Eucalyptol Ameliorates Retinal Microvascular Defects through Modulating ER Stress and Angiopoietin-Tie Signaling in Diabetic Eyes.

Loss of the inner blood-retinal barrier (BRB) integrity is a main feature of ocular diseases such as diabetic macular edema. However, there is a lack of clarity on how inner BRB function is modulated within the diabetic retina. The current study examined whether eucalyptol inhibited inner BRB destruction and aberrant retinal angiogenesis in 33 mM glucose-exposed human retinal microvascular endothelial (RVE) cells and db/db mice. This study further examined the molecular mechanisms underlying endothelial dysfunction including retinal endoplasmic reticulum (ER) stress and angiopoietin (Ang)/Tie axis in conjunction with vascular endothelial growth factor (VEGF). Eucalyptol is a naturally occurring monoterpenoid and an achiral aromatic component of many plants including eucalyptus leaves. Nontoxic eucalyptol reduced the production of amyloid-ß (Aß) protein in glucose-loaded RVE cells and in diabetic mice. This natural compound blocked apoptosis of Aß-exposed RVE cells in diabetic mouse eyes by targeting ER stress via the inhibition of PERK-eIF2α-ATF4-CHOP signaling. Eucalyptol promoted activation of the Ang-1/Tie-2 pathway and dual inhibition of Ang-2/VEGF in Aß-exposed RVE cells and in diabetic eyes. Supply of eucalyptol reversed the induction of junction proteins in glucose/Aß-exposed RVE cells within the retina and reduced permeability. In addition, oral administration of eucalyptol reduced vascular leaks in diabetic retinal vessels. Taken together, these findings clearly show that eucalyptol inhibits glucose-induced Aß-mediated ER stress and manipulates Ang signaling in diabetic retinal vessels, which ultimately blocks abnormal angiogenesis and loss of inner BRB integrity. Therefore, eucalyptol provides new treatment strategies for diabetes-associated RVE defects through modulating diverse therapeutic targets including ER stress, Ang-1/Tie-2 signaling, and Ang-2/VEGF.

Impact of IL-1ß on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1ß maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1ß in the host's defense against MAB. The IL-1ß production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1ß production in response to MAB. NLRP3 and IL-1ß deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1ß-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1ß deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1ß-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, in vitro co-culture analysis showed that IL-1ß signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1ß production contribute to MAB-induced lung pathology via the elevation of IL-17 production.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

PURPOSE: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe. PROCEDURES: We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed. RESULTS: Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin. CONCLUSIONS: We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.

Ellagic acid, a functional food component, ameliorates functionality of reverse cholesterol transport in murine model of atherosclerosis.

BACKGROUND/OBJECTIVES: High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS: Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS: Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION: Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.

Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study.

BACKGROUND: In this study, we explored the potential of human adipose tissue-derived extracellular matrix (adECM) sheets augmented with crosslinked hyaluronic acid (HA) as advanced wound dressings. We aimed to enhance healing efficacy while optimizing cost efficiency. METHODS: The adECM was processed from healthy donor tissue and combined with crosslinked HA to form ECM-HA sheets (Scaffiller, Medikan, Korea). In vitro experiments involved seeding adipose-derived stem cells (ASCs) onto these sheets and assessing cell survival and cytokine production. In vivo testing utilized a rat wound model, comparing ECM-HA sheet with HA-based dressing and polyurethane foam dressing. Re-epithelialization and collagen deposition were examined through histopathological examinations, whereas immunohistochemistry was used to assess CD31, alpha smooth muscle actin (α-SMA), and Tenascin C expression as contributing factors to wound healing. RESULTS: Results indicated that ECM-HA sheets were produced efficiently, with enhanced growth factor production and ASC survival observed in vitro. In vivo, ECM-HA sheets demonstrated accelerated wound healing, evidenced by improved epithelialization, thicker dermis, increased collagen deposition, and enhanced vascularity. Notably, they exhibited reduced myofibroblast activity and increased expression of Tenascin C, suggesting a favorable healing environment. CONCLUSION: ECM-HA sheets offer a promising approach for wound management, combining the benefits of adECM and HA. They present improved stability and cost-effectiveness while promoting essential aspects of wound healing such as angiogenesis and collagen formation. This study underscores the therapeutic potential of ECM-HA sheets in clinical applications aimed at facilitating wound repair.

