Bioactivity of human dental pulp-derived stem cells with boron-controlled S-PRG filler eluate by anion exchange.

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive glass filler capable of releasing various ions. A culture medium to which was added an S-PRG filler eluate rich in boron was reported to enhance alkaline phosphatase (ALP) activity in human dental pulp-derived stem cells (hDPSC). To clarify the role of boron eluted from S-PRG fillers, the modified S-PRG filler eluate with different boron concentrations was prepared by using an anion exchange material. Therefore, elemental mapping analysis of anion exchange material, adsorption ratio, hDPSCs proliferation and ALP activity were evaluated. For statistical analysis, Kruskal-Wallis test was used, with statistical significance determined at p<0.05. ALP activity enhancement was not observed in hDPSC cultured in the medium that contained the S-PRG filler eluate from which boron had been removed. The result suggested the possibility that an S-PRG filler eluate with controlled boron release could be useful for the development of novel dental materials.

Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study.

OBJECTIVE: Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain-sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital. METHODS: The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated. RESULTS: Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.

Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by caffeic acid phenethyl ester, a major component of Chinese propolis.

OBJECTIVES: We evaluated the immune-modulatory effects of Chinese propolis (CP) and its major constituent, caffeic acid phenethyl ester (CAPE), on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. METHODS: Mouse spleen cells stimulated by anti-CD3 monoclonal antibody were co-cultured with CP, CAPE, and HC030031, a specific antagonist of the TRPA1 Ca2+-permeable cation channel. Cytokine production was assayed by enzyme-linked immunosorbent assay. Interleukin (IL)-2 mRNA expression was examined by reverse transcription-quantitative polymerase chain reaction. RESULTS: In stimulated spleen cells treated with 1/16,000 CP diluent, IL-2 production was markedly enhanced, while IL-4 and IL-10 productions were not significantly affected. In contrast, interferon (IFN)-γ, IL-6, and IL-17 productions were markedly reduced. These effects of CP were reproduced by the CAPE treatment. A time-course observation demonstrated that, compared to control cells, IL-2 mRNA expression and production were significantly enhanced in the spleen cells stimulated by CAPE; however, IL-2 production was markedly delayed compared to that in the untreated control cells. The enhancement of IL-2 production by CAPE was scarcely alleviated by the addition of HC030031. These effects of CAPE upon IL-2 mRNA production were abolished in spleen cells without anti-CD3 antibody stimulation. CONCLUSIONS: CAPE is an important regulator of CP for cytokine regulation in anti-CD3 antibody-stimulated spleen cells. The agent specifically reduced IFN-γ, IL-6, and IL-17 and slightly enhanced Th2 cytokine production while significantly enhancing IL-2 production at the transcriptional level.

One Year Outcomes of Zilver PTX Versus Eluvia for Femoropopliteal Disease in Real-World Practice: REALDES Study.

PURPOSE: This multicenter, prospective, observational study aimed to compare Zilver PTX and Eluvia stents in real-world settings for treating femoropopliteal lesions as the differences in the 1-year outcomes of these stents have not been elucidated. MATERIALS AND METHODS: Overall, 200 limbs with native femoropopliteal artery disease were treated with Zilver PTX (96 limbs) or Eluvia (104 limbs) at 8 Japanese hospitals between February 2019 and September 2020. The primary outcome measure of this study was primary patency at 12 months, defined as a peak systolic velocity ratio of ≤2.4, without clinically-driven target lesion revascularization (TLR) or stenosis ≤50% based on angiographic findings. RESULTS: The baseline clinical and lesion characteristics of Zilver PTX and Eluvia groups were roughly comparable (of all limbs analyzed, approximately 30% presented with critical limb-threatening ischemia, approximately 60% presented with Trans-Atlantic Inter-Society Consensus II C-D, and approximately half had total occlusion), except for the longer lesion lengths in the Zilver PTX group (185.7±92.0 mm vs 160.0±98.5 mm, p=0.030). The Kaplan-Meier estimates of primary patency at 12 months were 84.9% and 88.1% for Zilver PTX and Eluvia, respectively (log-rank p=0.417). Freedom from clinically-driven TLR rates were 88.8% and 90.9% for Zilver PTX and Eluvia, respectively (log-rank p=0.812). CONCLUSIONS: The results of the Zilver PTX and Eluvia stents were not different regarding primary patency and freedom from clinically-driven TLR at 12 months after treating patients with femoropopliteal peripheral artery disease in real-world settings. CLINICAL IMPACT: This is the first study to reveal that the Zilver PTX and Eluvia have similar results in real-world practice when the proper vessel preparation is performed. However, the type of restenosis in the Eluvia stent may differ from that in the Zilver PTX stent. Therefore, the results of this study may influence the selection of DES for femoropopliteal lesions in routine clinical practice.

