The pervasiveness of Posttraumatic stress disorder (PTSD) and its detrimental effects on sufferers, society, and the economy at large underscore the importance of interventions for PTSD. This mental ...disorder is currently documented in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) as an anxiety illness. This article explores the negative effects of PTSD on individuals and those around them and analyzes various PTSD interventions. Major negative effects include effects on individuals, effects on family relationships, and effects on parent-child relationships. Interventions include but are not limited to mindfulness therapy, cognitive behavioral therapy (CBT), and exposure therapy. The scientific literature on PTSD impacts and interventions was reviewed, including but not limited to interviews with patients, case studies, and scientific analyses of intervention effectiveness. The diversity of negative effects of PTSD and the effectiveness of different interventions are discussed. Include recommendations for future research and the use of interventions.
En el centro de los debates sobre la desaparición y el resurgimiento del espacio público se encuentra el concepto de lo público, que a menudo se utiliza para definir las cualidades más deseables que ...desde el punto de vista normativo y prescriptivo debe poseer un espacio público. Este artículo, en lugar de proponer un ideal abstracto y normativo universalmente aplicable a lo público, aboga por su desnormalización, abordando este concepto como un estado del espacio que es público de una determinada manera y en un contexto determinado. Para ilustrar las múltiples capas posibles de lo público, el artículo utiliza como estudio de caso la regeneración del espacio público de la ribera del río Huangpu en Shanghai. Examinando la transformación de esta ribera en las dos últimas décadas y centrados en el reciente proyecto de conexión del espacio público, el artículo muestra las diferentes formas en las que el diseño y el desarrollo del espacio público se entrelazan con el ideal de metrópolis orientada a las personas, propuesto como la clave de la pretensión ambiciosa de que Shanghái se convierta en una «excellent global city» (ciudad global excelente). A partir del análisis de la retórica y de la realidad del desarrollo del espacio público en la ribera en Shanghái orientado a las personas, este artículo muestra tres capas diferentes de lo público: lo público localizado, lo público procedimental y lo público simbólico, que se refieren no solo a la calidad material sino también a los procesos de distribución y construcción discursiva del espacio público. Este debate sobre las múltiples caras posibles de lo público servirá de punto de partida para seguir investigando cómo abordar lo público más allá del confinamiento de los límites espaciales como parte de la amplia y compleja dinámica de poder de las ciudades contemporáneas.
Even though there is still a dearth of scholarship in L2 simplified Chinese reading among adults, a growing body of research has contributed to this area to examine L2 Chinese reading process and ...performance. Due to this advancement in current literature, it is imperative to reflect on what has been researched in L2 Chinese reading in recent years and shed light on potential future research directions and pedagogical practices. To fill this gap, a qualitative analytic method was adopted to synthesize 25 selected studies (2009-2018) in L2 simplified Chinese reading among adult learners. Using analytic coding to identify emergent patterns regarding the research questions, methodologies, findings, and research implications, this study proposes that scholars interested in adult L2 Chinese reading conduct research looking at L2 Chinese reading processes embedded in learners’ social and cultural environment, adopting diverse methodological approaches that uncover readers’ voices, advancing understanding in social factors that impact L2 Chinese reading acquisition in classrooms, and attending to different processing levels and various forms of characters/ words/sentences/texts. Pedagogical implications were also discussed.
Abstract Development of multifunctional theranostic nanoplatforms for targeted cancer imaging and therapy still remains a great challenge. Herein, we report the use of multifunctional ...dendrimer-entrapped gold nanoparticles (Au DENPs) covalently linked with α-tocopheryl succinate (α-TOS) as a platform for targeted cancer computed tomography (CT) imaging and therapy. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2 ) conjugated with fluorescein isothiocyanate (FI), polyethylene glycol (PEG)-modified α-TOS, and PEGylated folic acid (FA) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. We show that the Au DENPs conjugated with approximately 9.8 α-TOS molecules per dendrimer and with an Au core size of 3.3 nm are water-dispersible, and stable under different pH and temperature conditions and in different aqueous media. The FA modification onto the Au DENPs enables efficient targeting of the particles to cancer cells overexpressing FA receptors (FAR), and effective targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo . Likewise, the covalent conjugation of α-TOS does not compromise its therapeutic activity, instead significantly improves its water solubility. Importantly, thanks to the role of FA-directed targeting, the formed multifunctional Au DENPs are able to exert the specific therapeutic efficacy of α-TOS to the FAR-overexpressing cancer cells in vitro and the xenografted tumor model in vivo . The developed multifunctional Au DENPs may hold a great promise to be used as a unique theranostic nanoplatform for targeted CT imaging and therapy of different types of cancer.
Objectives
The purpose of this study was to investigate the grades of endolymphatic hydrops determined by gadolinium‐contrast magnetic resonance (MR) and correlation to the clinical features in ...patients with Meniere disease.
Study Design
Prospective study.
Methods
A total of 24 patients suffering from unilateral Meniere disease with either definite or probable clinical diagnosis were included. The duration of vertigo, duration of tinnitus, duration of vertigo attacks, hearing thresholds, and canal paresis (CP) value of caloric tests were assessed. Three‐dimensional fluid‐attenuated inversion recovery magnetic resonance imaging (MRI) was performed 4 hours after intravenous injection of double dose of gadobutrol (Gd) to show endolymph and perilymph, and the grades of endolymphatic hydrops were measured. Additionally, the correlation between clinical features and the grades of endolymphatic hydrops of cochlea and vestibular were evaluated.
