Do Patients Detect Changes in Breathing After Orthognathic Surgery?

BACKGROUND: Orthognathic surgery addresses facial aesthetics and function in patients with dentofacial deformities. It is associated with changes in upper airway volume (UAV). If changes in UAV are perceived by asymptomatic patients is unclear. PURPOSE: The purpose was to measure associations between changes in UAV and patient-reported benefits using patient-reported outcome measures. STUDY DESIGN: A sample presenting dentofacial deformities without reported breathing problems undergoing orthognathic surgery was retrospectively studied. Patients aged 18-30 years with 12-month follow-up were included. Patients with systemic disease, drug abuse, mental health disorder, or temporomandibular joint dysfunction were excluded. PREDICTOR: The predictor variable was changes in UAV measured in 3-dimensional computed tomography. Subjects were grouped into increased or decreased UAV. MAIN OUTCOME VARIABLE: The primary outcome variable was changes in health-related quality of life measured with Oral Health Impact Profile 49 (OHIP-49). COVARIATES: Weight, height, age, sex, and sub-scaled OHIP-49 were registered. Cephalometric measurements of hard tissue movements were recorded. ANALYSES: Mean, standard deviation, and a level of statistical significance at P < .05 were used. Differences in OHIP-49 were compared using unpaired t-test. The correlation between covariates and outcomes was analyzed using the Spearman's rank test. Analysis of covariance between the predictor and outcome, adjusted for covariates (body mass index), was performed. RESULTS: Fifty-four subjects with a mean age of 20.89 years and 52% males were enrolled. The mean change in UAV was 0.12 cm3 (standard deviation [SD] 9.21, P = .93) with a mean absolute deviation of 7.28 cm3 (SD 5.54). The mean change in OHIP-49 score was 20.93 (SD 28.90). Twenty-seven (50%) subjects had increased UAV (7.4 cm3, SD 6.13) and the other had decreased (-7.17 cm3, SD 5.01) (P = .01). At follow-up, equal levels of mean OHIP-49 score were found, but because of a baseline difference (15.74, P = .048), the subjects with and without increased UAV improved in OHIP-49 score 13.04 (SD 30.53) and 28.81 (SD 25.33), respectively (P = .04). CONCLUSIONS: Because equal levels of OHIP-49 score at follow-up, changes in UAV could not be associated with patient-reported health-related quality of life. Patient-reported outcome measure evaluations of orthognathic surgical treatment for airway obstruction should be performed in patients with a perceived impairment.

Quantification of growth and nutrient consumption of bacterial and fungal cultures in microfluidic microhabitat models.

Understanding microbes in nature requires consideration of their microenvironment. Here, we present a protocol for quantifying biomass and nutrient degradation of bacterial and fungal cultures (Pseudomonas putida and Coprinopsis cinerea, respectively) in microfluidics. We describe steps for mask design and fabrication, master printing, polydimethylsiloxane chip fabrication, and chip inoculation and imaging using fluorescence microscopy. We include procedures for image analysis, plotting, and statistics. For complete details on the use and execution of this protocol, please refer to Arellano-Caicedo et al. (2023).1.

Habitat complexity affects microbial growth in fractal maze.

The great variety of earth's microorganisms and their functions are attributed to the heterogeneity of their habitats, but our understanding of the impact of this heterogeneity on microbes is limited at the microscale. In this study, we tested how a gradient of spatial habitat complexity in the form of fractal mazes influenced the growth, substrate degradation, and interactions of the bacterial strain Pseudomonas putida and the fungal strain Coprinopsis cinerea. These strains responded in opposite ways: complex habitats strongly reduced fungal growth but, in contrast, increased the abundance of bacteria. Fungal hyphae did not reach far into the mazes and forced bacteria to grow in deeper regions. Bacterial substrate degradation strongly increased with habitat complexity, even more than bacterial biomass, up to an optimal depth, while the most remote parts of the mazes showed both decreased biomass and substrate degradation. These results suggest an increase in enzymatic activity in confined spaces, where areas may experience enhanced microbial activity and resource use efficiency. Very remote spaces showing a slower turnover of substrates illustrate a mechanism which may contribute to the long-term storage of organic matter in soils. We demonstrate here that the sole effect of spatial microstructures affects microbial growth and substrate degradation, leading to differences in local microscale spatial availability. These differences might add up to considerable changes in nutrient cycling at the macroscale, such as contributing to soil organic carbon storage.

Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Starting a Swedish national quality registry for orthognathic surgery: a tool for auditing fundamentals of care.

BACKGROUND: National quality registries (NQRs) provide open data for user-directed acquisition. National Quality Registry (NQR) data are often used to analyze the rates of treatment success and adverse events for studies that aim to improve treatment quality and patient satisfaction. Thus, NQRs promote the goal of achieving evidence-based therapies. However, the scientific literature seldom focuses on the complex process of initiating, designing, and implementing an NQR. Starting an NQR may be particularly challenging in a setting where specialized care is decentralized, such as orthognathic surgery in Sweden. The present study describes the initiation and early phases of a new NQR for orthognathic surgery in Sweden. METHODS: The initial inventory phase included gaining knowledge on regulations, creating economic plans, and identifying pitfalls in existing NQRs. Next, a crude framework for the registry was achieved. Outcome measures were selected with a nation-wide questionnaire, followed by a Delphi-like process for selecting parameters to include in the NQR. Our inclusive process comprised a stepwise introduction, feedback-based modifications, and preparatory educational efforts. Descriptive data were collected, based on the first 2 years (2018-2019) of registry operation. RESULTS: Two years after implementation, 862 patients that underwent 1320 procedures were registered. This number corresponded to a 91% coverage rate. Bimaxillary treatments predominated, and the most common were a Le Fort I osteotomy combined with a bilateral sagittal split osteotomy (n = 275). Reoperations were conducted in 32 patients (3.6%), and the rate of patient satisfaction was 95%. CONCLUSIONS: A National Quality Registry should preferentially be started and maintained by an appointed task force of active clinicians. A collaborative, transparent, inclusive process may be an important factor for achieving credibility and high coverage, particularly in a decentralized setting.

Habitat geometry in artificial microstructure affects bacterial and fungal growth, interactions, and substrate degradation.

Microhabitat conditions determine the magnitude and speed of microbial processes but have been challenging to investigate. In this study we used microfluidic devices to determine the effect of the spatial distortion of a pore space on fungal and bacterial growth, interactions, and substrate degradation. The devices contained channels differing in bending angles and order. Sharper angles reduced fungal and bacterial biomass, especially when angles were repeated in the same direction. Substrate degradation was only decreased by sharper angles when fungi and bacteria were grown together. Investigation at the cellular scale suggests that this was caused by fungal habitat modification, since hyphae branched in sharp and repeated turns, blocking the dispersal of bacteria and the substrate. Our results demonstrate how the geometry of microstructures can influence microbial activity. This can be transferable to soil pore spaces, where spatial occlusion and microbial feedback on microstructures is thought to explain organic matter stabilization.

Do patient-reported outcome measures correlate with clinical follow-up after arthroscopic treatment of internal derangement of the temporomandibular joint?

INTRODUCTION: Arthroscopic treatment of the temporomandibular joint (TMJ) has traditionally been evaluated with clinical measurements. Additional recordings of patient reported outcome measures (PROM) is expected to make the evaluation more complete. The aim of the study was to evaluate if PROM correlates with clinical follow-up measures after arthroscopic treatment of internal derangement of the TMJ. MATERIAL AND METHODS: Patients with temporomandibular dysfunction (TMD), treated with arthroscopic lysis and lavage of the TMJ, were followed with a PROM questionnaire; Jaw Functional Limitation Scale 20 (JFLS-20) and a review of patient medical records. Out of 239 patients treated, 134 were eligible for inclusion to the study. RESULTS: 91 subjects, 21 males and 70 females, with mean age 42.6 years completed the follow-up. The JFLS-20 mean score was 25.43 (range: 0-148). A correlation was found between JFLS and mouth opening. The JFLS-20 score was decreased by 1.48 (p = 0.0001) for ever millimeter larger mouth opening and with 1.16 (p = 0.001) for every gained millimeter of mouth opening after arthroscopic treatment of the TMJ. The mean maximal mouth opening was 38.43 mm preoperatively (15 to 75 mm) compared to 42.19 mm postoperatively (range: 21-75 mm). A total of 80 subjects with TMD associated pain preoperatively was reduced to 25 postoperatively (p = 0.0001). DISCUSSION: Advantageous treatment effect with arthroscopic lysis and lavage was presented. The outcome of the JFLS-20 questionnaire indicates a correlation with the clinical findings. Future studies will focus on larger cohorts and using PROM with a case-control setting.

