Investigation of Liquid Collagen Ink for Three-Dimensional Printing.

Three-dimensional printing provides more versatility in the fabrication of scaffold materials for hard and soft tissue replacement, but a critical component is the ink. The ink solution should be biocompatible, stable, and able to maintain scaffold shape, size, and function once printed. This paper describes the development of a collagen ink that remains in a liquid pre-fibrillized state prior to printing. The liquid stability occurs due to the incorporation of ethylenediaminetetraacetic acid (EDTA) during dialysis of the collagen. Collagen inks were 3D-printed using two different printers. The resulting scaffolds were further processed using two different chemical crosslinkers, 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)/N-hydroxysuccinimide (EDC/NHS) and genipin; gold nanoparticles were conjugated to the scaffolds. The 3D-printed scaffolds were characterized to determine their extrudability, stability, amount of AuNP conjugated, and overall biocompatibility via cell culture studies using fibroblast cells and stroma cells. The results demonstrated that the liquid collagen ink was amendable to 3D printing and was able to maintain its 3D shape. The scaffolds could be conjugated with gold nanoparticles and demonstrated enhanced biocompatibility. It was concluded that the liquid collagen ink is a good candidate material for the 3D printing of tissue scaffolds.

Functional performance of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold: a pre-clinical in vitro tribological study.

Osteochondral grafts are used for repair of focal osteochondral lesions. Autologous grafts are the gold standard treatment; however, limited graft availability and donor site morbidity restrict use. Therefore, there is a clinical need for different graft sources/materials which replicate natural cartilage function. Chitosan has been proposed for this application. The aim of this study was to assess the biomechanics and biotribology of a bioresorbable chitosan/chitosan-nano-hydroxyapatite osteochondral construct (OCC), implanted in an in vitro porcine knee experimental simulation model. The OCC implanted in different surgical positions (flush, proud and inverted) was compared to predicate grafts in current clinical use and a positive control consisting of a stainless steel graft implanted proud of the cartilage surface. After 3 h (10 800 cycles) wear simulation under a walking gait, subsidence occurred in all OCC samples irrespective of surgical positioning, but with no apparent loss of material and low meniscus wear. Half the predicate grafts exhibited delamination and scratching of the cartilage surfaces. No graft subsidence occurred in the positive controls but wear and deformation of the meniscus were apparent. Implanting a new chitosan-based OCC either optimally (flush), inverted or proud of the cartilage surface resulted in minimal wear, damage and deformation of the meniscus.

Reduced Sliding Friction of Lubricant-Impregnated Catheters.

During urethral catheterization, sliding friction can cause discomfort and even hemorrhaging. In this report, we use a lubricant-impregnated polydimethylsiloxane coating to reduce the sliding friction of a catheter. Using a pig urethra attached to a microforce testing system, we found that a lubricant-impregnated catheter reduces the sliding friction during insertion by more than a factor of two. This suggests that slippery, lubricant-impregnated surfaces have the potential to enhance patient comfort and safety during catheterization.

Point-of-care rapid immunoassay performed on voided urine, refrigerated up to 24 hours, accurately detects bacteriuria.

OBJECTIVE: To collect voided urine from dogs with clinical signs of lower UTI and determine the diagnostic performance of a commercially available rapid immunoassay (RIA) immediately after urine collection and after refrigeration at 4 and 24 hours. ANIMALS: 40 client-owned dogs. METHODS: Aerobic urine culture was performed on urine collected by cystocentesis. Urine samples were collected by voiding, and the RIA performed in triplicate within 30 minutes (time 0) and again in triplicate after 4 and 24 hours of refrigeration. Test precision and agreement between culture results and RIA results at each time point were determined, and factors possibly associated with false results investigated. RESULTS: 14 of 40 dogs (35%) had UTI verified by aerobic urine culture, and all had positive RIA. Three dogs had false positive RIA results. Sensitivity, specificity, positive predictive value, and negative predictive value of the RIA were 100, 88%, 82%, and 100%, respectively, and results were not different after 4 and 24 hours of refrigeration. Precision was excellent. CLINICAL RELEVANCE: This point-of-care RIA, performed on voided urine refrigerated up to 24 hours, rapidly and accurately identifies bacteriuria in dogs with lower urinary tract clinical signs, inexpensively.

