Trends In Levels Research Articles

Groundwater Dynamics in the Middle Brahmaputra River Basin: A Case Study of Shallow Aquifers in Inner Guwahati City, Assam, India

This study investigated the hydrogeological characteristics and groundwater dynamics in the shallow aquifer zones of inner Guwahati city, Assam, India. Sixteen dug wells spread across the city, specifically used for domestic purposes, were selected for this study. Additionally, ten wells were selected for trend analysis. The borehole lithology reveals predominant compositions of clay, sand, and granules, with thin clay cappings indicating significant groundwater potential. Depth-to-water level analysis revealed varying water levels across the study area, with shallow levels in the northern and western regions and gradual deepening toward the eastern and southern parts. The groundwater flow directions show nonuniform patterns and reflect the influence of topography and domestic pumping in urban residential zones. The general groundwater flow direction is toward the Brahmaputra River. Trends in groundwater level, assessed using the Mann–Kendall test and Sen’s slope, suggest both falling and rising trends across different locations, indicating complex groundwater dynamics influenced by factors such as recharge, extraction, and topography. However, the long-term rainfall data indicate no significant trend over the studied period, suggesting limited natural influence on groundwater level trends. These findings may contribute to a comprehensive understanding of groundwater dynamics in the study area and are essential for sustainable water resource management and mitigation of groundwater depletion risks.

A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

Impact of Hypoxia and the Levels of Transcription Factor HIF-1α and JMJD1A on Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cell Lines.

This study aimed to assess the impact of hypoxia on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC), focusing on the involvement of transcription factors hypoxia inducible factor 1 (HIF-1α) and Jumonji Domain-Containing Protein 1A (JMJD1A). FaDu and Cal33 cell lines were subjected to hypoxic and normoxic conditions. Cell proliferation was quantified electronically, while PCR and western blot analyses were used to measure mRNA and protein levels of HIF-1α, JMJD1A, and EMT markers. EMT was further characterized through immunofluorescence, migration, and invasion assays. Hypoxic conditions significantly reduced cell proliferation after 48 hours in both cell lines. HIF-1α mRNA levels increased initially during short-term hypoxia but declined thereafter, while JMJD1A mRNA levels showed a sustained increase with prolonged hypoxia. Western blot analysis revealed contrasting trends in protein levels. EMT marker expression varied markedly over time at both the mRNA and protein levels, suggesting EMT induction in hypoxia within 24 hours. Immunofluorescence, migration, and invasion assays supported these findings. The study provides evidence of hypoxia-induced EMT in HNSCC, although conflicting results suggest a complex interplay among molecular regulators involved in this process.

Three decades of lipid-lowering therapy in type 2 diabetic patients with angiographically proven stable coronary artery disease

Abstract Lipid-lowering therapy (LLT) is key to reducing the burden of macrovascular diabetes complications. Here, we aim to assess long-term trends in LLT and LDL-C levels among patients with type 2 diabetes (T2DM) with angiographically proven coronary artery disease (CAD). We investigated T2DM patients (n=590), who were referred to elective coronary angiography and were diagnosed with CAD in one of three observational cohort studies (OS) spanning 25 years: OS1: 1999-2000 (n=190); OS2: 2005-2008 (n=241); OS3: 2022-2023 (n=159). These studies were conducted at the same cardiology unit of a tertiary care hospital in Central Europe. The proportion of patients receiving statin therapy (C10AA and C10AB) increased significantly from 57.9% in OS1 to 64.3% in OS2 and 78.6% in OS3 (ptrend<0.001). Further, there was an increase in patients receiving high-intensity statin therapy, rising from none in OS1 to 8.5% in OS2 and 73.4% in OS3 (ptrend<0.001). The proportion of patients receiving more than one LLT compound also increased (OS1: 2.1%; OS2: 2.1%; OS3: 35.2%; ptrend<0.001). Use of ezetimibe (C10AX09) increased (OS1: 0.0%; OS2: 1.2%; OS3: 39.0%; ptrend<0.001) and fibrate use (C10AB) decreased (OS1: 5.3%; OS2: 3.3%; OS3: 0.6%; ptrend=0.015). Newly approved compounds (C10AX13 - C10AX16) were prescribed for 3.8% of patients in OS3. Among statin combination therapies, ezetimibe was predominantly used (93.5%). Mean LDL-C levels declined significantly from 123±38 mg/dL (OS1) to 115±39 mg/dL (OS2) and 77±38 mg/dL (OS3; ptrend<0.001). However, only 2.2% of patients in OS1, 2.5% in OS2 and 32.1% in OS3 reached an LDL-C target of <55 mg/dL (ptrend<0.001). This analysis suggests an upward trend in treatment intensity and a substantial improvement in LDL-C levels among T2DM patients with CAD. However, the majority of these patients still does not reach their LDL-C target.

