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Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals. The comorbidity of the two neurological disorders represents a grave health threat to older populations. This review presents a brief background of the development of novel concepts and their clinical potentials. The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca 2+ influx is critical for neuronal function. An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca 2+ mainly via N-methyl-D-aspartate receptors, particularly of those at the extrasynaptic site. This Ca 2+ -evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity. Furthermore, mild but sustained Ca 2+ increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic, but gradually set off deteriorating Ca 2+ -dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways. Based on the Ca 2+ hypothesis of Alzheimer's disease and recent advances, this Ca 2+ -activated "silent" degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis. The N-methyl-D-aspartate receptor subunit GluN3A, primarily at the extrasynaptic site, serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity. Ischemic stroke and Alzheimer's disease, therefore, share an N-methyl-D-aspartate receptor- and Ca 2+ -mediated mechanism, although with much different time courses. It is thus proposed that early interventions to control Ca 2+ homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia. This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.
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Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-ß (CSF1R/CCR2/TGF-ß Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.
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Monocitos , Receptor de Factor Estimulante de Colonias de Macrófagos , Receptores CCR2 , Microambiente Tumoral , Humanos , Receptores CCR2/metabolismo , Receptores CCR2/antagonistas & inhibidores , Monocitos/metabolismo , Monocitos/inmunología , Receptor de Factor Estimulante de Colonias de Macrófagos/antagonistas & inhibidores , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Microambiente Tumoral/inmunología , Animales , Línea Celular Tumoral , Femenino , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Ratones , Movimiento Celular/efectos de los fármacos , Neoplasias/inmunología , Neoplasias/patologíaRESUMEN
Purpose: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features. Methods: We enrolled 616 highly myopic eyes of 616 patients. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering. Results: With 83.35% total variance explained, highly myopic eyes were classified into four AI categories. The percentages of AI categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. Contrast acuity of the eyes in AI category 1 was the highest, which decreased by half in AI category 2. For AI categories 2 to 4, every increase in category led to a decrease of 0.23 logarithm of the minimum angle of resolution in contrast acuity. Compared with those in AI category 1, eyes in AI category 2 presented a higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in AI categories 3 and 4 presented significantly higher percentage of MMD ≥ 3, thinner nasal macular thickness and p-RNFL (P < 0.05). Multivariate regression showed AI category 4 had higher MMD grades and thinner macular compared with AI category 3. Conclusions: We proposed an AI-based classification of highly myopic eyes with clear relevance to visual function and fundus features. Translational Relevance: This classification helps to discover the early hidden visual deficits of highly myopic patients, becoming a useful tool to evaluate the disease comprehensively.
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Inteligencia Artificial , Sensibilidad de Contraste , Fondo de Ojo , Tomografía de Coherencia Óptica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Anciano , Sensibilidad de Contraste/fisiología , Agudeza Visual/fisiología , Adulto , Miopía Degenerativa/fisiopatología , Miopía Degenerativa/diagnóstico por imagen , Miopía Degenerativa/diagnóstico , Miopía Degenerativa/clasificación , Miopía Degenerativa/patología , Degeneración Macular/clasificación , Degeneración Macular/fisiopatología , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Degeneración Macular/diagnóstico por imagen , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/fisiopatología , Fibras Nerviosas/patologíaRESUMEN
Di(2-ethylhexyl)phthalate (DEHP) and di-n-butylphthalate (DBP) frequently coexist in different environmental compartments. Thus, in this study, model aquatic and terrestrial microcosms were prepared to analyze the combined effect of DEHP and DBP on their fate, toxicity, and ecological risk. In the aquatic microcosms, with the addition of the same amount of DEHP and DBP, a higher total amount of DEHP was detected in water, suspended particles, and sediment than DBP due to the higher Kow and half-life of DEHP than DBP. Sediment was the major sink of both phthalates, as the highest percentages of DEHP (90.0 % â¼ 95.6 %) and DBP (68.7 % â¼ 78.1 %) were found in the sediment. The results of the whole sediment toxicity test showed that DBP (LC50/LC10: 6.75/1.171 µg/g dw) was more toxic than DEHP (LC50/LC10: 158.75/27.25 µg/g dw) to the tubificid oligochaete Monopylephorus limosus, with a synergistic toxic effect of the mixture of DEHP and DBP (LC50/LC10: 100.3/4.6 µg/g dw). The mobility of DEHP and DBP in soil was low during irrigation, with the release of 0.054 % â¼ 2.29 % DEHP and 0.097 % â¼ 1.86 % DBP. The bioconcentration factors/biota-sediment accumulation factors for DEHP (70.8-145 L/kg/0.093-0.359) in the muscle of the fish Carassius auratus were lower than those for DBP (82.2-300 L/kg/0.514-1.625). The bioaccumulation factors of DEHP and DBP for earthworms were 0.373 and 0.682, respectively. The levels of DEHP and DBP in the water and sediment of aquatic systems and in the soil of terrestrial systems might pose high ecological risks to some fish species, M. limosus and earthworms, according to the risk quotient values. These data provide valuable insights for the development of government control strategies to minimize the ecological risks of DEHP and DBP.
