α-Carbonyl Radicals from N-Enoxybenzotriazoles: De Novo Synthesis of 9-Phenanthrols.

Visible-light-induced energy transfer to N-enoxybenzotriazoles in the presence of hydrogen atom donors or alcoholic solvents led to α-carbonyl radicals. The utility of the α-carbonyl radicals was demonstrated in intramolecular tandem cyclization and in the synthesis of 9-phenanthrols and their analogues. The mechanistic experiments suggested that quenching of the reactive benzotriazolyl radical by the alcohol was accompanied by the formation of an α-hydroxy radical that mediated hydrogen atom transfer or, itself, oxidized into aldehydes.

Energy Transfer Photocatalytic Radical Rearrangement in N-Indolyl Carbonates.

A new type of sp3-like N-centered radical has been generated by selective energy transfer catalysis. Upon photoexcitation, homolytic N-O bond cleavage of N-indolyl carbonate in the presence of an Ir complex produced N- and O-centered radicals. The high spin density at the C3 position of indole led to radical recombination with the O-centered radical, affording valuable 3-oxyindole derivatives without decarboxylation. Transformations of the desired products into various molecules were also demonstrated.

Recent Progress in Enolonium Chemistry under Metal-Free Conditions.

Umpolung approach through inversion of the polarity of conventional enolates, has opened up an unprecedented opportunity in the cross-coupling via alkylation. The enolonium equivalents can be accessed either by hypervalent iodine reagents, activation/oxidation of amides, or the oxidation of alkynes. Under umpolung conditions, highly basic conditions required for classical enolate chemistry can be avoided, and they can couple with unmodified nucleophiles such as heteroatom donors and electron-rich arenes.

Enantioselective Synthesis of Tertiary α,α-Diaryl Carbonyl Compounds Using Chiral N,N'-Dioxides under Umpolung Conditions.

Brønsted acid-catalyzed addition of the chiral N,N'-dioxide into ynamides generated enolonium ions in situ which underwent enantioselective alkylation by indoles, pyrroles, and phenols, without racemization of the formed tertiary center. This external oxidant approach allows for the use of unmodified nucleophiles and does not leave trace groups from the oxidant, which significantly increases the synthetic efficiency and the product diversity. Furthermore, the byproduct of the N,N'-dioxide could be efficiently recycled into an optically pure form.

Optical coherence tomography angiography findings of type 1 diabetic patients with diabetic retinopathy, in comparison with type 2 patients.

PURPOSE: To compare optical coherence tomography angiography (OCT-A) parameters between type 1 and type 2 diabetic patients with diabetic retinopathy (DR). METHODS: A total of 70 patients with type 1 diabetes and 70 with type 2 diabetes were retrospectively analyzed. DR was graded as no DR, mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). Using OCT-A, the foveal avascular zone (FAZ) area (mm2) and vascular density (VD) (%) were calculated in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS: In both type 1 and 2 diabetes patients, the FAZ area (mm2) in both capillary plexuses (CP) increased with DR progression, whereas the VD (%) progressively decreased. The changes in the FAZ area and the VD were significantly greater in the DCP than in the SCP in both types of diabetes patients(p < 0.001). In the analysis of decreasing slope of the VD in the DCP, attenuation was not significant until severe NPDR stage but then abruptly decreased when it progressed to PDR stage in type 1 diabetes. In type 2 diabetes, the DCP VD decreased gradually as DR stage progressed. CONCLUSIONS: As DR progression, the increasing in FAZ area and the decreasing in VD are more severe in the DCP than in the SCP in both types of diabetes. In type 1 diabetes eyes, they were remained in relatively healthy until it gets to the advanced stage of DR, while the gradual deterioration of FAZ area and VD was found from the early stage to the advanced stage of DR in type 2 diabetes.

Fabrication and Comparison of Self-Organized Ag and Au Nanodots on Ti/MgO(001) Substrates.

