Anaphylactic shock following the mad honey consumption: a case report.

Introduction: Mad honey consumption is a common practice in Nepal for medicinal and consumption purposes, but it can lead to severe adverse effects. Grayanotoxin I and Grayanotoxin III isoforms found in rhododendron interfere with voltage-gated sodium channels resulting in gastrointestinal symptoms, and cardiovascular effects such as low blood pressure, abnormal heart rhythms, cardiac arrest, and abnormal electrical conduction in the heart, as well as rare central nervous system disorders. Here the authors report a case of Mad honey consumption leading to anaphylactic shock along with its investigations and management. Case presentation: The authors present a case of a 51-year-old female who developed anaphylactic shock after consuming mad honey. The patient experienced symptoms including nausea, vomiting, abdominal pain, sweating, dizziness, facial and lip swelling, but no chest pain, loss of consciousness, abnormal body movement, or dyspnoea. The patient had no prior medical conditions, regular medications, or history of allergic reactions to honey or pollen. Discussion: Mad honey intoxication is caused by grayanotoxins, with distinct cardiac effects for different types of grayanotoxins. Symptoms include bradycardia, hypotension, abdominal pain, dizziness, and nausea, which subsided within 24 h following the initial management. The presence of grayanotoxin can be detected using specialized instrumentation, but it may not be available in all medical facilities. Co-intoxication with alcohol or propolis may also occur. Conclusion: This case highlights the importance of recognizing and managing complications associated with mad honey consumption, particularly in regions where it is prevalent. Prompt medical attention is advised if unusual symptoms occur after honey consumption.

Referral parameters for diagnosis of glaucoma in general eye clinic at Tilganga Institute of Ophthalmology.

OBJECTIVE: To find out the most common referral parameter among the glaucoma suspects patients from general eye clinic and to establish glaucoma diagnosis. METHODS: This study is a retrospective cohort hospital based study. Two hundred patients from January to February 2017 sent to glaucoma clinic as glaucoma suspects were re-evaluated meticulously by glaucoma specialist and were diagnosed as glaucoma, non glaucoma, suspects and ocular hypertension. RESULTS: Out of the 200 patients referred to glaucoma clinic as glaucoma suspects only19% were diagnosed to have glaucoma. The mean age at which glaucoma diagnosed was 55.29(14.4) compared to 41.6(15.1) in normal group. One hundred and sixty five patients were referred on the basis of suspicious optic nerve head, among them 14.5% (24/165) had glaucoma. This study showed that, open angle glaucoma (OAG) 28.9% was the most common type of total glaucoma diagnosed. The mean vertical cup discratio in the OAG group was 0.69±0.1 (0.4 -0.9) compared to 0.56 ± 0.11((0.2-0.8)(p=0.00) normal. The mean intra ocular pressure (IOP) in OAG group was 19.73 ±4.95(11-32) mmHg compared to 16.74± 3.36(10-30) mmHg (p=0.00) in normal group. The mean central corneal thickness (CCT) in OAG group was 533.05 ± 31.24µm (467-606) compared to normal was 534.9±33.6 µm (432-696) (p=0.670). CONCLUSIONS: Suspicious optic nerve head is the most common referral parameter between the general ophthalmologist and residents, but this study shows only few of them were diagnosed with glaucoma. This gives us a clue that the ophthalmologists and residents are to be trained better to help them identify the signs of glaucoma on the optic nerve head beside its size, which will reduce unnecessary burden to the resources of patients and hospital.

HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.

Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comparison of DoTT/DoG transcription between HSV-1 infection, salt and heat stress in primary human fibroblasts using 4sU-seq and ATAC-seq. Although DoTT at late times of HSV-1 infection was substantially more prominent than DoG transcription in salt and heat stress, poly(A) read-through due to DoTT/DoG transcription and affected genes were significantly correlated between all three conditions, in particular at earlier times of infection. We speculate that HSV-1 either directly usurps a cellular stress response or disrupts the transcription termination machinery in other ways but with similar consequences. In contrast to previous reports, we found that inhibition of Ca2+ signaling by BAPTA-AM did not specifically inhibit DoG transcription but globally impaired transcription. Most importantly, HSV-1-induced DoTT, but not stress-induced DoG transcription, was accompanied by a strong increase in open chromatin downstream of the affected poly(A) sites. In its extent and kinetics, downstream open chromatin essentially matched the poly(A) read-through transcription. We show that this does not cause but rather requires DoTT as well as high levels of transcription into the genomic regions downstream of genes. This raises intriguing new questions regarding the role of histone repositioning in the wake of RNA Polymerase II passage downstream of impaired poly(A) site recognition.