How ambient NO2 impacts the mortality burden of ischemic heart disease in Portugal (2011-2021)?

Abstract Background Air pollution is a major environmental risk to human health, contributing to premature death and disease. Nitrogen dioxide (NO2) is a pollutant of significant public health concern, associated with increased risks of all-cause mortality, particularly in cardiovascular and respiratory deaths. In 2021, NO2 exposure exceeding the World Health Organization Air Quality Guidelines resulted in 69,000 deaths in the European Union. This study aims to estimate the impact of ambient NO2 exposure on ischemic heart disease (IHD) in Portugal, from 2011 to 2021, estimated in years of life lost (YLL). Methods Data on ambient NO2 levels were obtained from the Portuguese Environment Agency’s online database QualAr. Only monitoring stations that reported valid data for at least 75% of the time in a year were considered. The number of IHD mortality cases from 2011 to 2021 was sourced from Statistics Portugal. The burden of IHD attributed to NO2 exposure was estimated in YLL for the Portuguese population aged 25 years and older, categorized by five-years age groups, regions of mainland Portugal and sex, using the population attributable fraction (PAF). Results Between 2011 and 2021, mainland Portugal experienced a declining trend in NO2 mean levels, with occasional fluctuations. Regarding IHD YLL attributed to NO2 exposure, the same trend was followed with an overall decline over the study period. In total, 94,843.75 (95% CI 53,408.35-134,766.17) IHD YLL were attributed to NO2 exposure, with an estimated number of IHD YLLs higher for males than for females. Conclusions These findings underscore the significant impact of air pollution on human health. Despite an overall reduction in YLL across mainland Portugal, persistent health effects emphasize the need to reduce NO2 concentrations, with informed decision-making being crucial to mitigate these impacts and protect public health. Key messages • Ambient NO2 exposure significantly impacts ischemic heart disease mortality in Portugal. • These estimates underscore the necessity of well-informed decision-making to safeguard public health.

Collagen VI and endotrophin: potential extracellular matrix targets to attenuate adverse cardiac remodeling post-infarction

Abstract Background The extracellular matrix (ECM) is a key component of cardiac repair after myocardial infarction (post-MI). After tissue damage following myocardial ischaemia, the ECM becomes enriched in proteases that are known to induce partial enzymatic cleavage and fragmentation of native structural and fibrillar macromolecules such as collagens. While some of the resulting protein fragments (matrikines) may have beneficial effects by mediating an active scar formation, other such as the collagen VI (COL6) proteolytic component "endothrophin" has been related to deleterious evolution and fibrosis, particularly in the presence of cardiovascular risk factors. Purpose We aimed to investigate the collagen profile in the structural fraction of ECM (enriched in fibrillar and structural proteins) of post-MI hearts at late evolution stages after MI. Methods The ECM protein profile was investigated in the ischemic (ISCH) and non-ischemic (NISCH) zones of the post-MI myocardium in pigs. MI was induced by closed-chest balloon occlusion of the LAD for 90 minutes. Studies were performed in normo- and hypercholesterolemic (diet induced) animals. Myocardial tissue was obtained 30d after MI. ECM proteins were selectively extracted, identified by LC/MS-MS and validated by Western Blot. Plasma levels of endothrophin were quantified by ELISA. Myocardial tissue from the same areas was characterized by immunohistochemistry. Results The ECM in the ISCH zone showed a differential signature of 39 proteins (14 upregulated / 25 downregulated) 30 days after MI compared to the NISCH area of the same animals. In the ISCH region, significant changes in collagen referring to COL6A3 and COL6A1 (increase) and COL6A2 and COL6A6 (decrease) were detected. COL6A3 protein content was 1.8fold higher (p=0.01) in the ISCH-ECM. A similar increase was found in normo- and hypercholesterolemic animals. A higher trend in COL6A3 levels was found in the ISCH- vs, the NISCH-zone in the myocardial cellular fraction suggesting that the COL6 ECM-related increase in ISCH is produced at a transcript level. Importantly, the COL6A3 found in the ECM did not contain the protein peptide (C5 domain) corresponding to endotrophin matrikine, suggesting its cleavage and release. Using a specific ELISA, hypercholesterolemic animals showed significantly higher endothrophin plasma levels than normolipemic controls (p=0.003) even in the absence of MI. Conclusion Our results evidence an increase in COL6A3 content in the ECM of the ischemic myocardium at 30 days post-MI. COL6A3 is depleted in a peptide of the C5 domain corresponding to endotrophin, found to be enhanced in hypercholesterolemia. These findings support a role for collagen type VI in adverse cardiac remodeling post-MI.

