Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

BACKGROUND: Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. RESULTS: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. CONCLUSION: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Developing RPC-Net: Leveraging High-Density Electromyography and Machine Learning for Improved Hand Position Estimation.

OBJECTIVE: The purpose of this study was to develop and evaluate the performance of RPC-Net (Recursive Prosthetic Control Network), a novel method using simple neural network architectures to translate electromyographic activity into hand position with high accuracy and computational efficiency. METHODS: RPC-Net uses a regression-based approach to convert forearm electromyographic signals into hand kinematics. We tested the adaptability of the algorithm to different conditions and compared its performance with that of solutions from the academic literature. RESULTS: RPC-Net demonstrated a high degree of accuracy in predicting hand position from electromyographic activity, outperforming other solutions with the same computational cost. Including previous position data consistently improved results across subjects and conditions. RPC-Net showed robustness against a reduction in the number of electromyography electrodes used and shorter input signals, indicating potential for further reduction in computational cost. CONCLUSION: The results demonstrate that RPC-Net is capable of accurately translating forearm electromyographic activity into hand position, offering a practical and adaptable tool that may be accessible in clinical settings. SIGNIFICANCE: The development of RPC-Net represents a significant advancement. In clinical settings, its application could enable prosthetic devices to be controlled in a way that feels more natural, improving the quality of life for individuals with limb loss.

Expanding our view of the cold-water coral niche and accounting of the ecosystem services of the reef habitat.

Coral reefs are iconic ecosystems that support diverse, productive communities in both shallow and deep waters. However, our incomplete knowledge of cold-water coral (CWC) niche space limits our understanding of their distribution and precludes a complete accounting of the ecosystem services they provide. Here, we present the results of recent surveys of the CWC mound province on the Blake Plateau off the U.S. east coast, an area of intense human activity including fisheries and naval operations, and potentially energy and mineral extraction. At one site, CWC mounds are arranged in lines that total over 150 km in length, making this one of the largest reef complexes discovered in the deep ocean. This site experiences rapid and extreme shifts in temperature between 4.3 and 10.7 °C, and currents approaching 1 m s-1. Carbon is transported to depth by mesopelagic micronekton and nutrient cycling on the reef results in some of the highest nitrate concentrations recorded in the region. Predictive models reveal expanded areas of highly suitable habitat that currently remain unexplored. Multidisciplinary exploration of this new site has expanded understanding of the cold-water coral niche, improved our accounting of the ecosystem services of the reef habitat, and emphasizes the importance of properly managing these systems.

Conformational Manifold Sampled by Two Short Linear Motif Segments Probed by Circular Dichroism, Vibrational, and Nuclear Magnetic Resonance Spectroscopy.

Disordered protein segments called short linear motifs (SLiM) serve as recognition sites for a variety of biological processes and act as targeting signals, modification, and ligand binding sites. While SLiMs do not adopt one of the known regular secondary structures, the conformational distribution might still reflect the structural propensities of their amino acid residues and possible interactions between them. In the past, conformational analyses of short peptides provided compelling evidence for the notion that individual residues are less conformationally flexible than locally expected for a random coil. Here, we combined various spectroscopies (NMR, IR, vibrational, and UV circular dichroism) to determine the Ramachandran plots of two SLiM motifs, i.e., GRRDSG and GRRTSG. They are two representatives of RxxS motifs that are capable of being phosphorylated by protein kinase A, an enzyme that plays a fundamental role in a variety of biological processes. Our results reveal that the nearest and non-nearest interactions between residues cause redistributions between polyproline II and ß-strand basins while concomitantly stabilizing extended relative to turn-forming and helical structures. They also cause shifts in basin positions. With increasing temperature, ß-strand populations become more populated at the expense of polyproline II. While molecular dynamics simulations with Amber ff14SB and CHARMM 36m force fields indicate residue-residue interactions, they do not account for the observed structural changes.

The Adjustable Cranial Plate: A Novel Implant Designed to Eliminate the Need for Cranioplasty Surgery Following a Hemicraniectomy Operation.

