M2 macrophage-derived cathepsin S promotes peripheral nerve regeneration via fibroblast-Schwann cell-signaling relay.

BACKGROUND: Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that macrophages accumulate at the site of injury. Numerous studies indicate that the phenotypic shift from M1 macrophage to M2 macrophage plays a crucial role in the process of axon regeneration. This polarity change is observed exclusively in peripheral macrophages but not in microglia and CNS macrophages. However, the molecular basis of axonal regeneration by M2 macrophage is not yet fully understood. Herein, we aimed to identify the M2 macrophage-derived axon regeneration factor. METHODS: We established a peripheral nerve injury model by transection of the inferior alveolar nerve (IANX) in Sprague-Dawley rats. Transcriptome analysis was performed on the injured nerve. Recovery from sensory deficits in the mandibular region and histological reconnection of IAN after IANX were assessed in rats with macrophage depletion by clodronate. We investigated the effects of adoptive transfer of M2 macrophages or M2-derived cathepsin S (CTSS) on the sensory deficit. CTSS initiating signaling was explored by western blot analysis in IANX rats and immunohistochemistry in co-culture of primary fibroblasts and Schwann cells (SCs). RESULTS: Transcriptome analysis revealed that CTSS, a macrophage-selective lysosomal protease, was upregulated in the IAN after its injury. Spontaneous but partial recovery from a sensory deficit in the mandibular region after IANX was abrogated by macrophage ablation at the injured site. In addition, a robust induction of c-Jun, a marker of the repair-supportive phenotype of SCs, after IANX was abolished by macrophage ablation. As in transcriptome analysis, CTSS was upregulated at the injured IAN than in the intact IAN. Endogenous recovery from hypoesthesia was facilitated by supplementation of CTSS but delayed by pharmacological inhibition or genetic silencing of CTSS at the injured site. Adoptive transfer of M2-polarized macrophages at this site facilitated sensory recovery dependent on CTSS in macrophages. Post-IANX, CTSS caused the cleavage of Ephrin-B2 in fibroblasts, which, in turn, bound EphB2 in SCs. CTSS-induced Ephrin-B2 cleavage was also observed in human sensory nerves. Inhibition of CTSS-induced Ephrin-B2 signaling suppressed c-Jun induction in SCs and sensory recovery. CONCLUSIONS: These results suggest that M2 macrophage-derived CTSS contributes to axon regeneration by activating SCs via Ephrin-B2 shedding from fibroblasts.

Oral Glucose Tolerance Test (OGTT) Evidence for the Postprandial Anti-Hyperglycemic Property of Salacca zalacca (Gaertn.) Voss Seed Extract.

Salak seed extract (Salacca zalacca) is known for its high antioxidant content and low caffeine levels, making it a promising candidate for the development of value-added health products. However, there is a lack of scientific evidence for its anti-hyperglycemic effects. To address this, we investigated the in vitro and in vivo anti-hyperglycemic and antioxidant effects of salak seed extract. The HPLC chromatogram of salak seed extract shows a prominent peak that corresponds to chlorogenic acid. In vitro studies revealed that salak seeds inhibited α-glucosidase activity and glucose uptake in Caco-2 cells in a concentration-dependent manner, while also exhibiting antioxidant properties. The extract exhibits a non-competitive inhibition on α-glucosidase activity, with an IC50 and Ki of 16.28 ± 7.22 and 24.81 µg/mL, respectively. In vivo studies utilizing streptozotocin-nicotinamide-induced diabetic mice showed that the extract significantly reduced fasting blood glucose (FBG) levels in the oral glucose tolerance test. Continuous administration of the salak seed extract resulted in lower FBG levels by 13.8% as compared with untreated diabetic mice, although this change was not statistically significant. The estimated LD50 value of salak seed extract exceeds 2000 mg/kg, and no toxicity symptoms have been detected. Our research supports that salak seed extract has the potential to serve as a functional food or supplement that may be beneficial in reducing postprandial hyperglycemia among people with type 2 diabetes. This effect was explained by the salak's inhibitory mechanisms of glucose absorption due to inhibition of both α-glucosidase activity and intestinal glucose uptake, coupled with its antioxidant effects.

