Analysis on key parameters in subretinal injection facilitating a predictable and automated robot-assisted treatment in gene therapy.

BACKGROUND: Subretinal injection (SRI) has become an important surgical method for treating vitreoretinal diseases. Nevertheless, the optimisation of bleb formation in SRI, for the attainment of desired therapeutic outcomes, still requires further investigation. METHODS: This study analysed the influence of surgical parameters on SRI using a robotic setup. The surgical procedure was automated using visual guidance. A predictive model for bleb formation was established through regression analysis. To validate the model, we compared the clinical data's target area with the simulated SRI's actual area using parameters determined by the predictive model. RESULTS: The insertion angle dominated the eccentricity and area of the bleb. The injection speed dominated the axial angle. Automated SRI increased success rate and produced predictable outcomes. CONCLUSIONS: We could provide accurate SRI on phantom models by adjusting surgical parameters based on the patient's clinical information. Automatic robot-assisted SRI is a promising surgical technique with highly predictable results.

Zero-fluoroscopy ablation of left-sided arrhythmia substrates in children - Mid-term safety and feasibility study from transaortic approach.

BACKGROUND: A widely used method of treating left-sided arrhythmia substrates in children is retrograde transaortic ablation under fluoroscopic guidance. However, the feasibility, safety, and efficacy of this approach under zero fluoroscopy (ZF) guidance, especially the mid-term safety of anatomy and function of aortic valves, have yet to be proven. METHODS: All consecutive patients who received ablation of left-sided arrhythmias between January 2012 and June 2020 and below 20 years-old were enrolled. The study group submitted to 55 ZF-guided procedures using cardiac mapping system (EnSite Precision), whereas 49 procedures were performed under fluoroscopic guidance in the control group. Echocardiographic studies took place before and 6-months after ablative procedures. RESULTS: One-hundred-and-two patients (male, 66; female, 36) underwent a total of 104 ablative procedures. Mean procedural durations were 83.9 ± 44.4 min in the study group and 64.8 ± 29.1 min in the control group, respectively (p = .01; the 95% confidence interval, -33.57 to -4.63). Corresponding fluoroscopic times were .5 ± 2.2 min and 24.7 ± 13.9 min (p < .001; the 95% confidence interval, 20.15 to 28.22). ZF may be reasonably applied after a learning curve of 20 cases. Immediate procedural success and recurrence rates were similar in each groups. There was no detectable progression of aortic regurgitation in any of the patients during serial follow-up of echocardiography. CONCLUSION: ZF-guided retrograde transaortic ablation of left-sided arrhythmia substrates proved safe in children at midterm follow-up, reducing radiation exposure significantly within a learning curve of <20 cases.

Diagnostic Performance of FibroTouch Ultrasound Attenuation Parameter and Liver Stiffness Measurement in Assessing Hepatic Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.

On the spore ornamentation of the microsoroid ferns (microsoroideae, polypodiaceae).

Microsoroideae is the third largest of the six subfamilies of Polypodiaceae, containing over 180 species. These ferns are widely distributed in the tropical and subtropical regions of the Old World and Oceania. We documented the spore ornamentation and integrated these data into the latest phylogenetic hypotheses, including a sampling of 100 taxa representing each of 17 major lineages of microsoroid ferns. This enabled us to reconstruct the ancestral states of the spore morphology. The results show verrucate ornamentation as an ancestral state for Goniophlebieae and Lecanoptereae, globular for Microsoreae, and rugulate surface for Lepisoreae. In addition, spore ornamentation can be used to distinguish certain clades of the microsoroid ferns. Among all five tribes, Lecanoptereae show most diversity in spore surface ornamentation.

Semiautomated optical coherence tomography-guided robotic surgery for porcine lens removal.

