Local Receptor-interacting Protein Kinase 2 inhibition mitigates HDM-induced asthma.

House dust mite (HDM) is the most frequent trigger of allergic asthma with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the NOD1/RIPK2 signalling pathway as a relevant contributor to murine HDM-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using an HDM-induced asthma model in Wild-type (WT) and humanized (h)NOD1 mice harbouring an asthma associated risk allele, and its relevance using airway liquid interface (ALI) epithelial cultures from asthmatics.A RIPK2 inhibitor was administered intra-nasally either preventively or therapeutically in a murine HDM-induced asthma model. Airway hyperresponsiveness (AHR), bronchoalveolar lavage composition, cytokine/chemokines expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices (PCLS). Furthermore, the inhibitor was tested on ALI cultures from asthmatics and controls.While local preventive administration of the RIPK2 inhibitor reduced AHR, eosinophilia, mucus production, Th2 cytokines and IL-33 in WT mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in hNOD1 mice. Results of PCLS emphasized an early role of TSLP and IL-33 in the NOD1-dependent response to HDM, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor down-regulated TSLP and chemokines in HDM-stimulated ALI epithelial cultures from asthma patients.These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in HDM-induced asthma.

Single-walled Carbon Nanotubes Wrapped with Charged Polysaccharides Enhance Extracellular Electron Transfer.

Microbial electrochemical systems (MESs) rely on the microbes' ability to transfer charges from their anaerobic respiratory processes to electrodes through extracellular electron transfer (EET). To increase the generally low output signal in devices, advanced bioelectrical interfaces tend to augment this problem by attaching conducting nanoparticles, such as positively charged multiwalled carbon nanotubes (CNTs), to the base carbon electrode to electrostatically attract the negatively charged bacterial cell membrane. On the other hand, some reports point to the importance of the magnitude of the surface charge of functionalized single-walled CNTs (SWCNTs) as well as the size of functional groups for interaction with the cell membrane, rather than their polarity. To shed light on these phenomena, in this study, we prepared and characterized well-solubilized aqueous dispersions of SWCNTs functionalized by either positively or negatively charged cellulose-derivative polymers, as well as with positively charged or neutral small molecular surfactants, and tested the electrochemical performance of Shewanella oneidensis MR-1 in MESs in the presence of these functionalized SWCNTs. By simple injection into the MESs, the positively charged polymeric SWCNTs attached to the base carbon felt (CF) electrode, and as fluorescence microscopy revealed, allowed bacteria to attach to these structures. As a result, EET currents continuously increased over several days of monitoring, without bacterial growth in the electrolyte. Negatively charged polymeric SWCNTs also resulted in continuously increasing EET currents and a large number of bacteria on CF, although SWCNTs did not attach to CF. In contrast, SWCNTs functionalized by small-sized surfactants led to a decrease in both currents and the amount of bacteria in the solution, presumably due to the detachment of surfactants from SWCNTs and their detrimental interaction with cells. We expect our results will help researchers in designing materials for smart bioelectrical interfaces for low-scale microbial energy harvesting, sensing, and energy conversion applications.

The Role of S100b Protein Biomarker in Brain Death: A Literature Review.

Brain death (BD) represents the irreversible loss of all brain functions, including the brainstem, and is equivalent to clinical death established by neurological criteria. However, clinical diagnosis, mainly based on the absence of primary reflexes post-acute brain injury, remains a challenge in hospital settings. The S100 calcium-binding protein beta (S100b) is used to monitor brain injuries, as recommended by neurotrauma care guidelines in some countries. Its levels are associated with severity and mortality, particularly after traumatic brain injury (TBI) and cerebral hemorrhage. The evaluation of S100b levels in investigating brain death is promising; however, aspects such as cutoff values remain to be elucidated. This paper reviews the literature on the use of S100b as a biomarker in diagnosing brain death. It is noteworthy that there is still no defined cutoff for S100b levels in confirming brain death. Additionally, when considering the use of S100b in emergency situations, a point-of-care methodology should be established to support clinical decision-making quickly and easily in the early identification of patients who are more likely to progress to brain death. In this context, S100b levels may assist in establishing the diagnosis of brain death, complementing existing clinical evidence. This, in turn, can optimize and qualify the organ donation process, reducing costs with ineffective therapies and minimizing the suffering of the families involved.