A rare case of an expanded perigraft seroma with heart failure after thoracic aortic surgery.

Perigraft seroma (PS) is an occasional complication of abdominal and femoral aortic graft implantation. We report a rare case with heart failure due to expanded PS compressing the right atrium 5 years after ascending aorta replacement for an acute type A aortic dissection. The PS was drained and sealed with biological tissue adhesive and wrapped using bovine xenopericardial sheet. We believe that mild hemorrhage through a vascular graft caused the expanded PS. Furthermore, wrapping vascular grafts using bovine xenopericardial sheet after sealing with biological tissue adhesive was effective for PS, particularly in cases in which it is impossible to use greater omentum. Learning objective: Cases of perigraft seroma (PS) after thoracic aortic repair have rarely been reported. The mechanism, indications, and treatments are unclear. We report a case of heart failure caused by expanded PS due to a small hemorrhage through a vascular graft. Furthermore, wrapping vascular grafts using bovine xenopericardial sheet after sealing with biological tissue adhesive may be effective for PS, particularly in cases where it is impossible to use the greater omentum.

[Initial and Long-term Results of Omental Flap Coverage for the Complications after Thoracic Aortic Aneurysm Repair].

OBJECTIVE: Here, we will review the initial remote results of omental flap coverage (OFC) after thoracic aortic aneurysm repair and report on its efficacy and problems. METHODS: We performed 567 thoracic aortic aneurysm surgeries from January 2007 to December 2021, including OFC in 16 patients( 2.8%, 10 males, mean age 65 years:range 30-82 years) who underwent OFC. RESULTS: OFC was performed in 14 cases of mediastinitis and 2 cases of perigraft seroma. 13 cases were performed at the same admission as the initial surgery, and 3 cases were performed after the discharge. The causative organisms of mediastinitis were methicillin-resistant Staphylococcus aureus (MRSA) in 4 cases, methicillin-resistant coagulase negative Staphylococcus( MRCNS) in 2 cases, Staphylococcus, Acinetobacter, Klebsiella, and methicillin-resistant Staphylococcus epidermidis( MRSE) in 1 case each, and unknown in 4 cases. All cases underwent successful reoperation with OFC alone, except in 1 case in which redo root replacement was performed for an anastomotic pseudoaneurysm. The overall hospital mortality was 31% (4 cases for MOF, 1 case for anastomotic hemorrhage). Of the 11 patients who were discharged alive, two died remotely (heart failure, senility), and no cases of reinfection were encountered. CONCLUSION: OFC is an effective treatment not only for mediastinitis but also for perigraft seroma while significantly reducing the risk of reinfection.

Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis.

OBJECTIVES: In this report, we attempt to clarify the immune modulatory effects of Brazilian green propolis (BGP) and its major component, artepillin C, on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. We also estimate the physiological mechanism affecting artepillin C's upon the cells. METHODS: Male C3H/HeN mouse spleen cells stimulated by antiCD3 monoclonal antibody were co-cultured with BGP, artepillin C, and HC030031, a transient receptor potential ankyrin 1 (TRPA1) Ca2+ channel antagonist. The synthesis of interferon (IFN)-γ, interleukin (IL)-6, IL-17, IL-4, IL-10, and IL-2 was assayed by enzyme-linked immunoassay. The expression of IL-2 mRNA and the protein product were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analyses, respectively. RESULTS: The production of IL-2 was markedly enhanced, while that of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6, and IL-17 was significantly reduced in the antibody-stimulated spleen cells treated with BGP at a non-cytostatic concentration. These effects were reproduced in the cells treated with artepillin C. The expression of IL-2 mRNA was unaffected; however, that of the protein was significantly enhanced in the artepillin C-treated cells compared to untreated control cells. The enhancement of protein expression and the production of IL-2 by artepillin C was significantly alleviated by adding HC030031. CONCLUSIONS: Artepillin C is an important regulator of cytokine synthesis from activated spleen cells. The agent specifically augmented the expression of IL-2 via the Ca2+-permeable cation channel, TRPA1, at least in part, at the translational or secretion levels.

Effects of multi-components released from S-PRG filler on the activities of human dental pulp-derived stem cells.

