Posterior Tissue Research Articles

Comparison of Gene Expression of Inflammation- and Fibrosis-Related Factors Between the Anterior and Posterior Capsule in Patients With Rotator Cuff Tear and Shoulder Stiffness.

Background:Arthroscopic capsular release is an effective treatment for refractory shoulder stiffness, yet there are no basic studies that can explain the extent of the release.Purpose:This study aimed to compare the genetic expression of inflammation- and fibrosis-related factors between the anterior and posterior capsules in patients with shoulder stiffness and rotator cuff tear.Study Design:Descriptive laboratory study.Methods:Enrolled in this study were 35 patients who underwent arthroscopic capsular release for shoulder stiffness along with the rotator cuff repair. Anterior and posterior glenohumeral joint capsular tissues were obtained during the capsular release. For the control tissue, anterior capsule was obtained from 40 patients without stiffness who underwent arthroscopic rotator cuff repair. The gene expression of collagen types I and III, fibronectin, extracellular matrix, basic fibroblast growth factor, transforming growth factor–β, connective tissue growth factor, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, intercellular adhesion molecule 1, interleukin 1, and tumor necrotizing factor–α were analyzed using real-time reverse transcription polymerase chain reaction. Differences in gene expression between the anterior capsule, the posterior capsule, and the control tissue were compared with the Kruskal-Wallis test.Results:The expression levels of collagen types I and III were significantly higher in the anterior capsule with stiffness com (pared with both the posterior capsule with stiffness (P = .010 for both) and the control (P = .038 and .010, respectively). The levels of fibronectin, MMP-2, and MMP-9 in the anterior capsule were significantly higher than in both the posterior capsule (P = .013, .003, and .006, respectively) and the control (P = .014, .003, and .005, respectively).Conclusion:Genetic analysis of the shoulder capsule revealed that more fibrogenic processes occur in the anterior capsule compared with the posterior capsule in patients with shoulder stiffness.Clinical Relevance:Capsular release for shoulder stiffness should be more focused on the anterior capsule than on the posterior capsule.

MiRNA-26b suppresses the TGF-β2-induced progression of HLE-B3 cells via the PI3K/Akt pathway

To study the effect of miR-26b on lens epithelial cells induced by transforming growth factor beta (TGF-β) 2 and the underlying signaling pathways. Human lens epithelial cell line B-3 (HLE-B3) was incubated with TGF-β2 (5 ng/mL) and then transfected with miR-26b mimics. The expression of miR-26b was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), while 5'-bromodeoxyuridine (BrdU) and wound-healing assays were used to measure the growth and migration of HLE-B3 cells, respectively. The expression of epithelial-mesenchymal transition (EMT) markers and the activity of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway were measured by Western blotting assay and immunofluorescence staining. Electron microscopy was also used to observe cellular morphology. The expression levels of miR-26b were significantly reduced in human posterior capsular opacification-attached lens tissue and TGF-β2-stimulated HLE-B3 cells. In the presence of TGF-β2, the growth, migration, and EMT of HLE-B3 cells were distinctly enhanced; these effects were attenuated by the administration of miR-26b mimics. Furthermore, the overexpression of miR-26b significantly reduced upregulation of the PI3K/Akt pathway when stimulated by TGF-β2 in HLE-B3 cells. Moreover, the addition of an activator (740 Y-P) led to the upregulation of the PI3K/Akt pathway and abolished the protective effect of miR-26b on the HLE-B3 cells that was mediated by TGF-β2. The miR-26b suppresses TGF-β2-induced growth, migration, and EMT in HLE-B3 cells by regulating the PI3K/Akt signaling pathway.

Posterior left atrial epicardial adipose tissue: scope of the problem and impact of new technology.

Patients with persistent forms of atrial fibrillation are seeking treatments based on the promise of better restoration of sinus rhythm with newer therapies. Successful catheter ablation and maintenance of atrial fibrillation in this subgroup is negatively impacted by the presence of epicardial adipose tissue (EAT) associated with the posterior left atrium. EAT is now understood to be hormonally active and promotes adverse atrial remodelling, including fibrosis and myopathy. Despite being dominantly adipose tissue, it is known to be electrically active, comprising ganglia, neural tissue and ectopic atrial myocardium that may contribute to endo-epicardial dissociation and persistent electrical activity and atrial fibrillation despite good endocardial electrical silencing. Hybrid procedures that include direct epicardial ablation of the posterior wall, including the EAT, are associated with superior outcomes in nonparoxysmal atrial fibrillation. Therapies for persistent atrial fibrillation that also ablate the EAT as part of a well tolerated transmural posterior wall ablation may improve outcomes in this challenging subset of patients.

