Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.

A novel chemically engineered multifunctional statin conjugate as self-assembled nanoparticles inhibiting bile acid transporters.

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.

Ultra-Compact Pulse Charger for Lithium Polymer Battery with Simple Built-in Resistance Compensation in Biomedical Applications.

Active implantable medical devices (AIMDs) rely on batteries for uninterrupted operation and patient safety. Therefore, it is critical to ensure battery safety and longevity. To achieve this, constant current/constant voltage (CC/CV) methods have been commonly used and research has been conducted to compensate for the effects of built-in resistance (BIR) of batteries. However, conventional CC/CV methods may pose the risk of lithium plating. Furthermore, conventional compensation methods for BIR require external components, complex algorithms, or large chip sizes, which inhibit the miniaturization and integration of AIMDs. To address this issue, we have developed a pulse charger that utilizes pulse current to ensure battery safety and facilitate easy compensation for BIR. A comparison with previous research on BIR compensation shows that our approach achieves the smallest chip size of 0.0062 mm2 and the lowest system complexity using 1-bit ADC. In addition, we have demonstrated a reduction in charging time by at least 44.4% compared to conventional CC/CV methods, validating the effectiveness of our system's BIR compensation. The compact size and safety features of the proposed charging system make it promising for AIMDs, which have space-constrained environments.

Analysis of Self-Assembled Low- and High-Molecular-Weight Poly-L-Lysine-Ce6 Conjugate-Based Nanoparticles.

In cancer therapy, photodynamic therapy (PDT) has attracted significant attention due to its high potential for tumor-selective treatment. However, PDT agents often exhibit poor physicochemical properties, including solubility, necessitating the development of nanoformulations. In this study, we developed two cationic peptide-based self-assembled nanomaterials by using a PDT agent, chlorin e6 (Ce6). To manufacture biocompatible nanoparticles based on peptides, we used the cationic poly-L-lysine peptide, which is rich in primary amines. We prepared low- and high-molecular-weight poly-L-lysine, and then evaluated the formation and performance of nanoparticles after chemical conjugation with Ce6. The results showed that both molecules formed self-assembled nanoparticles by themselves in saline. Interestingly, the high-molecular-weight poly-L-lysine and Ce6 conjugates (HPLCe6) exhibited better self-assembly and PDT performance than low-molecular-weight poly-L-lysine and Ce6 conjugates (LPLCe6). Moreover, the HPLCe6 conjugates showed superior cellular uptake and exhibited stronger cytotoxicity in cell toxicity experiments. Therefore, it is functionally beneficial to use high-molecular-weight poly-L-lysine in the manufacturing of poly-L-lysine-based self-assembling biocompatible PDT nanoconjugates.

Design and development of novel self-assembled catechol-modified bile acid conjugates as pH-responsive apical sodium-dependent bile acid transporter targeting nanoparticles.

Catechol-based biomaterials demonstrate biocompatibility, making them suitable for a wide range of therapeutic applications when integrated into various molecular frameworks. However, the development of orally available catechol-based biomaterials has been hindered by significant pH variations and complex interactions in the gastrointestinal (GI) tract. In this study, we introduce a novel catechol-modified bile acid (CMBA), which is synthesized by anchoring the FDA-approved drug, ursodeoxycholic acid to the neurotransmitter dopamine. This modification could form a new apical sodium-dependent bile acid transporter (ASBT) inhibitor (ASBTi) due to the bile acid moiety. The computational analysis using the TRAnsient Pockets in Proteins (TRAPP) module, coupled with MD simulations, revealed that CMBA exhibits a strong binding affinity at residues 51-55 of ASBT with a low inhibitory constant (Ki) value. Notably, in slightly alkaline biological conditions, CMBA molecules self-assemble into carrier-free nanoparticles with an average size of 240.2 ± 44.2 nm, while maintaining their ability to bind with ASBT. When administered orally, CMBA accumulates in the ileum and liver over 24 h, exhibiting significant therapeutic effects on bile acid (BA) metabolism in a high-fat diet (HFD)-fed mouse model. This study underscores the therapeutic potential of the newly developed catechol-based, pH-responsive ASBT-inhibiting nanoparticles presenting a promising avenue for advancing therapy.

