Insight into the Speciation of Heavy Metals in the Contaminated Soil Incubated with Corn Cob-Derived Biochar and Apatite.

Soil heavy metal contamination is a severe issue. The detrimental impact of contaminated heavy metals on the ecosystem depends on the chemical form of heavy metals. Biochar produced at 400 °C (CB400) and 600 °C (CB600) from corn cob was applied to remediate Pb and Zn in contaminated soil. After a one month amendment with biochar (CB400 and CB600) and apatite (AP) with the ratio of 3%, 5%, 10%, and 3:3% and 5:5% of the weight of biochar and apatite, the untreated and treated soil were extracted using Tessier's sequence extraction procedure. The five chemical fractions of the Tessier procedure were the exchangeable fraction (F1), carbonate fraction (F2), Fe/Mn oxide fraction (F3), organic matter (F4), and residual fraction (F5). The concentration of heavy metals in the five chemical fractions was analyzed using inductively coupled plasma mass spectroscopy (ICP-MS). The results showed that the total concentration of Pb and Zn in the soil was 3023.70 ± 98.60 mg kg-1 and 2034.33 ± 35.41 mg kg-1, respectively. These figures were 15.12 and 6.78 times higher than the limit standard set by the United States Environmental Protection Agency (U.S. EPA 2010), indicating the high level of contamination of Pb and Zn in the studied soil. The treated soil's pH, OC, and EC increased significantly compared to the untreated soil (p > 0.05). The chemical fraction of Pb and Zn was in the descending sequence of F2 (67%) > F5 (13%) > F1 (10%) > F3 (9%) > F4 (1%) and F2~F3 (28%) > F5 (27%) > F1 (16%) > F4 (0.4%), respectively. The amendment of BC400, BC600, and apatite significantly reduced the exchangeable fraction of Pb and Zn and increased the other stable fractions including F3, F4, and F5, especially at the rate of 10% of biochar and a combination of 5:5% of biochar and apatite. The effects of CB400 and CB600 on the reduction in the exchangeable fraction of Pb and Zn were almost the same (p > 0.05). The results showed that CB400, CB600, and the mixture of these biochars with apatite applied at 5% or 10% (w/w) could immobilize lead and zinc in soil and reduce the threat to the surrounding environment. Therefore, biochar derived from corn cob and apatite could be promising materials for immobilizing heavy metals in multiple-contaminated soil.

Chemical Fractionations of Lead and Zinc in the Contaminated Soil Amended with the Blended Biochar/Apatite.

Heavy metal contamination in agricultural land is an alarming issue in Vietnam. It is necessary to develop suitable remediation methods for environmental and farming purposes. The present study investigated the effectiveness of using peanut shell-derived biochar to remediate the two heavy metals Zn and Pb in laboratory soil assays following Tessier's sequential extraction procedure. The concentration of heavy metals was analyzed using Inductively coupled plasma mass spectrometry (ICP-MS). This study also compared the effectiveness of the blend of biochar and apatite applied and the mere biochar amendment on the chemical fractions of Pb and Zn in the contaminated agricultural soil. Results have shown that the investigated soil was extremely polluted by Pb (3047.8 mg kg−1) and Zn (2034.3 mg kg−1). In addition, the pH, organic carbon, and electrical conductivity values of amended soil samples increased with the increase in the amendment's ratios. The distribution of heavy metals in soil samples was in the descending order of carbonate fraction (F2) > residue fraction (F5) > exchangeable fraction (F1) > Fe/Mn oxide fraction (F3) > organic fraction (F4) for Pb and F5 ≈ F2 > F1 > F3 > F4 for Zn. The peanut shell-derived biochar produced at 400 °C and 600 °C amended at a 10% ratio (PB4:10 and PB6:10) could significantly reduce the exchangeable fraction Zn from 424.82 mg kg−1 to 277.69 mg kg−1 and 302.89 mg kg−1, respectively, and Pb from 495.77 mg kg−1 to 234.55 mg kg−1 and 275.15 mg kg−1, respectively, and immobilize them in soil. Amending the biochar and apatite combination increased the soil pH, then produced a highly negative charge on the soil surface and facilitated Pb and Zn adsorption. This study shows that the amendment of biochar and biochar blended with apatite could stabilize Pb and Zn fractions, indicating the potential of these amendments to remediate Pb and Zn in contaminated soil.

