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Stem cell regulation and hierarchical organization of human skeletal progenitors remain largely unexplored. Here, we report the isolation of a self-renewing and multipotent human skeletal stem cell (hSSC) that generates progenitors of bone, cartilage, and stroma, but not fat. Self-renewing and multipotent hSSCs are present in fetal and adult bones and can also be derived from BMP2-treated human adipose stroma (B-HAS) and induced pluripotent stem cells (iPSCs). Gene expression analysis of individual hSSCs reveals overall similarity between hSSCs obtained from different sources and partially explains skewed differentiation toward cartilage in fetal and iPSC-derived hSSCs. hSSCs undergo local expansion in response to acute skeletal injury. In addition, hSSC-derived stroma can maintain human hematopoietic stem cells (hHSCs) in serum-free culture conditions. Finally, we combine gene expression and epigenetic data of mouse skeletal stem cells (mSSCs) and hSSCs to identify evolutionarily conserved and divergent pathways driving SSC-mediated skeletogenesis. VIDEO ABSTRACT.
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Desarrollo Óseo/fisiología , Huesos/citología , Células Madre Hematopoyéticas/citología , Animales , Huesos/metabolismo , Cartílago/citología , Diferenciación Celular , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/fisiología , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Análisis de la Célula Individual/métodos , Células Madre/citología , Células del Estroma/citología , Transcriptoma/genéticaRESUMEN
Kinetic models parameterized by ab-initio calculations have led to significant improvements in understanding chemical reactions in heterogeneous catalysis. These studies have been facilitated by implementations which determine steady-state coverages and rates of mean-field micro-kinetic models. As implemented in the open-source kinetic modeling program, CatMAP, the conventional solution strategy is to use a root-finding algorithm to determine the coverage of all intermediates through the steady-state expressions, constraining all coverages to be non-negative and to properly sum to unity. Though intuitive, this root-finding strategy causes issues with convergence to solution due to these imposed constraints. In this work, we avoid explicitly imposing these constraints, solving the mean-field steady-state micro-kinetic model in the space of number of sites instead of solving it in the space of coverages. We transform the constrained root-finding problem to an unconstrained least-squares minimization problem, leading to significantly improved convergence in solving micro-kinetic models and thus enabling the efficient study of more complex catalytic reactions.
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INTRODUCTION: This prospective, single-arm, pragmatic implementation study evaluated the feasibility of a nurse-led symptom-screening program embedded in routine oncology post-treatment outpatient clinics by assessing (1) the acceptance rate for symptom distress screening (SDS), (2) the prevalence of SDS cases, (3) the acceptance rate for community-based psychosocial support services, and (4) the effect of referred psychosocial support services on reducing symptom distress. METHODS: Using the modified Edmonton Symptom Assessment System (ESAS-r), we screened patients who recently completed cancer treatment. Patients screening positive for moderate-to-severe symptom distress were referred to a nurse-led community-based symptom-management program involving stepped-care symptom/psychosocial management interventions using a pre-defined triage system. Reassessments were conducted at 3-months and 9-months thereafter. The primary outcomes included SDS acceptance rate, SDS case prevalence, intervention acceptance rate, and ESAS-r score change over time. RESULTS: Overall, 2988/3742(80%) eligible patients consented to SDS, with 970(32%) reporting ≥1 ESAS-r symptom as moderate-to-severe (caseness). All cases received psychoeducational material, 673/970(69%) accepted psychosocial support service referrals. Among 328 patients completing both reassessments, ESAS-r scores improved significantly over time (p < 0.0001); 101(30.8%) of patients remained ESAS cases throughout the study, 112(34.1%) recovered at 3-month post-baseline, an additional 72(22%) recovered at 9-month post-baseline, while 43(12.2%) had resumed ESAS caseness at 9-month post-baseline. CONCLUSION: Nurse-led SDS programs with well-structured referral pathways to community-based services and continued monitoring are feasible and acceptable in cancer patients and may help in reducing symptom distress. We intend next to develop optimal strategies for SDS implementation and referral within routine cancer care services.
