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Photothermal therapy (PTT) is a novel cancer treatment using a photoabsorber to cause hyperthermia to kill tumors by laser irradiation. Prussian blue nanoparticles (PB NPs) are considered as next-generation photothermal agents due to the facile synthesis and excellent absorption of near-infrared light. Although PB NPs demonstrate remarkable PTT capabilities, their clinical application is limited due to their systemic toxicity. Bacterial cellulose (BC) has been applied to various bio-applications based on its unique properties and biocompatibility. Herein, we design composites with PB NPs and BC as an injectable, highly biocompatible PTT agent (IBC-PB composites). Injectable bacterial cellulose (IBC) is produced through the trituration of BC, with PB NPs synthesized on the IBC surface to prepare IBC-PB composites. IBC-PB composites show in vitro and in vivo photothermal therapeutic effects similar to those of PB NPs but with significantly greater biocompatibility. Specifically, in vitro therapeutic index of IBC-PB composites is 26.5-fold higher than that of PB NPs. Furthermore, unlike PB NPs, IBC-PB composites exhibit no overt toxicity in mice as assessed by blood biochemical analysis and histological images. Hence, it is worth pursuing further research and development of IBC-PB composites as they hold promise as safe and efficacious PTT agents for clinical application.
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Nanocompuestos , Nanopartículas , Neoplasias , Animales , Ratones , Terapia Fototérmica , Nanopartículas/química , Fototerapia , Nanocompuestos/uso terapéutico , Nanocompuestos/química , Neoplasias/terapiaRESUMEN
We describe the conceptual design of a portable, liquid-helium-free, all-REBCO, 0.5-T/560-mm point-of-care magnetic resonance imaging (MRI) magnet. It is free from an external power supply and a refrigeration system during operation. In our portable MRI magnet, we use a detachable "cryocirculator" that circulates, in a closed circuit, cold working fluid, and most importantly for portability, it can be readily coupled to or decoupled from the magnet, in contrast, a conventional cryocooler is mechanically attached to the magnet. Another unique feature of our system is a volume of solid nitrogen (SN2) in the cold chamber that adds enough thermal mass to the magnet in the 30-36-K operating temperature range, enabling it to maintain its field over a period of, for this system, ≥10 hours, plenty enough for this portable MRI system, uncoupled from its cryocirculator, to perform its mission before it needs recooling.
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As a preliminary work, we have completed a 12.5-mm-cold-bore high-temperature superconducting (HTS) REBCO magnet prototype and successfully operated it up to 25 T at 10 K cooled by a cryocooler only, without liquid helium. In this paper we present the first-cut design of a cryogen-free all-REBCO 23.5-T/25-mm-warm-bore magnet having a high homogeneity of <0.1 ppm over a 1-cm diameter of spherical volume for a benchtop 1-GHz microcoil NMR spectroscopy. We also investigate a shielding design to reduce a 5-gauss fringe field radius to ≤1.5 m. This benchtop magnet will incorporate all the innovative design and operation concepts validated by the prototype magnet: 1) all-HTS composition and operation at above 4.2 K; 2) no-insulation winding technique with an extra shunting that makes this high-field REBCO magnet compact, mechanically robust, and self-protecting; 3) a single coil formation that leads, compared with the traditional multi-nested high-field NMR magnet, to simpler and more affordable manufacturing processes; 4) operational temperature-controlled screening-current reduction method which reduces peak stresses within the REBCO coil and field errors; and 5) cryogenic design for conduction-cooling operation.
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The metal tape co-winding or a metal-as-insulation (MI) winding method is an excellent way to improve the mechanical properties and reduce the average current density, thereby decreasing the stress in high-field REBCO magnet without completely losing the benefits of the no-insulation (NI) winding method. However, the MI winding increases the resistance between turns, which is known as characteristic resistance. The increased characteristic resistance can reduce the bypass current during abnormal transition situation, such as quench, which may not be desirable from a magnet protection point of view. To take advantage of both the MI and NI winding, one possible solution to reduce characteristic resistance of the MI winding coils is to add a shunt on top of the winding surface of the coil. We call this method surface-shunted-metal-as-insulation (SSMI). In this presentation, we compare the characteristic resistances and their correlated self-protecting characteristics between NI, MI, and SSMI. We present the test results of single pancake coils which wound using different winding methods (NI, MI, and SSMI) with same winding pressure of 20 N. In particular, we investigated how the SSMI method affects the characteristic resistance.