Effect of phacoemulsification on measurement of retinal nerve fiber layer and optic nerve head parameters using spectral-domain-optical coherence tomography.

PURPOSE: The purpose of this study is to determine the effect of phacoemulsification cataract extraction on measurement of retinal nerve fiber layer and optic nerve head parameters using spectral domain optical coherence tomography. MATERIAL AND METHODS: A prospective, hospital-based study of 100 patients of 40 years of age and above, with no other ocular morbidity except cataract and planned for phacoemulsification with IOL implantation (SN60WF) at a tertiary centre at AIIMS, New Delhi, India. All patients underwent imaging with Cirrus SD-OCT model 400 and the optic disc cube 200x200 protocol at baseline and at 1 month follow up. Paired sample t-test was used to compare the RNFL parameters and ONH parameters. RESULTS: The mean age of subjects was 56.6 ± 12.3 years (70 males, 30 females). The average RNFL increased from 92.6 ± 5.4 µm to 101.3 ± 5.6 µm after phacoemulsification, an increase of 9% (P = 0.003) and the signal strength increased from 5.6 ± 0.5 to 7.6 ± 0.7, increasing by 35.7% (P = 0.004). There was a significant increase in the disc area (P = 0.004) and rim area (P = 0.004) but no significant change in vertical cup-disc ratio (P = 0.45) or average cup-disc ratio (P = 0.075). The quadrant-wise RNFL thickness increase in inferior, superior, nasal, and temporal quadrants was 12.6% (P = 0.001), 10% (P = 0.001), 5.6% (P = 0.001), and 3.2% (P = 0.001), respectively. The change in RNFL thickness was maximum in posterior subcapsular cataract (P = 0.001) followed by cortical (P = 0.001) and nuclear (P = 0.001) subtypes. CONCLUSIONS: A significant increase in RNFL thickness and signal strength was observed after cataract surgery using SD-OCT. The maximum change in RNFL thickness was in the inferior quadrant, where RNFL thinning is a significant predictor of glaucoma progression. The posterior subcapsular cataract interfered with RNFL measurement maximally due to its density and proximity to nodal point. After the cataract surgery, a new baseline needs to be established by obtaining fresh OCT images for assessing the longitudinal follow-up of a glaucoma patient.

Visual outcome and early complications of sutureless and glueless scleral fixated intraocular lens.

INTRODUCTION: In the absence of capsular support, anterior chamber intraocular lens (IOL), iris fixated IOL and sutured scleral fixated intraocular lens (SFIOL) implantation have been performed for many years. Recently sutureless glued SFIOL have been used as a primary or secondary procedure to correct aphakia. In this study we have used sutureless and glueless technique of SFIOL implantation. METHODOLOGY: An interventional case series was conducted. Aphakic patients without capsular support, sub-luxated lens (>180°), dislocated lens and dislocated IOL were the inclusion criteria. The patients with hazy cornea, non-dilating pupil, macular scar and glaucoma were not enrolled in the study. RESULTS: Of 62 eyes who completed 1 month follow- up, 48 were men and 14 women. There was a significant improvement in uncorrected distance visual acuity after surgery (p less than 0.001). One month postoperative best corrected distance visual acuity was 6/18 or better in 45 eyes (72.6%). The common early postoperative complications were hypotony, corneal edema. No serious complications such as endophthalmitis and retinal detachment were seen. CONCLUSION: Our technique of sutureless and glueless SFIOL implantation showed good visual outcome in the absence of serious complications. SFIOL will be the only choice in eyes that have anatomic contraindications like non constricting pupil, large sectoral iridectomy and peripheral anterior synechia in which other types of lens are not suitable.

The DRBD13 RNA binding protein is involved in the insect-stage differentiation process of Trypanosoma brucei.