Characterization of a new radiochromic film (LD-V1) using mammographic beam qualities.

PURPOSE: Radiochromic film (RCF) is a detector that can obtain a two-dimensional dose distribution with high resolution; it is widely used in medical and industrial fields. Several types of RCFs exist based on their application. The type of RCF mainly used for mammography dose assessment has been discontinued; however, a new type of RCF (LD-V1) has been distributed as a successor. Since the medical use of LD-V1 has rarely been studied, we investigated the response characteristics of LD-V1 in mammography. METHODS: Measurements were performed using Mo/Mo and Rh/Ag on a Senographe Pristina mammography device (GE, Fairfield, CT, USA). The reference air kerma was measured using a parallel-plate ionization chamber (PPIC) (C-MA, Applied Engineering Inc, Tokyo, Japan). Pieces of LD-V1 film model were irradiated at the same position where the reference air kerma in air was measured by the PPIC. Irradiation was performed using the time scale method based on the load on the equipment. Two methods of irradiation were considered: placing the detector in air and on the phantom. The LD-V1 was scanned five times at 72 dpi in RGB (48 bit) mode using a flatbed scanner (ES-G11000, Seiko Epson Corp, Nagano, Japan) 24 h following irradiation. The response ratio of the reference air kerma and the air kerma obtained from the LD-V1 were compared and examined for each beam quality and air kerma range. RESULTS AND DISCUSSION: When the beam quality was altered, the response ratio varied from 0.8 to 1.2 with respect to the measurement value of the PPIC; however, some outliers were observed. Response ratios were highly variable in the low-dose range; however, as the air kerma increased, the ratios approached 1. Thus, LD-V1 does not need calibration for each beam quality used in mammography. LD-V1 enables air kerma evaluation by creating air kerma response curves under certain X-ray conditions used in mammography. CONCLUSION: We suggest that the dose range be limited to 12 mGy or more to keep the response variation with beam qualities below ±20%. If further measurement is required for reducing the response variation, the dose range should be shifted to a higher dose range.

Residential radon exposure in Astana and Aqsu, Kazakhstan.

A pilot study was carried out to measure indoor radon concentrations in a uranium mining area of northern Kazakhstan. A total of 80 places at kindergartens, elementary schools, and dwellings were selected in Aqsu village and Astana city as the uranium mining area and background area for comparison, respectively. In Astana and Aqsu, the 3-month radon concentrations from late summer to autumn in 2022 were measured using the RADUET passive radon detectors. Radon concentrations ranged from 4 to >2000 Bq m-3(mean ± standard deviation: 290 ± 173 Bq m-3) throughout the study areas. The concentrations were higher in Aqsu, and 70% of the dwellings there exceeded 300 Bq m-3, whereas only 5% of them exceeded 300 Bq m-3in Astana. Accordingly, the new dose conversion factor for radon recommended by International Commission on Radiological Protection Publication 137 was applied to calculate the annual effective dose. The annual effective dose from the inhalation of radon was estimated to be 3.6 ± 4.6 mSv y-1for Astana and 23.7 ± 15.6 mSv y-1, for Aqsu, which are both higher than the world average value of 2.5 mSv y-1.

Digital Breast Tomosynthesis: Three-Dimensional Measurement of Breast-Absorbed Dose Distribution.

