Intranasal delivery of Duox2 DNA using cationic polymer can prevent acute influenza A viral infection in vivo lung.

We studied the contribution of Duox2 in mucosal host defense against influenza A virus (IAV) infection in in vivo lung. We found that Duox2 was required for the induction of type I and III interferon (IFN)s and transient Duox2 overexpression using cationic polymer polyethyleneimine (PEI) leads to suppression of IAV infection in in vivo lung. Twenty mice (C57BL/6J) were anesthetized and challenged by intranasal administration of 213 pfu/30 µl of IAV (WS/33/H1N1), and IAV-infected mice were euthanized at 1, 3, 5, 7, 10, 14 days post infection (dpi). Duox2 small hairpin RNA (shRNA) and pCMV-Duox2 formulated with PEI were inoculated to mice to assess the regulatory mechanism between Duox2 and IFN secretion. Following intranasal IAV inoculation, viral infection was significantly aggravated from 3 dpi in in vivo lung and viral titer was highest at 7 dpi. Consistent with this, Duox2 messenger RNA (mRNA) and protein expressions were significantly induced from 3 dpi in the lung tissue of IAV-infected mice. Viral titer was much higher in IAV-infected mice that were inoculated with Duox2 shRNA accompanied with lower survival rate and extensive lung pathologies. Interestingly, severe lung pathologies in IAV-infected mice were not observed and viral titer was significantly reduced in mice with pulmonary administration of pCMV-Duox2 formulated with PEI before IAV inoculation. Both mRNA and secreted protein levels of IFN-ß and IFN-λ2/3 were highly elevated in IAV-infected mice with pCMV-Duox2 formulated with PEI. Duox2 is necessary for the regulation of IFN secretion in in vivo lung, and pulmonary administration of Duox2 DNA using cationic polymer triggers the induction of type I and III IFNs resulting in more complete suppression of IAV infection.

Reconstruction of Thin and Pliable Oral Mucosa After Wide Excision of Oral Cancer Using a Trimmed Anterolateral Thigh Free Flap as an Adipofascial Flap.

A 21-year-old female patient underwent wide excision of the buccal mucosa and tongue as well as selective neck dissection due to squamous cell carcinoma on the left side of the tongue. She had a severe limitation in opening her mouth, owing to fibrosis of the mucosa and scar contracture after adjuvant radiation therapy. Reconstruction of the oral mucosa and tongue defect was performed after removal of the scar to improve mouth opening. An anterolateral thigh (ALT) flap was used, trimmed to an adipofascial flap for the reconstruction of the thin and pliable oral mucosa and tongue. The maximum mouth opening improved to 40 mm intraoperatively and was 30 mm after surgery. The adipofascial ALT flap had excellent viability and presented neomucosa after secondary healing. An adipofascial flap obtained by trimming an ALT flap could be a reliable option for the reconstruction of thin and pliable oral mucosa after wide excision of oral cancer.

Antiangiogenic Therapeutic mRNA Delivery Using Lung-Selective Polymeric Nanomedicine for Lung Cancer Treatment.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

Effects of surgical vs. nonsurgical therapy on erectile dysfunction and quality of life in obstructive sleep apnea syndrome: a pilot study.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with erectile dysfunction (ED). The improvement of ED after medical therapy including continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is still controversial. Furthermore, the efficacy of surgical treatment has been little investigated. AIM: The aim of this nonrandomized prospective study was to evaluate the effects of surgical (uvulopalatopharyngoplasty [UPPP]) and nonsurgical approaches (CPAP and MAD) on ED and quality of life (QOL) in OSAS. METHODS: OSAS patients underwent UPPP (N = 30), CPAP (N = 16), or MAD (N = 10) and completed the Korean versions of the International Index of Erectile Function questionnaire (KIIEF-5) and the Calgary Sleep Apnea Quality of Life Index (SAQLI) before and after a median of 7 months of treatment (interquartile range, 4-15 months). All patients underwent a full-night in-laboratory polysomnography at baseline and follow-up. MAIN OUTCOME MEASURE: The main outcome measures are the KIIEF-5 and SAQLI scores. RESULTS: CPAP group showed older age, higher body mass index, and more severe OSAS than other groups. Apnea-hypopnea index and lowest oxygen saturation level improved significantly in all groups, but Epworth Sleepiness Scale score decreased significantly in UPPP and MAD groups. Significant increase of KIIEF-5 was observed in patients who underwent UPPP (P = 0.039, paired t-test), but not in nonsurgical treatment group. All groups had the tendency of better QOL after treatment, but statistical significance was found only in MAD group. Neck circumference (r = 0.360, P = 0.006) and KIIEF-5 score (r = -0.484, P < 0.001) at baseline were significantly related to the improvement of KIIEF-5. CONCLUSIONS: This study demonstrated that ED in OSAS may improve following UPPP. Better disease-specific QOL was observed after both surgical and nonsurgical therapies in OSAS. These findings suggest that interventions for OSAS can provide the alleviation of ED and increase QOL in OSAS patients with ED, especially if they had pronounced complaints of ED and wide neck circumferences.