PURPOSE: To evaluate semiautomated surgical lens extraction procedures using the optical coherence tomography (OCT)-integrated Intraocular Robotic Interventional Surgical System. SETTING: Stein Eye Institute and Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, USA. DESIGN: Experimental study. METHODS: Semiautomated lens extraction was performed on postmortem pig eyes using a robotic platform integrated with an OCT imaging system. Lens extraction was performed using a series of automated steps including robot-to-eye alignment, irrigation/aspiration (I/A) handpiece insertion, anatomic modeling, surgical path planning, and I/A handpiece navigation. Intraoperative surgical supervision and human intervention were enabled by real-time OCT image feedback to the surgeon via a graphical user interface. Manual preparation of the pig-eye models, including the corneal incision and capsulorhexis, was performed by a trained cataract surgeon before the semiautomated lens extraction procedures. A scoring system was used to assess surgical complications in a postoperative evaluation. RESULTS: Complete lens extraction was achieved in 25 of 30 eyes. In the remaining 5 eyes, small lens pieces (≤1.0 mm3) were detected near the lens equator, where transpupillary OCT could not image. No posterior capsule rupture or corneal leakage occurred. The mean surgical duration was 277 seconds ± 42 (SD). Based on a 3-point scale (0 = no damage), damage to the iris was 0.33 ± 0.20, damage to the cornea was 1.47 ± 0.20 (due to tissue dehydration), and stress at the incision was 0.97 ± 0.11. CONCLUSIONS: No posterior capsule rupture was reported. Complete lens removal was achieved in 25 trials without significant surgical complications. Refinements to the procedures are required before fully automated lens extraction can be realized.

Value of prenatal diagnosis of meconium peritonitis: Comparison of outcomes of prenatal and postnatal diagnosis.

Advancements in diagnostic modalities have improved the diagnosis of meconium peritonitis (MP) both in utero and ex utero. This study aimed to determine the efficacy of prompt prenatal and postnatal diagnoses of MP on the postnatal outcomes of these patients.We conducted a retrospective chart review of neonates with MP admitted to the Mackay Memorial Hospital Systems from 2005 to 2016. The prenatal diagnoses, postnatal presentations, surgical indications, operative methods, types of MP, operative findings, associated anomalies, morbidities, patient outcomes, and survival rates were analyzed. Morbidities included postoperative adhesion ileus, bacteremia, and short bowel syndrome. We also performed subgroup analyses of the morbidity and survival rates of prenatally versus postnatally diagnosed patients, as well as inborn versus outborn neonates.Thirty-seven neonates with MP were enrolled. Of this number, 24 (64.9%) were diagnosed prenatally. Twenty-two (59.5%) were born preterm. The most common prenatal sonographic findings included fetal ascites followed by dilated bowel loops. Abdominal distention was the most frequent postnatal symptom. Thirty-four (91.9%) neonates underwent surgery, whereas 3 were managed conservatively. Volvulus of the gastrointestinal tract was the most frequent anatomic anomaly. The total morbidity and survival rates were 37.8% and 91.9%, respectively. The morbidity and survival rates did not differ significantly between prenatally and postnatally diagnosed patients (37.5% vs 33.3%, P = 1.00; 91.7% vs 92.3%, P = 1.00, respectively). Inborn and outborn patients did not differ in terms of morbidity and survival rates (27.3% vs 53.3%, P = .17; 100% vs 80.0%, P = .06, respectively).Although not statistically significant, inborn MP neonates had higher survival rates when compared with outborn MP neonates. Prompt postnatal management at tertiary centers seemed crucial.

[Incidence and risk factors of early deep venous thrombosis after knee arthroscopy operation under conventional tourniquet].

OBJECTIVE: To find out the incidence of early DVT in patients after knee arthroscopic surgery with routine use of tourniquet and discuss the associate risk factors. METHODS: Total 1 561 cases undertaken primary knee arthroscopic surgery was reviewed retrospectively from January 2013 to January 2017, including 651 males and 910 females with a mean age of (65.7±8.7) years old ranging from 62 to 81 years old. The cases were divided into DVT group and non-DVT group according to ultrasonic Doppler after surgery. The DVT occurrence rate was calculated and the basic information was analyzed to filter out the risk factors through univariate analysis and multivariate analysis. The cases of DVT group received 6 months anticoagulation therapy and were undertaken a follow-up of 1, 3, 6 months by ultrasonic Doppler. RESULTS: Out of the 1 561 cases, 226(14.5%) developed early DVTs following surgery, 32(2.0%) cases had the proximal DVTs, and 194(12.4%) cases had the isolated distal DVTs. The risk factors include the age(>=73 years), female sex and gastrocnemius vein dilation (GVD), hypertension, longer tourniquet time(>=74 min). The GVD and the length of tourniquet time was considered to be the best predictor of the early DVTs after surgery, with an odds ratio of 2.337 (95% CI, 1.644-3.611) and 2.112 (95%CI, 1.452-3.301). Twelve isolated distal DVTs(6.6%) and 11 proximal DVTs(36.7%) still showed thrombus at 6-month follow-up, but exhibit decreased size and at various stage of resolution. CONCLUSIONS: The incidence of early DVTs after knee arthroscopic surgery is 14.5%. Out of all risk factors, the GVD and the length of tourniquet time have the best power for prediction of DVTs after surgery. Both proximal and distal DVTs received accepted outcomes after formal therapy.