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The No-insulation-like (NI) coil's turn-to-turn current paths prevent local heating by forcing the current to bypass into nearby turns when a hot spot appears in a coil. However, the changing direction of the current by bypassing will change the magnetic flux, which generates unwanted induced currents in the adjacent coils in a multiply-stacked HTS magnet. This induced current can temporarily exceed the designed maximum currents in the NI coils, damaging the magnet. A partial-insulation (PI) coil, in which a single or multiple insulated, with a polyimide-like material or a thin ceramic film, is inserted between windings to hinder the current paths, can reduce the peak induced currents in the NI HTS coil's current paths. In this paper, we present the results of a simulation study on the peak-induced current upon a quench of the PI HTS magnet with a double pancake. The study shows that the peak-induced current varies with the number of insulated turns. We also discuss the induced current turn-by-turn simulation. According to the simulation result, the PI effectively reduces overall induced current, especially insulation applied every two turns.
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We present the operation result of a cryogen-free 23.5 T/φ12.5 mm-cold-bore magnet prototype composed of a stack of 12 no-insulation (NI) REBCO single pancake coils-ten middle coils of 6-mm wide and two end coils of 8-mm wide tape-forming 6 double pancake (DP) coils with inner joints. Each coil was wound with the tape having only 1-µm-thick copper layer on each side to overcome the conductor thickness uniformity issue and enhance the mechanical strength within the winding, and then, additional electrical shunting by thin layers of solder was applied on the top and bottom surfaces of each DP coil for effective cooling and quench protection-called extreme-NI winding technique. With this small prototype magnet towards a benchtop 1-GHz NMR, we validate our coil design that include conductor performance, screening-current-induced field and stresses, and conduction-cooling cryogenics. Included in the paper are: 1) conductor issues and our counterproposal in winding; 2) screening-current reduction method; 3) design and manufacture summary of the magnet; and 4) operating test results of the magnet up to 25 Tesla.
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BACKGROUND: Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. RESULTS: Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and 64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g-1 from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. CONCLUSION: Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent.
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Sistemas de Liberación de Medicamentos , Liposomas/farmacología , Nanoestructuras , Terapia Fototérmica/métodos , Medicina de Precisión/métodos , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Oro/farmacología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/tratamiento farmacológico , Polietilenglicoles , Tomografía de Emisión de Positrones , Nanomedicina Teranóstica/métodosRESUMEN
We present a design overview of the MIT 1.3-GHz LTS/HTS NMR magnet (1.3G) with a newly designed 835-MHz REBCO insert (H835) as a replacement for the 800-MHz REBCO insert (H800) that was damaged when it quenched during operation in 2018. The new H835 is designed to contribute 19.6 T in a background field of 10.93 T by an LTS NMR magnet that normally rated at 11.74 T (500 MHz): combined, 1.3G generates a total field of 30.53 T corresponding to a proton resonance frequency of 1.3 GHz. H835 is designed to operate stably while meeting 1.3G design constraints. We have also designed H835 to protect it from permanent damage in an improbable event like a quench. Key design features are: 1) a single-coil formation, composed of 38 stacked metal-co-wound no-insulation and 2 stacked no-insulation double-pancake coils, all with mechanically improved cross-over sections; 2) enhanced thermal stability; and 3) reduced current margin with a detect-and-heat method. This paper includes: 1) electromagnetic and mechanical design of H835; 2) cryogenics overview; 3) quench protection strategy; and 3) discussion on the next steps to successfully complete 1.3G.