BACKGROUND: The dose exposure associated with digital breast tomosynthesis (DBT) is evaluated by multiplying the mean glandular dose (MGD) of mammography (MMG) with the correction coefficient of the angle of X-ray incidence. However, it has been pointed out that there are various problems when using the MGD as a standard for risk assessment in breast cancer screening. Therefore, the aim of this study was to assess the breast-absorbed dose for different breast sizes for dose assessment. Furthermore, in this study, by measuring the dose distribution three-dimensionally, we aimed to examine the MGD correction method using the breast size as a factor. METHODS: A simulated breast phantom with a diameter of 40-160 mm and a total thickness of 40 mm, made with polymethyl methacrylate, was created by simulating the phantom shape used in the simulation calculation for calculating the MGD. It was made with polymethyl methacrylate. Radiochromic films were placed at different depths, which measured the breast-absorbed dose distribution three-dimensionally. The MGD was calculated from the breast-absorbed dose distribution obtained. RESULTS: The three-dimensional dose distribution revealed that there was a difference in the distribution of MMG and DBT with increasing depth. In addition, a lower X-ray energy and a smaller breast size resulted in a greater difference in the absorbed dose between DBT and MMG. CONCLUSION: Incorporating the DBT correction according to the breast size into the MGD improves the accuracy of dose evaluation by the MGD. Additionally, a corrected MGD provides useful information for risk assessment when DBT is used for breast cancer screening.

Association between pazopanib exposure and safety in Japanese patients with renal cell carcinoma or soft tissue sarcoma.

The safety and effectiveness of pazopanib are related to plasma trough concentrations in renal cell carcinoma (RCC); however, data on pazopanib plasma trough concentrations with soft tissue sarcoma (STS) are limited. This study investigated the relationship between plasma trough concentrations and pazopanib safety in 45 Japanese patients with RCC or STS. Among the 33 patients included, the median pazopanib trough concentration was 37.5 (range, 12.1-67.6) µg/mL, which was not significantly different between Japanese RCC and STS patients. The plasma trough concentrations showed significant and positive correlations with aspartate aminotransferase and alanine aminotransferase values in blood samples taken for pharmacokinetic measurements after the administration. The incidence of pazopanib treatment discontinuation were significantly higher in RCC patients (p = 0.027). The primary reason for treatment discontinuation was hepatic dysfunction (5/6, 83.3%). Furthermore, this study revealed that pazopanib trough concentration was affected significantly by proton pump inhibitors but not by histamine 2-receptor blockers. In conclusion, the observed pazopanib trough levels and their safety in the Japanese RCC and STS populations in this study were similar to those of the global population. This is the first study to correlate the hepatotoxicity and pharmacokinetic property of pazopanib plasma trough levels by comparing Japanese patients with RCC or STS.

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo.

CONTEXT: Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) (Fabaceae) has traditionally been used to treat diabetes mellitus. OBJECTIVE: This study demonstrates the antidiabetic and antioxidant effects of aqueous extract of LS leaves in vivo and in vitro. MATERIALS AND METHODS: The effects of aqueous LS leaf extract on glucose uptake, sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) mRNA expression in Caco-2 cells, α-glucosidase, and lipid peroxidation were evaluated in vitro. The antidiabetic effects were evaluated using an oral glucose tolerance test (OGTT) and a 28-day consecutive administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. RESULTS: The extract significantly inhibited glucose uptake (IC50: 236.2 ± 36.05 µg/mL) and downregulated SGLT1 and GLUT2 mRNA expression by approximately 90% in Caco-2 cells. Furthermore, it non-competitively inhibited α-glucosidase in a concentration-dependent manner with the IC50 and Ki of 6.52 ± 0.42 and 1.32 µg/mL, respectively. The extract at 1000 mg/kg significantly reduced fasting blood glucose levels in both the OGTT and 28-day consecutive administration models as compared with untreated STZ-NA-induced diabetic mice (p < 0.05). Significant improvements of serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and GLUT4 levels were observed. Furthermore, the extract markedly decreased oxidative stress markers by 37-53% reduction of superoxide dismutase 1 (SOD1) in muscle and malondialdehyde (MDA) in muscle and pancreas, which correlated with the reduction of MDA production in vitro (IC50: 24.80 ± 7.24 µg/mL). CONCLUSION: The LS extract has potent antihyperglycemic activity to be used as alternative medicine to treat diabetes mellitus.

