Relative Levels Research Articles

Cross-cultural adaptation and primary approbation of the Russian version of Posttraumatic Growth and Depreciation Inventory — Expanded version

Numerous studies suggest that caring for someone with a chronic disease is often associated with the various negative consequences for the patient’s informal caregivers. At the same time, positive changes caused by the stress influence of patient’s disease can be also noted. For example, the so-called posttraumatic growth. Currently, there is a lack of assessment tools in domestic psychology, that allow to investigate the relation between constructive (developmental) and destructive aspects of the relative’s mental response in a situation of chronic illness of a loved one.The aim of this work was to carry out cross-cultural adaptation and primary approbation of the Posttraumatic Growth and Depreciation Inventory — Expanded version (PTGDI-X). Primary approbation was performed on a focus group of relatives of patients with cerebral pathology (n = 61, mean age 51,2 [SD = 15,3] years). Convergent and discriminant validity of the PTGDI-X assessed using World Assumption Scale (WAS), Symptom Checklist-90-Revised (SCL-90-R), Level of Relatives’ Emotional Burnout Questionnaire (LREB). In addition, a specially adapted for the research Burden questionnaire was used.The analysis revealed good psychometric characteristics of the PTGDI-X Russian version in terms of: internal subscales consistency (Cronbach’s α coefficients varied from 0,73 to 0,86), internal and external construct validity

Recovery and trauma among urban African Americans with serious mental illness.

Traumatic experiences are prevalent among people with serious mental illness and can significantly worsen outcomes. This study aimed to identify an urban cluster of trauma types, compare continuous distress ratings versus categorical experience of trauma for predicting outcomes such as depression and quality of life, and investigate the mediating role of recovery orientation in the impact of trauma exposure on outcomes. Data came from an intervention study on African Americans with serious mental illness living in a large urban area; 212 participants completed baseline self-report measures of past trauma experiences, related distress levels, recovery, depression, and quality of life. Data were assessed using correlations and regressive path modeling. Overall, 56.6% of participants reported experiences with trauma. Analyses suggested an urban cluster of trauma types that was self-reported by over 25% of participants. Distress due to trauma strongly correlated with greater depression as well as reduced quality of life and recovery. Interestingly, the categorical presence of trauma history (yes/no) had no significant relationship with any outcomes. Path analyses revealed that recovery mediated the impact of trauma distress on depression and quality of life, specifically implicating the recovery subfactor of hope. Results suggested that cognitive reframing focused on positive appraisals of overall recovery, and the hope subfactor can have a positive influence on trauma outcomes. The study supported the role of recovery in posttraumatic growth and suggests that hope can be used to help patients process trauma healthily. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Identification of key genes and signalling pathways in clear cell renal cell carcinoma: An integrated bioinformatics approach.

Clear cell Renal Cell Carcinoma (ccRCC) is one of the most prevalent types of kidney cancer. Unravelling the genes responsible for driving cellular changes and the transformation of cells in ccRCC pathogenesis is a complex process. In this study, twelve microarray ccRCC datasets were chosen from the gene expression omnibus (GEO) database and subjected to integrated analysis. Through GEO2R analysis, 179 common differentially expressed genes (DEGs) were identified among the datasets. The common DEGs were subjected to functional enrichment analysis using ToppFun followed by construction of protein-protein interaction network (PPIN) using Cytoscape. Clusters within the DEGs PPIN were identified using the Molecular Complex Detection (MCODE) Cytoscape plugin. To identify the hub genes, the centrality parameters degree, betweenness, and closeness scores were calculated for each DEGs in the PPIN. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) was utilized to validate the relative expression levels of hub genes in the normal and ccRCC tissues. The common DEGs were highly enriched in Hypoxia-inducible factor (HIF) signalling and metabolic reprogramming pathways. VEGFA, CAV1, LOX, CCND1, PLG, EGF, SLC2A1, and ENO2 were identified as hub genes. Among 8 hub genes, only the expression levels of VEGFA, LOX, CCND1, and EGF showed a unique expression pattern exclusively in ccRCC on compared to other type of cancers.