Numerous studies have shown that the sustained release of ions from dental restorative materials have acid buffering capacity, prevents tooth enamel demineralization, and inhibits bacterial adhesion. Herein, the release behavior and bioresponsiveness of ions released from surface pre-reacted glass-ionomer (S-PRG) fillers were investigated in different types of media based on human dental pulp-derived stem cell (hDPSC) responses. The hDPSCs were cultured for 1-7 days in S-PRG eluates diluted with varying amounts of cell culture media. S-PRG released several types of ions, such as F-, Sr2+, Na+, Al3+, BO33-, and SiO32-. The balance of eluted ions differed depending on the dilution and solvent, which in turn affected the cytotoxicity, cell morphology, cell proliferation, and alkane phosphatase activity of hDPSCs, among other properties. The results suggest that tailored S-PRG filler eluates could be designed and prepared for application in dental practice.

Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) vcells caused by serum deprivation and hypoxia promotes immune suppressive activity of mesenchymal stromal cells.

OBJECTIVES: We have previously reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, produces interleukin (IL)-1α, which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal 10T1/2 cells. This study assessed the conditions promoting the production of IL-1α in Sq-1979-1 cells, which could further enhance the immunosuppressive function of 10T1/2 cells, and evaluated its expression in OSCC tissues. METHODS: The expression of IL-1α was examined by RT-PCR, western blotting, and enzyme-linked immune sorbent assay (ELISA). The interferon (IFN)- γ-producing capability of anti-CD3 antibody-stimulated mouse spleen cells co-cultured with 10T1/2 cells and conditioned medium (CM) from Sq-1979-1 cells was examined by ELISA. The function of IL-1α was examined using an anti-IL1α antibody. Immunohistochemical analysis of the OSCC tissues was performed. RESULTS: The production of IL-1α from Sq-1979-1 cells was synergistically enhanced in lower serum (0.5% or 1.0% FBS) at the transcriptional level, and under hypoxia (1.0% oxygen) at the release level compared to that in the control medium supplemented with 10% FBS under normoxia. The IFN-γ-producing capability of stimulated spleen cells co-cultured with 10T1/2 cells was significantly reduced in the CMs prepared with the lower serum or under hypoxia. These functions of CMs were completely abolished by the anti-IL-1α antibody. The expression of IL-1α in OSCC tissues was prominent in the midst of a carcinomatous cellular lesion or a nearby necrotic lesion, where a supply deficiency could occur. CONCLUSION: s: IL-1α production by Sq-1979-1 cells was synergistically augmented under low serum and hypoxic conditions, which could promote the immunosuppressive activity of mesenchymal cells.

Hydrophobic *BEA-Type Zeolite Membranes on Tubular Silica Supports for Alcohol/Water Separation by Pervaporation.

Hydrophobic pure-silica *BEA-type zeolite membranes with large pores were prepared on tubular silica supports by hydrothermal synthesis using a secondary growth method and were applied to the separation of alcohol/water mixtures by pervaporation (PV), an alternative energy-efficient process for production of biofuels. Amorphous pure-silica tubular silica supports, free of Al atoms, were used for preparing the membranes. In this study, the effects of the synthesis conditions, such as the H2O/SiO2 and NH4F/SiO2 ratios in the synthetic gel, on the membrane formation process and separation performance were systematically investigated. The successfully prepared dense and continuous membranes exhibited alcohol selectivity and high flux for the separation of ethanol/water and butanol/water mixtures. The pure-silica *BEA membranes obtained under optimal conditions (0.08SiO2:0.5TEAOH:0.7NH4F:8H2O) showed high PV performance with a separation factor of 229 and a flux of 0.62 kg·m-2·h-1 for a 1 wt % n-butanol/water mixture at 318 K. This result was attributed to the hydrophobicity and large pore size of the pure-silica *BEA membrane. This was the first successful synthesis of hydrophobic large-pore zeolite membranes on tubular supports with alcohol selectivity, and the obtained results could provide new insights into the research on hydrophobic membranes with high permeability.

Effects of Silica-Particle Coating on a Silica Support for the Fabrication of High-Performance Silicalite-1 Membranes by Gel-Free Steam-Assisted Conversion.