We analyze and compare the differences in the dewetting phenomena and crystal structure between Ag(5.0 nm) and Au(5.0 nm) layers deposited on a Ti(1.0 nm) seed layer coated onto a MgO(001) substrate. The samples are deposited at room temperature and annealed at 350-450 °C for 5 h. The surfaces of both Ag/Ti and Au/Ti films exhibit a completely separated island structure, subsequently leading to the formation of a nanodot array after annealing. Based on atomic force microscopy (AFM) analysis, we conclude that the dewetting progression speed of Ag/Ti films is higher than that of Au/Ti films. Based on X-ray diffraction (XRD) results, the Ti thin film acts as a seed layer, assisting the epitaxial growth of fcc-Ag(001) nanodots on the MgO(001) substrate, whereas in the case of Au/Ti, the Au layer grows non-epitaxially on the MgO(001) substrate, which is related to the difference in the surface energies of Ag and Au. Furthermore, the optical absorbance spectra of the self-organized Ag and Au nanodots with the Ti seed layer are obtained in the visible light range and the optical properties of Ag and Au nanodots are compared.

Abnormal choroidal flow on optical coherence tomography angiography in central serous chorioretinopathy.

IMPORTANCE: Analysing choroidal flow in central serous chorioretinopathy (CSC) with novel device. BACKGROUND: To examine the abnormal morphology of choriocapillary flow with optical coherence tomography angiography (OCTA) according to the presence of subretinal fluid (SRF) in CSC. DESIGN: A hospital-based retrospective study. PARTICIPANTS: We analysed OCTA results of 68 eyes (68 patients) diagnosed as CSC with or without SRF (active and resolved CSC, respectively) at the Asan Medical Center. METHODS: We classified OCTA choriocapillary images into three pattern groups: mixed perfusion, hyper-perfusion and normal perfusion. Data analysis included age, follow-up duration, treatment modalities, number of treatments, subfoveal choroidal thickness and SRF height. MAIN OUTCOME MEASURES: The relationship between CSC activity and choriocapillary pattern. RESULTS: Abnormal choroidal flow (mixed and hyper-perfusion) was more frequently found in eyes with active CSC (100%) than resolved CSC (47.5%, P < 0.001). In active CSC eyes, mixed perfusion was predominant (71.4%), while hyper-perfusion was predominant in those with resolved CSC (73.7%). Eyes with recently resolved CSC (SRF absorption present for <2 months) had abnormal choriocapillary flow more often than the remaining eyes with resolved CSC (83.3% vs 32.1%, P = 0.005). Resolved CSC eyes with abnormal choriocapillary flow demonstrated more recurrence than eyes with normal choriocapillary flow (42.1% vs 9.5%, P = 0.017). CONCLUSIONS AND RELEVANCE: The pattern of choriocapillary flow abnormalities on OCTA can indicate CSC disease activity. Because eyes with resolved CSC showing abnormal choroidal flow have a high recurrence rate, they should be carefully followed-up.

Metal-Free Iodine-Catalyzed Oxidation of Ynamides and Diaryl Acetylenes into 1,2-Diketo Compounds.

Metal-free oxidation of ynamides is described, employing pyridine- N-oxides as oxidants under molecular iodine catalysis. In stark contrast to Brønsted acid catalysis, iodophilic activation of ynamides diverts the reaction manifold into a dioxygenation pathway. This oxidation is very rapid at room temperature with only 2.5 mol % I2. Furthermore, this protocol could be extended to nonactivated alkynes, such as diarylacetylenes, to deliver various benzil derivatives.

Correlation between Deep Capillary Plexus Perfusion and Long-Term Photoreceptor Recovery after Diabetic Macular Edema Treatment.

