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1.
Surg Open Sci ; 19: 223-229, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846775

ABSTRACT

Introduction: The process by which surgery residency programs select applicants is complex, opaque, and susceptible to bias. Despite attempts by program directors and educational researchers to address these issues, residents have limited ability to affect change within the process at present. Here, we present the results of a design thinking brainstorm to improve resident selection and propose this technique as a framework for surgical residents to creatively solve problems and generate actionable changes. Methods: Members of the Collaboration of Surgical Education Fellows (CoSEF) used the design thinking framework to brainstorm ways to improve the resident selection process. Members participated in one virtual focus group focused on identifying pain points and developing divergent solutions to those pain points. Pain points and solutions were subsequently organized into themes. Finally, members participated in a second virtual focus group to design prototypes to test the proposed solutions. Results: Sixteen CoSEF members participated in one or both focus groups. Participants identified twelve pain points and 57 potential solutions. Pain points and solutions were grouped into the three themes of transparency, fairness, and applicant experience. Members subsequently developed five prototype ideas that could be rapidly developed and tested to improve resident selection. Conclusions: The design thinking framework can help surgical residents come up with creative ideas to improve pain points within surgical training. Furthermore, this framework can supplement existing quantitative and qualitative methods within surgical education research. Future work will be needed to implement the prototypes devised during our sessions and turn them into complete interventions. Key message: In this paper, we demonstrate the results of a resident-led design thinking brainstorm on improving resident selection in which our team identified twelve pain points in resident selection, ideated 57 solutions, and developed five prototypes for further testing. In addition to sharing our results, we believe design thinking can be a useful framework for creative problem solving within surgical education.

2.
Lancet Planet Health ; 8 Suppl 1: S6, 2024 04.
Article in English | MEDLINE | ID: mdl-38632921

ABSTRACT

BACKGROUND: Although existing literature provides various tools, frameworks, and guidelines for building health-care facilities that can withstand the impacts of climate change, there is little research focused on the practical implementation of such strategies. This gap in the research is particularly noticeable when applying these guidelines to specific geographical and environmental contexts. We focus specifically on the southeast Asia region, a region that has been identified as one of the most susceptible to the effects of a changing climate. By offering practical, region-specific recommendations, we hope to contribute to the ongoing efforts to mitigate the effects of climate change on health-care infrastructure and services. METHODS: To gain a comprehensive understanding of the specific challenges, needs, and feasible indicators for progress towards climate resilience in health-care facilities, we conducted in-depth interviews with members of the Global Green and Healthy Hospital Network in southeast Asia. Participants were selected based on a mix of facility and system parameters and were took into account various contexts, including urban and rural settings as well as low-income and high-income countries. Both private and public health systems and facilities were considered. This network comprises health-care professionals who are committed towards environmental sustainability and climate justice. FINDINGS: From Oct 6 to 28, 2023, we conducted interviews with eight participants and augmented this analysis with data drawn from existing published reports. The interview findings highlighted various primary areas of focus, which encompassed disaster readiness, low-carbon strategies, and the financial aspects of climate resilience. A prevailing theme was the importance of behaviour change alongside staff training and education. The unique perspective centres around the notion of health equity and its relationship with climate change. This perspective underscores the heightened awareness of environmental, economic, and social disparities that are exacerbated by climate change in southeast Asia. Issues include resistance to change, lack of public awareness, and economic versus ecological priorities. The absence of a standardised and systematic approach to implementing climate-resilient healthcare indicates a need for flexible and adaptable regional policies. INTERPRETATION: The findings of this study contribute to the broader understanding of how health services can be reoriented to face the realities of climate change effectively. This research outlines tangible recommendations for health services from both a process and impact points of view, and offers valuable insights for health policy makers, health-care providers, and researchers in the field. FUNDING: Health Care Without Harm southeast Asia.