From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.

Vaccination can help prevent infection and can also be used to treat cancer, allergy, and potentially even drug overdose. Adjuvants enhance vaccine responses, but currently, the path to their advancement and development is incremental. We used a phenotypic small-molecule screen using THP-1 cells to identify nuclear factor-κB (NF-κB)-activating molecules followed by counterscreening lead target libraries with a quantitative tumor necrosis factor immunoassay using primary human peripheral blood mononuclear cells. Screening on primary cells identified an imidazopyrimidine, dubbed PVP-037. Moreover, while PVP-037 did not overtly activate THP-1 cells, it demonstrated broad innate immune activation, including NF-κB and cytokine induction from primary human leukocytes in vitro as well as enhancement of influenza and SARS-CoV-2 antigen-specific humoral responses in mice. Several de novo synthesis structural enhancements iteratively improved PVP-037's in vitro efficacy, potency, species-specific activity, and in vivo adjuvanticity. Overall, we identified imidazopyrimidine Toll-like receptor-7/8 adjuvants that act in synergy with oil-in-water emulsion to enhance immune responses.

Tuning the Emission of Bis-ethylenedioxythiophene-thiophenes upon Aggregation.

The ability of small lipophilic molecules to penetrate the blood-brain barrier through transmembrane diffusion has enabled researchers to explore new diagnostics and therapies for brain disorders. Until now, therapies targeting the brain have mainly relied on biochemical mechanisms, while electrical treatments such as deep brain stimulation often require invasive procedures. An alternative to implanting deep brain stimulation probes could involve administering small molecule precursors intravenously, capable of crossing the blood-brain barrier, and initiating the formation of conductive polymer networks in the brain through in vivo polymerization. This study examines the aggregation behavior of five water-soluble conducting polymer precursors sharing the same conjugate core but differing in side chains, using spectroscopy and various computational chemistry tools. Our findings highlight the significant impact of side chain composition on both aggregation and spectroscopic response.

The Alcohol Flush Response.

Nearly 540 million people world-wide have facial flushing and an increased heart rate after consuming alcohol. Known as the alcohol flushing response, this reaction to alcohol is a result of a genetic variant in an enzyme aldehyde dehydrogenase 2 (ALDH2), known as ALDH2*2. Mainly carried by those of East Asian descent, the genetic variant is likely the most common genetic variant carried in the world. Carrying this ALDH2*2 genetic variant has important health implications with respect cancer risk which is increased when carriers of the ALDH2*2 genetic variant frequently use of alcohol or tobacco products. This comic explains the alcohol flush response and the health risks associated with alcohol and tobacco use for those who carry an ALDH2*2 variant.

Three-dimensional EPI with shot-selective CAIPIRIHANA for rapid high-resolution quantitative susceptibility mapping at 3 T.

PURPOSE: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot-selective 2D CAIPIRIHANA to acquire high-resolution, whole-brain data for QSM with minimal distortion and blurring. METHODS: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1-mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1-mm, 0.78-mm, and 0.65-mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. RESULTS: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. CONCLUSION: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high-quality, clinically relevant susceptibility maps.

Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Vertical organic electrochemical transistor platforms for efficient electropolymerization of thiophene based oligomers.