siRNA Nanoparticle Targeting PD-L1 Activates Tumor Immunity and Abrogates Pancreatic Cancer Growth in Humanized Preclinical Model.

Pancreatic cancer is characterized by late detection, frequent drug resistance, and a highly metastatic nature, leading to poor prognosis. Antibody-based immunotherapy showed limited success for pancreatic cancer, partly owing to the low delivery rate of the drug into the tumor. Herein, we describe a poly(lactic-co-glycolic acid;PLGA)-based siRNA nanoparticle targeting PD-L1 (siPD-L1@PLGA). The siPD-L1@PLGA exhibited efficient knockdown of PD-L1 in cancer cells, without affecting the cell viability up to 6 mg/mL. Further, 99.2% of PDAC cells uptake the nanoparticle and successfully blocked the IFN-gamma-mediated PD-L1 induction. Consistently, the siPD-L1@PLGA sensitized cancer cells to antigen-specific immune cells, as exemplified by Ovalbumin-targeting T cells. To evaluate its efficacy in vivo, we adopted a pancreatic PDX model in humanized mice, generated by grafting CD34+ hematopoeitic stem cells onto NSG mice. The siPD-L1@PLGA significantly suppressed pancreatic tumor growth in this model with upregulated IFN-gamma positive CD8 T cells, leading to more apoptotic tumor cells. Multiplex immunofluorescence analysis exhibited comparable immune cell compositions in control and siPD-L1@PLGA-treated tumors. However, we found higher Granzyme B expression in the siPD-L1@PLGA-treated tumors, suggesting higher activity of NK or cytotoxic T cells. Based on these results, we propose the application of siPD-L1@PLGA as an immunotherapeutic agent for pancreatic cancer.

Osteogenesis imperfecta and combined orthodontics and orthognathic surgery: a case report on two siblings.

Osteogenesis imperfecta is a heterogeneous group of connective tissue diseases that is predominantly characterized by bone fragility and skeletal deformity. Two siblings with undiagnosed type I osteogenesis imperfecta underwent orthognathic surgery for the treatment of facial asymmetry and mandibular prognathism. The authors report two cases of combined orthodontics and orthognathic surgery in patients with type I osteogenesis imperfecta, mandibular prognathism, and facial asymmetry.

Flexible transparent conducting single-wall carbon nanotube film with network bridging method.

We fabricated random network films of highly pure single-wall carbon nanotubes (SWCNTs) on flexible polyethylene terephthalate substrate by dip- and spray-coatings and their combination method for application to flexible transparent conducting films (TCFs). The dip-coating treatment was a more efficient method for fabricating the SWCNT-TCFs of high electrical conductivity without drastic drop in the optical transmittance, compared to the spray-coating one. This should be primarily due to more loose contact in intertube and interbundle junctions of the spray-coated SWCNT networks. Although the electrical conductivity of the SWCNT-TCFs was dramatically enhanced as increasing the number of dipping times, the dip-coating treatment with a large number of dipping times considerably reduced the transmittance without corresponding improvement in the electrical conductivity, indicating the patch-wise coating of the SWCNTs. On the other hand, the combination of the spray- and dip-coatings gave a supplementary effect for formation of a highly transparent film of better electrical conductivity. For SWCNT-TCF coated with 100 dipping times, an additional spray-coating dramatically decreased the sheet resistance from 1300 to 340 Omega/square, which is accompanied by slight reduction of the transmittance from 88 to 80%. Therefore, the post spray-coating can efficiently bridge the patch-wise SWCNT networks produced by the successive dip-coating.

