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BACKGROUND: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. METHODS: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. RESULTS: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. CONCLUSIONS: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.
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Doenças Cardiovasculares , Neoplasias , Inquéritos Nutricionais , Humanos , Estados Unidos/epidemiologia , Reino Unido/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Doenças Cardiovasculares/mortalidade , Adulto , Estudos de Coortes , Idoso , Bancos de Espécimes Biológicos , Fatores de Risco , Biobanco do Reino UnidoRESUMO
Bioorthogonal nanozymes have emerged as a potent tool in biomedicine due to their unique ability to perform enzymatic reactions that do not interfere with native biochemical processes. The integration of stimuli-responsive mechanisms into these nanozymes has further expanded their potential, allowing for controlled activation and targeted delivery. As such, intelligent bioorthogonal nanozymes have received more and more attention in developing therapeutic approaches. This review provides a comprehensive overview of the recent advances in the development and application of stimuli-responsive bioorthogonal nanozymes. By summarizing the design outlines for anchoring bioorthogonal nanozymes with stimuli-responsive capability, this review seeks to offer valuable insights and guidance for the rational design of these remarkable materials. This review highlights the significant progress made in this exciting field with different types of stimuli and the various applications. Additionally, it also examines the current challenges and limitations in the design, synthesis, and application of these systems, and proposes potential solutions and research directions. This review aims to stimulate further research toward the development of more efficient and versatile stimuli-responsive bioorthogonal nanozymes for biomedical applications.
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The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses.
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Administração Oftálmica , Sistemas de Liberação de Medicamentos , Géis , Salvia , Animais , Salvia/química , Sistemas de Liberação de Medicamentos/métodos , Distribuição Tecidual , Temperatura , Poloxâmero/química , Coelhos , Olho/efeitos dos fármacos , Olho/metabolismo , Química Farmacêutica/métodos , Derivados da Hipromelose/química , Masculino , Reologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinéticaRESUMO
Healthcare providers need to simultaneously identify with their own profession and the broader interprofessional group to improve interprofessional team functioning and collaboration. The purpose of this study was to explore firstyear healthcare students' interprofessional identity development following a brief introductory interprofessional activity. The Extended Professional Identity Theory (EPIT) served as the framework for this qualitative study. The sample included 1,047 students from 19 different health professions at one institution in the first semester of their professional program. Deductive content analysis was used to analyze students' reflections from two reflective questions in a mandatory course evaluation survey. The 24-item version of the Extended Professional Identity Scale was used as a structured categorization matrix for deductive coding of student reflections to the three EPIT constructs: interprofessional belonging, commitment, and beliefs. Participant responses, spanning all three EPIT constructs, support the ability of early health professions learners to demonstrate the development of an emerging interprofessional identity. Future research is needed to assess IPI at various points across the curriculum and to explore between profession differences and the implications for foundational IPE design and learning along the continuum into practice.
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BACKGROUND: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). METHODS: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. RESULTS: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m2) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%. CONCLUSIONS: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Predisposição Genética para Doença , Adoçantes não Calóricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco de Doenças Cardíacas , Incidência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Biobanco do Reino Unido , Reino Unido/epidemiologia , Adoçantes não Calóricos/efeitos adversosRESUMO
BACKGROUND: Previous studies underscore the protective role of physical activity (PA) in bone health, yet the relationship between different PA categories and osteoporosis risk remains less explored. Understanding the relationships helps tailor health recommendations and policies to maximize the effects of preventing osteoporosis. METHODS: The cross-sectional study involves 488,403 UK Biobank participants with heel quantitative ultrasound-estimated bone mineral density (eBMD) data. The longitudinal cohort involves 471,394 UK Biobank participants without initial osteoporosis and with follow-up records. PA exposure categories in our study included sedentary behavior (SB), total PA (TPA), and different category-specific PA including household, leisure, and work PA. The cases of osteoporosis were assessed using the International Classification of Diseases, 10th revision (ICD-10). The linear, logistic, and Cox proportional hazard regression models were used in our study. RESULTS: In the cross-sectional study, 15,818 (3.28 %) participants had osteoporosis. TPA levels have a positive correlation with eBMD and a negative correlation with osteoporosis prevalence. Among different categories of PA, higher levels of leisure PA were correlated with increased eBMD and a lower osteoporosis risk (leisure PA: OR: 0.83, 95 % CI: 0.79 to 0.86;). In the longitudinal study, 16,058 (17.6 % male, 82.4 % female) (3.41 %) individuals developed osteoporosis during an average follow-up of 13 years. We observed consistent protective effects of high levels of PA on osteoporosis incidence risk, particularly within the category of leisure PA (TPA: HR: 0.78, 95 % CI: 0.74 to 0.82; leisure PA:HR: 0.83, 95 % CI: 0.80 to 0.87). Such associations are independent of genetic predisposition, with no evidence of gene-PA interactions, and keep steady among individuals using drugs affecting bone-density. Moreover, among different leisure PA items, strenuous sports, other exercises, and walking for pleasure conferred a substantial protective effect against osteoporosis. Additionally, non-elderly individuals and males exhibited lower osteoporosis risk from PA. CONCLUSION: This study highlights activity categories differently associated with the risk of osteoporosis. Adherence to frequent leisure PA may have a protective effect against osteoporosis. Such associations are independent of genetic susceptibility to osteoporosis and keep steady among individuals using drugs affecting bone-density. This highlights that leisure PA could be suggested as a more effective intervention in the primary prevention of osteoporosis.