Organic electrochemical transistors (OECTs) have emerged as promising candidates for various fields, including bioelectronics, neuromorphic computing, biosensors, and wearable electronics. OECTs operate in aqueous solutions, exhibit high amplification properties, and offer ion-to-electron signal transduction. The OECT channel consists of a conducting polymer, with PEDOT:PSS receiving the most attention to date. While PEDOT:PSS is highly conductive, and benefits from optimized protocols using secondary dopants and detergents, new p-type and n-type polymers are emerging with desirable material properties. Among these, low-oxidation potential oligomers are highly enabling for bioelectronics applications, however the polymers resulting from their polymerization lag far behind in conductivity compared with the established PEDOT:PSS. In this work we show that by careful design of the OECT geometrical characteristics, we can overcome this limitation and achieve devices that are on-par with transistors employing PEDOT:PSS. We demonstrate that the vertical architecture allows for facile electropolymerization of a family of trimers that are polymerized in very low oxidation potentials, without the need for harsh chemicals or secondary dopants. Vertical and planar OECTs are compared using various characterization methods. We show that vOECTs are superior platforms in general and propose that the vertical architecture can be expanded for the realization of OECTs for various applications.

Continuous iontronic chemotherapy reduces brain tumor growth in embryonic avian in vivo models.

Local and long-lasting administration of potent chemotherapeutics is a promising therapeutic intervention to increase the efficiency of chemotherapy of hard-to-treat tumors such as the most lethal brain tumors, glioblastomas (GBM). However, despite high toxicity for GBM cells, potent chemotherapeutics such as gemcitabine (Gem) cannot be widely implemented as they do not efficiently cross the blood brain barrier (BBB). As an alternative method for continuous administration of Gem, we here operate freestanding iontronic pumps - "GemIPs" - equipped with a custom-synthesized ion exchange membrane (IEM) to treat a GBM tumor in an avian embryonic in vivo system. We compare GemIP treatment effects with a topical metronomic treatment and observe that a remarkable growth inhibition was only achieved with steady dosing via GemIPs. Daily topical drug administration (at the maximum dosage that was not lethal for the embryonic host organism) did not decrease tumor sizes, while both treatment regimes caused S-phase cell cycle arrest and apoptosis. We hypothesize that the pharmacodynamic effects generate different intratumoral drug concentration profiles for each technique, which causes this difference in outcome. We created a digital model of the experiment, which proposes a fast decay in the local drug concentration for the topical daily treatment, but a long-lasting high local concentration of Gem close to the tumor area with GemIPs. Continuous chemotherapy with iontronic devices opens new possibilities in cancer treatment: the long-lasting and highly local dosing of clinically available, potent chemotherapeutics to greatly enhance treatment efficiency without systemic side-effects. SIGNIFICANCE STATEMENT: Iontronic pumps (GemIPs) provide continuous and localized administration of the chemotherapeutic gemcitabine (Gem) for treating glioblastoma in vivo. By generating high and constant drug concentrations near the vascularized growing tumor, GemIPs offer an efficient and less harmful alternative to systemic administration. Continuous GemIP dosing resulted in remarkable growth inhibition, superior to daily topical Gem application at higher doses. Our digital modelling shows the advantages of iontronic chemotherapy in overcoming limitations of burst release and transient concentration profiles, and providing precise control over dosing profiles and local distribution. This technology holds promise for future implants, could revolutionize treatment strategies, and offers a new platform for studying the influence of timing and dosing dependencies of already-established drugs in the fight against hard-to-treat tumors.

Laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS) demonstrates a direct impact of hypochlorous acid stress on PQS-mediated quorum sensing in Pseudomonas aeruginosa.