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Supervivientes de Cáncer , Neoplasias , Humanos , Estudios de Factibilidad , Estudios Prospectivos , Rol de la Enfermera , Detección Precoz del Cáncer , Neoplasias/epidemiología , Evaluación de SíntomasRESUMEN
BACKGROUND: This study aimed to assess the acceptability and attitudes of women towards human papillomavirus (HPV) self-sampling and compare the effectiveness of two delivery modes utilising face-to-face and online website for cervical cancer screening in Hong Kong. METHODS: Women aged 30-65 years were invited to participate by distributing the study information pamphlets at the specialist clinics of a regional acute hospital. Those who were interested in participating were given the option to join directly face-to-face or through an online website. All participants provided informed consent and received self-sampling kits and acceptability questionnaires either immediately (face-to-face) or through the post after registering at the website (online). All participants were requested to collect their own vaginal samples using a swab which was then brushed on a DNA sample storage card and returned to the hospital either in person or by post. The self-collected samples were tested for high-risk HPV using the Sentis™ HPV assay, a validated isothermal nucleic acid amplification real-time fluorescent detection assay. The primary outcome was the uptake rate of HPV self-sampling. RESULTS: Of the 1998 women recruited (1200 face-to-face, 798 online), 1377 returned their samples, giving an overall uptake rate of 68.9%. The uptake rate was significantly greater in the face-to-face mode than in the online mode (74.6% vs. 60.4%, p < 0.001). The median age of the participants was 49 years, 43.7% were never or under-screened, and 7.1% had high-risk HPV detected. Overall, 82.1% of the participants reported self-sampling convenient, and 79.3% were not embarrassed when collecting self-samples. However, only 49.8% were confident that they had collected the self-samples correctly. Most (91.1%) of the participants expressed willingness to perform self-sampling again, mostly because it was simple (79.2%) and quick (56.3%). CONCLUSIONS: HPV self-sampling can serve as an alternative primary screening method for cervical cancer in Hong Kong, especially for individuals who have not been adequately screened in the past. Both face-to-face and online website recruitment were associated with high acceptability, emphasising the potential benefits of utilising different platforms and strategies for reaching diverse populations.
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Detección Precoz del Cáncer , Aceptación de la Atención de Salud , Manejo de Especímenes , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Hong Kong , Anciano , Detección Precoz del Cáncer/métodos , Manejo de Especímenes/métodos , Aceptación de la Atención de Salud/estadística & datos numéricos , Infecciones por Papillomavirus/diagnóstico , Autocuidado , Internet , Frotis Vaginal/métodos , Papillomaviridae/aislamiento & purificación , Encuestas y Cuestionarios , Virus del Papiloma HumanoRESUMEN
BACKGROUND: Percutaneous cholecystostomy (PC) is a therapeutic intervention for acute cholecystitis. The benefits of cholecystostomy have been demonstrated in the medical literature, with up to 90% of acute cholecystitis cases shown to resolve postoperatively, and only 40% of patients subsequently undergoing an interval cholecystectomy. PURPOSE: To compare the survival outcomes between acute complicated and uncomplicated cholecystitis in patients undergoing PC as an initial intervention, as there is a paucity of evidence in the literature on this perspective. MATERIAL AND METHODS: A retrospective search was conducted of all patients who underwent PC for acute cholecystitis between August 2016 and December 2020 at a tertiary institution. A total of 100 patients were included in this study. RESULTS: The outcome, in the form of 30-day mortality, 90-day mortality, being alive after six months, and reintervention, was compared between complicated and uncomplicated cases using the chi-square test or Fisher's exact test. There was no statistically significant difference in any of the compared outcomes. The only variable that showed a statistically significant association with the risk of mortality was acute kidney injury (AKI) at admission. Patients who had stage 1, 2, or 3 AKI had a higher hazard for mortality as compared to patients with no kidney disease. CONCLUSION: Our results demonstrate that PC is a safe and effective procedure. Mortality is not affected by the presence of complications. The results have, however, highlighted the importance of recognizing and treating AKI, an independent risk factor affecting mortality.
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Colecistitis Aguda , Colecistostomía , Humanos , Colecistostomía/métodos , Masculino , Femenino , Estudios Retrospectivos , Colecistitis Aguda/cirugía , Colecistitis Aguda/diagnóstico por imagen , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , AdultoRESUMEN
This pilot study used functional near-infrared spectroscopy (fNIRS) to examine brain activity in selected regions of the left motor and sensory cortex while doing swallowing-related tasks. Specifically, differences in cortical activation during normal saliva swallows, effortful swallows, and tongue pressing were investigated. Nine healthy, right-handed adults (5 female, 4 male; Age: 22-30 years) were recruited. The tasks included were (1) normal saliva swallowing, (2) effortful saliva swallowing, and (3) lingual pressing against the palate. Each task was completed three times in a block, for a total of five blocks. Blocks were randomized and presented with set time intervals using PsychoPy. Motor activity was highest during effortful swallows, followed by normal swallows, and lingual presses. Activation in the sensory region was not significantly different across tasks; however, effortful swallows elicited the highest mean peak activation. Our findings suggest that fNIRS can be a viable imaging method used to examine differences in cortical activity in the context of swallowing. Its applicability in future dysphagia research should be explored.