BACKGROUND: Decompressive hemicraniectomy (DHC) is performed to relieve life-threatening intracranial pressure elevations. After swelling abates, a cranioplasty is performed for mechanical integrity and cosmesis. Cranioplasty is costly with high complication rates. Prior attempts to obviate second-stage cranioplasty have been unsuccessful. The Adjustable Cranial Plate (ACP) is designed for implantation during DHC to afford maximal volumetric expansion with later repositioning without requiring a second major operation. METHODS: The ACP has a mobile section held by a tripod fixation mechanism. Centrally located gears adjust the implant between the up and down positions. Cadaveric ACP implantation was performed. Virtual DHC and ACP placement were done using imaging data from 94 patients who had previously undergone DHC to corroborate our cadaveric results. Imaging analysis methods were used to calculate volumes of cranial expansion. RESULTS: The ACP implantation and adjustment procedures are feasible in cadaveric testing without wound closure difficulties. Results of the cadaveric study showed total volumetric expansion achieved was 222 cm3. Results of the virtual DHC procedure showed the volume of cranial expansion achieved by removing a standardized bone flap was 132 cm3 (range, 89-171 cm3). Applied to virtual craniectomy patients, the total volume of expansion achieved with the ACP implantation operation was 222 cm3 (range, 181-263 cm3). CONCLUSIONS: ACP implantation during DHC is technically feasible. It achieves a volume of cranial expansion that will accommodate that observed following survivable hemicraniectomy operations. Moving the implant from the up to the down position can easily be performed as a simple outpatient or inpatient bedside procedure, thus potentially eliminating second-stage cranioplasty procedures.

Acute subcutaneous emphysema: A rare clinical presentation of large bowel perforation.

These atypical presentations of colonic perforation illustrate the importance of considering acute intra-abdominal pathology when subcutaneous emphysema is identified.

Amyand's Hernia: A Radiological Solution of a Surgical Dilemma.

Amyand's hernia is a rare condition whereby the appendix lies within the sac of an inguinal hernia; rarer still, the appendix can become inflamed (acute appendicitis) and is frequently misdiagnosed as a strangulated inguinal hernia. We report a case of Amyand's hernia complicated with acute appendicitis. In this case an accurate preoperative diagnosis was provided by a preoperative Computerised Tomography (CT) scan, permitting planning of treatment by a laparoscopic approach.

How do salt and lipids affect conformational dynamics of Aß42 monomers in water?

It is well established that amyloid ß-protein (Aß) self-assembly is involved in triggering of Alzheimer's disease. On the other hand, evidence of physiological function of Aß interacting with lipids has only begun to emerge. Details of Aß-lipid interactions, which may underlie physiological and pathological activities of Aß, are not well understood. Here, the effects of salt and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids on conformational dynamics of Aß42 monomer in water are examined by all-atom molecular dynamics (MD). We acquired six sets of 250 ns long MD trajectories for each of the three lipid concentrations (0, 27, and 109 mM) in the absence and presence of 150 mM salt. Ten replica trajectories per set are used to enhance sampling of Aß42 conformational space. We show that salt facilitates long-range tertiary contacts in Aß42, resulting in more compact Aß42 conformations. By contrast, addition of lipids results in lipid-concentration dependent Aß42 unfolding concomitant with enhanced stability of the turn in the A21-A30 region. At the high lipid concentration, salt enables the N-terminal region of Aß42 to form long-range tertiary contacts and interact with lipids, which results in formation of a parallel ß-strand. Aß42 forms stable lipid-protein complexes whereby the protein is adhered to the lipid cluster rather than embedded into it. We propose that the inability of Aß42 monomer to get embedded into the lipid cluster may be important for facilitating repair of leaks in the blood-brain barrier without penetrating and damaging cellular membranes.

Computation of Activating Fields for Approximation of the Orientation-Specific Neural Response to Electrical Stimulation.

Computational methods of determining the response of neural tissue to electrical stimulation have demonstrated value for the development of novel devices and the programming of neuromodulation therapies. Detailed biophysical models are excessively computationally intensive for many applications; simple metrics to approximate activation can speed up progress in this area. The activating function provides such a useful metric. However, this measure, defined for a specific axon orientation, is not immediately applicable to computed electric fields to assess their effects. We demonstrate a method for computation of the activating function generalized to a field in order to allow rapid computation of the effects of stimulation on neural tissue while preserving information on axon orientation. Clinical Relevance- This demonstrates a useful method of approximating the effect of electrical stimulation on nervous tissue for the development of devices and the optimization of parameters for electrical neuromodulation.

Effect of the Current Intensity and Inter-Electrode Distance in Surface Electrical Stimulation: A FEM Simulation Study.

