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The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation of maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute the compound embryonic transcriptome in zebrafish. While mitochondrial zygotic transcripts prevailed prior to MZT, we uncover the spurious transcription of hundreds of short and intron-poor nuclear genes as early as the 2-cell stage. Upon ZGA, most zygotic transcripts originate from thousands of maternal-zygotic (MZ) genes that are transcribed at rates comparable to those of hundreds of purely zygotic genes and replenish maternal mRNAs at distinct timescales. Rapid replacement of MZ transcripts involves transcript decay features unrelated to major maternal degradation pathways and promotes de novo synthesis of the core gene expression machinery by increasing poly(A)-tail length and translation efficiency. SLAMseq hence provides unprecedented insights into the timescales, molecular features and regulation of MZT during zebrafish embryogenesis.

Repository corticotropin injection (RCI) has recently gained attention in the field of ocular inflammatory disease. Data supporting the use of RCI therapy in ocular inflammation are limited to case reports or small series subject to publication bias toward positive results. How this therapy differs significantly from oral corticosteroids, which are significantly cheaper, is unknown. Clinical trials to investigate the efficacy of RCI are currently limited to open-labeled non-comparative studies. Side effects of RCI are not insignificant, have been reported in other fields of medicine, and require further scrutiny. Finally, the price of RCI has skyrocketed with average yearly cost of therapy estimated to be between $480,000-$850,000 with allegations of the RCI manufacturing drug company providing remuneration to induce healthcare providers to prescribe RCIs but without any repercussions from a regulatory standpoint. The significant cost of RCI combined with lack of evidence-based guidance on efficacy, safety, and indications for use in ocular inflammation warrant caution in utilizing this therapy.

Tinosporacordifoliaisapopularmedicinal plant which is used in several traditional medicines to cure various diseases. The common names are Amrita and Guduchi, belonging to the family of Menispermaceae. The aim of the study was to study the stem extract of traditional medicinal plant, T. cordifolia for qualitative estimation of phytoconsituents and subsequently to determine its antibacterialactivityagainsttwotestmicroorganisms Escherichia coliand Pseudomonas aeruginosato authenticate its use in traditional medicines. Stems were air-dried and coarsely powdered samples were subjectedto Soxhlet extractionusingdiversesolvents(Hexane,chloroform, ethyl acetate and methanol and water). Freshly prepared extracts were exposed to standard phytochemical analysis for qualitative estimation of phytoconsituents. The antibacterial activity of the stem extract of T. cordifolia was determined by agar well diffusion method. Phytochemical analysis revealed the presence of several phytochemicals viz., alkaloids, flavonoids, steroids, phenol, tannins, steroid, terpenoids, saponins and sugars. The methanolic extract displayed the presence of highest number of phytochemical compounds. It may be due to the higher solubility of active components in this solvent as compared to other solvents. The results revealed that the methanolic extract exhibit the effective antibacterial activity against the tested bacterial species . The studies justify the use of T. cordifolia in traditional medicines. The investigation further proposed that the metabolites present in leaf tissue of T. cordifolia can be potential source of novel natural antibacterial and antioxidant agents and can be prospective applications in food industry as an antioxidant

INTRODUCTION: Urinary tract infections are the most common infections seen in the hospital setting and take the second lead after respiratory tract infection in community acquired infections. Nitrofurantoin and Fosfomycin are older drugs that are being revived and recommended as first-line agents in treating uncomplicated UTI. AIMS AND OBJECTIVES: To assess the comparative efficacy of 5day nitrofurantoin versus single dose fosfomycin for clinical resolution in uncomplicated UTI. MATERIALS AND METHODS: This randomized clinical trial was conducted from January 2019 to September 2019 at the Department of Obstetrics and Gynaecology, AIMS, B G Nagara, Mandya, Karnataka. Patients were randomized to either oral nitrofurantoin 100mg twice daily for 5 days or single dose of oral fosfomycin 3g. Baseline urine routine was done. They were followed up at 14(+/-2) and 28(+/-7) days after completion of antibiotic therapy which was considered at day 5 as fosfomycin has long half-life. The data was entered in Microsoft Excel and outcomes were analysed using Epi Info software. RESULTS: Out of total 92 patients screened,63 were enrolled and randomized. Thirty-two (50.7%) were given nitrofurantoin and 31 (49.2%) received fosfomycin. Of total enrolled after screening 3 (4.7%) patients were lost to follow-up, so only 60 patients (n=92, 65.2%) comprised the study population. CONCLUSION: Five-day nitrofurantoin is superior to single dose fosfomycin in treatment of acute uncomplicated UTI.