Predictive value of the National Early Warning Score 2 for hospitalised patients with viral respiratory illness is improved by the addition of inspired oxygen fraction as a weighted variable.

OBJECTIVES: The National Early Warning Score 2 (NEWS2) is validated for predicting acute deterioration, however, the binary grading of inspired oxygen fraction (FiO2) may limit performance. We evaluated the incorporation of FiO2 as a weighted categorical variable on NEWS2 prediction of patient deterioration. SETTING: Two hospitals at a single medical centre, Guy's and St Thomas' NHS Foundation Trust. DESIGN: Retrospective cohort of all ward admissions, with a viral respiratory infection (SARS-CoV-2/influenza). PARTICIPANTS: 3704 adult ward admissions were analysed between 01 January 2017 and 31 December 2021. METHODS: The NEWS-FiO2 score transformed FiO2 into a weighted categorical variable, from 0 to 3 points, substituting the original 0/2 points. The primary outcome was a composite of cardiac arrest, unplanned critical care admission or death within 24 hours of the observation. Sensitivity, positive predictive value (PPV), number needed to evaluate (NNE) and area under the receiver operating characteristic curve (AUROC) were calculated. Failure analysis for the time from trigger to outcome was compared by log-rank test. RESULTS: The mean age was 60.4±19.4 years, 52.6% were men, with a median Charlson Comorbidity of 0 (IQR 3). The primary outcome occurred in 493 (13.3%) patients, and the weighted FiO2 score was strongly associated with the outcome (p=<0.001). In patients receiving supplemental oxygen, 78.5% of scores were reclassified correctly and the AUROC was 0.81 (95% CI 0.81 to 0.81) for NEWS-FiO2 versus 0.77 (95% CI 0.77 to 0.77) for NEWS2. This improvement persisted in the whole cohort with a significantly higher failure rate for NEWS-FiO2 (p=<0.001). At the 5-point threshold, the PPV increased by 22.0% (NNE 6.7) for only a 3.9% decrease in sensitivity. CONCLUSION: Transforming FiO2 into a weighted categorical variable improved NEWS2 prediction for patient deterioration, significantly improving the PPV. Prospective external validation is required before institutional implementation.

Combining Experimental with Computational Infrared and Mass Spectra for High-Throughput Nontargeted Chemical Structure Identification.

The inability to identify the structures of most metabolites detected in environmental or biological samples limits the utility of nontargeted metabolomics. The most widely used analytical approaches combine mass spectrometry and machine learning methods to rank candidate structures contained in large chemical databases. Given the large chemical space typically searched, the use of additional orthogonal data may improve the identification rates and reliability. Here, we present results of combining experimental and computational mass and IR spectral data for high-throughput nontargeted chemical structure identification. Experimental MS/MS and gas-phase IR data for 148 test compounds were obtained from NIST. Candidate structures for each of the test compounds were obtained from PubChem (mean = 4444 candidate structures per test compound). Our workflow used CSI:FingerID to initially score and rank the candidate structures. The top 1000 ranked candidates were subsequently used for IR spectra prediction, scoring, and ranking using density functional theory (DFT-IR). Final ranking of the candidates was based on a composite score calculated as the average of the CSI:FingerID and DFT-IR rankings. This approach resulted in the correct identification of 88 of the 148 test compounds (59%). 129 of the 148 test compounds (87%) were ranked within the top 20 candidates. These identification rates are the highest yet reported when candidate structures are used from PubChem. Combining experimental and computational MS/MS and IR spectral data is a potentially powerful option for prioritizing candidates for final structure verification.