Surgical management of idiopathic bone cavity: case series of consecutive 27 patients.

OBJECTIVES: Idiopathic bone cavity (IBC) is an uncommon intra-osseous cavity of unknown etiology. Clinical features of IBC are not well known and treatment modalities of IBC are controversial. The purpose of this study was to investigate the clinical characteristics of 27 IBC patients who underwent surgical exploration. MATERIALS AND METHODS: A total of 27 consecutive patients who underwent surgery due to a jaw bone cavity from April 2006 to February 2016 were included in this study. Nine male and 18 female patients were enrolled. Patients were examined retrospectively regarding primary site, history of trauma, graft material, radiographic size of the lesion, presence of interdental scalloping, erosion of the inferior border of the mandible, complications, results of bone graft, and recurrence. RESULTS: Female dominance was found. Maxillary lesion was found in one patient, and bilateral posterior mandibular lesions were found in two patients. The other patients showed a single mandibular lesion. The posterior mandible (24 cases) was the most common site of IBC, followed by the anterior mandible (5 cases). Two patients with anterior mandibular lesion reported history of trauma due to car accident, while the others denied any trauma history. Radiographic cystic cavity length over 30 mm was found in 10 patients. Seven patients showed erosion of the mandibular inferior border. The operations performed were surgical exploration, curettage, and bone or collagen graft. One bilateral IBC patient showed recurrence of the lesion during follow-up. Grafted bone was integrated into the native mandibular bone without infection. One patient reported necrosis of the mandibular incisor pulp after operation. CONCLUSION: Differential diagnosis of IBC is difficult, and IBC is often confused with periapical cyst. Surgical exploration and bone graft are recommended for treating IBC. Endodontic treatment of involved teeth should be evaluated before operation. Bone graft is recommended to reduce the healing period.

Influencing factors on CPAP adherence and anatomic characteristics of upper airway in OSA subjects.

Although continuous positive airway pressure (CPAP) is the most effective treatment modality, poor adherence still remains a problem for obstructive sleep apnea (OSA) treatment and there is little evidence regarding how this might be improved. This study aims to analyze the anatomic and clinical factors of OSA subjects who failed to comply with CPAP therapy.The medical records of 47 OSA subjects who received CPAP therapy as a first-line treatment modality were retrospectively reviewed. The medical records were reviewed for demographic and polysomnographic data and anatomic findings of the nasal cavity and oropharynx.24 patients who adhered to CPAP therapy and 23 patients who were nonadherent were enrolled in the study. There were no statistically significant differences in sleep parameters between CPAP-adherent patients and CPAP nonadherent subjects. Mean body mass index of CPAP nonadherent group was significantly higher than CPAP adherent group. Higher grades of septal deviation and hypertrophic change of the inferior turbinate were observed more in the CPAP nonadherent group. In addition, CPAP nonadherent subjects showed considerably bigger tonsils and higher grade palatal position comparing with the CPAP adherent subjects. Subjective discomfort including inconvenience, mouth dryness, and chest discomfort were the main problems for OSA subjects who did not comply with CPAP therapy.Excessive upper airway blockage in the nasal cavity and oropharynx was predominant in CPAP nonadherent subjects, which might cause the reported subjective discomfort that reduces CPAP compliance. Therefore, resolution of these issues is needed to enhance CPAP compliance for control of OSA.

Two-stage, acetic acid-aqueous ammonia, fractionation of empty fruit bunches for increased lignocellulosic biomass utilization.

Fractionation of EFB was conducted in two consecutive steps using a batch reaction system: hemicellulose hydrolysis using acetic acid (AA; 3.0-7.0 wt.%) at 170-190°C for 10-20 min in the first stage, and lignin solubilization using ammonium hydroxide (5-20 wt.%) at 140-220°C for 5-25 min in the second stage. The two-stage process effectively fractionated empty fruit bunches (EFB) in terms of hemicellulose hydrolysis (53.6%) and lignin removal (59.5%). After the two-stage treatment, the fractionated solid contained 65.3% glucan. Among three investigated process parameters, reaction temperature and ammonia concentration had greater impact on the delignification reaction in the second stage than reaction time. The two-stage fractionation processing improved the enzymatic digestibility to 72.9% with 15 FPU of cellulase/g of glucan supplemented with 70 pNPG of ß-glycosidase (Novozyme 188)/g-glucan, which was significantly enhanced from the equivalent digestibility of 28.3% for untreated EFB and 45.7% for AAH-fractionated solid.