Patient Adherence to Immunosuppressive Therapy for Chronic Inflammatory Eye Disease To investigate adherence rates to immunosuppressive therapy (IMT) for treatment of noninfectious inflammatory eye disease (IED), adherence and disease control, and factors associated with nonadherence. Retrospective review of medical charts from 2015 to 2020 was conducted on patients with IED at 6 months, 1 and 2 years after initiation of IMT. Of 183 patients, adherence rates at 6 months and 1 year were 70% and 58% by 2 years. Eighty-two percent, 78%, and 65% of patients with disease quiescence were adherent at 6 months, 1 and 2 years, respectively. Adherent patients have 1.86 (95% CI 1.09, 3.20) times greater likelihood for disease control compared to nonadherent. Primary reason for nonadherence was patient self-discontinuation. No specific factors were associated with nonadherence. Patients on IMT for IED had steady adherence rates up to 1 year, with decreased adherence at 2 years. Adherence to IMT significantly correlates with disease quiescence.

Introduction: Fibroids are most common benign tumours of female reproductive tract. Fibroid in pregnancy is associated with complications like preterm labor, malpresentations, etc. Aims and Objectives: The aim of this study is to the incidence, clinical presentation, maternal and fetal outcomes among pregnant women with Leiomyoma and its management. Materials and Methods: This is a prospective observational study in Department of OBG, Adichunchanagiri hospital, from Jan 2017 to July 2019. Parameters such as age, parity, size and type of fibroid, mode of delivery and perinatal outcomes were analysed using Epi info software. Results: Out of 5043 deliveries conducted, 30 cases were detected with fibroid during pregnancy, incidence being 0.5%. Majority belonged to age group 25-29 years (50%), 18 (60%) were Primigravida, 26(86.66%) underwent LSCS,4(13.33%) underwent preterm vaginal delivery,16.66% had malpresentation, 2(15%) underwent myomectomy, and 6(20%) had PROM,5(16.6%) were infertility treated, 20(66.66%) had pain abdomen, 3(10%) had PPH, and Abruption in 3.3%, IUGR in 16%, LBW in 26.66% of deliveries. Conclusion: Pregnancy with fibroid is considered as high risk. Timely diagnosis and management of antepartum, intrapartum, postpartum complications with good neonatal care leads to successful outcome. Caesarean myomectomy in selected cases can prove beneficial. Keywords: Fibroid in pregnancy, Myomectomy, Caesarean section.

Uveitis patients represent a unique subset of the population undergoing cataract surgery and pose several challenges that require special consideration and strategy. Maintenance of disease quiescence for at least three months prior to surgery maximizes postoperative outcomes, though these patients remain at increased risk for pseudophakic cystoid macular edema, which can be refractory to the traditional steroid treatments. In this review, we detail the pillars of preoperative optimization, intraoperative considerations, and postoperative management of uveitic cataracts, with special attention on the evidence surrounding prevention and treatment of refractory postoperative cystoid macular edema.

To evaluate the utility and side effect profile of subcutaneous repository corticotropin gel (RCI) in ocular sarcoidosis.Retrospective chart review.Among six identified patients on RCI therapy, 4 had uveitis, one had optic neuritis and one had uveitis and optic neuritis secondary to sarcoidosis. The average follow-up was 43.5 months. RCI therapy was continuous in 4 patients (average 7.7 months) and intermittent in 2 patients (24 and 12 months). Five of the 6 patients continued with local and/or systemic corticosteroids for ocular inflammation control while on RCI therapy. Two-thirds of patients experienced adverse effects including hyperpigmentation, alopecia, and severe hypertension. RCI therapy was discontinued in 5 of the 6 patients due to continued inflammation and side/adverse effects (4 patients) and loss of follow-up (1 patient).In this small cohort, the majority of patients failed to achieve adequate steroid-sparing ocular inflammation control and experienced side effects while on RCI therapy. Additional studies are needed to elucidate the role of RCI in ocular inflammation.

Alternative cleavage and polyadenylation generates mRNA 3' isoforms in a cell type-specific manner. Due to finite available RNA sequencing data of organisms with vast cell type complexity, currently available gene annotation resources are incomplete, which poses significant challenges to the comprehensive interpretation and quantification of transcriptomes. In this chapter, we introduce 3'GAmES, a stand-alone computational pipeline for the identification and quantification of novel mRNA 3'end isoforms from 3'mRNA sequencing data. 3'GAmES expands available repositories and improves comprehensive gene-tag counting by cost-effective 3' mRNA sequencing, faithfully mirroring whole-transcriptome RNAseq measurements. By employing R and bash shell scripts (assembled in a Singularity container) 3'GAmES systematically augments cell type-specific 3' ends of RNA polymerase II transcripts and increases the sensitivity of quantitative gene expression profiling by 3' mRNA sequencing. Public access: https://github.com/AmeresLab/3-GAmES.git.

