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1.
J Int AIDS Soc ; 27 Suppl 1: e26278, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965981

ABSTRACT

INTRODUCTION: Successful implementation of evidence-based practices depends on contextual factors like stakeholder engagement, the socio-political environment, resource availability, and stakeholders' felt needs and preferences. Nevertheless, inequities in implementation exist and undermine efforts to address HIV in marginalized key populations. Implementation science shows promise in addressing such inequities in the HIV response, but can be limited without meaningful engagement from citizens or communities. DISCUSSION: We define the concept of a citizen-engaged HIV implementation science as one that involves citizens and communities deeply in HIV implementation science activities. In this commentary, we discuss how citizen science approaches can be leveraged to spur equity in HIV implementation science. Drawing on three areas previously defined by Geng and colleagues that serve to drive impactful implementation science in the HIV response, we discuss how citizens can be engaged when considering "whose perspectives?", "what questions are being asked?" and "how are questions asked?". With respect to "whose perspectives?" a citizen-engaged HIV implementation science would leverage participatory methods and tools, such as co-creation, co-production and crowdsourcing approaches, to engage the public in identifying challenges, solve health problems and implement solutions. In terms of "what questions are being asked?", we discuss how efforts are being made to synthesize citizen or community-led approaches with existing implementation science frameworks and approaches. This also means that we ensure communities have a say in interrogating and deconstructing such frameworks and adapting them to local contexts through participatory approaches. Finally, when considering "how are questions asked?", we argue for the development and adoption of broad, guiding principles and frameworks that account for dynamic contexts to promote citizen-engaged research in HIV implementation science. This also means avoiding narrow definitions that limit the creativity, innovation and ground-up wisdom of local citizens. CONCLUSIONS: By involving communities and citizens in the development and growth of HIV implementation science, we can ensure that our implementation approaches remain equitable and committed to bridging divides and ending AIDS as a public health threat. Ultimately, efforts should be made to foster a citizen- and community-engaged HIV implementation science to spur equity in our global HIV response.


Subject(s)
HIV Infections , Implementation Science , Humans , HIV Infections/prevention & control , Citizen Science/methods , Community Participation/methods
2.
Ann Acad Med Singap ; 53(2): 101-112, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38920234

ABSTRACT

Introduction: Plantar fasciitis (PF) is a common cause of heel pain among the general population. The lack of standard practice guideline in Singapore presents challenges in education and clinical practice for this painful condition. These consensus statements and guideline were developed to streamline and improve the management of PF, covering key aspects such as diagnosis, investigations, risk factors, treatment modalities, monitoring and return to work/play. Method: A multidisciplinary expert panel consisting of 6 sports physicians, 2 orthopaedic surgeons, 2 podiatrists and 1 physiotherapist from SingHealth Duke-NUS Sport & Exercise Medicine Centre (SDSC) was convened based on their clinical and academic experience with PF. The Grading of Recommen-dations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of the evidence and subsequently prepare a set of clinical recommen-dations pertaining to the manage-ment of PF. A modified Delphi process was used to reach consensus. Results: Eighteen consensus statements were developed to cover key components of PF management, from initial diagnosis to treatment modalities and finally, clinical progression. They were subsequently consolidated under a proposed treatment pathway guideline for PF. Conclusion: The SDSC consensus statements and guideline provide concise recommendations for the management of PF in Singapore.


Subject(s)
Consensus , Fasciitis, Plantar , Humans , Delphi Technique , Fasciitis, Plantar/therapy , Fasciitis, Plantar/diagnosis , Singapore
3.
Front Neurol ; 15: 1325527, 2024.
Article in English | MEDLINE | ID: mdl-38803648

ABSTRACT

Background: The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms. Methods: The TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with de novo intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length). Results: 150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%, p < 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%). Conclusion: In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.