To establish infections in human hosts, Pseudomonas aeruginosa must overcome innate immune-generated oxidative stress, such as the hypochlorous acid (HOCl) produced by neutrophils. We set out to find specific biomarkers of oxidative stress through the development of a protocol for the metabolic profiling of P. aeruginosa cultures grown in the presence of different oxidants using a novel ionization technique for mass spectrometry, laser desorption rapid evaporative ionization mass spectrometry (LD-REIMS). We demonstrated the ability of LD-REIMS to classify samples as untreated or treated with a specific oxidant with 100% accuracy and identified a panel of 54 metabolites with significantly altered concentrations after exposure to one or more of the oxidants. Key metabolic changes were conserved in P. aeruginosa clinical strains isolated from patients with cystic fibrosis lung infections. These data demonstrated that HOCl stress impacted the Pseudomonas quinolone signal (PQS) quorum sensing system. Ten 2-alkyl-4-quinolones (AHQs) associated with the PQS system were significantly lower in concentration in HOCl-stressed P. aeruginosa cultures, including 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS), the most active signal molecule of the PQS system. The PQS system regulates the production of virulence factors, including pyocyanin and elastase, and their levels were markedly affected by HOCl stress. No pyocyanin was detectable and elastase concentrations were reduced by more than 75% in cultures grown with sub-lethal concentrations of HOCl, suggesting that this neutrophil-derived oxidant may disrupt the ability of P. aeruginosa to establish infections through interference with production of PQS-associated virulence factors. IMPORTANCE: This work demonstrates that a high-throughput ambient ionization mass spectrometry method can be used successfully to study a bacterial stress response. Its application to the opportunistic pathogen Pseudomonas aeruginosa led to the identification of specific oxidative stress biomarkers, and demonstrated that hypochlorous acid, an oxidant specifically produced by human neutrophils during infection, affects quorum sensing and reduces production of the virulence factors pyocyanin and elastase. No pyocyanin was detectable and elastase levels were reduced by more than 75% in bacteria grown in the presence of hypochlorous acid. This approach has the potential to be widely applicable to the characterization of the stress responses of bacteria.

Magnetic resonance elastography resolving all gross anatomical segments of the kidney during controlled hydration.

Introduction: Magnetic resonance elastography (MRE) is a non-invasive method to quantify biomechanical properties of human tissues. It has potential in diagnosis and monitoring of kidney disease, if established in clinical practice. The interplay of flow and volume changes in renal vessels, tubule, urinary collection system and interstitium is complex, but physiological ranges of in vivo viscoelastic properties during fasting and hydration have never been investigated in all gross anatomical segments simultaneously. Method: Ten healthy volunteers underwent two imaging sessions, one following a 12-hour fasting period and the second after a drinking challenge of >10 mL per kg body weight (60-75 min before the second examination). High-resolution renal MRE was performed using a novel driver with rotating eccentric mass placed at the posterior-lateral wall to couple waves (50 Hz) to the kidney. The biomechanical parameters, shear wave speed (cs in m/s), storage modulus (Gd in kPa), loss modulus (Gl in kPa), phase angle (Υ=2πatanGlGd) and attenuation (α in 1/mm) were derived. Accurate separation of gross anatomical segments was applied in post-processing (whole kidney, cortex, medulla, sinus, vessel). Results: High-quality shear waves coupled into all gross anatomical segments of the kidney (mean shear wave displacement: 163 ± 47 µm, mean contamination of second upper harmonics <23%, curl/divergence: 4.3 ± 0.8). Regardless of the hydration state, median Gd of the cortex and medulla (0.68 ± 0.11 kPa) was significantly higher than that of the sinus and vessels (0.48 ± 0.06 kPa), and consistently, significant differences were found in cs, Υ, and Gl (all p < 0.001). The viscoelastic parameters of cortex and medulla were not significantly different. After hydration sinus exhibited a small but significant reduction in median Gd by -0.02 ± 0.04 kPa (p = 0.01), and, consequently, the cortico-sinusoidal-difference in Gd increased by 0.04 ± 0.07 kPa (p = 0.05). Only upon hydration, the attenuation in vessels became lower (0.084 ± 0.013 1/mm) and differed significantly from the whole kidney (0.095 ± 0.007 1/mm, p = 0.01). Conclusion: High-resolution renal MRE with an innovative driver and well-defined 3D segmentation can resolve all renal segments, especially when including the sinus in the analysis. Even after a prolonged hydration period the approach is sensitive to small hydration-related changes in the sinus and in the cortico-sinusoidal-difference.

