Intraocular Pressure-Lowering and Retina-Protective Effects of Exosome-Rich Conditioned Media from Human Amniotic Membrane Stem Cells in a Rat Model of Glaucoma.

Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12-17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9-4.5 × 108 exosomes in 10 µL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 µg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.

Alpha-Lipoic Acid Attenuates Apoptosis and Ferroptosis in Cisplatin-Induced Ototoxicity via the Reduction of Intracellular Lipid Droplets.

Alpha-lipoic acid (α-LA) is a potent antioxidant that can prevent apoptosis associated with cisplatin-induced ototoxicity through ROS. Ferroptosis is defined as an iron-dependent cell death pathway that has recently been highlighted and is associated with the accumulation of intracellular lipid droplets (LDs) due to an inflammatory process. Herein, we investigated the impact of α-LA on ferroptosis and analyzed the characteristics of LDs in auditory hair cells treated with cisplatin using high-resolution 3D quantitative-phase imaging with reconstruction of the refractive index (RI) distribution. HEI-OC1 cells were treated with 500 µM α-LA for 24 h and then with 15 µM cisplatin for 48 h. With 3D optical diffraction tomography (3D-ODT), the RI values of treated cells were analyzed. Regions with high RI values were considered to be LDs and labelled to measure the count, mass, and volume of LDs. The expression of LC3-B, P62, GPX4, 4-hydroxynonenal (4-HNE), and xCT was evaluated by Western blotting. HEI-OC1 cells damaged by cisplatin showed lipid peroxidation, depletion of xCT, and abnormal accumulation of 4-HNE. Additionally, the count, mass, and volume of LDs increased in the cells. Cells treated with α-LA had inhibited expression of 4-HNE, while the expression of xCT and GPX4 was recovered, which restored LDs to a level that was similar to that in the control group. Our research on LDs with 3D-ODT offers biological evidence of ferroptosis and provides insights on additional approaches for investigating the molecular pathways.

Interactions of Nanoparticles with Macrophages and Feasibility of Drug Delivery for Asthma.

Understanding the interaction between nanoparticles and immune cells is essential for the evaluation of nanotoxicity and development of nanomedicines. However, to date, there is little data on the membrane microstructure and biochemical changes in nanoparticle-loaded immune cells. In this study, we observed the microstructure of nanoparticle-loaded macrophages and changes in lipid droplets using holotomography analysis. Quantitatively analyzing the refractive index distribution of nanoparticle-loaded macrophages, we identified the interactions between nanoparticles and macrophages. The results showed that, when nanoparticles were phagocytized by macrophages, the number of lipid droplets and cell volume increased. The volume and mass of the lipid droplets slightly increased, owing to the absorption of nanoparticles. Meanwhile, the number of lipid droplets increased more conspicuously than the other factors. Furthermore, alveolar macrophages are involved in the development and progression of asthma. Studies have shown that macrophages play an essential role in the maintenance of asthma-related inflammation and tissue damage, suggesting that macrophage cells may be applied to asthma target delivery strategies. Therefore, we investigated the target delivery efficiency of gold nanoparticle-loaded macrophages at the biodistribution level, using an ovalbumin-induced asthma mouse model. Normal and severe asthma models were selected to determine the difference in the level of inflammation in the lung. Consequently, macrophages had increased mobility in models of severe asthma, compared to those of normal asthma disease. In this regard, the detection of observable differences in nanoparticle-loaded macrophages may be of primary interest, as an essential endpoint analysis for investigating nanomedical applications and immunotheragnostic strategies.

Enhanced Bone Regeneration in Variable-Type Biphasic Ceramic Phosphate Scaffolds Using rhBMP-2.