SBRT treatment of abdominal and pelvic oligometastatic lymph nodes using ring-mounted Halcyon Linac.

PURPOSE/OBJECTIVES: This work seeks to evaluate the plan quality, treatment delivery efficiency, and accuracy of single-isocenter volumetric modulated arc therapy (VMAT) of abdominal/pelvic oligometastatic lymph nodes (LNs) stereotactic body radiation therapy (SBRT) on Halcyon Linac. MATERIALS AND METHODS: After completing the in-house multitarget end-to-end phantom testing and independent dose verification using MD Anderson's single-isocenter/multi-target (lung and spine target inserts) thorax phantom, eight patients with two to three abdominal/pelvic oligometastatic LNs underwent highly conformal single-isocenter VMAT-SBRT treatment using the Halcyon Linac 6MV flattening filter free (FFF) beam. Targets were identified using an Axumin PET/CT scan co-registered with planning CT images and a single-isocenter was placed between/among the targets. Doses between 25 and 36.25 Gy in 5 fractions were delivered. Patients were treated every other day. Plans were calculated in Eclipse with advanced AcurosXB algorithm for heterogeneity corrections. For comparison, Halcyon VMAT-SBRT plans were retrospectively generated for SBRT-dedicated TrueBeam with a 6MV-FFF beam using identical planning geometry and objectives. Target coverage, conformity index (CI), dose to 2 cm away from each target (D2cm) and dose to adjacent organs-at-risk (OAR) were evaluated. Additionally, various treatment delivery parameters including beam-on time were recorded. RESULTS: Phantom measurements showed acceptable spatial accuracy of conebeam CT-guided Halcyon SBRT treatments including compliance with MD Anderson's single-isocenter/multi-targets phantom credentialing results. For patients, the mean isocenter to tumor center distance was 3.4 ± 1.2 cm (range, 1.5-4.8 cm). The mean combined PTV was 18.9 ± 10.9 cc (range, 5.6-39.5 cc). There was no clinically significant difference in dose to LNs, CI, D2cm and maximal doses to OAR between single-isocenter Halcyon and Truebeam VMAT-SBRT plans, although, Halcyon plans provided preferably lower maximal dose to adjacent OAR. Additionally, total monitor units, beam-on time and overall treatment time was lower with Halcyon plans. Halcyon's portal dosimetry demonstrated a high pass rate of 98.1 ± 1.6% for clinical gamma passing criteria of 2%/2 mm. CONCLUSION: SBRT treatment of abdominal/pelvic oligometastatic LNs with single-isocenter VMAT on Halcyon was dosimetrically equivalent to TrueBeam. Faster treatment delivery to oligometastatic LNs via single-isocenter Halcyon VMAT can improve clinic workflow and patient compliance, potentially reducing intrafraction motion errors for well-suited patients. Clinical follow-up of these patients is ongoing.

Clinical validation of ring-mounted halcyon linac for lung SBRT: comparison to SBRT-dedicated C-arm linac treatments.

Stereotactic body radiotherapy (SBRT) of lung tumors via the ring-mounted Halcyon Linac, a fast kilovoltage cone beam CT-guided treatment with coplanar geometry, a single energy 6MV flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for selected lung cancer patients. Four-dimensional (4D) CT-based treatment plans were generated using advanced AcurosXB algorithm with heterogeneity corrections using an SBRT board and Halcyon couch insert. Halcyon VMAT-SBRT plans with stacked and staggered multileaf collimators produced highly conformal radiosurgical dose distribution to the target, lower intermediate dose spillage, and similar dose to adjacent organs at risks (OARs) compared to SBRT-dedicated highly conformal clinical noncoplanar Truebeam VMAT plans following the RTOG-0813 requirements. Due to low monitor units per fraction and less multileaf collimator (MLC) modulation, the Halcyon VMAT plan can deliver lung SBRT fractions with an overall treatment time of less than 15 min (for 50 Gy in five fractions), significantly improving patient comfort and clinic workflow. Higher pass rates of quality assurance results demonstrate a more accurate treatment delivery on Halcyon. We have implemented Halcyon for lung SBRT treatment in our clinic. We suggest others use Halcyon for lung SBRT treatments using abdominal compression or 4D CT-based treatment planning, thus expanding the access of curative ultra-hypofractionated treatments to other centers with only a Halcyon Linac. Clinical follow-up results for patients treated on Halcyon Linac with lung SBRT is ongoing.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Pyrolyzed biowastes deactivated potentially toxic metals and eliminated antibiotic resistant genes for healthy vegetable production.

