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Jeewan S Titiyal,1 Samar K Basak,2 Naren Shetty,3 Umang Mathur,4 Prema Padmanabhan,5 Sri Ganesh,6 Arindam Dey,7 Dandapani Ramamurthy8 1Department of Cornea and Refractive Surgery, All India Institute of Medical Sciences, New Delhi, India; 2Department of Cornea and Cataract Services, Disha Eye Hospitals, Kolkata, India; 3Department of Cataract and Refractive Services, Narayana Nethralaya, Bengaluru, India; 4Department of Ophthalmology, Dr. Shroff’s Charity Eye Hospital, New Delhi, India; 5Department of Ophthalmology, Sankara Nethralaya, Chennai, India; 6Department of Phaco and Refractive Surgery, Nethradhama Superspeciality Eye Hospital, Bengaluru, India; 7Alcon Laboratories (India) Private Ltd, Bengaluru, India; 8Department of Cornea, Cataract and Refractive Services, The Eye Foundation, Coimbatore, IndiaCorrespondence: Jeewan S Titiyal, Department of Cornea and Refractive Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India, Email titiyal@gmail.comPurpose: To assess real-world clinical outcomes and safety of the Clareon® intraocular lens (IOL) and AutonoMe® automated preloaded delivery system in an Indian population.Patients and methods: This was a prospective, single-arm, multicenter, 12-month clinical study in patients aged ≥ 20 years with unilateral or bilateral cataracts. Surgery was performed by phacoemulsification followed by implantation of the Clareon monofocal IOL (CNA0T0). Monocular best-corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were assessed at 1 week and 1, 6, and 12 months after implantation. Posterior capsular opacification (PCO), surface haze, and glistenings were evaluated at all visits. Surgeons’ satisfaction with automated injector system was also evaluated using a questionnaire. Safety was assessed by monitoring adverse events (AEs).Results: A total of 151 eyes received the CNA0T0 IOL. Mean ± SD monocular BCDVA improved from 0.53± 0.44 logMAR preoperatively to 0.00± 0.08 logMAR at week 1 and − 0.03± 0.08 logMAR at 12 months after implantation. At 12 months, 137/137 (100%) of eyes achieved BCDVA of 0.3 logMAR or better. Mean ± SD monocular UCDVA was 0.78± 0.40 logMAR preoperatively, 0.11± 0.15 logMAR at week 1, and 0.08± 0.13 logMAR at 12 months after implantation. At 12 months, 132/137 (96%) eyes achieved UCDVA of 0.3 logMAR or better. Serious intraoperative AEs were posterior capsule rupture (n=1) and ciliary zonular dehiscence (n=1). Surgeons reported that the automated preloaded device was more intuitive compared with other push- or screw-style preloaded injector systems. None of the eyes in this study presented surface haze; all were graded as 0 glistenings at all visits. No clinically significant PCO or neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomies were reported.Conclusion: The hydrophobic IOL preloaded in an automated injector system provided good visual and refractive outcomes, as well as no surface haze and grade 0 glistenings. None of the patients required Nd:YAG capsulotomy.Keywords: glistenings, posterior capsular opacification, visual acuity

Recombinant adenoviral vectors (AdV) have been used experimentally as vaccines to present antigenic transgenes in vivo. However, administration of first-generation vectors (FG-AdV) is often limited by their induction of antiviral immunity. To address this limitation, helper-dependent vectors (HD-AdV) were developed that lack viral coding regions. While the administration of HD-AdV results in long-term gene expression in vivo, their utility as immunogens has never been examined. Direct vaccination with 108 blue- forming units (BFU) of HD-AdV injected into C57BL/6 mice lead to superior transgene-specific CTL and antibody responses when compared to the same amount of a FG-AdV. The antibody responses to viral antigens were high in response to both the vectors. As a mechanism to reduce viral exposure, dendritic cells (DC) were transduced with HD-AdV in vitro and then used as a cell-based vaccine. DC transduced with HD-AdV expressed higher levels of transgene-specific mRNA and up to 1200-fold higher levels of transgene protein than did DC transduced with a FG-AdV. In addition, HD-AdV-transduced DC stimulated superior transgene-specific CTL responses when administered in vivo, an effect that was further enhanced by maturing the DC with LPS prior to administration. In contrast to direct immunization with HD-AdV, vaccination with HD-AdV-transduced DC was associated with limited antibody responses against the AdV. We conclude that HD-AdV stimulates superior transgene-specific immune responses when compared to a FG-AdV, and that immunization with a DC-based vaccine maintains this efficacy while limiting antiviral reactivity. [ABSTRACT FROM AUTHOR]

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further. [ABSTRACT FROM AUTHOR]

The milky sap or latex of Euphorbia plant is highly toxic and an irritant to the skin and eye. This report illustrates the spectrum of ocular inflammation caused by accidental inoculation of latex of Euphorbia plant. Three patients presented with accidental ocular exposure to the milky sap of Euphorbia species of recent onset. The initial symptoms in all cases were severe burning sensation with blurring of vision. Visual acuity reduced from 20/60 to counting fingers. Clinical findings varied from kerato-conjunctivitis, mild to severe corneal edema, epithelial defects, anterior uveitis and secondary elevated intraocular pressure. All symptoms and signs had resolved by 10-14 days with active supportive medication. People who handle Euphorbia plants should wear eye protection. It is always advisable to ask the patient to bring a sample of the plant for identification. [ABSTRACT FROM AUTHOR]