Subject(s)
Resilience, Psychological , Humans , Delivery of Health Care , Asia, Southeastern , Health Facilities , Health Personnel
3.
Sci Rep ; 13(1): 22622, 2023 12 18.
Article in English | MEDLINE | ID: mdl-38114721

ABSTRACT

Recent studies showed significant associations between socio-demographic, lifestyle factors, polymorphic variant rs6265, and smoking cessation behaviours. We examined rs6265 TT, TC and CC genotypes and their association with socio-demographic and other variables, including mental health status, drinking, exercise, and smoking behaviour among Taiwanese adults. Data on rs6265 were retrieved from the Taiwan Biobank, which contained genetic data collected between 2008 to 2019 from 20,584 participants (aged 30-70 years). Participants who smoked for more than 6 months prior to enrolment were categorized as smokers. If they had smoked and later quit for more than 6 months, they were classified as former smokers. Information regarding drinking, exercise, depression, and bipolar disorder were obtained through questionnaires and were categorized as either as affirmative (yes) or negative (no) responses. In contrast to previous studies, we found that the association between the polymorphism rs6265 and smoking behaviour was not significant (P-value = 0.8753). Males with lower education levels, young persons, and alcohol drinkers showed significant smoking behaviours (P-value < .0001). This population-based study indicates that rs6265 has no significant correlations with smoking cessation behaviour among adults in Taiwan.


Subject(s)
Smoking Cessation , Adult , Humans , Male , Life Style , Smoking/genetics , Smoking/epidemiology , Surveys and Questionnaires , Taiwan/epidemiology , Brain-Derived Neurotrophic Factor/genetics
4.
J Surg Res ; 287: 149-159, 2023 07.
Article in English | MEDLINE | ID: mdl-36933546

ABSTRACT

INTRODUCTION: Due to the COVID-19 pandemic, the recruitment cycle for the 2021 Match was performed virtually. This Association for Surgical Education (ASE)-sponsored survey set out to study applicants' ability to assess the factors contributing to fit through video interviews. METHODS: An IRB-approved, online, anonymous survey was distributed to surgical applicants at a single academic institution and through the ASE clerkship director distribution list between the rank order list certification deadline and Match Day. Applicants used 5-point Likert-type scales to rate factors for importance to fit and their ease of assessment through video interviewing. A variety of recruitment activities were also rated by applicants for their perceived helpfulness in assessment of fit. RESULTS: One hundred and eighty-three applicants responded to the survey. The three most important factors for applicant fit were how much the program cared, how satisfied residents seem with their program, and how well residents get along. Resident rapport, diversity of the patient population, and quality of the facilities were hardest to assess through video interviews. In general, diversity-related factors were more important to female and non-White applicants, but not more difficult to assess. Interview day and resident-only virtual panels were the most helpful recruitment activities, while virtual campus tours, faculty-only panels, and a program's social media were the least helpful. CONCLUSIONS: This study provides valuable insight into the limitations of virtual recruitment for surgical applicants' perception of fit. These findings and the recommendations herein should be taken into consideration by residency program leadership to ensure successful recruitment of diverse residency classes.


Subject(s)
COVID-19 , Internship and Residency , Humans , Female , Pandemics , Interpersonal Relations , Personnel Selection , Surveys and Questionnaires
6.
Article in English | MEDLINE | ID: mdl-35955116

ABSTRACT

OBJECTIVE: Non-communicable and chronic diseases (NCDs) have become a public health problem that seriously threatens the population's health, especially in rapidly industrialized countries. Given the complexity of managing NCDs, there is growing evidence that interventions embedding or incorporating health promotion strategies can help reduce the disease burden of NCDs. This review aims to identify and map existing control and prevention policies for NCDs in China and identify gaps or opportunities for policy modifications and development, to transfer evidence-based guidelines into empirical public health intervention practices and research. DESIGN: A review was conducted to evaluate the policy documents to manage NCDs in China. Keywords "chronic disease", "health", and "policy" were used to search documents published on the Chinese official national websites. Nvivo 12.0 was used to conduct a content analysis of the policy documents. RESULTS: Fifty-six NCD prevention policies were retrieved from the search, and ten documents that incorporated the health promotion component were analyzed. The Healthy China 2030 Plan and Recommendations on Implementing the Healthy China Action are the core health policies of China's Central Government. These, coupled with three nationwide community-based projects, have provided a foundational transformation platform for health promotion implementation. CONCLUSION: This review revealed the Chinese Government's determination and commitment toward the prevention and control of NCDs and the promotion public health. Additional efforts and a focus on accelerating policy transformation and strengthening policy evaluation are required to achieve this commitment.


