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The capitate is often considered the "keystone" of the carpus, not simply because of its central and prominent position in the wrist, but also because of its mechanical interactions with neighboring bones. The purpose of this study was to determine in vivo three-dimensional capitate kinematics. Twenty uninjured wrists were investigated using a recently developed, non-invasive markerless bone registration (MBR) technique. Surface contours of the capitate, third metacarpal and radius were extracted from computed tomography images of seven wrist positions and the three-dimensional motions of the capitate and third metacarpal were calculated with respect to the radius in wrist flexion-extension and radio-ulnar deviation. We found that in vivo capitate motion does not simply occur about a single pivot point like a universal joint, as demonstrated by non-intersecting rotation axes for different capitate motions. The distance between flexion and ulnar deviation axes was 3.9+/-2.0 mm, and the distance between extension and ulnar deviation axes was 3.9+/-1.4 mm. Furthermore, capitate axes for males tended to be located more distally than axes for females. However, we believe that this result is related to subject size and not to gender. We also found that there is minimal relative motion between the capitate and third metacarpal during these in vivo wrist motions. These findings demonstrate the complexity of capitate kinematics, as well as the different mechanisms through which wrist flexion, extension, radial deviation and ulnar deviation occur.

Despite several studies that have commonly used exosomes as systems to deliver therapeutic agents in the treatment of several diseases, extensive research on exosomes is limited by the extremely small quantity of exosomes produced by cells (Thry et al., 2006). Large-scale production and purification of exosomes is time consuming and expensive (Jang et al., 2013; Oh et al., 2015). However, production of exosome mimetics (EMs) is more feasible compared to exosome production. Therefore, EMs can serve as suitable nanocarriers for drug delivery in translation medicine in the future. As mentioned above, most cells produce exosomes that may have entirely different fates of distribution in vivo. Hence, the in vivo visualization and tracking of exosomes in animals or humans is crucial for the development of exosomes as drug delivery vehicles that target specific organs or diseases.

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Radiochemical purity and stability of 99mTc-labeled RBC-EMs (A) Illustration of the procedure for labeling RBC-EMs with 99mTc. (B,C) The counts of radioactivity for 99mTc and 99mTc-RBC-EMs were measured by thin layered chromatography. (D) Serum stability was determined by the percent change in the radiochemical purity of 99mTc-RBC-EMs for the indicated time periods. The values are expressed as mean SD.

In vivo fluorescent imaging of RBC-EMsDiD injected in mice. (A) Representative in vivo fluorescent imaging of RBC-EMsDiD in mice. RBC-EMsDiD or PBS (control) was administered via the tail vein (n = 3). (B,C) Representation and quantification of RBC-EMsDiD or PBS (control) signal from the liver and spleen 1 h after EMs administration; the values are expressed as mean SD.

For the successful use of exosomes as drug delivery vehicles in research and clinical translation, large-scale production of exosomes and in vivo tracking of exosomes are essential. EMs have similar characteristics as that of exosomes, but have a 100-fold higher production yield (Jang et al., 2013). It is important to note that crucial components of exosomes are still largely unknown, and the integrative studies are required to elucidate the biological functions of these components. Furthermore, EMs have been used to deliver chemotherapeutic drugs to inhibit tumors and RNAi to attenuate the target gene expression (Jang et al., 2013; Lunavat et al., 2016).

In this study, we employed radio-labeling of RBC-EMs to apply real time in vivo nuclear imaging in living animals. Visualization and tracking of the exosomes were mostly carried out with BLI or FLI by transducing the cells with reporter genes (Takahashi et al., 2013; Lai et al., 2014; Kalimuthu et al., 2016; Gangadaran et al., 2017b) or with FLI by labeling the cells with lipophilic dyes (Mittelbrunn et al., 2011; Gangadaran et al., 2017b). However, optical imaging suffers from low spatial resolution and tissue penetration and is still not suitable for clinical translation (Tavri et al., 2009; Gangadaran and Ahn, 2017). Nuclear imaging provides excellent sensitivity and good tissue penetration (Ahn, 2014). To our knowledge, there are only a few studies that have reported the development of radio-labeled exosomes to assess biodistribution. However, three out of those reports, showed only the ex vivo biodistribution (Morishita et al., 2015; Smyth et al., 2015; Varga et al., 2016), and one study used streptavidin reporters which need genetically modified cells (Morishita et al., 2015).