DRBD13 RNA-binding protein (RBP) regulates the abundance of AU-rich element (ARE)-containing transcripts in trypanosomes. Here we show that DRBD13 regulates RBP6, the developmentally critical protein in trypanosomatids. We also show DRBD13-specific regulation of transcripts encoding cell surface coat proteins including GPEET2, variable surface glycoprotein (VSG) and invariant surface glycoprotein (ISG). Accordingly, alteration in DRBD13 levels leads to changes in the target mRNA abundance and parasite morphology. The high consistency of the observed phenotype with known cell membrane exchanges that occur during progression of T. brucei through the insect stage of its life cycle suggests that DRBD13 is an important regulator in this largely unknown developmental process.

Depletion of the Trypanosome Pumilio domain protein PUF2 or of some other essential proteins causes transcriptome changes related to coding region length.

Pumilio domain RNA-binding proteins are known mainly as posttranscriptional repressors of gene expression that reduce mRNA translation and stability. Trypanosoma brucei has 11 PUF proteins. We show here that PUF2 is in the cytosol, with roughly the same number of molecules per cell as there are mRNAs. Although PUF2 exhibits a low level of in vivo RNA binding, it is not associated with polysomes. PUF2 also decreased reporter mRNA levels in a tethering assay, consistent with a repressive role. Depletion of PUF2 inhibited growth of bloodstream-form trypanosomes, causing selective loss of mRNAs with long open reading frames and increases in mRNAs with shorter open reading frames. Reexamination of published RNASeq data revealed the same trend in cells depleted of some other proteins. We speculate that these length effects could be caused by inhibition of the elongation phase of transcription or by an influence of translation status or polysomal conformation on mRNA decay.

Application of anterior segment optical coherence tomography in glaucoma.

Optical coherence tomography (OCT) is a cross-sectional, three-dimensional, high-resolution imaging modality that uses low coherence interferometry to achieve axial resolution in the range of 3-20 µm. Two OCT platforms have been developed: time domain (TD-OCT) and spectral (or Fourier) domain (SD/FD-OCT). Visante anterior segment OCT (Carl Zeiss Meditec) is a TD-OCT widely used for anterior segment imaging. The SD-OCT systems with both posterior and anterior segment imaging capabilities include the RTVue, iVue (Optovue), the Cirrus (Carl Zeiss Meditec), and the Spectralis (Heidelberg Engineering, Inc.). Each of the SD-OCTs has a wavelength in the range of 820-879 nm. Anterior segment OCT is a non-contact method providing high resolution tomographic cross-sectional imaging of anterior segment structures. Anterior segment OCT provides qualitative and quantitative assessment of the anterior segment structures important to the pathogenesis and the anatomical variations of glaucoma, and the approach to and success of treatment. We summarize the clinical applications of anterior segment OCT in glaucoma.

The trypanosome Pumilio domain protein PUF5.

PUF proteins are a conserved family of RNA binding proteins found in all eukaryotes examined so far. This study focussed on PUF5, one of 11 PUF family members encoded in the Trypanosoma brucei genome. Native PUF5 is present at less than 50000 molecules per cell in both bloodstream and procyclic form trypanosomes. C-terminally myc-tagged PUF5 was mainly found in the cytoplasm and could be cross-linked to RNA. PUF5 knockdown by RNA interference had no effect on the growth of bloodstream forms. Procyclic forms lacking PUF5 grew normally, but expression of PUF5 bearing a 21 kDa tandem affinity purification tag inhibited growth. Knockdown of PUF5 did not have any effect on the ability of trypanosomes to differentiate from the mammalian to the insect form of the parasite.

Expression of the RNA recognition motif protein RBP10 promotes a bloodstream-form transcript pattern in Trypanosoma brucei.

