Side- and Sinus-Specific Relationships between Chronic Rhinosinusitis and Ischemic Stroke Using Imaging Analyses.

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund-Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer's V = 0.479, p < 0.001), anterior (Cramer's V = 0.396, p < 0.001)/posterior (Cramer's V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer's V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer's V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer's V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204-2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke.

Nanoengineered Polymeric RNA Nanoparticles for Controlled Biodistribution and Efficient Targeted Cancer Therapy.

RNA nanotechnology, including rolling circle transcription (RCT), has gained increasing interest as a fascinating siRNA delivery nanoplatform for biostable and tumor-targetable RNA-based therapies. However, due to the lack of fine-tuning technologies for RNA nanostructures, the relationship between physicochemical properties and siRNA efficacy of polymeric siRNA nanoparticles (PRNs) with different sizes has not yet been fully elucidated. Herein, we scrutinized the effects of size/surface chemistry-tuned PRNs on the biological and physiological interactions with tumors. PRNs with adjusted size and surface properties were prepared using sequential engineering processes: RCT, condensation, and nanolayer deposition of functional biopolymers. Through the RCT process, nanoparticles of three sizes with a diameter of 50-200 nm were fabricated and terminated with three types of biopolymers: poly-l-lysine (PLL), poly-l-glutamate (PLG), and hyaluronic acid (HA) for different surface properties. Among the PRNs, HA-layered nanoparticles with a diameter of ∼200 nm exhibited the most effective systemic delivery, resulting in superior anticancer effects in an orthotopic breast tumor model due to the CD44 receptor targeting and optimized nanosized structure. Depending on the type of PRNs, the in vivo siRNA delivery with protein expression inhibition differed by up to approximately 20-fold. These findings indicate that the types of layered biopolymers and the PRNs size mediate efficient polymeric siRNA delivery to the targeted tumors, resulting in high RNAi-induced therapeutic efficacy. This RNA-nanotechnology-based size/surface editing can overcome the limitations of siRNA therapeutics and represents a potent built-in module method to design RNA therapeutics tailored for targeted cancer therapy.

Mucoadhesive chitosan microcapsules for controlled gastrointestinal delivery and oral bioavailability enhancement of low molecular weight peptides.

A bioactive compound, collagen peptide (CP), is widely used for biological activities such as anti-photoaging and antioxidant effects, with increased oral bioavailability because of its low molecular weight and high hydrophilicity. However, controlling release time and increasing retention time in the digestive tract for a more convenient oral administration is still a challenge. We developed CP-loaded chitosan (CS) microcapsules via strong and rapid ionic gelation using a highly negative phytic acid (PA) crosslinker. The platform enhanced the oral bioavailability of CP with controlled gastrointestinal delivery by utilizing the mucoadhesiveness and tight junction-opening properties of CS. CS and CP concentrations varied from 1.5 to 3.5% and 0-30%, respectively, for optimal and stable microcapsule synthesis. The physicochemical properties, in vitro release profile with intestinal permeability, in vivo oral bioavailability, in vivo biodistribution, anti-photoaging effect, and antioxidant effect of optimized CS microcapsules were analyzed to investigate the impact of controlling parameters. The structure of CS microcapsules was tuned by PA diffused gradient ionic cross-linking degree, resulting in a controlled CP release region in the gastrointestinal tract. The optimized microcapsules increased Cmax, AUC, and tmax by 1.5-, 3.4-, and 8.0-fold, respectively. Furthermore, CP in microcapsules showed anti-photoaging effects by downregulating matrix metalloproteinases-1 via antioxidant effects. According to our knowledge, this is the first study to microencapsulate CP for oral bioavailability enhancement. The peptide delivery method employed is simple, economical, and can be applied to customize bioactive compound administration.

Single-Cell Hemoprotein Diet Changes Adipose Tissue Distributions and Re-Shapes Gut Microbiota in High-Fat Diet-Induced Obese Mice.