4.
Nat Rev Mol Cell Biol ; 25(2): 119-132, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37783784

ABSTRACT

The expression of mitochondrial genes is regulated in response to the metabolic needs of different cell types, but the basic mechanisms underlying this process are still poorly understood. In this Review, we describe how different layers of regulation cooperate to fine tune initiation of both mitochondrial DNA (mtDNA) transcription and replication in human cells. We discuss our current understanding of the molecular mechanisms that drive and regulate transcription initiation from mtDNA promoters, and how the packaging of mtDNA into nucleoids can control the number of mtDNA molecules available for both transcription and replication. Indeed, a unique aspect of the mitochondrial transcription machinery is that it is coupled to mtDNA replication, such that mitochondrial RNA polymerase is additionally required for primer synthesis at mtDNA origins of replication. We discuss how the choice between replication-primer formation and genome-length RNA synthesis is controlled at the main origin of replication (OriH) and how the recent discovery of an additional mitochondrial promoter (LSP2) in humans may change this long-standing model.


Subject(s)
DNA Replication , Transcription, Genetic , Humans , DNA Replication/genetics , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Mitochondria/genetics , Mitochondria/metabolism , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism
5.
Interv Neuroradiol ; 29(4): 481-487, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37455501

ABSTRACT

Intrasaccular flow disruption is a viable alternative to other endovascular treatments for saccular or wide-necked bifurcation intracranial aneurysms; however, wide neck aneurysms with irregular shapes or shallow depth may not be amenable to treatment currently available intrasaccular devices. Here, we present the first ever case report of the novel Saccular Endovascular Aneurysm Lattice Embolization System (SEAL™). The versatile utility of the SEAL™ device is demonstrated in a patient with acute subarachnoid hemorrhage (SAH) from a ruptured, complex, left middle cerebral artery (MCA) trilobed shallow wide-necked bifurcation aneurysm. Deployment and implantation of the SEAL device were technically feasible, safe, and conformed well to the irregular shape of the complex, ruptured aneurysm. Immediate total aneurysm occlusion was observed after implantation. Importantly, 1-year angiographic follow-up demonstrated durable, complete occlusion with no safety concerns. The SEAL device is a promising new novel technology which has the potential to treat very shallow aneurysms with limited height and irregular, multilobulated aneurysms.


Subject(s)
Aneurysm, Ruptured , Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Embolization, Therapeutic , Endovascular Procedures , Intracranial Aneurysm , Humans , Intracranial Aneurysm/therapy , Intracranial Aneurysm/surgery , Follow-Up Studies , Treatment Outcome , Aortic Aneurysm, Abdominal/surgery , Retrospective Studies , Endovascular Procedures/methods , Aneurysm, Ruptured/therapy , Aneurysm, Ruptured/surgery , Embolization, Therapeutic/methods , Cerebral Angiography
6.
Front Public Health ; 11: 1063466, 2023.
Article in English | MEDLINE | ID: mdl-36860378

ABSTRACT

Purpose: The COVID-19 pandemic has drastically disrupted global healthcare systems. With the higher demand for healthcare and misinformation related to COVID-19, there is a need to explore alternative models to improve communication. Artificial Intelligence (AI) and Natural Language Processing (NLP) have emerged as promising solutions to improve healthcare delivery. Chatbots could fill a pivotal role in the dissemination and easy accessibility of accurate information in a pandemic. In this study, we developed a multi-lingual NLP-based AI chatbot, DR-COVID, which responds accurately to open-ended, COVID-19 related questions. This was used to facilitate pandemic education and healthcare delivery. Methods: First, we developed DR-COVID with an ensemble NLP model on the Telegram platform (https://t.me/drcovid_nlp_chatbot). Second, we evaluated various performance metrics. Third, we evaluated multi-lingual text-to-text translation to Chinese, Malay, Tamil, Filipino, Thai, Japanese, French, Spanish, and Portuguese. We utilized 2,728 training questions and 821 test questions in English. Primary outcome measurements were (A) overall and top 3 accuracies; (B) Area Under the Curve (AUC), precision, recall, and F1 score. Overall accuracy referred to a correct response for the top answer, whereas top 3 accuracy referred to an appropriate response for any one answer amongst the top 3 answers. AUC and its relevant matrices were obtained from the Receiver Operation Characteristics (ROC) curve. Secondary outcomes were (A) multi-lingual accuracy; (B) comparison to enterprise-grade chatbot systems. The sharing of training and testing datasets on an open-source platform will also contribute to existing data. Results: Our NLP model, utilizing the ensemble architecture, achieved overall and top 3 accuracies of 0.838 [95% confidence interval (CI): 0.826-0.851] and 0.922 [95% CI: 0.913-0.932] respectively. For overall and top 3 results, AUC scores of 0.917 [95% CI: 0.911-0.925] and 0.960 [95% CI: 0.955-0.964] were achieved respectively. We achieved multi-linguicism with nine non-English languages, with Portuguese performing the best overall at 0.900. Lastly, DR-COVID generated answers more accurately and quickly than other chatbots, within 1.12-2.15 s across three devices tested. Conclusion: DR-COVID is a clinically effective NLP-based conversational AI chatbot, and a promising solution for healthcare delivery in the pandemic era.