A Paradigm Shift in Ocular Drug Delivery to Posterior Segment: Review on Current Drug Delivery Approaches

Objectives: Owing to the increasing number of patients suffering from posterior eye disorders, efficient medicine delivery to the posterior segment is now in great demand in the clinical services. With unmet medical requirements, the posterior eye segment is an important therapeutic target. So, physicians should be informed of new indications and current strategies of drug delivery when new technologies enter the market.
 Summary: The most common causes of vision impairment in developed nations are abnormalities of the posterior eye tissues. Poor drug distribution to lesions in patient's eyes is a key barrier to ocular disease therapy. The existence of barriers, such as the corneal barrier, aqueous barrier, and inner and outer blood-retinal barriers, severely limits medication accessibility in these locations. Because of its anatomical peculiarities, the posterior portion is particularly difficult to access for medications. The use of several new strategies for drug delivery is therefore a viable option for enhanced therapy of ocular disorders since recent advances in ocular drug delivery systems research have brought fresh insights into drug development.
 Conclusion: This article provides an overview of several aspects of ocular medication administration to the posterior region, with a focus on nano carrier-based approaches, suprachoroidal drug delivery system and ophthalmic devices, including the structure of the eye, its barriers, delivery routes, and the present status of drugs/devices.

Arthroscopic Distal Tibial Allograft for Posterior Glenoid Reconstruction

Background: Posterior glenoid bone loss occurs in more than two-thirds of patients with posterior glenohumeral instability, with 14% to 22% having greater than subcritical bone loss (13.5%), a marker for potential need for bony augmentation versus soft tissue-only procedures. Several techniques are described to augment either the version or volume of the glenoid surface including osteotomies, autograft transfers, and allograft tibia transfers. Indications: Arthroscopic-assisted allograft distal tibia bone block augmentation to the posterior glenoid is indicated for revision posterior instability procedures with posterior bone loss and in primary cases of posterior instability with critical bone loss. Technique Description: Arthroscopic posterior glenoid reconstruction with allograft distal tibia and posterior labral repair in the lateral position is presented. This technique uses standard instrument sets and requires no patient repositioning. The preplanned tibial bone block is prepared on a back table either prior to, or concurrently with, arthroscopic procedure. After creation of high posterior portal and standard anterior portal, a sucker-shaver and burr are used to create a perpendicular edge for apposition of the allograft tibia. The bone block is introduced through a longitudinal incision and underdelivered to the prepared surface under the liberated labrum. The articular surface of the graft and glenoid are aligned and cannulated screws are used to compress the bone block against the native glenoid. The posterior labral tissue is then mobilized over the graft and repaired to the native glenoid. Results: Arthroscopic distal tibial allograft augmentation for posterior bone loss restored stability and function in a small cohort of patients. Patients reported improved stability in the immediate postoperative course, with restoration of motion by 2 months. Push-ups, pull-ups, and return to full active duty without restrictions is allowed at 6 months postoperatively. Imaging at 3 months postoperatively has shown excellent graft healing. Discussion: The benefits of allograft tibia augmentation for posterior instability with glenoid bone loss include an anatomic joint surface restoration including articular cartilage, lack of donor site morbidity, and a minimally invasive approach. When performed arthroscopically, this technique permits concurrent posterior labral repair and anatomic reconstruction.

Controlling Pseudomonas aeruginosa infection in Oreochromis niloticus spawners by cefotaxime sodium

Spawners are considered the cornerstone in aquaculture; bacterial diseases are one of the most serious challenges facing this sector. The present study aimed to determine the efficacy of cefotaxime in treating the experimentally infected Oreochromis niloticus brooders with virulent Pseudomonas aeruginosa. Fish were grouped into normal group (N), infected non-treated group (INT) and infected-cefotaxime treated groups (ICT-W, ICT-24 & ICT-72) that administrated cefotaxime at 10 mg/l, and 10 mg/kg BW, administrated intraperitoneally at 24 h and 72 h intervals. Serum biochemical parameters, histopathological findings and cefotaxime concentration were studied in different groups. Tested P. aeruginosa was highly sensitive to cefotaxime with MIC equals 0.5 μg/ml and LD50 for O. niloticus was 0.2 ml of 8 × 107 CFU.fish−1. Mortality percent were 0, 50, 6.66, 23.33 and 13.33% for (N, INT, ICT-W, ICT-24 & ICT-72) respectively. There was significant amelioration in the serum biochemical parameter values (AST, ALT, creatinine, urea, uric acid and serum proteins) of all treated groups in comparison with the INT group, histopathological findings represented a marked improvement in hepatopancreas and posterior kidney tissues architecture when compared with (INT). Serum cefotaxime level were 0.517 ± 0.23, 0.951 ± 0.34 and 0.589 ± 0.18 μg/ml while, cefotaxime residues were 1.086 ± 0.12, 1.670 ± 0.36 and 1.261 ± 0.37 μg/g in muscular tissue for (ICT-W, ICT-24 & ICT-72) groups respectively. Cefotaxime considered effective antibiotic in the treatment of P. aeruginosa infection in O. niloticus brooders when administrated as 10 mg/litter medicated water or 10 mg/kg B·W. by I/P administration at 72 h interval.