Perioperative and Complication Related Outcomes for Robotic-Assisted vs Open Radical Cystectomy: A Comparative National Surgical Quality Improvement Project Analysis.

Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk, with half of the patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARCs) have aimed to decrease patient morbidity and been increasingly adopted in North America. Currently, both open radical cystectomies (ORCs) and RARCs are frequently performed. The aim of this study is to contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors, including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019 and 2021 were identified in NSQIP and the corresponding cystectomy-targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robot assisted, including unplanned conversion to open cases for intention to treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes, including major complications, minor complications, and 30-day mortality rates, while adjusting for baseline differences significant on univariate analysis. Results: Five thousand three hundred forty-three RC cases were identified. Of these, 70% underwent planned ORC, while 30% received RARC. RARC was associated with longer operative times and shorter hospital length of stay compared with ORC. On multivariate analysis, there was no difference between the cohorts in 30-day rates of major complications, hospital readmissions, need for reoperation, or mortality. ORC was, however, associated with higher rates of minor complications, bleeding, superficial surgical site infections, and anastomotic leak. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30-day minor complications, most notably bleeding, compared with RARC. However, there is no difference in regard to perioperative major morbidity or mortality rates. This study is unique in the size of the cohorts compared, timeliness of data (2019-2021), applicability to a variety of different practice settings across the country, and ability to control for factors, such as type of urinary diversion and pathological bladder cancer staging, as well as use of neoadjuvant chemotherapy. This study was approved by the Institutional Review Board (IRB) specific to Thomas Jefferson University.

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro-magnetic tissue properties study group.

This article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi-echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Predicting dynamic, motion-related changes in B0 field in the brain at a 7T MRI using a subject-specific fine-trained U-net.

PURPOSE: Subject movement during the MR examination is inevitable and causes not only image artifacts but also deteriorates the homogeneity of the main magnetic field (B0 ), which is a prerequisite for high quality data. Thus, characterization of changes to B0 , for example induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. METHODS: We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo gradient-echo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-trained the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. RESULTS: Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. CONCLUSION: It is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of MR acquisitions without the use of navigators.

Institutional Failures as Structural Determinants of Suicide: The Opioid Epidemic and the Great Recession in the United States.

We investigate recent trends in U.S. suicide mortality using a "structural determinants of health" framework. We access restricted-use multiple cause of death files to track suicide rates among U.S. Black, White, American Indian/Alaska Native, and Latino/a men and women between 1990 and 2017. We examine suicide deaths separately by poisonings and nonpoisonings to illustrate that (1) women's suicide rates from poisonings track strongly with increases in prescription drug availability and (2) nonpoisoning suicide rates among all adult Americans track strongly with worsening economic conditions coinciding with the financial crash and Great Recession. These findings suggest that institutional failures elevated U.S. suicide risk between 1990 and 2017 by increasing access to more lethal means of self-harm and by increasing both exposure and vulnerability to economic downturns. Together, these results support calls to scale up to focus on the structural determinants of U.S. suicide.

Fiberbots: Robotic fibers for high-precision minimally invasive surgery.

Precise manipulation of flexible surgical tools is crucial in minimally invasive surgical procedures, necessitating a miniature and flexible robotic probe that can precisely direct the surgical instruments. In this work, we developed a polymer-based robotic fiber with a thermal actuation mechanism by local heating along the sides of a single fiber. The fiber robot was fabricated by highly scalable fiber drawing technology using common low-cost materials. This low-profile (below 2 millimeters in diameter) robotic fiber exhibits remarkable motion precision (below 50 micrometers) and repeatability. We developed control algorithms coupling the robot with endoscopic instruments, demonstrating high-resolution in situ molecular and morphological tissue mapping. We assess its practicality and safety during in vivo laparoscopic surgery on a porcine model. High-precision motion of the fiber robot delivered endoscopically facilitates the effective use of cellular-level intraoperative tissue identification and ablation technologies, potentially enabling precise removal of cancer in challenging surgical sites.