Our aim was to investigate the bone regeneration capacity of powder-type biphasic ceramic scaffold (BCP powder), block-type BCP (BCP block), and collagen-added block-type BCP (BCP collagen) with different concentrations of recombinant human bone morphogenetic protein 2 (rhBMP-2) in an animal model. Four rabbits were assigned to each of the following groups: no graft + rhBMP-2 (0.1/0.2 mg/mL), BCP powder + rhBMP-2 (0.1/0.2 mg/mL), BCP block + rhBMP-2 (0.1/0.2 mg/mL), and BCP collagen + rhBMP-2 (0.1/0.2 mg/mL), i.e., a total of 32 rabbits. Polycarbonate tubes (Φ 7 mm × 5 mm) for supporting scaffolds were fixed into a 7 mm round border. Subsequently, 0.1 mL of rhBMP-2 solutions with different concentrations was injected into the tubes. Both radiological and histomorphometric analyses showed that osteogenesis was not enhanced by increasing the concentration of rhBMP-2 in all groups at both 3 and 6 weeks. Radiological analysis showed that bone formation was higher in the BCP collagen group than in the BCP powder and BCP block groups at both rhBMP-2 concentrations at 3 weeks. rhBMP-2 enhanced bone formation; however, as the concentration increased, bone formation could not be enhanced infinitely. Collagen-added alloplastic graft material may be useful for mediating rapid bone formation in initial stages.

Bone Regeneration of a 3D-Printed Alloplastic and Particulate Xenogenic Graft with rhBMP-2.

This study aimed to evaluate the bone regeneration capacity of a customized alloplastic material and xenograft with recombinant human bone morphogenetic protein-2 (rhBMP-2). We prepared hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic bone blocks made using a 3D printing system and added rhBMP-2 to both materials. In eight beagle dogs, a total of 32 defects were created on the lower jaws. The defective sites of the negative control group were left untreated (N group; 8 defects), and those in the positive control group were filled with particle-type Bio-Oss (P group; 12 defects). The defect sites in the experimental group were filled with 3D-printed synthetic bone blocks (3D group; 12 defects). Radiographic and histological evaluations were performed after healing periods of 6 and 12 weeks and showed no significant difference in new bone formation and total bone between the P and 3D groups. The 3D-printed custom HA/TCP graft with rhBMP-2 showed bone regeneration effects similar to that of particulate Bio-Oss with rhBMP-2. Through further study and development, the application of 3D-printed customized alloplastic grafts will be extended to various fields of bone regeneration.

Analysis of the relationship between periodontitis and osteoporosis/fractures: a cross-sectional study.

BACKGROUND: Chronic periodontitis is a multifactorial inflammatory disease resulting in patients exhibiting high levels of inflammatory factors causing systemic inflammatory bone destruction that may lead to osteoporosis development. The association between periodontitis and osteoporosis has been documented; however, the findings remain unclear. This study aimed to identify the association between periodontitis and osteoporosis using a cross-sectional study design and Korean Genome and Epidemiology Study (KoGES) health examinee data. METHODS: This cross-sectional study used epidemiological data from the KoGES during 2004-2016. Of 125,324 participants (age, 40-79 years), 9969 with periodontitis and 115,332 controls (without periodontitis) were selected. We analyzed the history of osteoporosis and fractures of all participants. All participants were examined according to age, sex, income group, obesity, smoking habits, alcohol consumption, and food intake. To analyze the odds ratio (OR) of periodontitis for those with osteoporosis and fractures, a logistic regression model was used. RESULTS: The adjusted odds ratio (aOR) of periodontitis for osteoporosis was 2.16 (95% confidence interval [CI], 2.01-2.31; P < 0.001). The aOR of periodontitis for any fracture was 1.54 (95% CI 1.46-1.62; P < 0.001). CONCLUSION: Osteoporosis and fractures are associated with periodontitis. Performing regular oral hygiene and examinations of bone mineral density are recommended to prevent aggravation of osteoporosis and periodontitis.

Effect of Intermittent Hypoxia on Metabolic Syndrome and Insulin Resistance in the General Male Population.