Men's mental health and the arts: perceived benefits and dynamics of engagement.

Arts engagement is gaining recognition as a non-clinical approach to promote mental health and well-being. However, the perceived utility of the arts to promote mental health among men with low socioeconomic status (SES) and how to best engage them is underexplored. This study explores the lived experiences of men with low SES who engage with the arts in Northern Ireland (n = 41). Data collected via focus groups (n = 5) and interviews (n = 11) were analysed using reflexive thematic analysis to inductively derive four themes. Theme 1 highlights how the arts facilitated friendship, a collective identity, peer support and a reason to socialize. Themes 2 and 3 explore how the arts enhanced self-esteem and emotional regulation by developing a routine, purpose, sense of mastery, a sense of catharsis through immersion in a soothing endeavour and an alternative outlet for self-expression. Theme 4 covers strategies that facilitate male engagement in the arts such as using a familiar space, delivering to an existing male group, framing the programme around male interests not health or creativity, building on existing strengths and capacities, enabling ownership, using tangible action-orientated activities, and being non-authoritative and flexible with delivery. This is one of the first studies to highlight the gendered dimensions in which men with low SES engage with and experience mental health benefits through arts engagement. This study points towards relevant theories to further understand the pathways between the arts and improved mental health among men which can inform development of tailored arts programmes for men.

Pulmonary Cystic Echinococcosis in a Child Presenting in the United Kingdom with Fever and Chest Pain: A Brief Report and Discussion on Management.

Cystic echinococcosis is a zoonosis caused by the larvae of Echinococcus granulosus . Pulmonary disease may be asymptomatic until the cyst ruptures or becomes secondarily infected. We report a case of pulmonary cystic echinococcosis presenting in the United Kingdom, with discussion on management: optimum antihelminthic agent, length of treatment and type of operative intervention. Treatment should be individualized to the clinical scenario.

Modeling human health behavior with a new index that measures connectivity.

Objective: Health behavior is an important determinant of health. Adherence to medication and abstinence from harmful substances are two critical health behaviors. Although conceptually related, both are assessed using disparate measures. The goal of this study was to develop and test a new index, gamma, which models health behavior by quantifying the connectedness of discrete incidents of health behavior. Study design and setting: We derive gamma from first principles and use it to reanalyze data from a published trial of treatment for alcohol use disorders. We model a primary endpoint, changes in binge drinking, using gamma and a traditional measure: change in number of monthly binges. The original trial was conducted in an urban hospital emergency department in the U.S. Results: Incorporating gamma into the model provided additional insights into the relationship between the intervention and long-term changes in drinking. Conclusion: Gamma provides an additional tool to model the effects of interventions on outcomes in trials of substance use interventions or medication adherence. Gamma measures the pattern of behavior and may increase the explanatory power of models assessing differences between various treatments. The gamma index offers the possibility of novel real-time interventions to promote healthy behaviors.

Development and Characterization of a AuNP-Genipin-Viscoelastic Collagen Material.

Lower back pain is one of the leading causes of disability, affecting 11.9% of the population worldwide and studies have shown that intervertebral disc degeneration is a common cause for chronic lower back pain. We have explored the combination of three components, viscoelastic collagen, genipin, and gold nanoparticles to determine its potential to promote regeneration of the intervertebral disc, specifically for nucleus pulposus regeneration. The goal of this study was to develop, fabricate and characterize different formulations of viscoelastic collagen conjugated with gold nanoparticles and genipin to assess the feasibility as a tissue template. Results demonstrated the successful attachment of gold nanoparticles to the viscoelastic collagen utilizing the genipin crosslinker. For each of the viscoelastic collagen compositions examined, cell biocompatibility was achieved. The results also demonstrated an increase in stiffness of the material with different sizes and concentrations of AuNPs. Results from the TEM and STEM also demonstrated that the viscoelastic collagen that was developed did not display the characteristic D banding pattern of polymerized collagen. The findings from this study could lead to the development of a more efficient and cost-effective treatment for patients with chronic back pain caused by IVD degeneration.