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BACKGROUND: Interprofessional education (IPE) has the potential to shape students' collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. METHODS: Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson's correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. RESULTS: Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p < .001) after participating in IPE. The positive relationship between collaboration perception and interprofessional identity strengthened after participating in IPE, as evident from the correlation (Time 1: r = .69; p < .001; Time 2: r = .79; p < .001). Furthermore, collaboration perception in Time 1 significantly predicted the variance in interprofessional identity at Time 2 (ß = 0.347, p < .001). Qualitative findings indicated that 85.2% of students expressed that IPE played a role in promoting their interprofessional identity and collaboration attitudes. CONCLUSIONS: Incorporating the IPE program into the curriculum can effectively enhance students' collaboration perception and interprofessional identity, ultimately preparing them for collaborative practice in the healthcare system. By engaging students in interprofessional teamwork, communication, and joint decision-making processes, the IPE program provides a valuable context for students to develop a sense of belonging and commitment to interprofessional collaboration.
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Conducta Cooperativa , Educación Interprofesional , Relaciones Interprofesionales , Identificación Social , Humanos , Femenino , Masculino , Estudiantes del Área de la Salud/psicología , Actitud del Personal de Salud , Adulto Joven , Adulto , CurriculumRESUMEN
BACKGROUND: Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood. METHODS: PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations. RESULTS: Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers. CONCLUSIONS: This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
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MicroARNs , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Cromatografía Liquida , Proteómica , Espectrometría de Masas en Tándem , Neoplasias Ováricas/genética , MicroARNs/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Microambiente TumoralRESUMEN
BACKGROUND: Regarding primary and secondary cervical cancer prevention, the World Health Organization proposed the cervical cancer elimination strategy that requires countries to achieve 90% uptake of human papillomavirus (HPV) vaccines and 70% screening uptake. The optimal cervical screening strategy is likely different for unvaccinated and vaccinated cohorts upon national HPV immunization. However, health authorities typically only provide a one-size-fits-all recommendation for the general population. We aimed to evaluate the cost-effectiveness for determining the optimal screening strategies for vaccinated and unvaccinated cohorts. METHODS: We considered the women population in Hong Kong which has a unique HPV infection and cervical cancer epidemiology compared to other regions in China and Asia. We used mathematical models which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of screening strategies for cervical screening. Following the recommendations in local guidelines in Hong Kong, we considered strategies that involved cytology, HPV testing, or co-testing as primary cervical screening. We also explored the impacts of adopting alternative de-intensified strategies for vaccinated cohorts. The 3-year cytology screening was used as the base comparator while no screening was also considered for vaccinated cohorts. Women's lifetime life years, quality-adjusted life years, and costs of screening and treatment were estimated from the societal perspective based on the year 2022 and were discounted by 3% annually. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US $47,792). Probabilistic and one-way sensitivity analyses were conducted. RESULTS: Among unvaccinated cohorts, the strategy that adds reflex HPV to triage mild cytology abnormality generated more life years saved than cytology-only screening and could be a cost-effective alternative. Among vaccinated cohorts, when vaccine uptake was 85% (based on the uptake in 2022), all guideline-based strategies (including the cytology-only screening) had ICERs above the WTP threshold when compared with no screening if the vaccine-induced protection duration was 20 years or longer. Under the same conditions, HPV testing with genotyping triage had ICERs (compared with no screening) below the WTP threshold if the routine screening interval was lengthened to 10 and 15 years or screening was initiated at ages 30 and 35 years. CONCLUSIONS: HPV testing is a cost-effective alternative to cytology for vaccinated cohorts, and the associated optimal screening frequency depends on vaccine uptake. Health authorities should optimize screening recommendations by accounting for population vaccine uptake.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Análisis Costo-Beneficio , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/complicaciones , Detección Precoz del Cáncer/métodos , Vacunación , Tamizaje Masivo/métodos , Hong Kong/epidemiologíaRESUMEN