Fungal foraging behaviour and hyphal space exploration in micro-structured Soil Chips.

How do fungi navigate through the complex microscopic maze-like structures found in the soil? Fungal behaviour, especially at the hyphal scale, is largely unknown and challenging to study in natural habitats such as the opaque soil matrix. We monitored hyphal growth behaviour and strategies of seven Basidiomycete litter decomposing species in a micro-fabricated "Soil Chip" system that simulates principal aspects of the soil pore space and its micro-spatial heterogeneity. The hyphae were faced with micrometre constrictions, sharp turns and protruding obstacles, and the species examined were found to have profoundly different responses in terms of foraging range and persistence, spatial exploration and ability to pass obstacles. Hyphal behaviour was not predictable solely based on ecological assumptions, and our results obtained a level of trait information at the hyphal scale that cannot be fully explained using classical concepts of space exploration and exploitation such as the phalanx/guerrilla strategies. Instead, we propose a multivariate trait analysis, acknowledging the complex trade-offs and microscale strategies that fungal mycelia exhibit. Our results provide novel insights about hyphal behaviour, as well as an additional understanding of fungal habitat colonisation, their foraging strategies and niche partitioning in the soil environment.

Time stamped list mode data from gamma-ray spectroscopic measurements on 47 nuclear fuel assemblies performed at Clab, Sweden, September 2016 through March 2019.

Using a high-purity Germanium gamma-ray energy spectroscopic detector system, time-stamped list-mode data sets were acquired during axial scanning of 19 boiling water reactor (BWR) and 28 pressurized water reactor (PWR) type of nuclear fuel assemblies. The data sets were collected during two measurements campaigns in September 2016 and March 2019 at the Central Interim Storage Facility for Spent Nuclear (Clab) in Sweden. A certified calibration source of 137Cs was positioned along the central line of sight between the measured fuel assembly and the detector. Data sets from measurements with only the calibration source and other background sources, i.e. without a nuclear fuel assembly present, are also included. The list-mode structure of the measured data allows for an axially-resolved as well as energy-spectral resolved intensity of nuclide-specific gamma lines emitted from the spent nuclear fuel. Data presented here can be used e.g. for validation of gamma-ray transport simulation tools or for development of methods to estimate parameters of the spent nuclear fuel based on data from gamma-ray spectroscopy.

Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage.

OBJECTIVE: The present study assessed somatosensory changes related to trigeminal nerve damage using extensive evaluation tools and assessed the effect of such damage on the patients' psychosocial status and quality of life compared with healthy participants. METHODS: In 37 patients with intraorally or extraorally presenting trigeminal nerve damage diagnosed as painful or nonpainful posttraumatic trigeminal neuropathy, psychophysical tests like quantitative sensory testing (QST) and qualitative sensory testing and the electrophysiological "nociceptive-specific" blink reflex were performed. The patients and 20 healthy participants completed a set of questionnaires assessing their psychosocial status and quality of life. RESULTS: A loss or gain of somatosensory function was seen in at least 1 QST parameter in >88.9% of the patients. Patients in whom extraoral QST was performed showed an overall loss of somatosensory function, whereas intraoral QST showed a general gain of somatosensory function. Qualitative sensory testing identified a side-to-side difference in the tactile and pinprick stimulation in >77% of the patients. An abnormal "nociceptive-specific" blink reflex response was seen in 42.1% to 71.4% of patients dependent on the trigeminal branch stimulated, though comparisons with healthy reference values showed ambiguous results. Compared with the healthy participants, patients showed higher scores for pain catastrophizing, symptoms of depression and anxiety, limited jaw function, more somatic symptoms, and significantly impaired oral health-related quality of life (all P<0.038). DISCUSSION: The results from the present study showed presence of varied somatosensory abnormalities when assessed using psychophysical and electrophysiological investigations and a significantly impaired psychosocial status.