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Bancos de Espécimes Biológicos , Exercício Físico , Atividades de Lazer , Osteoporose , Humanos , Estudos Transversais , Feminino , Masculino , Osteoporose/epidemiologia , Reino Unido/epidemiologia , Exercício Físico/fisiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Prevalência , Incidência , Idoso , Densidade Óssea/fisiologia , Adulto , Biobanco do Reino UnidoRESUMO
Nanozymes have garnered considerable research interest for their unique capacity to bridge nanotechnology and biology. Current studies predominantly concentrate on exploring nanozymes with diverse catalytic activities and their potential applications across various disciplines. Among them, nanoscale metal-organic frameworks (MOFs) are promising nanomaterials for constructing nanozymes. In this review, we firstly introduce the general construction strategies for MOF-based nanozymes. In addition, we also classify the MOF-based nanozymes in detail based on their catalytic performance. Thirdly, the recent research progress of MOF-based nanozymes in the field of biosensing, cancer therapy, antibacterial infection, and antioxidation are also comprehensively reviewed. Finally, we discuss the current challenges and future perspectives of MOF-based nanozymes, with the aim of assisting in their construction and maximizing their potential in bioapplications. It is hoped that we could provide scientists in materials science and biomedical research with valuable and comprehensive information, fostering advancements in interdisciplinary fields.
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Técnicas Biossensoriais , Estruturas Metalorgânicas , Nanoestruturas , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Humanos , Nanoestruturas/química , Catálise , Nanotecnologia/métodos , Animais , Neoplasias/tratamento farmacológicoRESUMO
Aim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF). Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships. Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results. Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.
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BACKGROUND: The aim of this study was to explore the efficacy of a novel intramedullary fixation technique using the ortho-bridge system (OBS) for midshaft clavicle fractures. METHODS: A total of 63 patients were included in this study: 35 underwent plate internal fixation (LP group) and 28 underwent OBS intramedullary fixation (OBS group). Surgical time, intraoperative blood loss, incision length, fracture healing time, removal of the internal fixation agent, visual analog scale (VAS) score for shoulder pain, Constant-Murley shoulder score and complication occurrence were compared between the two groups. RESULTS: Preoperative general data, such as sex, age and fracture type, were not significantly different between the two groups (P > 0.05). However, the OBS group exhibited better outcomes than the LP group exhibited in terms of surgical time, intraoperative blood loss and total incision length (P < 0.05). Additionally, the OBS group exhibited a significantly shorter fracture healing time and internal-fixation removal time than the LP group exhibited (P < 0.05). The VAS scores on postoperative day 1, week 1, month 1 and month 3 were lower in the OBS group than in the LP group (P < 0.05). Furthermore, the Constant-Murley shoulder scores at 1, 3, and 6 months postoperatively were higher in the OBS group than in the LP group (P < 0.05), with no significant difference at 1 year after surgery (P > 0.05). None of the patients in the OBS group experienced scarring of the surgical incision, and 6 patients in the LP group experienced scarring of the surgical incision. Finally, the complication incidence in the OBS group was lower than that in the LP group. CONCLUSION: For midshaft clavicle fractures, OBS intramedullary fixation is better than locking-plate internal fixation because it led to less trauma, a faster recovery, better efficacy, and better esthetic outcomes and comfort. Therefore, this technique may have potential as a novel treatment for midshaft clavicle fractures. LEVEL OF EVIDENCE: III, retrospective observational study.