Intraocular robotic interventional surgical system (IRISS): Semi-automated OCT-guided cataract removal.

BACKGROUND: With the development of laser-assisted platforms, the outcomes of cataract surgery have been improved by automating several procedures. The cataract-extraction step continues to be manually performed, but due to deficiencies in sensing capabilities, surgical complications such as posterior capsule rupture and incomplete cataract removal remain. METHODS: An optical coherence tomography (OCT) system is integrated into our intraocular robotic interventional surgical system (IRISS) robot. The OCT images are used for preoperative planning and intraoperative intervention in a series of automated procedures. Real-time intervention allows surgeons to evaluate the progress and override the operation. RESULTS: The developed system was validated by performing lens extraction on 30 postmortem pig eyes. Complete lens extraction was achieved on 25 eyes, and "almost complete" extraction was achieved on the remainder due to an inability to image small lens particles behind the iris. No capsule rupture was found. CONCLUSION: The IRISS successfully demonstrated semiautomated OCT-guided lens removal with real-time supervision and intervention.

Retrograde Ureteral Catheterization: A Possible New Treatment for Renal Fungal Balls in Very Low Birth Weight Infants.

Invasive candidiasis is a serious pathogen of late-onset sepsis in very low birth weight infants. Kidney is the most common organ involved, and it causes morbidity and mortality, especially when fungal balls are formed. We report a 34-day-old female infant (born at 28 weeks' gestation, 1152 g) with systemic fungal infection complicated obstructive uropathy. On sonography, the fungal balls filled the entire pelvis without hydronephrosis. Percutaneous nephrostomy was not feasible. In addition to systemic antifungals, we successfully performed cystoscopy-assisted retrograde ureteral catheterization to decompress the pelvis, which also provided a route for local amphotericin B irrigation to achieve therapeutic concentration without nephrotoxicity.

Intraocular robotic interventional surgical system (IRISS): Mechanical design, evaluation, and master-slave manipulation.

BACKGROUND: Since the advent of robotic-assisted surgery, the value of using robotic systems to assist in surgical procedures has been repeatedly demonstrated. However, existing technologies are unable to perform complete, multi-step procedures from start to finish. Many intraocular surgical steps continue to be manually performed. METHODS: An intraocular robotic interventional surgical system (IRISS) capable of performing various intraocular surgical procedures was designed, fabricated, and evaluated. Methods were developed to evaluate the performance of the remote centers of motion (RCMs) using a stereo-camera setup and to assess the accuracy and precision of positioning the tool tip using an optical coherence tomography (OCT) system. RESULTS: The IRISS can simultaneously manipulate multiple surgical instruments, change between mounted tools using an onboard tool-change mechanism, and visualize the otherwise invisible RCMs to facilitate alignment of the RCM to the surgical incision. The accuracy of positioning the tool tip was measured to be 0.205±0.003 mm. The IRISS was evaluated by trained surgeons in a remote surgical theatre using post-mortem pig eyes and shown to be effective in completing many key steps in a variety of intraocular surgical procedures as well as being capable of performing an entire cataract extraction from start to finish. CONCLUSIONS: The IRISS represents a necessary step towards fully automated intraocular surgery and demonstrated accurate and precise master-slave manipulation for cataract removal and-through visual feedback-retinal vein cannulation.

End of an enigma: Aenigmopteris belongs in Tectaria (Tectariaceae: Polypodiopsida).

The phylogenetic affinities of the fern genus Aenigmopteris have been the subject of considerable disagreement, but until now, no molecular data were available from the genus. Based on the analysis of three chloroplast DNA regions (rbcL, rps16-matK, and trnL-F) we demonstrate that Aenigmopteris dubia (the type species of the genus) and A. elegans are closely related and deeply imbedded in Tectaria. The other three species of genus are morphologically very similar; we therefore transfer all five known species into Tectaria. Detailed morphological comparison further shows that previously proposed diagnostic characters of Aenigmopteris fall within the range of variation of a broadly circumscribed Tectaria.