Randomized Clinical Trial comparing clinical adjustment times of CAD/CAM screw-retained posterior crowns on ti-base abutments created with digital or conventional impressions. One-year follow-up.

ObjectivesThe purpose of this randomized clinical trial was to compare the required time of potential clinical adjustments of posterior screw‐retained monolithic zirconia implant retained crowns based on intraoral optical scanning (IOS) or conventional impressions.Materials and methodsPatients with posterior tissue level implants (Straumann RN) replacing solitary teeth were recruited. Of all patients, impressions were taken with both an IOS (3M™ TDS) and a conventional (polyether) pick‐up impression. Randomization was performed after impression taking and patients were to receive either a crown based on the digital or the conventional impression. The time required for adjustments at placement was recorded. Additionally, restoration survival and mechanical complications with a follow‐up of one year were documented.ResultsThirty two patients with 45 implants were included: 23 restorations in the test (IOS) and 22 in the control (conventional) group. The average adjustment time was 3.35 min (SD ± 3.38, range: 0–11 min) for the digital versus 6.09 min (SD ± 4.63, range: 0–18 min) for the conventional impressions (p = .039). A proper fit (no adjustments required) was achieved 39,1% in the digital and 18,2% conventional group respectively. All 45 restorations could be placed within the two planned appointments and only two minor mechanical complications occurred during the first year of function.ConclusionsThe use of IOS resulted in shorter adjustment times at try‐in than conventional impressions for solitary CAD/CAM implant restorations. Screw‐retained solitary monolithic zirconia restorations on ti‐base abutments show low complication‐ and survival rates in the short term.

Mechanistic Model for the Prediction of Small-Molecule Vitreal Clearance Combining Diffusion-Limited and Permeability-Limited Clearance.

The discovery of new small-molecule drugs for intravitreal administration would benefit from simple models to predict vitreal clearance (CL). The current models available have limitations in their applicability to small-molecule drugs and translatability to humans. We developed a mechanistic model combining the diffusion rate of the molecule in the vitreous and permeability across posterior segment tissues and applied it to 30 small molecules with observed CL available mostly from literature. We used Caco-2 permeability as a surrogate for ocular tissue permeability. The model predicted rabbit vitreal CL well, with 80% of the predictions being within a 2-fold range of the observed CL. For an accurate prediction, it was crucial to consider the anterior diffusion CL from the vitreous to the aqueous and a limiting diffusion CL for the whole eye. We observed no major differences in model accuracy when using literature permeability values from retinal pigment epithelial cell models. Importantly, by adopting the specific dimensions of the human eye, the model was able to accurately predict vitreal CL of four compounds for which human vitreal CL data are available. In summary, this mechanistic model enables a simple, accurate, and translatable estimation of small-molecule vitreal CL.

Salvage Oblique Lateral Interbody Fusion for Pseudarthrosis after Posterior/Transforaminal Lumbar Interbody Fusion: A Technical Note

This study aims to demonstrate the efficacy of salvage oblique lumbar interbody fusion (OLIF) surgery for pseudarthrosis after posterior/transforaminal lumbar interbody fusion (PLIF/TLIF). The study group were patients with leg or back pain induced by pseudarthrosis after PLIF/TLIF. These patients underwent salvage OLIF surgeries in our institutions between July 2015 and Oct 2019. We retrospectively evaluated their clinical and radiographic outcomes. Seven consecutive patients (all male; mean age 68.4 ± 9.3 years, range 53-81 years) were included in this study. There was no intraoperative complications in all cases. Six of 7 patients achieved bone union (at average 33.4 months follow-up) and had a successful postoperative course. Only 1 patient failed to gain bony fusion and required additional revision surgery due to progression of sagittal and coronal malalignment at 18 months after salvage OLIF surgery. The salvage OLIF approach was useful option for pseudarthrosis after PLIF/TLIF. It enabled us to build a rigid anterior support, allowed for extensive curettage of intervertebral scar tissue, and reduced the rate of the complications associated with dealing with posterior scar tissue.

