Societal impact of increasing the visibility of women in biomedical and clinical research

Gender disparity between men and women has been brought to light recently, highlighting inequalities within the fields of medicine and academia. Achieving equality within these professions is beneficial not only to women but for medicine, research, and patients. Diversity in fields of practice ensures a variety of thought, innovation, stronger teams and better outcomes for all. Women are less likely to be recognised as experts and leaders, with fewer women speaking at national medical conferences, receiving prestigious awards, being promoted or holding leadership roles. This article presents the societal impacts based on outcomes from several sources, including our recent research exploring gendered transitions experienced by female surgeons, our recent women's conference and best practices from industry and the university sector aimed at addressing the barriers faced by women in academic and clinical medicine. The main societal impacts include (i) increasing awareness of gender disparity through knowledge transfer, (ii) improving representation and advancement opportunities for Women, and (iii) developing partnerships to achieve and promote equity.</p

Optimising the method for isolating ocular surface microRNA using impression cytology

Conjunctival impression cytology (CIC) has evolved as a reliable method for obtaining superficial epithelial cells from the ocular surface in comparison to more invasive harvesting techniques such as brush cytology, smears and biopsies. Its use in research has played a critical role in adding to our understanding of ocular surface pathology and as its molecular applications broaden, it may facilitate the development of targeted therapies and personalised medicine in the future </p

Relationship between clinical parameters and quality of life in primary Sjögren's Syndrome: a prospective study

Objectives: To quantify the impact of dry eye disease (DED) on health and vision related quality of life (HR-QOL, VR-QOL) in patients with Primary Sjögren's Syndrome (pSS). Methods: Thirty-four participants with a confirmed diagnosis of pSS as per the 2016 ACR EULAR criteria participated. Main outcome measures included ocular surface parameters and HR-QOL and VR-QOL questionnaires. Clinical examination included visual acuity, Schirmer I testing, ocular surface staining (OSS) and measurement of tear film breakup time. The questionnaires included Ocular Surface Disease Index, National Eye Institute Visual Function Questionnaire-25, Short Form-36 (SF-36) and EULAR Sjogren's Syndrome Patient Reported Index. Results: Despite the majority of participants (28 female, 6 male, mean age 61.3 years) having attained LogMAR 0.3 or better visual acuity, participants scored low on VR-QOL measures, representing DED related fluctuation in functional vision. All participants suffered from moderate to severe DED. OSS did not correlate with DED symptoms or QOL parameters. Lubricant usage and symptom severity had a statistically moderate to strong negative correlation with VR-QOL and HR-QOL. This was most evident in relation to physical and physiological wellbeing. Compared with normative data, participants had a lower HR-QOL in all scales of the SF-36 ((MD = 9.91 ± 5.16); t(7) = 5.43, p = 0.001). Conclusions: Participants with pSS have a lower perceived QOL especially in relation to physical and mental wellbeing, correlating to severity of DED symptoms and treatment burden. Clinical signs do not align with symptoms. Therefore, clinicians should remain cognisant, adjusting treatment in accordance with patient reported perceptions.</p

Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study

Background: Sjögren’s (“SHOW-grins”) is a chronic debilitating autoimmune disease characterised by dry eyes and dry mouth, secondary to reduced exocrine function of both the lacrimal and salivary glands. The persistent, severe and serious systemic complications of Sjögren’s are poorly understood and often unappreciated, resulting in significant morbidity and treatment burden. This study aimed to explore experiences of those living with Sjögren’s, specifically access to healthcare and attitude towards telemedicine. Additionally, we sought to collect information regarding the impact of the pandemic on their quality of life (QoL). Methods: Attendees (n=194) of an Irish Sjögren’s Webinar were invited to participate in two online surveys. The first survey gathered information related to demographics, disease, and experiences during the COVID-19 pandemic. A combination of bespoke items and validated questionnaires (EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), COV19-QoL) was used. The second survey consisted of a shortened Telehealth Usability Questionnaire. Both were prepared in collaboration with a patient advocate. Results: Survey 1: n=76; response rate=39.2%. Thirty-one respondents (41.4%) to Survey 1 reported a delay of ≥5 years between the onset of symptoms and diagnosis. Dry mouth was the most common symptom experienced (76.8% n=63), followed by dry eye (74.4% n=61), fatigue (57.3%, n=47) and joint pain (53.7% n=44), but a range of other symptoms were also reported. COV19-QoL results indicated that the pandemic had a detrimental effect on participants’ overall QoL (4.0 ± 1.0) and physical health (4.0 ± 0.8) in particular. COV19-QoL and ESSPRI scores were moderately correlated (0.36, p=0.002). Over 70% of respondents had a medical appointment cancelled, delayed or rescheduled (n=60). Survey 2: n=57; response rate=29.4%. Those that had interacted with telemedicine reported largely positive experiences with the virtual model. Conclusion: Clinicians should be aware of the range of symptoms experienced by patients with Sjögren’s beyond those of sicca and fatigue. COVID-19 has negatively influenced the self-reported health and well-being of those with Sjögren’s, particularly those with higher symptom scores. It is vital that optimised telemedicine models are implemented to ensure continuity in the provision of healthcare for those with chronic illness such as Sjögren’s and in preparation for possible future pandemics. Patient or Public Contribution: A group of people living with Sjögren’s co-designed the structure and content of the webinar where the survey was shared. A PPI contributor also collaborated in the selection of questionnaires used in the study ensuring that the questions asked would best reflect the priorities of patients. They contributed to the writing of this manuscript as co-authors. Additionally, the research team and Sjögren’s patients who contributed to this work have gone on to establish Sjögren’s Research Ireland, a collaboration between patient advocates, researchers, and PPI facilitators

Quality of life questionnaires validate a remote approach to ophthalmic management of primary Sjögren's syndrome

Those with underlying autoimmune conditions were met with unparalleled challenges and were disproportionately affected by the COVID-19 pandemic. As such, we aimed to measure the impact of the pandemic on symptoms and the health and vision related quality of life (HR-QoL, VR-QoL) in patients with Primary Sjögren's Syndrome (pSS). Nineteen (55.9%) participants returned questionnaires for analysis, (17 female and 2 male, 61.6 years ± 9.9). There was no significant change in participants HR-QoL or VR-QoL, indicating that those with pSS remained resilient with regard to their physical and mental health throughout the pandemic. Furthermore, QoL was maintained despite 73.7% of participants having had outpatient appointments cancelled, delayed or rescheduled. Participants reported a lower QoL and feeling tenser in the COV19-QoL (3.3 ± 1.4 and 3.2 ± 1.3) representing feelings of apprehension and stress felt amongst the general population since the pandemic. Overall, and in spite of the concern caused by the COVID-19 pandemic for patients with autoimmune diseases, the health and well-being of patients with pSS remained stable. These findings strongly support the use of validated HR and VR-QoL questionnaires as an adjunct to the telemedicine consultation when assessing patients with pSS, offering an alternative to face-to-face consultations in post-pandemic era. </p

The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3

Induction of type I IFNs is a fundamental cellular response to both viral and bacterial infection. The role of the transcription factor IRF3 is well established in driving this process. However, equally as important are cellular mechanisms for turning off type I IFN production to limit this response. In this respect, IRF3 has previously been shown to be targeted for ubiquitin-mediated degradation postviral detection to turn off the IFN-beta response. In this study, we provide evidence that the E3 ligase Ro52 (TRIM21) targets IRF3 for degradation post-pathogen recognition receptor activation. We demonstrate that Ro52 interacts with IRF3 via its C-terminal SPRY domain, resulting in the polyubiquitination and proteasomal degradation of the transcription factor. Ro52-mediated IRF3 degradation significantly inhibits IFN-beta promoter activity, an effect that is reversed in the presence of the proteasomal inhibitor MG132. Specific targeting of Ro52 using short hairpin RNA rescues IRF3 degradation following polyI:C-stimulation of HEK293T cells, with a subsequent increase in IFN-beta production. Additionally, shRNA targeting of murine Ro52 enhances the production of the IRF3-dependent chemokine RANTES following Sendai virus infection of murine fibroblasts. Collectively, this demonstrates a novel role for Ro52 in turning off and thus limiting IRF3-dependent type I IFN production by targeting the transcription factor for polyubiquitination and subsequent proteasomal degradation

How has medical student learning changed with the pivot to online delivery of ophthalmology in the pandemic?