Spatial Changes of Driving Parameters Affecting Cyclonic Activity over the North Indian Ocean from 1960 to 2020

This study undertakes a thorough analysis of the elements that influence the variability of tropical cyclones (TC) in the North Indian Ocean (NIO) from 1960 to 2020, with a specific focus on the periods before and after the monsoon season. The study utilizes historical satellite data to investigate the factors that impact the formation, strength, and trajectories of cyclones. The primary method for evaluating cyclone strength is by calculating the Accumulated Cyclone Energy (ACE). The study observes a decreasing trend in ACE levels during 1991–2005, which started increasing just after from 2006 to 2020. The Bay of Bengal (BoB) has a more uniform distribution of ACE in comparison to the Arabian Sea (AS), with higher average values and more variability over the Main Development Region (MDR), which is the area where cyclone development occurs most frequently. Cyclones of greater intensity generally occur following the monsoon season. Examination of storm paths reveals that cyclones with greater intensity frequently hit the northeastern and southeastern coastal regions of India. The study emphasizes notable discrepancies in parameters within the MDR, which impact cyclone strength and ACE values throughout various periods.

COVID-19 and University Students' Well-Being: An Ecological and Multidimensional Perspective on Post-Pandemic Effects.

In February 2020, the Italian government started to adopt measures to contain the spread of COVID-19. This emergency had a strong impact on people's lives and daily activities, negatively affecting their well-being. One of the groups of people that suffered the most from the pandemic emergency and the related isolation was university students. Based on these considerations, this article analyzes the effects of COVID-19 on Italian students' well-being during three periods: the first lockdown (March-April 2020), one year later (March-April 2021), and two years after the lockdowns (March-April 2022). Three samples comprising a total of 765 participants (M = 21 years, SD = 2.87) completed an online self-report questionnaire, which included the I COPPE scale (its short form), a tool that measures the perception of present and future well-being, both as an overall evaluation and its six specific domains: interpersonal, community, occupational, physical, psychological, and economic. The results indicated a general trend in the well-being levels of university students from the beginning of the pandemic to 2022. Compared to 2020, in 2021, there was a sharp decline in well-being, whereas in 2022, there was an increase in well-being levels. Practical implications, limitations, and future recommendations arising from the present study are extensively discussed.

The Structure Analysis and mRNA Expression of CaV2 Gene Responding to Hypoxia Stress in Anadara granosa

The blood clam (Anadara granosa) is an economic bivalve that is relatively tolerant to hypoxia, but its molecular mechanism of hypoxia tolerance is unclear. We found that a significant decrease in extracellular Ca2+ concentration and a marked increase in intracellular Ca2+ concentration was observed in the blood clam through the fluorescence probe method, under hypoxic conditions at 0.5 mg/L. Concomitantly, there was a downward trend in the expression level of CaV2 mRNA, whereas NFAT (nuclear factor of activated T cells) expression increased by qRT-PCR. These findings suggest that the elevated intracellular Ca2+ concentration may activate negative transcription factors of NFAT, which subsequently suppresses the transcription of CaV2, leading to its decreased expression. Then, the NFAT RNA interference experiments supported this hypothesis. Sequence analysis and 3D structure prediction revealed conserved and mutated residue sites in blood clam compared to other bivalves. Hypoxia-induced changes in intracellular and extracellular Ca2+ concentrations, activating transcription factor NFAT and suppressing CaV2 expression. This study highlights the key roles of CaV2 and NFAT in hypoxia adaptation, paving the way for further exploration of hypoxia tolerance mechanisms in mollusca.