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The No-Insulation (NI) winding provides intrinsic bypassing current paths that enable self-protection from overheating. The self-protection of the NI coil is one of the most promising protection techniques for the high field high-temperature superconductor (HTS) magnet applications. Since the additional paths are valid for an HTS magnet with a thinner matrix, the self-protection mechanism is applicable even for the higher current density magnet with reduced matrix thickness inside the HTS tape. However, reducing the matrix can cause damage to the magnet by producing excessive heat during the quench. This research introduces a new modeling method to investigate the hot-spot characteristics in the REBCO NI pancake coil. The model is also validated with a sample NI HTS coil experiment result. Radial direction Normal Zone Propagation (NZP) velocity of the sample coil is estimated based on the suggested model. The calculated radial direction NZP velocity is applied to calculate the center field drop of the NI HTS coil, and the result is well-matched with the experiment result. We also introduce one example of the model applications. The maximum current density that will not exceed a given reference temperature in the adiabatic cooling condition is estimated using the model.
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We suggested an MgB2 joint process with its own heat-treatment schedule to apply it for our 1.5-T MgB2 "finger" MRI magnet. In fabricating the MgB2 magnet, the optimal heat-treatment schedule to attain a reproducible and high critical current is different in a joint and a coil. To solve this problem, we introduced an additional heating system, which is composed of a cartridge heater and a thermocouple connected with a copper block, into a box-type furnace. Then, we carried out heat-treatments with exclusively increasing the joint-part temperature above the Mg melting point of 645 °C-the joint was actually heated up to 700 °C. We evaluated a critical current and a crystal structure of the obtained MgB2 joint. From experimental results, we found that the joint heated with the own heat-treatment schedule, which is 700 °C for 1 h + 600 °C for 11 h, showed a good I c of over 450 A at 15K under self-field. The joint resistance was estimated by the coil operation for 18 days, and it was expected to be less than 10-12 Ω.
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BACKGROUND: The purpose of this study was to determine the unloading effect of total hip arthroplasty (THA) on the ipsilateral knee joint through the joint line convergence angle (JLCA) change and determine the changes in other coronal radiographic parameters after THA, and evaluate the sensitivity of JLCA. PATIENTS AND METHODS: We retrospectively assessed 70 patients who underwent unilateral THA. Hip parameters such as neck shaft angle (NSA), neck length, and femoral offset and coronal alignment parameters of the lower extremity such as hip-knee-ankle angle (HKA), femur length, mechanical lateral distal femoral angle (mLDFA), JLCA, medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), and plafond talus angle (PTA) were measured in the operative and non-operative sides. We compared all hip and coronal alignment parameters between before and 1 year after THA, and the amount of standardized changes (Δ) between all hip and coronal alignment parameters on the operative side, respectively. RESULTS: All mean hip and coronal alignment parameters on the operative side changed significantly 1-year after THA; however, those on the non-operative side did not. On the operative side, mean JLCA and PTA changed in the direction of closing the joint lateral space, from 1.81° and 0.47° to 1.22° and 0.11°, respectively (p<0.001 and 0.046, respectively). Mean NSA, HKA, and mLDFA changed in the valgus direction, from 129.39°, 2.62°, and 86.69° to 133.54°, 1.53°, and 85.91°, respectively (p<0.001). Mean femoral offset, neck length, and femur length increased from 36.45mm, 47.83mm, and 429.20mm to 39.85mm, 55.06mm, and 436.33mm, respectively (p<0.001). Mean MPTA and LDTA increased from 85.43° and 87.50° to 86.73° and 90.38, respectively (p<0.001). JLCA was more vulnerable to change than HKA, femur length, mLDFA, MPTA, and PTA (p<0.05). DISCUSSION: JLCA change on the operative side was more sensitive than changes of other coronal alignments after THA. According to the cohort, THA might have an unloading effect on the medial compartment of the knee joint. LEVEL OF EVIDENCE: IV; retrospective case-control and cohort studies.