Phylogenetic analyses place the monotypic Dryopolystichum within Lomariopsidaceae.

The monotypic fern genus Dryopolystichum Copel. combines a unique assortment of characters that obscures its relationship to other ferns. Its thin-walled sporangium with a vertical and interrupted annulus, round sorus with peltate indusium, and petiole with several vascular bundles place it in suborder Polypodiineae, but more precise placement has eluded previous authors. Here we investigate its phylogenetic position using three plastid DNA markers, rbcL, rps4-trnS, and trnL-F, and a broad sampling of Polypodiineae. We also provide new data on Dryopolystichum including spore number counts, reproductive mode, spore SEM images, and chromosome counts. Our maximum-likelihood and Bayesian-inference phylogenetic analyses unambiguously place Dryopolystichum within Lomariopsidaceae, a position not previously suggested. Dryopolystichum was resolved as sister to a clade comprising Dracoglossum and Lomariopsis, with Cyclopeltis as sister to these, but clade support is not robust. All examined sporangia of Dryopolystichum produced 32 spores, and the chromosome number of sporophyte somatic cells is ca. 164. Flow cytometric results indicated that the genome size in the spore nuclei is approximately half the size of those from sporophyte leaf tissues, suggesting that Dryopolystichum reproduces sexually. Our findings render Lomariopsidaceae as one of the most morphologically heterogeneous fern families. A recircumscription is provided for both Lomariopsidaceae and Dryopolystichum, and selected characters are briefly discussed considering the newly generated data.

A plastid phylogeny and character evolution of the Old World fern genus Pyrrosia (Polypodiaceae) with the description of a new genus: Hovenkampia (Polypodiaceae).

The Old World fern genus Pyrrosia (Polypodiaceae) offers a rare system in ferns to study morphological evolution because almost all species of this genus are well studied for their morphology, anatomy, and spore features, and various hypotheses have been proposed in terms of the phylogeny and evolution in this genus. However, the molecular phylogeny of the genus lags behind. The monophyly of the genus has been uncertain and a modern phylogenetic study of the genus based on molecular data has been lacking. In the present study, DNA sequences of five plastid markers of 220 accessions of Polypodiaceae representing two species of Drymoglossum, 14 species of Platycerium, 50 species of Pyrrosia, and the only species of Saxiglossum (subfamily Platycerioideae), and 12 species of other Polypodiaceae representing the remaining four subfamilies are used to infer a phylogeny of the genus. Major results and conclusions of this study include: (1) Pyrrosia as currently circumscribed is paraphyletic in relation to Platycerium and can be divided into two genera: Pyrrosia s.s. and Hovenkampia (gen. nov.), with Hovenkampia and Platycerium forming a strongly supported clade sister to Pyrrosia s.s.; (2) Subfamily Platycerioideae should contain three genera only, Hovenkampia, Platycerium, and Pyrrosia s.s.; (3) Based on the molecular phylogeny, macromorphology, anatomical features, and spore morphology, four major clades in the genus are identified and three of the four are further resolved into four, four, and six subclades, respectively; (4) Three species, P. angustissima, P. foveolata, and P. mannii, not assigned to any groups by Hovenkamp (1986) because of their unusual morphology, each form monospecific clades; (5) Drymoglossum is not monophyletic and those species previously assigned to this genus are resolved in two different subclades; (6) Saxiglossum is resolved as the first lineage in the Niphopsis clade; and (7) The evolution of ten major morphological characters in the subfamily is inferred based on the phylogeny and various morphological synapomorphies for various clades and subclades are identified.

Not only in the temperate zone: independent gametophytes of two vittarioid ferns (Pteridaceae, Polypodiales) in East Asian subtropics.