Data from calorimetric decay heat measurements of five used PWR 17x17 nuclear fuel assemblies.

Raw data from calorimetric measurements of five nuclear fuel assemblies of the PWR 17 × 17 type are provided. Measurements of the temperature both inside a calorimeter, in which the fuel assembly was placed, as well as outside, were performed as a function of time while water circulating inside the calorimeter heats up from radiation emitted in the radioactive decay of material in the fuel assembly. The data contain also measurements of dose rate in the water outside the calorimeter. Data from 38 measurements using an electrically heated model of a fuel assembly are also provided to be used for, e.g., calibration. The data can be used for validation of computer codes for modelling of nuclear systems, e.g. nuclear reactors, storage and transport of nuclear fuel or systems for geological disposal.

Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist.

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration.

Treatment outcomes and patient-reported quality of life after orthognathic surgery with computer-assisted 2- or 3-dimensional planning: A randomized double-blind active-controlled clinical trial.

INTRODUCTION: Thorough treatment planning is essential for a good clinical outcome in orthognathic treatment. The planning is often digital. Both 2-dimensional (2D) and 3-dimensional (3D) software options are available. The aim of this randomized 2-arm parallel double-blinded active-controlled clinical trial was to compare the outcomes of computer-based 2D and 3D planning techniques according to patient-reported health related quality of life. The hypothesis was that a 3D technique would give a better treatment outcome compared with a 2D technique. METHODS: Orthognathic treatment for 62 subjects, aged 18 to 28 years, with severe Class III malocclusion was planned with both 2D and 3D techniques. After treatment planning but before surgery, the patients were randomly allocated via blind collection of 1 enveloped card for each subject in a 1:1 ratio to the test (3D) or the control (2D) group. Thus, the intervention was according to which planning technique was used. The primary outcome was patient-reported outcome measures. The secondary outcome was relationship between patient-reported outcome measures and cephalometric accuracy. Questionnaires on the patient's health-related quality of life (HRQoL) were distributed preoperatively and 12 months after surgical treatment. The questionnaires were coded, meaning blinding throughout the analysis. Differences between groups were tested with the Fisher permutation test. The HRQoL was also compared with measurements of cephalometric accuracy for the 2 groups. RESULTS: Three subjects were lost to clinical follow-up, leaving 57 included. Of these, 55 subjects completed the questionnaires, 28 in the 2D and 27 in the 3D groups. No statistically significant difference regarding HRQoL was found between the studied planning techniques: the Oral Health Impact Profile total showed -3.69 (95% confidence interval, -19.68 to 12.30). Consistent results on HRQoL and cephalometric accuracy showed a difference between pretreatment and posttreatment that increased in both groups but to a higher level in the 3D group. A difference between pretreatment and posttreatment HRQoL was shown for both groups, indicating increased quality of life after treatment. This supports recent findings comparing 3D and 2D planning techniques. No serious harm was observed during the study. CONCLUSIONS: Improvements of HRQoL were shown after treatment independent of which planning technique, 2D or 3D, was used. No statistically significant difference was found between the planning techniques. REGISTRATION: This trial was not registered. PROTOCOL: The protocol was not published before trial commencement. FUNDING: This project was supported by personal grants to Martin Bengtsson from the Scandinavian Association of Oral and Maxillofacial Surgeons (25000 SEK), the Southern Region of the Swedish Dental Association (50000 SEK), and the Swedish Association of Oral and Maxillofacial Surgeons (25000 SEK). The sponsors had no influence on the study design, analysis of the data, or the writing of the article.

Treatment outcome in orthognathic surgery - A prospective comparison of accuracy in computer assisted two and three-dimensional prediction techniques.