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Currently, research on superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic hyperthermia applications is steadily increasing. In this work, SPIONs were synthesized by the bromide-assisted polyol method and angle-shaped SPIONs were successfully generated with the optimized concentration of bromide. The influence of bromide concentration on the shape of the generated SPIONs as well as the heating characteristics under an alternating magnetic field (AMF) was thoroughly investigated. At a concentration of 20 mg mL-1 of the angle-shaped SPIONs, the highest temperature curve up to 23 °C was observed under AMF with 140 Oe and 100 kHz for 10 min. With the biotoxicity assay, no significant cytotoxicity was observed in the normal fibroblast of HFB-141103 as well as tumor cells of U87MG and FSall treated with the angle-shaped SPIONs at a concentration below 100 µg mL-1. However, significantly decreased cellular viability was observed in tumor cells of U87MG and FSall treated with 100 µg mL-1 of the angle-shaped SPIONs under AMF with 140 Oe and 100 kHz. Based on these results, it is thought that the angle-shaped SPIONs synthesized by the bromide-assisted polyol method will provide highly efficient magnetic hyperthermia therapy for cancers under biologically safe AMF with 140 Oe and 100 kHz.
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Purpose: To study the effects of rotator cuff tear size, operation time, and the use of anticoagulant on blood loss in elderly patients undergoing arthroscopic rotator cuff surgery. Methods: Patients aged older than 65 years who underwent arthroscopic rotator cuff repair with subacromial decompression at our hospital from January 2015 to December 2021 were identified. We measured hemoglobin levels preoperatively, postoperatively, and 7 days after surgery. First, subjects were divided according to the operation time (group I, <90 minutes; group II, <120 minutes; group III <150 minutes; and group IV, >150 minutes). Second, we classified the subjects by the size of the rotator cuff tear (group A, <3 cm; group B, <5 cm; and group C, >5 cm). Lastly, we categorized the subjects into 2 groups according to the use of anticoagulant medication. Results: A total of 566 patients were included. The mean hemoglobin (Hgb) levels were 13.8 ± 1.4 g/dL preoperatively, 13.2 ± 1.4 g/dL postoperatively, and 12.8 ± 1.3 g/dL 7 days after surgery, and the differences among them were statistically significant (P < .001). The Hgb level changes 7 days after surgery showed a significant decrease in the group with a longer operation time, and the Hgb loss increased from group 1 to group 4 (P < .001). They did not show any difference in the Hgb levels among the groups according to the size of a cuff tear preoperatively, postoperatively, and 7 days after surgery. The subjects with anticoagulant use showed more decrease in Hgb levels between immediately after the surgery and 7 days after the surgery (P = .031). Still, both groups did not show a statistical difference in the Hgb level 7 days after surgery (P = .115). Conclusions: In this study, blood loss after arthroscopic rotator cuff repair in elderly patients was greater than expected. Bleeding increased in elderly patients who had longer surgical times or were taking anticoagulant medications after surgery. Tear size was not associated with a decrease in Hgb levels. Level of Evidence: Level III, retrospective comparative study.
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Nanoparticles are primarily taken up by immune cells after systemic administration. Thus, they are considered an ideal drug delivery vehicle for immunomodulation. Because the spleen is the largest lymphatic organ and regulates the systemic immune system, there have been studies to develop spleen targeting nanoparticles for immunomodulation of cancer and immunological disorders. Inflammatory bowel disease (IBD) includes disorders involving chronic inflammation in the gastrointestinal tract and is considered incurable despite a variety of treatment options. Hydrogen sulfide (H2S) is one of the gasotransmitters that carries out anti-inflammatory functions and has shown promising immunomodulatory effects in various inflammatory diseases including IBD. Herein, we developed a delicately tuned H2S donor delivering liposome for spleen targeting (ST-H2S lipo) and studied its therapeutic effects in a dextran sulfate sodium (DSS) induced colitis model. We identified the ideal PEG type and ratio of liposome for a high stability, loading efficiency, and spleen targeting effect. In the treatment of the DSS-induced colitis model, we found that ST-H2S lipo and conventional long-circulating liposomes loaded with H2S donors (LC-H2S lipo) reduced the severity of colitis, whereas unloaded H2S donors did not. Furthermore, the therapeutic effect of ST-H2S lipo was superior to that of LC-H2S lipo due to its better systemic immunomodulatory effect than that of LC-H2S lipo. Our findings demonstrate that spleen targeting H2S lipo may have therapeutic potential for IBD.