We have previously observed that feeding with single-cell hemoprotein (heme-SCP) in dogs (1 g/day for 6 days) and broiler chickens (1 ppm for 32 days) increased the proportion of lactic acid bacteria in the gut while reducing their body weights by approximately 1~2%. To define the roles of heme-SCP in modulating body weight and gut microbiota, obese C57BL/6N mice were administered varied heme-SCP concentrations (0, 0.05, and 0.5% heme-SCP in high fat diet) for 28 days. The heme-SCP diet seemed to restrain weight gain till day 14, but the mice gained weight again later, showing no significant differences in weight. However, the heme-SCP-fed mice had stiffer and oilier bodies compared with those of the control mice, which had flabby bodies and dull coats. When mice were dissected at day 10, the obese mice fed with heme-SCP exhibited a reduction in subcutaneous fat with an increase in muscle mass. The effect of heme-SCP on the obesity-associated dyslipidemia tended to be corroborated by the blood parameters (triglyceride, total cholesterol, and C-reactive protein) at day 10, though the correlation was not clear at day 28. Notably, the heme-SCP diet altered gut microbiota, leading to the proliferation of known anti-obesity biomarkers such as Akkermansia, Alistipes, Oscillibacter, Ruminococcus, Roseburia, and Faecalibacterium. This study suggests the potential of heme-SCP as an anti-obesity supplement, which modulates serum biochemistry and gut microbiota in high-fat diet-induced obese mice.

A case of vocal cord gnathostomiasis diagnosed with sectional morphologies in a histopathological specimen from a Chinese woman living in Korea.

This study aimed to describe a rare case of gnathostomiasis in the vocal cord. A 54-year-old Chinese woman living in Korea visited with a chief complaint of voice change at the outpatient department of otorhinolaryngology in Hallym Sacred Heart Hospital, Hallym University on August 2, 2021. She had eaten raw conger a few weeks before the voice change developed, but her medical history and physical examinations demonstrated neither gastrointestinal symptoms nor other health problems. A round and red cystic lesion, recognized in the anterior part of the right vocal cord, was removed using forceps and scissors through laryngeal microsurgery. The histopathological specimen of the cyst revealed 3 cross-sections of a nematode larva in the lumen of the cyst wall composed of inflammatory cells and fibrotic tissues. They differ in diameter, from 190 µm to 235 µm. They showed characteristic cuticular layers with tegumental spines, somatic muscle layers, and gastrointestinal tracts such as the esophagus and intestine. Notably, intestinal sections consisted of 27-28 lining cells containing 0-4 nuclei per cell. We tentatively identified the nematode larva recovered from the vocal cord cystic lesion as the third-stage larva of Gnathostoma, probably G. nipponicum or G. hispidum, based on the sectional morphologies.

Single-cell hemoprotein (heme-SCP) exerts the prebiotic potential to establish a healthy gut microbiota in small pet dogs.

To investigate the effect of the single-cell hemoprotein (heme-SCP) source on animals, a dog-treat (100 g for each dog) harboring 0.2% heme-SCP was manufactured and fed to seven pet dogs (< 10 kg) in a randomized manner (irrespective of owner's feeding style, dogs' health conditions, and staple diets), and the feces before and after the dog-treat diet were analyzed to define the structure of the microbiota. The total bacterial species of the seven dogs showed no difference (564-584), although the bacterial compositions varied significantly. The Firmicutes phylum increased (54.7-73.7%), showing differential species composition before and after heme-SCP intake. Proteobacteria, Bacteroidetes, and Fusobacteria decreased (5.4-3.8%, 32.9-16.8%, and 6.3-3.6%, respectively), which agreed with the previous observation of deliberate feeding. Therefore, it is conceivable that heme-SCP as a prebiotic can shape the gut microbiota regardless of the administration method. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01195-9.

Surface-Functionalized Polymeric siRNA Nanoparticles for Tunable Targeting and Intracellular Delivery to Hematologic Cancer Cells.