To date, degraded mangrove ecosystem restoration accomplished worldwide primarily aligns towards rehabilitation with monotypic plantations, while ecological restoration principles are rarely followed in these interventions. However, researchers admit that most of these initiatives' success rate is not appreciable often. An integrative framework of ecological restoration for degraded mangroves where site-specific observations could be scientifically rationalized, with co-located reference pristine mangroves as the target ecosystem to achieve is currently distinctively lacking. Through this experimental scale study, we studied the suitability of site-specific strategies to ecologically restore degraded mangrove patches vis-à-vis the conventional mono-species plantations in a highly vulnerable mangrove ecosystem in Indian Sundarbans. This comprehensive restoration framework was trialed in small discrete degraded mangrove patches spanning ~ 65 ha. Site-specific key restoration components applied are statistically validated through RDA analyses and Bayesian t-tests. 25 quantifiable metrics evaluate the restoration success of a ~ 3 ha degraded mangrove patch with Ridgeline distribution, Kolmogorov-Smirnov (K-S) tests, and Mahalanobis Distance (D 2 ) measure to prove the site's near-equivalence to pristine reference in multiple ecosystem attributes. This restoration intervention irrevocably establishes the greater potential of this framework in the recovery of ecosystem functions and self-sustenance compared to that of predominant monoculture practices for vulnerable mangroves., (© 2024. The Author(s).)

Introduction: Biological nitrogen fixation (BNF), an unparalleled metabolic novelty among living microorganisms on earth, globally contributes ~88-101 Tg N year -1 to natural ecosystems, ~56% sourced from symbiotic BNF while ~22-45% derived from free-living nitrogen fixers (FLNF). The success of symbiotic BNF is largely dependent on its interaction with host-plant, however ubiquitous environmental heterotrophic FLNFs face many limitations in their immediate ecological niches to sustain unhindered BNF. The autotrophic FLNFs like cyanobacteria and oceanic heterotrophic diazotrophs have been well studied about their contrivances acclimated/adapted by these organisms to outwit the environmental constraints for functional diazotrophy. However, FLNF heterotrophs face more adversity in executing BNF under stressful estuarine/marine/aquatic habitats., Methods: In this study a large-scale cultivation-dependent investigation was accomplished with 190 NCBI accessioned and 45 non-accessioned heterotrophic FLNF cultivable bacterial isolates (total 235) from halophilic estuarine intertidal mangrove niches of Indian Sundarbans, a Ramsar site and UNESCO proclaimed World Heritage Site. Assuming ~1% culturability of the microbial community, the respective niches were also studied for representing actual bacterial diversity via cultivation-independent next-generation sequencing of V3-V4 rRNA regions., Results: Both the studies revealed a higher abundance of culturable Gammaproteobacteria followed by Firmicutes, the majority of 235 FLNFs studied belonging to these two classes. The FLNFs displayed comparable selection potential in media for free nitrogen fixers and iron-oxidizing bacteria, linking diazotrophy with iron oxidation, siderophore production, phosphorus solubilization, phosphorus uptake and accumulation as well as denitrification., Discussion: This observation validated the hypothesis that under extreme estuarine mangrove niches, diazotrophs are naturally selected as a specialized multidimensional entity, to expedite BNF and survive. Earlier metagenome data from mangrove niches demonstrated a microbial metabolic coupling among C, N, P, S, and Fe cycling in mangrove sediments, as an adaptive trait, evident with the co-abundant respective functional genes, which corroborates our findings in cultivation mode for multiple interrelated metabolic potential facilitating BNF in a challenging intertidal mangrove environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mondal, Biswas, Chowdhury, Sengupta, Mandal, Kotal, Giri, Ghosh, Saha, Begam, Mukherjee, Das, Basak, Mitra Ghosh and Ray.)

Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial-mesenchymal transition through inhibition of Snail., Significance: Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Disease and therapy-related hypoproliferative thrombocytopenia is a significant barrier to managing acute lymphoblastic leukaemia (ALL) patients. To reduce the risk of haemorrhage, apheretic platelet transfusion is a modern, effective, and expensive option. Since most ALL patients in Bangladesh have financial constraints, this study can shed light on the magnitude of benefit regarding the effectiveness of apheretic platelet prophylactically and therapeutically in children of ALL receiving induction chemotherapy., Materials and Methods: This observational cross-sectional study was conducted in the department of transfusion medicine and the department of paediatric haematology and oncology at a tertiary level hospital in Bangladesh from June 2020 to June 2021. A total of 33 cases of ALL were enroled in this study according to inclusion and exclusion criteria. After receiving written informed consent, relevant data were collected using a face-to-face interview with the guardian of the patients, thorough clinical examination, and relevant investigation. After the collection of all the required data, analysis was done by Stata (v.16)., Results: Mean age of the patients was 7.39±4.46 (SD), ranging from 1 to 18 years. The majority of children were aged younger than or equal to 10 years (69.70%). Male children were slightly predominant (51.5%). Significant post-transfusion platelet increment (Median pre-transfusion count 16×10 3 /μl vs. Median post-transfusion count 133×10 3 /μl, P <0.001) was observed. WHO bleeding grades also improved after apheretic platelet transfusion ( P <0.05). Age was a significant factor associated with corrected count increment (CCI) in both univariate and multivariate analysis. In subgroup analysis, age and gender were significant predictors of CCI in therapeutic transfusion group but not in prophylactic transfusion group., Conclusions: Significant improvement in bleeding status and platelet count was observed following apheretic platelet transfusion., Competing Interests: The authors have declared that they have no competing interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In the vicinity of the coast, predominantly groundwater is the sole reliable resource for potable purposes as the surface water sources are highly saline and unfit for human consumption. However, the groundwater in Sagar Island is highly vulnerable to saltwater intrusion. The majority of drinking water comes from government-owned hand pump-equipped tube wells. But during the summer season, many of these tube wells yield significantly less water. Hence, in the current scenario, water quality assessment has become important to the quantity available. Total of 31 samples of deep tube wells (groundwater) are collected at variegated locations during pre-monsoon season throughout Sagar, and then, the physical and chemical quality parameters of these water samples are analysed. Furthermore, a multivariate statistical technique is executed with the aid of the SPSS program. The hydro-chemical parameters that are taken into account for the quality analysis are pH, salinity, electrical conductivity (EC), total dissolved solids (TDS), total hardness, aluminium, arsenic, bi-carbonate, cadmium, iron, chloride, copper, chromium, cobalt, lead, magnesium, manganese, nickel, potassium, sulphate, zinc, and sodium. Then, the analysed data evaluates the water quality index (WQI). Five components are identified through the principal component analysis (PCA) technique, and 82.642% total variance is found. The outcomes of the quality assessment study illustrate that about 54.84% of collected samples come in the "excellent" water quality class when calculated by the "weighted arithmetic WQI method," and 90.32% of collected groundwater samples come in the "good" water quality class when computed using the "modified weighted arithmetic WQI method." This study helps for the interpretation of WQI to assess groundwater quality., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bibenzyl derivatives comprising two benzene rings are secondary plant metabolites with significant therapeutic value. To date, bibenzyl derivatives in the Plant kingdom have been primarily identified in bryophytes, orchids, and Cannabis sativa . The metabolic cost investment by plant species for the synthesis of these bioactive secondary metabolites is rationalized as a mechanism of plant defense in response to oxidative stress induced by biotic/abiotic factors. Bibenzyl derivatives are synthesized from core phenylpropanoid biosynthetic pathway offshoots in plant species. Mangrove and mangrove associate species thrive under extreme ecological niches such as a hypersaline intertidal environment through unique adaptive and acclimative characteristics, primarily involving osmotic adjustments followed by oxidative stress abatement. Several primary/secondary bioactive metabolites in mangrove species have been identified as components of salinity stress adaptation/acclimation/mitigation; however, the existence of a bibenzyl scaffold in mangrove species functioning in this context remains unknown. We here report the confirmed detection of a core bibenzyl scaffold from extensive gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses of 28 mangrove and mangrove associate species from the Indian Sundarbans. We speculate that the common presence of this bibenzyl core molecule in 28 mangrove and associate species may be related to its synthesis via branches of the phenylpropanoid biosynthetic pathway induced under high salinity, which functions to detoxify reactive oxygen species as a protection for the maintenance of plant metabolic processes. This finding reveals a new eco-physiological functional role of bibenzyls in unique mangrove ecosystem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sarkar, Kotal, Giri, Mandal, Hudait, Madhu, Saha, Basak, Sengupta and Ray.)

Fuchs endothelial corneal dystrophy (FECD) is an age-related, bilateral corneal condition, characterized by apoptosis of the terminally differentiated endothelial cells. A genome-wide association study (GWAS) conducted in the European population in 2017, identified a new single nucleotide polymorphism (SNP), rs1200114 in the intergenic region between long intergenic non-protein coding RNA 970 (LINC00970) and ATPase Na + /K + transporting subunit beta 1 (ATP1B1). The major focus of the current study is to understand the genetic association of this intergenic variant, rs1200114 with FECD in the Indian population. Sanger sequencing followed by statistical analysis indicated a significant difference in the allelic frequency between controls and cases (P = 0.01) with the minor allele 'G' of rs1200114 imparting a 1.64 fold increased risk for the disease. Luciferase reporter assay revealed no significant difference in the luciferase activity between allele 'A' and 'G' of rs1200114. However, quantitative RT-PCR assay revealed lower expression of ATP1B1 in FECD subjects compared with controls (P = 0.007). Therefore, to find whether another nearby SNP imparts regulatory effect, tag SNP association analysis was carried out; which revealed a significant association of another SNP, rs1200108, present in the intergenic region between LINC00970 and ATP1B1 with FECD (P = 0.009). The protective allele 'A' of rs1200108 displayed reduced reporter activity as opposed to the risk allele 'G' (P = 0.014). Furthermore, haplotype 'A-A' of rs1200108 - rs1200114 was present at a higher frequency in control subjects, suggesting it as a protective haplotype. Altogether, this study inferred the genetic association of rs1200114 and rs1200108 along with the decreased expression of ATP1B1 related to FECD pathogenesis in the Indian population., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Asia's pharmaceutical sector has experienced remarkable growth over the last two decades, with companies in the region producing bulk of the world's specialty generics, biologicals, and active pharmaceutical ingredients (APIs). The Asian pharma growth story has had several pillars for a strong and sustainable foundation that provided non-linear growth. This report introduces three models showing how Asian countries at different development stages - India, South Korea, and Singapore - have nurtured their own, self-sustaining pharmaceutical sectors.