Subject(s)
Health Policy , Policy Making , China , Chronic Disease , Health Promotion , Humans
7.
BMJ Glob Health ; 7(4)2022 04.
Article in English | MEDLINE | ID: mdl-35414567

ABSTRACT

Social media can be both a source of information and misinformation during health emergencies. During the COVID-19 pandemic, social media became a ubiquitous tool for people to communicate and represents a rich source of data researchers can use to analyse users' experiences, knowledge and sentiments. Research on social media posts during COVID-19 has identified, to date, the perpetuity of traditional gendered norms and experiences. Yet these studies are mostly based on Western social media platforms. Little is known about gendered experiences of lockdown communicated on non-Western social media platforms. Using data from Weibo, China's leading social media platform, we examine gendered user patterns and sentiment during the first wave of the pandemic between 1 January 2020 and 1 July 2020. We find that Weibo posts by self-identified women and men conformed with some gendered norms identified on other social media platforms during the COVID-19 pandemic (posting patterns and keyword usage) but not all (sentiment). This insight may be important for targeted public health messaging on social media during future health emergencies.


Subject(s)
COVID-19 , Pandemics , Communicable Disease Control , Emergencies , Female , Humans , SARS-CoV-2
8.
Global Health ; 18(1): 9, 2022 02 04.
Article in English | MEDLINE | ID: mdl-35120533

ABSTRACT

BACKGROUND: During the course of the COVID-19 pandemic, states were called upon by the World Health Organization to introduce and prioritise the collection of sex-disaggregated data. The collection of sex-disaggregated data on COVID-19 testing, infection rates, hospital admissions, and deaths, when available, has informed our understanding of the biology of the infectious disease. The collection of sex-disaggregated data should also better inform our understanding of the gendered impacts that contribute to risk of exposure to COVID-19. In China, the country with the longest history of fighting the COVID-19 infection, what research was available on the gender-differential impacts of COVID-19 in the first 6 months of the COVID-19 pandemic? METHODS: In this scoping review, we examine the first 6 months (January-June 2020) of peer-reviewed publications (n = 451) on sex and gender experiences related to COVID-19 in China. We conducted an exhaustive search of published Chinese and English language research papers on COVID-19 in mainland China. We used a COVID-19 Gender Matrix informed by the JPHIEGO gender analysis toolkit to examine and illuminate research into the gendered impacts of COVID-19 within China. RESULTS: In China, only a small portion of the COVID-19-related research focused on gender experiences and differences. Near the end of the six-month literature review period, a small number of research items emerged on women healthcare workers, women's mental health, and pregnant women's access to care. There was an absence of research on the gendered impact of COVID-19 amongst populations. There was minimal consideration of the economic, social and security factors, including gender stereotypes and expectations, that affected different populations' experiences of infection, treatment, and lockdown during the period of review. CONCLUSION: At the outset of health emergencies in China, gender research needs to be prioritised during the first stage of an outbreak to assist with evaluation of the most effective public health measures, identifying access to healthcare and social welfare barriers amongst priority communities. Gender stereotypes and gendered differences lead to different patterns of exposure and treatment. The exclusion of this knowledge in real time affects the design of effective prevention and recovery.


Subject(s)
COVID-19 , COVID-19 Testing , China/epidemiology , Communicable Disease Control , Female , Humans , Pandemics , Pregnancy , SARS-CoV-2
9.
Med Educ ; 56(6): 641-650, 2022 06.
Article in English | MEDLINE | ID: mdl-35014076

ABSTRACT

INTRODUCTION: 'Fit' refers to an applicants' perceived compatibility to a residency programme. A variety of structural, identity-related and relational factors contribute to self-assessments of fit. The 2021 residency recruitment cycle in the USA was performed virtually due to the COVID-19 pandemic. Little is known about how video-interviewing may affect residency applicants' ability to gauge fit. METHODS: A multidisciplinary, anonymous survey was distributed to applicants at a large academic institution between rank order list (ROL) certification deadline and Match Day 2021. Using Likert-type scales, applicants rated factors for importance to 'fit' and their ease of assessment through video-interviewing. Applicants also self-assigned fit scores to the top-ranked programme in their ROL using Likert-type scales with pairs of anchoring statements. RESULTS: Four hundred seventy-three applicants responded to the survey (25.7% response rate). The three most important factors to applicants for assessment of fit (how much the programme seemed to care, how satisfied residents seem with their programme and how well the residents get along) were also the factors with the greatest discrepancy between importance and ease of assessment through video-interviewing. Diversity-related factors were more important to female applicants compared with males and to non-White applicants compared with White applicants. Furthermore, White male applicants self-assigned higher fit scores compared with other demographic groups. CONCLUSION: There is a marked discrepancy between the most important factors to applicants for fit and their ability to assess those factors virtually. Minoritised trainees self-assigned lower fit scores to their top-ranked programme, which should raise concern amongst medical educators and highlights the importance of expanding current diversity, equity and inclusion efforts in academic medicine.