PURPOSE: To determine the association between baseline deep capillary plexus (DCP) integrity and long-term photoreceptor recovery as well as visual outcome after treatment in patients with diabetic macular edema (DME). DESIGN: Retrospective, interventional case series. PARTICIPANTS: Sixty-seven eyes with DME that resolved successfully with initial treatment (baseline) and that remained edema free for 12 months after the initial DME resolution. METHODS: Best-corrected visual acuity (BCVA), spectral-domain (SD) OCT, and OCT angiography findings were collected at baseline and at 6 and 12 months after baseline. Correlations were analyzed between DCP integrity parameters (vascular flow density [VD] and area of the foveal avascular zone [FAZ]) and photoreceptor integrity parameters (ellipsoid zone [EZ] and external limiting membrane [ELM] integrity). Multivariate linear regression analysis was conducted to identify the baseline predictors for photoreceptor recovery and visual improvement. MAIN OUTCOME MEASURES: The association between baseline DCP integrity and recovery of photoreceptor integrity over 12 months. RESULTS: At baseline, the mean central retinal thickness was 306.1±51.8 µm. The mean baseline DCP VD and FAZ were 14.4±5.2% and 0.71±0.36 mm2, and the mean baseline EZ and ELM integrity were 57.2±26.1% and 76.4±19.8%, respectively. Ellipsoid zone and ELM integrity recovered significantly at 12 months from baseline (both P < 0.001). The degree of EZ and ELM integrity recovery was well correlated with the baseline DCP VD (P = 0.004 and P = 0.009, respectively) and DCP FAZ (P = 0.007 and P = 0.009, respectively). Moreover, the mean change in BCVA from baseline to 12 months was significantly greater with higher baseline DCP VD (P = 0.003) and smaller DCP FAZ (P = 0.042). Compared with anti-vascular endothelial growth factor (VEGF) nonresponders, anti-VEGF responders had higher baseline DCP integrity and a significantly greater degree of photoreceptor recovery at 12 months. CONCLUSIONS: The degree of DCP preservation at the time of initial DME resolution is correlated closely with long-term recovery of photoreceptor integrity and visual outcome in patients with resolved DME.

Brønsted acid-catalyzed α-halogenation of ynamides from halogenated solvents and pyridine-N-oxides.

The keteniminium ions generated from the protonation of ynamides formed reversible adducts with counter anions and pyridine-N-oxides as well as halogenated solvents. Above 80 °C, the halonium ions selectively undergo a rate-limiting attack by pyridine-N-oxides, leading to (E)-haloenamides in good yields.

The Degree of Diabetic Retinopathy in Patients with Type 2 Diabetes Correlates with the Presence and Severity of Coronary Heart Disease.

Both diabetic retinopathy (DR) and coronary heart disease (CHD) are clinically significant in diabetic patients. We investigated the correlation between the severity of DR and the presence and severity of CHD among type 2 diabetic patients. A total of 175 patients who were examined at the DR clinic and underwent dual-source computed tomography (DSCT) angiography within 6 months were included. The degree of DR was graded as no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). The severity of CHD and the numbers of significant stenotic coronary artery on DSCT angiography according to DR grade were assessed. The mean Agatston Calcium Score (ACS) in patients with PDR was significantly higher than other groups (P < 0.001). The overall odds of an ACS increase were about 4.7-fold higher in PDR group than in no DR group (P < 0.001). In PDR group, in comparison with in no DR, the odds of having 1 or 2 arterial involvement were 3-fold higher (P = 0.044), and those of having 3 were 17-fold higher (P = 0.011). The c-index, one of the predictability values in regression analysis model, was not significantly increased when PDR was added to classical CHD risk factors (0.671 to 0.706, P = 0.111). Conclusively, patients with PDR develop a greater likelihood of not only having CHD, but being more severe nature. PDR has no additional effect to classical CHD risk factors for predicting CHD.

Electrically Controllable Microparticle Synthesis and Digital Microfluidic Manipulation by Electric-Field-Induced Droplet Dispensing into Immiscible Fluids.