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Succinate dehydrogenase (SDH) plays pivotal roles in maintaining cellular metabolism, modulating regulatory control over both the tricarboxylic acid cycle and oxidative phosphorylation to facilitate energy production within mitochondria. Given that SDH malfunction may serve as a hallmark triggering pseudo-hypoxia signaling and promoting tumorigenesis, elucidating the impact of SDH assembly defects on mitochondrial functions and cellular responses is of paramount importance. In this study, we aim to clarify the role of SDHAF2, one assembly factor of SDH, in mitochondrial respiratory activities. To achieve this, we utilize the CRISPR/Cas9 system to generate SDHAF2 knockout in HeLa cells and examine mitochondrial respiratory functions. Our findings demonstrate a substantial reduction in oxygen consumption rate in SDHAF2 knockout cells, akin to cells with inhibited SDH activity. In addition, in our in-gel activity assays reveal a significant decrease not only in SDH activity but also in cytochrome c oxidase (COX) activity in SDHAF2 knockout cells. The reduced COX activity is attributed to the assembly defect and remains independent of SDH inactivation or SDH complex disassembly. Together, our results indicate a critical role of SDHAF2 in regulating respiration by facilitating the assembly of COX.
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[This retracts the article DOI: 10.1515/biol-2020-0040.].
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Phosphosignaling networks control cellular processes. We built kinase-mediated regulatory networks elicited by thrombin stimulation of brain endothelial cells using two computational strategies: Temporal Pathway Synthesizer (TPS), which uses phosphoproetiomics data as input, and Temporally REsolved KInase Network Generation (TREKING), which uses kinase inhibitor screens. TPS and TREKING predicted overlapping barrier-regulatory kinases connected with unique network topology. Each strategy effectively describes regulatory signaling networks and is broadly applicable across biological systems.
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This report describes the case of a patient who presented to the Emergency Department (ED) with a one-week history of difficulty in breathing, generalized weakness, dysphagia, and difficulty in walking. She had self-administered 100 units of onabotulinumtoxin A (BoNT-A) by injection into her face two weeks prior for cosmetic purposes. This case study highlights the rare but potential complication of systemic botulism.
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BACKGROUND: Abdominal aortic aneurysm (AAA) poses a considerable global health challenge; however, population-based studies on AAA are scarce. The current study determined the hospitalization rates, surgical trends, mortality, and reintervention rates for ruptured (r-AAA) and nonruptured (nr-AAA) AAA by using a national health insurance database. METHODS: We conducted a population-based retrospective cohort study by analyzing data from 2007 to 2018 from the Taiwanese National Health Insurance Research Database. Individuals over 20 years of age with a new diagnosis of AAA were included in this study. RESULTS: A total of 70 457 patients were given a diagnosis of aortic aneurysm or dissection over the study period; 22 538 (32%) adult patients (≥20 years) had AAA. The annual incidence of AAA was approximately 7.7 to 10.3 per 100 000 (r-AAA: 0.8-1.3 per 100 000 versus nr-AAA: 6.8-9.0 per 100 000). Most of the patients with AAA were older adults (85%); 15 392 (68%) patients had a documented hospitalization, and 4885 (32%) underwent surgery within 14 days of diagnosis. The percentage of patients receiving endovascular aneurysm repair (EVAR) increased from 28% to 96% over the study period. The long-term survival rates were higher among the patients who underwent open surgical repair (OSR) compared with those of the patients who received EVAR or conservative treatment, regardless of whether they had r-AAA or nr-AAA. CONCLUSION: AAA is more common among older individuals, and the annual standardized incidence indicates a downward trend. Since the introduction of EVAR, the proportion of patients undergoing EVAR has continually increased, whereas that of those undergoing OSR have decreased. Although EVAR and OSR were both associated with lower mortality rates among patients with r-AAA, OSR resulted in better long-term survival outcomes.