Background and objectives: Obstructive sleep apnea (OSA) is closely associated with insulin resistance (IR) and is an independent risk factor for incident type 2 diabetes mellitus (T2DM). Most studies evaluate the correlation between OSA and IR in only obese or T2DM patients. Therefore, we tried to investigate the effect of OSA on metabolic syndrome and IR in the general healthy male population. Materials and Methods: 184 subjects who visited a preventive health examination program were recruited for this study. All subjects received overnight polysomnography by a portable device (Watch-PAT 200). We examined several metabolic parameters and a homeostasis model of assessment for insulin resistance index (HOMA-IR). The subjects were divided into three groups by AHI (Apnea-hyponea index): normal group (AHI < 5), mild OSA group (5 ≤ AHI < 15), and moderate-severe OSA group (AHI ≥ 15). They were also divided into two groups according to minimum oxygen saturation: low group, Min-SpO2 < 88%; and high group, Min-SpO2 ≥ 88%. Results: Parameters of metabolic syndrome, including waist circumference, systolic and diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol showed significant differences among the AHI groups. Furthermore, HOMA-IR showed significant differences among the AHI groups. Those parameters, including metabolic syndrome and HOMA-IR, also showed differences between Min-SpO2 groups. Conclusions: In summary, this study helps confirm that AHI is associated with HOMA-IR in the general male population. Furthermore, the severity of AHI correlated with the parameters of metabolic syndrome. Therefore, AHI might be an indicator for evaluating both T2DM and metabolic syndrome, even in the general male population.

Feasibility of Powered Intracapsular Tonsillectomy in Pediatric Patients with Tonsil Problem, Including Recurrent Tonsillitis: A Single Surgeon's Experience.

INTRODUCTION: Powered intracapsular tonsillectomy (PIT) is a technique that protects the tonsillar capsule by using a microdebrider, resulting in faster wound-healing and reduced suffering. Many studies have found PIT to be effective, particularly in pediatric patients with obstructive sleep apnea (OSA). However, previous studies have not included patients with a history of recurrent tonsillitis. OBJECTIVE: The aim of this study was to determine the efficacy of PIT in pediatric patients even with a history of recurrent tonsillitis, and therefore, we want to expand the indication for PIT and reveal its safety. METHODS: A total of 886 pediatric patients underwent PIT between February 2013 and March 2016. All patients rated their postoperative pain using a visual analog scale (VAS) and completed the Korean obstructive sleep apnea (KOSA)-18 questionnaire for assessment of their quality of life (QOL). There were 539 males and 347 females. Their mean age was 6.2 years (range 2-14 years). The majority (77.7%) underwent the operation for OSA, and the rest (22.3%) had a history of recurrent tonsillitis. To compare the efficacy of PIT with traditional tonsillectomy, we selected 191 patients who underwent extracapsular tonsillectomy (ECT), a conventional technique, during the same time period. The median follow-up period was 16.7 months. During the follow-up period, instances of delayed bleeding and recurrent pharyngitis were monitored. RESULTS: In comparison to the patients who underwent ECT, the PIT group showed significantly fewer cases of postoperative bleeding (p = 0.027). Thirteen patients in the PIT group (1.5%) visited the hospital during the follow-up period for pharyngitis, while 8 in the ECT group (4.2%) visited for pharyngitis. The mean postoperative pain score, as assessed by a VAS, was 4.6 ± 3.2, and pain improved within an average of 2.9 days after surgery in the PIT group. The mean KOSA-18 score for the QOL of the patients was 65.9 preoperatively and 35.6 postoperatively in the PIT group. CONCLUSIONS: Pediatric tonsillectomy using PIT is valid for reducing postoperative pain and improving the QOL of OSA patients. PIT is also effective and safe for patients with a history of recurrent tonsillitis.

3D-Printed Ceramic Bone Scaffolds with Variable Pore Architectures.