Purpose: The purpose of this study was to report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) using corneas from elderly donors aged 80 years and older., Methods: Eighty eyes of 78 patients who underwent DMEK-only or DMEK combined with cataract extraction (triple-DMEK) with surgeon-prepared graft between April 2016 and March 2020 were reviewed. Corrected distance visual acuity, endothelial cell density (ECD), and endothelial cell loss after 6 months, 1 year, and 2 years were analyzed., Results: The mean donor age was 83.6 ± 3.7 years (range: 80-100 years), and the mean donor ECD was 2889 ± 177 cells/mm 2 (range: 2604-3460 cells/mm 2 ). The mean recipient age was 67.2 ± 6.9 years (range: 60-89 years), and the mean follow-up was 21 ± 11 months (range: 6-52 months). The mean corrected distance visual acuity improved from a preoperative value of 1.36 ± 0.67 logarithm of the minimum angle of resolution to 0.22 ± 0.18 at 6 months (n = 75), 0.21 ± 0.2 at 1 year (n = 64), and 0.23 ± 0.3 logarithm of the minimum angle of resolution at 2 years (n = 41), respectively ( P < 0.001). In 72 eyes (96%), the graft remained transparent until the last follow-up visit. The mean postoperative ECD was 2073 ±336 (n = 75), 1951 ± 379 (n = 65), and 1807 ± 431 cells/mm 2 (n = 41) at 6 months, 1 year, and 2 years, respectively. Five eyes (6.7%) had donor detachments of which 4 required rebubbling. Two grafts failed after 1 year, and 2 eyes (2.6%) had graft rejection, of which 1 eye was reverted successfully by medical management., Conclusions: Cornea from elderly donors aged 80 years and older with good selection criteria may be considered for DMEK with successful outcomes. For India and other countries with unmet tissue needs, every best single cornea counts., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: None

Purpose: The purpose of this study was to report a novel technique of donor lenticule insertion in Descemet stripping endothelial keratoplasty (DSEK) in aphakic corneal edema with large iris defect and without any posterior capsular support., Methods: This was a retrospective consecutive interventional case series. Clinical records of ten 1-eyed aphakic patients with corneal edema with large iris defect and no capsular support who underwent air-assisted donor lenticule insertion in DSEK were evaluated. After making 6.0- to 6.5-mm sclerocorneal tunnel and 2 side ports, limited anterior vitrectomy was performed if required. Then, Descemetorhexis was performed under air through side ports. Manually dissected donor lenticule was inserted into the anterior chamber under full-chamber air by a 30-G needle push-in technique. Further air tamponade was given if necessary. No fluid-air exchange was performed. The patient was kept on the same operating table for at least 1 hour and then shifted. Graft attachments in early postoperative period, corrected distant visual acuity, and endothelial cell density after 3, 6, and 12 months were analyzed., Results: The mean postoperative follow-up period was 19.2 ± 6.7 months. There was no donor dislocation in this small group. All patients achieved a corrected distant visual acuity of 0.70 (20/100) after 3 months and maintained until 12 months. The endothelial cell density at 3 months (n = 8) was 2028 ± 151/mm 2 , at 6 months (n = 7) 1776 ± 198/mm 2 , and at 12 months (n = 7) 1721 ± 172/mm 2 . The corresponding endothelial cell loss was 25.8% ± 5.6%, 34.4% ± 5.1%, and 37.8% ± 7.1%, respectively. One graft failed after 15 months., Conclusions: "Air-assisted" donor lenticule insertion in DSEK is a safe surgical technique in aphakic patients with corneal edema with large iris defect and no capsular support., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Liquid biopsies are gaining more traction as non-invasive tools for the diagnosis and monitoring of cancer. In a new paradigm of cancer treatment, a synergistic botanical drug combination (APG-157) consisting of multiple molecules, is emerging as a new class of cancer therapeutics, targeting multiple pathways and providing a durable clinical response, wide therapeutic window and high level of safety. Monitoring the efficacy of such drugs involves assessing multiple molecules and cellular events simultaneously. We report, for the first time, a methodology that uses circulating plasma cell-free RNA (cfRNA) as a sensitive indicator of patient response upon drug treatment. Plasma was collected from six patients with head and neck cancer (HNC) and four healthy controls receiving three doses of 100 or 200 mg APG-157 or placebo through an oral mucosal route, before treatment and on multiple points post-dosing. Circulating cfRNA was extracted from plasma at 0-, 3- and 24-hours post-treatment, followed by RNA sequencing. We performed comparative analyses of the circulating transcriptome and were able to detect significant perturbation following APG-157 treatment. Transcripts associated with inflammatory response, leukocyte activation and cytokine were upregulated upon treatment with APG-157 in cancer patients, but not in healthy or placebo-treated patients. A platelet-related transcriptional signature could be detected in cancer patients but not in healthy individuals, indicating a platelet-centric pathway involved in the development of HNC. These results from a Phase 1 study are a proof of principle of the utility of cfRNAs as non-invasive circulating biomarkers for monitoring the efficacy of APG-157 in HNC., Competing Interests: PM and LA are employees of Aveta Biomics Inc, which provided partial funding for the current study, and have a patent pending for Polypharmaceutical Drug Compositions and Related Methods. PM and LA had no role in the recruitment of the subjects and collection and analysis of the samples. All authors were blinded to the study and its results until the study was completed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tosevska, Morselli, Basak, Avila, Mehta, Wang, Srivatsan and Pellegrini.)