Oral administration of Bacillus coagulans TQ-35 alleviates allergic responses in OVA-sensitive BALB/c mice

Bacillus coagulans has been extensively studied so far, but there has been a lack of research on its usage in allergy. In this study, we designed to assess the effect of different concentrations of B. coagulans on food allergy in a BALB/c mouse model of ovalbumin (OVA)-induced food allergy and its effect on gut microbes. The assessment of symptoms, specific immunoglobulin E (IgE), T-cell differentiation, and related gene expression levels in sensitized mice by assay indicated that high doses of oral B. coagulans could alleviate allergic symptoms. Treatment with B. coagulans, in the high-dose group, significantly reduced IgE and IgG1 levels and modulated the balance of T helper type 1 cell (Th1) and Th2 and the expression of relevant genes in the spleen. 16S rRNA analysis showed that probiotics improved the structure of the microbiota, in particular by boosting the percentage of Clostridia, Bacteroides vulgatus and Enterococcus faecium, and by increasing the abundance of microbial species, thereby modulating the immune system. Therefore, this study can provide insights into the practical application of B. coagulans doses to alleviate OVA allergy.

TURKISH-RUSSIAN RELATIONS FROM THE COLD WAR TO 2002 AS THE BEGINNING OF CURRENT RELATIONS

In this study, Turkish-Russian relations in the Cold War period and the Post-Cold War time till 2002 are discussed. Since 2002 is accepted as the beginning of current relations and a breakthrough year in relations, a separate analysis is required for the next period. It is seen that the relations between Türkiye and Russia were tense between the years 1945-1965, and then went through a soft period until the end of the Cold War period. It is clearly understood that Turkish-Russian relations gained a new dimension after the collapse of the USSR. Economic-commercial relations constituted the most important area of this period, in which competition also predominated. In the first part of this study, the historical development of Turkish-Soviet relations in the Cold War period is tried to be discussed. Economic and commercial relations assumed the locomotive role in the cooperation between the two countries, giving a different quality to the political, military and security issues and relations with third countries. In the second part, the new era for the affairs is analyzed and, in this regard, it should be noted that the leaders of the two countries have made great efforts since the beginning of the 1990s. In these years, many strategic projects were signed and implemented in the context of bilateral relations. It is obvious that the relations between the two countries reached a strategic dimension in areas such as economic-commercial and energy. It is also analyzed that the momentum gained in Turkish-Russian relations and the good level of relations also served regional stability and common interests. Finally, it may be assumed that the years examined by this paper is also a period that helped to create strong relations between two countries in the 21st century.

Quality of life in ICU survivors and their relatives with post-intensive care syndrome: A systematic review.

Post-intensive care syndrome (PICS) is characterized by all three adverse survivorship dimensions: physical function, cognitive function and mental health status. This review aimed to describe the quality of life (QoL) of Intensive Care Unit (ICU) survivors with PICS after discharge and of their relatives with Family Post-intensive care syndrome (PICS-F) and to report anxiety, depression and Post-Traumatic Stress Disorders (PTSD) in studies investigating PICS. A systematic review was carried out. We searched PubMed, Scopus, Web of Science and the Cumulative Index to Nursing and Allied Health Literature. This review was registered in the PROSPERO database (CRD42022382123). We included 19 studies of PICS and PICS-F in this systematic review. Fourteen observational studies report the effects of PICS on depression, 12 studies on anxiety and nine on post-traumatic stress disorder and 10 on QoL. Mobility, personal care, usual activities and pain/discomfort in QoL were the domains most affected by PICS. A significant association was demonstrated between a high level of ICU survivors' anxiety and high levels of ICU relatives' burden. Strain-related symptoms and sleep disorders were problems encountered by ICU relatives with PICS-F. PICS and PICS-F were widespread experiences among ICU survivors and their ICU relatives, respectively. The results of this review showed the adverse effects of PICS and PICS-F on QoL. PICS and PICS-F strongly impact the rehabilitation process and are measured in terms of health costs, financial stress and potentially preventable readmission.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Rasch model assessment of algebraic word problem among year 8 Malaysian students

