Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles

Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.ope

韓国産野生ゲンゴロウブナの斃死に関与したマミズヒダビル

2002年に韓国忠清南道にある溜池でゲンゴロウブナに斃死が発生し，衰弱魚はカザリビル属の1種の寄生を受け鰓に著しい貧血症状が見られたため，このヒルが斃死原因であると報告された。今回，そのときに採集されたヒル標本を観察した結果，それらはカザリビル属ではなくヒダビル属のマミズヒダビルLimnotrachelobdella sinensisに同定された。本論文では，その外部形態を記載した。これは韓国における本虫の2度目の発見であり，ゲンゴロウブナは同国における新宿主である。宿主の斃死との関連でマミズヒダビルの病害性を議論した。Mortality occurred in Japanese crucian carp Carassius cuvieri in a reservoir in Chungnam Province, Korea, in March 2002. Moribund fish showed severe anemia in the gills and piscicolid leeches that were identified as Trachelobdella sp. were reported as the cause of the mortality. Re-examination of the preserved leech specimens reveals that they are not Trachelobdella sp. but Limnotrachelobdella sinensis. The external morphology of the specimens is described. This finding represents the second record of L. sinensis in Korea. The impact of infestation by L. sinensis on a host is discussed in relation to fish mortality.Part of this work received financial support from the Japan Society for the Promotion of Science (No. 20658046 for the Exploratory Research) and the Fisheries Science Institute of Kunsan National University

Comparative effectiveness and safety of concomitant treatment with Chuna Manual Therapy and usual care for whiplash injuries: a multicenter randomized controlled trial

Objectives: We aimed to compare the effectiveness and safety of Chuna manual therapy combined with usual care to those of usual care alone for treating whiplash injuries. Design: A two-arm, parallel, assessor-blinded, multicenter pragmatic randomized clinical trial. Setting: Three hospitals in Korea. Participants: Overall, 132 participants between 19 and 70 years of age, involved in traffic accidents and treated at three hospitals in Korea, >2 but <13 weeks prior to enrollment, with neck pain consistent with whiplash-associated disorder grades I and II and a numeric rating scale score ≥5 were included. Interventions: Participants were equally and randomly allocated to the Chuna manual therapy and usual care (n = 66) or usual care (n = 66) groups and underwent corresponding treatment for three weeks. Primary and secondary outcome measures: The primary outcome was the number of days to achieve a 50% pain reduction. Secondary outcomes included areas under the 50% numeric rating scale reduction curve: pain, disability, quality of life, and safety. Results: The Chuna manual therapy + usual care group (23.31 ± 21.36 days; p = 0.01) required significantly fewer days to achieve 50% pain reduction compared to the usual care group (50.41 ± 48.32 days; p = 0.01). Regarding pain severity, functional index, and quality of life index, Chuna manual therapy and usual care were more effective than usual care alone. Safety was acceptable in both groups. Conclusions: In patients with subacute whiplash injury, Chuna manual therapy showed a rapid rate of recovery, high effectiveness, and safety

Premixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties

Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In the present study, a premixed calcium silicate root canal sealer reinforced with BGn (pre-mixed-RCS@BGn) was developed and its physicochemical features and biological effects were analyzed. Three specimens were in the trial: 0%, 0.5%, and 1% bioactive glass nanoparticles (BGns) were gradually added to the premixed type of calcium silicate-based sealer (pre-mixed-RCS). To elucidate the surface properties, scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy were used and flowability, setting time, solubility, and radiopacity were analyzed to evaluate the physical properties. Chemical properties were investigated by water contact angle, pH change, and ion release measurements. The antibacterial effects of the bioactive set sealers were tested with Enterococcus faecalis and the viability of human bone marrow-derived mesenchymal stem cells (hMSCs) with this biomaterial was examined. In addition, osteogenic differentiation was highly stimulated, which was confirmed by ALP (Alkaline phosphatase) activity and the ARS (Alizarin red S) staining of hMSCs. The pre-mixed-RCS@BGn satisfied the ISO standards for root canal sealers and maintained antimicrobial activity. Moreover, pre-mixed-RCS@BGn with more BGns turned out to have less cytotoxicity than pre-mixed-RCS without BGns while promoting osteogenic differentiation, mainly due to calcium and silicon ion release. Our results suggest that BGns enhance the biological properties of this calcium silicate-based sealer and that the newly introduced pre-mixed-RCS@BGn has the capability to be applied in dental procedures as a root canal sealer. Further studies focusing more on the biocompatibility of pre-mixed-RCS@BGn should be performed to investigate in vivo systems, including pulp tissue