In functional electric stimulation, variables such as electrode size, shape, and inter-electrodes distance can produce different neural and functional responses. In this work, a computational model combining FEM and MRG axon models is implemented to replicate two experimental studies that compare the effect of changing inter-electrode distance when applying FES to induce knee flexion. One work affirms that the stronger torque happens for greater distances, while the other obtain its maximum at lower distances. Using a simplified computational model gave another study perspective to understand why these two stimulation methodologies obtain different results. According to our results, an anodic stimulation occurs with greater current intensities and inter-electrode distances. This anodic effect can activate other nerve or motor points in the vicinity of the anode, explaining that more muscle fibers are recruited and generate an increased torque. Clinical Relevance - This work gives another view to understanding how the distance between electrodes affects neural activation, which has implications for optimizing clinical and exercise protocols using electrical stimulation techniques.

The effect of Functional Electrical Stimulation-assisted posture-shifting in bone mineral density: case series-pilot study.

STUDY DESIGN: A training intervention study using standing dynamic load-shifting Functional Electrical Stimulation (FES) in a group of individuals with complete spinal cord injury (SCI) T2 to T10. OBJECTIVES: Investigate the effect of FES-assisted dynamic load-shifting exercises on bone mineral density (BMD). SETTING: University Lab within the Biomedical Engineering METHODS: Twelve participants with ASIA A SCI were recruited for this study. Three participants completed side-to-side load-shifting FES-assisted exercises for 29 ± 5 weeks, 2× per week for 1 h, and FES knee extension exercises on alternate days 3× per week for 1 h. Volumetric Bone Mineral density (vBMD) at the distal femur and tibia were assessed using peripheral quantitative computed tomography (pQCT) before and after the intervention study. RESULTS: Participants with acute and subacute SCI showed an absolute increase of f trabecular vBMD (vBMDTRAB) in the proximal (mean of 26.9%) and distal tibia (mean of 22.35%). Loss of vBMDTRAB in the distal femur was observed. CONCLUSION: Improvements in vBMDTRAB in the distal tibia were found in acute and subacute SCI participants, and in the proximal tibia of acute participants, when subjected to anti-gravity FES-assisted load-bearing exercises for 29 ± 5 weeks. No vBMD improvement in distal femur or tibial shaft were observed in any of the participants as was expected. However, improvements of vBMD in the proximal and distal tibia were observed in two participants. This study provides evidence of an improvement of vBMDTRAB, when combining high-intensity exercises with lower intensity exercises 5× per week for 1 h.

Comparing imaging biomarkers of cerebral edema after TBI in young adult male and female rats.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 h after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjectsex vivo.We found that both males and females had similarly elevated T2 values after TBI compared with sham controls. Apparent diffusion coefficient (ADC) was more variable than T2 and did not show significant injury effects in males or females. Brain water was elevated in male TBI rats compared with sham controls, but there was no difference between female TBI and sham groups. Notably, MRI biomarkers of edema were more closely correlated with brain water in male rats; female rats did not show any relationship between brain water and T2 or ADC. These observations raise questions about the interpretation of radiological findings traditionally interpreted as edema in female TBI patients. A better understanding of sex differences and similarities in the pathophysiology of post-traumatic edema is needed to help improve patient management and the development of effective treatment strategies for men and women.

Non-invasive phrenic nerve stimulation to avoid ventilator-induced diaphragm dysfunction in critical care.

BACKGROUND: Diaphragm muscle atrophy during mechanical ventilation begins within 24 h and progresses rapidly with significant clinical consequences. Electrical stimulation of the phrenic nerves using invasive electrodes has shown promise in maintaining diaphragm condition by inducing intermittent diaphragm muscle contraction. However, the widespread application of these methods may be limited by their risks as well as the technical and environmental requirements of placement and care. Non-invasive stimulation would offer a valuable alternative method to maintain diaphragm health while overcoming these limitations. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. Respiratory pressure and flow, diaphragm electromyography and mechanomyography, and ultrasound visualization were used to assess the diaphragmatic response to stimulation. The electrode positions and stimulation parameters were systematically varied in order to investigate the influence of these parameters on the ability to induce diaphragm contraction with non-invasive stimulation. RESULTS: We demonstrate that non-invasive capture of the phrenic nerve is feasible using surface electrodes without the application of pressure, and characterize the stimulation parameters required to achieve therapeutic diaphragm contractions in healthy volunteers. We show that an optimal electrode position for phrenic nerve capture can be identified and that this position does not vary as head orientation is changed. The stimulation parameters required to produce a diaphragm response at this site are characterized and we show that burst stimulation above the activation threshold reliably produces diaphragm contractions sufficient to drive an inspired volume of over 600 ml, indicating the ability to produce significant diaphragmatic work using non-invasive stimulation. CONCLUSION: This opens the possibility of non-invasive systems, requiring minimal specialist skills to set up, for maintaining diaphragm function in the intensive care setting.