Presumed ocular histoplasmosis syndrome is an ocular syndrome of peripheral punched-out chorioretinal lesions (histo spots), peripapillary atrophy, macular scarring with or without choroidal neovascular membranes and absence of vitritis. It is caused by presumed exposure to the dimorphic fungus Histoplasma capsulatum, which grows in soil (mold) and inside animals/birds (yeast) and is endemic in the Ohio and Mississippi River valleys, the “Histo belt.”

Background The coronavirus disease-2019 (COVID-19) pandemic has affected academic ophthalmology departments globally, causing changes in educational, research, and clinical operations in the short and long term. Healthcare workers are at higher risk of contracting the disease and given early reports suggestive of transmission through the tear film in COVID-19 cases with conjunctivitis, and close proximity during examination, eye care providers in particular may be at increased risk. Objective To provide the experience from a single academic ophthalmology program in responding to the COVID-19 pandemic. Methods This article describes the changes executed in the Department of Ophthalmology and Visual Sciences at the University of Illinois at Chicago, Illinois Eye and Ear Infirmary, with emphasis on the implementation of a tele-triage process for urgent visits. Results In response to the pandemic, our department made rapid changes to its departmental protocols for education, research, and patient management. Early measures focused on limiting face-to-face interactions among patients, staff, residents, and faculty, decreasing the risk of exposure to disease while also providing access for patients in urgent need of care. Conclusion We hope that the UIC experience will assist other academic tertiary referral centers in maximizing their opportunities to deliver excellent patient care while minimizing risks to patient and provider, all while continuing to provide a quality graduate medical educational experience during and beyond the pandemic.

Background: Anaemia is a significant problem worldwide, particularly in women. Several intravenous iron preparations are available for the treatment of anaemia. Some of them cause life-threatening anaphylactic reactions while others require multiple small infusions to prevent iron reactions. Ferric carboxy maltose (FCM), a non-dextran intravenous iron, is safe and effective option that can be administered as single high dose without serious adverse effects.Methods: A prospective study was undertaken in the department of obstetrics and gynecology, Adichunchungiri institute of medical sciences, B G Nagara, from August 2020 to November 2021 in which 50 cases with iron deficiency anaemia were enrolled. IV FCM 1g was given. Change in the laboratory parameters such as haemoglobin (Hb), mean corpuscular value, serum ferritin levels over a 4 weeks period were observed.Results: A significant increase in mean Hb from 8.14 to 11.71 g was observed in patients treated with FCM after 4 weeks of therapy. Majority belonged to age group of 21-30 years and moderate type of anaemia was most common. No serious drug reaction was reported.Conclusions: IV FCM is safe and effective option for improving Hb in iron deficiency anaemia, in terms of restoring iron stores in short duration of time as well as patient compliance.

Gene expression profiling by high-throughput sequencing reveals qualitative and quantitative changes in RNA species at steady-state but obscures the intracellular dynamics of RNA transcription, processing and decay. We developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), an orthogonal chemistry-based RNA sequencing technology that detects 4-thiouridine (s4U)-incorporation in RNA species at single-nucleotide resolution. In combination with well-established metabolic RNA labeling protocols and coupled to standard, low-input, high-throughput RNA sequencing methods, SLAM-seq enables rapid access to RNA polymerase II-dependent gene expression dynamics in the context of total RNA. We validated the method in mouse embryonic stem cells by showing that the RNA-polymerase II-dependent transcriptional output scales with Oct4/Sox2/Nanog-defined enhancer activity; and we provide quantitative and mechanistic evidence for transcript-specific RNA turnover mediated by post-transcriptional gene regulatory pathways initiated by microRNAs and N6-methyladenosine. SLAM-seq facilitates the dissection of fundamental mechanisms that control gene expression in an accessible, cost-effective, and scalable manner.

Recent developments in novel engineered mass timber products and connection systems have created the possibility to design and construct tall timber-based buildings. This research presents the experiments conducted on the steel-wood connection as main energy dissipating part of a novel steel–timber hybrid system labelled Finding the Forest Through the Trees (FFTT). The performance was investigated using quasi-static monotonic and reversed cyclic tests. The influence of different steel beam profiles (wide flange I-sections and hollow rectangular sections) and the embedment approaches (partial and full embedment) was investigated. The test results demonstrated that appropriate connection layouts can lead to the desired failure mechanism while avoiding excessive crushing of the mass timber panels. The research can serve as a precursor for developing design guidelines for the FFTT system as an option for tall wood-hybrid building systems in seismic regions.

Introduction: Autoimmune retinopathy (AIR) is a rare condition characterized by profound vision loss, presence of anti-retinal antibodies and association with systemic malignancy within the paraneo...

