Exploring the protective potential of NRF2 overexpressed neural extracellular vesicles against cisplatin-induced neurotoxicity via NRF2/ARE pathway.

Neurotoxicity is characterized by the accumulation of harmful chemicals such as heavy metals and drugs in neural tissue, resulting in subsequent neuronal death. Among chemicals platinum-based cancer drugs are frequently used due to their antineoplastic effects, but this drug is also known to cause a wide range of toxicities, such as neurotoxicity. The nuclear-factor-erythroid 2-related factor-2 (NRF2) is crucial in combating oxidative stress and maintaining cellular homeostasis. This study thoroughly explores the protective effects of extracellular vesicles derived from NRF2 gene overexpressed neural progenitor cells (NEVs) on cisplatin-induced neurotoxicity. Therefore, extracellular vesicles derived from neural progenitor cells were isolated and characterized. The Cisplatin neurotoxicity dose was 75 µM in mature, post-mitotic neurons. 1.25 µM of tert-butyl hydroquinone that induces NRF2/ARE pathway was used as the positive control. The effects of extracellular vesicles (EVs) were investigated using functional and molecular assays such as PCR and protein-based assays. Here, we observed that NEVs dose-dependently protected post-mitotic neuron cells in response to cisplatin. The study also examined whether the effect was EV-induced by limiting EV biogenesis. The molecular basis of preventive treatment was established. When pre-administered, 1×108 particles/ml of NEVs maintained antioxidant and detoxifying gene and protein expression levels similar to control cell levels. Furthermore, NEVs reduced both cellular and mitochondrial ROS levels and preserved mitochondrial membrane potential. In addition, Catalase and SOD levels were found higher in NEV-treated cells compared to cisplatin control. The findings in NRF2-based protection of cisplatin-induced neurotoxicity may provide further evidence for the relationship between EVs and inhibition of neuronal stress through the NRF2/ARE pathway, increasing the understanding of neuroprotective responses and the development of gene-engineered EV therapy options for peripheral neuropathy or other neurodegenerative diseases. This is the first study in the literature to investigate the neutralizing potency of NRF2 overexpressed neural EVs against cisplatin-induced neurotoxicity.

Unveiling the potential: Extracellular vesicles from plant cell suspension cultures as a promising source.

Extracellular vesicles are secreted by all eukaryotic cells and they have an important role in intercellular signaling. Plant extracellular vesicles (PEVs) are a novel area of research that has gained attention due to their potential implications in biomolecule transport and therapeutic applications. PEVs are lipid bilayer-enclosed structures that contain a diverse cargo of biomolecules such as proteins and lipids. Moreover, it is known that PEVs have a noticeable therapeutic potential for various conditions such as inflammation and oxidative stress. However, there are critical problems such as removing the endosomes and plant-derived biomolecules that decrease the standardization and therapeutic efficacy of PEVs. In our study, the aim was to characterize plant cell suspension-derived extracellular vesicles (PCSEVs) obtained from two different plant cell suspension cultures: Stevia rebaudiana and Vaccaria hispanica. These vesicles were isolated using ultrafiltration and characterized with nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM). The molecular composition of PCSEVs was profiled and the cellular uptake assay was performed. Our results demonstrated that PCSEVs have a spherical shape, less than 200 nm. In the fatty acid analysis, the primary components in PCSEVs were palmitic acid, linoleic acid, and cis-vaccenic acid. The protein content of Stevia rebaudiana-derived EVs (SDEVs) was largely associated with proteins involved in extracellular structures and functions. Conversely, Vaccaria hispanica-derived EVs (HDEVs) displayed a higher presence of cytosolic proteins. These findings contribute to the understanding of PCSEVs and open up potential avenues in extracellular vesicle research, pointing to promising prospects for future innovations in various fields.

Impact of molecular and histopathological findings on FIGO 2009 stage I endometrial cancer: Transition to FIGO 2023 staging system.

