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BACKGROUND: Chuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care. METHODS: This is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments. DISCUSSION: This will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0009210. Registered on February 28, 2024.
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Dor Lombar , Manipulações Musculoesqueléticas , Humanos , Dor Lombar/terapia , Manipulações Musculoesqueléticas/métodos , República da Coreia , Adulto , Masculino , Pesquisa Comparativa da Efetividade , Feminino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicina Tradicional Coreana , Análise Custo-BenefícioRESUMO
The present paper examines the role of campaign-induced communication on the effects of a social norms campaign by focusing on cognitive elaboration, perceived injunctive norms, and message recall as mediating variables. Participants (n = 252; mage = 20.26) read an injunctive norms campaign message about choosing not to drink at parties or when socializing and were randomly assigned to one of three conditions (control: received no prompts, prompt only; received prompts to engage in interpersonal communication about the campaign message with close others during the following week; prompt & plan: received prompts to engage in interpersonal communication with close others during the following week and to write a plan for the communication). The results revealed that the prompt (either alone or with the plan) significantly motivated participants to engage in positive conversations about the campaign message during the next week. Similar to past findings, higher frequency of positive conversations about the campaign message indirectly predicted better behavioral outcomes via higher cognitive elaboration. The findings suggest that social norms campaign developers should be encouraged to design social norms messages with a brief prompt to motivate the target audience to engage in interpersonal communication and need to account for such interpersonal communication and its indirect effects in evaluating campaign messages.
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Recent studies have indicated significant correlation between the concentration of immune checkpoint markers borne by extracellular vesicles (EVs) and the efficacy of immunotherapy. This study introduces a high-resolution spiral microfluidic channel-integrated electrochemical device (HiMEc), which is designed to isolate and detect EVs carrying the immune checkpoint markers programmed death ligand 1 (PD-L1) and programmed death protein 1 (PD-1), devoid of plasma-abundant lipoprotein contamination. Antigen-antibody reactions were applied to immobilize the lipoproteins on bead surfaces within the plasma, establishing a size differential with EVs. A plasma sample was then introduced into the spiral microfluidic channel, which facilitated the acquisition of nanometer-sized EVs and the elimination of micrometer-sized lipoprotein-bead complexes, along with the isolation and quantification of EVs using HiMEc. PD-L1 and PD-1 expression on EVs was evaluated in 30 plasma samples (10 from healthy donors, 20 from lung cancer patients) using HiMEc and compared to the results obtained from standard tissue-based PD-L1 testing, noting that HiMEc could be utilized to select further potential candidates. The obtained results are expected to contribute positively to the clinical assessment of potential immunotherapy beneficiaries.
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[This corrects the article DOI: 10.1007/s10068-023-01265-6.].
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BACKGROUD: Accurate estimation of post-mortem interval (PMI) is crucial in forensic investigations. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable within the cell nucleus despite post-mortem changes. OBJECTIVE: We assessed three target genes (miR-122, miR-133a, and miR-206) for PMI estimation using 72 healthy adult male BALB/c mice exposed to two different temperatures (4 and 21â) at nine different time points over 10 days. METHODS: Initially, the stability of the two reference genes (RNU6B and 5 srRNA) was evaluated using gene stability analysis tools (Delta Ct, Best Keeper, and Genorm) to select the optimal reference gene. RNU6B was found to be the most stable endogenous control. Subsequently, the expression patterns of miR-122, miR-133a, and miR-206 were analyzed within a 10-day PMI period using the heart, skeletal muscle, liver, and brain tissues. RESULTS: At 4â, miR-122 levels significantly decreased on days 8 and 10 in all tissues, with only the liver showing significant changes at 21â. MiR-133a decreased over time in the heart, muscles, and brain, showing a dramatic decrease on days 8 and 10 in the heart and muscles at both temperatures. Although miR-206 levels decreased over time in muscles and liver at 4 â, these increased in the brain at 21 â, with no expression changes in other organs. CONCLUSION: In summary, miR-122, miR-133a, and miR-206 are potential PMI markers in heart and skeletal muscle tissues.
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Camundongos Endogâmicos BALB C , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Masculino , Camundongos , Biomarcadores/metabolismo , Músculo Esquelético/metabolismo , Mudanças Depois da Morte , Miocárdio/metabolismo , Fígado/metabolismo , Encéfalo/metabolismoRESUMO
Biological assays involve the lysis of biological particles, enzyme reactions, and gene amplification, and require a certain amount of time for completion. Microfluidic chips are regarded as powerful devices for biological assays and in vitro diagnostics; however, they cannot achieve a high mixing efficiency, particularly in some time-consuming biological reactions. Herein, we introduce a microfluidic reverse-Tesla (reTesla) valve structure in which the fluid is affected by vortices and branch flow convergence, resulting in flow retardation and a high degree of mixing. The reTesla is passively operated by a microfluidic capillary force without any pumping facility. Compared with our previously developed micromixers, this innovative pumpless microfluidic chip exhibited high performance, with a mixing efficiency of more than 93%. The versatility of our reTesla chip will play a pivotal role in the study of various biological and chemical reactions.