The main objective of the present study was to assess the accuracy of two- and three-dimensional prediction techniques in orthognathic surgery. It was also a test of the very planning sequence. The scientific question was how well does the software support the surgeon in his way to find the perfect correction of the facial appearance while normalizing the occlusion? Thirty patients with a class III occlusion were included in this prospective study. Surgical planning with both techniques were undertaken for all patients. Surgery was performed according to the two-dimensional technique. The cephalometric measurements from two-dimensional and three dimensional predictions were compared with the postoperative results at the 12 months follow-up respectively. Together with an analysis of tracing error, placements of 2020 markers, 1860 measurements and 1280 comparisons was performed. The analysis showed an equally high accuracy for the studied techniques. The highest accuracy was found in the anterior maxilla. There was a tendency for an overestimation for the three-dimensional technique and an underestimation for the two-dimensional technique. CONCLUSIONS: The present study indicates an equal high accuracy in predicting facial outcome for both studied techniques. However, in those patients with asymmetric malocclusion and/or facial appearance the three-dimensional technique has an obvious advantage.

Treatment outcome in orthognathic surgery-A prospective randomized blinded case-controlled comparison of planning accuracy in computer-assisted two- and three-dimensional planning techniques (part II).

PURPOSE: The aim of the present study was to compare the accuracy of two-dimensional (2D) and three-dimensional (3D) prediction methods. The hypothesis was that a 3D technique would give a more accurate outcome of the postoperative result. MATERIAL AND METHODS: Patients with severe class III occlusion were included and planed with both a 2D and 3D prediction technique. They were there after randomly subdivided into a control (2D) and test (3D) group and treated according to the technique randomized for. Cephalometric measurements from 2D and 3D predictions were compared with 12-month follow-up respectively. Together with an analysis of tracing error, placements of 3580 cephalometric markers, 2460 measurements, 680 intra-individual analyses and 1200 preop/postop comparisons were performed in 57 individuals. RESULTS: Statistically significant differences for accuracy between the two groups were seen for 11/NSL-112/NSL2 and for A-A2 (p < 0.05). Both groups showed a high level of accuracy for SNA and SNB. The test group also showed a relatively high level of accuracy for 11/NSL and for the A-point. No prediction method achieves a perfect accuracy. As expected from this, measuring accuracy within each group showed statistically significant difference for all markers and cephalometric measurements (p < 0.001). Mandibular markers showed greater differences than maxillary markers. CONCLUSION: The present study indicates an equal high accuracy in predicting facial outcome for both studied techniques. However, in patients with asymmetry the three-dimensional technique has an obvious advantage.

Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

OBJECTIVE: Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? APPROACH: Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (~150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). MAIN RESULTS: We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. SIGNIFICANCE: The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.

Mandibular Access Osteotomy for Tumor Ablation: Could a More Tissue-Preserving Technique Affect Healing Outcome?

PURPOSE: Paramedial mandibulotomy facilitates access for the resection of tumors in the oral and oropharyngeal space; however, severe complications related to surgical techniques and radiotherapy have been reported for this procedure. This study evaluated whether preservation of the periosteum during a mandibulotomy would decrease postoperative complications owing to the increased healing capacity provided by preserving more tissue. MATERIALS AND METHODS: Patients who underwent mandibulotomy for surgical tumor ablation from 2007 through 2012 were included in a retrospective controlled cohort study. The trial was comprised of 2 groups: 1 group underwent subperiosteal and 1 group underwent supraperiosteal surgical dissection in the area of the mandibulotomy. The primary predictor variable was surgical technique and the primary outcome variable was surgical complications. The groups were matched according to tumor type, age, and gender. Clinical and radiographic follow-up was performed 12 months after surgery. Complications regarding bone exposure, plate exposure, osteoradionecrosis, nonunion, infection of the soft tissue flap, abscesses, fistulas, and gingival necrosis were recorded. Recordings of other factors, such as age, smoking habits, and timing of radiotherapy and chemotherapy, were performed and the 2 groups were compared for postoperative complications. Data analysis used the χ(2) test (Fisher exact test) to compare the sub- and supraperiosteal groups for postoperative complications. RESULTS: Thirty-two patients were included (16 per group; 14 women and 18 men; mean age, 56 yr). Thirteen patients in the subperiosteal group and 7 in the supraperiosteal group showed complications during the first 12 months. Seven patients had complications that persisted to the 12-month follow-up (6 in the subperiosteal group and 1 in the supraperiosteal group); however, the difference was not statistically relevant. CONCLUSION: This study found more persistent complications in the subperiosteal group compared with the supraperiosteal group at 12-month follow-up, which could imply that a more tissue-preserving surgical technique promotes mandibular healing in patients undergoing mandibular access osteotomy in combination with radiotherapy.