Photochemically produced SO2 in the atmosphere of WASP-39b.

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 µm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-µm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.

Production of Nano Hydroxyapatite and Mg-Whitlockite from Biowaste-Derived products via Continuous Flow Hydrothermal Synthesis: A Step towards Circular Economy.

Biowastes from agriculture, sewage, household wastes, and industries comprise promising resources to produce biomaterials while reducing adverse environmental effects. This study focused on utilising waste-derived materials (i.e., eggshells as a calcium source, struvite as a phosphate source, and CH3COOH as dissolution media) to produce value-added products (i.e., calcium phosphates (CaPs) derived from biomaterials) using a continuous flow hydrothermal synthesis route. The prepared materials were characterised via XRD, FEG-SEM, EDX, FTIR, and TEM analysis. Magnesium whitlockite (Mg-WH) and hydroxyapatite (HA) were produced by single-phase or biphasic CaPs by reacting struvite with either calcium nitrate tetrahydrate or an eggshell solution at 200 °C and 350 °C. Rhombohedral-shaped Mg-WH (23-720 nm) along with tube (50-290 nm diameter, 20-71 nm thickness) and/or ellipsoidal morphologies of HA (273-522 nm width) were observed at 350 °C using HNO3 or CH3COOH to prepare the eggshell and struvite solutions, and NH4OH was used as the pH buffer. The Ca/P (atomic%) ratios obtained ranged between 1.3 and 1.7, indicating the formation of Mg-WH and HA. This study showed that eggshells and struvite usage, along with CH3COOH, are promising resources as potential sustainable precursors and dissolution media, respectively, to produce CaPs with varying morphologies.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec G395H.

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems1,2. Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based3-5 and high-resolution ground-based6-8 facilities. Here we report the medium-resolution (R ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 µm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref. 9), obtained with the Near Infrared Spectrograph (NIRSpec) G395H grating of JWST. Our observations achieve 1.46 times photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO2 (28.5σ) and H2O (21.5σ), and identify SO2 as the source of absorption at 4.1 µm (4.8σ). Best-fit atmospheric models range between 3 and 10 times solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO2, underscore the importance of characterizing the chemistry in exoplanet atmospheres and showcase NIRSpec G395H as an excellent mode for time-series observations over this critical wavelength range10.

Considerations regarding carotid artery dose in radiotherapy of the cervical spine.

Radiation to the carotid arteries, e.g. in the context of head and neck cancer treatment, is one of several risk factors for artery stenosis. In principle, this fact may also have implications for stereotactic cervical spine radiotherapy, because long-term survival can be achieved in patients with oligometastatic disease and favorable prognostic features. Here, we suggest that radiation dose distributions with reduced dose to the carotid artery are achievable when planning stereotactic cervical spine radiotherapy. Patients with high likelihood of long-term survival may benefit from such vessel-sparing approaches.

An Education Intervention to Raise Awareness Reduces Self-reported Opioid Overprescribing by Plastic Surgery Residents.