This study evaluated the mechanical properties and bone regeneration ability of 3D-printed pure hydroxyapatite (HA)/tricalcium phosphate (TCP) pure ceramic scaffolds with variable pore architectures. A digital light processing (DLP) 3D printer was used to construct block-type scaffolds containing only HA and TCP after the polymer binder was completely removed by heat treatment. The compressive strength and porosity of the blocks with various structures were measured; scaffolds with different pore sizes were implanted in rabbit calvarial models. The animals were observed for eight weeks, and six animals were euthanized in the fourth and eighth weeks. Then, the specimens were evaluated using radiological and histological analyses. Larger scaffold pore sizes resulted in enhanced bone formation after four weeks (p < 0.05). However, in the eighth week, a correlation between pore size and bone formation was not observed (p > 0.05). The findings showed that various pore architectures of HA/TCP scaffolds can be achieved using DLP 3D printing, which can be a valuable tool for optimizing bone-scaffold properties for specific clinical treatments. As the pore size only influenced bone regeneration in the initial stage, further studies are required for pore-size optimization to balance the initial bone regeneration and mechanical strength of the scaffold.

Bone Regeneration Capability of 3D Printed Ceramic Scaffolds.

In this study, we evaluated the bone regenerative capability of a customizable hydroxyapatite (HA) and tricalcium phosphate (TCP) scaffold using a digital light processing (DLP)-type 3D printing system. Twelve healthy adult male beagle dogs were the study subjects. A total of 48 defects were created, with two defects on each side of the mandible in all the dogs. The defect sites in the negative control group (sixteen defects) were left untreated (the NS group), whereas those in the positive control group (sixteen defects) were filled with a particle-type substitute (the PS group). The defect sites in the experimental groups (sixteen defects) were filled with a 3D printed substitute (the 3DS group). Six dogs each were exterminated after healing periods of 4 and 8 weeks. Radiological and histomorphometrical evaluations were then performed. None of the groups showed any specific problems. In radiological evaluation, there was a significant difference in the amount of new bone formation after 4 weeks (p < 0.05) between the PS and 3DS groups. For both of the evaluations, the difference in the total amount of bone after 8 weeks was statistically significant (p < 0.05). There was no statistically significant difference in new bone between the PS and 3DS groups in both evaluations after 8 weeks (p > 0.05). The proposed HA/TCP scaffold without polymers, obtained using the DLP-type 3D printing system, can be applied for bone regeneration. The 3D printing of a HA/TCP scaffold without polymers can be used for fabricating customized bone grafting substitutes.

Preoperative Prophylactic Balloon-Assisted Occlusion of the Internal Iliac Arteries in the Management of Placenta Increta/Percreta.

Background and Objectives: Preoperative prophylactic balloon-assisted occlusion (PBAO) of the internal iliac arteries minimizes blood loss and facilitates surgery performance, through reductions in the rate of uterine perfusion, which allow for better control in hysterectomy performance, with decreased rates of bleeding and surgical complications. We aimed to investigate the maternal and fetal outcomes associated with PBAO use in women with placenta increta or percreta. Material and Methods: The records of 42 consecutive patients with a diagnosis of placenta increta or percreta were retrospectively reviewed. Of 42 patients, 17 patients (40.5%) with placenta increta or percreta underwent cesarean delivery after prophylactic balloon catheter placement in the bilateral internal iliac artery (balloon group). The blood loss volume, transfusion volume, postoperative hemoglobin changes, rates of hysterectomy and hospitalization, and infant Apgar score in this group were compared to those of 25 similar women who underwent cesarean delivery without balloon placement (surgical group). Results: The mean intraoperative blood loss volume in the balloon group (2319 ± 1191 mL, range 1000-4500 mL) was significantly lower than that in the surgical group (4435 ± 1376 mL, range 1500-10,500 mL) (p = 0.037). The mean blood unit volume transfused in the balloon group (2060 ± 1154 mL, range 1200-8000 mL) was significantly lower than that in the surgical group (3840 ± 1464 mL, range 1800-15,200 mL) (p = 0.043). There was no significant difference in the postoperative hemoglobin change, hysterectomy rates, length of hospitalization, or infant Apgar score between the groups. Conclusion: PBAO of the internal iliac artery prior to cesarean delivery in patients with placenta increta or percreta is a safe and minimally invasive technique that reduces the rate of intraoperative blood loss and transfusion requirements.