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Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Liposomas/efectos adversos , Bazo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Colitis/tratamiento farmacológico , InmunomodulaciónRESUMEN
A compact benchtop high-field REBCO NMR is one of the most promising HTS applications. An all-REBCO, conduction-cooled magnet is a very attractive design option for demonstrating the unique potential of REBCO for forefront magnets. In this research, we have successfully constructed and tested a prototype all-REBCO, conduction-cooled, 23.5 T magnet operating at 10 K. We have applied the concept of an extreme No-Insulation (NI) winding technique, coupled with a solder-shunting procedure to improve magnet performance. We have also used a temperature-controlled charging sequence (TCCS) to reduce the screening current. The magnet was energized to 23.6 T at 14 K; it was further operated to 25 T at 10 K for nearly 60 hours.
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Here, we present experimental and analytical results of a preventive approach applied to a fault-mode phenomenon caused by electrodes or power-source failure in a no-insulation (NI) high-temperature superconducting REBa2Cu3O7-x (REBCO, RE = rare earth) magnet. It is generally agreed that the NI magnets, at least those of laboratory scale, are self-protected from overheating and, therefore, from quenching, chiefly because of turn-to-turn current bypassing unique to NI. However, these NI magnets do experience unexpected quenches, e.g., when the current through the magnet suddenly drops due to the aforementioned fault-mode phenomenon. Here, we report this phenomenon of a sudden-discharging-triggered quench of an NI REBCO coil, conduction-cooled, and operated at 4.2 K. We also present our preventive approach for this phenomenon that relies on an appropriately designed resistor shunted across the coil terminals. With this shunt resistor, a quench was prevented by suppressing the quench initiating turn-to-turn heat and induced overcurrent within the NI winding, and the coil current decayed safely.
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Extracellular vesicles (EVs) have been found to be effective therapeutic drug delivery vehicles in a wide range of human diseases, including cancer and neurodegenerative diseases. Proinflammatory (M1) macrophages can modulate the suppressive immune environment of tumor tissues to be more inflammatory and have been considered as candidates for cancer immunotherapy. Furthermore, macrophage-derived exosome-mimetic nanovesicles (MNVs) could effectively induce antitumor response and enhance the efficacy of immune checkpoint inhibitors in a recent paper. However, multiple studies indicate that EVs were rapidly cleared by the reticuloendothelial system, and therefore, their tumor targeting efficiencies were limited. Herein, we developed a simple surface modification method of MNVs using polyethylene glycol (PEG) to enhance the in vivo tumor targeting efficiency. PEG-MNVs had 7-fold higher blood circulation than bare MNVs in the animal tumor model. Also, MNVs had a 25-fold higher protein amount than exosomes. Overall, the nanovesicle preparation strategies presented in this study may expedite the clinical translation of EV-based therapeutics in various diseases.
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Exosomas , Vesículas Extracelulares , Neoplasias , Animales , Sistemas de Liberación de Medicamentos , Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Neoplasias/tratamiento farmacológico , Polietilenglicoles/farmacologíaRESUMEN
BACKGROUND: It is unclear whether stemless shoulder prosthesis lead to better clinical outcomes than conventional stemmed shoulder prosthesis. The purpose is to compare clinical outcomes and complication rates after surgery in patients with shoulder arthropathy treated with stemless or conventional stemmed shoulder prosthesis. METHOD: All studies comparing the constant score (CS), range of motion (ROM), and complication rates after surgery in patients with shoulder arthropathy treated with stemless or conventional stemmed shoulder prosthesis were included. The major databases MEDLINE, EMBASE, the Cochrane Library, Web of Science, and SCOPUS were searched for appropriate studies from the earliest available date of indexing through March 31, 2019. No restrictions were placed on language of publication. RESULTS: A total of 6 studies met the inclusion criteria and were analyzed in detail. Overall postoperative ROM (95% CI: 3.27 to 11.92; Pâ<â.01) was significantly greater for stemless prosthesis compared to conventional stemmed prosthesis. However, postoperative CS (95% CI: -2.98 to 7.13; Pâ=â.42) and complication rates (OR 1.22, 95% CI: 0.48-3.08; Pâ=â.68) were did not differ significantly between the 2 groups. CONCLUSION: This meta-analysis revealed that postoperative CS and complication rates did not differ significantly between the 2 treatment methods, stemless shoulder prosthesis and conventional stemmed shoulder prosthesis, for shoulder arthropathy. However, stemless shoulder prosthesis resulted in better outcomes than conventional stemmed shoulder prosthesis in terms of postoperative ROM. LEVEL OF EVIDENCE: Level III, Therapeutic study.