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Placas Ósseas , Clavícula , Fixação Intramedular de Fraturas , Consolidação da Fratura , Fraturas Ósseas , Duração da Cirurgia , Humanos , Clavícula/lesões , Clavícula/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Fraturas Ósseas/cirurgia , Adulto , Fixação Intramedular de Fraturas/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Medição da Dor , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Fixação Interna de Fraturas/métodosRESUMO
Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified lecithin cholesterol acyltransferase (LCAT) as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth-promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and to dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC. Significance: Estrogen mediates the sex differences in hepatocellular carcinoma development by reducing cholesterol biosynthesis through activation of an LCAT/HDL-C axis, providing strategies for improving liver cancer prevention, prognosis, and treatment.
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Carcinoma Hepatocelular , Colesterol , Estrogênios , Homeostase , Neoplasias Hepáticas , Fosfatidilcolina-Esterol O-Aciltransferase , Animais , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , Estrogênios/metabolismo , Colesterol/metabolismo , Feminino , Masculino , Proliferação de Células/efeitos dos fármacos , Prognóstico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , HDL-Colesterol/metabolismo , HDL-Colesterol/sangue , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genéticaRESUMO
BACKGROUND: The intricate balance between the advantages and risks of low-dose computed tomography (LDCT) impedes the utilization of lung cancer screening (LCS). Guiding shared decision-making (SDM) for well-informed choices regarding LCS is pivotal. There has been a notable increase in research related to SDM. However, these studies possess limitations. For example, they may ignore the identification of decision support and needs from the perspective of health care providers and high-risk groups. Additionally, these studies have not adequately addressed the complete SDM process, including pre-decisional needs, the decision-making process, and post-decision experiences. Furthermore, the East-West divide of SDM has been largely ignored. This study aimed to explore the decisional needs and support for shared decision-making for LCS among health care providers and high-risk groups in China. METHODS: Informed by the Ottawa Decision-Support Framework, we conducted qualitative, face-to-face in-depth interviews to explore shared decision-making among 30 lung cancer high-risk individuals and 9 health care providers. Content analysis was used for data analysis. RESULTS: We identified 4 decisional needs that impair shared decision-making: (1) LCS knowledge deficit; (2) inadequate supportive resources; (3) shared decision-making conceptual bias; and (4) delicate doctor-patient bonds. We identified 3 decision supports: (1) providing information throughout the LCS process; (2) providing shared decision-making decision coaching; and (3) providing decision tools. CONCLUSIONS: This study offers valuable insights into the decisional needs and support required to undergo LCS among high-risk individuals and perspectives from health care providers. Future studies should aim to design interventions that enhance the quality of shared decision-making by offering LCS information, decision tools for LCS, and decision coaching for shared decision-making (e.g., through community nurses). Simultaneously, it is crucial to assess individuals' needs for effective deliberation to prevent conflicts and regrets after arriving at a decision.
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Tomada de Decisão Compartilhada , Detecção Precoce de Câncer , Pessoal de Saúde , Neoplasias Pulmonares , Pesquisa Qualitativa , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Feminino , China , Pessoa de Meia-Idade , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/métodos , Pessoal de Saúde/psicologia , Idoso , Tomografia Computadorizada por Raios X/métodos , Adulto , Participação do PacienteRESUMO
Introduction: Rates of lung cancer screening among Latinos remain low. The purpose of the study was to understand the perceived benefits, barriers, and cues to action for lung cancer screening among Latinos. Methods: Participants (N=20) were recruited using community-based recruitment strategies. Eligibility criteria included: 1) self-identified as Hispanic/Latino, 2) spoke English and/or Spanish, and 3) met the USA Preventive Services Task Force eligibility criteria for lung cancer screening. Interviews were conducted in Spanish and English, audio recorded, and transcribed verbatim. Using the health belief model, a qualitative theoretical analysis was used to analyze the interviews. Results: Participants' mean age was 58.3 years old (SD=5.8), half of the participants were female, 55% had completed high school or lower educational level, and 55% reported speaking more Spanish than English. All participants were currently smoking. Fourteen participants (70%) were unaware of lung cancer screening, and eighteen (90%) did not know they were eligible for lung cancer screening. Regarding lung cancer screening, participants reported multiple perceived benefits (e.g., smoking cessation, early detection of lung cancer, increased survivorship) and barriers (e.g., fear of outcomes, cost, lung cancer screening not being recommended by their clinician). Lastly, multiple cues to actions for lung cancer screening were identified (e.g., family as a cue to action for getting screened). Conclusions: Most Latinos who were eligible for lung cancer screening were unaware of it and, when informed, they reported multiple perceived benefits, barriers, and cues to action. These factors provide concrete operational strategies to address lung cancer screening among Latinos.