Electrochemical CO2 reduction (eCO2R) enables the conversion of waste CO2 to high-value fuels and commodity chemicals powered by renewable electricity, thereby offering a viable strategy for reaching the goal of net-zero carbon emissions. Research in the past few decades has focused both on the optimization of the catalyst (electrode) and the electrolyte environment. Surface-area normalized current densities show that the latter can affect the CO2 reduction activity by up to a few orders of magnitude.In this Account, we review theories of the mechanisms behind the effects of the electrolyte (cations, anions, and the electrolyte pH) on eCO2R. As summarized in the conspectus graphic, the electrolyte influences eCO2R activity via a field (ε) effect on dipolar (µ) reaction intermediates, changing the proton donor for the multi-step proton-electron transfer reaction, specifically adsorbed anions on the catalyst surface to block active sites, and tuning the local environment by homogeneous reactions. To be specific, alkali metal cations (M+) can stabilize reaction intermediates via electrostatic interactions with dipolar intermediates or buffer the interfacial pH via hydrolysis reactions, thereby promoting the eCO2R activity with the following trend in hydrated size (corresponding to the local field strength ε)/hydrolysis ability: Cs+ > K+ > Na+ > Li+. The effect of the electrolyte pH can give a change in eCO2R activity of up to several orders of magnitude, arising from linearly shifting the absolute interfacial field via the relationship USHE = URHE - (2.3kBT)pH, homogeneous reactions between OH- and desorbed intermediates, or changing the proton donor from hydronium to water along with increasing pH. Anions have been suggested to affect the eCO2R reaction process by solution-phase reactions (e.g., buffer reactions to tune local pH), acting as proton donors or as a surface poison.So far, the existing models of electrolyte effects have been used to rationalize various experimentally observed trends, having yet to demonstrate general predictive capabilities. The major challenges in our understanding of the electrolyte effect in eCO2R are (i) the long time scale associated with a dynamic ab initio picture of the catalyst|electrolyte interface and (ii) the overall activity determined by the length-scale interplay of intrinsic microkinetics, homogeneous reactions, and mass transport limitations. New developments in ab initio dynamic models and coupling the effects of mass transport can provide a more accurate view of the structure and intrinsic functions of the electrode-electrolyte interface and the corresponding reaction energetics toward comprehensive and predictive models for electrolyte design.
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Dióxido de Carbono , Electrólitos , Dióxido de Carbono/química , Catálisis , Electrólitos/química , Transporte de Electrón , ProtonesRESUMEN
BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is distinct from acute decompensation (AD) of cirrhosis in its clinical presentation, pathophysiology, and prognosis. There are limited published Australian ACLF data. METHODS: We performed a single-center retrospective cohort study of all adults with cirrhosis admitted with a decompensating event to a liver transplantation (LT) centre between 2015 and 2020. ACLF was defined using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) definition while those who did not meet the definition were classified as AD. The primary outcome of interest was 90-day LT-free survival. RESULTS: A total of 615 patients had 1039 admissions for a decompensating event. On their index admission, 34% (209/615) of patients were classified as ACLF. Median admission model for end-stage liver disease (MELD) and MELD-Na scores were higher in ACLF patients compared with AD (21 vs 17 and 25 vs 20 respectively, both P < 0.001). Both the presence and severity of ACLF (grade ≥ 2) significantly predicted worse LT-free survival compared with patients with AD. The EASL-CLIF ACLF score (CLIF-C ACLF), MELD and MELD-Na scores performed similarly in predicting 90-day mortality. Patients with index ACLF had a higher risk of 28-day mortality (28.1% vs 5.1%, P < 0.001) and shorter times to readmission compared with those with AD. CONCLUSION: ACLF complicates over a third of hospital admissions for cirrhosis with decompensating events and is associated with a high short-term mortality. The presence and grade of ACLF predicts 90-day mortality and should be identified as those at greatest risk of poor outcome without intervention such as LT.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Adulto , Humanos , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/etiología , Estudios Retrospectivos , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Australia/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , PronósticoRESUMEN
Approved drugs for the treatment of osteoporosis can prevent further bone loss but do not stimulate bone formation. Approaches that improve bone density in metabolic diseases are needed. Therapies that take advantage of the ability of mesenchymal stem cells (MSCs) to differentiate into various osteogenic lineages to treat bone disorders are of particular interest. Here we examine the ability of small interfering RNA (siRNA) to enhance osteoblast differentiation and bone formation by silencing the negative suppressor gene GNAS in bone MSCs. Using clinically validated lipid nanoparticle (LNP) siRNA delivery systems, we show that silencing the suppressor gene GNAS in vitro in MSCs leads to molecular and phenotypic changes similar to those seen in osteoblasts. Further, we demonstrate that these LNP-siRNAs can transfect a large proportion of mice MSCs in the compact bone following intravenous injection. Transfection of MSCs in various animal models led to silencing of GNAS and enhanced differentiation of MSCs into osteoblasts. These data demonstrate the potential for LNP delivery of siRNA to enhance the differentiation of MSCs into osteoblasts, and suggests that they are a promising approach for the treatment of osteoporosis and other bone diseases.
