Summary It is believed that the 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, while the preceding and succeeding introns are removed co-transcriptionally.

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.

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Background: Resistance to antibiotics is an extremely common phenomenon in bacteria isolated from clinical material. This is a serious threat to patient care all over the world. In India, antibiotic resistance has far reaching public health consequences. In this observational study, we aimed to generate data on the prevailing pattern of antibiotic resistance from Eastern India. Methods: This was a hospital based study involving both indoor and outdoor patients. Patients with history of antibiotic use in the past 3 months were excluded. The clinical specimens (blood, urine, pus etc.) were incubated for up to 7 days under aerobic conditions before declaring them as negative. Antibiotic sensitivity was tested by modified Kirby-Bauer disc diffusion method according to CLSI guidelines. Results: There were a total of 93 specimens with the majority being blood culture (n=43) and urine (n=33). Majority (n=57; 61.3%) of isolated organisms were gram negative with E. coli predominating (n=36). Of the gram-positive isolates, Staphylococcus predominated (32 out of 36). 100% of isolates from urine were gram negative while for blood, 60% of the isolates were gram positive. Resistance to penicillin group and cotrimoxazole was up to 100% in certain species. For carbapenem group, resistance varied from 17 to 75%. Resistance to aminoglycosides was 75% in Pseudomonas and 85% in Klebsiella. Conclusions: Our study has demonstrated very high levels of resistance to different common antibiotics in different classes of bacteria. Such data can be used for antibiotic stewardship and also to formulate antibiotic use protocols.

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