Do molecular dynamics force fields accurately model Ramachandran distributions of amino acid residues in water?

Molecular dynamics (MD) is a powerful tool for studying intrinsically disordered proteins, however, its reliability depends on the accuracy of the force field. We assess Amber ff19SB, Amber ff14SB, OPLS-AA/M, and CHARMM36m with respect to their capacity to capture intrinsic conformational dynamics of 14 guest residues x (=G, A, L, V, I, F, Y, DP, EP, R, C, N, S, T) in GxG peptides in water. The MD-derived Ramachandran distribution of each guest residue is used to calculate 5 J-coupling constants and amide I' band profiles to facilitate a comparison to spectroscopic data through reduced χ2 functions. We show that the Gaussian model, optimized to best fit the experimental data, outperforms all MD force fields by an order of magnitude. The weaknesses of the MD force fields are: (i) insufficient variability of the polyproline II (pPII) population among the guest residues; (ii) oversampling of antiparallel at the expense of transitional ß-strand region; (iii) inadequate sampling of turn-forming conformations for ionizable and polar residues; and (iv) insufficient guest residue-specificity of the Ramachandran distributions. Whereas Amber ff19SB performs worse than the other three force fields with respect to χ2 values, it accounts for residue-specific pPII content better than the other three force fields. Additional testing of residue-specific RSFF1 and Amber ff14SB combined with TIP4P/2005 on six guest residues x (=A, I, F, DP, R, S) reveals that residue specificity derived from protein coil libraries or an improved water model alone do not result in significantly lower χ2 values.

Additively Manufactured NdFeB Polyphenylene Sulfide Halbach Magnets to Generate Variable Magnetic Fields for Neutron Reflectometry.

Halbach arrays are the most efficient closed structures for generating directed magnetic fields and gradients, and are widely used in various electric machines. We utilized fused deposition modeling-based Big Area Additive Manufacturing technology to print customized, compensated concentric Halbach array rings, using polyphenylene sulfide-bonded NdFeB permanent magnets for polarized neutron reflectometry. The Halbach rings could generate a 0 ≤ B ≤ 0.30 T field, while preserving 90% polarization of an axial neutron beam. Polarized neutron beams are used to study a wide range of structural and magnetic phenomena spanning physics, chemistry, and biology. In this study, we demonstrate the effectiveness of additive manufacturing for producing prototype Halbach arrays, characterize their magnetic properties, and generated magnetic fields, and discuss the conservation of neutron beam polarization as a function of magnetic field.

Pediatric Odontogenic and Maxillofacial Bone Pathology: A Global Analysis.

BACKGROUND: Although pathology in the maxillary and mandibular bones is rare in young patients, the differential diagnosis is broad. The World Health Organization (WHO) updated its classification of maxillofacial bone pathology in 2017. Using these updated guidelines, a systematic review of common maxillofacial bone lesions in the pediatric population was performed. METHODS: A PubMed search was conducted capturing English language articles from inception to July 2020. Thirty-one articles were identified that described the frequency of maxillofacial bone pathology. Data were extracted and organized using the WHO 2017 classification of odontogenic and maxillofacial bone tumors. Prevalence data were analyzed among diagnostic categories and geographical regions. The SAS version 9.4 was used to complete statistical analyses. RESULTS: The articles included patients from birth to a maximum age of 14 to 19 years. The most common odontogenic cysts included radicular cyst (42.7%) and dentigerous cyst (39.0%) followed by odontogenic keratocyst (15.0%). Among odontogenic bone tumors, odontoma (49.3%) was most common followed by ameloblastoma (29.1%). The most common nonodontogenic bone tumor was fibrous dysplasia (42.4%), and the most common malignant bone tumor was osteosarcoma (75.0%). Significant variations were found by geographic region, with dentigerous cyst more common than radicular cyst, and ameloblastoma more common than odontoma in African and Asian countries (P < 0.0001). CONCLUSIONS: This systematic review uses the WHO 2017 guidelines to classify common odontogenic and nonodontogenic maxillofacial bone lesions around the world. Pathogenesis, presentation, and available treatment options for the most common maxillofacial bone lesions are reviewed.

Outcomes and Utility of Intracranial Free Tissue Transfer.