Design of chimeric GLP-1A using oligomeric bile acids to utilize transporter-mediated endocytosis for oral delivery.

BACKGROUND: Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT). METHODS: In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (mD-G1A, bD-G1A, and tD-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic db/db mice model were evaluated. RESULTS: In silico results showed that tetraDOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover, bD-G1A and tD-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on db/db mice, tD-G1A (50 µg/kg) lowered the glucose level more than bD-G1A (50 µg/kg) compared with the control (35.5% vs. 26.4%). CONCLUSION: GLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment.

Comparative Genomic Analysis of Biofilm-Forming Polar Microbacterium sp. Strains PAMC22086 and PAMC21962 Isolated from Extreme Habitats.

The members of Microbacterium isolated from different environments are known to form peptidoglycan. In this study, we compared the biofilm-forming abilities of Microbacterium sp. PAMC22086 (PAMC22086), which was isolated from the soil in the South Shetland Islands and Microbacterium sp. PAMC21962 (PAMC21962), which was isolated from algae in the South Shetland Islands. The analysis of average nucleotide identity and phylogeny of PAMC22086 revealed a 97% similarity to Microbacterium oxydans VIU2A, while PAMC21962 showed a 99.1% similarity to Microbacterium hominis SGAir0570. For the comparative genomic analysis of PAMC22086 and PAMC21962, the genes related to biofilm formation were identified using EggNOG and KEGG pathway databases. The genes possessed by both PAMC22086 and PAMC21962 are cpdA, phnB, rhlC, and glgC, which regulate virulence, biofilm formation, and multicellular structure. Among the genes indirectly involved in biofilm formation, unlike PAMC21962, PAMC22086 possessed csrA, glgC, and glgB, which are responsible for attachment and glycogen biosynthesis. Additionally, in PAMC22086, additional functional genes rsmA, which is involved in mobility and polysaccharide production, and dksA, GTPase, and oxyR, which play roles in cell cycle and stress response, were identified. In addition, the biofilm-forming ability of the two isolates was examined in vivo using the standard crystal violet staining technique, and morphological differences in the biofilm were investigated. It is evident from the different distribution of biofilm-associated genes between the two strains that the bacteria can survive in different niches by employing distinct strategies. Both strains exhibit distinct morphologies. PAMC22086 forms a biofilm that attaches to the side, while PAMC21962 indicates growth starting from the center. The biofilm formation-related genes in Microbacterium are not well understood. However, it has been observed that Microbacterium species form biofilm regardless of the number of genes they possess. Through comparison between different Microbacterium species, it was revealed that specific core genes are involved in cell adhesion, which plays a crucial role in biofilm formation. This study provides a comprehensive profile of the Microbacterium genus's genomic features and a preliminary understanding of biofilm in this genus, laying the foundation for further research.

An amphiphilic material arginine-arginine-bile acid promotes α-synuclein amyloid formation.

Amyloid generation plays essential roles in various human diseases, biological functions, and nanotechnology. However, developing efficient chemical and biological candidates for regulating amyloid fibrillation remains difficult because information on the molecular actions of modulators is insufficient. Thus, studies are needed to understand how the intermolecular physicochemical properties of the synthesised molecules and amyloid precursors influence amyloidogenesis. In this study, we synthesised a novel amphiphilic sub-nanosized material, arginine-arginine (RR)-bile acid (BA), by conjugating positively charged RR to hydrophobic BA. The effects of RR-BA on amyloid formation were investigated on α-synuclein (αSN) in Parkinson's disease and on K18 and amyloid-ß (1-42) (Aß42) in Alzheimer's disease. RR-BA showed no appreciable effect on the kinetics of K18 and Aß42 amyloid fibrillation because of their weak and non-specific interactions. However, RR-BA specifically bound to αSN with moderate binding affinity through electrostatic interactions between the positively charged RR and the negatively charged cluster in the C-terminus of αSN. In addition, hydrophobic BA in the αSN-RR-BA complex transiently condensed αSN for primary nucleation, thereby accelerating αSN amyloid fibrillation. We propose an electrostatic binding and hydrophobic condensation model of RR-BA-driven amyloid formation of αSN, which will contribute to the rational design and development of molecules for controlling amyloid aggregation in diverse fields.