Purpose: This study aimed to measure stakeholder satisfaction with our usual delivery format, which previously relied on a blend of didactic lectures and clinical skills sessions compared to a revised format, which had more emphasis on online learning. We hypothesised that the online flipped classroom (OFC) would facilitate delivery of content in the wake of the pandemic, and result in improved levels of student satisfaction and knowledge gain. Design: Non randomised intervention study. Group 1 = Traditional delivery (TD) and Group 2 = OFC group. Methods: A validated course evaluation questionnaire (CEQ) compared perspectives of teaching faculty (n = 5) and students with the traditional delivery (TD) of the 4th year ophthalmology clinical attachment and an OFC approach (TD n = 129 v OFC n = 114). Results: The OFC group (n = 114; response rate = 24.6%) reported significantly reduced satisfaction with staff motivation of students and provision of feedback, compared to TD (n = 129; response rate = 17.8%). OFC students also felt it was harder to determine what standard of work was expected and found the course less beneficial at helping develop problem-solving skills. Students were dissatisfied with the level of choice afforded by the OFC, specifically how they would learn and assessment options. No significant difference in exam score was observed between the TD and OFC groups. For faculty (n = 5), there was no evidence of a difference between OFC and TD. Conclusions: Students indicated a preference for the TD compared to the OFC approach. However, both delivery approaches led to comparable student performances as determined by MCQ examination.</p

miR-744-5p contributes to ocular inflammation in patients with primary Sjogrens Syndrome

In primary Sjögren's syndrome (pSS) the exocrine glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal glands causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated localized and systemic inflammation contributes to the development and pathogenesis of pSS. A miR microarray performed in primary human conjunctival epithelial cells (PECs) demonstrated significant differences in miR expression at the ocular surface between pSS patients and healthy controls. MicroRNA-744-5p (miR-744-5p) was identified as being of particular interest, as its top predicted target is Pellino3 (PELI3), a known negative regulator of inflammation. Validation studies confirmed that miR-744-5p expression is significantly increased in PECs from pSS patients, whilst PELI3 was significantly reduced. We validated the miR-744 binding site in the 3' untranslated region (UTR) of PELI3 and demonstrated that increasing PELI3 levels with a miR-744-5p antagomir in an inflammatory environment resulted in reduced levels of IFN dependent chemokines Rantes (CCL5) and CXCL10. These results reveal a novel role for miR-744-5p in mediating ocular inflammation via Pellino3 expression in pSS patients and suggest that miR-744-5p may be a potential therapeutic target for the management of severe dry eye disease and ocular inflammation in pSS patients

Beyond dry eye: the greater extent of Sjögren’s systemic disease symptoms, impact of COVID-19 and perceptions towards Telemedicine identified through a patient co-designed study