AIM: This study aims to investigate the impact of integrating molecular and histopathological findings into the revised International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system on patients initially diagnosed with stage I endometrial cancer (EC) according to the FIGO 2009 criteria. METHODS: A cohort of 197 EC patients, initially classified as stage I under FIGO 2009, underwent restaging based on the updated FIGO 2023 criteria. The patients' molecular and histopathological characteristics were documented, and their impact on upstaging was analyzed. RESULTS: Molecular profiling was conducted for 81.2% (160/197) of the patients, revealing that 55.3% (109/197) were classified as non-specific molecular profile, 14.7% (29/197) as mismatch repair deficiency, 11.2% (22/197) as p53 abnormality (p53abn), and 18.8% (37/197) as unknown. Upstaging was identified in 26.9% (43/160) of the 160 patients with known molecular profiles. Among the upstaged patients, 51.2% experienced upstaging due to p53 abnormality, 20.9% due to substantial lymphovascular space invasion (LVSI), 20.9% due to aggressive histological types, and 6.9% due to high grade. CONCLUSIONS: The introduction of the molecular profile into the revised FIGO 2023 staging system for stage I EC has led to notable changes in the staging of approximately one-fifth of patients. While p53 abnormalities have emerged as the most influential factor contributing to the upstaging, LVSI and aggressive histological types also represent significant contributing factors.

Assessment of Anxiety, Depression, Self-Esteem, and Quality-of-Life in Patients Undergoing Surgical Removal of an Eye.

Objectives: The objective of this study was to compare anxiety, depression, self-esteem, and quality of life in patients who underwent surgical removal of an eye with those of controls as well as to test the correlations of these variables in both groups. Methods: Beck anxiety inventory (BAI), Beck depression inventory (BDI), 36-item short-form health survey (SF-36), and Rosenberg self-esteem scale were administered to 29 patients with surgical removal of an eye and 30 control subjects. Results: The patient group had significantly lower scores on physical functioning, role limitations due to physical and emotional problems, pain, and general health perception domains of SF-36, as well as significantly higher BDI (p=0.004) scores as compared to controls. The study groups did not differ significantly with respect to BAI scores and energy/vitality, mental health, and social functioning domain scores of SF-36 (p>0.05). Conclusion: This population of monocular patients had similar mental health-related and Beck's Anxiety Inventory scores equivalent to the control group despite the surgical removal of one eye. However, lower scores for some SF-36 domains and higher depression levels in this patient group suggest that psychiatric rehabilitation should be considered after eye removal to improve the psychological outcomes and quality of life in these patients.

A Perspective on the Characterization of Early Neural Progenitor Cell-Derived Extracellular Vesicles for Targeted Delivery to Neuroblastoma Cells.

As an element of the cellular signaling systems, extracellular vesicles (EVs) exhibit many desirable traits for usage as targeted delivery vehicles. When administered, EVs cause little to no toxic or immune response, stay in circulation for longer periods compared to synthetic carriers, preferentially accumulate in tissues that are the same or similar to their cell-of-origin and can pass through the blood-brain barrier. Combined, these traits make neural EVs a particularly promising tool for delivering drugs to the brain. This study aims to combine tissue and EVs engineering to prepare neural differentiated cells derived EVs that exhibit neural properties, to develop an effective, tissue-homing drug and gene delivery platform for the brain. Early neural differentiated cell-derived EVs were produced with neural characteristics from neural differentiated human neonatal dermal fibroblasts. The EVs carried key neural proteins such as Nestin, Sox2 and Doublecortin. The cellular uptake of early neural differentiated cell-derived EVs was higher compared to non-neural EVs during in vitro uptake assays on neuroblastoma cells. Moreover, eND-EVs were significantly decreased the viability of neuroblastoma cells. In conclusion, this study revealed that early neural differentiated cell-derived EVs have potential as a promising drug carrier for the treatment of various neural disorders.

Extracellular vesicles derived from human foreskin cells (hFS-Exo) accelerate cell migration and angiogenesis through MAPK pathway: an in vitro study.

