurosurgeon and electrophysiologist, which can be time-consuming. In addition, the electrode grids that are used to measure brain activity and to identify the boundaries of pathological versus functional brain regions have low resolution and limited conformity to the brain surface. Here, we present the development of an intracranial electroencephalogram (iEEG)-microdisplay that consists of freestanding arrays of 2048 GaN light-emitting diodes laminated on the back of micro-electrocorticography electrode grids. With a series of proof-of-concept experiments in rats and pigs, we demonstrate that these iEEG-microdisplays allowed us to perform real-time iEEG recordings and display cortical activities by spatially corresponding light patterns on the surface of the brain in the surgical field. Furthermore, iEEG-microdisplays allowed us to identify and display cortical landmarks and pathological activities from rat and pig models. Using a dual-color iEEG-microdisplay, we demonstrated coregistration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The iEEG-microdisplay holds promise to facilitate monitoring of pathological brain activity in clinical settings.

Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapies.

Pseudomonas aeruginosa, a Gram-negative bacterium, is recognized for its adaptability and opportunistic nature. It poses a substantial challenge in clinical settings due to its complicated antibiotic resistance mechanisms, biofilm formation, and capacity for persistent infections in both animal and human hosts. Recent studies revealed a potential zoonotic transmission of P. aeruginosa between animals, the environment, and human populations which highlights awareness of this microbe. Implementation of the One Health approach, which underscores the connection between human, animal, and environmental health, we aim to offer a comprehensive perspective on the current landscape of P. aeruginosa management. This review presents innovative strategies designed to counteract P. aeruginosa infections. Traditional antibiotics, while effective in many cases, are increasingly compromised by the development of multidrug-resistant strains. Non-antibiotic avenues, such as quorum sensing inhibition, phage therapy, and nanoparticle-based treatments, are emerging as promising alternatives. However, their clinical application encounters obstacles like cost, side effects, and safety concerns. Effectively addressing P. aeruginosa infections necessitates persistent research efforts, advancements in clinical development, and a comprehension of host-pathogen interactions to deal with this resilient pathogen.

Utility of artificial intelligence in a binary classification of soft tissue tumors.

Soft tissue tumors (STTs) pose diagnostic and therapeutic challenges due to their rarity, complexity, and morphological overlap. Accurate differentiation between benign and malignant STTs is important to set treatment directions, however, this task can be difficult. The integration of machine learning and artificial intelligence (AI) models can potentially be helpful in classifying these tumors. The aim of this study was to investigate AI and machine learning tools in the classification of STT into benign and malignant categories. This study consisted of three components: (1) Evaluation of whole-slide images (WSIs) to classify STT into benign and malignant entities. Five specialized soft tissue pathologists from different medical centers independently reviewed 100 WSIs, representing 100 different cases, with limited clinical information and no additional workup. The results showed an overall concordance rate of 70.4% compared to the reference diagnosis. (2) Identification of cell-specific parameters that can distinguish benign and malignant STT. Using an image analysis software (QuPath) and a cohort of 95 cases, several cell-specific parameters were found to be statistically significant, most notably cell count, nucleus/cell area ratio, nucleus hematoxylin density mean, and cell max caliper. (3) Evaluation of machine learning library (Scikit-learn) in differentiating benign and malignant STTs. A total of 195 STT cases (156 cases in the training group and 39 cases in the validation group) achieved approximately 70% sensitivity and specificity, and an AUC of 0.68. Our limited study suggests that the use of WSI and AI in soft tissue pathology has the potential to enhance diagnostic accuracy and identify parameters that can differentiate between benign and malignant STTs. We envision the integration of AI as a supportive tool to augment the pathologists' diagnostic capabilities.

Investigating the influence of solvent type and pH on protein adsorption onto silica surface by evanescent-wave cavity ring-down spectroscopy.

Several studies have explored the adsorption of various proteins onto solid-liquid interfaces, revealing the crucial role of buffer solutions in biological processes. However, a comprehensive evaluation of the buffer's influence on protein absorption onto fused silica is still lacking. This study employs evanescent-wave cavity ring-down spectroscopy (EW-CRDS) to assess the influence of buffer solutions and pH on the adsorption kinetics of three globular proteins: hemoglobin (Hb), myoglobin (Mb), and cytochrome c (Cyt-C) onto fused silica. The EW-CRDS tool, with a ring-down time of 1.4 µ s and a minimum detectable absorbance of 1 × 10 - 6 , enabled precise optical measurements at solid-liquid interfaces. The three heme proteins' adsorption behavior was investigated at pH 7 in three different solvents: deionized (DI) water, tris(hydroxymethyl)-aminomethane hydrochloride (Tris-HCl), and phosphate buffered saline (PBS). For each protein, the surface coverage, the adsorption and desorption constants, and the surface equilibrium constant were optically measured by our EW-CRDS tool. Depending on the nature of each solvent, the proteins showed a completely different adsorption trend on the silica surface. The adsorption of Mb on the silica surface was depressed in the presence of both Tris-HCl and PBS buffers compared with unbuffered (DI water) solutions. In contrast, Cyt-C adsorption appears to be relatively unaffected by the choice of buffer, as it involves strong electrostatic interactions with the surface. Notably, Hb exhibits an opposite trend, with enhanced protein adsorption in the presence of Tris-HCl and PBS buffer. The pH investigations demonstrated that the electrostatic interactions between the proteins and the surface had a major influence on protein adsorption on the silica surface, with adsorption being greatest when the pH values were around the protein's isoelectric point. This study demonstrated the ability of the highly sensitive EW-CRDS tool to study the adsorption events of the evanescent-field-confined protein species in real-time at low surface coverages with fast resolution, making it a valuable tool for studying biomolecule kinetics at solid-liquid interfaces.