The dispensing of tiny droplets is a basic and crucial process in a myriad of applications, such as DNA/protein microarray, cell cultures, chemical synthesis of microparticles, and digital microfluidics. This work systematically demonstrates droplet dispensing into immiscible fluids through electric charge concentration (ECC) method. It exhibits three main modes (i.e., attaching, uniform, and bursting modes) as a function of flow rates, applied voltages, and gap distances between the nozzle and the oil surface. Through a conventional nozzle with diameter of a few millimeters, charged droplets with volumes ranging from a few µL to a few tens of nL can be uniformly dispensed into the oil chamber without reduction in nozzle size. Based on the features of the proposed method (e.g., formation of droplets with controllable polarity and amount of electric charge in water and oil system), a simple and straightforward method is developed for microparticle synthesis, including preparation of colloidosomes and fabrication of Janus microparticles with anisotropic internal structures. Finally, a combined system consisting of ECC-induced droplet dispensing and electrophoresis of charged droplet (ECD)-driven manipulation systems is constructed. This integrated platform will provide increased utility and flexibility in microfluidic applications because a charged droplet can be delivered toward the intended position by programmable electric control.

A new multiple noncontinuous puncture (pointage) technique for corneal tattooing.

AIM: To assess the safety and cosmetic efficacy of a new multiple noncontinuous transepithelial puncture technique for tattooing a decompensated cornea. METHODS: It was a non-comparative clinical case series study. The study examines 33 eyes in 33 patients with total corneal opacity due to corneal decompensation, which developed following intraocular surgery. Corneal tattooing was performed using the multiple noncontinuous transepithelial puncture technique (i.e. pointage). The safety of this new surgical strategy was assessed by occurrence of adverse events for the follow-up period. The cosmetic efficacy was determined by the patient's cosmetic satisfaction and independent observer's opinion about patient appearance. RESULTS: Seven women and 26 men were included in the study. The mean age was 46.4±17.5y (range: 7-67). In total, 30 of 33 patients (91%) reported cosmetic satisfaction within the follow-up period. Only 3 patients (9%) required additional tattooing due to cosmetic unsatisfaction. Cosmetic outcomes were analyzed and classified as excellent or good in 13 (39%) and 17 (52%) patients, respectively. No serious adverse events developed, except delayed epithelial healing in 3 cases. CONCLUSION: The cosmetic outcomes of the multiple noncontinuous transepithelial puncture technique for corneal tattooing were good. The safety of this method is higher than conventional procedures. This new procedure also provides improved cost-effectiveness and safety over current corneal tattooing techniques.

Changes in the clinical features and prognostic factors of endogenous endophthalmitis: fifteen years of clinical experience in Korea.

PURPOSE: To identify changes in the clinical features, management, and prognostic factors of endogenous endophthalmitis in Korea from 1996 through 2010. METHODS: We conducted a retrospective review of medical records of patients diagnosed with endogenous endophthalmitis from January 1996 to December 2010, which was divided into 3 periods: 1996 to 2000, 2001 to 2005, and 2006 to 2010. Variables included age, source of infection, systemic conditions, initial and final visual acuities, causative organisms, and treatment. RESULTS: Endophthalmitis was identified in 80 patients (97 eyes). Diabetes (42.5%) and liver cirrhosis (20%) were the common systemic problems in these patients. Liver abscess (25%) was the most common infection focus of the endophthalmitis. Klebsiella pneumoniae (48.4%) was the common causative agent, although more recently, endophthalmitis caused by gram-positive cocci has increased in frequency. The use of vitrectomy as an initial treatment has increased during the past 5 years. Good initial visual acuity greater than counting fingers (P < 0.001), early vitrectomy in patients with initially good visual presentation (P = 0.035), and gram-positive cocci (P = 0.033) as a causative agent were significantly related to a successful visual outcome. CONCLUSION: Although the prognosis of endogenous endophthalmitis is generally poor in most patients, some eyes can have relatively good visual outcomes if treated appropriately and early enough.