Subject(s)
COVID-19 , Internship and Residency , COVID-19/epidemiology , Female , Humans , Male , Pandemics , Perception , Surveys and Questionnaires
10.
Health Policy Plan ; 37(7): 935-941, 2022 Aug 03.
Article in English | MEDLINE | ID: mdl-34894132

ABSTRACT

Evidence shows that infectious disease outbreaks are not gender-neutral, meaning that women, men and gender minorities are differentially affected. This evidence affirms the need to better incorporate a gender lens into infectious disease outbreaks. Despite this evidence, there has been a historic neglect of gender-based analysis in health, including during health crises. Recognizing the lack of available evidence on gender and pandemics in early 2020 the Gender and COVID-19 project set out to use a gender analysis matrix to conduct rapid, real-time analyses while the pandemic was unfolding to examine the gendered effects of the coronavirus disease 2019 pandemic. This paper reports on what a gender analysis matrix is, how it can be used to systematically conduct a gender analysis, how it was implemented within the study, ways in which the findings from the matrix were applied and built upon, and challenges encountered when using the matrix methodology.


Subject(s)
COVID-19 , Communicable Diseases , COVID-19/epidemiology , Disease Outbreaks , Female , Humans , Male , Pandemics , SARS-CoV-2
11.
BMJ Open ; 11(9): e045557, 2021 09 02.
Article in English | MEDLINE | ID: mdl-34475144

ABSTRACT

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories. SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies. PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators. METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials. RESULTS: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard. CONCLUSIONS: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes.


Subject(s)
COVID-19 , Occupational Exposure , Respiratory Protective Devices , Adult , Equipment Design , Humans , N95 Respirators , Pandemics/prevention & control , SARS-CoV-2 , United States , Ventilators, Mechanical
12.
Glob Public Health ; 16(8-9): 1364-1380, 2021.
Article in English | MEDLINE | ID: mdl-33705248

ABSTRACT

Gender norms, roles and relations differentially affect women, men, and non-binary individuals' vulnerability to disease. Outbreak response measures also have immediate and long-term gendered effects. However, gender-based analysis of outbreaks and responses is limited by lack of data and little integration of feminist analysis within global health scholarship. Recognising these barriers, this paper applies a gender matrix methodology, grounded in feminist political economy approaches, to evaluate the gendered effects of the COVID-19 pandemic and response in four case studies: China, Hong Kong, Canada, and the UK. Through a rapid scoping of documentation of the gendered effects of the outbreak, it applies the matrix framework to analyse findings, identifying common themes across the case studies: financial discrimination, crisis in care, and unequal risks and secondary effects. Results point to transnational structural conditions which put women on the front lines of the pandemic at work and at home while denying them health, economic and personal security - effects that are exacerbated where racism and other forms of discrimination intersect with gender inequities. Given that women and people living at the intersections of multiple inequities are made additionally vulnerable by pandemic responses, intersectional feminist responses should be prioritised at the beginning of any crises.


Subject(s)
COVID-19 , Feminism , Pandemics , Politics , COVID-19/epidemiology , Canada/epidemiology , China/epidemiology , Female , Hong Kong/epidemiology , Humans , Male , Socioeconomic Factors , United Kingdom/epidemiology
13.
Acad Radiol ; 28(2): 158-165, 2021 02.
Article in English | MEDLINE | ID: mdl-33257256