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Técnicas Analíticas Microfluídicas , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip , Bioensaio/métodos , Bioensaio/instrumentação , Desenho de Equipamento , HumanosRESUMO
Cultural targeting and tailoring are different, yet they remain intertwined in the literature inhibiting theory development and limiting the possibility of determining their effects. This preregistered systematic literature review describes these constructs and provides a framework for cultural tailoring with evidence from a review of 63 studies, published from 2010 to 2020, to characterize the processes, elements, and theories used in the existing literature. The results show that 86% of studies self-defined as cultural tailoring, but coding revealed relatively few tailoring studies (25%) with 31% including both tailoring and targeting elements. Most studies used outreach and consultation as processes for tailoring or targeting with participatory approaches used in a fifth of the studies. Surface-level features of message content were commonly used to tailor or target with deep-cultural-values found in only a quarter of the studies. We argue from theories of communication accommodation and persuasion that cultural tailoring or targeting may provide gains in attention, recall, or source evaluation.
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Nitrogen trifluoride (NF3) is a potent and long-lived greenhouse gas that is widely used in the manufacture of semiconductors, photovoltaic cells, and flat panel displays. Using atmospheric observations from eight monitoring stations from the Advanced Global Atmospheric Gases Experiment (AGAGE) and inverse modeling with a global 3-D atmospheric chemical transport model (GEOS-Chem), we quantify global and regional NF3 emission from 2015 to 2021. We find that global emissions have grown from 1.93 ± 0.58 Gg yr-1 (± one standard deviation) in 2015 to 3.38 ± 0.61 Gg yr-1 in 2021, with an average annual increase of 10% yr-1. The available observations allow us to attribute significant emissions to China (0.93 ± 0.15 Gg yr-1 in 2015 and 1.53 ± 0.20 Gg yr-1 in 2021) and South Korea (0.38 ± 0.07 Gg yr-1 to 0.65 ± 0.10 Gg yr-1). East Asia contributes around 73% of the global NF3 emission increase from 2015 to 2021: approximately 41% of the increase is from emissions from China (with Taiwan included), 19% from South Korea, and 13% from Japan. For Japan, which is the only one of these three countries to submit annual NF3 emissions to UNFCCC, our bottom-up and top-down estimates are higher than reported. With increasing demand for electronics, especially flat panel displays, emissions are expected to further increase in the future.
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Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor ß (TGF-ß) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-ß1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-ß pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-ß1. Finally, TGF-ß1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.
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This study examined the tensile strength and biocompatibility properties of polyvinyl alcohol (PVA) hydrogel tissue regeneration scaffolds with polylactic acid (PLA) mesh fabric added as reinforcement, with a focus on the impact of heat treatment temperature and the number of layers of the PLA mesh fabric. The hydrogel scaffolds were prepared using a freeze-thaw method to create PVA hydrogel, with the PLA mesh fabric placed inside the hydrogel. The swelling ratio of the PVA/PLA hydrogel scaffolds decreased with increasing layer number and heat treatment temperature of the PLA mesh. The gel strength was highest when five layers of PLA mesh fabric were added, heat-treated at 120 °C, and confirmed to be properly placed inside the hydrogel by SEM images. The MTT assay and DAPI staining using HaCaT cells demonstrated that the cell proliferation was uninterrupted throughout the experimental period, confirming the biocompatibility of the scaffold. Therefore, we confirmed the possibility of using PLA mesh fabric as a reinforcement for PVA hydrogel to improve the strength of scaffolds for tissue regeneration, and we confirmed the potential of PLA mesh fabric as a reinforcement for various biomaterials.
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Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH.