Protective Effects of Lactobacillus Strains Against Oxidative Stress and Immune Suppression in Mice Receiving Aflatoxin-Contaminated Diet.

Mycotoxins like aflatoxins pose a significant threat to the health of both people and animals because of their deadly effects. This study aimed to investigate the potential of Lactobacillus strains in reducing the toxicity caused by aflatoxins in mice receiving a diet contaminated with aflatoxins. The mice were split up into various treatment groups, including a control group, an aflatoxin-treated group, and groups treated with the aflatoxin-contaminated diet along with Lactobacillus strains. Various parameters, including liver enzymes, blood parameters, malondialdehyde (MDA) levels, morphometric analysis of ileum, and gene expression, were analyzed to assess the effectiveness of the Lactobacillus strains in mitigating aflatoxins toxicity. Results showed that mice in the aflatoxin-treated group had increased MDA levels, indicating oxidative stress. Alternatively, the Lactobacillus cocktail treatment group showed a decreasing trend in MDA levels, suggesting a reduction in lipid peroxidation. The morphometric analysis of ileum tissue demonstrated that the Lactobacillus-treated group exhibited improved structural integrity compared to the aflatoxin-treated group. Additionally, gene expression analysis revealed that the Lactobacillus treatment attenuated the downregulation of SOD gene expression and mitigated the upregulation of iNOS gene expression induced by aflatoxins. These findings suggest that Lactobacillus strains have the potential to reduce aflatoxin-induced toxicity by alleviating oxidative stress, preserving intestinal tissue integrity, and modulating gene expression associated with antioxidant defense and inflammation. This study provides evidence for the beneficial effects of Lactobacillus strains in reducing aflatoxin toxicity in mice. The findings obtained may contribute to the development of preventive or therapeutic strategies against mycotoxin-induced toxicity.

HSP-UNet: An Accuracy and Efficient Segmentation Method for Carbon Traces of Surface Discharge in the Oil-Immersed Transformer

Restricted by a metal-enclosed structure, the internal defects of large transformers are difficult to visually detect. In this paper, a micro-robot is used to visually inspect the interior of a transformer. For the micro-robot to successfully detect the discharge level and insulation degradation trend in the transformer, it is essential to segment the carbon trace accurately and rapidly from the complex background. However, the complex edge features and significant size differences of carbon traces pose a serious challenge for accurate segmentation. To this end, we propose the Hadamard production-Spatial coordinate attention-PixelShuffle UNet (HSP-UNet), an innovative architecture specifically designed for carbon trace segmentation. To address the pixel over-concentration and weak contrast of carbon trace image, the Adaptive Histogram Equalization (AHE) algorithm is used for image enhancement. To realize the effective fusion of carbon trace features with different scales and reduce model complexity, the novel grouped Hadamard Product Attention (HPA) module is designed to replace the original convolution module of the UNet. Meanwhile, to improve the activation intensity and segmentation completeness of carbon traces, the Spatial Coordinate Attention (SCA) mechanism is designed to replace the original jump connection. Furthermore, the PixelShuffle up-sampling module is used to improve the parsing ability of complex boundaries. Compared with UNet, UNet++, UNeXt, MALUNet, and EGE-UNet, HSP-UNet outperformed all the state-of-the-art methods on both carbon trace datasets. For dendritic carbon traces, HSP-UNet improved the Mean Intersection over Union (MIoU), Pixel Accuracy (PA), and Class Pixel Accuracy (CPA) of the benchmark UNet by 2.13, 1.24, and 4.68 percentage points, respectively. For clustered carbon traces, HSP-UNet improved MIoU, PA, and CPA by 0.98, 0.65, and 0.83 percentage points, respectively. At the same time, the validation results showed that the HSP-UNet has a good model lightweighting advantage, with the number of parameters and GFLOPs of 0.061 M and 0.066, respectively. This study could contribute to the accurate segmentation of discharge carbon traces and the assessment of the insulation condition of the oil-immersed transformer.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