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

Low-temperature fabrication of TiO(2) electrodes for flexible dye-sensitized solar cells using an electrospray process.

Hierarchically structured TiO2 (HS-TiO2) was prepared on a flexible ITO-PEN (polyethylene naphthalate) substrate via electrospray deposition using a commercially available TiO2 nanocrystalline powder in order to fabricate flexible DSSCs under low-temperature (<150 °C) conditions. The cell efficiency increased when using flexible ITO-PEN substrates post-treated by either a mechanical compression treatment or a chemical sintering treatment using titanium n-tetrabutoxide (TTB). The mechanical compression treatment reduced the surface area and porosity of the HS-TiO2; however, this treatment improved the interparticle connectivity and physical adhesion between the HS-TiO2 and ITO-PEN substrate, which increased the photocurrent density of the as-pressed HS-TiO2 cells. The electron diffusion coefficients of the as-pressed HS-TiO2 improved upon compression treatment, whereas the recombination lifetimes remained unchanged. An additional chemical sintering post-treatment involving TTB was tested for its effects on DSSC efficiency. The freshly coated TiO2 submitted to TTB hydrolysis in water at 100 °C yielded an anatase phase. TTB treatment of the HS-TiO2 cell after compression treatment yielded faster electron diffusion, providing an efficiency of 5.57% under 100 mW cm(-2), AM 1.5 global illumination.

Mouth opening during sleep may be a critical predictor of surgical outcome after uvulopalatopharyngoplasty for obstructive sleep apnea.

STUDY OBJECTIVES: To evaluate the value of mouth opening during sleep for predicting surgical outcomes after uvulopalatopharyngoplasty (UPPP). METHODS: Retrospectively, 69 out of 120 consecutive patients with obstructive sleep apnea who underwent uvulopalatopharyngoplasty at an academic tertiary referral center were included in this study. Sixty-nine subjects underwent cephalometry, nocturnal polysomnography and sleep videofluoroscopy before and after UPPP. Multiple parameters from the above studies were evaluated as potential predictors of UPPP outcomes. RESULTS: Multivariate analysis showed that an increased angle of mouth opening during sleep was the only significant predictor for surgical failure (p < 0.001). The angle of mouth opening could predict surgical outcome with predictive values of 72.4% and 82.5% for success and failure, respectively. CONCLUSIONS: Sleep videofluoroscopy during sleep revealed that the simple measurement of mouth-opening angle could outstandingly predict surgical outcome.

Determinants of treatment outcome after use of the mandibular advancement device in patients with obstructive sleep apnea.

OBJECTIVE: To determine the predictors affecting treatment outcome after application of the mandibular advancement device (MAD). DESIGN: Retrospective analysis. SETTING: Tertiary care university hospital. PATIENTS: A total of 76 patients (68 men and 8 women) who were treated with the MAD for obstructive sleep apnea (OSA) were included from September 2005 through August 2008. All the subjects underwent cephalometry, nocturnal polysomnography, and sleep videofluoroscopy (SVF) before and at least 3 months after receipt of a custom-made MAD. Sleep videofluoroscopy was performed before and after sleep induction and was analyzed during 3 states of awakeness, normoxygenation sleep, and desaturation sleep. Subjects were divided into success and nonsuccess groups depending on treatment outcome. MAIN OUTCOME MEASURES: Multiple variables from cephalometry and SVF including the length of the soft palate, retropalatal space, retrolingual space, and mouth opening angle were evaluated during sleep events with or without the MAD between success and nonsuccess group. RESULTS: The soft palate was significantly longer in the nonsuccess group than in the success group. The retropalatal and retrolingual airway spaces and mouth opening angle were not different between 2 groups. Application of the MAD increased the retrolingual space and decreased the length of the soft palate and the mouth opening angle significantly in both success and nonsuccess groups. However, retropalatal space was widened only in the success group, which showed that retropalatal space may be important in determining treatment response of the MAD. CONCLUSION: The length of the soft palate showed a difference between success and nonsuccess groups, and widening of retropalatal space might be an important factor for successful outcome with MAD application.