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RATIONALE: Neuroblastoma amplified sequence (NBAS)-associated disease is an autosomal recessive disorder and a broad spectrum of clinical symptoms has been reported. However, autoimmune mediated hemolytic anemia (AIHA) is rarely reported in NBAS disease. PATIENT CONCERNS: A now 21-year-old male harbors heterozygous variants of c.6840G>A and c.335 + 1G>A and was found had retarded growth, hypogammaglobulinemia, B lymphopenia, optic atrophy, horizontal nystagmus, slight splenomegaly and hepatomegaly since childhood. This case had normal hemoglobin level and platelet count in his childhood. He developed AIHA first in his adulthood and then thrombocytopenia during the treatment of AIHA. The mechanism underlying a case with pronounced hypogammaglobulinemia and B lymphopenia is elusive. In addition to biallelic NBAS mutations, a germline mutation in the ANKRD26 (c.2356C>T) gene was also detected. So either autoimmune or ANKRD26 mutation-mediated thrombocytopenia is possible in this case. INTERVENTION AND OUTCOME: He was initially managed with steroid and intermittent intravenous immunoglobulin supplement. After treatment, he responded well with a normalization of hemoglobin and serum bilirubin. But the patient subsequently experienced severe thrombocytopenia in addition to AIHA. He was then given daily avatrombopag in addition to steroid escalation. He responded again to new treatment, with the hemoglobin levels and platelet counts went back to the normal ranges. Now he was on de-escalated weekly avatrombopag and low-dose steroids maintenance. CONCLUSION: The phenotype of this case indicates that c.335 + 1G>A NBAS variant is probably a pathogenic one and c.2356C>T ANKRD26 variant is improbably a pathogenic one. AIHA may respond well to steroid even when happened in patients with NBAS disease.
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Agamaglobulinemia , Anemia Hemolítica Autoimune , Linfopenia , Neuroblastoma , Tiazóis , Tiofenos , Trombocitopenia , Masculino , Humanos , Adulto , Criança , Adulto Jovem , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/tratamento farmacológico , Anemia Hemolítica Autoimune/genética , Agamaglobulinemia/complicações , Trombocitopenia/complicações , Mutação , Linfopenia/complicações , Hemoglobinas , Esteroides , Neuroblastoma/complicações , ChinaRESUMO
BACKGROUND: Promoting lung cancer screening (LCS) is complex. Previous studies have overlooked that LCS behaviors are stage based and thus did not identify the characteristics of LCS interventions at different screening stages. OBJECTIVE: The aims of this study were to explore the characteristics and efficacy of interventions in promoting LCS decision making and behaviors and to evaluate these interventions. METHODS: We conducted a study search from the inception of each bibliographic database to April 8, 2023. The precaution adoption process model was used to synthesize and classify the evidence. The RE-AIM framework was used to evaluate the effectiveness of LCS programs. Heterogeneity tests and meta-analysis were performed using RevMan 5.4 software. RESULTS: We included 31 studies that covered 4 LCS topics: knowledge of lung cancer, knowledge of LCS, value clarification exercises, and LCS supportive resources. Patient decision aids outperformed educational materials in improving knowledge and decision outcomes with a significant reduction in decision conflict (standardized mean difference, 0.81; 95% confidence interval, -1.15 to -0.47; P < .001). Completion rates of LCS ranged from 3.6% to 98.8%. Interventions that included screening resources outperformed interventions that used patient decision aids alone in improving LCS completion. The proportions of reported RE-AIM indicators were highest for reach (69.59%), followed by adoption (43.87%), effectiveness (36.13%), implementation (33.33%), and maintenance (9.68%). CONCLUSION: Evidence from 31 studies identified intervention characteristics and effectiveness of LCS interventions based on different stages of decision making. IMPLICATIONS FOR PRACTICE: It is crucial to develop targeted and systematic interventions based on the characteristics of each stage of LCS to maximize intervention effectiveness and reduce the burden of lung cancer.