Subject(s)
COVID-19 , Deep Learning , Humans , Natural Language Processing , Artificial Intelligence , Pandemics , India
7.
Mod Pathol ; 36(4): 100056, 2023 04.
Article in English | MEDLINE | ID: mdl-36788078

ABSTRACT

Mutations in the PI3K pathway, particularly PIK3CA, were reported to be intimately associated with triple-negative breast cancer (TNBC) progression and the development of treatment resistance. We profiled PIK3CA and other genes on 166 early-stage TNBC tumors from Singapore for comparison to publicly available TNBC cohorts. These tumors were profiled transcriptionally using a NanoString panel of immune genes and multiplex immunohistochemistry, then manually scored for PD-L1-positivity using 2 clinically relevant clones, SP142 and 22C3. We discovered a higher rate of PIK3CA mutations in our TNBC cohort than in non-Asian cohorts, along with TP53, BRCA1, PTPN11, and MAP3K1 alterations. PIK3CA mutations did not affect overall or recurrence-free survival, and when compared with PIK3CAWT tumors, there were no differences in immune infiltration. Using 2 clinically approved antibodies, PIK3CAmut tumors were associated with PD-L1 negativity. Analysis of comutation frequencies further revealed that PIK3CA mutations tended to be accompanied by MAP kinase pathway mutation. The mechanism and impact of PIK3CA alterations on the TNBC tumor immune microenvironment and PD-L1 positivity warrant further study.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/pathology , B7-H1 Antigen/genetics , Singapore , Phosphatidylinositol 3-Kinases/genetics , Mutation , Class I Phosphatidylinositol 3-Kinases/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Tumor Microenvironment
8.
Ann Acad Med Singap ; 52(5): 230-238, 2023 May 30.
Article in English | MEDLINE | ID: mdl-38904520

ABSTRACT

Introduction: Sudden cardiac death in athletes is a rare occurrence, the most common cause being hypertrophic cardiomyopathy, which increases the risk of sustained ventricular tachycardia or ventricular fibrillation. Most of these young athletes are asymptomatic prior to the cardiac arrest. Several electrocardiogram criteria such as the European Society of Cardiology group 2 Criteria changes, Seattle Criteria, Refined Criteria, and most recently the 2017 International Criteria, have sought to improve the accuracy of identifying these at-risk athletes during pre-participation screening while minimising unnecessary investigations for the majority of athletes at low risk.We aimed to compare the above four criteria in our Singapore athlete population to identify which criterion performed the best in detecting cardiac abnormalities on echocardiography. Method: Out of 1,515 athletes included in Changi General Hospital, Singapore registry between June 2007 and June 2014, the electrocardiograms of 270 athletes with further cardiac investigations were analysed. We compared the above four electrocardiographic criteria to evaluate which performed best for detecting cardiac abnormalities on echocardiography in our Southeast Asian athlete population. Results: The European Society of Cardiology, Seattle, Refined and 2017 International Criteria had a sensitivity of 20%, 0%, 20% and 5%, respectively; a specificity of 64%, 93%, 84% and 97%, respectively; a positive predictive value of 4%, 0%, 9% and 11%, respectively; and a negative predictive value of 91%, 92%, 93% and 93%, respectively for detecting abnormalities on echocardiography. Conclusion: The latest 2017 International Criteria performed the best as it had the highest specificity and positive predictive value, joint highest negative predictive value, and lowest false positive rate.