ABSTRACT

RATIONALE AND OBJECTIVE: Three-dimensional (3D) printing allows innovative solutions for personal protective equipment, particularly in times of crisis. Our goal was to generate an N95-alternative 3D-printed respirator that passed Occupational Safety and Health Administration (OSHA)-certified quantitative fit testing during the COVID-19 pandemic. MATERIALS AND METHODS: 3D printed prototypes for N95 solutions were created based on the design of commercial N95 respirators. Computed tomography imaging was performed on an anthropomorphic head phantom wearing a commercially available N95 respirator and these facial contour data was used in mask prototyping. Prototypes were generated using rigid and flexible polymers. According to OSHA standards, prototypes underwent subsequent quantitative respirator fit testing on volunteers who passed fit tests on commercial N95 respirators. RESULTS: A total of 10 prototypes were 3D printed using both rigid (n = 5 designs) and flexible materials (n = 5 designs), Prototypes generated with rigid printing materials (n = 5 designs) did not pass quantitative respirator fit testing. Three of the five prototypes with flexible materials failed quantitative fit testing. The final two prototypes designs passed OSHA-certified quantitative fit tests with an overall mean fit factor of 138 (passing is over 100). CONCLUSION: Through rapid prototyping, 3D printed N95 alternative masks were designed with topographical facial computed tomography data to create mask facial contour and passed OSHA-certified quantitative respiratory testing when flexible polymer was used. This mask design may provide an alternative to disposable N95 respirators in case of pandemic-related shortages. Furthermore, this approach may allow customization for those that would otherwise fail fit testing on standard commercial respirators.


Subject(s)
COVID-19 , Pandemics , Equipment Design , Humans , Masks , Materials Testing , N95 Respirators , Printing, Three-Dimensional , SARS-CoV-2 , Tomography, X-Ray Computed
15.
3D Print Med ; 6(1): 27, 2020 Sep 29.
Article in English | MEDLINE | ID: mdl-32990872

ABSTRACT

PURPOSE: Many commonly used mask designs are secured by elastic straps looping around the posterior auricular region. This constant pressure and friction against the skin may contribute to increased wearer pain, irritation, and discomfort. The purpose of this work is to report a modified 3D printed mask extender to alleviate discomfort and increase mask wearability by relieving posterior auricular pressure from isolation masks. METHODS: Our institutional review board designated this project as non-human research and exempt. As part of resourcing 3D printing laboratories along with individual 3D printers to provide resources to healthcare workers, mask extenders were printed to relieve posterior auricular pressure from individuals wearing isolation masks. The authors modifed an existing mask extender, increasing its length with accompanying peripheral rungs for isolation mask securement. 3D printing was performed with Ultimaker S5 (Ultimaker B.V.; Geldermalsen, Netherlands) and CR-10 (Creality3D; Shenzhen, China) 3D printers using polylactic acid filaments. The author's modified extended mask extenders were printed and freely delivered to healthcare workers (physicians, nurses, technologists, and other personnel) at the authors' institution. RESULTS: The final mask extender design was printed with the two 3D printers with a maximum 7 straps printed simultaneously on each 3D printer. Mean print times ranges from 105 min for the Ultimaker S5 printer and 150 min for the CR-10. Four hundred seventy-five mask extenders were delivered to healthcare workers at the authors' institution, with the demand far exceeding the available supply. CONCLUSION: We offer a modification of a 3D printed mask extender design that decreases discomfort and increases the wearability of isolation mask designs with ear loops thought to relieve posterior auricular skin pressure and ability to control strap tension. The design is simple, produced with inexpensive material (polylactic acid), and have been well-received by healthcare providers at our institution.

18.
J Am Coll Surg ; 230(4): 535-541, 2020 04.
Article in English | MEDLINE | ID: mdl-32032724

ABSTRACT

BACKGROUND: Nipple-sparing mastectomy (NSM) is an alternative to skin-sparing mastectomy in appropriately selected patients. The aim of this study was to review our experience with NSM and to evaluate for oncologic safety. STUDY DESIGN: Patients who underwent NSM at our institution from September 2008 through August 2017 were identified after IRB approval. Data included patient age, tobacco use, tumor size, hormone receptor status, lymph node status, radiation and chemotherapy use, incision type, and reconstruction type. Statistical analyses were performed using ANOVA and chi-square tests. RESULTS: There were 322 patients who underwent 588 NSM (83% bilateral, 17% unilateral), including 399 (68%) for malignancy (Stage 0 [27%], I [44%], II [25%] and III [4%]). The overall rate of wound complication was 18.9%. Tobacco use increased complication (37.5% vs 16.3%, p < 0.001), as did adjuvant radiation therapy (31.4% vs 17.4%, p = 0.014). Patients with lymph node involvement and larger tumor size had a higher rate of complication (31.3% vs 17.2%, p = 0.016). Patients undergoing circumareolar incisions had a higher rate of complication than those undergoing lateral radial, inframammary fold, or curvilinear incisions (43.5% vs 17.4% vs 17.4% vs 14.3%, respectively, p = 0.018). Six (1%) local chest wall recurrences occurred during the follow-up period, none of which involved the nipple-areolar complex. Four patients (1%) suffered a distant recurrence. CONCLUSIONS: Most NSM performed at our institution are in patients with malignancy. The oncologic safety is confirmed by the low locoregional recurrence rate. Tobacco use and adjuvant radiation therapy remain the most significant risk factors for complication, highlighting the need for careful patient selection and patient counseling regarding modifiable risk factors and expected outcomes.