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OBJECTIVE: Previous studies focused on the benefits of adequate prosthodontic treatment, while few studies have investigated the prosthodontic-related risks to health. As a modifiable oral health indicator, the association of ill-fitting prosthesis (IFP) with hypertension has not been fully explored. METHODS: This cross-sectional study involved 158,659 adults in Beijing (2009-2017) receiving intra-oral examinations and blood pressure measurements. Logistic regression models were applied to assess the association of IFP with the prevalence of hypertension, systolic blood pressure (SBP) ⧠140 mmHg and diastolic blood pressure (DBP) ⧠90 mmHg, as well as subgroup analyses by different fixed IFP subgroups (according to involved teeth number) and removable IFP subgroup. We further investigated effect modifications among stratified populations. RESULTS: 158,659 individuals were included for analysis, 346 (26.86%) in IFP group and 27,380 (17.40%) in non-IFP group (p < 0.001) were hypertensive. After adjustment of sex, age, obesity, dyslipidaemia, diabetes, hsCRP, family history of CVD, self-reported smoking, self-reported drinking and WC, ORs of hypertension, SBP ⧠140 mmHg and DBP ⧠90 mmHg were 1.330 (95% CI: 1.162-1.522), 1.277 (95% CI: 1.098-1.486) and 1.376 (95% CI: 1.186-1.596), respectively (p < 0.05). Furthermore, after full adjustment, the number of involved teeth showed a significant incremental trend with hypertension risk in the population with and without IFP (p for trend <0.001). The IFP-blood pressure associations were more pronounced in females, 18-60 years, non-obese and diabetic participants. CONCLUSION: As a modifiable oral indicator, IFP was significantly associated with a higher risk of hypertension.
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Hipertensão , Humanos , Hipertensão/epidemiologia , Feminino , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Prevalência , Idoso , Ajuste de Prótese , Pressão Sanguínea/fisiologia , Pequim/epidemiologia , Prótese Dentária/efeitos adversosRESUMO
OBJECTIVE: To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. METHODS: The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. RESULTS: Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference (P =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis(P =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. CONCLUSION: The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.
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Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Nefropatias , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Bortezomib/farmacologia , Estudos Retrospectivos , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Fatores de Risco , Transplante Autólogo , Antivirais/uso terapêutico , Antivirais/farmacologiaRESUMO
Introduction: This study aims to (1) explore physicians' perceptions and experiences of lung cancer screening in Hong Kong, (2) evaluate physicians' readiness of implementing lung cancer screening in Hong Kong, (3) explore high-risk smokers' health beliefs of lung cancer and screening, (4) identify barriers and facilitators for high-risk Hong Kong smokers to screening for lung cancer, and (5) validate the Chinese Lung Cancer Screening Health Belief Scale in relation to high-risk smokers in Hong Kong. Methods and analysis: A mixed methods design will be used in this study. Individual qualitative interviews will be conducted with physicians who have experience with high-risk smokers. Physicians' perceptions and experiences of lung cancer screening, and their readiness to accept lung cancer screening in Hong Kong, will be gathered through the qualitative interviews. A semi-structured interview guide will be used in the qualitative interviews. In addition, a quantitative survey with qualitative questions will be conducted on high-risk smokers to investigate their health beliefs of lung cancer and screening and barriers and facilitators for them to screening lung cancer. A lung cancer screening health belief scale, sociodemographic questionnaire, smoking and lung cancer screening history questionnaire, lung cancer and screening knowledge questionnaire, lung cancer stigma scale, generalized anxiety disorder scale, patient health questionnaire-9, patients' medical trust scale and preferred lung cancer screening intervention delivery questionnaire will be conducted in the quantitative survey. Constant comparison and content analysis will be used to analyze the qualitative data. Descriptive data analysis, validity and reliability analysis, one-way analysis of variance and post hoc analyses will be used to analyze quantitative data. Discussions: This study explores physicians' and high-risk smokers' perceptions and experiences toward lung cancer screening in Hong Kong. Findings from this study can help healthcare providers and policy makers become aware of the stakeholder's voices. In addition, these findings can help to inform the design of future interventional lung cancer screening programs and provide a tool to measure Chinese high-risk smokers' health beliefs toward lung cancer screening. A major limitation of this mixed methods study is the amount of time taken to complete the overall study. Also, its complexity requires more collaboration and networking among researchers. Ethics and dissemination: This study has minimal risk to the participants. It will be submitted to the university IRB for ethical approval. Findings related to physicians' perceptions and experiences of lung cancer screening in Hong Kong, physicians' readiness of implementing lung cancer screening, high-risk smokers' health beliefs of lung cancer and screening, barriers, and facilitators for high-risk Hong Kong smokers to screening lung cancer will be disseminated in journals and conferences. The reliability and validity of the Chinese lung cancer screening health belief scale will be reported in methodological research journals.