Subject(s)
Athletes , Death, Sudden, Cardiac , Echocardiography , Electrocardiography , Humans , Singapore/epidemiology , Electrocardiography/methods , Death, Sudden, Cardiac/prevention & control , Male , Female , Young Adult , Sensitivity and Specificity , Adult , Cardiomyopathy, Hypertrophic/diagnosis , Adolescent , Predictive Value of Tests , Registries
9.
Ann Acad Med Singap ; 52(6): 310-320, 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-38904512

ABSTRACT

Introduction: Early childhood is a critical period for growth and development. Adopting healthy lifestyle behaviours during this period forms the foundation for future well-being and offers the best protection against non-communicable diseases. Singapore studies have shown that many young children are not achieving the recommendations on physical activity, sedentary behaviour and sleep. A workgroup was set up to develop recommendations for caregivers of infants, toddlers and preschoolers (aged <7 years) on how to integrate beneficial activities within a daily 24-hour period for optimal development and metabolic health. Method: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- ADOLOPMENT approach was employed for adoption, adaption or de novo development of recommendations. International and national guidelines were used as references, and an update of the literature reviews up to September 2021 was conducted through an electronic search of PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: Four consensus statements were developed for each age group: infants, toddlers and preschoolers. The statements focus on achieving good metabolic health through regular physical activity, limiting sedentary behaviour, achieving adequate sleep and positive eating habits. The 13th consensus statement recognises that integration of these activities within a 24-hour period can help obtain the best results. Conclusion: This set of recommendations guides and encourages caregivers of Singapore infants, toddlers and preschoolers to adopt beneficial lifestyle activities within each 24-hour period.


Subject(s)
Consensus , Exercise , Sedentary Behavior , Sleep , Child, Preschool , Humans , Infant , Exercise/physiology , Feeding Behavior , Healthy Lifestyle , Singapore , Sleep/physiology , Child
10.
Sports Med Open ; 8(1): 125, 2022 Oct 11.
Article in English | MEDLINE | ID: mdl-36219269

ABSTRACT

BACKGROUND: Many countries have restricted public life in order to contain the spread of the novel coronavirus (SARS-CoV2). As a side effect of related measures, physical activity (PA) levels may have decreased. OBJECTIVE: We aimed (1) to quantify changes in PA and (2) to identify variables potentially predicting PA reductions. METHODS: A systematic review with random-effects multilevel meta-analysis was performed, pooling the standardized mean differences in PA measures before and during public life restrictions. RESULTS: A total of 173 trials with moderate methodological quality (modified Downs and Black checklist) were identified. Compared to pre-pandemic, total PA (SMD - 0.65, 95% CI - 1.10 to - 0.21) and walking (SMD - 0.52, 95% CI - 0.29 to - 0.76) decreased while sedentary behavior increased (SMD 0.91, 95% CI: 0.17 to 1.65). Reductions in PA affected all intensities (light: SMD - 0.35, 95% CI - 0.09 to - 0.61, p = .013; moderate: SMD - 0.33, 95% CI - 0.02 to - 0.6; vigorous: SMD - 0.33, - 0.08 to - 0.58, 95% CI - 0.08 to - 0.58) to a similar degree. Moderator analyses revealed no influence of variables such as sex, age, body mass index, or health status. However, the only continent without a PA reduction was Australia and cross-sectional trials yielded higher effect sizes (p < .05). CONCLUSION: Public life restrictions associated with the COVID-19 pandemic resulted in moderate reductions in PA levels and large increases in sedentary behavior. Health professionals and policy makers should therefore join forces to develop strategies counteracting the adverse effects of inactivity.