&lt;p&gt;Word problems continue to be a challenge for students today. All students must meet the prerequisites for problem solving and reasoning skills, which are important components of the critical thinking component of 21st century skills. This study is being conducted to assess students’ strategies for solving word problems with numbers, consecutives, and ages. The Rasch model is used to analyze the item difficulty level of word problems and students’ strategies for solving ten-word problems at various levels of item difficulty in a similar trait. Then, Pearson correlation analysis is used to investigate the item difficulty level in relation to linguistic, algebraic, and arithmetic factors of word problems before evaluating students’ performance on solving these word problems using various strategies. Rasch model found these algebraic word-problem questions are slightly harder for year 8 Malaysian students in relative to an international standard. Meanwhile, the item difficulty of word problems is driven by linguistic and algebra factors where students can score accurately if the word problems contained explicit information. However, the students encountered difficulties while losing their solution strategy when the questions contained implicit data that demanded critical thinking ability.&lt;/p&gt;

Abstract 5682: Micro RNA level changes in prostate cancer cells treated with MDMX and MDM2 inhibitors

Abstract INTRODUCTION: Prostate Cancer (PCa) is the most common non-cutaneous cancer and the second leading cause of cancer death among men in the United States. Most of the PCa cases are diagnosed in men between the ages of 65-74. Due to the recent push for frequent prostate screenings, these cancers are being detected early and treated much faster, leading to a 5-year survival of a localized or regional PCa to &amp;gt;99%. However, the 5-year survival of PCa with distant metastasis is significantly reduced to 32%, especially with involvement of osteoblastic bone lesions, lung lesions, and brain lesions. Therefore, there is a clinical need to identify prognostic markers and new targets for developing therapies and effectively treating advanced PCa. Previous studies have shown that levels of MDMX and MDM2, oncogenic inhibitors of p53 tumor suppressor protein, are significantly elevated in PCa cells. Inhibition of MDM2 and MDMX using specific inhibitors has been shown to elevate the levels of p21, p27, and p53 in LNCaP (Lymph Node Carcinoma of the Prostate) cells leading to cell death. Recent studies have demonstrated that micro RNAs (miRNAs) play an important role in supporting the tumor suppressor function of p53 through regulating the balance between p53 and MDM2. In this regard, several miRNAs were found to be significantly altered to modulate the level and intracellular mechanisms of p53 and MDM2 in various cancers. OBJECTIVES: To determine the relative levels of miRNA31, miRNA-34a and miRNA-128 in LNCaP cells that were treated with NSC-207895 (MDMX inhibitor), SJ-172550 (MDMX inhibitor), and RG-7388 (MDM2 inhibitor). METHODS: LNCaP cells were treated with NSC-207895 (20 uM), SJ-172550 (20 uM) or RG-7388 (2 uM) for 24 hrs. After completing the treatments, the miRNAs were extracted from the LNCaP cells using the miRNeasy Tissue/Cells Advanced Kit from Qiagen. We analyzed the levels of miRNA-31, miRNA-34a, and miRNA-128 in the treated samples using qRT-PCR analysis method and compared the levels to the control. During the qRT-PCR analysis the cDNA was amplified using Meridian Biosciences qPCR Master Mix and specific primers for miRNAs from Origene were used according to the manufacturer's protocol. RESULTS: Our experimental results indicate that inhibition of MDMX using NSC-207895 and SJ-172550 can elevate the levels of p21, p27, and p53 leading to cell death. Determination of cell death markers in the past revealed induction of necroptosis following drug treatments. Our current results indicate measurable changes in the levels of miRNA-31 and miRNA-34a following inhibition of MDMX using SJ-172550. We are in the process of determining the possible link between the changes in the levels of miRNAs and cell death. ACKNOWLEDGEMENT: This research was supported by the Royal Dames of Cancer Research, Ft. Lauderdale, Florida. Citation Format: Rojin Fatirkhorani, Ahmed Saleh Alsarrani, Shyam Sundar Jaganathan, Umamaheswari Natarajan, Appu Rathinavelu. Micro RNA level changes in prostate cancer cells treated with MDMX and MDM2 inhibitors [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 5682.