Auricular and laryngeal chondritis in nursery and finishing pigs.

This work aimed to characterize the clinic-pathological presentation of an outbreak of auricular and laryngeal chondritis in pigs. Visits were made to pig farms, where the clinical history was obtained, and clinical and postmortem examinations were performed. In those farms, 3% to 4% of pigs presented otohematomas, which started in the nursery and extended to the finishing phase. Moreover, some finishing pigs presented with respiratory distress, initially characterized as inspiratory dyspnea, associated by an uncommon respiratory stridor and culminating in death. Grossly, nursery piglets had enlarged ears, and on the cut surface, the cartilage was fragmented and associated with blood clots. In the finishing phase, in addition to auricular lesions, the epiglottis and arytenoid cartilages were thickened and distorted, which partially occluded the lumen. Microscopically, the laryngeal and auricular cartilages were fragmented, displayed a loss of matrix basophilia, and were surrounded by lymphohistiocytic inflammatory infiltrate, with occasional multinucleated giant cells and fibrosis. The lesions exclusively affected elastic cartilages. The disease in finishing pigs led to increased mortality and was a differential diagnosis to respiratory challenges. It was not possible to determine the factor that triggered this condition; however, a nutritional association is suspected. To the authors' knowledge, this is the first report of primary auricular and laryngeal chondritis in pigs.

Organic Electrochemical Transistor Aptasensor for Interleukin-6 Detection.

We demonstrate an organic electrochemical transistor (OECT) biosensor for the detection of interleukin 6 (IL6), an important biomarker associated with various pathological processes, including chronic inflammation, inflammaging, cancer, and severe COVID-19 infection. The biosensor is functionalized with oligonucleotide aptamers engineered to bind specifically IL6. We developed an easy functionalization strategy based on gold nanoparticles deposited onto a poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) gate electrode for the subsequent electrodeposition of thiolated aptamers. During this functionalization step, the reduction of sulfide bonds allows for simultaneous deposition of a blocking agent. A detection range from picomolar to nanomolar concentrations for IL6 was achieved, and the selectivity of the device was assessed against Tumor Necrosis Factor (TNF), another cytokine involved in the inflammatory processes.

Super-resolution QSM in little or no additional time for imaging (NATIve) using 2D EPI imaging in 3 orthogonal planes.

Quantitative Susceptibility Mapping has the potential to provide additional insights into neurological diseases but is typically based on a quite long (5-10 min) 3D gradient-echo scan which is highly sensitive to motion. We propose an ultra-fast acquisition based on three orthogonal (sagittal, coronal and axial) 2D simultaneous multi-slice EPI scans with 1 mm in-plane resolution and 3 mm thick slices. Images in each orientation are corrected for susceptibility-related distortions and co-registered with an iterative non-linear Minimum Deformation Averaging (Volgenmodel) approach to generate a high SNR, super-resolution data set with an isotropic resolution of close to 1 mm. The net acquisition time is 3 times the volume acquisition time of EPI or about 12 s, but the three volumes could also replace "dummy scans" in fMRI, making it feasible to acquire QSM in little or No Additional Time for Imaging (NATIve). NATIve QSM values agreed well with reference 3D GRE QSM in the basal ganglia in healthy subjects. In patients with multiple sclerosis, there was also a good agreement between the susceptibility values within lesions and control ROIs and all lesions which could be seen on 3D GRE QSMs could also be visualized on NATIve QSMs. The approach is faster than conventional 3D GRE by a factor of 25-50 and faster than 3D EPI by a factor of 3-5. As a 2D technique, NATIve QSM was shown to be much more robust to motion than the 3D GRE and 3D EPI, opening up the possibility of studying neurological diseases involving iron accumulation and demyelination in patients who find it difficult to lie still for long enough to acquire QSM data with conventional methods.