BACKGROUND: Wound healing is one of the important processes in the body. Attempts to create new drugs are of interest due to the side effects of natural and chemical wound healing compounds. To overcome this obstacle, stem cells have been used as healing agents. However, both difficulties in collection and risks such as rejection and teratoma in the recipient body have limited the use of stem cells, directly. Since the potential content of the stem cells can be transferred to the recipient cells by vesicles, small extracellular vesicles have recently become prominent agents. METHODS AND RESULTS: The wound-healing effect of extracellular vesicles derived from foreskin cells was investigated in both keratinocyte and endothelial cells. Migration assay, RT-PCR, Col1a1 ELISA and Western Blot experiments were utilized to reveal healing effect of EVs and its possible molecular pathways. EV-treated groups exhibited more proliferative, invasive, and migrative characteristics. When comparing to the control group, new vessel formation was induced in EV groups. An increase in gene levels of growth factors related to wound healing and change in the mitogen-activated protein kinase (MAPK) signaling pathway proteins in EV-treated groups were determined. Possible molecular mechanisms underlying cell movements were associated with the MAPK pathway. It was found that human foreskin cell EVs (hFS-Exo) may have a potential to heal wounds in a short period of time by triggering the MAPK pathway. CONCLUSIONS: hFS-Exo could be a new promising wound healing agent in the future.

Changes in physical properties of universal composites and CAD/CAM materials after bleaching and antioxidant applications: Scanning electron microscope and atomic force microscope evaluation.

To evaluate the effects of vital bleaching agents and the subsequent application of ascorbic acid (AA) to universal composites and resin-based CAD/CAM blocks on the physical properties of materials. In the study; G-enial A'chord (GCA), Filtek Ultimate (FU), Clearfil Majesty (CM) composites, and LAVA Ultimate (LU), Cerasmart (GCC) CAD/CAM blocks were used. The materials were divided into two subgroups based on the applied bleaching type (n = 30/group): office bleaching (OB) and home bleaching (HB). After bleaching, AA was applied to the samples. Surface roughness, microhardness, and color change values of all samples were measured at three stages: initial (I), post-bleaching (B), and post-bleaching+AA application (BA). Statistical analysis was performed using 3-way Mixed ANOVA with Bonferroni correction (p < .05). The BA of the HB group of CM; the B of the HB group of LU; the B roughness values of both the OB and HB groups of GCC were significantly lower than I. The microhardness values of all the materials examined decreased significantly after both bleaching (p < .05). With regard to the AA application, it significantly decreased Ra values in the HB group of CM. In addition, it significantly increased the microhardness values in the HB groups of CM and GCC. Also, the ΔE001 and ΔE002 values for the FU and GCC HB groups were significantly higher than in the OB groups (p < .05). Bleaching and AA application affected the physical properties of the materials. The physical properties of the materials either remained unchanged or improved with the application of AA after bleaching. RESEARCH HIGHLIGHTS: This article presents in vitro results of a new approach that has not been studied before. Ascorbic acid, used to increase the bond strength between the material-tooth after bleaching, was used to eliminate the adverse effects of bleaching on the physical properties of aesthetic restorative materials. Additionally, the effects of all procedures on the materials were examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). As a result of the study, it was concluded that the application of ascorbic acid after bleaching improved the physical properties of some of the materials.

Pharmacokinetic model of human exposure to ciprofloxacin through consumption of fish.

Fluoroquinolones are broad-spectrum antibiotics that accumulate in the environment. To assess human exposure through the food chain, we developed a pharmacokinetic model of fluoroquinolone accumulation in fish and a human pharmacokinetic model to predict gastrointestinal concentrations of ciprofloxacin, a common fluoroquinolone, following consumption of fish. At 70 ng/L ciprofloxacin, the average in North American surface waters, the fish steady-state concentration was calculated to be 7.5 × 10-6 µg/g. Upon human consumption of the FDA-recommended portion of 113 g of fish containing this ciprofloxacin level, the predicted human intestinal concentration was 2 × 10-6 µg/mL. At 4 × 106 ng/L (4 µg/mL) ciprofloxacin, the highest recorded environmental measurement, these numbers were 0.42 µg/g in fish and 0.1 µg/mL in the human intestine. Thus, based on the ciprofloxacin MIC for E. coli of 0.13 µg/mL, background environmental ciprofloxacin levels are unlikely to be problematic, but environmental pollution can result in high intestinal levels that may cause gut dysbiosis and antibiotic resistance.