Purpose: The purpose of this study was to describe a novel bandage contact lens (BCL) interface technique for marking the Descemet membrane endothelial keratoplasty (DMEK) graft so that a single donor cornea can be used effectively for 2 recipients during acute shortage., Methods: This was a retrospective comparative case series. In group A, 37 eyes underwent DMEK using a graft marked by the ‟BCL interface technique" that was compared with 49 conventional DMEK grafts marked through the stromal window (group B). In group A, a resized BCL with a central 3-mm hole with the concavity up was placed between the stroma and peeled-off DM. This BCL with DM was flipped for S-stamping on the DM side. Final trephination was performed on a second Teflon block. The remaining anterior lamellar tissues of group A were used on the same day for other keratoplasty procedures. Endothelial cell density (ECD) and endothelial cell loss between the 2 groups were compared after 3 and 6 months., Results: The ECD at 3 months in group A (n = 35) versus group B (n = 45) was 2228 ± 270/mm2 versus 2302 ± 254/mm2 (P = 0.48), and the ECD at 6 months (n = 23 and 22) was 2058 ± 324/mm2 versus 2118 ± 260/mm2 (P = 0.72). The corresponding endothelial cell loss was 23.3% ± 6.8% versus 20.3% ± 6.1% (P = 0.18) at 3 months and 29.1% ± 8.4% versus 26.7% ± 8.0% (P = 0.34) at 6 months. Among anterior tissues of group A, 17 (45.9%) were used for deep anterior lamellar keratoplasty, 18 (48.6%) were used for larger therapeutic and tectonic grafts, and 2 were used as keratoprosthesis carriers. Donor detachment rate (8.6% vs. 8.9%) was similar in both groups without primary graft failures., Conclusions: The BCL interface technique is a simple and safe technique for stamping DMEK grafts. Anterior corneal tissues can be used for additional keratoplasties during donor shortage., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys 382 -p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G 1 -S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (Published in the U.S.A.)

Mass mortalities of the larval stage of the giant freshwater prawn, Macrobrachium rosenbergii , have been occurring in Bangladesh since 2011. Mortalities can reach 100% and have resulted in an 80% decline in the number of hatcheries actively producing M. rosenbergii . To investigate a causative agent for the mortalities, a disease challenge was carried out using infected material from a hatchery experiencing mortalities. Moribund larvae from the challenge were prepared for metatranscriptomic sequencing. De novo virus assembly revealed a 29 kb single‑stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. Primers were designed against the novel virus and used to screen cDNA from larvae sampled from hatcheries in the South of Bangladesh from two consecutive years. Larvae from all hatcheries screened from both years were positive by PCR for the novel virus, including larvae from a hatchery that at the point of sampling appeared healthy, but later experienced mortalities. These screens suggest that the virus is widespread in M. rosenbergii hatchery culture in southern Bangladesh, and that early detection of the virus can be achieved by PCR. The hypothesised protein motifs of Macrobrachium rosenbergii golda virus (MrGV) suggest that it is likely to be a new species within the Nidovirales order. Biosecurity measures should be taken in order to mitigate global spread through the movement of post-larvae within and between countries, which has previously been linked to other virus outbreaks in crustacean aquaculture.

Competing Interests: None

Competing Interests: None

Purpose: To analyze the overall clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) in 600 consecutive cases., Methods: Retrospective, consecutive interventional case series operated by a single surgeon. Six hundred consecutive eyes of 524 patients with endothelial dysfunctions of different etiologies scheduled for DMEK were included in this study. All donor tissues were prepared by the operating surgeon during the procedure, using McCarey Kaufman medium or Cornisol-preserved cornea with endothelial cell density (ECD) of ≥2500 cells/mm 2 . Indications, postoperative best spectacle-corrected visual acuity (BSCVA), ECD, endothelial cell loss (ECL), and complications were analyzed postoperatively between 3 months and 2 years., Results: The commonest indication was post-cataract corneal edema/bullous keratopathy in 262 (43.7%) eyes followed by Fuchs' endothelial corneal dystrophy 218 (36.3%). Vision affected comorbidities were present in 91 (15.2%) eyes. In phakic eyes with cataract (222; 37%), DMEK was combined with cataract surgery (Triple-DMEK). BSCVA of ≥20/25 was achieved in 41.0%, 46.4%, 49.2%, and 48.7% of eyes at 3, 6, 12, and 24 months, respectively and stabilized at 6 months (P = 0.54). Mean ECD decreased from 2884 ± 178 cells/mm 2 (n = 600) before surgery to 2223 ± 321 (n = 597), 2099 ± 354 (n = 524), 1918 ± 373 (n = 374), and 1772 ± 439 cells/mm 2 (n = 158) at 3, 6, 12, and 24 months respectively. The corresponding mean ECL was 22.9 ± 11.4%, 27.2 ± 12.4%, 33.5 ± 13.0%, and 38.6 ± 14.3%, respectively (P < 0.05 for all-time points). The commonest complication was DM detachment in 59 (9.8%) eyes of which 23 (3.8%) eyes required rebubbling. Three (0.5%) eyes had primary graft failure. Endothelial rejection occurred in 7 (1.2%) eyes until the last follow-up., Conclusion: DMEK is a safe and effective procedure in different types of endothelial diseases with encouraging surgical and clinical outcomes. Complications are less and ECL percentage up to 2 years is acceptable., Competing Interests: None

A procedure is described to measure curcumin (C), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumim (TC) and their glucuronidated metabolites (CG, DMCG, and BDMCG) in plasma, brain, liver and tumor samples. The procedure involves converting the analytes to their boron difluoride derivatives and analyzing them by combined liquid chromatography coupled to an ion trap mass spectrometer operating in the negative ion MS n scan mode. The method has superb limits of detection of 0.01 nM for all curcuminoids and 0.5 nM for TC and the glucuroniated metabolites, and several representative chromatograms of biological samples containing these analytes are provided. In addition, the pharmacokinetic profile of these compounds in one human who daily consumed an over-the-counter curcuminoid product shows the peak and changes in circulating concentrations achieved by this mode of administration., (Copyright © 2020. Published by Elsevier Inc.)