Doxorubicin covalently conjugated heparin displays anti-cancer activity as a self-assembled nanoparticle with a low-anticoagulant effect.

Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti-inflammatory therapy beyond its anticoagulant effect. Here, we sought to utilize heparin molecules as drug carriers by directly conjugating the anticancer drug doxorubicin to the carboxyl group of unfractionated heparin. Given the molecular action of doxorubicin in intercalating DNA, it is expected to be less effective when structurally combined with other molecules. However, by utilizing doxorubicin molecules to produce reactive oxygen species (ROS), we found that the heparin-doxorubicin conjugates have significant cytotoxic ability to kill CT26 tumor cells with low anticoagulant activity. Several doxorubicin molecules were bound to heparin to provide sufficient cytotoxic capability and self-assembly ability due to their amphiphilic properties. The self-assembled formation of these nanoparticles was demonstrated through DLS, SEM and TEM. The cytotoxic ROS-generating doxorubicin-conjugated heparins could inhibit tumor growth and metastasis in CT26-bearing Balb/c animal models. Our results demonstrate that this cytotoxic doxorubicin-based heparin conjugate can significantly inhibit tumor growth and metastasis, thus showing promise as a potential new anti-cancer therapeutic.

Development of a Peptide-Based Nano-Sized Cathepsin B Inhibitor for Anticancer Therapy.

Numerous cathepsin B inhibitors have been developed and are under investigation as potential cancer treatments. They have been evaluated for their ability to inhibit cathepsin B activity and reduce tumor growth. However, they have shown critical limitations, including low anticancer efficacy and high toxicity, due to their low selectivity and delivery problems. In this study, we developed a novel peptide and drug conjugate (PDC)-based cathepsin B inhibitor using cathepsin-B-specific peptide (RR) and bile acid (BA). Interestingly, this RR and BA conjugate (RR-BA) was able to self-assemble in an aqueous solution, and as a result, it formed stable nanoparticles. The nano-sized RR-BA conjugate showed significant cathepsin B inhibitory effects and anticancer effects against mouse colorectal cancer (CT26) cells. Its therapeutic effect and low toxicity were also confirmed in CT26 tumor-bearing mice after intravenous injection. Therefore, based on these results, the RR-BA conjugate could be developed as an effective anticancer drug candidate for inhibiting cathepsin B in anticancer therapy.

Efficient Distributed Wireless Power Transfer System for Multiple Wearable Sensors through Textile Coil Array.

When it is necessary to detect various physiological signals of the human body, clothing embroidered with near-field effect patterns can be used as a long-term power supply medium to supply power to long-distance transmitters and receivers to form a wireless power supply system. The proposed system uses an optimized parallel circuit to achieve a power transfer efficiency of more than five times higher than that of the existing series circuit. The power transfer efficiency of simultaneously supplying energy to multiple sensors is increased higher than five times and even more when only one sensor is coupled. When powering eight sensors at the same time, the power transmission efficiency can reach 25.1%. Even when eight sensors powered by the coupled textile coils are reduced to one, the power transfer efficiency of the whole system can reach 13.21%. Additionally, the proposed system is also applicable when the number of sensors ranges from 2 to 12.

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic-DEVD-Doxorubicin Conjugate for Targeted Cancer Therapy.