The relationship between DNA mismatch repair gene and other prognostic parameters in pancreatic adenocarcinoma.

The aim of the study was to determine DNA mismatch repair (MMR) proteins by immunohistochemically using MLH1, MSH2, MSH6, and PMS2 antibodies in patients diagnosed as pancreatic ductal adenocarcinoma and to assess its relationship with histopathological and clinical prognostic parameters. Fifty cases with a diagnosis of pancreatic ductal adenocarcinoma who underwent surgical resection, were included in the study. Demographic and histopathological features of the patients were collected from the medical records. The relationships between microsatellite status and prognostic parameters were determined. The mean age of the patients was 66.5 ± 9.5 years (range: 47-87) and male/female ratio was 1.63 (31/19). No errors were detected in DNA MMR proteins in any of the cases, and were classified as microsatellite stable. The mean tumor diameter was 4.01 ± 1.77 cm and 74% of the tumors were localized in the pancreatic head. All of the cases had lymphatic invasion, whereas vascular invasion was detected in only 78% and perineural invasion in 98% of the patients. When the relationship between prognostic parameters and survival was evaluated, statistically significant correlation was observed in patient age and histopathological parameters such as tumor diameter, status of surgical margins, and vascular invasion (p < 0.05). Age, tumor size, presence of tumor at surgical margins, vascular invasion, and adjuvant treatment were correlated with survival. Although microsatellite instability was not detected in our cases, it is important to determine the microsatellite status by immunohistochemistry for predicting the chemotherapy response and determining the immunotherapy option in pancreatic adenocarcinomas.

Removal of two antidepressant active pharmaceutical ingredients from hospital wastewater by polystyrene-coated magnetite nanoparticles-assisted batch adsorption process.

This study employed simple polystyrene-coated magnetite nanoparticles (PS@MNPs)-assisted batch adsorption process for the removal of two antidepressant active ingredients (amitriptyline HCl and sertraline HCl) from hospital wastewater. Dominant parameters of the adsorption process including pH, adsorbent amount, and contact period were optimized through the univariate approach to enhance the adsorption efficiency. Upon reaching optimum adsorption conditions, equilibrium experiments were performed by spiking the adsorbates in hospital wastewater in the concentration range of 100-2000 µg/L. The concentrations of the adsorbates in the effluent were calculated using the matrix-matching calibration strategy to enhance the accuracy of quantification. A validated switchable solvent-based liquid phase microextraction (SS-LPME) method was employed to enrich the two active pharmaceutical ingredients (APIs) prior to sensitive determination with GC-MS (gas chromatography-mass spectrometry). The equilibrium data were mathematically modeled employing the Langmuir and Freundlich adsorption isotherm models. The isotherm constants were calculated, and the results showed that both the isotherm models fitted well with the experimental data. The efficient and simple batch adsorption strategy reported in this study was successfully employed to remove amitriptyline HCl and sertraline HCl from hospital wastewater at low concentrations.

The emerging role of breast cancer derived extracellular vesicles-mediated intercellular communication in ovarian cancer progression and metastasis.

Breast cancer is one of the most occurring cancer types in women worldwide and metastasizes to several organs such as bone, lungs, liver, brain, and ovaries. Extracellular vesicles (EVs) mediate intercellular signaling which has a profound effect on tumor development and metastasis. Recent developments in the field of EVs provide an opportunity to investigate the roles of EVs released from tumor cells in metastasis. In this study, we compared the effects of metastatic breast cancer-derived EVs on both nonluteinized granulosa HGrC1 and ovarian cancer OVCAR-3 cells in terms of proliferation, invasion, apoptosis, and gene expression levels. EVs were isolated from the culture medium of metastatic breast cancer cell line MDA-MB-231 by ultracentrifugation. Cell proliferation, apoptosis, cell cycle, invasion, and cellular uptake analysis were performed to clarify the roles of tumor-derived EVs in both cells. 6.85 × 108 nanoparticles of BCD-EVs were markedly increased cell proliferation as well as invasion capacity. Exposing the cells with BCD-EVs for 24 h, resulted in an accumulation of both cells in G2/M phase as determined by flow cytometry. The apoptosis assay results were consistent with cell proliferation and cell cycle results. The uptake of the BCD-EVs was efficiently internalized by both cells. In addition, marked variations in fatty acid composition between cells were observed. BCD-EVs appeared new fatty acids in HGrC1. Besides, BCD-EVs upregulated epithelial-mesenchymal transition (EMT) and proliferation-related genes. In conclusion, an environment of tumor-derived EVs changes the cellular phenotype of cancer and noncancerous cells and may lead to tumor progression and metastasis.

Spatio-temporal distribution of microplastic pollution in surface sediments along the coastal areas of Istanbul, Turkey.

Microplastics (MPs) have become prevalent in various environmental compartments, including air, water, and soil, attracting attention as significant pollutant parameters. This study investigated the prevalence of MP pollution in surface sediments along Istanbul's Marmara Sea, encompassing the megacity and the Bosphorus. A comprehensive sampling approach was employed, covering 43 stations across four seasons and depths ranging from 5 to 70 m. The objective was to assess the impact of terrestrial, social, and industrial activities on MPs. The average concentrations varied per season, with fall, winter, spring, and summer values recorded as 2000 ± 4100, 1600 ± 3900, 4300 ± 12,000, and 9500 ± 20,300 particles/kg-DW. The study identified river stations in the Golden Horn and sea discharge locations as hotspots for high concentrations. Notably, the dominant shape shifted from fibers in fall, winter, and spring to fragments during summer, coinciding with mucilage occurrences. The study identified 11 different polymers, with polyethylene (44 %) and polypropylene (31 %) being the most common.

Endothelial cell-derived extracellular vesicles induce pro-angiogenic responses in mesenchymal stem cells.

Angiogenesis is a central component of vital biological processes such as wound healing, tissue nourishment, and development. Therefore, angiogenic activities are precisely maintained with secreted factors such as angiopoietin-1 (Ang1), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF). As an element of intracellular communication, extracellular vesicles (EVs)-particularly EVs of vascular origin-could have key functions in maintaining angiogenesis. However, the functions of EVs in the control of angiogenesis have not been fully studied. In this study, human umbilical vein endothelial cell line (HUVEC)-derived small EVs (<200 nm; HU-sEVs) were investigated as a potential pro-angiogenic agent. Treating mesenchymal stem cells (MSCs) and mature HUVEC cells with HU-sEVs induced their tube formation under in vitro conditions and significantly increased the expression of angiogenesis-related genes, such as Ang1, VEGF, Flk-1 (VEGF receptor 2), Flt-1 (VEGF receptor 1), and vWF (von Willebrand Factor), in a dose-dependent manner. These results indicate that HU-sEVs take part in angiogenesis activities in physiological systems, and suggest endothelial EVs as a potential therapeutic candidate for the treatment of angiogenesis-related diseases.

Evaluation of the Long-Term Clinical Results of 3 Patients Implanted with the Argus II Retinal Prosthesis.

This study presents the long-term clinical results of Argus II retinal prosthesis implantation in eyes with light perception and projection in 3 patients with end-stage retinitis pigmentosa. No conjunctival erosion, hypotony, or implant displacement was observed during postoperative follow-up. The electrical threshold values were lower in the macular region and higher close to the tack fixation region and peripherally. Optical coherence tomography scans showed fibrosis and retinoschisis formation at the retina-implant interface in two cases. This was attributed to mechanical and electrical effects on the tissue due to the active daily use of the system and the electrodes' proximity to the retina. The patients were able to integrate the system into their daily lives and perform activities that they could not do before. Studies on retinal prostheses for the rehabilitation of hereditary retinal diseases are ongoing, so both social and clinical observations and experiences related to the implant are valuable.

Artificial intelligence for prediction of endometrial intraepithelial neoplasia and endometrial cancer risks in pre- and postmenopausal women.

BACKGROUND: The current approach to endometrial cancer screening requires that all patients be able to recognize symptoms, report them, and carry out appropriate interventions. The current approach to endometrial cancer screening could become a problem in the future, especially for Black women and women from minority groups, and could lead to disparities in receiving proper care. Moreover, there is a lack of literature on artificial intelligence in the prediction and diagnosis of endometrial intraepithelial neoplasia and endometrial cancer. OBJECTIVE: This study analyzed different artificial intelligence methods to help in clinical decision-making and the prediction of endometrial intraepithelial neoplasia and endometrial cancer risks in pre- and postmenopausal women. This study aimed to investigate whether artificial intelligence may help to overcome the challenges that statistical and diagnostic tests could not. STUDY DESIGN: This study included 564 patients. The features that were collected included age, menopause status, premenopausal abnormal bleeding and postmenopausal bleeding, obesity, hypertension, diabetes mellitus, smoking, endometrial thickness, and history of breast cancer. Endometrial sampling was performed on all women with postmenopausal bleeding and asymptomatic postmenopausal women with an endometrial thickness of at least 3 mm. Endometrial biopsy was performed on premenopausal women with abnormal uterine bleeding and asymptomatic premenopausal women with suspected endometrial lesions. Python was used to model machine learning algorithms. Random forest, logistic regression, multilayer perceptron, Catboost, Xgboost, and Naive Bayes methods were used for classification. The synthetic minority oversampling technique was used to correct the class imbalance in the training sets. In addition, tuning and boosting were used to increase the performance of the models with a 5-fold cross-validation approach using a training set. Accuracy, sensitivity, specificity, positive predictive value, and F1 score were calculated. RESULTS: The prevalence of endometrial or preuterine cancer was 7.9%. Data from 451 patients were randomly assigned to the training group, and data from another 113 patients were used for internal validation. Of note, 3 of 9 features were selected by the Boruta algorithm for use in the final modeling. Age, body mass index, and endometrial thickness were all associated with a high risk of developing precancerous and cancerous diseases, after fine-tuning for the multilayer computer to have the highest area below the receiver operating characteristic curve (area under the curve, 0.938) to predict a precancerous disease. The accuracy was 0.94 for predicting a precancerous disease. Precision, recall, and F1 scores for the test group were 0.71, 0.50, and 0.59, respectively. CONCLUSION: Our study found that artificial intelligence can be used to identify women at risk of endometrial intraepithelial neoplasia and endometrial cancer. The model is not contingent on menopausal status or symptoms. This may be an advantage over the traditional methodology because many women, especially Black women and women from minority groups, could not recognize them. We have proposed to include patients to provide age and body mass index, and measurement of endometrial thickness by either sonography or artificial intelligence may help improve healthcare for women in rural or minority communities.

Zoom-delivered Physical Activities Can Increase Perceived Physical Activity Level in Children with Autism Spectrum Disorder: a Pilot Study.

Although the benefits of regular physical activity are clearly expressed, children with Autism Spectrum Disorder (ASD) are less physically active than their typically developing peers. Recent empirical studies have revealed that the level of physical activity of children with ASD has further decreased during the novel coronavirus (COVID-19) pandemic, which has adversely affected the whole world. The aim of this study was to evaluate the potential efficacy of a Zoom-delivered physical activities for children with Autism Spectrum Disorder (ASD). Twenty-two families (parent and child dyads) participated in the study. Families were assigned randomly to an experimental group (n = 11) and a control group (n = 11). Families in the experimental group were engaged in 10 weeks of the Zoom-delivered physical activities. Data were collected using multiple data collection strategies (Personal Information Form- Leisure Time Exercise Questionnaire-Semi-Structured Interview). After the Zoom-delivered physical activities, a significant increase was observed in the physical activity level of children with ASD in the experimental group (F = 95.396, p = 0.000, È  2 = 0.834). Parents reported that Zoom-delivered physical activities are a viable and useful intervention to increase the level of physical activity of children with ASD. The findings suggest that Zoom-delivered physical activities merit further investigation as an intervention to increase physical activity in children with ASD.

A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™).

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.

Executive Functions, Intellectual Capacity, and Psychiatric Disorders in Adults with Type 1 Chiari Malformation.

OBJECTIVE: Contrary to popular belief, the cerebellum is involved not only in motor planning, balance, and coordination but also in cognitive processes. The present study aimed to investigate executive functions (EFs), intellectual capacity, and psychiatric disorders in adults with type 1 Chiari malformation, which is defined as a hindbrain anomaly that involves the cerebellum. METHODS: The study included 62 adults, with 29 in the CM group and 33 in the control group. EFs were evaluated using the Stroop test, number sequence learning test, and standardized mini-mental state examination (SMMSE). The intelligence quotient (IQ) was measured using the Kent EGY and Porteus maze tests, and psychiatric disorders were evaluated using the Structured Clinical Interview for DSM-5, Clinician Version (DSM-5-CV). RESULTS: The CM group took longer than the control to complete the Stroop test for each section (P < 0.005). Although the mean IQ scores of both groups were within the normal range, the CM group had a lower mean IQ score than the control group (P < 0.005). Although the mean SMMSE scores of both groups were within the normal range, the CM group had a lower mean SMMSE score than the control group (P < 0.005). The CM group had a higher rate of psychiatric comorbidities than the control group (P < 0.005). CONCLUSIONS: The study found that subjects with type 1 Chiari malformation performed worse in EFs than healthy controls and had a higher prevalence of psychiatric disorders.

A WhatsApp-delivered intervention to promote physical activity in young children with autism spectrum disorder.

Objective: The aim of this study was to examine the effects of WhatsApp-delivered physical activities on the physical activity level of children with Autism Spectrum Disorder (ASD). Method: This study used the mixed-method sequential exploratory design that consisted of the quantitative stage and the qualitative stage. The 42 family (parent and child dyads) participated in the study. Families were assigned randomly to an experimental group (n: 21) and a control group (n: 21). Families in the experimental group were engaged in 6 weeks of the WhatsApp-delivered physical activities. The data were collected through Leisure Time Exercise Questionnaire (LTEQ) and Semi-Structured Interview Questions. A two-way mixed ANOVA (2 groups × 2 time points) was used to determine the effects of WhatsApp-delivered physical activities on the physical activity level of children with ASD. Results: After the WhatsApp-delivered physical activities, a significant increase was observed in the physical activity level of children with ASD in the experimental group compared to the control group. Conclusions: The results provided evidence that WhatsApp-delivered physical activities positively affect the physical activity level of children with ASD.

All-Electrical Spin-to-Charge Conversion in Sputtered BixSe1-x.

One of the major obstacles to realizing spintronic devices such as MESO logic devices is the small signal magnitude used for magnetization readout, making it important to find materials with high spin-to-charge conversion efficiency. Although intermixing at the junction of two materials is a widely occurring phenomenon, its influence on material characterization and the estimation of spin-to-charge conversion efficiencies are easily neglected or underestimated. Here, we demonstrate all-electrical spin-to-charge conversion in BixSe1-x nanodevices and show how the conversion efficiency can be overestimated by tens of times depending on the adjacent metal used as a contact. We attribute this to the intermixing-induced compositional change and the properties of a polycrystal that lead to drastic changes in resistivity and spin Hall angle. Strategies to improve the spin-to-charge conversion signal in similar structures for functional devices are discussed.