Biodiversity is a multifaceted concept that often eludes simple operational definitions. As a result, a variety of definitions have been proposed each with varying levels of complexity and scope. Traditional approaches to the tracking of wild animals provide useful, yet spatially constrained information. Remote sensing offers the prospect for large area characterizations of biodiversity in a systematic, repeatable, and spatially exhaustive manner. Information and monitoring systems for the forest sector are beneficial for effective policies and planning, valuation of forest resources and proficient investments. This project presents a system for monitoring forest and its vicinity based on IoT based wireless sensor network technology. The need to be able to accurately monitor forest cover and quality is crucial to understanding the costs of deforestation. The monitoring of forest and the surrounding area can, however, still is considered an open research problem due to its substantial vast area. Even though sufficient manpower has been deployed, it is inefficient as it could be life-threatening. This project is an attempt to prevent forest mishaps, the intrusion of animals in the surrounding forest areas, illegal activities in the forest by using wireless sensor technology and eliminating manual power to the highest possible extent.

To describe scleral changes in chronic VKH.Medical records of patients with chronic VKH were retrospectively reviewed. Change of scleral architecture was defined as progressive posterior bowing on OCT, axial length elongation, and/or increased myopia more than -1.0 D, not explicable by other etiologies.In total, 28 eyes (16 patients) with mean age of disease onset 32.5 ± 14.0 years were included in the study. Disease duration was 15.1 ± 10.2 years. Eight eyes (28.6%) showed progressive scleral architectural changes. Five eyes (18%) developed scleral changes on OCT, not seen on prior imaging (2-12 years earlier). One eye had posterior bowing on OCT with increased axial length, both eyes of a bilateral pseudophake developed increased myopia with increased axial length. Well-circumscribed chorioretinal atrophy within the arcade was associated with progressive scleral change.Progressive scleral change may develop as a late complication of VKH. The association with well-circumscribed chorioretinal atrophy suggests that chronic choroidal inflammation may be responsible.

Gene expression profiling by high-throughput sequencing reveals qualitative and quantitative changes in RNA species at steady-state but obscures the intracellular dynamics of RNA transcription, processing and decay. We developed thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), an orthogonal chemistry-based epitranscriptomics-sequencing technology that uncovers 4-thiouridine (s4U)-incorporation in RNA species at single-nucleotide resolution. In combination with well-established metabolic RNA labeling protocols and coupled to standard, low-input, high-throughput RNA sequencing methods, SLAM-seq enables rapid access to RNA polymerase II-dependent gene expression dynamics in the context of total RNA. When applied to mouse embryonic stem cells, SLAM-seq provides global and transcript-specific insights into pluripotency-associated gene expression. We validated the method by showing that the RNA-polymerase II-dependent transcriptional output scales with Oct4/Sox2/Nanog-defined enhancer activity; and we provide quantitative and mechanistic evidence for transcript-specific RNA turnover mediated by post-transcriptional gene regulatory pathways initiated by microRNAs and N6-methyladenosine. SLAM-seq facilitates the dissection of fundamental mechanisms that control gene expression in an accessible, cost-effective, and scalable manner.One Sentence Summary:Chemical nucleotide-analog derivatization provides global insights into transcriptional and post-transcriptional gene regulation

There have been many recent advances in local therapeutic options for uveitis, both corticosteroid and non-corticosteroid. Long- and short-acting steroid implants are now available, with new ones being developed. There are also new locations for drug delivery (suprachoroidal space) and new non-corticosteroid options. This paper reviews the data on the currently available local treatment options, as well as those currently under investigation. The choice of local therapy depends on whether or not there is systemic inflammatory disease also requiring treatment, if the disease is unilateral or bilateral, expected disease duration, patient preference and co-existing ocular and systemic comorbidities. For chronic disease without systemic manifestations, long-term steroid releasing implants are a good option, whereas for breakthrough inflammation and cystoid macular edema, short-term intravitreal therapy, initially with corticosteroids then with alternative agents is considered.

Introduction: Intravitreal corticosteroid implants have dramatically changed the treatment of uveitis. This review focuses on available data on the safety and efficacy of the dexamethasone implant in context of other local therapies – the fluocinolone acetonide (FA) implant and intravitreal triamcinolone acetonide injections. Areas covered: The FDA approved Retisert® (intravitreal FA sustained release implant) in 2005 and Ozurdex® (biodegradable dexamethasone implant) in 2010, both for treatment of posterior segment noninfectious uveitis. A PubMed literature search was carried out using keywords: intravitreal implant, fluocinolone, dexamethasone implant, triamcinolone, intravitreal drug delivery and uveitis. Expert opinion: The dexamethasone implant reduces vitreous haze and cystoid macular edema (CME) and results in improved vision in patients with uveitis. While the reduction in CME does not persist for 26 weeks, the visual acuity increase does. One-fourth of patients treated with a single injection as ...

We would like to thank Drs Kaya and Yildirim1 for their interest in our article.2 We agree that choroidal atrophy may allow intraocular pressure to affect the sclera. However, choroidal atrophy alo...