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BACKGROUND AND OBJECTIVES: Low handgrip strength (HGS) and abdominal obesity (AO) have been reported to be linked to an increased all-cause mortality risk in older adults. However, the combined impact of AO with low HGS and/or HGS asymmetry on mortality risk remains unclear. Therefore, this study aimed to investigate the synergistic effects of AO and abnormal HGS on mortality risk among Chinese older adults. METHODS: Baseline data of the China Health and Retirement Longitudinal Study in 2011, along with mortality outcomes obtained in 2018 were used for the analysis. Low HGS was identified as HGS <18 kg in women or <28 kg in men, while HGS asymmetry is defined as an HGS of either hand > 10% stronger than the other. AO was characterized by a waist circumference ≥90 cm in men and ≥85 cm in women. Logistic regression analysis was used to evaluate the relationship between AO, abnormal HGS and mortality risk. RESULTS: A total of 5186 subjects aged 60 years or older were enrolled, 50.6% of whom were male. The proportions of participants with only AO, only low HGS, only HGS asymmetry, low HGS with asymmetry, both AO and low HGS, both AO and asymmetric HGS, and AO with both low HGS and asymmetry were 20.0%, 6.1%, 16.6%, 8.3%, 3.2%, 13.4%, and 3.9%, respectively. Over the course of a 7-year follow-up interval, 970 of these individuals died, with 13.4%, 12.4%, 13.6%, 15.5%, 4.1%, 10.1% and 6.9% of deaths in the above groups, respectively. The adjusted logistic regression analysis model confirmed that only low HGS (OR = 1.897, 95%CI: 1.386-2.596, p<0.001), low HGS with asymmetry (OR = 1.680, 95%CI: 1.265-2.231, p<0.001), and AO combined with both low HGS and asymmetry (OR = 2.029, 95%CI: 1.381-2.981, p<0.001) were associated with a higher risk of mortality. CONCLUSIONS: Low HGS, with or without asymmetry, is associated with increased mortality risk in older Chinese adults without AO, and the combination of low HGS and HGS asymmetry further elevates mortality risk in those with AO.
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Fuerza de la Mano , Obesidad Abdominal , Humanos , Masculino , Femenino , Obesidad Abdominal/mortalidad , Obesidad Abdominal/fisiopatología , Anciano , Fuerza de la Mano/fisiología , China/epidemiología , Persona de Mediana Edad , Estudios Longitudinales , Factores de Riesgo , Anciano de 80 o más Años , Circunferencia de la Cintura , Pueblos del Este de AsiaRESUMEN
BACKGROUND OBJECTIVES: Aedes albopictu and Culex pipiens pallens are important vectors of many viruses and have had resistance to chemical pesticide. Spinosad is a selective biological insecticide to control urban mosquito. The aim of this study was to reveal the sublethal effects of spinosad on mosquito and provide reference basis for integrated mosquito management. METHODS: The toxicity of spinosad against Ae. albopictus and Cx. pipiens pallens were determined under laboratory conditions by exposing early third-instar larvae to different concentrations. RESULTS: The LC50 values of spinosad to Ae. albopictus and Cx. Pipiens pallens larvaes were 4.44×10-3 mgâL-1 and 1.93×10-3 mgâL-1 respectively after 72 h exposure. Spinosad at sublethal concentrations has many negative effects on Ae. albopictus and Cx. Pipiens pallens larval, pupae, adult and offspring eggs, including significantly reduced their larvae pupation rate by 51.37% and 58.47%, significantly prolonged pupae length by 21.43% and 16.18%, reduced female wing-spans by 20.19% and 14.89%, reduced male wing-spans by 3.84% and 7.54%, reduced female weight by 29.04% and 31.52%, reduced male weight by 7.47% and 9.07%, reduced female and male ratio by 51.98% and 45.21%, reduced individual egg-laying amount by 15.73% and 35.51%, in addition, offspring egg hatchability were dramatically decreased by 25.71% and 34.04%, egg periods were significantly prolonged by 14.42% and 62.82% respectively. No significant effect on larval period, pupae emergence rate, female bite rates were observed. INTERPRETATION CONCLUSION: These results suggest that spinosad might affect pest population dynamics significantly and is fairly expected to be a candidate biological pesticide for mosquito control.