Association Between Patient Satisfaction and Preoperative Task-Shifting From Anesthesiologists to Perianesthesia Nurses: A Questionnaire Survey Study.

PURPOSE: We examined whether patients' satisfaction improved when patients' preoperative consultations were conducted with perianesthesia nurses (PANs) in collaboration with anesthesiologists, as compared with preoperative consultations conducted by anesthesiologists only. DESIGN: We conducted a study using questionnaires regarding outpatient satisfaction among patients who visited the perioperative management department of Yokohama City University Medical Center between July and December 2018. METHODS: There were 1,595 outpatients during the survey period. After exclusion criteria were applied, we analyzed 590 valid responses. FINDINGS: Regarding the level of understanding, 96.9% of the patients in the nurse-and-anesthesiologist group and 95.6% of the patients in the anesthesiologist-only group answered, "easy to understand," indicating no significant difference. A reduction in concerns, worries, and anxiety was reported by 86.3% of the patients in the nurse-and-anesthesiologist group and 70.4% in the anesthesiologist-only group, indicating a significant difference. Furthermore, 94.1% of the patients in the nurse-and-anesthesiologist group and 87.9% in the anesthesiologist-only group indicated patients' satisfaction with the overall evaluation, indicating another significant difference. A multiple logistic regression analysis was conducted to analyze the anxiety reduction and overall evaluation. We uncovered significant differences in PANs' examinations regarding anxiety reduction and overall evaluation. CONCLUSIONS: Collaboration between anesthesiologists and PANs might be associated with satisfaction and reduced anxiety in preoperative patients without adversely affecting patients' comprehension of anesthesia. Further research is necessary to verify the impacts of PANs' involvement in anesthesia patient care on intra and postoperative patient outcomes and on the cost and efficiency of anesthetic care.

Sensitivity of rapid antigen tests for COVID-19 during the Omicron variant outbreak among players and staff members of the Japan Professional Football League and clubs: a retrospective observational study.

OBJECTIVES: Rapid antigen tests have been used to prevent the spread of the COVID-19; however, there have been concerns about their decreased sensitivity to the Omicron variant. In this study, we assessed the sensitivity and specificity of the rapid antigen test compared with the PCR test among the players and staff members of the Japan Professional Football League and clubs. Furthermore, we evaluated the relationship between the sensitivity and the duration from the onset of symptoms to testing or vaccine status. DESIGN: This was a retrospective observational study. METHODS: We used 656 results from both the rapid antigen and PCR tests for COVID-19 using samples collected on the same day from 12 January to 2 March 2022, during the Omicron variant outbreak in Japan. RESULTS: The sensitivity of the rapid antigen test compared with the PCR test was 0.63 (95% CI: 0.53 to 0.73) and the specificity was 0.998 (95% CI: 0.995 to 1.000). There were no significant associations between the sensitivity and the duration from the onset of symptoms to testing (including asymptomatic cases in the category) or vaccination status (p>0.05) with small effect sizes (Cramer's V or φ: ≤0.22). CONCLUSIONS: Even during the Omicron outbreak, the sensitivity of the rapid antigen tests did not depend on the duration from the onset of symptoms to testing.

RELATIONSHIPS BETWEEN TYPES OF PROTECTIVE EYEWEAR AND EYE LENS DOSE WITHIN ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY.

In this study, variations in eye lens dose across different types of protective operator eyewear as well as the most appropriate protective methods when conducting endoscopic retrograde cholangiopancreatography were evaluated. The eye lens doses of 10 types of commercially available protective eyewear were compared. The ratio of the measured value near the eye to the measured value at the eye lens position ranged from 0.65 to 5.40 and it varied according to the mounting position of the dosemeter as well as the type of protective eyewear. Thus, the eye lens dose may have been overestimated or underestimated. Regardless of the working conditions, a face shield type of protective eyewear is recommended to reduce the eye lens dose. Moreover, it is preferable to attach a lens dosemeter near the eye to measure and evaluate the eye lens dose.