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Elevated white blood cell count and long-term clinical outcomes of patients with vasospastic angina.

OBJECTIVES: Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA). METHODS: A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (n = 546, <7490/ml); group II, tertile 3 (n = 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization. RESULTS: Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90-1.83, P  = 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14-7.17), P  = 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02-11.59, P  = 0.047). CONCLUSION: Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.

Electrochemical Evolution of Ru-Based Polyoxometalates into Si,W-Codoped RuOx for Acidic Overall Water Splitting.

Despite intensive studies over decades, the development of electrocatalysts for acidic water splitting still relies on platinum group metals, especially Pt and Ir, which are scarce, expensive, and poorly sustainable. Because such problems can be alleviated, Ru-based bifunctional catalysts such as rutile RuO2 have recently emerged. However, RuO2 has a relatively low activity for hydrogen evolution reactions (HER) and low stability for oxygen evolution reactions (OER) under acidic conditions. In this study, the synthesis of a RuOx -based bifunctional catalyst (RuSiW) for acidic water splitting via the electrochemical evolution from Ru-based polyoxometalates at cathodic potentials is reported. RuSiW consists of the nanocrystalline RuO2 core and Si,W-codoped RuOx shell. RuSiW exhibits outstanding HER and OER activity comparable to Pt/C and RuO2 , respectively, with high stability. Computational analysis suggests that the codoping of RuOx with W and Si synergistically improves the HER activity of otherwise poor RuO2 by shifting the d-band center and optimizing atomic configurations beneficial for proper hydrogen adsorption. This study provides insights into the design and synthesis of unprecedented bifunctional electrocatalysts using catalytically inactive and less explored elements, such as Si and W.

Purple perilla frutescens extracts containing α-asarone inhibit inflammatory atheroma formation and promote hepatic HDL cholesterol uptake in dyslipidemic apoE-deficient mice.

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Water Extract of Desalted Salicornia europaea Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice.

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.

Development of radical initiator based on o-imino-isourea capable of photo/thermal polymerization.

Using o-imino isourea, three photo- and thermal dual-responsive radical initiators dicyheDCC, CyheDCC, and BnDCC were systematically developed and synthesized. By adding an aromatic ring to the free radical initiators, the ultraviolet-visible absorption was redshifted, and the absorption coefficient was increased. Compared with other initiators, BnphDCC exhibited an exceptional photoinitiation rate under photo-differential scanning calorimetry (DSC) and a high absorption coefficient (ε = 15 420 M-1 cm-1). Therefore, it is an appropriate potential photoinitiator. DicyheDCC, which was composed of a cyclic hydrocarbon, exhibited rapid thermal initiation (Tpeak = 82 °C) during thermal DSC, making it a valuable thermal radical initiator. Because of the low stiffness of the N-O link in radical initiators, density functional theory predicts that the aliphatic ring has a significantly lower enthalpy than the aromatic ring. Moreover, in this study, CyhephDCC and BnphDCC, as dual-responsive radical initiators, indicated the potential for a photo- and heat dual-curing system through the universal free-radical polymerization of acrylates. These significant discoveries may be useful for developing efficient and diversified polymer network systems that require synergistic photo- and thermal effects.

Synthesis and evaluation of 18F-labeled procainamide as a PET imaging agent for malignant melanoma.