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Artroplastia/instrumentación , Artropatías/cirugía , Articulación del Hombro/cirugía , Prótesis de Hombro/efectos adversos , Anciano , Artroplastia/métodos , Artroplastia/estadística & datos numéricos , Manejo de Datos , Humanos , Estudios Observacionales como Asunto , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Diseño de Prótesis , Ensayos Clínicos Controlados Aleatorios como Asunto , Rango del Movimiento Articular/fisiología , Articulación del Hombro/patología , Prótesis de Hombro/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: As nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids have similar effects, steroids can be avoided to reduce adverse effects. This study aimed to compare the differences in symptom improvement after subacromial injection of steroids or NSAIDs. METHODS: Sixty patients with rotator cuff syndrome for at least 3 months were enrolled and divided into steroid and NSAID groups. The steroid group received a mixture of 1 mL of triamcinolone acetonide (40 mg/mL) and 1 mL of lidocaine hydrochloride 2%, while the NSAID group received a mixture of 1 mL of Ketorolac Tromethamine (30 mg/mL) and 1 mL of lidocaine hydrochloride 2%. The patients were assessed before and at 3, 6, and 12 weeks after the procedure. Shoulder scores from visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and University of California Los Angeles (UCLA) were used for evaluation. RESULTS: Both groups showed improvements in the clinical outcomes. Overall VAS, ASES, and UCLA scores improved from 6.9, 32.7, and 16.0 before the procedure to 2.0, 1.2, and 1.1; 81.5, 87.6, and 88.5; and 29.7, 31.8, and 32.0 at weeks 3, 6, and 12 weeks after the procedure, respectively. Twenty-six patients (86.7%) in the steroid group and 28 (93.3%) in the NSAID group reported satisfactory treatment outcomes. There were no significant differences in the outcomes between the two groups (p=0.671). CONCLUSIONS: Subacromial injection of NSAIDs for rotator cuff tendinitis with shoulder pain had equivalent outcomes with those of steroid injection at the 12-week follow-up.
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Exposure to tobacco smoke is known to have deleterious cardiovascular effects. In this study, we tested whether exposure to tobacco smoke exacerbates the severity of viral myocarditis in mice. Viral myocarditis was generated in 4-week-old male BALB/c mice by injection of Encephalomyocarditis virus (EMCV). Four groups were studied: (1) control (C, no smoke and no virus); (2) smoke only (S, exposure to cigarette smoke for 90 min/day for 15 days); (3) virus only (V); and (4) exposure to smoke for 5 days before plus 10 days following virus injection (S+V). We found that viral inoculation preceded by smoke exposure increased mortality more than twofold compared with virus inoculation alone. In addition, the mRNA level of atrial natriuretic factor was significantly higher in S+V than among any of the other 3 groups. Virus injection significantly decreased cardiac function compared with controls, with further deterioration observed in the S+V group. We also observed a significantly increased rate of apoptosis, with an increased activation of apoptosis-inducing factor in hearts exposed to S+V compared with those exposed to V alone. Our results suggest that preexposure to smoke significantly exacerbates the severity of viral myocarditis, likely through increased viral load and increased cardiomyocyte cell death.