Sundarbans mangrove forest, the world's largest continuous mangrove forests expanding across India and Bangladesh, in recent times, is immensely threatened by degradation stress due to natural stressors and anthropogenic disturbances. The degradation across the 19 mangrove forests in Indian Sundarbans was evaluated by eight environmental criteria typical to mangrove ecosystem. In an attempt to find competent predictors for mangrove ecosystem degradation, key eco-physiological resilience trait complex specific for mangroves from 4922 individuals for physiological analyses with gene expression and 603 individuals for leaf tissue distributions from 16 mangroves and 15 associate species was assessed along the degradation gradient. The degradation data was apparently categorized into four and CDFA discriminates 97% of the eco-physiological resilience data into corresponding four groups. Predictive Bayesian regression models and mixed effects models indicate osmolyte accumulation and thickness of water storage tissue as primary predictors of each of the degradation criteria that appraise the degradation status of mangrove ecosystem. RDA analyses well represented response variables of degradation explained by explanatory resilience variables. We hypothesize that with the help of our predictive models the policy makers could trace even the cryptic process of mangrove degradation and save the respective forests in time by proposing appropriate action plans.

Background: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target., Methods: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity., Results: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment., Conclusions: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy., Lay Summary: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs., (© 2020 American Cancer Society.)

Purpose: To evaluate the clinical outcomes and endothelial cell density (ECD) after Descemet membrane endothelial keratoplasty using peripherally trephinated donor tissue (DMEK-pD) and compare with DMEK using centrally trephinated donor tissue (DMEK-cD) in patients with Fuchs endothelial corneal dystrophy (FECD)., Methods: This was a prospective comparative interventional case series. One hundred twenty-five eyes of 110 patients with FECD and cataract who underwent either DMEK-pD (n = 60) or DMEK-cD (n = 65) combined with phacoemulsification, between June 2016 and November 2018, were included. Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA) and ECD were recorded at 6 months and 1 year., Results: All eyes had visually symptomatic FECD and cataract with a preoperative mean BSCVA of 1.03 logarithm of the minimum angle of resolution in both groups. Baseline donor mean ECD was 2944 ± 201 and 2907 ± 173 cells/mm in the DMEK-pD and DMEK-cD groups, respectively (P = 0.12). BSCVA improvement was comparable at 6 months and 1 year (P = 0.23 and P = 0.34). Mean ECD recorded after 6 months and 1 year was significantly higher in the DMEK-pD group than in the DMEK-cD group: 2508 ± 201 versus 2084 ± 298 cells/mm (P < 0.01) and 2338 ± 256 versus 1907 ± 339 cells/mm (P < 0.01), respectively. Complication rates were similar in both groups., Conclusions: DMEK-pD exhibited similar clinical outcomes with higher ECD compared with conventional DMEK-cD after 6 months and 1 year. The possibility of transplanting peripherally trephinated donor tissue in DMEK with more endothelial cells needs to be explored further in the future.

Purpose: To report the clinical outcome and postoperative course of Descemet membrane endothelial keratoplasty (DMEK) in irreversible corneal edema due to herpes simplex virus (HSV) endotheliitis., Methods: This is a retrospective, noncomparative, interventional case series. Nineteen eyes of 19 patients underwent standard DMEK combined with cataract surgery (triple DMEK) between May 2016 and April 2018. All patients received perioperative oral acyclovir (ACV) and prednisolone. Patients were followed up on day 1, on day 7, at 1 month, and then at 3 monthly intervals. Preoperative and postoperative best spectacle-corrected visual acuity (BSCVA), graft clarity, pachymetry, and endothelial cell loss after 1 year were recorded. Postoperative complications and HSV recurrence were noted until the last follow-up visit., Results: All eyes were phakic with variable grades of cataract with a preoperative BSCVA of 1.0 logarithm of the minimum angle of resolution or worse. The mean follow-up period was 19.3 ± 5.4 months. After 1 year, 14 (73.7%) eyes achieved a BSCVA of 0.3 or better. Seventeen (89.5%) patients had a clear graft at the last visit without any rejection episode. One graft failed after 16 months. After 3 months, the mean pachymetry reduced from 667.1 ± 62.1 to 512.8 ± 27.1 μm (P < 0.001). The mean endothelial cell loss after 1 year was 36.7 ± 13.4%. Three (15.8%) eyes had recurrence: one with recurrent endotheliitis and 2 with dendritic keratitis despite oral ACV, which responded to oral valacyclovir and ACV eye ointment. One patient had re-recurrence of endotheliitis after 20 months., Conclusions: DMEK in persistent corneal edema after HSV endotheliitis remains challenging but has encouraging outcomes. The postoperative course may be complicated by HSV recurrence. Prophylactic oral antivirals for 1 year or more and topical antivirals are useful for the prevention of recurrence.