Potentially toxic metals (PTEs) and antibiotic resistance genes (ARGs) present in bio-wastes were the major environmental and health risks for soil use. If pyrolyzing bio-wastes into biochar could minimize such risks had not been elucidated. This study evaluated PTE pools, microbial and ARGs abundances of wheat straw (WS), swine manure (SM) and sewage sludge (SS) before and after pyrolysis, which were again tested for soil amendment at a 2% dosage in a pot experiment with a vegetable crop of pak choi (Brassica campestris L.). Pyrolysis led to PTEs concentration in biochars but reduced greatly their mobility, availability and migration potential, as revealed respectively by leaching, CaCl2 extraction and risk assessment coding. In SM and SS after pyrolysis, gene abundance was removed by 4-5 orders for bacterial, by 2-3 orders for fungi and by 3-5 orders for total ARGs. With these material amended, PTEs available pool decreased by 25%-85% while all ARGs eliminated to background in the pot soil. Unlike a >50% yield decrease and a >30% quality decline with unpyrolyzed SM and SS, their biochars significantly increased biomass production and overall quality of pak choi grown in the amended soil. Comparatively, amendment of the biochars decreased plant PTEs content by 23-57% and greatly reduced health risk of pak choi, with total target hazard quotient values well below the guideline limit for subsistence diet by adult. Furthermore, biochar soil amendment enabled a synergic improvement on soil fertility, product quality, and biomass production as well as metal stabilization in the soil-plant system. Thus, biowastes pyrolysis and reuse in vegetable production could help build up a closed loop of production-waste-biochar-production, addressing not only circular economy but healthy food and climate nexus also and contributing to achieving the United Nations sustainable development goals.

Optical Recording of Action Potential Initiation and Propagation in Mouse Skeletal Muscle Fibers.

Skeletal muscle fibers have been used to examine a variety of cellular functions and pathologies. Among other parameters, skeletal muscle action potential (AP) propagation has been measured to assess the integrity and function of skeletal muscle. In this work, we utilize 1-(3-sulfonatopropyl)-4[ß[2-(Di-n-octylamino)-6-naphtyl]vinyl]pyridinium betaine, a potentiometric dye, and mag-fluo-4, a low-affinity intracellular Ca2+indicator, to noninvasively and reliably measure AP conduction velocity in skeletal muscle. We used remote extracellular bipolar electrodes to generate an alternating polarity electric field that initiates an AP at either end of the fiber. Using enzymatically dissociated flexor digitorum brevis (FDB) fibers and high-speed line scans, we determine the conduction velocity to be ∼0.4 m/s. We applied these methodologies to FDB fibers under elevated extracellular potassium conditions and confirmed that the conduction velocity is significantly reduced in elevated [K+]o. Because our recorded velocities for FDB fibers were much slower than previously reported for other muscle groups, we compared the conduction velocity in FDB fibers to that of extensor digitorum longus (EDL) fibers and measured a significantly faster velocity in EDL fibers than FDB fibers. As a basis for this difference in conduction velocity, we found a similarly higher level of expression of Na+ channels in EDL than in FDB fibers. In addition to measuring the conduction velocity, we can also measure the passive electrotonic potentials elicited by pulses by applying tetrodotoxin and have constructed a circuit model of a skeletal muscle fiber to predict passive polarization of the fiber by the field stimuli. Our predictions from the model fiber closely resemble the recordings acquired from in vitro assays. With these techniques, we can examine how various pathologies and mutations affect skeletal muscle AP propagation. Our work demonstrates the utility of using 1-(3-sulfonatopropyl)-4[ß[2-(Di-n-octylamino)-6-naphtyl]vinyl]pyridinium betaine or mag-fluo-4 to noninvasively measure AP initiation and conduction.