Microdistribution of internal radiation dose in biological tissues exposed to 56Mn dioxide microparticles.

Manganese-56 (56Mn) was one of the dominant neutron-activated radionuclides during the first hours following the atomic-bombing of Hiroshima and Nagasaki. The radiation spectrum of 56Mn and the radiation emission from excited levels of 56Fe following 56Mn beta-decay include gamma-quanta, beta-particles, Auger electrons and X-rays. The dispersion of neutron activated 56Mn in the air can lead to entering of radioactive microparticles into the lungs. The investigation of spatial microdistribution of an internal dose in biological tissue exposed to 56Mn is an important matter with regards to the possible elevated irradiation of the lung alveoli and alveolar ducts. The Monte Carlo code (MCNP-4C) was used for the calculation of absorbed doses in biological tissue around 56Mn dioxide microparticles. The estimated absorbed dose has a very essential gradient in the epithelium cells of lung alveoli and alveolar duct: from 61 mGy/decay on the surface of simple squamous cells of epithelium to 0.15 mGy/decay at distance of 0.3 µm, which is maximal cell thickness. It has been concluded that epithelial cells of these pulmonary microstructures are selectively irradiated by low-energy electrons: short-range component of beta-particles spectrum and Auger electrons. The data obtained are important for the interpretation of biological experiments implementing dispersed neutron-activated 56Mn dioxide powder.

Estimation of 'dose-depth' profile in the surface layers of a quartz-containing tile from the former Hiroshima University building indicates the possible presence of beta-irradiation from residual radioactivity after A-bombing.

The problem of differentiating between primary irradiation and exposure due to residual radioactivity following A-bombing (including beta-exposure), is the subject of special attention and discussions in order to understand the health effects following the Hiroshima and Nagasaki A-bombings, especially among newcomers to cities soon after the detonations. In this work, the method of single quartz grain luminescence retrospective dosimetry was applied for a retrospective estimation of the 'dose-depth' profile in a quartz-containing tile extracted from the building of former Hiroshima University (HU), which was a 'witness' of the Hiroshima atomic bombing on the 6 August 1945. It has been shown that results of retrospective estimates of the 'dose-depth' profile using the method of optically stimulated luminescence (OSL) from inclusions of quartz grains in very thin layers of the sample, in combination with the calculations of the 'dose-depth' profile using the Monte Carlo method, indicates the possible presence of beta irradiation of thin layers of the sample located near the surface of the tile facing the air, where there is no electronic equilibrium from gamma radiation.

External dose estimates of laboratory rats and mice during exposure to dispersed neutron-activated 56Mn powder.

Estimates of external absorbed dose in experimental animals exposed to sprayed neutron-activated 56Mn powder are necessary for comparison with internal absorbed doses estimated under the same exposure conditions, which is required for a correct interpretation of the observed biological effects. It has been established that the measured dose of external absorbed dose as a result of gamma irradiation range 1-15 mGy, which is order of magnitude less than the maximal dose of internal gamma and beta irradiation of the whole body of the same experimental animals irradiated under the same conditions: according to the available literature data, the maximal values ​​of absorbed dose of internal gamma-beta irradiation of the whole body are in the range of 330 mGy-1200 mGy for mice and 100 mGy-150 mGy for rats. It is concluded that under the conditions of experiments with dispersed neutron-activated powder 56MnO2, internal gamma-beta irradiation of experimental animals is the main factor of radiation exposure compared to external gamma irradiation.

Inhibitory effects of Triphala on CYP isoforms in vitro and its pharmacokinetic interactions with phenacetin and midazolam in rats.