Independent gametophyte ferns are unique among vascular plants because they are sporophyteless and reproduce asexually to maintain their populations in the gametophyte generation. Such ferns had been primarily discovered in temperate zone, and usually hypothesized with (sub)tropical origins and subsequent extinction of sporophyte due to climate change during glaciations. Presumably, independent fern gametophytes are unlikely to be distributed in tropics and subtropics because of relatively stable climates which are less affected by glaciations. Nonetheless, the current study presents cases of two independent gametophyte fern species in subtropic East Asia. In this study, we applied plastid DNA sequences (trnL-L-F and matK + ndhF + chlL datasets) and comprehensive sampling (~80%) of congeneric species for molecular identification and divergence time estimation of these independent fern gametophytes. The two independent gametophyte ferns were found belonging to genus Haplopteris (vittarioids, Pteridaceae) and no genetic identical sporophyte species in East Asia. For one species, divergence times between its populations imply recent oversea dispersal(s) by spores occurred during Pleistocene. By examining their ex situ and in situ fertility, prezygotic sterility was found in these two Haplopteris, in which gametangia were not or very seldom observed, and this prezygotic sterility might attribute to their lacks of functional sporophytes. Our field observation and survey on their habitats suggest microhabitat conditions might attribute to this prezygotic sterility. These findings point to consideration of whether recent climate change during the Pleistocene glaciation resulted in ecophysiological maladaptation of non-temperate independent gametophyte ferns. In addition, we provided a new definition to classify fern gametophyte independences at the population level. We expect that continued investigations into tropical and subtropical fern gametophyte floras will further illustrate the biogeographic significance of non-temperate fern gametophyte independence.

Thermo-Responsive Polyurethane Hydrogels Based on Poly(ε-caprolactone) Diol and Amphiphilic Polylactide-Poly(Ethylene Glycol) Block Copolymers.

Waterborne polyurethane (PU) based on poly(ε-caprolactone) (PCL) diol and an amphiphilic polylactide-poly(ethylene glycol) (PLA-PEG) diblock copolymer was synthesized. The molar ratio of PCL/PLA-PEG was 9:1 with different PLA chain lengths. The PU nanoparticles were characterized by dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and rheological analysis. The water contact angle measurement, infrared spectroscopy, wide angle X-ray scattering (WAXS), thermal and mechanical analyses were conducted on PU films. Significant changes in physio-chemical properties were observed for PUs containing 10 mol % of amphiphilic blocks. The water contact angle was reduced to 12°â»13°, and the degree of crystallinity was 5%⁻10%. The PU dispersions underwent sol-gel transition upon the temperature rise to 37 °C. The gelation time increased as the PLA chain length increased. In addition, the fractal dimension of each gel was close to that of a percolation cluster. Moreover, PU4 with a solid content of 26% could support the proliferation of human mesenchymal stem cells (hMSCs). Therefore, thermo-responsive hydrogels with tunable properties are promising injectable materials for cell or drug delivery.

Global phylogeny and biogeography of grammitid ferns (Polypodiaceae).

We examined the global historical biogeography of grammitid ferns (Polypodiaceae) within a phylogenetic context. We inferred phylogenetic relationships of 190 species representing 31 of the 33 currently recognized genera of grammitid ferns by analyzing DNA sequence variation of five plastid DNA regions. We estimated the ages of cladogenetic events on an inferred phylogeny using secondary fossil calibration points. Historical biogeographical patterns were inferred via ancestral area reconstruction. Our results supported four large-scale phylogenetic and biogeographic patterns: (1) a monophyletic grammitid clade that arose among Neotropical polypod ancestors about 31.4 Ma; (2) a paraphyletic assemblage of clades distributed in the Neotropics and the Afro-Malagasy region; (3) a large clade distributed throughout the Asia-Malesia-Pacific region that originated about 23.4 Ma; and, (4) an Australian or New Zealand origin of the circumaustral genus Notogrammitis. Most genera were supported as monophyletic except for Grammitis, Oreogrammitis, Radiogrammitis, and Zygophlebia. Grammitid ferns are a well-supported monophyletic group with two biogeographically distinct lineages: a primarily Neotropical grade exhibiting several independent successful colonizations to the Afro-Malagasy region and a primarily Paleotropical clade exhibiting multiple independent dispersals to remote Pacific islands and temperate, austral regions.

[Case-control study on modified femoral prosthesis in reducing the incidence of patellar clunk syndrome after the initial posterior stabilized total knee arthroplasty].