Abstract 1735: DNA demethylating agents have cell type-specific effects on viability and BRCA2 alternative splicing

Abstract Introduction: BRCA2 is one of two principal tumor suppressors responsible for hereditary breast/ovarian cancer syndrome (HBOC). Patients with strong family histories of breast/ovarian cancer may carry BRCA2 DNA sequence variants of unknown clinical significance (VUSs). To evaluate which of these VUSs may contribute to cancer risk by altering splicing patterns, naturally occurring BRCA2 mRNA alternate splicing events have been extensively characterized, but it is not yet known which if any of these alternate splicing events plays a role in BRCA2 function. One variant lacking exon 3 (∆3), which maintains the full length translational reading frame, lacks sequence encoding EMSY and PALB binding domains as well as transactivation function. Previous work has shown that, while some VUSs associated with increased levels of ∆3 in lymphoblastoid cell lines are not pathogenic, germline deletions that eliminate BRCA2 exon 3 are associated with increased breast cancer risk. It is therefore of interest to characterize the factors that influence the frequency of naturally occurring BRCA2 exon 3-skipping, including cell types and therapies. DNA demethylating agents are used as cancer therapy to promote expression of tumor suppressor genes that may be epigenetically silenced in tumors. However, DNA methylation has been shown to be more frequent in exonic than intronic regions of protein-coding genes, suggesting that methylation may play a role in recruiting spliceosomal components to nascent pre-mRNA. It is therefore of interest to determine whether genomic demethylation affects alternative splicing patterns. Here, we explore whether BRCA2 exon 3 alternative splicing patterns are altered by demethylating agents. Methods: To determine whether DNA demethylating agents can alter the levels of ∆3, MCF7 and/or the non-cancer breast cell line MCF 10A was treated with 5-aza 2’-deoxycytidine (5-AzadC) or 5-Azacytidine (5-AzaC), and isoform-specific RT-PCR was used to compare relative levels of splice junctions containing or skipping exon 3. Results and Conclusions: 1) While the IC50 for both 5-AzadC and 5-AzaC in MCF 10A was similar (less than 1 μM), MCF7 showed considerably more resistance to 5-AzaC than 5-AzadC (IC50 of ≥ 5 μM vs ≤ 0.2 μM). 2) 5-AzaC treatment reduces the proportion of MCF 10A cultures in apoptosis but does not increase the proportion of viable cells, indicating it causes cell death by some other means. 3) While both 5-AzaC and 5-AzadC reduce relative levels of ∆3 in MCF7, 5-azadC does not reduce relative levels of ∆3 in MCF 10A, suggesting there may be a cell type-specific splicing response to genomic demethylation therapies. Citation Format: Jordan Werner, Hiba Siddiqui, Samiha Syed, Osman Khan, Servando Casillas Garabito, James D. Fackenthal. DNA demethylating agents have cell type-specific effects on viability and BRCA2 alternative splicing [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 1735.

Effect of rifampicin on TLR4-signaling pathways in the nucleus accumbens of the rat brain during abstinence of long-term alcohol treatment.