Context: Direct evidence of Triphala-drug interactions has not been provided to date. Objective: This study was aimed to determine the effects of Triphala on cytochrome P450 (CYP) isoforms and P-glycoprotein (P-gp) in vitro, and to investigate pharmacokinetic interactions of Triphala with CYP-probes in rats. Materials and methods: Effects of Triphala on the activities of CYP isoforms and P-gp were examined using human liver microsomes (HLMs) and Caco-2 cells, respectively. Pharmacokinetic interactions between Triphala and CYP-probes (i.e., phenacetin and midazolam) were further examined in rats. Results: Triphala extract inhibited the activities of CYP isoforms in the order of CYP1A2>3A4>2C9>2D6 with the IC50 values of 23.6 ± 9.2, 28.1 ± 9.8, 30.41 ± 16.7 and 93.9 ± 27.5 µg/mL, respectively in HLMs. It exhibited a non-competitive inhibition of CYP1A2 and 2C9 with the K i values of 23.6 and 30.4 µg/mL, respectively, while its inhibition on CYP3A4 was competitive manner with the Ki values of 64.9 µg/mL. The inhibitory effects of Triphala on CYP1A2 and 3A4 were not time-dependent. Moreover, Triphala did not affect the P-gp activity in Caco-2 cells. Triphala, after its oral co-administration at 500 mg/kg, increased the bioavailabilities of phenacetin and midazolam by about 61.2% and 40.7%, respectively, in rats. Discussion and conclusions: Increases observed in the bioavailabilities of phenacetin and midazolam after oral co-administration of Triphala in rats provided a direct line of evidence to show Triphala-drug interactions via inhibition of CYP1A and CYP3A activities, respectively. These results, together with the lack of time-dependency of CYP 1A2 and 3A4 inhibition in vitro, suggested that the inhibitory effect of Triphala is primarily reversible.

Changes in oral function, swallowing function, and quality of life in patients with head and neck cancer: a prospective cohort study.

BACKGROUND: Head and neck cancer (HNC) treatment can cause oral morbidities, such as oral dryness and dysphagia, affecting the patient's quality of life (QOL). The relationship between oral functions and QOL in patients with early-stage HNC remains poorly studied. This study aimed to evaluate changes in the QOL of patients with early-stage HNC and identify factors that affect the QOL of these patients. METHODS: In this prospective cohort study, 37 patients who underwent early-stage (Stage I/Stage II) HNC treatment were evaluated for their oral function, swallowing function, and the QOL score at baseline (BL) and 12 months after surgical treatment (12 M). The participants were divided into two groups: patients who returned to the BL QOL score at 12 M (RE; n = 26) and those who did not (NR; n = 11). RESULTS: In total, 29.7% (11/37) patients with early-stage HNC did not return to the BL QOL score at 12 M. There was no significant difference between the RE and NR groups regarding the oral and swallowing function. Moreover, oral and swallowing function of all patients returned to the BL at 12 M. The NR group showed lower QOL scores than the RE group in the global health status, and "sticky saliva" parameters in the questionnaires. CONCLUSION: Restoration of the oral function is insufficient to improve the QOL of patients with early-stage HNC. The treatment of these patients should instead consider several factors that affect their QOL.

Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia.

OBJECTIVE: Acetaminophen (APAP) is widely used as an analgesic for postoperative pain relief. However, the pharmacokinetic-pharmacodynamic (PK-PD) properties of intravenous APAP administration remain unclear. We developed a PK-PD model in adult volunteers. METHODS: APAP (1 g) was intravenously administered to 15 healthy volunteers. The pain equivalent current (PEC) was then measured using the pulse current, corresponding to the quantitative value of pain perception. The PK model was developed using a 2-compartment model, and the PD model was developed using a linear model and an effect compartment model. RESULTS: APAP plasma concentration peaked just administration, whereas PEC significantly increased at 90 minutes and lasted through the experimental period (300 minutes). APAP plasma concentrations and PEC were processed for use in the PK-PD model. The developed PK-PD model delineates the analgesic effect profile, which peaked at 188 minutes and lasted until 327 minutes. CONCLUSION: We developed the PK/PD model for APAP administered intravenously. The analgesic effect can be expected ∼90 minutes after administration and to last >5 hours. It is suggested that APAP be administered ∼90 minutes prior to the onset of anticipated postoperative pain.

