Differential Effect of Proinflammatory Cytokines on Corneal and Conjunctival Epithelial Cell Mucins and Glycocalyx

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells. Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). The glycocalyx was imaged using confocal microscopy after staining with Alexa 488-conjugated wheat germ agglutinin lectin. Apoptotic and necrotic cell death was quantified using flow cytometry. Results: IL-6, TNF-α, and IFN-γ treatment resulted in a significant increase in mucins (MUC)1 and MUC4 gene and protein expression in human corneal epithelial cells but caused no significant changes in the levels of these mucins in conjunctival epithelial cells. Further, these cytokines decreased MUC16 expression in both corneal and conjunctival epithelial cells. Moreover, no notable change in glycocalyx or apoptotic cell death in corneal and conjunctival epithelial cells was noted with any of the tested cytokines, but IL-6 and TNF-α exposure increased necrotic cell death in corneal and conjunctival epithelial cells, respectively. Conclusions: Our results demonstrate that proinflammatory cytokines have differential effects on human corneal and conjunctival epithelial cell mucins expression, but do not cause any damage to ocular surface epithelial cell glycocalyx

A rare case of ruptured ovarian ectopic pregnancy

An ovarian ectopic pregnancy is a rare presentation. A 31 years old female presented with acute abdomen at period of gestation 8 weeks. Ultrasonography showed complex mass in Rt. adnexa of size of 6.32x3.80 cm. Emergency laparotomy was done under general anaesthesia and ruptured right ovary found. Right salpingo-oophrectomy and left tubectomy was done. The histopathological examination confirmed the ovarian ectopic pregnancy.

Pfam: clans, web tools and services

Pfam is a database of protein families that currently contains 7973 entries (release 18.0). A recent development in Pfam has enabled the grouping of related families into clans. Pfam clans are described in detail, together with the new associated web pages. Improvements to the range of Pfam web tools and the first set of Pfam web services that allow programmatic access to the database and associated tools are also presented. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://pfam.cgb.ki.se/)

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Silicon-on-insulator, free-spectral-range-free devices for wavelength-division multiplexing applications

Silicon-on-insulator (SOI) microring resonator (MRR)-based modulators and filters have been researched extensively for use in wavelength-division multiplexing (WDM) systems due to their attractive spectral characteristics and small device footprints. However, an inherent drawback of using MRRs in WDM systems is their free-spectral-ranges (FSR). The FSR limits the aggregate data rate of the system, as it limits the number of channels that can be selectively modulated in a WDM transmitter, or simultaneously de-multiplexed in a WDM receiver. The goal of this thesis is to present and demonstrate SOI, MRR-based modulators and filters with FSR-free responses. We first experimentally demonstrate an SOI, FSR-free, MRR-based filter with a reconfigurable bandwidth. The device uses a grating-assisted coupler integrated into the MRR cavity to achieve an FSR-free response. Here, we demonstrate a nonadjacent channel isolation, for 400-GHz WDM, greater than 26.7 dB. A thermally tunable coupling scheme is utilized to compensate for fabrication variations and to demonstrate the reconfigurable filter bandwidth. We then demonstrate how lithography effects affect the performance of SOI devices, which include grating-based components. Using lithography models developed for deep ultraviolet lithography processes, we analyze the effects of lithography on the performance of an MRR with an integrated, grating-assisted coupler. We show that, if the effects of lithography are not taken in account during device design flow, large discrepancies result between the predicted “as fabricated” and “as-designed” device performance. We also demonstrate how to use the lithography models to compensate for lithographic-effects in future device designs. Lastly, we experimentally demonstrate an FSR-free, MRR-based, coupling modulator. We demonstrate open eye diagrams at 2.5 Gbps and discuss how the effects of DUV lithography limited the electro-optic bandwidth of the fabricated modulator to 2.6 GHz. We also discuss the effects of lithography on the modulation crosstalk of the device and how to significantly improve the electro-optic bandwidth and how to minimize crosstalk in future implementations of the device.Applied Science, Faculty ofElectrical and Computer Engineering, Department ofGraduat

An investigation into sustainable patio heating solutions for Koerner’s Pub UBC

The University of British Columbia (UBC) strives to be a global leader in campus sustainability. Koerner’s Pub, a well-established pub and restaurant on campus, is committed to improve its reputation as a sustainable and eco-friendly establishment. To fulfill this goal, Koerner's is investigating possible solutions to contribute to the environmentally conscious mentality that UBC is world renowned for. This report will outline the investigation into the financial, environmental and social aspects of the implementation of a new energy efficient patio heating system at Koerner’s Pub. By implementing a sustainable patio heating system, Koerner's could extend their outdoor season thereby increasing capacity, improving their brand and attracting more customers and events during the winter and fall months. The purpose of this report is to provide a Triple Bottom Line assessment (TBL) that will advise the stakeholder, Tim Yu, how Koerner’s Pub can implement a sustainable, cost-effective and socially viable patio heating system. Several onsite visits to Koerner's Pub were conducted to gain a comprehensive understanding of the present patio heating situation. Currently, there are three forms of heating being used in the patio area: propane stand-alone heaters (mushroom design), an infrared heater as well as an inherited electric filament heater. Various surveys and meetings with local restaurants proved that propane heaters were the most popular choice and thus using them as a benchmark, alternatives were researched that were more efficient, eco-friendly and cost effective. To research alternative heaters using a TBL assessment, the economic, environmental and social impacts of each heater had to be considered. After narrowing down the preferences to infrared electric, infrared natural gas and propane mushroom heaters, the following summary shows how it was concluded that implementing a system of infrared electric heaters would be the best choice: Economic: Low overhead costs and utility expenses are included in the pub’s lease agreement. Environmental: No fossil fuels are burned leading to almost zero carbon emissions during operation. Social: No operating maintenance is required and each heater is portable as extension cords are safer to route around the patio area, as compared to natural gas lines and propane tanks. The subsequent areas of this report will go into detail regarding the environmental, financial and social aspects of procuring a suitable heating system for the Koerner's Pub patio area. Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Applied Science, Faculty ofUnreviewedUndergraduat