7269 Interim Analysis of Gonadotropin-Releasing Hormone Agonist (GnRHa) Treatment in Children with Central Precocious Puberty: Focus on FMV Urinary LH Levels and Clinical Outcomes

Abstract Disclosure: X. Luo: Advisory Board Member; Self; Takeda. L. Hou: Advisory Board Member; Self; Takeda. Y. Li: Advisory Board Member; Self; Takeda. Y. Sun: Advisory Board Member; Self; Takeda. X.K. Jin: Employee; Self; Takeda. Background: Central precocious puberty (CPP) refers to early activation of the hypothalamic–pituitary–gonadal (HPG) axis in children. There is an urgent need to understand the treatment pattern and clinical outcomes among children suffering from CPP. Studies have reported that first morning voided (FMV) urinary Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) have substantial association with CPP tested in GnRH stimulation test and can be useful in diagnosis and management of CPP in children. Gonadotropin-releasing hormone agonists (GnRHa) such as Leuprolide acetate (LA) are the recommended treatment for children suffering from CPP. The current study aimed to provide the information on level of LH and FSH in FMV urine when CPP diagnosis at baseline and the present results may also revealed trend of FMV-LH and FMV-FSH change during LA intervention in children with CPP. Here we present interim results from this study. Methods: This is an open-label, multicentre, single arm, prospective study that enrolled 31 subjects with CPP. Individuals were administered LA depot 11.25 mg, subcutaneously every 12 weeks. The study comprises a screening period; a 6-month treatment period: 24 weeks; and a post-treatment follow-up period: 12 weeks. The FMV urinary LH and FSH were diagnosed by Clopper-Pearson method with a 95% confidence interval. Results: Due to the data collection time point for the interim analysis, only 8 female subjects reached the 12-week visit time point and had a 12-week visit for FMV urinary Gn testing. Therefore, for this interim analysis, only FMV Gn decline at week 12 of the 8 subjects who had a 12-week visit will be presented. At baseline, the mean value of FMV urinary LH and FSH is 0.58 IU/L and 2.27 IU/L respectively. The FMV Gn urinary LH was demonstrated a decrease in 87.5% (95% CI: 47.35,99.68) of the children after LA intervention. Additionally, urinary FSH value of FMV urinary Gn was found to decrease in 75.00% of the children (95% CI: 34.91,96.81) compared to baseline FSH value. Conclusion: The present study reveals a decreasing trend in FMV Gn urinary LH and FSH levels in CPP children treated with LA during interim analysis. LA was shown to be safe and effective in ameliorating the level of LH and FSH in children suffering from CPP. From the study, it can be concluded that urinary LH and FSH may act as a potential biomarker for diagnosis and management of CPP. Presentation: 6/3/2024

8686 scRNA-seq of pituitary from letrozole-induced PCOS mouse model reveals abnormal prolactin secretion

Abstract Disclosure: G. De Robles: None. N. Ujagar: None. Z. Del Mundo: None. D. Nicholas: None. Polycystic ovary syndrome (PCOS) has a complex pathophysiology and is the most common endocrine disorder among reproductive-aged women. Ovarian hormonal dynamics are regulated via the secretion of the gonadotropin-releasing hormone (GnRH), which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. High serum levels of LH in PCOS patients indicate an increase in GnRH levels, but the mechanisms within the anterior pituitary at a cellular level are unclear. We performed single-cell mRNA sequencing (scRNA-seq) on the pituitaries of the letrozole-induced (LET) mouse model of PCOS to profile the functional genomics of endocrine cell populations relative to serum hormone levels. The population percentage of lactotropes significantly decreased; in contrast, two gonadotrope populations significantly increased in the LET mice compared to the placebo-treated mice. Consistent with these changes, an increasing trend of serum LH levels and a decreasing trend of serum prolactin (PRL) levels were observed in the LET mice, while no change occurred in serum growth hormone levels. A gene set enrichment analysis (GSEA) on the differentially expressed genes (DEGs) from the lactotropes revealed an association with negative regulation of protein kinase activity. These DEGs included Hspb1, Park7, Pcp4, and Ppia, which all share the function of mediating stress-induced apoptosis. A GSEA on the DEGs between the two gonadotrope clusters in the LET mice also confirmed a variation in biological pathways linked to ribosomal subunits, transcription regulation, and the regulation of steroid metabolic processes. Based on the scRNA-seq results of the anterior pituitaries of LET mice, alterations in the proportions of hormone-secreting cells may be a response to hyperandrogenism, in which functionally diverse gonadotropes could contribute to heterogeneity in reproductive phenotypes. Changes in the lactotrope population and PRL serum levels also support further research on the lactation hormone and its role in PCOS. PRL is involved in metabolic homeostasis and reproduction, and understanding its dysregulations may provide additional insight into the pathophysiology of PCOS. Presentation: 6/3/2024