A Case of Cervical Intraneural Lipoma That Was Removed by Intercapsular Resection with No Resultant Postoperative Neurological Deficit.

Intraneural lipomas in peripheral nerves of cervical lesions are extremely rare and have not been previously reported. We present a 48-year-old male with a gradually increasing right cervical mass since 5 years. He visited our department because of pain and difficulty in raising the right upper limb. A tumor about 80 mm in size was palpable in the right neck along the cervical nerve. The tumor was suspected to involve fatty degeneration in schwannoma of cervical nerve origin, for which intercapsular resection was performed under general anesthesia. Histopathologically, bifurcated growth of mature adipocytes with sparse fibrous septa and lack of tumor proliferation of Schwann cells was observed on H&E staining, suggesting a diagnosis of intraneural lipoma. The patient had no new motor or sensory deficits postoperatively and with improvement in his preoperative symptoms.

Effects of wearing surgical masks on fraction of inspired oxygen in spontaneously breathing patients: improving safety for frontline healthcare professionals under pandemic situations.

BACKGROUND: During pandemic situations, many guidelines recommend that surgical masks be worn by both healthcare professionals and infected patients in healthcare settings. The purpose of this study was to clarify the levels and changes of oxygen concentration over time while oxygen was administered over a surgical mask. METHODS: Patients scheduled to undergo general anesthesia (n = 99) were enrolled in this study. First, patients were administered oxygen at 6 L/min via an oxygen mask over a surgical mask for 5 min. The patients removed the surgical mask and then took a 3-min break; thereafter, the same amount of oxygen was administered for another 5 min via the oxygen mask. We measured the fraction of inspired oxygen (FiO2), the end-tidal CO2 (EtCO2), and respiratory frequency every minute for 5 min, both while administering oxygen with and without a surgical mask. The FiO2 was measured at the beginning of inspiration and the EtCO2 was measured at the end of expiration. RESULTS: The FiO2 at 5 min was significantly lower when breathing with a surgical mask than that without it (mean difference: 0.08 [95% CI: 0.067-0.10]; p <  0.001). In contrast, the EtCO2 at 5 min was significantly higher when breathing with a surgical mask than that without it (mean difference: 11.9 mmHg [95% CI: 10.9-12.9]; p <  0.001). CONCLUSION: The FiO2 was lower when oxygen was administered over surgical masks than when patients did not wear surgical masks. Oxygen flow may need to be adjusted in moderately ill patients requiring oxygen administration.

Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice.

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p < .05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN.

Delayed Epistaxis which Was Developed after Orthognathic Surgery with Le Fort I Osteotomy and Managed by Endoscopic Cauterization.

A case of delayed epistaxis from the mucosa behind the right side of the inferior nasal mucosa 11 days after orthognathic surgery by Le Fort I osteotomy is presented. The patient was a 31-year-old man who underwent orthognathic surgery under general anesthesia. No abnormal findings were found during or after the operation. The patient was discharged from the hospital 10 days postoperatively. However, bleeding from the right nasal cavity occurred suddenly on the night after discharge, and he presented to our hospital again. The epistaxis was stopped once by nasal packing containing 0.001% epinephrine and systemic infusion of carbazochrome sulfonic acid and tranexamic acid. However, when the nasal packing was removed the next day, right nasal epistaxis was observed again. Curvature of the nasal septum and thickening of the inferior turbinate mucosa were seen on inspection; although, no active bleeding point was identified. Decreased nasal mucosa thickening and bleeding were observed after nasal packing containing 0.02% epinephrine. When the inside of the nasal cavity was observed endoscopically, an approximately 2 mm laceration was found in the mucosa behind the side wall of the right inferior nasal mucosa, and bleeding from the same part was confirmed. After endoscopic cauterization for hemostasis of the nasal mucosa, no rebleeding was observed. Although delayed epistaxis after Le Fort I osteotomy are often performed CT angiography to confirm the bleeding site, endoscopic cauterization would be primarily useful because of less invasiveness.