In the development of new drugs, typical polymer- or macromolecule-based nanocarriers suffer from manufacturing process complexity, unwanted systematic toxicity, and low loading capacity. However, carrier-free nanomedicines have made outstanding progress in drug delivery and pharmacokinetics, demonstrating most of the advantages associated with nanoparticles when applied in targeted anticancer therapy. Here, to overcome the problems of nanocarriers and conventional cytotoxic drugs, we developed a novel, carrier-free, self-assembled prodrug consisting of a hydrophobic palmitic (16-carbon chain n-hexadecane chain) moiety and hydrophilic group (or moiety) which is included in a caspase-3-specific cleavable peptide (Asp-Glu-Val-Asp, DEVD) and a cytotoxic drug (doxorubicin, DOX). The amphiphilic conjugate, the palmitic-DEVD-DOX, has the ability to self-assemble into nanoparticles in saline without the need for any carriers or nanoformulations. Additionally, the inclusion of doxorubicin is in its prodrug form and the apoptosis-specific DEVD peptide lead to the reduced side effects of doxorubicin in normal tissue. Furthermore, the carrier-free palmitic-DEVD-DOX nanoparticles could passively accumulate in the tumor tissues of tumor-bearing mice due to an enhanced permeation and retention (EPR) effect. As a result, the palmitic-DEVD-DOX conjugate showed an enhanced therapeutic effect compared with the unmodified DEVD-DOX conjugate. Therefore, this carrier-free palmitic-DEVD-DOX prodrug has great therapeutic potential to treat solid tumors, overcoming the problems of conventional chemotherapy and nanoparticles.

Long-Term Analysis of Clinical Features and Treatment Outcomes of Inflammatory Choroidal Neovascularization.

PURPOSE: To investigate the long-term clinical features and treatment outcomes of patients with inflammatory choroidal neovascularization (CNV) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF). DESIGN: Retrospective, interventional, consecutive case series. METHODS: Sixty-five eyes of 65 patients with inflammatory CNV treated with anti-VEGF injections and followed up at least 12 months were included. Retrospective chart review was conducted at a single tertiary referral center. RESULTS: Study participants were followed up for 60.6 ± 42.8 (range, 16-160) months. Mean age was 33.4 ± 10.8 years, and mean refractive error was -3.94 ± 1.35 D in spherical equivalent. Final best-corrected visual acuity (BCVA) was 0.21 ± 0.20 logMAR after treatment. Patients were treated with bevacizumab (76.9%), ranibizumab (4.6%), aflibercept (3.1%), and drug combinations (15.4%). Systemic corticosteroid or immunosuppressant use was not correlated with visual outcome, required number of anti-VEGF injections, and recurrence. Commonly occurring optical coherence tomography (OCT) features included ellipsoid zone disruption, choroidal hypertransmission, retinal pigment epithelium atrophy or absence (RPEA), intraretinal hyperreflective foci (HRF), choroidal vessel engorgement, focal choroidal excavation, and irregular vascular loops (on OCT angiography). RPEA after treatment (ß = 0.238, P = .036) and BCVA (ß = 0.267, P = .029) showed significant correlation with final BCVA. A total of 28 patients (43.1%) experienced recurrence; intraretinal HRF after treatment was the single risk factor for recurrence (odds ratio = 2.712, P = .031). CONCLUSIONS: Inflammatory CNV recurrence showed higher rates over time after anti-VEGF treatment than previously reported, even though the overall visual outcome was good. Baseline BCVA and RPEA after treatment are significant predictors for visual outcome. Intraretinal HRF after anti-VEGF treatment suggests the potential risk of recurrence.

Sex-Biased Gene Expression and Isoform Profile of Brine Shrimp Artemia franciscana by Transcriptome Analysis.

The brine shrimp Artemia has a ZW sex determination system with ZW chromosomes in females and ZZ chromosomes in males. Artemia has been considered a promising model organism for ZW sex-determining systems, but the genes involved in sex determination and differentiation of Artemia have not yet been identified. Here, we conducted transcriptome sequencing of female and male A. franciscana using PacBio Iso-Seq and Illumina RNA-Seq techniques to identify candidate sex determination genes. Among the 42,566 transcripts obtained from Iso-Seq, 23,514 were analyzed. Of these, 2065 (8.8%) were female specific, 2513 (10.7%) were male specific, and 18,936 (80.5%) were co-expressed in females and males. Based on GO enrichment analysis and expression values, we found 10 female-biased and 29 male-biased expressed genes, including DMRT1 and Sad genes showing male-biased expression. Our results showed that DMRT1 has three isoforms with five exons, while Sad has seven isoforms with 2-11 exons. The Sad gene is involved in ecdysteroid signaling related to molting and metamorphosis in arthropods. Further studies on ecdysteroid biosynthetic genes are needed to improve our understanding of Artemia sex determination. This study will provide a valuable resource for sex determination and differentiation studies on Artemia and other crustaceans with ZW systems.