Malignant melanoma has an aggressive nature and a high metastatic propensity resulting in the highest mortality rate of any skin cancer. In this study, we synthesized 18F-labeled procainamide (PCA) for detection of melanoma using positron emission tomography (PET), and evaluated its biological characteristics. The non-decay-corrected radiochemical yield of 18F-PCA was 10-15% and its in vitro stability was over 98% for 2 h. At 1 h, cellular uptake of 18F-PCA was 3.8-fold higher in a group with the presence of l-tyrosine than in a non-l-tyrosine-treated group. Furthermore, 18F-PCA permitted visualization of B16F10 (mouse melanoma) xenografts on microPET after intravenous injection, and was retained in the tumor for 60 min, with a high tumor-to-liver uptake ratio. 18F-PCA showed specific melanoma uptake in primary lesions with a high melanin targeting ability in small animal models. 18F-PCA may have potential as a PET imaging agent for direct melanoma detection.

Participation and Influencing Factors in the Decision-Making of Life-Sustaining Treatment: A Focus on Deceased Patients with Hematologic Neoplasms.

Purpose: This study aimed to investigate the involvement of patients who died from hematologic neoplasms in the decision-making process surrounding the withdrawal of life-sustaining treatment (LST). Methods: A total of 255 patients diagnosed with hematologic neoplasms who ultimately died following decisions related to LST during their end-of-life period at a university hospital were included in the study. Data were retrospectively obtained from electronic medical records and analyzed utilizing the chi-square test, independent t-test, and logistic regression. Results: In total, 42.0% of patients participated in the decision-making process regarding LST for their hematologic neoplasms, while 58.0% of decisions were made with family involvement. Among these patients, 65.1% died in general wards and 34.9% in intensive care units (ICUs) as a result of decisions such as the suspension of LST. The period from the LST decision to death was longer when the decision was made by the patient (average, 27.15 days) than when it was made by the family (average, 7.48 days). Most decisions were made by doctors and family members in the ICU, where only 20.6% of patients exercised their right to make decisions regarding LST, a rate considerably lower than 79.4% observed in general wards. Decisions to withhold or withdraw LST were more commonly made by patients themselves than by their families. Conclusion: The key to discussing the decision to suspend hospice care and LST is respecting the patient's self-determination. If a patient is lucid prior to admission to the ICU, considerations about suspending LST should involve the patient input.

[Analysis of ROX Index, ROX-HR Index, and SpO2/FIO2 Ratio in Patients Who Received High-Flow Nasal Cannula Oxygen Therapy in Pediatric Intensive Care Unit].

PURPOSE: This study aimed to evaluate the use of the respiratory rate oxygenation (ROX) index, ROX-heart rate (ROX-HR) index, and saturation of percutaneous oxygen/fraction of inspired oxygen ratio (SF ratio) to predict weaning from high-flow nasal cannula (HFNC) in patients with respiratory distress in a pediatric intensive care unit. METHODS: A total of 107 children admitted to the pediatric intensive care unit were enrolled in the study between January 1, 2017, and December 31, 2021. Data on clinical and personal information, ROX index, ROX-HR index, and SF ratio were collected from nursing records. The data were analyzed using an independent t-test, χ² test, Mann-Whitney U test, and area under the curve (AUC). RESULTS: Seventy-five (70.1%) patients were successfully weaned from HFNC, while 32 (29.9%) failed. Considering specificity and sensitivity, the optimal cut off points for predicting treatment success and failure of HFNC oxygen therapy were 6.88 and 10.16 (ROX index), 5.23 and 8.61 (ROX-HR index), and 198.75 and 353.15 (SF ratio), respectively. The measurement of time showed that the most significant AUC was 1 hour before HFNC interruption. CONCLUSION: The ROX index, ROX-HR index, and SF ratio appear to be promising tools for the early prediction of treatment success or failure in patients initiated on HFNC for acute hypoxemic respiratory failure. Nurses caring for critically ill pediatric patients should closely observe and periodically check their breathing patterns. It is important to continuously monitor three indexes to ensure that ventilation assistance therapy is started at the right time.

Vastus Lateralis and Vastus Intermedius Myocutaneous Flap Reconstruction for Complicated Trochanteric and Ischial Pressure Sores with Extended Girdlestone Resection: A Case Series.