Conjunctival stromal tumour (COST) is a recently described rare conjunctival tumour of mesenchymal origin with only four publications describing a handful of cases thus far. In this report, we describe the anterior-segment optical coherence tomography (AS-OCT) characteristics in a case of COST for the first time, in addition to the clinical and histopathological characteristics. The AS-OCT showed an elevated, dome-shaped hyporeflective homogenous lesion in the conjunctival stroma lined by hyperreflective outer layer with mild posterior shadowing, consistent with histological description of a paucicellular tumour with large myxoid collagenous material inside. Immunohistochemistry showed positive CD34 and vimentin but negative S100 and smooth muscle actin, thereby differentiating it from conjunctival myxoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Recurrence of herpes simplex virus (HSV) keratitis is a problem of keratoplasty and the prognosis is often poor in spite of oral acyclovir (ACV) prophylaxis. This 64-year-old woman was a known case of recurrent HSV endotheliitis with irreversible corneal oedema in the left eye for 2 years. She underwent Descemet membrane endothelial keratoplasty with intraocular lens implantation under perioperative oral ACV and prednisolone. After 4 weeks, her cornea cleared with the best-corrected vision of 6/9. After 2.5 months, she presented with sudden photophobia and visual loss. An increasing focal endothelial lesion was noticed even after oral ACV. Suspecting fungal interface infection, anterior chamber tap was done for PCR for panfungal and viruses. It was only positive for HSV. Oral ACV was changed to oral valacyclovir. The patient responded dramatically within 2 weeks, and after 12 weeks, the lesion disappeared completely, leaving behind a faint scar with 6/9 p vision. Oral valacyclovir, a prodrug of ACV, may work better than oral ACV., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To report the outcomes of the Boston type I keratoprosthesis (KPro) as the primary penetrating corneal procedure., Methods: In this retrospective review of all KPro procedures performed by 2 surgeons from May 1, 2004, to December 31, 2015, indications and outcomes were compared between KPros performed as the primary keratoplasty procedure (primary KPro) versus after failed keratoplasty (previous keratoplasty)., Results: A total of 262 KPros were implanted in 231 eyes, including 67 primary KPro procedures. The most common indications for primary KPros were corneal scarring/vascularization (43%), Stevens-Johnson syndrome (22%), and chemical/thermal injury (22%). Although preoperative corrected distance visual acuity (CDVA) was similar in the 2 groups (P = 0.36), a significantly higher proportion of the eyes in the primary KPro group had a CDVA ≥ 20/200 each of the first 4 years after surgery (all P ≤ 0.023). The most common postoperative complications in the primary KPro and previous keratoplasty groups were retroprosthetic membrane (40% vs. 51%, P = 0.15), persistent epithelial defect (37% vs. 24%, P = 0.05), and elevated intraocular pressure, which was the only complication significantly more common in either group (31% vs. 18%, P = 0.03). No difference in KPro retention was observed between the 2 groups (P = 0.63)., Conclusions: In the setting of preexisting ocular comorbidities in which PK is associated with poor outcomes and KPros have been associated with an increased incidence of postoperative complications, primary KPro is associated with significantly greater % of eyes with CDVA ≥ 20/200 in the first 4 years. However, given a significantly higher incidence of postoperative intraocular pressure elevation in these eyes, longer follow-up is needed to determine whether the difference in CDVA is maintained.

Background: Descemet Membrane Endothelial Keratoplasty (DMEK) is now becoming the popular form of endothelial keratoplasty using only donor DM with healthy endothelium as true component lamellar corneal surgery., Objective: To analyze the results of visual outcomes, endothelial cell loss and complications of Descemet membrane endothelial keratoplasty in first consecutive 100 Indian eyes., Methods: 100 eyes of 95 consecutive patients with endothelial dysfunctions of different etiologies scheduled for DMEK, were included in this study. In each case, surgeon prepared tissue using McCarey Kaufman medium- or Cornisol-preserved donor cornea with a cell count of ≥2500 cells/mm 2 . Surgical complications, Best Spectacle Corrected Visual Acuity (BSCVA); Endothelial Cell Density (ECD) and Endothelial Cell Loss (ECL) were analyzed for each patient after a minimum follow-up of three months., Results: The Main indication was pseudophakic corneal edema or bullous keratopathy in 52 (52%) eyes. 38 (38%) eyes had Fuchs' dystrophy with various grades of cataract. In 43 phakic eyes, DMEK was combined with cataract surgery and intraocular lens implantation. Mean DM-roll preparation time was 7.5 ± 2.8 min and in 3 eyes, DM-graft were damaged. After 3-months, BSCVA was ≥20/25 in 57 (57.6%) cases. Mean ECD was 2123 ± 438/mm 2 (range: 976 - 3208/ mm 2 ) and the mean endothelial cell loss after 3-months was 26.92 ± 13.40 (range: 4.90 - 66.6%). Partial DM detachment occurred in 8 (8.0%) eyes and rebubbling required in 4 eyes. Iatrogenic primary graft failure occurred in one eye., Conclusion: Descemet membrane endothelial keratoplasty is a safe and effective procedure in several types of endothelial diseases among Indian patients with encouraging surgical and visual outcomes. Complications are less and endothelial cell loss percentage is acceptable.

Diseases have been recognized as the major obstacle to the shrimp ( Penaeus monodon ) and prawn ( Macrobrachium rosenbergii ) aquaculture production in Bangladesh. This study provides an assessment of shrimp and prawn diseases/syndromes, health management practices, and occupational health hazards associated with the handling of chemical and biological products to prevent and treat shrimp and prawn diseases. A survey was conducted using a semi-structured questionnaire with 380 shrimp and prawn farmers in the southwest of Bangladesh during February and June of 2016. The farms were categorized on the basis of the three cropping patterns: shrimp polyculture, prawn polyculture, and shrimp and prawn polyculture. Eight different diseases and/or symptoms were reported by the surveyed farmers. The white spot disease and the broken antenna and rostrum symptom were the most common in shrimp and prawn species, respectively. In total, 35 chemical and biological products (4 antibiotics, 15 disinfectants, 13 pesticides, 2 feed additives and probiotics) were used to treat and/or prevent diseases in the all farm categories. The major constraints for disease management were limited access to disease diagnostic service, inadequate product application information and lack of knowledge on better management practices. Handling chemicals and preparation of medicated feed with bare hands was identified as a potential occupational health hazard. This study suggests improvements in farmers' knowledge and skill in disease diagnostics and health management practices, and appropriate handling of potentially hazardous chemicals., (© 2018 The Authors.)