Background: Sjögren's (‘SHOW-grins’) is a chronic debilitating autoimmune disease characterised by dry eyes and dry mouth, secondary to reduced exocrine function of both the lacrimal and salivary glands. The persistent, severe and serious systemic complications of Sjögren's are poorly understood and often unappreciated, resulting in significant morbidity and treatment burden. This study aimed to explore the experiences of those living with Sjögren's, specifically access to healthcare and attitude towards telemedicine. Additionally, we sought to collect information regarding the impact of the pandemic on their quality of life (QoL). Methods: One hundred and ninety-four individuals attended an Irish Sjögren's Webinar. Attendees were invited to participate in two online surveys after the webinar. The first survey gathered information related to demographics, disease and experiences during the COVID-19 pandemic. A combination of bespoke items and validated questionnaires (EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI], COVID-19 Impact on Quality of Life [COV19-QoL]) was used. The second survey consisted of a shortened Telehealth Usability Questionnaire. Both were prepared in collaboration with a patient advocate. Results: Survey 1: n = 76; response rate = 39.2%. Thirty-one respondents (41.4%) to survey 1 reported a delay of ≥5 years between the onset of symptoms and diagnosis. Dry mouth was the most common symptom experienced (76.8%, n = 63), followed by dry eye (74.4%, n = 61), fatigue (57.3%, n = 47) and joint pain (53.7%, n = 44), but a range of other symptoms were also reported. COV19-QoL results indicated that the pandemic had a detrimental effect on participants' overall QoL (4.0 ± 1.0) and physical health (4.0 ± 0.8) in particular. COV19-QoL and ESSPRI scores were moderately correlated (0.36, p = .002). Over 70% of respondents had a medical appointment cancelled, delayed or rescheduled (n = 60). Survey 2: n = 57; response rate = 29.4%. Those that had interacted with telemedicine reported largely positive experiences with the virtual model. Conclusion: Clinicians should be aware of the range of symptoms experienced by patients with Sjögren's beyond those of sicca (dry eye and dry mouth) and fatigue. COVID-19 has negatively influenced the self-reported health and well-being of those with Sjögren's, particularly those with higher symptom scores. It is vital that optimised telemedicine models are implemented to ensure continuity in the provision of healthcare for those with chronic illness such as Sjögren's and in preparation for possible future pandemics.</p

Beyond dry eye: the greater extent of Sjögren's systemic disease symptoms, the impact of COVID-19 and perceptions towards telemedicine identified through a patient co-designed study

Background: Sjögren's (‘SHOW-grins’) is a chronic debilitating autoimmune disease characterised by dry eyes and dry mouth, secondary to reduced exocrine function of both the lacrimal and salivary glands. The persistent, severe and serious systemic complications of Sjögren's are poorly understood and often unappreciated, resulting in significant morbidity and treatment burden. This study aimed to explore the experiences of those living with Sjögren's, specifically access to healthcare and attitude towards telemedicine. Additionally, we sought to collect information regarding the impact of the pandemic on their quality of life (QoL). Methods: One hundred and ninety-four individuals attended an Irish Sjögren's Webinar. Attendees were invited to participate in two online surveys after the webinar. The first survey gathered information related to demographics, disease and experiences during the COVID-19 pandemic. A combination of bespoke items and validated questionnaires (EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI], COVID-19 Impact on Quality of Life [COV19-QoL]) was used. The second survey consisted of a shortened Telehealth Usability Questionnaire. Both were prepared in collaboration with a patient advocate. Results: Survey 1: n = 76; response rate = 39.2%. Thirty-one respondents (41.4%) to survey 1 reported a delay of ≥5 years between the onset of symptoms and diagnosis. Dry mouth was the most common symptom experienced (76.8%, n = 63), followed by dry eye (74.4%, n = 61), fatigue (57.3%, n = 47) and joint pain (53.7%, n = 44), but a range of other symptoms were also reported. COV19-QoL results indicated that the pandemic had a detrimental effect on participants' overall QoL (4.0 ± 1.0) and physical health (4.0 ± 0.8) in particular. COV19-QoL and ESSPRI scores were moderately correlated (0.36, p = .002). Over 70% of respondents had a medical appointment cancelled, delayed or rescheduled (n = 60). Survey 2: n = 57; response rate = 29.4%. Those that had interacted with telemedicine reported largely positive experiences with the virtual model. Conclusion: Clinicians should be aware of the range of symptoms experienced by patients with Sjögren's beyond those of sicca (dry eye and dry mouth) and fatigue. COVID-19 has negatively influenced the self-reported health and well-being of those with Sjögren's, particularly those with higher symptom scores. It is vital that optimised telemedicine models are implemented to ensure continuity in the provision of healthcare for those with chronic illness such as Sjögren's and in preparation for possible future pandemics.</p