6680 GLP-1 Agonists in Type 1 Diabetes - Indications and Use

Abstract Disclosure: P. Panjawatanan: None. N. Radovanovic: None. R.J. Comi: None. Introduction: Insulin therapy is the mainstream treatment in patients with Type 1 diabetes. The use of insulin, though mimicking normal physiology, is associated with weight gain. Glucagon-like peptide 1 (GLP-1) agonists are a class of antidiabetic medication that lowers blood sugar levels and helps promote weight loss. We propose that GLP-1 agonists can reverse the trend of weight gain and help lower hemoglobin A1C (A1C) levels in patients with Type 1 diabetes who were gaining weight. Method: A retrospective chart review was performed at a single institution’s endocrine practice over five years. Patients with Type 1 diabetes with concomitant GLP-1 agonists used for at least one year were included. Observed outcomes were the change in A1C, weight, and basal insulin use compared at baseline, 6 months, and 12 months using mixed models repeated measures. The result was reported as estimated means (95%CI). Statistical significance was determined by a p-value less than 0.05. Results: There were 49 patients included in the study. The mean age was 44.7 years old. There were 32 females (65.3%) and 17 males (34.7%). The mean duration of diabetes was 24.6 years. Thirty-five patients (71.4%) used insulin pumps, and fourteen (28.6%) were on multiple daily injections. Overall, patients had been gaining an average of 2.0 kg per year. After the treatment with GLP-1 agonists, weight was significantly reduced at 12 months (90.0 kg (95%CI 84.9-95.1), p&amp;lt;0.001) compared to baseline (97.6 kg (95%CI 92.7-102.5)). The A1C was significantly improved at 12 months (7.6% (95%CI 7.2-7.9), p&amp;lt;0.001) compared to the baseline (8.2% (95%CI 7.9-8.6)). Total daily basal dose was significantly reduced at 12 months (35.8 units (95%CI 29.8-41.9), p&amp;lt;0.001) compared to the baseline (39.2 units (95%CI 33.3-45.1)). The improvement in the parameters was more pronounced at 6 months after treatment but persisted at 12 months. Conclusion: Weight gain is a consequence of insulin usage in both Type 1 and Type 2 diabetes, which considerably impacts treatment outcomes and the development of comorbidities. We conclude that GLP-1 agonists are helpful to reverse the trend of weight gain and help lower A1C levels in patients with Type 1 diabetes who require life-long insulin treatment. Presentation: 6/3/2024

Effects of simulated natural light brightness on visual perception in virtual reality forests: An eye-tracking study

Although natural light is essential for human health and well-being, the potential effects of different brightness levels of light on the visual perception of forests have not been discussed. Using controlled eye-tracking experiments, this study explored the impact of seven simulated natural brightness levels, from the darkest to the brightest, on the visual perception of 118 participants in a virtual reality (VR) forest environment. One of the most significant findings of this study was the marginal effect of natural light brightness levels on visual physiological stress in VR forests, with the pupillary unrest index decreasing significantly with the increase of natural light brightness; Secondly, the study analyzed the influence of natural light brightness levels in VR forests on the visual engagement behavior of eye tracking, that is, bright forest environments showed an overall trend associated with longer fixation duration, less saccade duration, and greater fixation direction ratio; Thirdly, in terms of visual perception evaluation, the study found an inverted U-shaped trend of mood, restorative perception, perceived safety, and natural light brightness level in VR forests. In addition, the study also found a significant correlation between visual physiological and psychological indicators in VR forest natural light visual perception experiments. These findings help us understand the visual perception effect of forest nature light exposure as a whole, and provided important clues and a basis for future research on improving the visual comfort of forest natural light.