Ocular Distribution of Papaverine Using Non-aqueous Vehicles.

Papaverine, a poorly soluble opium alkaloid, has recently been shown to reduce retinal inflammation due to which it may have therapeutic application in the management of Leber's hereditary optic neuropathy. In this study, papaverine eyedrops based on medium chain triglycerides were prepared and the effect of diethyl glycol monoethyl ether (DGME) on their ocular distribution was evaluated using an ex vivo porcine eye model. The route of drug penetration was also studied by orienting the eye to expose either only the cornea or the sclera to the formulation. Furthermore, in vivo studies were performed to confirm ocular tolerability and evaluate ocular drug distribution. Our results showed increased papaverine concentrations in the cornea and sclera in the presence of DGME butwith a slight reduction in theretina-choroid (RC) drug concentration when administered via the corneal route, suggesting that DGME enhances drug accumulation in the anterior ocular tissues but with little effect on posterior drug delivery. In vivo, the papaverine eyedrop with DGME showed good ocular tolerability with the highest drug concentration being observed in the cornea (1.53 ± 0.28 μg/g of tissue), followed by the conjunctiva (0.74 ± 0.18 μg/g) and sclera (0.25 ± 0.06 μg/g), respectively. However, no drug was detected in the RC, vitreous humor or plasma. Overall, this study highlighted that DGME influences ocular distribution and accumulation of papaverine. Moreover, results suggest that for hydrophobic drugs dissolved in hydrophobic non-aqueous vehicles, transcorneal penetration via the transuveal pathway may be the predominant route for drug penetration to posterior ocular tissues. Graphical abstract.

Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration

In several ocular diseases, vascular endothelial growth factor (VEGF) level has been found to be unregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for diabetic retinopathy (DR). The present study was to evaluate the chitosan-coated poly (lactide-co-glycolic acid) nanoparticles (CS-PLGA NPs) for sustained and effective delivery of bevacizumab to posterior ocular tissues. The penetration of NP through sclera was studied by confocal laser scanning microscopy (CLSM). For pharmacokinetic study, bevacizumab loaded NPs were administered into the rat eye through subconjunctival injection (SCJ) and pharmacokinetic parameters were compared to drug solution. CLSM and pharmacokinetic study showed better penetration of formulation and higher concentration of bevacizumab in posterior ocular tissues. In retinopathy model, CS-PLGA NPs by SCJ route showed more reduction of VEGF level in retina than the topical and intravitreal administration of formulation. Thus, CS-coated PLGA NPs can be potentially useful as carriers to target retina.

Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits.

The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

Biomechanical, histological, and molecular characterization of a new posttraumatic model of arthrofibrosis in rats.

Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats. Forty eight rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N-cm of torque in the 4-week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p = 0.007) and 8-week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p = 0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p < 0.05). Gene expression values evaluated in each group were comparable. This study presents a novel rat model of arthrofibrosis with severe and persistent knee contractures demonstrated biomechanically and histologically. Statement of clinical significance: Arthrofibrosis is a common complication following contemporary total knee arthroplasties. The proposed model is reproducible, cost-effective, and can be employed for translational investigations studying the pathogenesis of arthrofibrosis and efficacy of neoadjuvant pharmacologic agents.

Material properties and effect of preconditioning of human sclera, optic nerve, and optic nerve sheath

The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.

Embryonic Tissues as Active Foams.

The physical state of embryonic tissues emerges from non-equilibrium, collective interactions among constituent cells. Cellular jamming, rigidity transitions and characteristics of glassy dynamics have all been observed in multicellular systems, but it is unclear how cells control these emergent tissue states and transitions, including tissue fluidization. Combining computational and experimental methods, here we show that tissue fluidization in posterior zebrafish tissues is controlled by the stochastic dynamics of tensions at cell-cell contacts. We develop a computational framework that connects cell behavior to embryonic tissue dynamics, accounting for the presence of extracellular spaces, complex cell shapes and cortical tension dynamics. We predict that tissues are maximally rigid at the structural transition between confluent and non-confluent states, with actively-generated tension fluctuations controlling stress relaxation and tissue fluidization. By directly measuring strain and stress relaxation, as well as the dynamics of cell rearrangements, in elongating posterior zebrafish tissues, we show that tension fluctuations drive active cell rearrangements that fluidize the tissue. These results highlight a key role of non-equilibrium tension dynamics in developmental processes.