OBJECTIVE: Most paraplegic patients with complicated trochanter sores or ischial sores present with lower limb muscle atrophy. Therefore, in patients who have undergone Girdlestone arthroplasty, filling the dead space and replacing the volume defect through an appropriate surgical technique is extremely challenging. This study presents a case series of vastus lateralis and vastus intermedius myocutaneous flap reconstruction after extended proximal femoral osteotomy in paraplegic patients. The aim of study is to investigate (i) whether sufficient volume replacement was achieved, (ii) whether muscle volume was maintained during long-term follow-up, and (iii) the presence of donor site morbidity. METHOD: A retrospective review was conducted with eight patients who underwent this method from March 2017 to December 2021. A total of nine flaps was elevated, and the defect was successfully reconstructed without dead space. Computed tomography was performed to identify the changes in thickness and volume of the muscle portion. The Wilcoxon signed-rank test was performed to assess the significance of the differences in muscle thickness between pre- and post-measurements. RESULTS: After surgery, all patients healed within 1 month; three patients experienced minor complications. The average follow-up period was 14.5 months, during which only one patient with an ischial pressure ulcer developed wound disruption and recurrence. The average thickness of the rotated muscle was 51.95 mm at 2 to 4 weeks postoperatively and 53.07 mm at 6 months postoperatively (𝑝 = 0.071). CONCLUSION: All nine cases healed well without major complications. When comparing the volume of the rotated muscle on radiological examinations before and after surgery, no significant differences were observed. Our modified Girdlestone resection technique provides a simple and reliable method for reconstructing complex trochanteric or ischial sores in paraplegic patients. It ensures anatomical consistency, ample volume, and structural stability by leaving the rectus femoris (RF) in place. Careful tension management is required when using this flap in the ischial area.

The effects of music therapy on labor pain, childbirth experience, and self-esteem during epidural labor analgesia in primiparas: a non-randomized experimental study.

PURPOSE: This non-randomized study was performed to evaluate the effects of music therapy on labor pain, the childbirth experience, and self-esteem in women during vaginal delivery. METHODS: In total, 136 primiparous women over 37 weeks of gestation receiving epidural analgesia during vaginal delivery were recruited via convenience sampling. To minimize diffusion effects, data from the control group (n=71) were collected first (April 2020 to March 2021), followed by data from the music group (n=65; April 2021 to May 2022). Participants in the music group listened to classical music during labor, while the control group was offered usual care (no music). Labor pain was measured using a numeric rating scale (NRS), and self-esteem and childbirth experience were collected using self-report questionnaires. Data were analyzed using the independent t-test, chi-square test and Cronbach's α coefficients. RESULTS: The overall pain level (NRS) at baseline was 0 in both groups. Mothers in the music therapy group had lower levels of latent pain (t=1.95, p=.005), active pain (t=3.69, p<.001) and transition-phase pain (t=7.07, p<.001) than the control group. A significant difference was observed between the two groups, and the music therapy group expressed more positive perceptions of the childbirth experience (t=-1.36, p=.018). For self-esteem, the experimental group's score was slightly higher, but without a statistically significant difference from the control group. CONCLUSION: Using music therapy during labor decreased labor pain and improved the childbirth experience. Music therapy can be clinically recommended as a non-pharmacological, safe, and easy method for nursing care in labor. Clinical trail number: KCT008561.

Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

Current concepts of craniofacial fibrous dysplasia: pathophysiology and treatment.

Fibrous dysplasia is an uncommon genetic disorder in which bone is replaced by immature bone and fibrous tissue, manifesting as slowgrowing lesions. Sporadic post-zygotic activating mutations in GNAS gene result in dysregulated GαS-protein signaling and elevation of cyclic adenosine monophosphate in affected tissues. This condition has a broad clinical spectrum, ranging from insignificant solitary lesions to severe disease. The craniofacial area is the most common site of fibrous dysplasia, and nine out of 10 patients with fibrous dysplasia affecting the craniofacial bones present before the age of 5. Surgery is the mainstay of treatment, but the technique varies according to the location and severity of the lesion and associated symptoms. The timing and indications of surgery should be carefully chosen with multidisciplinary consultations and a patient-specific approach.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.