The treatment with the antibiotic rifampicin (Rif) led to a decrease in the frequency of neurodegenerative pathologies. There are suggestions that the mechanism of action of Rif may be mediated by its effect on toll-like receptor (TLR)4-dependent pathways. We evaluated the expression status of TLR4-dependent genes during abstinence from long-term alcohol treatments in the nucleus accumbens (NAc) of the rat brain, and also studied the effects of Rif to correct these changes. The long-term alcohol treatment was performed by intragastric delivery of ethanol solution. At the end of alcohol treatment intraperitoneal injections of Rif (100mg/kg) or saline were made. Extraction of the brain structures was performed on the 10th day of abstinence from alcohol. We used the SYBR Green qPCR method to quantitatively analyze the relative expression levels of the studied genes. The long-term alcohol treatment promotes an increase in the level of TLR4 mRNA and mRNA of its endogenous ligand high-mobility group protein B1 during abstinence drop alcohol in NAc of rats. The use of Rif in our study led to a decrease in the increased expression of high-mobility group protein B1, Tlr4, and proinflammatory cytokine genes (Il1β, Il6) in the NAc of the rat brain during abstinence of long-term alcohol treatment. In addition, Rif administration increased the decreased mRNA levels of anti-inflammatory cytokines (Il10, Il11). The data obtained indicate the ability of Rif to correct the mechanisms of the TLR4 system genes in the NAc of the rat brain during alcohol abstinence.

Establishment of a hydrodynamic delivery system in ducks.

Chronic hepatitis B virus (HBV) poses a significant global health challenge as it can lead to acute or chronic liver disease and hepatocellular carcinoma (HCC). To establish a safety experimental model, a homolog of HBV-duck HBV (DHBV) is often used for HBV research. Hydrodynamic-based gene delivery (HGD) is an efficient method to introduce exogenous genes into the liver, making it suitable for basic research. In this study, a duck HGD system was first constructed by injecting the reporter plasmid pLIVE-SEAP via the ankle vein. The highest expression of SEAP occurred when ducks were injected with 5µg/mL plasmid pLIVE-SEAP in 10% bodyweight volume of physiological saline for 6s. To verify the distribution and expression of exogenous genes in multiple tissues, the relative level of foreign gene DNA and β-galactosidase staining of LacZ were evaluated, which showed the plasmids and their productswere located mainly in the liver. Additionally, β-galactosidase staining and fluorescence imaging indicated the delivered exogenous genes could be expressed in a short time. Further, the application of the duck HGD model on DHBV treatment was investigated by transferring representative anti-HBV genes IFNα and IFNγ into DHBV-infected ducks. Delivery of plasmids expressing IFNα and IFNγ inhibited DHBV infection and we established a novel efficient HGD method in ducks, which could be useful for drug screening of new genes, mRNAs and proteins for anti-HBV treatment.

Physical and socioeconomic driving forces of land use and land cover changes: the case of Hawassa City, Ethiopia

Background and objectives: Hawassa served as the country’s southern region’s capital from 1990 to 2019 and is currently experiencing rapid urbanization. Urban planners use the physical and socioeconomic driving elements of Land Use Land Cover Change (LULCC) to identify the variables influencing the trend of urbanization and then make appropriate plans.Methods: The study primarily employed advanced technologies like Geographic Information Systems and Remote Sensing to collect and analyze accurate and reliable information. The data were collected through questionnaires, interviews, and key interviews. Finally, the data were analyzed in different ways, using figures and tables, for example. Descriptive and econometric models were also used to analyze the data and probit regression models were used to investigate the impact of urban expansion on the livelihood of displaced farmers in the surrounding area.Findings: Multivariate analysis of variance indicated that the effect of urban expansion on the combined dependent variables, namely, on land use, socioeconomic activities, culture, and environmental change, is statistically significant F(8, 616) =12.704, p = 0.000, Wilk’s Lambda (λ) = .737, partial eta squared(partial η2) = 0.142, observed power = 1.000. Comparatively, the area covered by farmland, built-up areas, and bushland increased from 19.46% to 26.51%, 11.97% to 18.71%, and 3.07% to 4.51%, respectively. The mean score for the level of social relationship and values after land expropriation was 1.7 moderate, with a standard deviation of 0.852 in comparison with the mean score for the level of social relationship and values before land expropriation, which was 3.21 high, with a standard deviation of 0.79. This shows that the land expropriation program negatively affected farmers’ social relationships and values; their social relations levels were high before displacement and between low and moderate after displacement.Conclusion: Policy and strategy gaps in the urban expansion program and this policy issue have hindered the growth of the city and resulted in a serious issue regarding good governance in the area.