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Insect developmental transitions are precisely coordinated by ecdysone and juvenile hormone (JH). We previously revealed that accumulated H3K27 trimethylation (H3K27me3) at the locus encoding JH signal transducer Hairy is involved in the larval-pupal transition in insects, but the underlying mechanism remains to be fully defined. Here, we show in Drosophila and Bombyx that Rpd3-mediated H3K27 deacetylation in the prothoracic gland during the last larval instar promotes ecdysone biosynthesis and the larval-pupal transition by enabling H3K27me3 accumulation at the Hairy locus to induce its transcriptional repression. Importantly, we find that the homeodomain transcription factor Schlank acts to switch active H3K27 acetylation (H3K27ac) to repressive H3K27me3 at the Hairy locus by directly binding to the Hairy promoter and then recruiting the histone deacetylase Rpd3 and the histone methyltransferase PRC2 component Su(z)12 through physical interactions. Moreover, Schlank inhibits Hairy transcription to facilitate the larval-pupal transition, and the Schlank signaling cascade is suppressed by JH but regulated in a positive feedback manner by ecdysone. Together, our data uncover that Schlank mediates epigenetic reprogramming of H3K27 modifications in hormone actions during insect developmental transition.
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Proteínas de Drosophila , Ecdisona , Regulación del Desarrollo de la Expresión Génica , Histonas , Larva , Animales , Histonas/metabolismo , Acetilación , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Ecdisona/metabolismo , Larva/metabolismo , Larva/crecimiento & desarrollo , Larva/genética , Bombyx/metabolismo , Bombyx/genética , Bombyx/crecimiento & desarrollo , Hormonas Juveniles/metabolismo , Metilación , Drosophila melanogaster/metabolismo , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/genética , Transducción de Señal , Pupa/metabolismo , Pupa/crecimiento & desarrollo , Pupa/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas Represoras , Factores de Transcripción con Motivo Hélice-Asa-Hélice BásicoRESUMEN
PURPOSE: This retrospective cohort study explores the impact of the COVID-19 pandemic on pediatric trauma cases in Singapore's National University Hospital from January 2015 to July 2021. The pandemic prompted unprecedented measures, altering societal dynamics. The study hypothesizes a reduction in major trauma incidents during the pandemic period. METHODS: This is a single-center retrospective study including all pediatric patients presenting with trauma-related ICD-9 codes, and an Injury Severity Score (ISS) greater than 8. Patients were stratified into two time periods: pre-pandemic (January 2015 to March 2020) and pandemic (April 2020 to July 2021) periods. RESULTS: Out of 254 pediatric trauma cases, 201 occurred pre-pandemic, and 53 during the pandemic. While overall trauma incidence remained similar, the pandemic period saw a shift in injury patterns. Home-based falls increased, vehicular accidents decreased, while deliberate self-harm and caregiver abuse rose significantly. The incidence of serious trauma attributed to non-accidental injury increased during the pandemic. CONCLUSION: The study reveals changing trauma patterns, emphasizing the importance of understanding societal impacts during pandemics. Notably cases of deliberate self-harm and caregiver abuse surged, echoing global concerns highlighted in other studies during the pandemic. The study underscores the need to preempt physical and psychological stressors in vulnerable populations during future pandemics.
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COVID-19 , Conducta Autodestructiva , Poblaciones Vulnerables , Heridas y Lesiones , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Niño , Femenino , Masculino , Heridas y Lesiones/epidemiología , Heridas y Lesiones/psicología , Singapur/epidemiología , Poblaciones Vulnerables/estadística & datos numéricos , Preescolar , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Incidencia , Adolescente , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Lactante , SARS-CoV-2 , Pandemias , Puntaje de Gravedad del TraumatismoRESUMEN
The Leishmania life cycle alternates between promastigotes, found in the sandfly, and amastigotes, found in mammals. When an infected sandfly bites a host, promastigotes are engulfed by phagocytes (i.e., neutrophils, dendritic cells, and macrophages) to establish infection. When these phagocytes die or break down, amastigotes must be re-internalized to survive within the acidic phagolysosome and establish disease. To define host kinase regulators of Leishmania promastigote and amastigote uptake and survival within macrophages, we performed an image-based kinase regression screen using a panel of 38 kinase inhibitors with unique yet overlapping kinase targets. We also targeted inert beads to complement receptor 3 (CR3) or Fcγ receptors (FcR) as controls by coating them with complement/C3bi or IgG respectively. Through this approach, we identified several putative host kinases that regulate receptor-mediated phagocytosis and/or the uptake of L. amazonensis. Findings included kinases previously implicated in Leishmania uptake (such as Src family kinases (SFK), Abl family kinases (ABL1/c-Abl, ABL2/Arg), and spleen tyrosine kinase (SYK)), but we also uncovered many novel kinases. Our methods also predicted host kinases necessary for promastigotes to convert to amastigotes or for amastigotes to survive within macrophages. Overall, our results suggest that the concerted action of multiple interconnected networks of host kinases are needed over the course of Leishmania infection, and that the kinases required for the parasite's life cycle may differ substantially depending on which receptors are bound and the life cycle stage that is internalized. In addition, using our screen, we identified kinases that appear to preferentially regulate the uptake of parasites over beads, indicating that the methods required for Leishmania to be internalized by macrophages may differ from generalized phagocytic mechanisms. Our findings are intended to be used as a hypothesis generation resource for the broader scientific community studying the roles of kinases in host-pathogen interactions.