Silicalite-1 membranes with high pervaporation performance were prepared successfully on a silica-particle-coated tubular silica support using a gel-free steam-assisted conversion (SAC) method. The effects of the silica-particle layer formed on the top surface of the silica support and the physical properties of the silica particles themselves on the membrane-formation process were investigated. The silica particles coated served as the additional silica source for growing the silicalite-1 seed crystal layer into the silicalite-1 membrane. As a result, it was possible to form a dense and continuous membrane even under gel-free conditions. Furthermore, it was found that the properties of the silica particles, such as their primary particle diameter, had a determining effect on their solubility during the steam treatment, that is, on the supply rate of the silica source. The silicalite-1 membrane obtained using the spherical-silica-particle-coated support had an approximately 9-µm-thick separation layer and showed very high pervaporation performance, exhibiting a separation factor of 105 and a flux of 3.72 kg m-2 h-1 for a 10 wt % ethanol/water mixture at 323 K. Thus, the gel-free SAC method can be used with a silica support coated with silica particles to readily prepare high-performance membranes without producing any chemical waste.

What Did Endovascular Aortic Repair Bring for the Treatment Strategy of Abdominal Aortic Aneurysm?

Objective: We examined the effects of the introduction of endovascular aortic repair (EVAR) on treatment for abdominal aortic aneurysms (AAAs). Subjects: We compared patients in the following three periods: period I (January 2002-December 2006, 105 patients), period II (January 2007-December 2011, 242 patients, duration of 5 years after the introduction of EVAR), and period III (January 2012-December 2016, 237 patients, duration of 5 years after period II). We used the American Society of Anesthesiologists (ASA) classification for risk assessment. Results: In the Open repair (OR) group, the incidences of ASA class 2 increased and classes 3 and 4 decreased significantly in periods II and III compared with period I. In all periods, there were no in-hospital deaths. Suprarenal aortic cross-clamping was required in 18 patients (19.1%) in period III and 5 patients (6.3) in period I, and the difference was significant (P<0.05). In the EVAR group, no differences in age, sex, or ASA classification class were observed between periods II and III. In period II, one patient died due to aneurysm rupture during surgery. Significant differences were observed when comparing both groups in periods II and III: patients in the EVAR group were older (P<0.01) and the OR group had a higher proportion of ASA class 2 patients and the EVAR group had a higher proportion of ASA class 3 or 4 patients (P<0.01). Among all AAA surgeries, rupture occurred in 25 patients (23.8%) in period I, 18 patients (7.4) in period II, and 16 patients (6.8) in period III. The number of ruptures was significantly lower in periods II and III than in period I (P<0.01). Conclusions: The findings of this study suggest that EVAR should be indicated for high-risk patients and had the good outcome of AAA treatment. (This is a translation of Jpn J Vasc Surg 2018; 27: 27-32.).

[Surgical Embolectomy for Acute Massive Pulmonary Thromboembolism Requiring Percutaneous Cardiopulmonary Support after Thoracoabdominal Aorta Replacement].

A 48-year-old man was admitted to our hospital and underwent thoracoabdominal aorta replacement. Eight days postoperatively, he developed severe dyspnea and transient drop in blood pressure suddenly following walk rehabilitation. Contrast-enhanced computed tomography showed thrombi in the bilateral main pulmonary artery. Respiratory failure and unstable hemodynamics developed, which required percutaneous cardiopulmonary support (PCPS). Because catheter embolectomy and thrombolytic therapy via pulmonary artery catheter were not effective, surgical thrombectomy was performed. PCPS was successfully removed on the following day. The patient was extubated on postoperative day 10 and discharged without complications on day 46 following rehabilitation. It is important to save a critically ill patient with acute pulmonary embolism requiring PCPS, and surgical treatment should be performed without delay in such patients.

[Efficacy of Total Debranching Thoracic Endovascular Aortic Repair for the Re-operation of Aortic Arch Aneurysm].

Thoracic endovascular aortic repair (TEVAR) combined with all-neck-branch reconstruction (total debranching TEVAR)[td TEVAR] is applied to aortic arch aneurysms as a minimally invasive procedure to improve treatment results. We report the initial and long-term results of td TEVAR for the reoperation of aortic arch aneurysm. By September 2016, td TEVAR for reoperation had been applied in 5 cases. The reasons for the reoperation were dilation of the arch aneurysm after ascending aorta replacement in 4 cases and localized dissection of the proximal landing zone after zone 2 TEVAR in 1 case. We reconstructed the neck branches under cardiopulmonary bypass (CPB). At that time, we kept in mind to perform anastomosis with an artificial graft at just above the sinus of Valsalva by using a single aortic clamp. Both the 30-day operative mortality and CPB-related complication rates were 0%. One patient had paraparesis, and one had left upper limb ischemia. Our strategy of td TEVAR provided durable results in the patients who underwent reoperation for aortic arch aneurysms.