To date, the application of RNA therapeutics to hematologic malignancies has been challenging owing to the resistance of blood cancer cells against conventional transfection methods. Herein, triple-targeting moiety-functionalized polymeric small interfering RNA (siRNA) nanoparticles were systematically developed for efficient targeted delivery of RNA therapeutics to hematologic cancer cells. Polymeric siRNAs were synthesized using rolling circle transcription and were surface-functionalized with three types of targeting moieties─a natural ligand and two additional combinations of cell-specific antibodies─for tunable targetability. As a proof of concept, the optimization of the hyaluronic acid/antibody conjugation ratio was performed for selective intracellular delivery to various non-Hodgkin's lymphoma (NHL) cell lines (Daudi, Raji, Ramos, and Toledo cells) via receptor-mediated endocytosis. The engineered nanoparticles showed almost 10-fold enhanced NHL-specific intracellular delivery and induced significant in vitro anticancer effects. This multitargeted nanoparticle platform may effectively support the intracellular delivery of polymeric siRNA sequences, and thus promote therapeutic effects in hematopoietic malignancies.

Prevention of Adjacent Segmental Disease after Fusion in Degenerative Spinal Disorder: Correlation between Segmental Lumbar Lordosis Ratio and Pelvic Incidence-Lumbar Lordosis Mismatch for a Minimum 5-Year Follow-up.

Study Design: Retrospective study. Purpose: Associations among risk factors related to adjacent segmental disease (ASD) remain unclear. We evaluated the risk factors and segmental lordosis ratio to prevent ASD developing after lumbar spinal fusion. Overview of Literature: Risk factors related to ASD development are age, sex, obesity, pre-existing degeneration, number of fusion segments, and decreased postoperative lumbar lordosis (LL). However, the associations among these factors are still unclear and should be clearly identified. Methods: We retrospectively reviewed data on 274 patients who underwent lumbar spinal fusion of three segments or below for lumbar degenerative disease from January 2010 to December 2012, with over 5 years of follow-up. Patients with preoperative sagittal vertical axis (SVA) >5 cm were excluded due to sagittal imbalance. A total of 37 patients with ASD and 40 control patients (CTRL) were randomly selected in a similar distribution of matching variables: age, sex, and preoperative degenerative changes. Sex, age, number of fusion segments, radiologic measurements, L4-5-S1/L1-S1 LL ratio, and spinopelvic parameters (pelvic incidence [PI], pelvic tilt [PT], sacral slope [SS], and SVA) were analyzed. Logistic regression was used to analyze the correlation between PI-LL mismatch and L4-5-S1 segmental lordosis rate. Results: No significant difference was found between ASDs and CTRL groups regarding age, sex, number of fusion segments, fusion method, and preoperative and postoperative spinopelvic parameters (PI, SS, PT, and LL). However, regarding the L4-5-S1/L1-S1 lordosis ratio, 50% (p=0.045), 60% (p=0.031), 70% (p=0.042), 80% (p=0.023), and 90% (p=0.023) were statistically significant; <20% (p=0.478), 30% (p=0.223), and 40% (p=0.089) were not statistically significant. In the postoperative PI-LL <10 group, ASD occurred less frequently than in the PI-LL >10 group, and the difference was statistically significant (p=0.048). Conclusions: Patients with a postoperative L4-5-S1/L1-S1 lordosis ratio >50% had less occurrence of ASD. Correcting LL according to PI and physiologic segmental lordosis ratio is important in preventing ASD.

A novel combination regimen with intense focused ultrasound and pressure- and dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution for lifting and tightening of the aging face.