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Hiperplasia , Neointima , Ratos Sprague-Dawley , Ligante Indutor de Apoptose Relacionado a TNF , Animais , Neointima/patologia , Neointima/prevenção & controle , Ratos , Masculino , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Veias Jugulares/patologia , Artéria Femoral/lesões , Artéria Femoral/patologia , Artéria Femoral/cirurgiaRESUMO
BACKGROUND: The increased demand for genetic testing and counseling necessitates healthcare professionals (HCPs) to improve their genetic competency through training programs. This systematic review identified HCPs' learning needs and their perspectives on essential information for families with hereditary cancer. METHODS: This review covered studies published from 2013 to 2024 across five databases. Data were analyzed using a content analysis. RESULTS: Thirteen studies involving 332 HCPs were analyzed. Most studies focused on the learning needs of physicians caring for families affected by Hereditary Breast and Ovarian Cancer in North America and Europe. HCPs required training emphasizing practical counseling skills over the basics of genetics. Learning needs varied by profession: physicians needed training in assessing cancer risk and supporting decision-making in risk management; nurses required information on resources and the genetic care system; genetic counselors sought guidance on family communication and planning. Essential information identified for families included risk-reducing strategies, personalized cancer risk assessment, family implications, psychological issues, (cascade) genetic testing, and social concerns. CONCLUSIONS: The findings have implications for the development of training programs for HCPs, emphasizing the need for tailored training based on professions. Future research should explore the needs of HCPs caring for families with diverse hereditary cancers and cultural backgrounds.
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Although many states in the U.S. restricted indoor social gatherings to prevent the spread of COVID-19 in the Fall of 2020, college students' large social gatherings still caused many cluster infections. The present study aimed to explore whether perceived injunctive norms negatively influence behavioral intentions through perceived freedom threat and anger and to probe the ways that different political party affiliations interact with the normative effects. Undergraduate students were recruited to participate in an online survey (n = 170). Counter to predictions, perceived injunctive norms positively influenced Republican participants' behavioral intentions through perceived freedom threat and anger. They reported lower perceived freedom threat as perceived injunctive norms increased, whereas Democrat participants reported higher perceived freedom threat as perceived injunctive norms increased. The findings suggested that injunctive social norms campaigns would be more effective for Republican students to promote COVID-19 preventive behaviors as contrasted with Democrat students.
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BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.
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Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Proteínas de Homeodomínio , Neoplasias Hepáticas , Fenótipo , Proteínas Supressoras de Tumor , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Movimento Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.
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Predisposição Genética para Doença , Testes Genéticos , Humanos , Feminino , Predisposição Genética para Doença/psicologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Síndrome Hereditária de Câncer de Mama e Ovário/psicologia , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Neoplasias da Mama/diagnóstico , Família/psicologiaRESUMO
Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in ob/ob mice. The TAT38 (a.a. 20-57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20-35 TACTNCYCAKCCFQVC), core-domain (a.a. 36-46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47-57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4-11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.
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Adipogenia , PPAR gama , Proteína de Ligação a Elemento Regulador de Esterol 1 , Produtos do Gene tat do Vírus da Imunodeficiência Humana , Animais , PPAR gama/metabolismo , Adipogenia/efeitos dos fármacos , Camundongos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Células 3T3-L1 , Humanos , Regulação da Expressão Gênica , Camundongos Obesos , Masculino , Ciclina T/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Estimuladoras de Ligação a CCAATRESUMO
Skin microbiota, such as acne-related Cutibacterium acnes, Staphylococcus aureus, and fungal Candida albicans, can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and multispecies biofilms under aerobic and anaerobic conditions. Minimum inhibitory concentrations of shikonin were 10 µg/mL against C. acnes, S. aureus, and C. albicans, and at 1-5 µg/mL, shikonin efficiently inhibited single biofilm formation and multispecies biofilm development by these three microbes. Shikonin increased porphyrin production in C. acnes, inhibited cell aggregation and hyphal formation by C. albicans, decreased lipase production, and increased hydrophilicity in S. aureus. In addition, shikonin at 5 or 10 µg/mL repressed the transcription of various biofilm-related genes and virulence-related genes in C. acnes and downregulated the gene expression levels of the quorum-sensing agrA and RNAIII, α-hemolysin hla, and nuclease nuc1 in S. aureus, supporting biofilm inhibition. In addition, shikonin prevented multispecies biofilm development on porcine skin, and the antimicrobial efficacy of shikonin was recapitulated in a mouse infection model, in which it promoted skin regeneration. The study shows that shikonin inhibits multispecies biofilm development by acne-related skin microbes and might be useful for controlling bacterial infections.
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Acne Vulgar , Anti-Infecciosos , Naftoquinonas , Infecções Estafilocócicas , Animais , Camundongos , Candida albicans/genética , Staphylococcus aureus , Biofilmes , Anti-Infecciosos/farmacologiaRESUMO
If a solitary spinal lesion is found in an older patient, bone metastasis can be primarily considered as the diagnosis. Bone metastasis can occur anywhere, but it mostly occurs in the vertebral body and may sometimes show typical imaging findings, presenting as a single lesion. Therefore, differentiating it from other lesions that mimic bone metastases can be challenging, potentially leading to delayed diagnosis and initiation of primary cancer treatment. This review provides an overview of imaging findings and clinical guidelines for bone metastases and discusses its differences from other diseases that can occur as solitary spinal lesions in older patients.