When Trypanosoma brucei differentiates from the bloodstream form to the procyclic form, there are decreases in the levels of many mRNAs encoding proteins required for the glycolytic pathway, and the mRNA encoding the RNA recognition motif protein RBP10 decreases in parallel. We show that RBP10 is a cytoplasmic protein that is specific to bloodstream-form trypanosomes, where it is essential. Depletion of RBP10 caused decreases in many bloodstream-form-specific mRNAs, with increases in mRNAs associated with the early stages of differentiation. The changes were similar to, but more extensive than, those caused by glucose deprivation. Conversely, forced RBP10 expression in procyclics induced a switch towards bloodstream-form mRNA expression patterns, with concomitant growth inhibition. Forced expression of RBP10 prevented differentiation of bloodstream forms in response to cis-aconitate, but did not prevent expression of key differentiation markers in response to glucose deprivation. RBP10 was not associated with heavy polysomes, showed no detectable in vivo binding to RNA, and was not stably associated with other proteins. Tethering of RBP10 to a reporter mRNA inhibited translation, and halved the abundance of the bound mRNA. We suggest that RBP10 may prevent the expression of regulatory proteins that are specific to the procyclic form.

Selective Laser Trabeculoplasty: An Overview.

Given the obvious quality of life concerns with medical and surgical lowering of intraocular pressure (IOP), lasers have received considerable attention as a therapeutic modality for glaucoma. Selective laser trabeculoplasty (SLT) is increasingly being used in clinical practice as both the primary procedure and as an adjunct to medical and surgical therapy. Preliminary published evidence suggests that SLT is an effective, compliance-free, repeatable and safe therapeutic modality having only minor, transient, self-limiting or easily controlled side effects with no sequelae. This review attempts a broad overview of the current knowledge of its mechanism, efficacy, indications and limitations, point out the knowledge lacunae that still exist with respect to this highly promising technology which has captured the attention of glaucoma surgeons all over the world. HOW TO CITE THIS ARTICLE: Jha B, Bhartiya S, Sharma R, Arora T, Dada T. Selective Laser Trabeculoplasty: An Overview. J Current Glau Prac 2012;6(2):79-90.

Processing of a phosphoglycerate kinase reporter mRNA in Trypanosoma brucei is not coupled to transcription by RNA polymerase II.

Capping of mRNAs is strictly coupled to RNA polymerase II transcription and there is evidence, mainly from metazoans, that other steps in pre-mRNA processing show a similar linkage. In trypanosomes, however, the mRNA cap is supplied by a trans spliced leader sequence. Thus pre-mRNAs transcribed by RNA Polymerase I are capped by trans splicing, and translation-competent transgenic mRNAs can be produced by RNA Polymerase I and T7 RNA polymerase so long as the primary transcript has a splice acceptor signal. We quantified the efficiency of processing of trypanosome pre-mRNAs produced from a plasmid integrated either at the tubulin locus, or in an rRNA spacer, and transcribed by RNA polymerase II, RNA polymerase I or T7 RNA polymerase. The processing efficiencies were similar for primary transcripts from the tubulin locus, produced by RNA polymerase II, and for RNA from an rRNA spacer, transcribed by RNA polymerase I. Primary transcripts produced by T7 RNA polymerase from the tubulin locus were processed almost as well. There was therefore no evidence for recruitment of the 3'-splicing apparatus by the RNA polymerase. Abundant transcripts transcribed from the rRNA locus by T7 RNA polymerase were somewhat less efficiently processed.

The role of deadenylation in the degradation of unstable mRNAs in trypanosomes.

Removal of the poly(A) tail is the first step in the degradation of many eukaryotic mRNAs. In metazoans and yeast, the Ccr4/Caf1/Not complex has the predominant deadenylase activity, while the Pan2/Pan3 complex may trim poly(A) tails to the correct size, or initiate deadenylation. In trypanosomes, turnover of several constitutively-expressed or long-lived mRNAs is not affected by depletion of the 5'-3' exoribonuclease XRNA, but is almost completely inhibited by depletion of the deadenylase CAF1. In contrast, two highly unstable mRNAs, encoding EP procyclin and a phosphoglycerate kinase, PGKB, accumulate when XRNA levels are reduced. We here show that degradation of EP mRNA was partially inhibited after CAF1 depletion. RNAi-targeting trypanosome PAN2 had a mild effect on global deadenylation, and on degradation of a few mRNAs including EP. By amplifying and sequencing degradation intermediates, we demonstrated that a reduction in XRNA had no effect on degradation of a stable mRNA encoding a ribosomal protein, but caused accumulation of EP mRNA fragments that had lost substantial portions of the 5' and 3' ends. The results support a model in which trypanosome mRNAs can be degraded by at least two different, partially independent, cytoplasmic degradation pathways attacking both ends of the mRNA.