Biocompatibility of a polymer based on Off-Stoichiometry Thiol-Enes + Epoxy (OSTE+) for neural implants.

BACKGROUND: The flexibility of implantable neural probes has increased during the last 10 years, starting with stiff materials such as silicone to more flexible materials like polyimide. We have developed a novel polymer based on Off-Stoichiometry Thiol-Enes + Epoxy (OSTE+, consisting of a thiol, two allyls, an epoxy resin and two initiators), which is up to 100 times more flexible than polyimide. Since a flexible neural probe should be more biocompatible than a stiff probe, an OSTE+ probe should be more biocompatible than one composed of a more rigid material. We have investigated the toxicity of OSTE+ as well as of OSTE+ that had been incubated in water for a week (OSTE+H2O) using MTT assays with mouse L929 fibroblasts. We found that OSTE+ showed cytotoxicity, but OSTE+H2O did not. Extracts were analyzed using LC-MS and GC-MS in order to identify leaked chemicals. RESULTS: Most constituents were found in extracts of OSTE+, whereas only initiators were found in OSTE+H2O extracts. The detected levels of each chemical found in the LC-MS and the GC-MS analysis were below the toxicity level when compared to MTT assays of all the individual chemicals, except for one of the initiators that had an IC50 value close to the detected levels. CONCLUSION: Our notion is that the toxicity of OSTE+ was caused by one of the initiators, by impurities in the constituents or by synergistic effects of low doses of leaked chemicals. However, our conclusion is that if OSTE+ is incubated for one week in water, OSTE+ is not cytotoxic and suitable for further in vivo studies.

Na+ current properties in islet α- and ß-cells reflect cell-specific Scn3a and Scn9a expression.

Mouse pancreatic ß- and α-cells are equipped with voltage-gated Na(+) currents that inactivate over widely different membrane potentials (half-maximal inactivation (V0.5) at -100 mV and -50 mV in ß- and α-cells, respectively). Single-cell PCR analyses show that both α- and ß-cells have Nav1.3 (Scn3) and Nav1.7 (Scn9a) α subunits, but their relative proportions differ: ß-cells principally express Nav1.7 and α-cells Nav1.3. In α-cells, genetically ablating Scn3a reduces the Na(+) current by 80%. In ß-cells, knockout of Scn9a lowers the Na(+) current by >85%, unveiling a small Scn3a-dependent component. Glucagon and insulin secretion are inhibited in Scn3a(-/-) islets but unaffected in Scn9a-deficient islets. Thus, Nav1.3 is the functionally important Na(+) channel α subunit in both α- and ß-cells because Nav1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Nav1.7 sequence in brain and islets is identical and yet the V0.5 for inactivation is >30 mV more negative in ß-cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation.

µ-Foil Polymer Electrode Array for Intracortical Neural Recordings.

We have developed a multichannel electrode array-termed [Formula: see text]-foil-that comprises ultrathin and flexible electrodes protruding from a thin foil at fixed distances. In addition to allowing some of the active sites to reach less compromised tissue, the barb-like protrusions that also serves the purpose of anchoring the electrode array into the tissue. This paper is an early evaluation of technical aspects and performance of this electrode array in acute in vitro/in vivo experiments. The interface impedance was reduced by up to two decades by electroplating the active sites with platinum black. The platinum black also allowed for a reduced phase lag for higher frequency components. The distance between the protrusions of the electrode array was tailored to match the architecture of the rat cerebral cortex. In vivo acute measurements confirmed a high signal-to-noise ratio for the neural recordings, and no significant crosstalk between recording channels.