11.
Sci Rep ; 12(1): 16257, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36171219

ABSTRACT

Our study sought to examine the impact of the pandemic and the Circuit-breaker (CB) measures on dietary behaviours of healthcare workers (HCW). In addition, the association between self-regulatory eating behaviours and psychological stress was explored. Our study employed a cross-sectional anonymous survey that examined the demographics, dietary habits, self-regulatory eating behaviours (SR) and their association to stress levels of healthcare workers (HCWs) before and during the Circuit Breaker (CB) in Singapore. The survey was conducted over four weeks from May 17 to June 18, 2020. Snowball sampling was performed in the final week. A total of 707 participants took part in the survey. Due to the CB measures and modifications of work scope and work areas, there were significant changes in their dietary behaviors before CB versus during the CB period (n = 707), with many reducing the intake of vegetables (p = 0.018) while increasing their intake of unhealthy food choices such as canned drinks (p = 0.002), convenience food (p ≤ 0.001) and alcoholic drinks (p = 0.034). Before the CB period, 91.8% (602/656) of participants who intended to have a healthy diet were classified in medium-to-high SR groups whereas during the CB period, 87.7% (575/656) were in medium-to-high SR groups and the difference was statistically significant (p = 0.011). Nurses, administrative staff, HCWs of Chinese and Indian ethnicities, staff who did not complete university education and those who did not have domestic helpers were more likely to have reduced SR. Importantly, amongst participants who intended to have a healthy diet, 70.9% displayed no change or improved eating habits and showed medium-to-high levels of SR during CB. Participants with no changes in SR were 2.11 times more likely to be stress-free as compared to those who had deteriorated SR (OR 2.11 95% CI 1.27-3.48, p = 0.004). Due to CB measures and work modifications, dietary behaviours of HCWs deteriorated with increased intake of unhealthy food choices. HCWs who maintain their self-regulatory eating behaviour are more likely to be stress-free. Short screening questionnaires based on SR changes should be developed and explored as surveillance tools for assessment of HCWs' general well-being such that personalized interventions to vulnerable groups of workers could be implemented effectively on the ground.


Subject(s)
COVID-19 , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Feeding Behavior , Health Personnel , Humans , Singapore/epidemiology
12.
Front Immunol ; 13: 978760, 2022.
Article in English | MEDLINE | ID: mdl-36172383

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Comorbidity , Humans , Immune Checkpoint Inhibitors , Immunologic Memory , Morbidity , SARS-CoV-2 , Transcriptome , Tumor Microenvironment/genetics
13.
Mol Cell ; 82(19): 3646-3660.e9, 2022 10 06.
Article in English | MEDLINE | ID: mdl-36044900

ABSTRACT

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.


Subject(s)
Genome, Mitochondrial , Adenosine Triphosphate/metabolism , DNA, Mitochondrial/metabolism , Humans , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Transcription, Genetic
14.
Cell ; 185(13): 2309-2323.e24, 2022 06 23.
Article in English | MEDLINE | ID: mdl-35662414

ABSTRACT

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.


Subject(s)
DNA, Mitochondrial , Mitochondrial Proteins , Animals , DNA, Mitochondrial/genetics , DNA-Directed RNA Polymerases/metabolism , Dimerization , Humans , Mammals/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , RNA/metabolism , RNA, Mitochondrial , RNA, Small Cytoplasmic , Signal Recognition Particle , Transcription, Genetic
15.
Ann Acad Med Singap ; 51(5): 292-299, 2022 05.
Article in English | MEDLINE | ID: mdl-35658152

ABSTRACT

INTRODUCTION: Lifestyle activities, such as regular physical activity, are important for good metabolic health and the prevention of non-communicable diseases. Epidemiological studies highlight an increase in the proportion of overweight children in Singapore. A workgroup was formed to develop recommendations to encourage children and adolescents (aged 7-17 years) to adopt a holistic approach towards integrating beneficial activities within a daily 24-hour period for good metabolic and general health. METHODS: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to formulate the public health question, assess the evidence and draw conclusions for the guide. The evidence for international 24-hour movement guidelines, and guidelines for physical activity, sedentary behaviour, and sleep and eating habits were reviewed. An update of the literature review from August 2018 to end of September 2020 was conducted through an electronic search of Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. RESULTS: Ten consensus statements were developed. The statements focused on the overall aim of achieving good metabolic health through integration of these activities and initiatives: light and moderate- to vigorous-intensity physical activity on a regular basis; muscle- and bone-strengthening activities; limiting sedentary behaviour; regular and adequate sleep; good eating habits and choosing nutritionally balanced foods and drinks; practise safety in exercise; and aiming to achieve more or all aforementioned recommendations for the best results. CONCLUSION: This set of recommendations provides guidance to encourage Singapore children and adolescents to adopt health-beneficial activities within a 24-hour period.