Crossed cerebellar hyperperfusion in patients with seizure-related cerebral cortical lesions: an evaluation with arterial spin labelling perfusion MR imaging.

PURPOSE: Crossed cerebellar (CC) diaschisis refers to a decrease in cerebellar perfusion in the presence of contralateral supratentorial lesions. Most of the previous studies have examined stroke patients. In contrast to strokes, seizure-related cerebral cortical lesions (SCCLs) usually show hyperperfusion, and therefore, cerebellar perfusion patterns are expected to be different from those of strokes. With arterial spin labelling (ASL), we evaluated the cerebellar perfusion status in patients with SCCLs. MATERIALS AND METHODS: Using a search of the recent database over the last 31 months, 26 patients were enrolled in this study. The inclusion criteria were as follows: (1) a history of seizures, (2) MR examination taken within 24 h from the last seizure, (3) the presence of SCCLs on T2/FLAIR or DWI, (4) hyperperfusion in the corresponding areas of SCCLs on ASL, and (5) no structural abnormality in the cerebellum. The perfusion status in the contralateral cerebellum was evaluated and categorized as hyper-, iso- and hypoperfusion. The asymmetric index (AI) of cerebellar perfusion was calculated by ROI measurement of the signal intensity on ASL. RESULTS: The mean time between the last seizure and MR examinations was 5 h 30 min. CC hyperperfusion was observed in 17 patients (65.4%), hypoperfusion in 7 (26.9%) and isoperfusion in 2 (7.7%). Regarding the location of SCCLs, CC hyperperfusion was more frequent (71.4 vs. 58.3%), and the mean AI was higher (42.0 vs. 11.5) when the lesion involved the frontal lobe. CONCLUSIONS: In patients with SCCLs, CC hyperperfusion occurred more often than hypo- and isoperfusion, especially when the lesions involved the frontal lobe.

Nanoparticle-loaded macrophage-mediated photothermal therapy: potential for glioma treatment.

Gold-based nanoparticles have been used in a number of therapeutic and diagnostic applications. The purpose of this study was to investigate the efficacy of gold-silica nanoshells (AuNS) in photothermal therapy (PTT) of rat gliomas. Rat alveolar macrophages (Ma) were used as nanoparticle delivery vectors. Uptake of AuNS (bare and PEGylated) was investigated in Ma. AuNS were incubated with Ma for 24 h. Phase contrast microscopy was used to visualize the distribution of loaded Ma in three-dimensional glioma spheroids. PTT efficacy was evaluated for both empty (Ma) and AuNS-loaded Ma (Ma(NS)) in both monolayers and spheroids consisting of C6 rat glioma cells and Ma. Monolayers/spheroids were irradiated for 5 min with light from an 810-nm diode laser at irradiances ranging from 7 to 28 W cm(-2). Monolayer survival was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay while PTT efficacy in spheroids was determined from growth kinetics and live/dead fluorescence microscopy. PTT efficacy was investigated in vivo using a Sprague-Dawley rat glioma model. Five rats received direct intracranial injection of a mixture of 10(4) C6 glioma cells and, 2 days later, an equal number of Ma(NS). Three rats received laser treatment (810 nm; 10 min; 1 W) while the remaining two served as controls (no laser treatment). The uptake ratio of bare to PEGylated AuNS by Ma was 4:1. A significant photothermal effect was observed in vitro, albeit at relatively high radiant exposures (2.1-4.2 kJ cm(-2)). PTT proved effective in vivo in preventing or delaying tumor development in the PTT-treated animals.

Combined concurrent photodynamic and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous cell head and neck carcinoma.