Detection of flood trends and drivers in the Taihu Basin, China

Study regionTaihu Basin, China Study focusFloods threaten humans, the environment, economic activity, and infrastructure. In this study, a new trend test and flood-frequency methods were adopted to detect extreme floods and their distributions based on flood-event identification. To fully understand the phased process of the influence of human activities on extreme hydrological processes, 12 copula functions were employed creatively in combined static and dynamic time-varying correlation aspects between extreme precipitation and floods. New hydrological insights for the regionAlthough both significant and insignificant increasing trends of the annual maximum water level in all three hydrological districts were examined, the periodic oscillations of all the stations were similar. Thus, it was significant to fully detect the periodical variation of floods. Extreme floods occurred mainly in the 1990s, as measured by frequency estimates. Generally, the nonstationary response relationship between heavy rain and an extreme water level was gradually strengthened; that is, a certain magnitude precipitation seemed to induce a greater-intensity flood event as time passed. Through the identification of historical flood events and the analysis of the rise and fall processes of floods, we found that the main reason for variation in the response relationship was the increase in the water level before the rising stage, rather than the water level rising in the Taihu Basin. Our study findings further existing knowledge on the regional flood-control design standard and can ensure the coexistence of humans and water systems in the future.

Identification of Disulfidptosis-Related LncRNA Subtypes, Establishment of a Prognostic Signature, and Characterization of Immune Infiltration in Ovarian Cancer.

Ovarian Cancer (OC) is a lethal malignant tumor with a poor prognosis. Disulfidptosis is a newly identified form of cell death caused by disulfide stress. Targeting disulfidptosis is a new metabolic therapeutic strategy in cancer treatment. We aimed to establish a disulfidptosis- related lncRNA signature for prognosis prediction and explore its treatment values in OC patients. Data from the TCGA and GTEx databases and a disulfidptosis gene set were used to establish a disulfidptosis-related lncRNA signature for prognosis prediction in OC patients. Then, we internally and externally (PCR) validated our model. We also built a nomogram to improve our model's predictive power. Afterward, GSEA was employed to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate the immune landscape. Finally, the drug sensitivity of certain drugs for OC patients was analyzed. We built a prognosis model based on seven drlncRNAs, including AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1. Our model performed well by internal validation. PCR data also confirmed the same trend in the lncRNA levels. Furthermore, the nomogram-integrated age, grade, stage, and risk score could accurately predict the survival outcomes of OC patients. Subsequently, GSEA unveiled that our model genes enriched the Hedgehog signaling pathway, a key regulator in OC tumorigenesis. Our predictive signature was associated with immune checkpoints, such as PD-1(P < 0.01), PD-L1(P < 0.001), and CTLA4 (P < 0.01), which might help screen out OC patients who are sensitive to immunotherapy. Small molecule drugs, such as AZD-2281, GDC-0449, imatinib, and nilotinib, might benefit OC patients with different risk scores. Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.

A-133 Trusted Test Goes Awry: Investigating Dilution Aberrations for Total Bilirubin