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BACKGROUND: Quantitative nuclear magnetic resonance (NMR) metabolomics techniques provide detailed measurements of lipoprotein particle concentration. Metabolic dysfunction often represents a cluster of conditions, including dyslipidaemia, hypertension, and diabetes, that increase the risk of cardiovascular diseases (CVDs). However, the causal relationship between lipid profiles and blood pressure (BP) remains unclear. We performed a Mendelian Randomisation (MR) study to disentangle and prioritize the potential causal effects of major lipids, lipoprotein particles, and circulating metabolites on BP and pulse pressure (PP). METHODS: We employed single-nucleotide polymorphisms (SNPs) associated with major lipids, lipoprotein particles, and other metabolites from the UK Biobank as instrumental variables. Summary-level data for BP and PP were obtained from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Two-sample MR and MR Bayesian model averaging approaches (MR-BMA) were conducted to analyse and rank causal associations. FINDINGS: Genetically predicted TG was the most likely causal exposure among the major lipids to increase systolic blood pressure (SBP) and diastolic blood pressure (DBP), with marginal inclusion probabilities (MIPs) of 0.993 and 0.847, respectively. Among the majority of lipoproteins and their containing lipids, including major lipids, genetically elevated TG in small high-density lipoproteins (S_HDL_TG) had the strongest association with the increase of SBP and DBP, with MIPs of 0.416 and 0.397, respectively. HDL cholesterol (HDL_C) and low-density lipoprotein cholesterol (LDL_C) were potential causal factors for PP elevation among the major lipids (MIP = 0.927 for HDL_C and MIP = 0.718 for LDL_C). Within the sub-lipoproteins, genetically predicted atherogenic lipoprotein particles (i.e., sub-very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL particles) had the most likely causal impact on increasing PP. INTERPRETATION: This study provides genetic evidence for the causality of lipids on BP indicators. However, the effect size on SBP, DBP, and PP varies depending on the lipids' components and sizes. Understanding this potential relationship may inform the potential benefits of comprehensive management of lipid profiles for BP control. FUNDING: Key Research and Development Program of Hubei Province, Science and Technology Innovation Project of Huanggang Central Hospital of Yangtze University, the Hubei Industrial Technology Research Institute of Heart-Brain Diseases, and the Hubei Provincial Engineering Research Centre of Comprehensive Care for Heart-Brain Diseases.
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Encefalopatias , Lipoproteínas , Adulto , Humanos , Pressão Sanguínea/genética , Triglicerídeos , Teorema de Bayes , Lipoproteínas/genética , LDL-Colesterol , HDL-Colesterol , Análise da Randomização Mendeliana , Fatores de RiscoRESUMO
Small moving objects at far distance always occupy only one or a few pixels in image and exhibit extremely limited visual features, which bring great challenges to motion detection. Highly evolved visual systems endow flying insects with remarkable ability to pursue tiny mates and prey, providing a good template to develop image processing method for small target motion detection. The insects' excellent sensitivity to small moving objects is believed to come from a class of specific neurons called small target motion detectors (STMDs). However, existing STMD-based methods often experience performance degradation when coping with complex natural scenes. In this paper, we propose a bio-inspired visual system with spatio-temporal feedback mechanism (called Spatio-Temporal Feedback STMD) to suppress false positive background movement while enhancing system responses to small targets. Specifically, the proposed visual system is composed of two complementary subnetworks and a feedback loop. The first subnetwork is designed to extract spatial and temporal movement patterns of cluttered background by neuronal ensemble coding. The second subnetwork is developed to capture small target motion information where its output and signal from the first subnetwork are integrated together via the feedback loop to filter out background false positives in a recurrent manner. Experimental results demonstrate that the proposed spatio-temporal feedback visual system is more competitive than existing methods in discriminating small moving targets from complex natural environments.
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Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuroprotective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitors in the treatment of glaucoma from beach to bedside.