Posterior Left Atrial Adipose Tissue Attenuation Assessed by Computed Tomography and Recurrence of Atrial Fibrillation After Catheter Ablation.

[Figure: see text].

Solitary Subcutaneous Tissue Metastasis as Recurrence in a Case of Primary Angiosarcoma of Breast: Findings on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Primary angiosarcomas of the breast are rare tumors, with a fatal outcome. We present a rare case of an operated primary angiosarcoma of the right breast in a 20-year-old female who showed disease recurrence in the right posterior arm subcutaneous tissue on 18F-fluorodeoxyglucose positron emission tomography-computed tomography after 1 year of surgery without any other visceral metastasis.

Predictive factors of asymptomatic airway hyperresponsiveness in chronic rhinosinusitis with nasal polyps

Objective:To explore the predictive factors for asymptomatic airway hyperresponsiveness（AAHR） in patients with chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:A total of 76 CRSwNP patients who were hospitalized in the Department of Otorhinolaryngology of Fenyang Hospital affiliated to Shanxi Medical University from May 2016 to October 2020 were retrospectively analyzed, including 40 patients in AAHR group and 36 patients in non-airway hyperresponsiveness（non-airway hyperresponsiveness, NAHR） group. The clinical symptoms, CT score of paranasal sinuses, eosinophil（EOS） count in peripheral blood and nasal polyp tissue were compared and analyzed. Logistic regression was used to analyze the risk factors of AAHR, and receiver operating characteristics curve was used to judge the predictive value of the parameters. Results:Compared with NAHR group, AAHR group had more symptoms of mouth breathing and postnasal drip, higher total score of CT in ethmoid sinus, sphenoid sinus, olfactory cleft, and more EOS count in peripheral blood and nasal polyp tissue. The differences were statistically significant. There was a positive correlation between EOS count in peripheral blood and in nasal polyp tissue（r=0.324, P<0.01）. Postnasal drip, high posterior ethmoid sinus（PE） score and nasal polyp tissue EOS count were risk factors for AAHR. The predictive value of nasal polyp tissue EOS count was higher than that of PE score（AUC=0.786 and 0.685, respectively）. When the PE score was ≥1.5, the sensitivity was 80.0% and the specificity was 55.6%. When the nasal polyp tissue EOS count was ≥5.67/HPF, the sensitivity was 82.5% and the specificity was 66.7%. Conclusion:The occurrence of AAHR in patients with CRSwNP was related to clinical symptoms, paranasal sinus CT score, peripheral and nasal polyp tissue EOS count. PE score and nasal polyp tissue EOS count can be used to predict AAHR, however nasal polyp tissue EOS has higher predictive value.

Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region.

Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (1H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30–50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4–32.7 days and 4.3–9.5 days. The intravitreal clearance values were 1.7–8.7 µL/h and 3.6–5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6–1.3 mL for polymeric micelles and 1.9–3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.

Widespread anorectal lymphovascular networks and tissue drainage: analyses from submucosal India ink injection and indocyanine green fluorescence imaging.

AimAbdominoperineal resection is associated with poor prognosis in patients with advanced lower rectal cancer. This study aimed to analyse the functional lymphovascular network and tissue drainage in the anorectal region.MethodsIn this descriptive study, we performed microanatomical evaluations and intra‐operative imaging analysis in a cadaver and patients with rectal cancer. Specimens with India ink injection were collected from a cadaver and from six patients who underwent abdominoperineal resection. Intra‐operative indocyanine green fluorescence imaging was performed on four patients who underwent surgery for lower rectal cancer. India ink was injected into the submucosa at the dentate line of specimens. Tissue sections were examined by immunohistochemistry for D2‐40 and CD31. Intra‐operative indocyanine green was injected into the submucosa at the dentate line. Lymph flow was traced using a near‐infrared camera system.ResultsFascia branching from the rectal longitudinal muscle layer extended to the posterior hiatal ligament and lateral endopelvic fascia connective tissue lamina on the surface of the levator ani muscle. The fascia contained veins labelled with ink in their lumina and initial lymphatics. Intra‐operative indocyanine green fluorescence imaging revealed extensive lymph flow from the muscle layer of the anal canal to the hiatal ligament and endopelvic fascia along the longitudinal muscle layer fibres.ConclusionsThe anorectal region contained widespread venous and lymphatic networks in proportion to its specific connective tissue framework around the longitudinal‐muscle‐layer‐extending muscle bundles, which provides extensive networks for tissue fluid and cells.