Toward precision medicine and health: Opportunities and challenges in allergic diseases.

Precision medicine (also called personalized, stratified, or P4 medicine) can be defined as the tailoring of preventive measures and medical treatments to the characteristics of each patient to obtain the best clinical outcome for each person while ideally also enhancing the cost-effectiveness of such interventions for patients and society. Clearly, the best clinical outcome for allergic diseases is not to get them in the first place. To emphasize the importance of disease prevention, a critical component of precision medicine can be referred to as precision health, which is defined herein as the use of all available information pertaining to specific subjects (including family history, individual genetic and other biometric information, and exposures to risk factors for developing or exacerbating disease), as well as features of their environments, to sustain and enhance health and prevent the development of disease. In this article I will provide a personal perspective on how the precision health-precision medicine approach can be applied to the related goals of preventing the development of allergic disorders and providing the most effective diagnosis, disease monitoring, and care for those with these prevalent diseases. I will also mention some of the existing and potential challenges to achieving these ambitious goals.

IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity.

BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.

Low-Cost Intra-Articular Distraction Technique Using Kirschner Wires and a Toothed Lamina Spreader.

We describe a low-cost (instrument cost) technique for joint distraction using 2 Kirschner wires and a toothed lamina spreader in lieu of a Hintermann distractor. The described technique allows for temporary intra-articular distraction and visualization and preservation of the articular surface with extra-articular instrumentation. The technique can also allow for closed reduction and percutaneous treatment in cases of soft tissue compromise. Additionally, the technique uses common orthopedic surgical instruments, leading to a minimal learning curve for novice surgeons. We have found this distraction technique to be most effective for intra-articular preparation of hindfoot and midfoot arthrodeses and for navicular fracture reduction.

Drivers of coastal shoreline change: case study of hon dat coast, Kien Giang, Vietnam.

Coastal shorelines are naturally dynamic, shifting in response to coastal geomorphological processes. Globally, land use change associated with coastal urban development and growing human population pressures is accelerating coastal shoreline change. In southern Vietnam, coastal erosion currently is posing considerable risks to shoreline land use and coastal inhabitants. The aim of this paper is to quantify historical shoreline changes along the Hon Dat coast between 1995 and 2009, and to document the relationships between coastal mangrove composition, width and density, and rates of shoreline change. The generalized linear mixed-effects models were used to quantify the major biophysical and land-use factors influencing shoreline change rates. Most significant drivers of the rates of change are cutting of mangroves, the dominant mangrove genus, changes in adjacent shoreline land use, changes of shoreline land cover, and width of fringing mangroves. We suggest that a possible and inexpensive strategy for robust mangrove shoreline defense is direct mangrove planting to promote mangrove density with the presence of breakwater structures. In the shorter term, construction of coastal barriers such as fence-structured melaleuca poles in combination with mangrove restoration schemes could help retain coastal sediments and increase the elevation of the accretion zone, thereby helping to stabilize eroding fringe shorelines. It also is recommended that implementation of a system of payments for mangrove ecosystem services and the stronger regulation of mangrove cutting and unsustainable land-use change to strengthen the effectiveness of mangrove conservation programs and coastal land-use management.

Double-vertebral segment SBRT via novel ring-mounted Halcyon Linac: Plan quality, delivery efficiency and accuracy.