Cost-effectiveness of chuna manual therapy and usual care, compared with usual care only for people with neck pain following traffic accidents: a multicenter randomized controlled trial

This is the first cost-effectiveness analysis of Chuna manual therapy (CMT) plus usual Korean traditional medicine for traffic accident victims using a randomized controlled trial. A total of 132 participants were equally allocated to the intervention group receiving 6–11 sessions of CMT plus usual Korean traditional medicine care for three weeks or usual care including acupuncture, cupping, herbal medicine, moxibustion, and traditional physiotherapy at three hospitals. At 12 weeks, from a healthcare perspective, the intervention group had significantly higher costs (mean (SD), $778 (435) vs.$618 (318); difference, $160; 95$15 to $289; p = 0.005). From a societal perspective, total costs were insignificantly lower in the intervention group (mean (SD),$1077 (1081) vs. $1146 (1485); difference,$−69; 95% CI, $−568 to$377; p = 0.761). The intervention group dominated, with significantly higher QALYs gained at lower overall cost with a 72% chance of being cost-effective. From a societal perspective, the intervention was cost-saving for individuals who had neck pain after car accidents, although it was not cost-effective from the healthcare perspective ($40,038 per QALY gained). Findings support use of CMT as an integrated care treatment for whiplash from a societal perspective. Further studies with larger sample sizes are needed to determine cost-effectiveness in other cultural contexts

Remodeling Pattern of Spinal Canal after Full Endoscopic Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression: One Year Repetitive MRI and Clinical Follow-Up Evaluation

Objective: There is limited literature on repetitive postoperative MRI and clinical evaluation after Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression. Methods: Clinical visual analog scale, Oswestry Disability Index, McNab's criteria evaluation and MRI evaluation of the axial cut spinal canal area of the upper end plate, mid disc and lower end plate were performed for patients who underwent single-level Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression. From the evaluation of the axial cut MRI, four types of patterns of remodeling were identified: type A: continuous expanded spinal canal, type B: restenosis with delayed expansion, type C: progressive expansion and type D: restenosis. Result: A total of 126 patients with single-level Uniportal Lumbar Endoscopic Unilateral Laminotomy for Bilateral Decompression were recruited with a minimum follow-up of 26 months. Thirty-six type A, fifty type B, thirty type C and ten type D patterns of spinal canal remodeling were observed. All four types of patterns of remodeling had statistically significant improvement in VAS at final follow-up compared to the preoperative state with type A (5.59 +/- 1.58), B (5.58 +/- 1.71), C (5.58 +/- 1.71) and D (5.27 +/- 1.68), p &lt; 0.05. ODI was significantly improved at final follow-up with type A (49.19 +/- 10.51), B (50.00 +/- 11.29), C (45.60 +/- 10.58) and D (45.60 +/- 10.58), p &lt; 0.05. A significant MRI axial cut increment of the spinal canal area was found at the upper endplate at postoperative day one and one year with type A (39.16 +/- 22.73; 28.00 +/- 42.57) mm(2), B (47.42 +/- 18.77; 42.38 +/- 19.29) mm(2), C (51.45 +/- 18.16; 49.49 +/- 18.41) mm(2) and D (49.10 +/- 23.05; 38.18 +/- 18.94) mm(2), respectively, p &lt; 0.05. Similar significant increment was found at the mid-disc at postoperative day one, 6 months and one year with type A (55.16 +/- 27.51; 37.23 +/- 25.88; 44.86 +/- 25.73) mm(2), B (72.83 +/- 23.87; 49.79 +/- 21.93; 62.94 +/- 24.43) mm(2), C (66.85 +/- 34.48; 54.92 +/- 30.70; 64.33 +/- 31.82) mm(2) and D (71.65 +/- 16.87; 41.55 +/- 12.92; 49.83 +/- 13.31) mm(2) and the lower endplate at postoperative day one and one year with type A (49.89 +/- 34.50; 41.04 +/- 28.56) mm(2), B (63.63 +/- 23.70; 54.72 +/- 24.29) mm(2), C (58.50 +/- 24.27; 55.32 +/- 22.49) mm(2) and D (81.43 +/- 16.81; 58.40 +/- 18.05) mm(2) at postoperative day one and one year, respectively, p &lt; 0.05. Conclusions: After full endoscopic lumbar decompression, despite achieving sufficient decompression immediately postoperatively, varying severity of asymptomatic restenosis was found in postoperative six months MRI without clinical significance. Further remodeling with a varying degree of increment of the spinal canal area occurs at postoperative one year with overall good clinical outcomes