Daily dynamics of feeling loved by parents and their prospective implications for adolescent flourishing.

Feeling loved by one's caregiver is essential for individual flourishing (i.e., high levels of psychological well-being in multiple dimensions). Although similar constructs are found to benefit adolescent well-being, research that directly tests parental love as a feeling from the recipient's perspective is rare. Historically, parental love has been measured using single-assessment methods and assumed to be a stable, trait-like characteristic; yet, like any feeling, it may fluctuate in meaningful ways on a day-to-day basis-the implications of which are unknown. Using a sample of 150 adolescents (59.3% female; ages 14-16), this study estimated level (person's mean level across days) and instability (fluctuations across days) of feeling loved by a caregiver across 21 days for each adolescent, and then examined their prospective effects on adolescent flourishing 1 year later. After controlling for demographics (adolescent age, gender, family income, and parent's sex) and variable baseline levels, feeling more loved by one's caregiver in daily life significantly predicted higher levels of flourishing in two global measures 1 year later. Moreover, level and instability of feeling loved by one's caregiver played different roles for different dimensions of flourishing: higher levels significantly predicted higher levels of autonomy, purpose in life, and personal growth, whereas higher instability significantly predicted lower levels of positive relations with others and environmental mastery. Findings emphasized the importance of considering daily dynamics of feeling loved by one's caregiver and demonstrated that level (of feeling loved) is particularly important for intrapersonal aspects while instability is particularly important for interpersonal aspects of flourishing. RESEARCH HIGHLIGHTS: Adolescents feeling more loved by their caregiver in daily life had higher levels of overall flourishing 1 year later. Level (of feeling loved) is particularly important for intrapersonal aspects of adolescent flourishing, including autonomy, purpose in life, and personal growth. Stability (of feeling loved) is particularly important for interpersonal aspects of adolescent flourishing, including positive relations with others and environmental mastery.

High-resolution wave modeling of the Southwestern Nigerian coastal shelf: Implications on geomorphic contrasts between barrier-lagoon and mud coasts

This study characterizes the spatio-temporal wave variability along Southwestern Nigerian coastal and shelf areas in the Gulf of Guinea. This is to provide further insight into the hydrodynamic factors that influence geomorphologic changes on the low-lying coast. Reanalysis wind-field datasets are employed to generate hourly wind forcing for an unstructured WAVEWATCH III model to simulate some bulk wave parameters. The model is validated against data from offshore buoys and satellite altimetry at selected locations near the coast. Results show that the waves have an annual average of significant wave height (Hs), peak period (Tp), and wind speed (u) of ∼0.5 m, 4.1 s, and 3.9 m/s, respectively. They exhibit seasonal spatial variability that is highest in the peak rainy season from July to September (Av. Hs: 0.56–0.79 m; Av. Tp: 4.68–5.18 s; Av. u: 4.30–5.22 m/s) and lowest in the early dry season from November to January (Av. Hs: 0.26–0.34 m; Av. Tp: 3.37–3.80 s; Av. u: 3.25–3.50 m/s). Also, the monthly averaged wave power varies from 0.2 to 2.8 kW/m annually. However, a maximum Hs of 2.2 m that generated power of 9.4 kW/m for 11.1 s was recorded during the peak of the rainy season in August. Overall, waves with relatively low intensity, which can be classified as smooth to moderate, propagate from the southwest direction and decrease towards the coast. The higher Hs and Tp recorded during the peak of rainy and end of dry seasons are attributed to the influence of far-away swells. A comparative assessment indicates that the Barrier-Lagoon coast is highly controlled by waves, while the Mahin mud coast, which witnesses frequent flooding events that degrade its shoreline, has little wave influence. Thus, local subsidence that increases the relative sea level is suggested to be taking place at sections of the muddy coast. This information is crucial for the sustainable engineering design and management of low-lying coasts.