BACKGROUND AND OBJECTIVE: Treatment modalities, such as hyperthermia and photodynamic therapy (PDT) have been used in the treatment of a variety of head and neck squamous cell carcinoma (HNSCC), either alone or as an adjuvant therapy. Macrophages loaded with gold nanoshells, which convert near-infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on HNSCC cells. STUDY DESIGN/MATERIALS AND METHODS: Gold nanoshell loaded rat macrophages either alone or combined with human FaDu squamous cells in hybrid monolayers were subjected to PTT, PDT, or a simultaneous combination of the two light treatments. Therapies were given concurrently employing two laser light sources of λ = 670 nm (PDT) and λ = 810 nm (PTT), respectively. RESULTS: Significant uptake of gold nanospheres (AuNS) by rat alveolar macrophages was observed thus providing the rationale for their use as delivery vectors. Viability of the AuNS-loaded Ma was reduced to 35 and 12% of control values at an irradiance of 14 or 28 W/cm(2) administered over a 5 minute period respectively. No significant cytotoxicity was observed for empty Ma for similar PTT exposure. AlPcS2a mediated PDT at a fluence level of 0.25 J/cm(2) and PTT at 14 W/cm(2) irradiance had little effect on cell viability for the FaDu/Ma (ratio 2:1) hybrid monolayers. In contrast, combined treatment reduced the cell viability to less than 40% at these same laser power settings. CONCLUSIONS: The results of this study provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

Convolutional neural network model for automatic recognition and classification of pancreatic cancer cell based on analysis of lipid droplet on unlabeled sample by 3D optical diffraction tomography.

INTRODUCTION: Pancreatic cancer cells generally accumulate large numbers of lipid droplets (LDs), which regulate lipid storage. To promote rapid diagnosis, an automatic pancreatic cancer cell recognition system based on a deep convolutional neural network was proposed in this study using quantitative images of LDs from stain-free cytologic samples by optical diffraction tomography. METHODS: We retrieved 3D refractive index tomograms and reconstructed 37 optical images of one cell. From the four cell lines, the obtained fields were separated into training and test datasets with 10,397 and 3,478 images, respectively. Furthermore, we adopted several machine learning techniques based on a single image-based prediction model to improve the performance of the computer-aided diagnostic system. RESULTS: Pancreatic cancer cells had a significantly lower total cell volume and dry mass than did normal pancreatic cells and were accompanied by greater numbers of lipid droplets (LDs). When evaluating multitask learning techniques utilizing the EfficientNet-b3 model through confusion matrices, the overall 2-category accuracy for cancer classification reached 96.7 %. Simultaneously, the overall 4-category accuracy for individual cell line classification achieved a high accuracy of 96.2 %. Furthermore, when we added the core techniques one by one, the overall performance of the proposed technique significantly improved, reaching an area under the curve (AUC) of 0.997 and an accuracy of 97.06 %. Finally, the AUC reached 0.998 through the ablation study with the score fusion technique. DISCUSSION: Our novel training strategy has significant potential for automating and promoting rapid recognition of pancreatic cancer cells. In the near future, deep learning-embedded medical devices will substitute laborious manual cytopathologic examinations for sustainable economic potential.