Abstract Background A patient with acute decompensated cirrhosis was hospitalized due to lightheadedness and jaundice, undergoing evaluation for a liver transplant. The attending physician brought to the laboratory’s attention a perplexing pattern in the patient's total bilirubin results. Initially, the patient displayed a consistent trend of elevated total bilirubin levels above the upper limit of linearity, ULOL (&amp;gt; 30 mg/dL), which then plummeted to under the limit of quantification (&amp;lt; 0.1 mg/dL) before surging back to &amp;gt; 30 mg/dL. Methods The total bilirubin in heparinized plasma was measured on the AU5800 by Beckman Coulter. Samples &amp;gt; ULOL are diluted automatically 1:3 utilizing the instrument’s on-board dilution feature. The final test results are reported automatically to an electronic medical record. Following the reported incident, an investigation and troubleshooting plan was developed, encompassing the following steps: Repeat patient testing with total bilirubin concentration &amp;gt; 30 mg/dL and &amp;lt;0.1 mg/dL; Rule out the previously reported potential interferences, including Immunoglobin M and acetaminophen; Conduct a 90-day quality control (QC) review; Perform split test analysis on two instruments within the laboratory and at a reference laboratory; Conduct patient chart reviews to identify discrepancies based on previously reported values; Complete a root cause analysis and develop corrective/preventive action plan. Results Patient sample &amp;lt; 0.1 mg/dL was tested on an alternative instrument, resulting &amp;gt; 30 mg/dL. Patient with normal IgM of 161 mg/dL didn’t reveal any other potential drug interferences in chart review. The 3-month QC review found consistent with peer performance. Split comparison of 6 patients revealed discrepancies for samples &amp;gt; 30 mg/dL on one of the two instrument units. When total bilirubin &amp;gt; 30 mg/dL, the malfunctioning unit erroneously reported values &amp;lt; 0.1 mg/dL after dilution. Review of 34 patient charts showed the impact dates were spanned for 39 days. Since the on-board dilution feature is utilized by 10 other analytes, 892 diluted samples were analyzed for discrepancies. 36 discrepant results were identified among 4 affected assays including total bilirubin, direct bilirubin, creatine kinase, and alanine aminotransferase. These results were corrected, and providers were notified. Conclusions The root cause was traced to a malfunction in one instrument unit, despite no malfunction flags. The laboratory QC concentrations fell within the analytical measurement range, missing the dilution issue during the daily QCs. During an extensive repair period, the on-board dilution was disabled on the affected unit and samples were re-routed to alternative instrument for testing. Policy changes and operator training were initiated for a new result verification process, impacting the laboratory productivity. Autoverification of diluted sample results was disabled for all chemistry analyzers. The vendor identified the issue as sample transfer unit crane misalignment in the up/down direction. It is worth noting that proficiency testing or QCs often do not extend beyond the analytical measurement ranges, leading to undetected incidents. Additional quality measures like periodic patient chart reviews, patient sample comparisons, and other quality assurance tools can aid in on-going dilution performance verification. Open communication between the physicians and laboratories is crucial for prompt issue identification and resolution.

Spatiotemporal variation of water level in wetlands based on multi-source remote sensing data and responses to changing environments

Under changing environmental conditions, water level is a crucial indicator for assessing the wetland hydrological cycle. However, due to some wetlands being located in remote and widely dispersed areas, acquiring data on wetland water level changes presents significant challenges, making wetland water level monitoring exceptionally difficult. Wetlands are extensively distributed in western Jilin Province, China, and are experiencing significant degradation due to various factors including natural conditions, agricultural activities, and social development. To address this challenge, this study proposes a monitoring method that combines Sentinel-3 radar altimetry satellites with optical remote sensing images to obtain wetland water level data. Additionally, the study takes into account the Chinese government's Interconnected River System Network Project (IRSNP), classifying wetlands in western Jilin Province into three different water recharge scenarios: direct recharge through main and branch canals, indirect recharge through ditches, and no recharge to isolated wetlands. This study analyses the relationship between wetland water level changes and climatic factors, and assesses how IRSNP can mitigate the negative impacts of climate factors on wetland water levels across different recharge scenarios. The results show that: (1) the wetland water level monitoring method, has high accuracy and feasibility. The average difference between the in-situ measured and satellite-monitored water levels was 0.254 m. (2) There was an overall increasing trend in wetland water levels directly influenced by IRSNP, an insignificant decreasing trend in wetland water levels indirectly influenced by IRSNP. (3) Increased precipitation and decreased evaporation are the predominant climatic factors contributing to rising wetland water levels. Conversely, lower relative humidity and higher temperatures primarily lead to declining water levels. The construction of IRSNP can mitigate the impact of climate change on water levels. Thus, under changing environmental conditions, the implementation of IRSNP has positively impacted wetland protection and provides valuable insights for understanding wetland water level changes and managing water resources effectively.