To evaluate the plan quality, treatment delivery efficiency, and accuracy of single-isocenter/multi-target (SIMT) volumetric modulated arc therapy (VMAT) of double-vertebral segments stereotactic body radiation therapy (SBRT) on Halcyon ring delivery system (RDS). In-house multi-target end-to-end phantom testing and independent dose verification using the MD Anderson's single-isocenter/multi-target (lung/spine targets) thorax phantom were completed. Six previously treated patients with 2-vertebral segments on thoracic and/or lumber spine were replanned on Halcyon RDS with 6MV-FFF beam using a single-isocenter placed between the vertebral segments. Three full VMAT arcs with 0° and ±10° collimator angles and advanced Acuros-based dose engine for heterogeneity corrections were used. Prescription was 35 Gy in 5 fractions to each vertebral-segment, simultaneously. For comparison, Halcyon VMAT-SBRT plans were retrospectively created on SBRT-dedicated Truebeam with a 6MV-FFF beam using identical planning geometry and optimization objectives. Target coverage, conformity index (CI), heterogeneity index (HI), gradient index (GI), dose to 2-cm away from each target (D2-cm), and dose to adjacent organs-at-risk (OAR) were evaluated per NRG-BR002 protocol. Treatment delivery parameters were evaluated for both plans. In-house phantom measurements showed acceptable spatial accuracy (< 1mm within 5-cm from the isocenter) of conebeam CT-guided Halcyon SBRT treatments. The MD Anderson phantom irradiation credentialing results met IROC requirements for protocol patients. Mean isocenter-to-tumor center distance was 3.3 ± 0.6-cm (range 2.4 to 4.3-cm). Mean combined PTV was 57.3 ± 31.3 cc (range 20.1 to 99.9 cc). Both Halcyon and Truebeam SIMT-VMAT plans met NRG-BR002 compliance criteria and show similar CI, HI, GI, D2-cm. Maximal and volumetric doses to adjacent OAR including dose to partial spinal cord were lower with Halcyon RDS. Average total monitor units, modulation, and overall treatment time were lower with Halcyon plans by 130 MU, 0.2, 3.8 min, respectively, with similar beam-on time. Average pre-treatment patient-specific portal-dosimetry QA results on Halcyon showed a high pass rate of 99.6%, compared to SBRT-dedicated Truebeam pass rate of 96.8%, for 2%/2 mm clinical gamma passing criteria, suggesting more accurate treatment delivery on Halcyon RDS. SBRT treatment of double-vertebral segments via SIMT-VMAT plans on Halcyon for selected patients is feasible and dosimetrically superior to Truebeam Linac. Faster treatment delivery (<10 min) of double-vertebral segment SBRT on Halcyon could reduce patient intolerance due to severe back pain, potentially reduce intra-fraction motion errors, and improve patient throughput, and clinic workflow.

Imagining the city in lockdown: Place in the COVID-19 self-recordings of the Lothian Diary Project.

The COVID-19 pandemic brought about a profound change to the organization of space and time in our daily lives. In this paper we analyze the self-recorded audio/video diaries made by residents of Edinburgh and the Lothian counties during the first national lockdown. We identify three ways in which diarists describe a shift in place-time, or "chronotope", in lockdown. We argue that the act of making a diary for an audience of the future prompts diarists to contrast different chronotopes, and each of these orientations illuminates the differential impact of the COVID-19 lockdowns across the community.

A Mechanistic DNA Repair and Survival Model (Medras): Applications to Intrinsic Radiosensitivity, Relative Biological Effectiveness and Dose-Rate.

Variations in the intrinsic radiosensitivity of different cells to ionizing radiation is now widely believed to be a significant driver in differences in response to radiotherapy. While the mechanisms of radiosensitivity have been extensively studied in the laboratory, there are a lack of models which integrate this knowledge into a predictive framework. This paper presents an overview of the Medras model, which has been developed to provide a mechanistic framework in which different radiation responses can be modelled and individual responses predicted. This model simulates the repair of radiation-induced DNA damage, incorporating the overall kinetics of repair and its fidelity, to predict a range of biological endpoints including residual DNA damage, mutation, chromosome aberration, and cell death. Validation of this model against a range of exposure types is presented, including considerations of varying radiation qualities and dose-rates. This approach has the potential to inform new tools to deliver mechanistic predictions of radiation sensitivity, and support future developments in treatment personalization.

Understanding the role of gut microbiota in the pathogenesis of schizophrenia.