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OBJECTIVES: This study aims to develop an automated approach for estimating the vertical rotation of the thorax, which can be used to assess the technical adequacy of chest X-ray radiographs (CXRs). METHODS: Total 800 chest radiographs were used to train and establish segmentation networks for outlining the lungs and spine regions in chest X-ray images. By measuring the widths of the left and right lungs between the central line of segmented spine and the lateral sides of the segmented lungs, the quantification of thoracic vertical rotation was achieved. Additionally, a life-size, full body anthropomorphic phantom was employed to collect chest radiographic images under various specified rotation angles for assessing the accuracy of the proposed approach. RESULTS: The deep learning networks effectively segmented the anatomical structures of the lungs and spine. The proposed approach demonstrated a mean estimation error of less than 2° for thoracic rotation, surpassing existing techniques and indicating its superiority. CONCLUSIONS: The proposed approach offers a robust assessment of thoracic rotation and presents new possibilities for automated image quality control in chest X-ray examinations. ADVANCES IN KNOWLEDGE: This study presents a novel deep learning-based approach for the automated estimation of vertical thoracic rotation in chest X-ray radiographs. The proposed method enables a quantitative assessment of the technical adequacy of CXR examinations and opens up new possibilities for automated screening and quality control of radiographs.
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INTRODUCTION: Antiviral treatment can reduce the burden of COVID-19. But utilisation can be suboptimal, even in a setting like Singapore where it is fully subsidized for those with selected medical conditions and older adults (≥ 50 years). We hence investigated the factors affecting awareness, acceptance, and initiative to request Paxlovid. METHODS: We assessed the Paxlovid awareness, factors impacting its uptake in a survey conducted from August 2022 to September 2022 through the SOCRATES cohort. Multivariable logistic regression was used to investigate associations between sociodemographics, perceptions, and attitudes with the key study outcomes. RESULTS: Among respondents to the Paxlovid survey, 54% were aware of Paxlovid. On being provided essential details about Paxlovid, 75% reported they would likely be receptive to taking it if prescribed, and 38% indicated the initiative to request for it if it was not suggested by their doctors. Factors associated with awareness of Paxlovid include aged 40 years old and above, higher education, citing websites as an information source, greater trust in healthcare providers (aOR: 1.65, 95% CI 1.26 - 2.15) and government communications (aOR: 0.69, 95% CI 0.55 - 0.86), and higher perceived risk of COVID-19 infection (aOR: 1.25, 95% CI 1.10 - 1.42). Factors associated with acceptance to take Paxlovid include male gender, citing trust in healthcare providers (aOR: 1.49, 95% CI 1.11 - 1.99) and government communications (aOR: 1.38, 95% CI 1.09 - 1.76), and higher perceived severity of COVID-19 (aOR: 1.23, 95% CI 1.07 - 1.42). Factors associated with initiative to request Paxlovid include male gender, having pre-existing diabetes and higher perceived severity of COVID-19 (aOR: 1.24, 95% CI 1.09 - 1.40). The most common reasons for why respondents might not take Paxlovid were concerns about side effects (64%), concerns about costs (29%), and the perception that COVID-19 is a mild (25%). CONCLUSION: The majority of our respondents would take Paxlovid if it was prescribed to them, but a much smaller proportion would have the initiative to request for this. Key factors that may influence uptake are COVID-19 threat perceptions, trust in healthcare and government, and perceptions of the drug's side effects and cost.