Subject(s)
Exercise , Sedentary Behavior , Adolescent , Child , Humans , Public Health , Singapore , Sleep
16.
Support Care Cancer ; 30(6): 4867-4878, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35156143

ABSTRACT

PURPOSE: Exercise can help cancer survivors manage sequela, treatment side effects, improve overall quality of life, and is recommended for most. The purpose of this study was to investigate exercise behavior and factors influencing exercise engagement among cancer survivors at the National Cancer Centre, Singapore (NCCS). METHODS: This cross-sectional study was inclusive of survivors of all cancer types and stages who were at least 21 years of age and had undergone chemotherapy at the NCCS. Surveys were utilized to assess survivor barriers and facilitators to exercise and to retrospectively assess physical activity and exercise behaviors at 4 cancer-related time periods (pre-diagnosis and post-diagnosis before, during, or after chemotherapy). RESULTS: A total of 102 cancer survivors were enrolled; 60% were diagnosed with stage IV cancer. Predominant cancer types included lower gastrointestinal tract (25.5%) and breast cancer (21.6%). Prior to cancer diagnosis, 90.2% of participants reported aerobic activity satisfying NCCN guidelines. Significant reductions in reported exercise, and physical activity, were observed following cancer diagnosis that persisted during chemotherapy. Key exercise facilitators included the desire to remain healthy (86.3%) and to improve sleep and mental well-being (73.5%). Key barriers included side effects of treatment (52.0%). Only 46.1% of survivors reported receiving exercise guidance from healthcare professionals following diagnosis. CONCLUSION: Overall, even among this notably active cohort of Singaporean survivors, opportunities for increased exercise engagement throughout the survivorship continuum remain. Increased education regarding the benefits of exercise to survivors as well as guidance regarding exercise modalities including resistance training is greatly needed as well.


Subject(s)
Breast Neoplasms , Cancer Survivors , Adult , Cross-Sectional Studies , Exercise , Female , Humans , Quality of Life , Retrospective Studies , Singapore
19.
Stress Health ; 38(1): 171-179, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34231968

ABSTRACT

The outbreak of COVID-19 has precipitated international lockdown measures to curb disease transmissions. The closure of public activity spaces as well as changes in pandemic workload may disrupt healthcare workers' physical activity and self-care routines. We sought to examine the association between physical activity levels and mental health burden of healthcare workers during the COVID-19 lockdown in Singapore. This cross-sectional study comprised of an multidomain survey that was administered digitally to 707 healthcare workers between 17 May and 18 June 2020. Exercise frequency, duration and intensity of these healthcare workers had reduced significantly during the lockdown compared to pre-lockdown. 25.3%, 37.2%, and 11.9% had screened positive for moderate-to-extremely-severe depression, anxiety and stress respectively. Reductions in exercise duration was a significant risk factor for mild stress and moderate-to-severe depression while increase in exercise frequency was found to be a protective factor against depressed mood. Our study revealed that a short-term reduction in physical activity levels during lockdown was associated with poorer psychological outcomes. Given the protection that exercise confers on depression, physical activity should be promoted at the workplace and at home to support healthcare workers to cope through this protracted health crisis.


Subject(s)
COVID-19 , Mental Health , Anxiety , Communicable Disease Control , Cross-Sectional Studies , Depression/epidemiology , Exercise , Health Personnel , Humans , SARS-CoV-2
20.
Eur Cardiol ; 16: e44, 2021 Feb.
Article in English | MEDLINE | ID: mdl-34815752

ABSTRACT

Sports-related sudden cardiac death is a rare but devastating consequence of sports participation. Certain pathologies underlying sports-related sudden cardiac death could have been picked up pre-participation and the affected athletes advised on appropriate preventive measures and/or suitability for training or competition. However, mass screening efforts - especially in healthy young populations - are fraught with challenges, most notably the need to balance scarce medical resources and sustainability of such screening programmes, in healthcare systems that are already stretched. Given the rising trend of young sports participants across the Asia-Pacific region, the working group of the Asian Pacific Society of Cardiology (APSC) developed a sports classification system that incorporates dynamic and static components of various sports, with deliberate integration of sports events unique to the Asia-Pacific region. The APSC expert panel reviewed and appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. Consensus was reached when 80% of votes for a recommendation were agree or neutral. The resulting statements described here provide guidance on the need for cardiovascular pre-participation screening for young competitive athletes based on the intensity of sports they engage in.

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