Increased nanoparticle-loaded exogenous macrophage migration into the brain following PDT-induced blood-brain barrier disruption.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT)-induced disruption of the blood-brain barrier (BBB) has been investigated as a technique for the delivery of therapeutic agents to selective regions of the brain. The purpose of this study was to determine the effects of PDT on the migration of systemically administered exogenous macrophages (Ma) loaded with iron oxide nanoparticles in non-tumor bearing rats. MATERIALS AND METHODS: A control group consisting of three Sprague-Dawley rats was injected with iron oxide-loaded rat alveolar Ma via jugular vein catheter while two animals were subjected to intracranial injection of iron oxide-loaded Ma. PDT-treated animals were injected with photosensitizer (AlPcS2a ; 1 mg/kg i.p.) followed by light irradiation (wavelength = 670 nm; light dose = 2.5 J) 48 hours later. Light irradiation was performed through the skull. Prior to light irradiation, iron oxide-loaded Ma were administered to each animal. Animals in all groups were imaged in a 7 Tesla (T) magnetic resonance (MR) imager to determine the extent of PDT-induced edema and to evaluate for the presence of iron oxide nanoparticles. Animals were sacrificed 7 days post-Ma administration and their brains analyzed for the presence of iron oxide using Perls staining. RESULTS: Significant uptake of iron oxide nanoparticles by rat alveolar Ma was observed thus providing the rationale for their use as delivery vectors. Histopathological analyses failed to find evidence of iron oxide in normal rat brain. Accumulations of iron oxide-loaded Ma were observed in both MR images and histological sections of non-tumor bearing rat brain following PDT-induced disruption of the BBB. CONCLUSIONS: MR imaging was shown to be useful for localizing iron-oxide loaded Ma in rat brains. Exogenous Ma are incapable of traversing the normal BBB and therefore, the use of Ma as delivery vehicles into the brain requires selective disruption of the BBB.

Serum Zonulin Is a Biomarker for Severe Asthma.

Zonulin is a regulator of epithelial and endothelial barrier function. It regulates intestinal permeability through disrupting tight junctions. Defective epithelial barrier function is a hallmark of airway inflammation in asthma. This study aimed to investigate the role of zonulin in the pathogenesis of severe asthma. We enrolled 56 adult patients with asthma (29 severe asthma and 27 mild-to-moderate asthma) and 33 normal controls. The clinical data, sera, and lung tissues of the patients were provided by the Cohort for Reality and Evolution of adult Asthma in Korea (COREA) and the Biobank of Soonchunhyang University Bucheon Hospital, South Korea. Serum zonulin levels were estimated using an enzyme-linked immunosorbent assay, and zonulin expression in the bronchial tissue was evaluated by immunohistochemical staining. The serum zonulin levels were significantly higher in patients with severe asthma (51.98 ± 19.66 ng/mL) than in those with mild-to-moderate asthma and normal controls (26.35 ± 13.70 vs. 17.26 ± 10.29 ng/mL, P < 0.001). They significantly correlated with percent predicted forced expiratory volume in one second (%FEV1) (r = -0.35, P = 0.009). The zonulin expression in the bronchial epithelium was greater in patients with severe asthma. A serum zonulin cutoff value to distinguish between severe and mild-to-moderate asthmatics was 38.83 ng/mL. Zonulin may play an important role in the pathogenesis of severe asthma, and serum zonulin could be a potential biomarker for severe asthma.

Craniofacial Phenotype in Obstructive Sleep Apnea and Its Impact on Positive Airway Pressure (PAP) Adherence.

Positive airway pressure (PAP) is an important treatment tool for patients with moderate and severe obstructive sleep apnea (OSA), and adherence to PAP significantly affects treatment outcomes. Disease severity, adverse effects, and psychosocial factors are known to predict medication adherence. Cephalometric parameters have been reported to positively correlate with upper airway collapse. However, research on the correlation between these cephalometric parameters and PAP adherence remains insufficient. This study aimed to identify this relationship. This study included 185 patients with OSA who were prescribed PAP. Polysomnography (PSG) was performed to diagnose OSA, and paranasal sinus computed tomography (PNS CT) was performed to check for comorbidities of the upper airway. In addition, cephalometric parameters such as the hyoid-posterior nasal spine (H-PNS), posterior nasal spine-mandibular plane (PNS-MP), and hyoid-mandibular plane (H-MP) were measured in the midsagittal and axial CT views. Adherence was evaluated 3-12 months after the PAP prescription. A total of 136 patients were PAP-adherent, and 49 were nonadherent. There were more males in the adherent group and a higher average height in the adherent group. The PSG results showed that the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index (ODI), arousal index (AI), rapid eye movement (REM) AHI, and supine AHI were significantly higher, and the lowest oxygen saturation was lower in the adherent group. In the analysis of covariance (ANCOVA) model adjusted for sex and height, among the cephalometric parameters, H-MP was significantly longer in the adherent group (p = 0.027), and H-PNS showed a longer tendency (p = 0.074). In the logistic regression analysis model, the odds ratio (OR) and 95% confidence intervals (95% CI) of adherence and severe OSA in the third tertile compared to the first tertile of H-MP were 2.93 (1.25-6.86) and 4.00 (1.87-8.56). In the case of H-PNS, they were 2.58 (1.14-5.81) and 4.86 (2.24-10.54), respectively. This study concluded that an inferiorly placed hyoid bone in adult patients is associated with PAP adherence and disease severity.

