Implications and management of suction loss during refractive lenticule extraction (ReLEx).

PURPOSE: To describe a case in which the ReLEx procedure was abandoned following suction loss on two occasions due to an uncooperative patient. METHODS: Case report with anterior segment optical coherence tomography and aberrometry changes before and after surgery. RESULTS: Lamellar haze was present but diminished in the early postoperative period. The patient successfully underwent a femtosecond LASIK procedure in the same eye 2 months later. CONCLUSIONS: This case demonstrates the possibility of performing femtosecond LASIK after failed ReLEx, with good visual outcomes.

Cost effective and reliable cell based ELISA as an alternative method of flow cytometry for assessment of binding activity of Vedolizumab.

Vedolizumab is a humanized monoclonal antibody used for inflammatory bowel disease treatment. Vedolizumab binds to the α4ß7 integrin complex and inhibits its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1). To evaluate the binding efficacy and quality control check of Vedolizumab, flow cytometry is performed by using HuT78 cells. As we know, flow cytometer is costly and require high equipment maintenance with a designated technical manpower to handle it. In this regard, the aim of study was to develop and validate an economical, simple and efficient cell based ELISA assay for potency estimation of Vedolizumab which has not been reported in any pharmacopoeia. The proposed bioassay method was optimized by investigating Vedolizumab binding to α4ß7 integrin which is expressed by HuT78 cells. The validation of this method was done at different parameters including specificity, linearity, range, repeatability, precision, and accuracy. The Vedolizumab binding by ELISA results were found specific for Vedolizumab with linearity (R2 = 0.99) and precision (%Geometric Coefficient of variance) observed for repeatability and intermediate precision were 3.38% and 2.6% respectively. The relative bias was calculated as 8.68% for repeated performances by different analysts and found in accordance with parameter of accuracy as per various pharmacopoeial guidelines. The developed method is established as robust, effective, and less expensive than high maintenance setup like flow cytometry based assay.

Analysis of resident-performed manual small incision cataract surgery (MSICS): an efficacious approach to mature cataracts.

To examine and improve outcomes of resident-performed manual small incision cataract surgery (MSICS) cases via analysis of visual recovery, intraoperative adverse events, and early postoperative course. Particular focus was directed toward mature cataracts extracted by MSICS. A retrospective review was performed to identify MSICS cases performed by resident surgeons unfamiliar with the technique (initial ten cases) in an academic setting. Preoperative history, intraoperative adverse events, and postoperative course were reviewed. Of 30 cases identified, mean preoperative acuity was 1.8 ± 0.9 logMAR units (Snellen equivalent = 20/1262) improving to 0.20 ± 0.35 logMAR units (20/31) at final follow-up (p < 0.0001). Mean follow-up was 22.1 ± 19.0 days. The most frequent intraoperative adverse events were wound leak requiring intraoperative suturing (33 %), vitreous loss (6.7 %), and capsulorhexis radialization (6.7 %). Transient cornea edema was the most frequent (56.7 %) early postoperative minor complication. Two major complications occurred that required wound revision in one eye and iridoplasty in one eye. Of the 30 eyes undergoing surgery, 19 were noted to have mature cataracts. In this subset, mean acuity was 2.25 ± 0.64 logMAR units (20/3557) improving to 0.28 ± 0.42 logMAR (20/38) at final follow-up (p < 0.0001). Complications were similar in nature and frequency to the entire population in this subgroup. Supervised resident MSICS cataract surgery can result in excellent anatomic and visual outcomes. Appropriate wound construction is a frequently encountered difficulty, so particular attention should be directed to this step by both trainers and trainees.

Cancer informatics analysis indicates high CHAC2 associated with unfavorable prognosis in breast cancer.

Breast cancer remains the most commonly diagnosed cancer worldwide and exhibits a poor prognosis. The induction of genetic changes deregulates several genes that increase the disposal towards this life-threatening disease. CHAC2, a member of the glutathione degrading enzyme family has been shown to suppress gastric and colorectal cancer progression, however, the expression of CHAC2 in breast cancer has not been reported. We did an analysis of CHAC2 expression in breast cancer patients from various online tools like UALCAN, GEPIA2, GENT2, TIMER2, and bcGenExminer v4.8. Further, we used the Kaplan-Meier plotter to establish the significance of CHAC2 in BC patient survival and prognosis while TISIDB and TIMER databases were used to investigate the filtration of immune cells. The results showed that CHAC2 levels were high in breast cancer patients and elevated CHAC2 was associated with low overall survival. Taken together, the results of the present study show that like its paralog CHAC1, CHAC2 may also be an important biomarker and could have a potential therapeutic implication in breast cancer.

National Control Laboratory Assessment of Quality of Rituximab Biosimilars in India.

