Virtual screening of ultra-large chemical libraries identifies cell-permeable small-molecule inhibitors of a "non-druggable" target, STAT3 N-terminal domain.

STAT3 N-terminal domain is a promising molecular target for cancer treatment and modulation of immune responses. However, STAT3 is localized in the cytoplasm, mitochondria, and nuclei, and thus, is inaccessible to therapeutic antibodies. Its N-terminal domain lacks deep pockets on the surface and represents a typical "non-druggable" protein. In order to successfully identify potent and selective inhibitors of the domain, we have used virtual screening of billion structure-sized virtual libraries of make-on-demand screening samples. The results suggest that the expansion of accessible chemical space by cutting-edge ultra-large virtual compound databases can lead to successful development of small molecule drugs for hard-to-target intracellular proteins.

Detection of retinal laser injury using confocal scanning laser imaging.

The use of laser energy in medical practice requires specific safety measures. Accidental ocular exposure of laser can have vision-threatening consequences. We report a case of accidental laser exposure in a dentist who was working with a diode laser. The patient presented within 24 hours of exposure and the clinical fundus examination and spectral-domain optical coherence tomography (SDOCT) were unremarkable at this time. Blue light autofluorescence (BAF) and multicolor images obtained using the Spectralis SDOCT system revealed the laser impact site. The multicolor image showed a larger extent of retinal involvement highlighting its role in imaging.

Unilateral full-thickness macular hole formation following low-energy Nd:YAG peripheral iridotomy.

Macular hole formation is a rare complication after YAG peripheral iridotomy. We report a case of post-YAG peripheral iridotomy macular hole in 1 eye of a patient with preexisting vitreomacular adhesion in that eye. Possibly because of the vitreomacular adhesion, a single-shot low-energy YAG laser shot resulted in macular hole formation.

Vitrectorhexis versus forceps posterior capsulorhexis in pediatric cataract surgery.

This study was done to compare the results of posterior continuous curvilinear capsulorhexis created using forceps with those created using vitrector in eyes suffering from congenital cataract. Vitrectorhexis term was first used by Wilson et al in 1999. [1] Fifty eyes with congenital and developmental cataract were included in this study. The posterior capsulorhexis was created using utrata forceps in 17 eyes or through a vitrector in 33 eyes. Forceps capsulorhexis was performed before IOL implantation, while vitrectorhexis was performed after IOL implantation in the bag. The results of both the surgery were compared using the following criteria: incidence of extension of rhexis, ability to achieve posterior rhexis of appropriate size, ability to implant the IOL in the bag, the surgical time, and learning curve. Vitrectorhexis after IOL implantation was an easy to learn alternative to manual posterior continuous curvilinear capsulorhexis in pediatric cataract surgery. It was more predictable and reproducible, with a short learning curve and lesser surgical time.

Single-molecule imaging of transcriptionally coupled and uncoupled splicing.

Introns are removed from pre-mRNAs during transcription while the pre-mRNA is still tethered to the gene locus via RNA polymerase. However, during alternative splicing, it is important that splicing be deferred until all of the exons and introns involved in the choice have been synthesized. We have developed an in situ RNA imaging method with single-molecule sensitivity to define the intracellular sites of splicing. Using this approach, we found that the normally tight coupling between transcription and splicing is broken in situations where the intron's polypyrimidine tract is sequestered within strong secondary structures. We also found that in two cases of alternative splicing, in which certain exons are skipped due to the activity of the RNA-binding proteins Sxl and PTB, splicing is uncoupled from transcription. This uncoupling occurs only on the perturbed introns, whereas the preceding and succeeding introns are removed cotranscriptionally. PAPERCLIP:

Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration.

CONTEXT: Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD). AIMS: To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD. SETTINGS AND DESIGN: Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India. MATERIALS AND METHODS: One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant. RESULTS: The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed. CONCLUSIONS: Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD.

Intraocular cysticercosis: clinical characteristics and visual outcome after vitreoretinal surgery.

PURPOSE: To report the clinical characteristics of, discuss the surgical options for, and analyze the factors affecting the anatomic and visual outcome of intraocular cysticercosis. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Forty-five eyes of 44 Indian patients with posterior segment intraocular cysticercosis. METHODS: The charts of 45 eyes, in which intraocular cysticercosis was removed by vitreoretinal surgery (either transscleral or transvitreal), were reviewed. MAIN OUTCOME MEASURES: These included the postoperative retinal status and the best-corrected Snellen visual acuity. RESULTS: Intraocular cysticercosis was present in the vitreous cavity of 27 eyes (60%) and in the subretinal space of 18 eyes (40%). Anterior segment inflammation was seen in 13 eyes (28.8%) and vitreous inflammation in 38 eyes (84.4%). Retinal detachment was observed in 22 eyes (48.8%), with proliferative vitreoretinopathy in 13 eyes (59.09%). Subretinal cysts anterior to the equator (4 eyes) were removed transsclerally, whereas subretinal cysts posterior to the equator and intravitreal cysts (41 eyes) were removed transvitreally. The mean follow-up was 10.5 months. At the last follow-up, the retina was attached in 39 eyes (86.6%); visual acuity of >/=5/200 was achieved in 67.5%. CONCLUSIONS: Current vitreoretinal surgical techniques enable removal of intraocular cysticercosis in all cases, with reattachment of the retina in 86.6% and recovery of ambulatory vision in approximately 67% of cases.