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Células Madre Mesenquimatosas , Osteoporosis , Animales , Diferenciación Celular/genética , Células Cultivadas , Liposomas , Células Madre Mesenquimatosas/metabolismo , Ratones , Nanopartículas , Osteoblastos/metabolismo , Osteogénesis/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Osteoporosis/terapia , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismoRESUMEN
OBJECTIVES: To perform a systematic review and meta-analysis of the techniques and outcomes associated with percutaneous decannulation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) using the Manta vascular closure device. BACKGROUND: Peripheral VA-ECMO can be used to treat critically ill patients with conditions such as refractory cardiogenic shock. After percutaneous implantation of VA-ECMO, VA-ECMO can also be decannulated completely percutaneously by using a vascular closure device. The Manta vascular closure device is a dedicated device used in the closure of large-bore arteriotomies by sandwiching the arteriotomy with an intra-arterial toggle and an extraluminal collagen plug. METHODS: We performed a thorough literature search using various electronic databases. We included studies that reported outcomes after peripheral femorofemoral VA-ECMO decannulation with the Manta vascular closure device. We performed a meta-analysis of proportions on outcome measures, including technical success, bleeding complications, vascular complications, wound complications, major amputation, and procedural-related deaths. RESULTS: We included seven studies with a total of 116 patients. The overall technical success of percutaneous decannulation of VA-ECMO with the Manta vascular closure device was 93.7%. The overall incidence of bleeding, vascular and wound complications was 1.7%, 13.8%, and 3.4%, respectively. No patient required lower limb amputation or died due to VA-ECMO decannulation. CONCLUSION: Percutaneous decannulation with the Manta vascular closure device is an effective and safe procedure that should be considered in suitable patients on VA-ECMO.
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Oxigenación por Membrana Extracorpórea , Dispositivos de Cierre Vascular , Humanos , Dispositivos de Cierre Vascular/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Choque Cardiogénico/cirugía , Choque Cardiogénico/complicaciones , Hemorragia/etiología , Remoción de Dispositivos/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction. METHODS: Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient). RESULTS: Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively. CONCLUSIONS: Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.
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Oftalmopatía de Graves , Aparato Lagrimal , Humanos , Oftalmopatía de Graves/diagnóstico por imagen , Oftalmopatía de Graves/patología , Aparato Lagrimal/diagnóstico por imagen , Aparato Lagrimal/patología , Imagen de Difusión Tensora/métodos , Imagen por Resonancia Magnética , Evaluación de Resultado en la Atención de SaludRESUMEN
PURPOSE: Monkeypox (or "mpox" as preferred by the World Health Organization) is an emerging infectious disease with sustained global transmission occurring outside of West Africa and the Democratic Republic of Congo. The recent 2022 mpox outbreak has involved widespread atypical presentations. Infected patients requiring surgery can increase the exposure of health care professionals and other patients to the virus. As it is a relatively new infectious disease internationally, there is less familiarity in managing this risk, especially in the surgical and anesthesia setting. This paper aims to provide information about mpox and how to manage suspected or confirmed cases. SOURCE: Various authorities such as the World Health Organization, Infection Prevention and Control Canada, Public Health Agency of Canada, the Centers for Disease Control and Prevention (USA), and the National Centre for Infectious Diseases (Singapore) have recommended that public health and hospital systems prepare to recognize, isolate, and care for suspected and confirmed cases appropriately, as well as manage any possible exposure of staff and patients. PRINCIPAL FINDINGS: Local authorities and hospitals should set up protocols for health care providers (HCPs) to minimize nosocomial transmission and risk to HCPs. Antivirals used in patients with more severe disease may cause renal or hepatic impairment and thus anesthetic drug pharmacology. Anesthesiologists and surgeons should be able to recognize mpox, and work with local infection control and epidemiologic programs to familiarize themselves with relevant infection prevention guidelines. CONCLUSION: Essential measures include clear protocols for transferring and managing surgical patients who are suspected or confirmed to be infected with the virus. Care in use of personal protective equipment and handling contaminated material is necessary to prevent inadvertent exposure. Risk stratification after exposure should be done to determine need for post-exposure prophylaxis for staff.