BACKGROUND: Intense focused ultrasound (IFUS) has demonstrated moderate efficacy for facial laxity of the aging face. Pressure- and dose-controlled transcutaneous pneumatic injections of hypertonic glucose solution (TPIG) are a minimally invasive way to deliver solution into the skin for therapeutic purposes. Recently, its application around temporal areas is known to exert early-onset lifting effects with facial contour rejuvenation. AIMS: We sought to evaluate the safety and efficacy of this novel combination regimen with IFUS and TPIG for lifting and tightening of aging face. PATIENTS AND METHODS: Twenty-two Korean subjects with mild-to-moderate facial skin laxity were evaluated after receiving a sequential single session of IFUS and TPIG treatments. Dermatologists' objective assessments for general appearance, and mid- and low faces based on photographic images were performed at 1- and 12-week post-treatment follow-ups. Patients' subjective assessments were also conducted. Skin biopsies were taken at baseline and the last visit. RESULTS: Among 22 subjects, twenty (91%) demonstrated improvement after 12-week follow-up. We also observed similarly improved state just after 1 week of treatments (82%: 18/22). Specifically, improvement of the mid-face was evident from the first week, while the progress of the low face improvement was observed at the twelve week. Subjective assessments paralleled these findings. No seriously adverse effect was observed during procedures. Histologic evaluation showed greater dermal collagen fibers throughout the dermis after treatments. CONCLUSION: Combination treatment with IFUS and TPIG has beneficial effects for skin lifting and tightening with early-onset time.

A comparison between orthogonal and parallel plating methods for distal humerus fractures: a prospective randomized trial.

With the continuing improvements in implants for distal humerus fractures, it is expected that newer types of plates, which are anatomically precontoured, thinner and less irritating to soft tissue, would have comparable outcomes when used in a clinical study. The purpose of this study was to compare the clinical and radiographic outcomes in patients with distal humerus fractures who were treated with orthogonal and parallel plating methods using precontoured distal humerus plates. Sixty-seven patients with a mean age of 55.4 years (range 22-90 years) were included in this prospective study. The subjects were randomly assigned to receive 1 of 2 treatments: orthogonal or parallel plating. The following results were assessed: operating time, time to fracture union, presence of a step or gap at the articular margin, varus-valgus angulation, functional recovery, and complications. No intergroup differences were observed based on radiological and clinical results between the groups. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes, mean operation time, union time, or complication rates. There were no cases of fracture nonunion in either group; heterotrophic ossification was found 3 patients in orthogonal plating group and 2 patients in parallel plating group. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes or complication rates. However, orthogonal plating method may be preferred in cases of coronal shear fractures, where posterior to anterior fixation may provide additional stability to the intraarticular fractures. Additionally, parallel plating method may be the preferred technique used for fractures that occur at the most distal end of the humerus.

Eleven levels of spinous process fractures in thoracolumbar spine.

Cases of over 5-level spinous process fractures are extremely rare. Thoracolumbar region of spine is superimposed on ribs; and as such additional studies such as computerized tomography are needed to diagnose fractures in this region. We report a case of 11 contiguous level thoracolumbar spinous process fractures, which has been treated conservatively.

Diagnosis of laryngopharyngeal reflux among globus patients.

OBJECTIVE: Laryngopharyngeal reflux (LPR) is suggested as one of the most common etiologic factors of globus; currently, however, only a few tools are available to carry out effective diagnosis of LPR in clinics. The goal of this study was to assess the validity of reflux finding score (RFS), reflux symptom index (RSI), and symptom checklist-90-revision (SCL-90-R) as diagnostic methods for LPR. STUDY DESIGN AND SETTING: We selected 57 globus patients who were divided into test and control groups according to the results of 24-hour double-probe ambulatory pH monitoring. RFS, RSI, and SCL-90-R were then compared between the 2 groups, and the logical products of the 3 tests were also compared. RESULTS: RFS and RSI showed low specificity and there was no significant difference between the test and control groups. However, SCL-90-R revealed significantly high scores in the control group. The logical product of combining positive RFS and negative SCL-90-R was significantly different between the groups. CONCLUSION: RFS and RSI are less valid as diagnostic tools for LPR when used independently. Patients with LPR are found to exhibit weaker psychological symptoms than non-LPR patients. EBM RATING: B-2b.