An investigation of upper airway changes associated with mandibular advancement device using sleep videofluoroscopy in patients with obstructive sleep apnea.

OBJECTIVE: To quantitatively evaluate the effects of the mandibular advancement device (MAD) on changes in the upper respiratory tract during sleep using sleep videofluoroscopy (SVF) in patients with obstructive sleep apnea (OSA). DESIGN: Retrospective analysis. SETTING: Academic tertiary referral center. PATIENTS: Seventy-six patients (68 men and 8 women) who were treated with the MAD for OSA were included from September 1, 2005, through August 31, 2008. INTERVENTION: All patients underwent nocturnal polysomnography and SVF before and at least 3 months after receipt of the custom-made MAD. Sleep videofluoroscopy was performed before and after sleep induction and was analyzed during 3 states of awakeness, normoxygenation sleep, and desaturation sleep. MAIN OUTCOME MEASURES: Changes in the length of the soft palate, retropalatal space, retrolingual space, and angle of mouth opening were evaluated during sleep events with or without the MAD. RESULTS: Without the MAD, the length of the soft palate and the angle of mouth opening increased during sleep events, especially in desaturation sleep, compared with the awake state. The retropalatal space and retrolingual space became much narrower during sleep compared with the awake state. The MAD had marked effects on the length of the soft palate, retropalatal space, retrolingual space, and angle of mouth opening. The retropalatal space and retrolingual space were widened, and the length of the soft palate was decreased. The MAD kept the mouth closed. CONCLUSIONS: Sleep videofluoroscopy showed dynamic upper airway changes in patients with OSA, and the MAD exerted multiple effects on the size and configuration of the airway. Sleep videofluoroscopy demonstrated the mechanism of action of the MAD in patients with OSA. The MAD increased the retropalatal and retrolingual spaces and decreased the length of the soft palate and the angle of mouth opening, resulting in improvement of OSA.

The mandibular advancement device and patient selection in the treatment of obstructive sleep apnea.

OBJECTIVES: To evaluate retrospectively the efficacy of the mandibular advancement device (MAD) in Korean patients with obstructive sleep apnea (OSA) in terms of severity and to evaluate prognostic factors deciding the success of MAD application. DESIGN: Retrospective analysis. SETTING: Academic tertiary referral center. PATIENTS: Of 142 patients who underwent MAD application for OSA management, 50 (46 men and 4 women; mean [SD] age, 50.2 [9.8] years) were included from March 2005 through August 2007. INTERVENTION: Full-overnight polysomnography was performed before and at least 3 months after intraoral MAD application in 50 patients. Questionnaires for sleep quality, Epworth sleepiness scale, and cephalometry were also studied. MAIN OUTCOME MEASURES: Treatment results were evaluated and prognostic factors deciding success of MAD application were assessed. RESULTS: The mean (SD) apnea-hypopnea index (AHI) decreased significantly (P < .001) from 36.6 (18.9) to 12.3 (11.4). The success rate, defined by an AHI of lower than 20 and a 50% decrease in AHI, were 74% (37 of 50 patients). Even patients who were not categorized into the success group had a decreased AHI. The success rates of patients with mild, moderate, and severe OSA were 43% (3 of 7), 82% (22 of 27), and 75% (12 of 16), respectively, and a higher success rate in patients with severe OSA showed that MAD could be applied even in patients with severe OSA. The duration of apnea and hypopnea, percentage of patients with snoring, and the Pittsburgh Sleep Quality Index were improved significantly after treatment. Epworth sleepiness scale scores and lowest oxygen saturation did not change significantly. An analysis of prognostic factors did not reveal any significant difference between the success and nonsuccess groups. CONCLUSIONS: The application of MAD significantly improved nocturnal respiratory function and sleep quality in patients with OSA, even in patients with severe OSA. In patients with OSA, MAD can be used as a good alternative treatment modality regardless of severity because it is noninvasive, easy to manufacture, and has good treatment results.