RéSUMé: OBJECTIF: La variole du singe (ou « mpox ¼, le terme privilégié en anglais par l'Organisation mondiale de la santé) est une maladie infectieuse émergente dont la transmission mondiale est soutenue en dehors de l'Afrique de l'Ouest et de la République démocratique du Congo. La récente épidémie de variole du singe de 2022 a donné lieu à des présentations atypiques généralisées. Les patients infectés nécessitant une intervention chirurgicale peuvent accroître l'exposition des professionnels de la santé et des autres patients au virus. Comme il s'agit d'une maladie infectieuse relativement nouvelle à l'échelle internationale, la gestion de ce risque d'exposition est moins familière, en particulier dans le cadre chirurgical et anesthésique. Cet article vise à fournir des informations sur la variole du singe et sur la prise en charge des cas suspects ou confirmés. SOURCES: Diverses autorités telles que l'Organisation mondiale de la Santé, Prévention et contrôle des infections Canada, l'Agence de la santé publique du Canada, les Centers for Disease Control and Prevention (États-Unis) et le National Centre for Infectious Diseases (Singapour) ont recommandé que les systèmes de santé publique et hospitaliers se préparent à reconnaître, isoler et soigner les cas suspects et confirmés de manière appropriée, ainsi qu'à gérer toute exposition possible du personnel et des patients. CONSTATATIONS PRINCIPALES: Les autorités locales et les hôpitaux devraient établir des protocoles pour les fournisseurs de soins de santé afin de minimiser la transmission nosocomiale et les risques pour eux. Les antiviraux utilisés chez les patients atteints d'une forme plus grave de la maladie peuvent entraîner une insuffisance rénale ou hépatique et, par conséquent, une altération de la pharmacologie anesthésique. Les anesthésiologistes et les chirurgiens devraient être en mesure de reconnaître la variole du singe et de travailler avec les programmes locaux de contrôle des infections et d'épidémiologie pour se familiariser avec les lignes directrices pertinentes en matière de prévention des infections. CONCLUSION: Les mesures essentielles comprennent des protocoles clairs pour le transfert et la prise en charge des patients chirurgicaux soupçonnés ou confirmés d'être infectés par le virus. Il faut faire preuve de prudence dans l'utilisation des équipements de protection individuelle et la manipulation des matières contaminées afin de prévenir une exposition accidentelle. La stratification du risque après l'exposition devrait être réalisée afin de déterminer la nécessité d'une prophylaxie post-exposition pour le personnel.
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Anestesia , Anestesiología , Mpox , Estados Unidos , Humanos , Mpox/epidemiología , Mpox/prevención & control , Anestesiólogos , CanadáRESUMEN
Electrochemical CO reduction can serve as a sequential step in the transformation of CO2 into multicarbon fuels and chemicals. In this study, we provide insights on how to steer selectivity for CO reduction almost exclusively toward a single multicarbon oxygenate by carefully controlling the catalyst composition and its surrounding reaction conditions. Under alkaline reaction conditions, we demonstrate that planar CuAg electrodes can reduce CO to acetaldehyde with over 50% Faradaic efficiency and over 90% selectivity on a carbon basis at a modest electrode potential of -0.536 V vs. the reversible hydrogen electrode. The Faradaic efficiency to acetaldehyde was further enhanced to 70% by increasing the roughness factor of the CuAg electrode. Density functional theory calculations indicate that Ag ad-atoms on Cu weaken the binding energy of the reduced acetaldehyde intermediate and inhibit its further reduction to ethanol, demonstrating that the improved selectivity to acetaldehyde is due to the electronic effect from Ag incorporation. These findings will aid in the design of catalysts that are able to guide complex reaction networks and achieve high selectivity for the desired product.