[Strategy of Thoracic Endovascular Aortic Repair for Uncomplicated Type B Aortic Dissection in Subacute and Chronic Phase;Interval From Onset and Maximum Diameter].

We classified 59 patients who underwent thoracic endovascular aortic repair for uncomplicated type B aortic dissection from April 2008 to April 2016 into 3 groups based on time from onset and maximum aortic diameter:SA (2weeks to 1 year since onset;n=29), C (>1 year since onset;n=17), and D(maximum aneurysm size≥60 mm;n=13). We used the Kaplan-Meier method tso analyze survival, major adverse cardiovascular event and the need for additional treatment. There was no significant difference in outcomes between the SA and C groups (p=0.998) or C and D groups (p=0.279), but the results in group D tended to be consistently inferior. The freedom from aneurysm rupture rate was inferior in this group, with a significant difference between groups C and D (p=0.044). The time from onset to the procedure and maximum aortic diameter were not significantly associated with the longterm outcomes;however, more aortic ruptures occurred in the group with maximum aortic diameter≥60 mm. Simultaneous treatment for re-entry closure or conventional surgical procedures should be considered for such cases.

[Clinical Results of Thoracic Endovascular Aortic Repair (TEVAR) for the Treatment of Aortic Arch Aneruysm].

Thoracic endovascular aortic repair( TEVAR) combined of neck branch reconstruction( debranching TEVAR:dTEVAR) is applied to aortic arch aneurysm for minimally invasive reduction and improvement of treatment results. We report the initial and long-term results of dTEVAR for the treatment of aortic arch aneurysm. TEVAR for zone 0-2 area was applied in 49 cases (Zone 0:1:2;8:5:36 cases). Total dTEVAR was applied in zone 1 cases and 2 dTEVAR was performed in zone 2 cases. One dTEVAR or TEVAR with simple coverage of left subclavian artery was applied in zone 2 cases. Operative mortality within 30 days was 0% and there was 1 case in hospital death due to coronary arterial rupture after percutaneous coronary intervention. Perioperative morbidity included 1 case(2.0%) spinal cord ischemia, 4( 8.2%)arm claudication. In long-term follow-up, 5 cases died during the observation period (stroke in 1 case, heart failure in 1, neoplasma in 2, unknown in 1), but not in aortic rupture. Secondary type1 endoleak occurred in 2 cases(4.1%). Graft occlusion for neck branch reconstruction was complicated with 3 cases(6.1%), however no complications related to the graft occlusion. Our strategy of TEVAR provided durable results in patients treated for aortic arch aneurysm, with few adverse events.

Long-term results of open stent-grafting using a Matsui-Kitamura stent to treat thoracic aortic aneurysm.

PURPOSE: We describe a retrospective study of initial and long-term outcomes with an open stent grafting (OSG) with a Matsui-Kitamura stent for treating thoracic aortic aneurysm. METHODS: Between August 2005 and September 2013, 50 patients with aortic arch disease extending to the descending aorta underwent OSG. Circulatory arrest with total cardiopulmonary bypass and selective cerebral perfusion were used, and the aorta was transected between the brachiocephalic and left subclavian artery. The stent-graft was inserted, sutured to a transected aortic edge, and anastomosed to a four-branched arch graft. Preoperative, operative, and short- and long-term postoperative data were obtained from the patients' medical records. RESULTS: The perioperative (within 30 days) mortality rate was 8%. Two patients (4%) had a stroke and 5 patients (10%) had a spinal cord injury resulting in paraplegia or paraparesis (1 patient each) or transient paraplegia (3 patients). Actuarial survival rates at 1, 3, 5, and 7 years postoperatively were 87.8%, 78.3%, 70.7%, and 65.3%, respectively; the rates of freedom from an aortic event were 100%, 89.1%, 82.2%, and 74.7%. There were no complications related to use of the stent-graft. CONCLUSION: Our OSG method provided durable results in patients treated for thoracic aortic aneurysm, with few adverse events.

[Open stent-grafting using the Matsui-Kitamura stent for a distal arch aneurysm; an idea for insertion of stent graft and organ protection].

For the improvement in the clinical results of open stent-grafting, the development of a device system and prevention of spinal cord injury are important. For that reasons, we devised 2 methods for the open stent-grafting with the Matsui-Kitamura (MK) stent. First, the applicator using transesophagial echo transducer cover made insertion of the stent-graft system easy and safe. Next, to prevent ischemic spinal injury and protect major abdominal organ, blood return to lower body was established from femoral artery with occluding the stent graft by balloon. However, these procedures might need to examine whether it really contributes to the improvement in the clinical results.