Role of dopamine in regulating microglia inflammatory responses through TLR4-NFb pathway

Parkinsons disease (PD) is a prevalent neurodegenerative disorder that affects a significant portion of the population. One of its distinguishing features is the gradual loss of dopaminergic cells in a specific region of the brain known as the substantia nigra. In recent years, researchers have uncovered that neuroinflammation facilitates the developmental process of PD. Specifically, studies have shown that the activation of microglia, the brains immune cells, is closely linked to the levels of dopamine secreted by neurons. However, the influence of dopamine on activated microglia in PD has not been fully explored. In this study, we aimed to explore the impact of dopamine on activated microglia. To establish an activated microglia model, we used BV-2 cell lines and treated them with lipopolysaccharide (LPS) at a concentration of 200 ng/ml. Two separate groups were then exposed to dopamine at concentrations of 2 M and 10 M, respectively, to simulate dopamine treatment in the brain. To assess the effects of dopamine, we performed real-time PCR to measure the relative mRNA levels of pro- and anti-inflammatory cytokines, conducted immunofluorescent staining to observe and analyze the cell morphology, carried out a phagocytosis assay to assess the cells phagocytic ability, and conducted western blotting to identify the specific pathway through which dopamine affects microglia activation. Our findings revealed that dopamine can modulate the activation state of microglia and reduce the cells inflammatory responses via the TLR4-NFB pathway. This suggests that dopamine has the potential to alleviate neuroinflammation in PD, opening up new avenues for future treatments and therapies.

Evidence of Middle Holocene landslide-generated tsunamis recorded in lake sediments from Saqqaq, West Greenland

Abstract. The Vaigat strait (Sullorsuaq) in West Greenland is well known for its susceptibility to landslides and historical landslide-generated tsunamis. Recent mapping of the seabed in the Vaigat strait has revealed several prehistoric giga-scale (volumes of 109 m3) tsunamigenic landslides. However, the timing of these giga-scale tsunamis is largely unconstrained, but they are assumed to have occurred after the last deglaciation. Here, we report on lake sediment core records from four coastal lakes located between 19 and 91 m above sea level (a.s.l.) on the Saqqaq foreland at the eastern end of the Vaigat strait. We use a multiproxy approach including X-ray fluorescence (XRF) and magnetic susceptibility core scanning along with a screening for marine diatoms to identify at least two tsunami deposits in two of the four sediment cores. Radiocarbon dating of aquatic macrofossils and bulk samples suggest that the tsunami events occurred at ca. 7.6 and 7.3 ka cal BP. Using a previously published relative sea level curve from Vaskebugt, Arveprinsen Ejland (Alluttoq), located 40 km southeast of Saqqaq, we infer wave runup heights of ca. 41–66 and 45–70 m, respectively, for the two tsunami events. These runup heights from prehistoric tsunamis are 1 to 2 orders of magnitude higher than the historic landslide-tsunami runup heights at Saqqaq which only reached an elevation of ca. 3 m in November 2000. While we found deposits from two tsunami events in the lake sediments, landforms from at least nine giga-scale landslides are present on the seafloor of Vaigat. We infer that these deposits probably represent the two most recent tsunamis identified in the Vaigat strait and that the older tsunamis must have happened between the last deglaciation and the oldest sediment in the lakes, i.e., between ca. 10.0 and 8.5 ka cal BP.