Discordance in Retinal and Choroidal Vascular Densities in Patients with Type 2 Diabetes Mellitus on Optical Coherence Tomography Angiography.

PURPOSE: In the present study, the retinal and choroidal vascular densities (VDs) in type 2 diabetes mellitus (DM) patients were analyzed using optical coherence tomography angiography (OCTA). METHODS: The study included 282 eyes of 152 patients with type 2 DM (114 without retinopathy, 79 nonproliferative diabetic retinopathy (NPDR), 48 severe NPDR, and 41 proliferative diabetic retinopathy (PDR) eyes). The superficial and deep retinal vessel, choriocapillaris, and choroidal VDs were measured using a binarization method on OCTA images. VDs were compared based on retinopathy severity. Correlations among densities were analyzed. RESULTS: Retinal and choriocapillaris VDs were lower in PDR than in NPDR (all P < 0.05). Correlation analysis showed significant positive correlations among densities of superficial and deep retinal vessels and choriocapillaris (all P < 0.001). Choroidal VD showed a negative correlation with superficial and deep retinal vessels and choriocapillaris (all P < 0.001). Retinal and choriocapillaris VDs showed a negative correlation with diabetic retinopathy (DR) grade (all P < 0.001); however, the choroidal VD showed a weak positive correlation (P=0.030). CONCLUSION: Choroidal VD increased as retinal and choriocapillaris VDs decreased, indicating that the outer layer of the choroid is less affected by DR severity and VD of larger choroidal vessels may even be increased as a compensatory mechanism for decreased retinal and choriocapillaris VDs in type 2 DM patients.

Cytokines associated with hemorrhage in proliferative diabetic retinopathy.

PURPOSE: To investigate aqueous cytokine levels in association with hemorrhage in proliferative diabetic retinopathy (PDR) in patients with type 2 diabetes mellitus. METHODS: Sixty-six eyes with treatment-naïve PDR, including 26 hemorrhagic and 40 nonhemorrhagic eyes were included in this institutional study. Aqueous humor levels of interleukin (IL)-1b, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and soluble VEGF receptor-1 were obtained by multiplex bead assay. Visual acuity and hemorrhage area measurements were obtained, and correlations between cytokine levels and hemorrhage were identified. RESULTS: Levels of MCP-1, TNF-α, and VEGF were higher in hemorrhagic eyes (1506.77 vs. 2131.31 pg/mL, 0.43 vs. 0.63 pg/mL, and 103.96 vs. 206.96 pg/mL; P = 0.050, 0.022, and 0.027, respectively). The levels of IL-8, MCP-1, TNF-α, and VEGF showed positive correlation with visual acuity (P = 0.019, 0.015, 0.001, and 0.014, respectively). The hemorrhage area revealed positive correlation with TNF-α and VEGF levels (P = 0.001 and < 0.001, respectively). CONCLUSION: The presence and amount of hemorrhage in PDR were associated not only with VEGF concentration, but also with the levels of certain inflammatory cytokines, suggesting a role of both VEGF and inflammation in hemorrhagic eyes.

Greater Tuberosity Bone Mineral Density and Rotator Cuff Tear Size Are Independent Factors Associated With Cutting-Through in Arthroscopic Suture-Bridge Rotator Cuff Repair.