Schizophrenia is a chronic mental disorder with marked symptoms of hallucination, delusion, and impaired cognitive behaviors. Although multidimensional factors have been associated with the development of schizophrenia, the principal cause of the disorder remains debatable. Microbiome involvement in the etiology of schizophrenia has been widely researched due to the advancement in sequencing technologies. This review describes the contribution of the gut microbiome in the development of schizophrenia that is facilitated by the gut-brain axis. The gut microbiota is connected to the gut-brain axis via several pathways and mechanisms, that are discussed in this review. The role of the oral microbiota, probiotics and prebiotics in shaping the gut microbiota are also highlighted. Lastly, future perspectives for microbiome research in schizophrenia are addressed.

Impact of Syndecan-2-Selected Mesenchymal Stromal Cells on the Early Onset of Diabetic Cardiomyopathy in Diabetic db/db Mice.

Background: Mesenchymal stromal cells (MSCs) are an attractive cell type for cell therapy given their immunomodulatory, anti-fibrotic, and endothelial-protective features. The heparin sulfate proteoglycan, syndecan-2/CD362, has been identified as a functional marker for MSC isolation, allowing one to obtain a homogeneous cell product that meets regulatory requirements for clinical use. We previously assessed the impact of wild-type (WT), CD362-, and CD362+ MSCs on local changes in protein distribution in left ventricular (LV) tissue and on LV function in an experimental model of early-onset diabetic cardiomyopathy. The present study aimed to further explore their impact on mechanisms underlying diastolic dysfunction in this model. Materials: For this purpose, 1 × 106 WT, CD362-, or CD362+ MSCs were intravenously (i.v.) injected into 20-week-old diabetic BKS.Cg-m+/+Leprdb/BomTac, i.e., db/db mice. Control animals (db+/db) were injected with the equivalent volume of phosphate-buffered saline (PBS) alone. After 4 weeks, mice were sacrificed for further analysis. Results: Treatment with all three MSC populations had no impact on blood glucose levels in db/db mice. WT, CD362-, and CD362+ MSC application restored LV nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels in db/db mice, which correlated with a reduction in cardiomyocyte stiffness. Furthermore, all stromal cells were able to increase arteriole density in db/db mice. The effect of CD362+ MSCs on NO and cGMP levels, cardiomyocyte stiffness, and arteriole density was less pronounced than in mice treated with WT or CD362- MSCs. Analysis of collagen I and III protein expression revealed that fibrosis had not yet developed at this stage of experimental diabetic cardiomyopathy. All MSCs reduced the number of cardiac CD3+ and CD68+ cells in db/db mice, whereas only splenocytes from CD362-- and CD362+-db/db mice exhibited a lower pro-fibrotic potential compared to splenocytes from db/db mice. Conclusion: CD362+ MSC application decreased cardiomyocyte stiffness, increased myocardial NO and cGMP levels, and increased arteriole density, although to a lesser extent than WT and CD362- MSCs in an experimental model of early-onset diabetic cardiomyopathy without cardiac fibrosis. These findings suggest that the degree in improvement of cardiomyocyte stiffness following CD362+ MSC application was insufficient to improve diastolic function.

3-Dimensional Printed Models May Be a Useful Tool When Planning Revision Anterior Cruciate Ligament Reconstruction.

PURPOSE: To determine whether using 3-dimensional (3D)-printed models in addition to computed tomography (CT) scans to evaluate the primary femoral and tibial tunnels before revision anterior cruciate ligament (ACL) reconstruction leads to better agreement with the surgical approach than CT alone. METHODS: Fifteen patients who underwent revision ACL reconstruction were retrospectively identified. The mean age was 24.3 years, and 73% were female. Using only CT images, 3 board-certified orthopaedists and 5 sports medicine orthopaedic fellows evaluated whether the existing tibial and femoral tunnels were acceptable for the revision surgery. Subsequently, 3D-printed models were made available in addition to the CT scan, and the same questions were asked. RESULTS: For the attending orthopaedic physicians, adding the 3D-printed models did not have a significant impact on the tibial or femoral tunnel agreement compared with the surgical approach. With the fellow physicians, however, using the 3D-printed models with tibial tunnel evaluation led to a higher agreement rate (76%) compared with CT images alone (63%) (P = .050). Furthermore, with the fellow physicians, there was a higher overall agreement when evaluating both the tibial and femoral tunnels with the addition of 3D-printed models (74%) compared with CT alone (65%) (P = .049). CONCLUSION: Our hypothesis that using 3D-printed models leads to better agreement with the surgical approach was unsupported based on the response of the board-certified orthopaedists. Based on the fellow response, it stands to reason that 3D-printed models may be a useful tool in understanding spatial orientation when planning for revision ACL surgery. LEVEL OF EVIDENCE: IV, retrospective case series.