Abstract B053: Lipid metabolism and lipidomics of ovarian clear cell carcinoma: a comprehensive analysis

Abstract Ovarian clear cell carcinoma (OCCC) is a chemoresistant subtype of ovarian cancer accounting for 5-12% of all epithelial ovarian cancer cases. Lipid metabolism has been reported to be involved in platinum resistance and resistance to ferroptosis induction in various cancer types. However, the metabolomic and lipidomic landscape of OCCC has not been characterized. To explore the metabolic processes driving the aggressive nature of advanced OCCC, we carried out global metabolomic and lipidomic profiling on 64 early and advanced ovarian cancer samples, including tumors with corresponding metastases. Snap frozen tissue from 29 OCCC, 22 high-grade serous carcinoma (HGSOC), and 13 endometrioid ovarian carcinoma (EnOC) cases were included. Hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry was performed to quantify the relative steady-state level of 318 unique metabolites. Principal component analysis (PCA) showed a distinct separation between OCCC and HGSOC/EnOC samples, mainly driven by short and medium chain acylcarnitine and hydroxylated acylcarnitine esters that were significantly more abundant in OCCC. Acylcarnitines are intermediaries of fatty acid beta-oxidation (FAO), and their enrichment in OCCC patient samples might indicate a difference in fatty acid utilization and lipid metabolism compared to OCCC and HGSOC/EnOC. FAO has been linked to redox homeostasis in cancer cells, acting as a protective factor against lipid peroxidation through selective depletion of certain lipid species. To explore whether deeper lipidomic changes in OCCC accompany increased acylcarnitine production, we performed global complex lipid detection on 7 OCCCs and 3 HGSOC tissue samples using reverse phase liquid chromatography and mass spectrometry. Six-hundred and fifty-seven unique lipid species were successfully identified. A comparison of lipid class abundances between OCCC and HGSOC uncovered increased levels of medium chain acylcarnitines in OCCC, corroborating the HILIC findings. Moreover, the levels of cholesterol esters and ceramides with polyunsaturated fatty acid chains were also more abundant in OCCC. Conversely, choline plasmalogens, a lipid class known to induce lipid peroxidation and ferroptosis cell death exhibited significantly lower abundance in OCCC. Additionally, saturated ethanolamine plasmalogens and ceramides containing saturated fatty acids were decreased in OCCC. In summary, our study reports significant differences in the lipid metabolism of OCCC compared to other major ovarian cancer subtypes. The observed decrease in peroxidation-prone lipid species might indicate the involvement of FAO in OCCC’s redox homeostasis and highlights FAO as a potential novel mechanism of platinum resistance in OCCC. Ongoing studies, presented at the meeting include the metabolomic and lipidomic profiling of a large panel of ovarian cancer cell lines to identify those that best model patient sample metabolism. These models will subsequently be used for in vitro and in vivo studies to evaluate FAO as a potential therapeutic target in OCCC. Citation Format: Agnes J. Bilecz, Roya AminiTabrizi, Hardik Shah, Ernst Lengyel. Lipid metabolism and lipidomics of ovarian clear cell carcinoma: a comprehensive analysis [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B053.

Rising sea levels and the increase of shoreline wave energy at American Samoa

American Samoa is experiencing rapid relative sea level rise due to increases in global sea level and significant post-2009 earthquake land subsidence, endangering homes and critical infrastructure. Wave and water-level observations collected over a fringing reef at Faga‘itua Bay, American Samoa, in 2017 reveal depth-limited shoreline sea-swell wave heights over the range of conditions sampled. Using field data to calibrate a one-dimensional, phase-resolving nonhydrostatic wave model (SWASH), we examine the influence of water level on wave heights over the reef for a range of current and future sea levels. Assuming a fixed reef bathymetry, model results predict rising sea levels will escalate nearshore extreme water levels that are dominated by an increase in nearshore sea-swell wave heights. Model results provide insight into how and at what reef depths rising sea levels reduce reef capacity to dissipate wave energy, compounding shoreline threats. This study aims to bring increased attention to the immediate threats to American Samoa’s way of life, and to demonstrate the utility of SWASH for extrapolating wave transformation to future sea level.

Docosahexaenoic Acid Modulates Nonalcoholic Fatty Liver Disease by Suppressing Endocannabinoid System.

Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system. In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid β-oxidation related protein expression levels. This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.