In past few years many rituximab (RTX) biosimilars have been launched in India. Biosimilars are products that are similar in terms of quality, safety, and efficacy to its innovator product and are expected to offer improved affordability. The less clinical examination is a significant source of reduction in the cost of development of a biosimilar. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. Therefore, the role of National Control Laboratory become very important to ensure the quality of these drugs by carrying out analytical characterization at the point of drug product release level as when referred by National Regulatory Authority for quality evaluation. To assess the similarity between innovator and biosimilars, different physicochemical and biological quality attributes were assessed. A multitude of state-of-the-art analysis of N = 3 RTX biosimilars marketed in India revealed that the impurity profiles of these biosimilars measured by charge variant analysis (cation exchange chromatography-high performance liquid chromatography [HPLC], capillary zone electrophoresis, and capillary isoelectric focusing), aggregates profiling (size exclusion chromatography-HPLC), fragments analysis (capillary electrophoresis-sodium dodecyl sulfate) were found to be significantly varying as compared with the innovator product. There were significant variations in acidic variants (p = 0.023) and basic variants (p = 0.0005), isoelectric point value (p < 0.0001), aggregates (p = 0.0231), and fragments (p < 0.0001) of biosimilars were found as that of innovator product. However, these differences were not affecting the biological activity in the cell-based potency analysis by complement-dependent cytotoxicity (CDC) assay (p = 0.1026), antibody-dependent cell-mediated cytotoxicity (ADCC) (p = 0.3736), and binding assay by flow cytometer fluorescence-activated cell sorting (p = 0.4005) of these biosimilars as compared with the innovator product.

Dynamic Energy Management System for a Smart Microgrid.

This paper presents the development of an intelligent dynamic energy management system (I-DEMS) for a smart microgrid. An evolutionary adaptive dynamic programming and reinforcement learning framework is introduced for evolving the I-DEMS online. The I-DEMS is an optimal or near-optimal DEMS capable of performing grid-connected and islanded microgrid operations. The primary sources of energy are sustainable, green, and environmentally friendly renewable energy systems (RESs), e.g., wind and solar; however, these forms of energy are uncertain and nondispatchable. Backup battery energy storage and thermal generation were used to overcome these challenges. Using the I-DEMS to schedule dispatches allowed the RESs and energy storage devices to be utilized to their maximum in order to supply the critical load at all times. Based on the microgrid's system states, the I-DEMS generates energy dispatch control signals, while a forward-looking network evaluates the dispatched control signals over time. Typical results are presented for varying generation and load profiles, and the performance of I-DEMS is compared with that of a decision tree approach-based DEMS (D-DEMS). The robust performance of the I-DEMS was illustrated by examining microgrid operations under different battery energy storage conditions.

Total synthesis of a pyrroloindoloquinazoline alkaloid.

A highly concise stereoselective synthesis of a newly identified alkaloid with a pyrroloindoloquinazoline skeleton has been achieved. To this end, a chiral auxiliary mediated asymmetric acetate aldol reaction on tryptanthrin was explored and the resulting adduct was converted to the product by a novel one-pot reductive cyclization/transamidation using NiCl2·6H2O/NaBH4 in methanol.

In-vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation by vitamins C and E.

Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 µM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 µM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H_{2}O_{2}, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress.

Stereoregulations of pyrimidinone based chiral auxiliary in aldol and alkylation reactions: a convenient route to oxyneolignans.

(S)-4-Isopropyl-1-phenyltetrahydropyrimidin-2(1H)-one was synthesized and evaluated as a chiral auxiliary for asymmetric acetate and propionate aldol reactions, by generation of titanium and lithium enolates, affording excellent yields and stereoselectivities for syn and anti aldol diastereomers, respectively. High stereoselectivities were also obtained in lithium mediated alkylation reactions. The application of the auxiliary was exemplified in the asymmetric synthesis of a natural oxyneolignan, (+)-(7S,8S)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-oic acid.

Factors modifying transcriptional regulation of signaling genes have putative role in tumor development and progression in humans.

Genes involved in signaling are highly regulated at the level of transcription. Several factors have been known to play role in transcriptional modification of genes. Among these DNA sequence variations present in the regulatory region and aberrant methylation of CpG Iceland in promoter region are the most important factors modifying transcriptional regulation of genes. DNA sequence variation interferes with assembling of regulatory protein TF (transcription factor) on the cis elements TFBS (transcription factor binding site). Presence of variations in regulatory region may alter the level of gene product via interaction of TF to TFBS (transcriptional modification). Promoter hypermethylation causes gene silencing and responsible for transcriptional dysregulation of gene. JAK-1, STAT-3, IL-6, MAPK and AR genes participate in signaling pathway and are tightly regulated. Overexpression of IL-6 and activated STAT3 may contribute to the development of prostate cancer and possibly other human cancers. Indeed, constitutively activated STAT3 have been found in a growing number of human tumors. In the present work, we have predicted 34 regulatory polymorphisms that lies in TFBS of 5 (JAK-1, STAT-3, IL-6, MAPK and AR) signaling genes and compare the methylation of CpG Iceland in promoter region of above motioned genes. On the basis of these predictions, it has been hypothesized that transcriptional modification of gene resulting from the DNA sequence variations in regulatory region or promoter hypermethylation increases the susceptibility to diseases such as cancer by alteration in the level of signaling genes product. Presence of DNA sequence variations may also influence the response to a particular drug.