PURPOSE: The aim of this study was to understand how opioid prescribing practices of plastic surgery residents changed after instituting opioid prescribing education (OPE) interventions. METHODS: Plastic surgery residents at a single academic institution completed a survey (fall 2017) assessing opioid prescribing following 8 common procedures. The Division then completed 3 multidisciplinary OPE interventions over 2.5 years, which provided passive learning to raise awareness without top-down prescribing guidelines. Residents were resurveyed at 2 time points after the interventions (fall 2018 and spring 2020). The primary outcome measure was self-reported morphine milligram equivalents prescribed. RESULTS: Survey response rates were 84% to 100%. Preintervention opioid prescriptions were characterized by high variability and absolute doses for all procedures. We observed statistically significant decreases in prescribed doses for most procedures at 9 months post intervention and further decreases at 2.5 years. In the most recently surveyed cohort, only 3 of 16 residents (18.8%) had OPE before residency, whereas 12 of 16 residents (75.0%) participated in OPE during residency. Eighty-eight percent of respondents "always" (8/16, 50%) or "usually" (6/16, 38%) considered the opioid epidemic when prescribing opioids, suggesting an improved prescribing culture. Barriers to better prescribing included duplicate prescriptions/accessing state-run prescription drug monitoring programs (75.0%), remote prescribing (75%), providing refills (56%), and prescribing opioids for patients on chronic opioid therapy (56%). CONCLUSION: This prospective cohort study demonstrates that a simple multidisciplinary, didactic OPE intervention that aimed to increase residents' awareness has the potential to reduce self-reported opioid prescribing and sustain prescribing practices over many years. We identify persistent barriers facing our resident prescribers today, enabling more opioid educational interventions in the future.

Extended Abdominal Pedicled Flap Using a Modified Abdominoplasty Incision for Reconstruction of an Extensive Forearm Defect.

Extensive upper extremity traumatic defects are challenging to reconstruct. Regional flaps are often too small or have pedicles in the zone of injury. Free microvascular flaps are not ideal options in the presence of extensive vascular injuries and in patients who cannot tolerate long procedures. We present a case featuring an extended abdominal flap using abdominoplasty-like incisions that facilitated simultaneous abdominoplasty and soft tissue coverage of an extensive, traumatic defect of the forearm and hand in a patient who was not a candidate for free flap.

Learners' Responses to a Virtual Cadaver Dissection Nerve Course in the COVID Era: A Survey Study.

Background Virtual education is an evolving method for teaching medical learners. During the coronavirus disease 2019 pandemic, remote learning has provided a replacement for conferences, lectures, and meetings, but has not been described as a method for conducting a cadaver dissection. We aim to demonstrate how learners perceive a virtual cadaver dissection as an alternative to live dissection. Methods A virtual cadaver dissection was performed to demonstrate several upper extremity nerve procedures. These procedures were livestreamed as part of an educational event with multimedia and interactive audience questions. Participants were queried both during and after the session regarding their perceptions of this teaching modality. Results Attendance of a virtual dissection held for three plastic surgery training institutions began at 100 and finished with 70 participants. Intrasession response rates from the audience varied between 68 and 75%, of which 75% strongly agreed that they were satisfied with the virtual environment. The audience strongly agreed or agreed that the addition of multimedia captions (88%), magnified video loupe views (82%), and split-screen multicast view (64%) was beneficial. Postsession response rate was 27%, and generally reflected a positive perspective about the content of the session. Conclusions Virtual cadaver dissection is an effective modality for teaching surgical procedures and can be enhanced through technologies such as video loupes and multiple camera perspectives. The audience viewed the virtual cadaver dissection as a beneficial adjunct to surgical education. This format may also make in-person cadaver courses more effective by improving visualization and allowing for anatomic references to be displayed synchronously.

Innovation in Delivering a Live, Virtual Cadaver Dissection Course.

SUMMARY: The availability of advanced telecommunication technology and the social restrictions introduced by a global pandemic have compelled the medical community to explore new avenues of surgical education. Although cadaver courses have long been a fundamental method for learning surgical anatomy and improving operative preparedness, the COVID-19 pandemic has made traditional dissections less practical. The need for quality virtual learning experiences motivated the authors to design and assess the feasibility of organizing a live, virtual upper extremity peripheral nerve cadaver dissection course. Three phases were critical when developing the course: preplanning, planning, and execution. The success of the live, virtual cadaver dissection depended not only on a detailed curriculum, but the technological audio-video-internet needs to effectively communicate and interact with the viewers. Virtual learning mitigates the risks of in-person dissection courses during a global pandemic and can be enhanced with interactive media (e.g., illustrations and schematics) to augment learning experiences.