Subject(s)
Breast Neoplasms/surgery , Mastectomy, Subcutaneous/methods , Adult , Aged , Cohort Studies , Female , Humans , Mastectomy, Subcutaneous/adverse effects , Middle Aged , Nipples , Organ Sparing Treatments , Retrospective Studies , Treatment Outcome , Young Adult
19.
Article in English | MEDLINE | ID: mdl-31426513

ABSTRACT

INTRODUCTION: Nepal was hit by two devastating earthquakes in 2015 that disrupted its socio-economic system and shattered many lives, resulting in increased mental health issues during the post-earthquake phase. Disasters can have severe mental health impacts on the affected population, making it necessary to enhance resilience within communities and to help them to adapt well in the face of adversities. From these earthquakes, this study looks to identify measures needed to develop community mental resilience for disaster preparedness in Nepal. METHOD: We conducted this research using the qualitative case study method and thematic analysis (TA). RESULT: Several activities were carried out by organizations to support the psycho-social aspects of communities, but were challenged by existing barriers. After considering the present context, this study presents five recommendations for mental resilience and also suggests the utilization of existing resources, such as faith-based organizations and teachers in the communities. Despite the considerable impact, communities demonstrate their own resilience, to some extent, through the culture of sharing and helping each other. CONCLUSIONS: A firm commitment is required from the government to enhance resilience by mainstreaming mental health in all areas of disaster management and planning.


Subject(s)
Earthquakes , Resilience, Psychological , Disaster Planning/methods , Humans , Mental Health , Nepal/epidemiology
20.
Mol Genet Genomic Med ; 7(7): e00733, 2019 07.
Article in English | MEDLINE | ID: mdl-31070020

ABSTRACT

BACKGROUND: Site-1 Protease (S1P) is a Golgi-resident protein required for the activation of regulatory proteins that drive key cellular functions, including, the unfolded protein response (UPR) and lipid and cholesterol biosynthesis. While disruptions in S1P function have been widely characterized in animal models, to date, the implications of disrupted S1P function in human disease states are not completely known. METHODS: The patient and both parents underwent whole exome and mitochondrial DNA sequencing, and Sanger sequencing was used to confirm the mutation. Western blotting and immunofluorescence studies were performed on either proband-derived fibroblasts or on an established cell line to assess protein expression and cellular localization of the mutated S1P protein. Quantitative real-time PCR and luciferase reporter assays were used to examine activation of S1P target pathways in the context of the S1P mutation. RESULTS: We describe a female patient with a de novo heterozygous missense mutation in the transmembrane domain of S1P (p. Pro1003Ser). The patient presented to our neuromuscular clinic with episodic, activity-induced, focal myoedema and myalgias with hyperCKemia. Her clinical phenotype was complex and included gastrointestinal hypomotility, ocular migraines, and polycystic ovary syndrome. Molecular analysis using proband-derived fibroblasts and cell lines harboring the Pro1003Ser mutation demonstrated increased activation of UPR and lipid and cholesterol regulatory pathways and localization of S1P Pro1003Ser in the Golgi. CONCLUSION: These findings suggest a critical function for S1P in several human organ systems and implicate an important role for S1P in various human disease states.


Subject(s)
Creatine Kinase/blood , Mutation, Missense , Myalgia/genetics , Phenotype , Proprotein Convertases/genetics , Serine Endopeptidases/genetics , Cells, Cultured , Cholesterol/metabolism , Edema/genetics , Edema/pathology , Female , Fibroblasts/metabolism , Golgi Apparatus/metabolism , Humans , Myalgia/pathology , Proprotein Convertases/metabolism , Serine Endopeptidases/metabolism , Syndrome , Young Adult
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