OBJECTIVE: Complications associated with intracranial vault compromise can be neurologically and systemically devastating. Primary and secondary repair of these deficits require an air and watertight barrier between the intracranial and extracranial environments. This study evaluated the outcomes and utility of using intracranial free tissue transfer as both primary and salvage surgical repair of reconstruction. METHODS: A retrospective review was performed of all subjects who underwent intracranial free tissue transfer as primary or salvage repair. RESULTS: A total of 13 intracranial free tissue transfers were performed on 11 subjects: osteocutaneous radial forearm free flaps (n = 6), partial myofascial rectus abdominis flaps (n = 5), temporoparietal fascia flap (n = 1), and serratus anterior myofascial flap (n = 1). Primary reconstruction was performed on 4 subjects with the remaining being salvage repair. Indications for surgery included neoplasm (n = 6 of 11), ballistic trauma (n = 3 of 11), motor vehicle accident (n = 1 of 11), and infection (n = 1 of 11). Three subjects required additional surgical repair for CSF leak and pneumocephalus, with 2 subjects requiring an additional free tissue transfer at a different site. CONCLUSION: In our experience, free tissue transfer is an effective primary and salvage surgical technique in the reconstruction of complex intracranial problems.

Microsurgical Management of Early Onset Alveolar Soft Part Sarcoma of the Oral Tongue: Case Report and Review of the Literature.

OBJECTIVES: Alveolar soft part sarcoma is a rare subset of soft tissue sarcomas, typically presenting in subjects 15 to 35 years of age. Usual presentation sites are the trunk, extremities, and the head and neck. Subjects younger than 5 years are rarely affected. METHODS: In this retrospective case report, we present a 16-month old male with a rapidly growing soft tissue mass of the anterior and posterior tongue, found to be alveolar soft part sarcoma. RESULTS: The subject was treated with primary surgical resection and the resulting defect was reconstructed with a radial forearm free flap. CONCLUSIONS: To our knowledge, this is the youngest subject to have been diagnosed with alveolar soft part sarcoma. Surgical extirpation and microvascular reconstruction were successful, and the patient remains disease free 4 years post-operatively.

Adapting the Finetech-Brindley Sacral Anterior Root Stimulator for Bioelectronic Medicine.

The Finetech-Brindley Sacral Anterior Root Stimulator (SARS) is a low cost and reliable system. The architecture has been used for various bioelectric treatments, including several thousand implanted systems for restoring bladder function following spinal cord injury (SCI). Extending the operational frequency range would expand the capability of the system; enabling, for example, the exploration of eliminating the rhizotomy through an electrical nerve block. The distributed architecture of the SARS system enables stimulation parameters to be adjusted without modifying the implant design or manufacturing. To explore the design degrees-of-freedom, a circuit simulation was created and validated using a modified SARS system that supported stimulation frequencies up to 600 Hz. The simulation was also used to explore high frequency (up to 30kHz) behaviour, and to determine the constraints on charge delivered at the higher rates. A key constraint found was the DC blocking capacitors, designed originally for low frequency operation, not fully discharging within a shortened stimulation period. Within these current implant constraints, we demonstrate the potential capability for higher frequency operation that is consistent with presynaptic stimulation block, and also define targeted circuit improvements for future extension of stimulation capability.

Anatomic Subunit Approach to Composite Reconstruction of Facial Gunshot Wounds.

ABSTRACT: With a rise in gun violence in the United States, surgeons are tasked with effectively managing penetrating facial trauma. The purpose of this study is to assess methods used for successful composite reconstruction of each anatomical facial subunit following penetrating trauma. A retrospective chart review was performed in subjects undergoing craniofacial reconstruction following penetrating trauma. Reconstructive methods were analyzed through operative reports. Subjects were categorized by anatomical subunit reconstructed (mandible, maxilla (malar complex and roof/palate), orbit, and cranium) and method of reconstruction (open reduction internal fixation only, bone graft, free flap, implant, and tissue expansion). Thirty-six subjects underwent reconstruction for penetrating facial trauma. Involved subunits include 24 mandible, 11 malar complex, 13 palate, 18 orbit, and 11 cranium. Predominate reconstruction method was open reduction internal fixation only for mandible (45.8%), bone grafting for malar complex (81.8%), implant for orbit (66.7%) and cranium (63.6%), and local tissue rearrangement for palate (84.6%). The predominate bone graft donor site was iliac for mandible (42.9%), rib for malar complex (36.3%) and orbit (40.0%), and frontal bone for cranium (42.8%). The predominate free flap was osteocutaneous for all mandible, orbit, and cranium and 7 of 10 (70.0%) palate reconstructions. Tissue expansion was used in all subunits except cranium. In conclusion, bone grafting, implants, free tissue transfer, and tissue expansion are all viable reconstruction options for penetrating trauma. There is no single approach to use, and decisions regarding definitive reconstruction method should be based upon anatomical subunit involved and the size/area of defects.