Lobar emphysema ratio of more than 1% in the lobe with lung cancer as poor predictor for recurrence and overall survival in patients with stage I non-small cell lung cancer.

BACKGROUND: The purpose of this study was to examine the relationship between the lobar emphysema ratio (LER) and tumor recurrence and survival in patients with stage I non-small cell lung cancer (NSCLC). METHODS: We enrolled 258 patients with surgically proven stage I NSCLC. These patients underwent noncontrast chest CT, and pulmonary lobe segmentation and lobar emphysema quantification were performed using commercially available software. We assessed the LER in the lobe with lung cancer. We divided the patients into two groups according to the LER, and the cut-off value was 1. Furthermore, we analyzed the disease-free survival of high LER and other clinical factors after surgical resection. RESULTS: The 258 patients were divided into two groups: low LER (n = 195) and high LER (n = 63). The right upper lobe was the most frequent location in lung cancer and the most severe location in emphysema. In the Kaplan‒Meier curve, high LER showed a significantly lower disease-free survival (8.21 ± 0.27 years vs 6.53 ± 0.60 years, p = 0.005) and overall survival (9.56 ± 0.15 years vs. 8.51 ± 0.49 years, p = 0.011) than low LER. Stage Ib (2.812 [1.661-4.762], p<0.001) and high LER (2.062 [1.191-3.571], p = 0.010) were poor predictors for disease-free survival in multivariate Cox regression analysis. Stage Ib (4.729 [1.674-13.356], p = 0.003) and high LER (3.346 [1.208-9.269], p = 0.020) were significant predictors for overall survival in multivariate Cox regression analysis. CONCLUSION: A LER of more than 1% in the lobe with lung cancer is a poor predictor for cancer recurrence and overall survival in patients with stage I NSCLC.

Association between asthma or chronic obstructive pulmonary disease and chronic otitis media.

We hypothesized that asthma/chronic obstructive pulmonary disease (COPD) might increase the risk of chronic otitis media (COM), as asthma or COPD affects other diseases. The aim of this research was to investigate whether the incidence of COM is affected by a diagnosis of asthma or COPD in patients compared to matched controls from the national health screening cohort. A COM group (n = 11,587) and a control group that was 1:4 matched for age, sex, income, and residence area (n = 46,348) were selected. The control group included participants who never received treatment for COM from Korean National Health Insurance Service-Health Screening Cohort from 2002 to 2015. The crude and adjusted odds ratios (ORs) of previous asthma/COPD before the index date for COM were analyzed using conditional logistic regression. The analyses were stratified by age, sex, income, and region of residence. The period prevalence of asthma (17.5% vs. 14.3%, p < 0.001) and COPD (6.6% vs. 5.0%, p < 0.001) were significantly higher in the COM group than in the control group. In addition, the odds of asthma and COPD were significantly higher in the COM group than in the control group. Both asthma (adjusted OR 1.23, 95% confidence interval [CI] 1.16-1.31, p < 0.001) and COPD (adjusted OR 1.23, 95% CI 1.13-1.35, p < 0.001) increased the ORs for COM. This positive association between asthma/COPD and COM indicates that asthma/COPD might increase the incidence of COM.