Further, we verified the in vivo biodistribution of RBC-EMs by dye-based direct labeling. The fluorescent signal (RBC-EMs DiD) was first observed in the region of the liver immediately after administration and at 1 h post-administration. Further, immunofluorescent assay showed sub cellular visualization of RBC-EMs DiD in liver. Most of the RBC-EMs DiD were co-localized with the CD68 positive kupffer cells. This is consistent with the previous report (Gangadaran et al., 2017b). As RBC-EMs are derived from RBCs, they potentially have advantages in preclinical and clinical uses for imaging and as drug carriers as well. Several studies have exploited exosomes as drug carriers for the treatment of several diseases (Jang et al., 2013; Banizs et al., 2014; Pascucci et al., 2014; Tian et al., 2014; Lunavat et al., 2016; Gangadaran et al., 2018). Our approach of producing EMs from RBCs is simple and it would pave the way for its large-scale production. RBC-EMs can be used to load drugs and deliver the loaded drug to Kupffer cells in the liver. Radiolabeled RBC-EMs can be used to track in vivo drug delivery in preclinical and clinical scenarios.

The most studied drug delivery platform are liposomes and polymeric nanoparticles, both nano-carriers have been used to deliver drug in vivo (Gangadaran et al., 2018). Recently exosomes have been investigated more in exosome-based therapies (Kalimuthu et al., 2016; Zhu et al., 2017, 2018) and drug deliveries (Tian et al., 2014; Gangadaran et al., 2018). RBC-EMs distributed to liver and spleen rapidly within 1 h, this character of RBC-EMs can be utilized in diseases such as hepatic fibrosis to target liver resident macrophages as macrophages are real mediator of these liver diseases (Tacke, 2017). RBC-EMs shown to have short-circulation time, which can be changed by various methodologies such as, a blocking of scavenger receptor class A (SR-A) as a monocyte/macrophage uptake receptor for exosomes. In vivo blockade of SR-A with dextran sulfate dramatically decreased exosome liver clearance in mice, while enhancing tumor accumulation (Watson et al., 2016; Zhu et al., 2018); macrophage-depletion by clodronate in mice shown to improve the longer circulation time and slower clearance in vivo (Imai et al., 2015); Recently, tumor-targeting peptides have been used to target tumors with cytotoxic T cells or anti-apoptotic peptides to inhibit the tumor in vivo (Sarangthem et al., 2016; Gunassekaran et al., 2018), and another report has shown that exosomes labeled with cardiac homing peptides can be used to target myocardial infarction in vivo (Vandergriff et al., 2018). Such a targeting approach can be used to direct the RBC-EMs to the target site with therapeutic drugs loaded in them, and the RBC-EMs containing therapeutic drugs can be feasibly monitored in vivo by 99mTc labeling which can accelerate development of the drug delivery system in clinics. Since RBC-EMs can be produced immediately after collecting the bloods from patient and injected into same patient, which should be a highly biocompatible compared to other drug carriers. In addition, specific exosome (NK exosome, macrophage-exosome) shown to have intrinsic properties to target, kill tumors and modulate inflammation in vivo (Yuan et al., 2017; Zhu et al., 2018). Further studies are needing to compare the utilization of RBC-EMs as an additional drug delivery carrier.

Radio Indgena 94.1 FM KIND-LP currently hosts 28 hours of weekly live programming, with 19 live radio shows ranging in topics from community organizing, healthcare access and mental health, self-help and wellbeing, as well as native indigenous musical programs. In 2023, we have added and launched new programs: "Justicia y Dignidad," and "La Hora del Inmigrante." Also, our radio program has launched a new Indigenous journalism, art, and Youth Suicide Prevention programs for the benefit of our listeners and community. Radio Indgena's educational and musical selection captures and defines our philosophy and culture.

In 1979, Northwest Communities Education Center (NCEC), launched a Spanish language, public radio station in the heart of the Yakima Valley located in Eastern Washington. Broadcasting on a frequency of 91.9 FM with an effective radiated power of 20,000 watts, from studios located in Granger, Washington, the station is governed by a minority Board of Directors representative of its listening community.

KDNA will direct its efforts as a minority public radio station in response to the cultural and informational isolation of Hispanic/Latino and other disadvantaged communities. Radio KDNA will produce quality radio programming to help such communities overcome barriers of literacy, language, discrimination, poverty, and illness. In this way, KDNA will empower these communities to more fully participate in our multiethnic society.

Comenzamos a compartir las distintas realizaciones personales y colectivas producidas en el marco del taller anual 2021 de Produccion integral en Radio UNAHUR En esta oportunidad "Sereneleter", magazine radial producido y realizado en vivo durante la maana del Sbado 4 de Diciembre en nuestro aula taller . Contenidos, arte y musicalizacin integralmente a cargo de los y las participantes. Jorge, Stella, Adriana, Ivanna y Adolfo nos presentan "Sereneleter". En los prximos dias compartiremos ms producciones . Radio UNAHUR . Universidad Nacional de Hurlingham. ff782bc1db