A 0.00179 mm2/Ch Chopper-Stabilized TDMA Neural Recording System with Dynamic EOV Cancellation and Predictive Mixed-Signal Impedance Boosting.

This article presents a digitally-assisted multi-channel neural recording system. The system uses a 16-channel chopper-stabilized Time Division Multiple Access (TDMA) scheme to record multiplexed neural signals into a single shared analog front end (AFE). The choppers reduce the total integrated noise across the modulated spectrum by 2.4× and 4.3× in Local Field Potential (LFP) and Action Potential (AP) bands, respectively. In addition, a novel impedance booster based on Sign-Sign least mean squares (LMS) adaptive filter (AF) predicts the input signal and pre-charges the AC-coupling capacitors. The impedance booster module increases the AFE input impedance by a factor of 39× with a 7.1% increase in area. The proposed system obviates the need for on-chip digital demodulation, filtering, and remodulation normally required to extract Electrode Offset Voltages (EOV) from multiplexed neural signals, thereby achieving 3.6× and 2.8× savings in both area and power, respectively, in the EOV filter module. The Sign-Sign LMS AF is reused to determine the system loop gain, which relaxes the feedback DAC accuracy requirements and saves 10.1× in power compared to conventional oversampled DAC truncation-error ΔΣ-modulator. The proposed SoC is designed and fabricated in 65 nm CMOS, and each channel occupies 0.00179 mm2 of active area. Each channel consumes 5.11 µW of power while achieving 2.19 µVrms and 2.4 µVrms of input referred noise (IRN) over AP and LFP bands. The resulting AP band noise efficiency factor (NEF) is 1.8. The proposed system is verified with acute in-vivo recordings in a Sprague-Dawley rat using parylene C based thin-film platinum nanorod microelectrodes.

Parents' Knowledge, Attitudes, and Practices Regarding Baby Walkers, Baby Car Seats, Oral Health, and Child Screen Time in Saudi Arabia: A Cross-Sectional Study.

Background Awareness of age-appropriate milestones and developmental stages is crucial for parents to identify any potential delays or concerns early on and seek appropriate interventions. This study aimed to assess the knowledge, attitudes, and practices of caregivers in Saudi Arabia regarding baby walkers, baby car seats, early dental visits, and screen time for young children. Methods A cross-sectional survey was conducted among parents in Saudi Arabia using a structured questionnaire. A convenience and snowball sampling method was employed to recruit participants from various regions of the country. The questionnaire aimed to assess parents' knowledge regarding the recommended use of baby walkers and baby car seats, their awareness of the importance of early dental visits, and their understanding of appropriate screen time guidelines. Additionally, the survey explored parents' practices toward these recommendations. Descriptive statistics were used to analyze the data, and associations between variables were examined using the chi-squared test. Results A total of 1318 participants were included. The analysis revealed that the majority of the participants (n=1066,81.3%) use a baby walker, while only (n=292,22.3%) consider that they should never be used. Overall, (n=388,29.6%) of the participants never used a car seat for their infants or children. In terms of early childhood dental visits, approximately (n=518,39.5%) of the participants reported actually taking their child to the dentist within the recommended timeframe. Regarding screen time for children, (n=148,11.3%) of the participants reported that their children spend >5 hours daily in front of the screen.  Conclusions Raising parents' awareness about recent childcare recommendations and safe practices is crucial for promoting optimal child development, preventing health problems, facilitating evidence-based decision-making, reducing risks, enhancing parental confidence and empowerment, and nurturing positive parent-child relationships.

Flexible, scalable, high channel count stereo-electrode for recording in the human brain.

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.

Modular Phoneme Processing in Human Superior Temporal Gyrus.

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe.

PURPOSE: Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI. METHODS AND MATERIALS: Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe 68Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quantified via autoradiography. 68Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects. RESULTS: Murine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and 68Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant 68Ga-CBP8 uptake in areas of RILI and minimal background uptake. CONCLUSIONS: These findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.

Synthesis of PEDOT:PSS Brushes Grafted from Gold Using ATRP for Increased Electrochemical and Mechanical Stability.

We report PEDOT:PSS brushes grafted from gold using surface-initiated atom-transfer radical polymerization (SI-ATRP) which demonstrate significantly enhanced mechanical stability against sonication and electrochemical cycling compared to spin-coated analogues as well as lower impedances than bare gold at frequencies from 0.1 to 105 Hz. These results suggest SI-ATRP PEDOT:PSS to be a promising candidate for use in microelectrodes for neural activity recording. Spin-coated, electrodeposited, and drop-cast PEDOT:PSS have already been shown to reduce impedance and improve biocompatibility of microelectrodes, but the lack of strong chemical bonds of the physisorbed polymer film to the metal leads to disintegration under required operational stresses including cyclic mechanical loads, abrasion, and electrochemical cycling. Rather than modifying the metal electrode or introducing cross-linkers or other additives to improve the stability of the polymer film, this work chemically tethers the polymer to the surface, offering a simple, scalable solution for functional bioelectronic interfaces.