Multi-use of the sea: A wide array of opportunities from site-specific cases across Europe.

The concept of multi-use of the sea has gained popularity in recent years as a result of ocean space (coastal areas and regions with relatively small sea space in particular) becoming increasingly crowded due to the development of the maritime economy. Competing claims for space can be a source of conflict, however this may also lead to mutual benefits for different users when sustainable combinations are sought. Despite increasing European-wide efforts, on-the-ground knowledge and practice of multi-use are still limited. Therefore, with the aim of investigating opportunities for multi-use development in the European seas, 10 case studies were selected, involving different site-specific contexts. This study analyses the characteristics and development potential for ocean multi-use, integrating results from desk analysis and stakeholder perceptions from different sectors in each of the case study locations. Similarities and differences between various combinations of sea uses are also identified. The results show a high heterogeneity of multi-use opportunities between case studies, with a range of combinations identified. The investigated combinations of maritime uses share an overall balance between factors promoting (drivers) and hindering (barriers) multi-use development. Based on stakeholder opinions, expected benefits (added values) of multi-use implementation outweigh potential negative impacts. Management actions are also proposed to further exploit multi-use potential at a local, regional (sub-national) and national levels.

The linear quadratic model: usage, interpretation and challenges.

The linear-quadratic model is one of the key tools in radiation biology and physics. It provides a simple relationship between cell survival and delivered dose: [Formula: see text], and has been used extensively to analyse and predict responses to ionising radiation both in vitro and in vivo. Despite its ubiquity, there remain questions about its interpretation and wider applicability-Is it a convenient empirical fit or representative of some deeper mechanistic behaviour? Does a model of single-cell survival in vitro really correspond to clinical tissue responses? Is it applicable at very high and very low doses? Here, we review these issues, discussing current usage of the LQ model, its historical context, what we now know about its mechanistic underpinnings, and the potential challenges and confounding factors that arise when trying to apply it across a range of systems.

A Medial Malleolar "Fleck Sign" May Predict Ankle Instability in Ligamentous Supination External Rotation Ankle Fractures.

BACKGROUND: Ankle joint stability dictates treatment in ligamentous supination external rotation ankle injuries (LSERAI). Investigation of the medial structures that support the ankle mortise is critical, and a small avulsion fracture, or "fleck", of the medial malleolus is occasionally encountered. This study aimed to assess the utility of this medial malleolus fleck sign (MMFS) in diagnosing instability requiring surgery in LSERAI. METHODS: This retrospective observational study examined 166 LSERAI at a single level I trauma center. A standardized diagnostic and treatment protocol for ankle fractures was followed. LSERAI at presentation were reported as having a normal, dynamically wide, or statically wide medial clear space. Patient demographics, MMFS characteristics, and the use of operative management were recorded. RESULTS: MMFS incidence in the cohort was 16 (10%) of 166 and was present in 25% of patients with unstable LSERAI. Fifteen (94%) of 16 patients with a MMFS were deemed to have an unstable LSERAI (P < .005). MMFS had a 25% sensitivity and 99% specificity in diagnosing an unstable LSERAI. For the subgroup of patients without a statically wide medial clear space, MMFS had a 50% sensitivity and 99% specificity in determining instability. CONCLUSION: A MMFS may be indicative of an unstable LSERAI. With previous MRI studies demonstrating complete deltoid disruption in unstable LSERAI, we deduce the MMFS may be associated with extensive deltoid incompetence. The MMFS may help to diagnose a complete deltoid injury in LSERAI with a normal medial clear space, which could influence treatment and reduce patient morbidity, radiation exposure, and healthcare costs. LEVELS OF EVIDENCE: Level III: Retrospective Cohort Study.