Results
Different grades of the endolymphatic hydrops in the impaired ear were revealed by MRI. The Spearman correlation showed a strong correlation between the hearing thresholds of low, middle, and high tone and the grades of cochlea and vestibular hydrops (P < .05); However, no significant correlation between the duration of vertigo, duration of tinnitus, duration of vertigo attacks, CP value, and endolymphatic hydrops was determined (P > .05).
Conclusion
By visualizing the endolymph and perilymph of inner ear in patients with Meniere disease assisted with intravenous injection of double doses of Gd, the grades of endolymphatic hydrops could be assessed. As a result, the grades of endolymphatic hydrops in patients with Meniere disease can be used to predict the level of hearing impairment.
Level of Evidence
4 Laryngoscope, 131:E144–E150, 2021
Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. ...Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin-annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1β1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1β1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.
Tumor tissues often exhibit unique integrin receptor presentation during development, such as high exposures of αvβ3 and αIIbβ3 integrins. These features are not present in normal tissues. The ...induction of selective thrombosis and infarction in the tumor-feeding vessels, as well as specific antagonism of αvβ3 integrin on the surface of tumor endothelial cells, is a potential novel antitumor strategy. The Echistatin–Annexin V (EAV) fusion protein is a novel Annexin V (ANV) derivative that possesses a high degree of αvβ3 and αIIbβ3 integrin receptor recognition and binding characteristics while retaining the specific binding ability of the natural ANV molecule for phosphatidylserine (PS). We systematically investigated the biological effects of this novel molecule with superimposed functions on mouse melanoma. We found that EAV inhibited the viability and migration of B16F10 murine melanoma cells in a dose-dependent manner, exhibited good tumor suppressive effects in a xenograft mouse melanoma model, strongly induced tumor tissue necrosis in mice, and targeted the inhibition of angiogenesis in mouse melanoma tumor tissue. EAV exhibited stronger biological effects than natural ANV molecules in inhibiting melanoma in mice. The unique biological effects of EAV are based on its high β3-type integrin receptor-specific recognition and binding ability, as well as its highly selective binding to PS molecules. Based on these findings, we propose that EAV-mediated tumor suppression is a novel and promising antitumor strategy that targets both PS- and integrin β3-positive tumor neovascularization and the tumor cells themselves, thus providing a possible mechanism for the treatment of melanoma.
The cancer cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize its own kind. These cell membranes are often used to coat spherical nanoparticles to ...enhance nanomedicines' targeting specificities and uptakes. A sphere, however, has only a point contact with a surface at any given time. It is shown here that, by retaining a flatter morphology of the cracked cell membrane through stiffening with
synthesized gold nanomaterials, an increased area of interaction could be maintained and hence improve upon the
and
homotypic targeting capabilities between cancer cell types. This enhancement is especially important
as any nanomedicine with targeting moieties probably has a single pass at interacting with the target cell before subsequent system clearance. Possible future clinical applications may involve the usage of a patient's autologous tumor biopsy tissues, which are very limited in supply, and therefore ensuring that we capitalize on the entire collective surface area of the cancer cell membrane available becomes an important consideration in the design and delivery our cell membrane-derived nanomedicines.
Optical-resolution photoacoustic microscopy (OR-PAM) has been developed for anatomical, functional, and molecular imaging but usually requires multiple scanning for different contrasts. We present ...five-wavelength OR-PAM for simultaneous imaging of hemoglobin concentration, oxygen saturation, blood flow speed, and lymphatic vessels in single raster scanning. We develop a five-wavelength pulsed laser via stimulated Raman scattering. The five pulsed wavelengths, i.e., 532, 545, 558, 570, and 620 / 640 nm, are temporally separated by several hundreds of nanoseconds via different optical delays in fiber. Five photoacoustic images at these wavelengths are simultaneously acquired in a single scanning. The 532- and 620 / 640-nm wavelengths are used to image the blood vessels and dye-labeled lymphatic vessels. The blood flow speed is measured by a dual-pulse method. The oxygen saturation is calculated and compensated for by the Grüneisen-relaxation effect. In vivo imaging of hemoglobin concentration, oxygen saturation, blood flow speed, and lymphatic vessels is demonstrated in preclinical applications of cancer detection, lymphatic clearance monitoring, and functional brain imaging.
Recent studies have shown that N.sup.6-methyladenosine (m.sup.6A) plays a critical role in numbers of biological processes and complex human diseases. However, the regulatory mechanisms of most ...methylation sites remain uncharted. Thus, in-depth study of the epi-transcriptomic patterns of m.sup.6A may provide insights into its complex functional and regulatory mechanisms. Due to the high economic and time cost of wet experimental methods, revealing methylation patterns through computational models has become a more preferable way, and drawn more and more attention. Considering the theoretical basics and applications of conventional clustering methods, an RNA Expression Weighted Iterative Signature Algorithm (REW-ISA) is proposed to find potential local functional blocks (LFBs) based on MeRIP-Seq data, where sites are hyper-methylated or hypo-methylated simultaneously across the specific conditions. REW-ISA adopts RNA expression levels of each site as weights to make sites of lower expression level less significant. It starts from random sets of sites, then follows iterative search strategies by thresholds of rows and columns to find the LFBs in m.sup.6A methylation profile. Its application on MeRIP-Seq data of 69,446 methylation sites under 32 experimental conditions unveiled 6 LFBs, which achieve higher enrichment scores than ISA. Pathway analysis and enzyme specificity test showed that sites remained in LFBs are highly relevant to the m.sup.6A methyltransferase, such as METTL3, METTL14, WTAP and KIAA1429. Further detailed analyses for each LFB even showed that some LFBs are condition-specific, indicating that methylation profiles of some specific sites may be condition relevant. REW-ISA finds potential local functional patterns presented in m.sup.6A profiles, where sites are co-methylated under specific conditions.
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