OBJECTIVE: To explore therapeutic effects of modified femoral prosthesis applied in the initial posterior stabilized total knee arthroplasty. METHODS: From April 1, 2012 to January 1, 2013, 156 patients with knee osteoarthritis underwent posterior stabilized total knee arthroplasty by the same director of orthopedic surgeon. Sixty-one patients were treated with modified femoral prosthesis, including 7 males and 54 females, with an average age of (68.34 +/- 5.41) years old; and 95 patients were treated with conventional designed femoral prosthesis, including 14 males and 81 females, with an average age of (69.92 +/- 5.11) years old. Indexes including age, body mass index, Insall-Salvati index, type of prosthesis, occurrence rate of patella click syndrome, postoperative line of force of lower extremity and postoperative function of the knee joint were observed and recorded. And American Knee Society (AKS) score was used to evaluate the clinical results. RESULTS: All the patients were followed up, and the duration ranged from 36 to 56 weeks, with a mean of 45.31 weeks. Among patients in the conventional designed femoral prosthesis group, 7 patients had patella click syndrome, but there was no patient having patellar click syndrome in the modified femoral prosthesis group. Postoperative knee activity of patients in the modified femoral prosthesis group was (110.98 +/- 10.32) degrees, which was better than (107.05 +/- 8.61) degrees in the conventional designed femoral prosthesis group. The AKS score in the modified femoral prosthesis group was 129.79 +/- 9.63 during 21 to 28 days after operation, which was higher than 126.85 +/- 7.79 in the conventional designed femoral prosthesis group. CONCLUSION: New designed femoral components are effective to reduce the occurrence rate of postoperative patellar click syndrome and obtain better early functional recovery from knee surgery.

Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery.

BACKGROUND: The purpose of this study was to demonstrate the effectiveness of an integrin peptide ligand-labeled liposomal delivery system loaded with vascular endothelial growth factor (VEGF)-siRNA in a model study of gene therapy for retinopathy using human retinal pigment epithelial cells. METHODS: Arg(R)-Gly(G)-Asp(D) motif peptide conjugating polyethylene glycol modified (RGD-PEGylated) liposomes were prepared using a thin-film hydration method and optimized for surface charge, particle size, small interfering RNA (siRNA) load, and entrapment efficiency. Reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine VEGF levels in retinal pigment epithelial cells. Cytotoxicity was determined using the 3-[4, 5-dimethylthiazol-2-yl]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and flow cytometry. RESULTS: Physicochemical properties, including particle size, zeta potential, and siRNA load, of the prepared RGD-PEGylated liposomes and their entrapment efficiency were determined to be within the following ranges: 123.8-234.1 nm, 17.31-40.09 m V, 5.27%-6.33%, and >97%, respectively. RGD-PEGylated liposome-mediated fluorescent-labeled siRNA delivery demonstrated significantly enhanced cellular uptake, and 3 mol% RGD-PEGylated liposomes (having 3ß-[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-cholesterol) DSPE and DSPE-PEG(2000)-RGD with molar ratio of 50/47/3) were shown to have better efficacy with regard to specificity for retinal pigment epithelial cells, reduced cytotoxicity, and knockdown of the target molecule. CONCLUSION: By integrin receptor-mediated endocytosis, 3 mol% RGD-PEGylated liposomes were shown to be a suitable vector when loaded with VEGF-siRNA for efficient downregulation of VEGF in retinal pigment epithelial cells at both the protein and gene levels. This integrin ligand-modified liposomal delivery system has therapeutic potential for ocular gene therapy.

A prolonged buried fish bone mimicking Ludwig angina.

Most migrated foreign bodies in the neck were removed immediately in patients with persistent symptoms. It is a rare condition that a fish bone was buried for a prolonged time in the tongue with little discomfort. We report a unique case of an ingested fish bone lodged in the tongue for 16 months until infection ensued. Ludwig angina was considered first because the patient had fever, odynophagia, swelling of the tongue, and mouth floor. The fish bone buried in the tongue was incidentally found on the computed tomography scan and successfully removed by surgical exploration. Although dental infection is the most common underlying cause in Ludwig angina, embedded foreign body should be considered as one of the pathogenesis. On the other hand, computed tomography scan can be useful in identifying extraluminal migration of fish bones in the neck.

Prediction of significant fibrosis in HBeAg-positive patients with chronic hepatitis B by a noninvasive model.

A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2-4 vs. stages 0-1). Consecutive treatment-naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified alpha2-macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg-positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB.