Therapeutic Focus Research Articles

Diagnostic and classification criteria of heart failure in the practice of doctors at the prehospital stage

The article deals with an overview of heart failure with an emphasis on identification criteria and models of its classification based on literary sources from the MEDLINE database on the PubMed, Web of Science, Scopus, and Google Scholar platforms. The subjective and objective signs of chronic heart failure accor­ding to the Framingham Heart Study using the methods of clinical epidemiology and presented with modern data in the international guidelines are shown. Clinical manifestations of acute heart failure in patients with myocardial infarction are outlined. In chronological order, the hemodynamic classification of heart failure is reproduced with the definition of systolic and diastolic dysfunction as markers for ranking patients in practical work. Based on the materials of international guidelines developed by the experts of the American College of Cardiology, American Heart Association, Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, the diagnostic indicators of cardiac decompensation are summarized. Given the modern perception, the diagnostic value of the left ventricular ejection fraction has been proven for determining heart failure phenotypes. The classification of heart failure of the New York Heart Association plays a significant role in determining the functional class; this was reflected in the article. Based on the provisions of international guidelines, the importance of natriuretic peptides as potential biomarkers of acute and chronic heart failure is proved. The advantages of assessing the structural and functional parameters of the heart in patients for detecting the preclinical stage of heart failure, association with clinical events and control of treatment are described. An update version of heart failure classification is presented with the identification of four stages and highlighting their characteristics. According to this classification, a relevant preventive measure is to shift the therapeutic focus to the initial stages of diseases that trigger heart failure.

Structural Family Therapy with Chinese Families in After-Violence Context

This article aims to apply structural family therapy to working with family and intimate partner violence in after-violence context, where risks and safety issues have been addressed. This practice research study uses case analyses based on the work done with a Chinese couple and a Chinese family in Singapore, respectively. It identifies the salient therapeutic focus and healing processes in after-violence context with Chinese families. Reflections and feedback of social workers and clients during and after the conjoint sessions were included systematically. Practice implications to apply Structural family therapy in working with Chinese couples and families in after-violence are highlighted.

The psoriasis severity, dermatology life quality index and sleep quality: The role of itch intensity and depression

Aim of the studyTo better understand the origin of sleep quality impairment among psoriasis patients, we sought to examine whether the psoriasis severity, health related life quality, itch and depression are significant predictors of sleep disruption; and whether itch intensity and depression are mediators of the relationship between the health- related life quality and sleep problems.Subject or material and methods42 patients diagnosed with chronic plaque psoriasis, (female: 40.5%; mean age=44.48 years; SD=17.57, age range=21-82) completed Polish versions of: the Pittsburgh Sleep Quality Index (PSQI), the Centre for Epidemiological Studies - Depression scale (CES-D). The itch intensity was measured according to the 10-point visual analogue scale (VAS). The Severity of patient’s psoriasis was evaluated by using The Psoriasis Area Severity Index (PASI), health related life quality was assessed using the Dermatology Life Quality Index (DLQI) .ResultsThe stronger the negative effect of psoriasis on patients’ life as measured by Dermatology Life Quality Index, the greater the sleep disturbances.DiscussionThe results confirm that poor health- related quality of life may account for higher sleep ditrubances among psoriasis patients, and suggest that this negative effect reveals itself, through enhancing depression.ConclusionsIt seems that a greater therapeutic focus on health related quality of life in psoriasis patients may lead to an improvement in their sleep quality.

Diagnostic and predictive significance of the ferroptosis-related gene TXNIP in lung adenocarcinoma stem cells based on multi-omics

BackgroundLung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosis-related genes within lung CSCs. MethodsWe systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein‒protein interaction networks to identify hub genes. LC‒MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene–thioredoxin-interacting protein (TXNIP).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between TXNIP and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of TXNIP, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. ResultsA total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and TXNIP were singled out as hub genes, with TXNIP showing particularly noteworthy expression. The expression of the ferroptosis-related gene TXNIP exhibited correlations with the presence of an immunosuppressive microenvironment, TNM stages, and the degree of histological differentiation.Also, the ferroptosis-markers GPX4 and NCOA4 displayed correlations with LUAD. This comprehensive analysis underscores the significance of TXNIP in the context of ferroptosis-related processes and their potential implications in cancer development and progression. ConclusionThe investigation conducted in this study systematically delved into the role of the ferroptosis-related gene TXNIP in Lung CSCs. The identification of TXNIP as a potentially valuable biomarker in this context could have significant implications for refining prognostic assessments and optimizing therapeutic strategies for advanced lung cancer.

Abstract LB272: Sequential inhibition of PARP and BET as a rational therapeutic strategy for glioblastoma multiforme

Abstract Glioblastoma multiforme (GBM), characterized as one of the most aggressive brain cancers, presents significant treatment challenges due to its rapid growth, heterogeneity, and robust defensive mechanisms. Despite advancements in neuro-oncology, GBM's prognosis remains grim, with the median survival of approximately 15 months, underscoring the urgent need for innovative therapeutic strategies. Facing these challenges, PARP inhibitors (PARPi) hold substantial promise in treating GBM, evidenced by over 20 ongoing clinical trials. However, their application has been limited by side effects such as nausea, fatigue, and particularly anemia, as well as a narrow therapeutic spectrum focusing mainly on patients with homologous recombination deficiency (HRDness). Through unbiased transcriptomic and proteomic sequencing, and employing Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA), and Transcriptome-Proteome Correlation Analysis, we discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, extending beyond the previously known impact of BET inhibition on homologous recombination repair. In vitro experiments using GBM cell lines and patient-derived primary GBM cells demonstrated that concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, we observed that DNA damage persists after the discontinuation of PARPi monotherapy. Leveraging these residual effects of PARPi, subsequent BETi administration elevated replication stress levels, leading to the inactivation of GBM cell cycle checkpoints, with efficacy comparable to concurrent treatment. The treatment-induced prolonged stalling of replication forks resulted in their collapse and the formation of double-ended double-strand breaks (DSBs). In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, while protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. In vivo orthotopic transplantation tumor experiments in zebrafish and nude mice demonstrated consistent effects, indicating that sequential administration of PARPi followed by BETi maintained anti-tumor efficacy, similar to concurrent treatment, while reducing toxicity, as evident by the reduced impact on hemoglobin levels. Our findings provide a broader and deeper understanding of the synergistic interaction between BETi and PARPi than previously recognized. This study offers compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy. Citation Format: Xin Peng, Xin Huang, Shaolu Zhang, Naixin Zhang, Shengfan Huang, Yingying Wang, Zhenxing Zhong, Shan Zhu, Haiwang Gao, Zixiang Yu, Xiaotong Yan, Zhennan Tao, Yuxiang Dai, Zhe Zhang, Xi Chen, Feng Wang, Francois X. Claret, Ning Ji, Yuxu Zhong, Dexin Kong. Sequential inhibition of PARP and BET as a rational therapeutic strategy for glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB272.

Diosgenin loaded cellulose nanoonion impedes different stages of protein aggregation induced cell death via alleviating mitochondrial dysfunction and upregulation of autophagy

Protein aggregation is a multifaceted phenomenon prevalent in the progression of neurodegenerative diseases, yielding aggregates of diverse sizes. Recently, increased attention has been directed towards early protein aggregates due to their pronounced toxicity, largely stemming from inflammation mediated by reactive oxygen species (ROS). This study advocates for a therapeutic approach focusing on inflammation control rather than mere ROS inhibition in the context of neurodegenerative disorders. Here, we introduced Camellia sinensis cellulose nanoonion (CS-CNO) as an innovative, biocompatible nanocarrier for encapsulating the phytosteroid diosgenin (DGN@CS-CNO). The resulting nano-assembly, manifesting as spherical entities with dimensions averaging ~180–220 nm, exhibits a remarkable capacity for the gradual and sustained release of approximately 39–44 % of DGN over a 60-hour time frame. DGN@CS-CNO displays a striking ability to inhibit or disassemble various phases of hen egg white lysozyme (HEWL) protein aggregates, including the early (HEWLEA) and late (HEWLLA) stages. In vitro experiments employing HEK293 cells underscore the potential of DGN@CS-CNO in mitigating cell death provoked by protein aggregation. This effect is achieved by ameliorating ROS-mediated inflammation and countering mitochondrial dysfunction, as evidenced by alterations in TNFα, TLR4, and MT-CO1 protein expression. Western blot analyses reveal that the gradual and sustained release of DGN from DGN@CS-CNO induces autophagy, a pivotal process in dismantling intracellular amyloid deposits. In summary, this study not only illuminates a path forward but also presents a compelling case for the utilization of phytosteroid as a formidable strategy against neuroinflammation incited by protein aggregation.

Abstract 59: Triple negative breast cancer (TNBC) targeting CAR-T cell constructs with phage display-derived peptides

Abstract Introduction: Triple Negative Breast Cancer (TNBC) poses treatment challenges due to the absence of effective targeted therapies. CAR-T cell therapy, successful in hematological cancers, is now being investigated for solid tumors. Finding new CAR-T targets is vital to overcome TNBC's therapeutic constraints. Methods: In this study, a Biopanning phage display strategy employing a library of random peptides was utilized to identify potential targets for CAR-T cell therapy against TNBC. Through this approach, Heat Shock Protein 60 (HSP60) emerged as a promising candidate due to its binding affinity to the selected phage clones. Subsequent validation of HSP60 surface expression on TNBC cell lines in comparison to normal cells was conducted using flow cytometry. Concurrently, patient survival data were gathered and analyzed to evaluate the clinical significance of HSP60 expression in TNBC. The identified peptides demonstrating high specificity and affinity for HSP60 on the surface of TNBC cells were chosen for the development of a third-generation CAR-T model, incorporating various optimizations and innovations. Results: The Biopanning strategy successfully identified HSP60 as a prominent target for CAR-T cell therapy in TNBC. Flow cytometry analysis confirmed significantly elevated surface expression of HSP60 on TNBC cell lines compared to their normal counterparts, substantiating its potential as an accessible antigen for targeted therapy. Patient survival analysis linked elevated HSP60 levels with poorer prognosis in TNBC, highlighting the protein's clinical relevance. Peptides showing high specificity and binding to TNBC's HSP60 were integrated into a meticulously engineered third-gen CAR-T cell model. This design aimed to boost the CAR-T's precision in targeting and eliminating HSP60-expressing TNBC cells. Iterative optimizations ensured the construct's accuracy, laying the groundwork for a potent, tailored TNBC immunotherapy. Discussion: The discovery of HSP60 as a prime target for CAR-T cell therapy in TNBC is a pivotal advancement. Its distinct presence on TNBC cell surfaces, confirmed via flow cytometry, highlights its suitability for targeted immunotherapy. The correlation between elevated HSP60 levels and poorer prognosis in TNBC patients underscores its value as both a biomarker and a therapeutic focus. The peptides' exceptional specificity and strong binding to HSP60 validate their use in crafting a third-generation CAR-T cell model. Their integration and careful refinements in CAR-T design aim to optimize efficacy while reducing off-target effects, laying a robust foundation for tailored TNBC immunotherapy. Preclinical evaluations are imperative to thoroughly assess the safety and effectiveness of this innovative CAR-T approach. Citation Format: Muhammad G. Khodary, Alehegne W. Yirsaw, Yumna A. Elsobky, Reshma Gurung, Jessie Jaynes, Temesgen Samuel, Maninder Sandey, Deepa Bedi. Triple negative breast cancer (TNBC) targeting CAR-T cell constructs with phage display-derived peptides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 59.

Abstract 5729: ADCK1 inhibition alters cell proliferation and cell cycle progression in liver cancer cells

Abstract In 2020, there were over 830,000 reported liver cancer deaths. Incidence rates of liver cancer have tripled, and death rates have doubled since the 1980s; giving this disease one of the highest mortality rates when compared to its incidence rate. Hepatocellular carcinoma (HCC) is derived from hepatocytes and is the main type of liver cancer in adults, accounting for 75-85% of all primary liver cancers. Current treatment options for HCC like radiation therapy and chemotherapy are imperfect and cause significant side effects. Tumorigenesis is dependent on an organism’s cellular metabolism. Metabolic reprogramming is a promising area of focus for cancer therapeutics. Cancer cells thrive in nutrient-deficient environments by hijacking and reprogramming the cells existing cellular metabolism. Metabolic reprogramming is driven by genetic alterations and environmental cues. AarF Domain Containing Kinase 1 (ADCK1) is a protein-coding gene that acts as a mitochondrial protein with putative kinase activity. The role of ADCK1 has not been well studied, particularly in liver cancer. Our group has sought to study how ADCK1 impacts the metabolism and cellular environment of HCC cells to help establish a more effective drug target. Bioinformatics performed by our lab report that ADCK1 was highly expressed in HCC tumor cells. The expression levels of ADCK1 were also correlated with a decrease in patient survival. ADCK1 knockout clones were generated; these knockout cells showed decreased proliferation and altered cell cycle progression. Proteomics analysis demonstrated that loss of ADCK1 was also seen to alter the expression of proteins involved in several cellular processes related to the cell cycle and cellular metabolism. How ADCK1 regulates these processes will be studied in the future. Citation Format: Noel A. Jacquet, Yunfeng Zhao. ADCK1 inhibition alters cell proliferation and cell cycle progression in liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5729.

Pioglitazone reverses alcohol-induced alterations in alveolar macrophage mitochondrial phenotype.

People with alcohol use disorder (AUD) have an increased risk of developing pneumonia and pulmonary diseases. Alveolar macrophages (AMs) are immune cells of the lower respiratory tract that are necessary for clearance of pathogens. However, alcohol causes AM oxidative stress, mitochondrial damage and dysfunction, and diminished phagocytic capacity, leading to lung injury and immune suppression. AMs were isolated by bronchoalveolar lavage from people with AUD and male and female C57BL/6J mice given chronic ethanol (20% w/v, 12 weeks) in drinking water. The peroxisome proliferator-activated receptor γ ligand, pioglitazone, was used to treat human AMs exvivo (10 μM, 24 h) and mice invivo by oral gavage (10 mg/kg/day). Levels of AM mitochondrial superoxide and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA, a marker of oxidative stress, were measured by fluorescence microscopy and RT-qPCR, respectively. Mouse AM phagocytic ability was determined by internalized Staphylococcus aureus, and mitochondrial capacity, dependency, and flexibility for glucose, long-chain fatty acid, and glutamine oxidation were measured using an extracellular flux analyzer. Invitro studies used a murine AM cell line, MH-S (±0.08% ethanol, 72 h) to investigate mitochondrial fuel oxidation and ATP-linked respiration. Pioglitazone treatment decreased mitochondrial superoxide in AMs from people with AUD and ethanol-fed mice and HIF-1α mRNA in ethanol-fed mouse lungs. Pioglitazone also reversed mouse AM glutamine oxidation and glucose or long-chain fatty acid flexibility to meet basal oxidation needs. Invitro, ethanol decreased the rate of AM mitochondrial and total ATP production, and pioglitazone improved changes in glucose and glutamine oxidation. Pioglitazone reversed chronic alcohol-induced oxidative stress in human AM and mitochondrial substrate oxidation flexibility and superoxide levels in mouse AM. Decreased ethanol-induced AM HIF-1α mRNA with pioglitazone suggests that this pathway may be a focus for metabolic-targeted therapeutics to improve morbidity and mortality in people with AUD.

Structural and Compositional Changes in Two Marine Shell Traditional Chinese Medicines: A Comparative Analysis Pre- and Post-Calcination.

Arcae concha and Meretricis concha cyclinae concha are two marine shellfish herbs with similar composition and efficacy, which are usually calcined and used clinically. This study investigated variations in the inorganic and organic components of Arcae concha and Meretricis concha cyclinae concha from different production regions, both Arcae concha and Meretricis concha cyclinae concha. The aim was to enhance the understanding of these two types of marine shell traditional Chinese medicine (msTCM) and provide a foundation for their future development and application. Spectroscopic techniques, including infrared spectroscopy, X-ray spectroscopy, and X-ray fluorescence spectroscopy, were used to analyze the calcium carbonate (CaCO3) crystal and trace elements. Thermogravimetric analysis was used to investigate the decomposition process during heating. The proteins were quantified using the BCA protein assay kit. Principal component analysis (PCA) was used to classify inorganic elements in the two marine shellfish traditional Chinese medicines. No significant differences were found among the various production regions. The crystal structure of CaCO3 in the raw products was aragonite, but it transformed into calcite after calcination. The contents of Ca, Na, Sr, and other inorganic elements were highest. The protein content was significantly reduced after calcination. Therefore, these factors cannot accurately reflect the internal quality of TCM, rendering qualitative identification challenging. CaCO3 dissolution in the decoction of Arcae concha and Meretricis concha cyclinae concha increased after calcination, aligning with the clinical application of calcined shell TCM. PCA revealed the inorganic elements in them, indicating that the variation in trace element composition among different drugs leads to differences in their therapeutic focus, which should be considered during usage. This study clarifies the composition and structure changes of corrugated and clam shell before and after calcining, and it lays the foundation for the comprehensive utilization of marine traditional Chinese medicine. These technical representations reveal the differences between raw materials and processed products, which will provide support for the quality control of other shellfish TCM.

Antiparasitic activity of the iron-containing milk protein lactoferrin and its potential derivatives against human intestinal and blood parasites

An iron-containing milk protein named lactoferrin (Lf) has demonstrated antiparasitic and immunomodulatory properties against a variety of human parasites. This protein has shown its capability to bind and transport iron molecules in the vicinity of the host–pathogen environment. The ability of parasites to sequester the iron molecule and to increase their pathogenicity and survival depends on the availability of iron sources. Lf protein has suggested a iron chelating effect on parasites iron and, hence, has shown its antiparasitic effect. Since the parasites have a complex life cycle and have developed drug resistance, vaccines and other treatments are a handful. Therefore, therapeutic research focusing on natural treatment regimens that target the parasite and are non-toxic to host cells is urgently needed. The antiparasitic efficacy of Lf protein has been extensively studied over the past 40 years using both in vitro and in vivo studies. This review article highlighted past important studies on Lf protein that revealed its potential antiparasitic activity against various intracellular and extracellular intestinal or blood-borne human parasites. This review article structures the role of Lf protein in its various forms, such as native, peptide, and nanoformulation, laying the groundwork for its function as an antiparasitic agent and its possible known mechanisms of action.

Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.

Recent genomics and epigenetic advances haveempowered the exploration of DNA/RNA methylation and histone modifications crucial for gene expression in response to stress, agingand disease. Interest in understanding neuronal plasticity's epigenetic mechanisms, influencing brain rewiring amid development, agingand neurodegenerative disorders, continues to grow. Histone acetylation dysregulation, a commonality in diverse brain disorders, hasbecomea therapeutic focus. Histone acetyltransferasesand histone deacetylases haveemerged as promising targets for neurodegenerative disorder treatment. This review delves into histone acetylation regulation, potential therapiesand future perspectives for disorders like Alzheimer's, Parkinson'sand Huntington's. Exploring genetic-environmental interplay through models and studies reveals molecular changes, behavioral insightsand early intervention possibilities targeting the epigenome in at-risk individuals.

Systematic Literature Review: Penerapan Layanan Konseling Kelompok Solution Focused Brief Therapy (SFBT) pada Peserta Didik di Sekolah Menengah

The era of disruption due to the pandemic has caused a decline in the mental condition of students, especially in secondary schools. Efforts to overcome this problem include implementing guidance and counseling services in schools, one of which is group counseling. The study aims to determine how the application of group counseling services with a Solution Focused Brief Therapy (SFBT) approach to students in secondary school (adolescents) which includes the understanding of SFBT group counseling, the scope of problems overcome, the procedure for implementing and the success of SFBT group counseling as an alternative to counseling that is considered to meet the needs of generation Z students. Systematic Literature Review (SLR). Data collection using documentation techniques. The amount of literature studied after data selection amounted to 21 literatures. The data analysis used is content analysis. The results revealed that the application of SFBT group counseling is a short therapeutic focusing on solutions because it can be done with 4 to 8 sessions with a duration of 40 to 70 minutes and the counseling process does not well on problems but focuses on awareness and the ability of counsellors to solve problems. SFBT group counseling has been proven effective in various problems as well as the development of students in secondary schools covering the fields of Guidance Counseling services, namely personal, social, academic and career.

What to do when the unwanted happens? Negative event management in studies on internet- and mobile-based interventions for youths and adults with two case reports

BackgroundDespite severely burdened individuals, often being excluded from research studies on internet- and mobile-based interventions (IMIs), negative events (NEs) including suicidal thoughts and behaviors (STBs) can still occur during a trial. NEs require monitoring and adequate safety measures. However, study protocols frequently lack comprehensive descriptions of procedures for managing NEs. AimsThis study aimed to illustrate the assessment, monitoring, and procedures for addressing NEs in two studies on IMIs in adults and youth using case reports, to identify strengths and weaknesses of the NE management approaches, and to derive key learnings and recommendations. MethodsTwo case reports were drawn from two distinct IMI studies. The first study, PSYCHOnlineTHERAPY, evaluates the combination of an IMI with on-site psychotherapy for anxiety and depressive disorders in adults (adult blended study). The second study evaluates a standalone, therapist-guided IMI for post-traumatic stress disorder (PTSD) in youth (youth standalone study). Potential NEs were predefined depending on the study sample. The case studies thoroughly document the systematic recording and ongoing monitoring of NEs through self-report and observer-based assessments during the interventions. The cases illustrate a variety of NE management strategies, including automated and personalized approaches, adapted to the specific nature and severity of the NEs. The NE management approaches are visualized using decision trees. ResultsIn the adult blended case study, online questionnaires detected STBs and triggered automated support information. As on-site therapy had already ended, a telephone consultation session allowed for the identification and discussion of the heightened intensity of suicidal thoughts, along with the development of specific additional help options. In the youth standalone case study, heightened tension in an adolescent with PTSD during trauma processing could be addressed in a telephone therapeutic session focusing on resource activation and emotion regulation. The referral to on-site treatment was supported. Overall, advantages of the NE management included automated procedures, multimodal assessment of a wide range of NEs, and standardized procedures tailored to different severity levels. Weaknesses included the use of single-item assessments for STBs and lack of procedures in case of deterioration or nonresponse to treatment. ConclusionThis study provides practical insights and derives key learnings and recommendations regarding the management of NEs in different IMI contexts for both adults and youth.

Selection of new pathogens during antibiotic treatment or prolonged antibiotic prophylaxis in orthopedic surgery

In orthopedic surgery regarding open or infected wounds, both the current antibiotic therapy as well as the perioperative antibiotic prophylaxis, may select new pathogens leading to iterative debridement and changing the antibiotic regimens targeting more resistant microorganisms. The risk of finding new and more resistant pathogens is relatively high (5%-15%) and exceeds the incidence of primary surgical site infections (SSI) after elective orthopedic surgery with primary wound closures. Based on a narrative review of the current scientific literature, we summarize mechanisms and associations of such a pathogen selection by therapeutic or prophylactic agents and focus on the importance of an adequate initial debridement and on an effective antibiotic stewardship.

불경 본생담 아난다 서사의 문학치료적 독해

This paper explores the therapeutic potential within the past life stories of Ananda from the Buddhist sutra Jataka, applying the literary therapy theories and methods of the Society of Korean Literary Therapy.Literary therapeutics regards humans as literary beings, and its main task is to reflect on and adjust the story-in-depth inherent in life through the story-in-depth inherent in works. Using Ananda's narratives as a reflective tool, this study aims to examine the mindsets and behaviors that modern individuals should adopt when pursuing religious practices and the path of sainthood. In the Jataka, Ananda, alongside Devadatta, emerges as the second most frequently depicted character after Buddha. Often depicted as someone living a worldly life, Ananda symbolizes the juncture between the paths of Buddha and Devadatta. Many stories vividly portray his journey, showcasing a qualitative transformation from worldly entanglements to becoming an authentic companion of the Buddha. This process offers profound insights for contemporary individuals ensnared by greed and ignorance, illustrating how to break free, undergo existential transformation, and progress towards enlightenment.
 Through a narrative analysis of various Jataka materials, this study identifies six conditions contributing to Ananda's transition from a worldly existence to a saintly one. Firstly, an open-minded approach to truth, embracing immediate acceptance devoid of prejudice. Secondly, the willingness to let go without remorse, embracing bold changes in direction. Thirdly, embodying humility, sincere honesty, and selflessness in actions. Fourthly, the capacity for cool-headed discernment and practical problem-solving. Fifthly, unwavering faith and resilience during crises. Sixthly, fostering a humanity of respect and engaging in practical acts of compassion. These aspects interconnect rather than stand alone, portraying a human existence passionately lived not only through thoughts but also actions. Ananda's portrayal in the Jataka stories can be seen as a literary representation of the ideal Buddhist figure, serving as inspiration for Buddhism followers.
 Ananda's portrayal in the Jataka stories can be seen as a literary representation of the ideal Buddhist figure, serving as inspiration for Buddhism followers. The findings of this analysis hold significance in the realm of Buddhist counseling. Ananda's narrative provides rich material for healing conversations between counselors and clients, each characteristic of Ananda offering potential as a therapeutic focus. Employing 'story-making,' a hallmark technique in literary therapy, where clients reconstruct Ananda stories and reflect upon them, could introduce a novel approach to Buddhist counseling. Moreover, incorporating Ananda stories into established Buddhist counseling methods, such as ascetic meditation healing, could diversify and enhance the counseling experience. Leveraging various literary works, including folk tales, could serve as a valuable avenue to enrich Buddhist counseling methodologies.

Utilization of Hydrogels in Mesenchymal Stem Cell-Based Therapy for Kidney Diseases.

Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven their safety and effectiveness in treating acute kidney injury (AKI) and chronic kidney disease (CKD), but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional (3D) networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and the factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.

NCMP-09. THE CURRENT LANDSCAPE OF SPINE ONCOLOGY SURGICAL TRIALS AND FUTURE OPPORTUNITIES

Abstract BACKGROUND Clinical trials have allowed the discovery of successful therapeutic intervention for cancer patients. The current number of cancer patients in the US has increased with an incidence of 442/100,000 population and yet with decreased yearly mortality rate. Spine metastatic disease occurs in approximately 90% of patients with cancer. The aim of this study is to analyze the current landscape of spine oncology trials to identify future opportunities. METHODS To assess active and ongoing clinical trials in the treatment of metastatic spinal disease, the authors queried https://clinicaltrials.gov/ under the searches “Spine Metastases” and “Spine Tumor.” Only clinical trials designated as “Recruiting” were included. Parametric and non-parametric statistical analysis was performed. RESULTS Our initial search yielded to 100 total studies; 18 clinical trials met entry criteria. Trial type was 16/18 therapeutic, 2/18 observational and trial design 6/18 (33%) randomized. All 18 trials were single center. Trials were were based in the United States (90%) and British Columbia, Canada. Across US geographical quadrants, a significant higher number of therapeutic trials was found in the South quadrant (12/16) compared to the other quadrants, (p< 0.001; Midwest: N=3/16, Northeast: N=1). The most common therapeutic focus included radiosurgery, followed by vertebral body augmentation and/or radiofrequency ablation, and laser interstitial thermal therapy (LITT). CONCLUSION Clinical trials are a cornerstone for the advancement oncological treatment. Our study shows that currently there is an ample opportunity to design clinical trials for our growing population of metastatic spine disease patients. Successful strategies to enhance the needed portfolio of spinal oncology trials, include focusing on including all US geographic quadrants. As new trials are designed, continued efforts devoted to data entry in national registry remains important.

Characterizing the Immature Immunophenotype of Sickle Cell Disease Monocytes during Vaso-Occlusive Crisis

Sickle cell disease (SCD) is marked by episodic vaso-occlusive crisis (VOC). Painful VOC is the leading cause of emergency room visits and hospitalization in SCD, contributing heavily to the morbidity and mortality of this disease. Recurrent VOC creates a pro-inflammatory state that induces phenotypic alterations in the innate immune system. This inflammation-induced immune profile remodeling results in chronically active monocytes and neutrophils that antagonizethe vascular endothelium and further predispose SCD patients to VOC. While the mechanism of neutrophil involvement in VOC has been elucidated, less is known about the pathologic role of monocytes. Monocytes are of particular interest to VOC pathophysiology because they are especially malleable to inflammatory signaling. Indeed, inflammatory disease states such as COPD, obesity and atherosclerosis are known to influence monocyte development and alter monocyte subpopulations. Recently, nonclassical monocytes (CD14 dimCD16 +) with high heme oxygenase-1 expression have been shown to have a critical role in preventing VOC, generating renewed interest in monocytes as a therapeutic focus in SCD. In this study, we describe the monocyte subsets found in SCD patients during VOC by performing immunophenotypic flow cytometric, enzymatic, and morphologic analysis on peripheral blood obtained during hospitalization for VOC. Herein, we add to the growing body of evidence suggesting aberrant monocyte populations underpin VOC pathophysiology. We found that SCD monocytes during VOC possess an immature phenotype as demonstrated by 1) decreased CD4 positivity (p < .01), 2) low α-naphthyl butyrate esterase (ANBE) expression, and 3) naïve morphologic features (high nuclear/cytoplasmic ratio, indented or less lobular nuclei, and decreased cytoplasmic vacuolization). We additionally found an increase in CD14 +CD16 -CD4 - monocytes (p < .01), a subset associated with the impaired immune response of post-trauma patients. Interestingly, we also found a large proportion of CD14 +CD4 -HLA-DR - monocytes which, under normal circumstances, are exclusively found in neonates (p < .01). Finally, we report an increase in nonclassical monocytes (CD14 dimCD16 +), providing further evidence for the connection between this subset and the molecular mechanisms driving VOC. Taken together, these findings suggest that SCD patients in VOC deploy relatively immature monocytes that possess a lower capacity for antigen presentation, likely contributing to the immune dysfunction observed in SCD.

In vitro studies of magnesium oxide nano-particles of Saccharum officinarum root extract: Evaluation of the antidiabetic effect using alpha-glucosidase enzyme

Objective: Magnesium oxide nanoparticle green synthesis is said to have a wide range of biomedical uses. Inhibiting the activity of pancreatic enzymes is one method for treating diabetes. The goal of this study was to show in-vitro evidence that Saccharum officinarum magnesium oxide nanoparticles may inhibit the activity of the enzyme α-glucosidase. This study had a therapeutic focus as this could be emerging candidates of new drugs for controlling hyperglycemia. Materials and Procedures: Saccharum officinarum root extract was used to create magnesium oxide nanoparticles, which were then examined for bioactive components and tested for α-glucosidase inhibition. When the enzyme substrate solution was incubated with various doses of the grass-root Magnesium oxide nanoparticles, the activity of the enzyme was monitored to identify the kind of inhibition. Result: Magnesium oxide nanoparticles synthesized from Saccharum officinarum root extract showed concentration and time-dependent inhibition of α-glucosidase. An 85% inhibition was observed with 0.6 mg/ml of the synthesized nanoparticles. Conclusion: The results showed that the ethanolic extract of MgO nanoparticles synthesized by Saccharum officinarum exhibited effective antidiabetic activity, supporting its use in the treatment and control of diabetes.