Purpose: To compare the serology profile of donors from Hospital Cornea Retrieval Programme-donors (HCRP-D) and voluntary cornea donors (VC-D) from a large eye bank in Eastern India., Methods: This is a retrospective analysis of donor details from January 2011 to December 2016. Donor demographics, cause of death, and serology reports were compiled. Postmortem blood was tested for human immunodeficiency virus 1 and 2 (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis using government-approved kits as per the National Programme for Control of Blindness Standards of Eye Banking. Donors for whom serology was not possible were excluded., Results: A total of 4300 of 4353 donors were included of which 74.3% were hospital donors and 25.7% were voluntary donors. A total of 93 (2.2%) donors with 94 seropositive reports were noted: 79 (84.9%) from HCRP-D and 14 (15.1%) from VC-D which was statistically significantly higher (P = 0.02). Among seropositive reports, HIV, HBV, HCV, and syphilis accounted for 12 (12.8%), 38 (40.4%), 36 (38.3%), and eight (8.5%), respectively. There was no correlation between the cause of death and seropositivity. A statistically significant decreasing trend in seroprevalence among hospital donors was observed over the years (5.3% in 2011 to 1.4% in 2016; P = 0.004). Two (0.47%) of 421 hospital donors with prior negative serology were found to be seropositive., Conclusion: Seropositive rates are significantly higher among hospital donors in spite of medical prescreening compared to nonscreened voluntary donors. Serology should be repeated even when prior reports are available.

PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.

Purpose: To know the perception of young ophthalmologists about their dissertation and academics during residency training in order to improve the research output during present residency programs in India., Methods: A survey was conducted by Academic and Research Committee of the All India Ophthalmological Society, the world's second largest ophthalmic professional's organization, in 2014-2016 of young ophthalmologists (those who completed residency between 2005 and 2012) to gauge usefulness of dissertation or thesis during postgraduate residency., Results: There were 1005 respondents, of whom 531 fulfilled inclusion criteria. On a scale of 0-10, residents rated level of supervision of their dissertation as adequate (mean 5.9/10, standard deviation [SD] = 3.1, median = 6). The level of infrastructure available was for dissertation rated as 5.9/10 (median = 7, SD = 3.1), and 6.2/10 was the score that residents said about value added by the dissertation (median = 7). The dissertation was presented at local (33.5%), state (28.1%), national (15.4%), and international (4%) levels. Students, not supervisors, did most of the local and state level presentations. It was published in some forms at local 210 (39.5%), state (140, 26.4%), national (94, 17.7%), and international (39, 7.3%) levels. On a scale of 0-4, seminars (3/4) and case presentations were (3/4) rated higher than didactic lectures (2.2/4), journal clubs (2.2/4), and wet laboratory (1.1/4)., Conclusion: Peer-reviewed publications from Indian residency training dissertations were few. Residents felt dissertation added value to their training, but there was a huge range among the responses. Journal clubs and wet laboratories were not graded high in academic programs, unlike seminars and case presentations.

We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKβ) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Purpose: To determine the factors influencing outcomes of Boston type I keratoprosthesis implantation in Stevens-Johnson syndrome (SJS) and to compare the results with those of individuals without SJS., Methods: This is a multicenter, retrospective, comparative consecutive case series of patients undergoing keratoprosthesis implantation in Los Angeles, Kolkata, and Manila. Statistical analysis was performed to identify significant differences in visual acuity, complications, and retention between SJS and non-SJS populations., Results: A total of 234 keratoprosthesis procedures were performed in 209 eyes, including 40 performed in 27 eyes of 26 patients with SJS. Procedures in patients with SJS were more frequently performed as repeat keratoprostheses (33% vs. 8%, P < 0.001) but less frequently in eyes with glaucoma (26% vs. 71%, P < 0.001) or multiple previous keratoplasties (15% vs. 59%, P < 0.001). A significantly greater percentage of individuals with SJS had a corrected distance visual acuity ≥20/200 12 months after surgery compared with individuals without SJS (100% vs. 67%, P = 0.002). Several postoperative complications were more common in SJS, including corneal stromal necrosis (59% vs. 8%, P < 0.001), corneal infiltrates (30% vs. 10%, P = 0.009), and persistent corneal epithelial defects (59% vs. 24% P < 0.001), which led to a higher retention failure rate (0.306/eye-year vs. 0.068/eye-year, P < 0.001) and secondary surgical procedures. However, after repeat implantation, eyes with SJS were no less likely to ultimately retain a keratoprosthesis (82% vs. 89%, P = 0.34)., Conclusions: The Boston type I keratoprosthesis is an effective means to restore vision in individuals with SJS. Although retention failure and several postoperative complications are more common in SJS, sight-threatening complications such as endophthalmitis and retinal detachment are not.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with 600,000 new cases every year worldwide. Although chemotherapeutics exist, five-year survival is only 50%. New strategies to overcome drug resistance are required to improve HNSCC treatment. Curcumin-difluorinated (CDF), a synthetic analog of curcumin, was packaged in liposomes and used to evaluate growth inhibition of cisplatin resistant HNSCC cell lines CCL-23R and UM-SCC-1R generated from the parental cell lines CCL-23 and UM-SCC-1 respectively. Growth inhibition in vitro and expression levels of the CD44 (cancer stem cell marker), cytokines, and growth factors were investigated after liposomal CDF treatment. The in vivo growth inhibitory effect of liposomal CDF was evaluated in the nude mice xenograft tumor model of UM-SCC-1R and the inhibition of CD44 was measured. Treatment of the resistant cell lines in vitro with liposomal CDF resulted in a statistically significant growth inhibition (p < 0.05). The nude mice xenograft study showed a statistically significant tumor growth inhibition of UM-SCC-1R cells and a reduction in the expression of CD44 (p < 0.05), indicating an inhibitory effect of liposomal CDF on CSCs. Our results demonstrate that delivery of CDF through liposomes may be an effective method for the treatment of cisplatin resistant HNSCC.