PURPOSE: To evaluate the correlation between cutting-through at the greater tuberosity (GT) in arthroscopic suture-bridge rotator cuff repair and the bone mineral density (BMD) of the lumbar spine, hip, and ipsilateral GT of the proximal humerus and to evaluate factors and clinical outcomes related to cutting-through. METHODS: This study prospectively enrolled patients who underwent arthroscopic knotted suture-bridge rotator cuff repair for full-thickness rotator cuff tears between June 2014 and October 2015 and who had undergone dual-energy X-ray absorptiometry cans within 1 month before surgery with a minimum 2-year follow-up. Cutting-through was defined as the occurrence of cortical breakage of the GT just medial to the lateral knotless anchor hole due to the tension of the sutures from the medial anchor, and it was assessed. Clinical and radiologic data were analyzed. Univariate and regression analyses were performed to evaluate factors related to cutting-through. RESULTS: A total of 78 patients were analyzed. Patients were divided into 2 groups: patients who had cutting-through (46, group I) and patients who did not (32, group II). In an analysis of lumbar spine, hip, and GT BMD, GT BMD was the most effective for predicting cutting-through (area under the receiver operating characteristic curve = 0.94, 95% confidence interval 0.89-0.99). GT BMD (P < .001) and tear size (P = .004) were independent factors for cutting-through. Although a significant difference was found between the 2 groups in terms of age, sex, lumbar spine and hip BMD, fatty infiltration of the supraspinatus and infraspinatus, and atrophy of the supraspinatus, these variables were not independent factors. Clinical and structural outcomes showed no significant difference between the 2 groups, and anchor failure was not identified intraoperatively. CONCLUSIONS: GT BMD and rotator cuff tear size are independent factors associated with cutting-through at the GT. A dual-energy X-ray absorptiometry scan of the proximal humerus is useful for predicting bone quality before arthroscopic suture-bridge rotator cuff repair. LEVEL OF EVIDENCE: Level II, Prospective cohort study.

Prevalence of rotator cuff diseases in adults older than 40 years in or near Chuncheon city, Korea.

BACKGROUND: To determine the prevalence of rotator cuff diseases in a population older than 40 years in or nearby Chuncheon city, Republic of Korea. METHODS: Sixty shoulders of 30 people older than 40 years who participated in a health lecture were examined for free by an orthopedic surgeon. Visual analog scale of pain and American Shoulder and Elbow Surgeons scores were assigned, and routine physical examination was performed. Ultrasonography was performed on the shoulder. RESULTS: On ultrasonographic examination, there were one shoulder with full thickness rotator cuff tear, 20 of 60 (33%) with partial thickness rotator cuff tear, five of 60 (8%) with calcific tendinitis, one of 60 (2%) with tear of the long head of the biceps, and five of 60 (8%) with tendinitis of the long head of the biceps. Participants older than 60 years showed significantly high proportions of lesion of the long head of the biceps and rotator cuff diseases (P=0.019 and P=0.015, respectively). Participants who performed physical labor had high proportions of rotator cuff tear and rotator cuff disease (P=0.001 and P<0.001, respectively). CONCLUSIONS: Rotator cuff diseases showed a high prevalence in aged persons and resulted in a decrease in shoulder function.

Evaluation of assembly methods combining long-reads and short-reads to obtain Paenibacillus sp. R4 high-quality complete genome.

We sequenced the Paenibacillus sp. R4 using Oxford Nanopore Technology (ONT), single molecule real-time (SMRT) technology from Pacific Biosciences (PacBio), and Illumina technologies to investigate the application of nanopore reads in de novo sequencing of bacterial genomes. We compared the differences in both genome sequences between genome assemblies using nanopore and PacBio reads and focused on the difference in the prediction of coding sequences. The results indicated that for more accurate predictions of open reading frames, contigs in the assemblies using only PacBio reads also needed to be corrected using short reads with high-quality bases, and repeat regions in genomes did not affect the increase of mispredicted coding sequences via genome polishing significantly. In assemblies using only nanopore reads, genome polishing was essential, but many repeat regions in genomes might increase the number of mispredicted coding sequences via genome polishing. The hybrid assembly combining the long reads and short reads represents the best result for coding sequence predictions in genome assemblies using nanopore reads.