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Emerging evidence suggests a resurgence of COVID-19 in the coming years. It is thus critical to optimize emergency response planning from a broad, integrated perspective. We developed a mathematical model incorporating climate-driven variation in community transmissions and movement-modulated spatial diffusions of COVID-19 into various intervention scenarios. We find that an intensive 8-wk intervention targeting the reduction of local transmissibility and international travel is efficient and effective. Practically, we suggest a tiered implementation of this strategy where interventions are first implemented at locations in what we call the Global Intervention Hub, followed by timely interventions in secondary high-risk locations. We argue that thinking globally, categorizing locations in a hub-and-spoke intervention network, and acting locally, applying interventions at high-risk areas, is a functional strategy to avert the tremendous burden that would otherwise be placed on public health and society.
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Control de Enfermedades Transmisibles/métodos , Enfermedades Transmisibles Emergentes/prevención & control , Infecciones por Coronavirus/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Salud Global/tendencias , Pandemias/prevención & control , Neumonía Viral/prevención & control , Betacoronavirus , COVID-19 , Clima , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Predicción , Humanos , Cooperación Internacional , Modelos Teóricos , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , SARS-CoV-2 , ViajeRESUMEN
Linear scaling relations have led to an understanding of trends in catalytic activity and selectivity of many reactions in heterogeneous and electro-catalysis. However, linear scaling between the chemisorption energies of any two small molecule adsorbates is not guaranteed. A prominent example is the lack of scaling between the chemisorption energies of carbon and oxygen on transition metal surfaces. In this work, we show that this lack of scaling originates from different re-normalized adsorbate valence energies of lower-lying oxygen vs higher-lying carbon. We develop a model for chemisorption of small molecule adsorbates within the d-band model by combining a modified form of the Newns-Anderson hybridization energy with an effective orthogonalization term. We develop a general descriptor to a priori determine if two adsorbates are likely to scale with each other.
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This study aimed to investigate the relationship between intensity-modulated radiation therapy (IMRT) dosimetry and swallowing kinematic and timing measures. Thirteen kinematic and timing measures of swallowing from videofluoroscopic analysis were used as outcome measures to reflect swallowing function. IMRT dosimetry was accessed for thirteen swallowing-related structures. A cohort of 44 nasopharyngeal carcinoma (NPC) survivors at least 3 years post-IMRT were recruited. The cohort had a mean age of 53.2 ± 11.9 years, 77.3% of whom were male. There was an average of 68.24 ± 14.15 months since end of IMRT; 41 (93.2%) had undergone concurrent chemotherapy. For displacement measures, female sex and higher doses to the cricopharyngeus, glottic larynx, and base of tongue were associated with reduced hyolaryngeal excursion and pharyngeal constriction, and more residue. For timing measures, higher dose to the genioglossus was associated with reduced processing time at all stages of the swallow. The inferior pharyngeal constrictor emerged with a distinctly different pattern of association with mean radiation dosage compared to other structures. Greater changes to swallowing kinematics and timing were observed for pudding thick consistency than thin liquid. Increasing radiation dosage to swallowing-related structures is associated with reduced swallowing kinematics. However, not all structures are affected the same way, therefore organ sparing during treatment planning for IMRT needs to consider function rather than focusing on select muscles. Dose-response relationships should be investigated with a comprehensive set of swallowing structures to capture the holistic process of swallowing.
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Trastornos de Deglución , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Adulto , Anciano , Fenómenos Biomecánicos , Deglución/fisiología , Trastornos de Deglución/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Dosis de Radiación , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , SobrevivientesRESUMEN
Ovarian cancer is the deadliest gynecological cancer, leading to over 152,000 deaths each year. A late diagnosis is the primary factor causing a poor prognosis of ovarian cancer and often occurs due to a lack of specific symptoms and effective biomarkers for an early detection. Currently, cancer antigen 125 (CA125) is the most widely used biomarker for ovarian cancer detection, but this approach is limited by a low specificity. In recent years, multimarker panels have been developed by combining molecular biomarkers such as human epididymis secretory protein 4 (HE4), ultrasound results, or menopausal status to improve the diagnostic efficacy. The risk of ovarian malignancy algorithm (ROMA), the risk of malignancy index (RMI), and OVA1 assays have also been clinically used with improved sensitivity and specificity. Ongoing investigations into novel biomarkers such as autoantibodies, ctDNAs, miRNAs, and DNA methylation signatures continue to aim to provide earlier detection methods for ovarian cancer. This paper reviews recent advancements in molecular biomarkers for the early detection of ovarian cancer.