Normal Response Research Articles

ASSOCIATION BETWEEN ORTHOSTATIC HYPERTENSION AND FRAILTY AMONG OLDER PATIENTS WITH HYPERTENSION

Objective: Frailty frequently co-exists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. Design and method: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and hand-grip strength. Orthostatic hypertension was defined as a >= 20-mmHg increase in systolic blood pressure within 3 min of standing and upright systolic blood pressure of >= 140 mmHg. Results: We analyzed the data of 2,065 participants who had been enrolled until December 31, 2022. The mean age was 73.2 ± 5.6 years and 52.0% were female. The mean blood pressure was 137.1 ± 14.9 / 75.1 ± 9.7 mmHg. Among the participants, 1,886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life (QOL). In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. Conclusions: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low QOL in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Control preoperative anxiety with self-relaxation

Anxiety experienced by preoperative patients is a normal response, but when the anxiety response causes disturbances in physiological and psychological function, this becomes an abnormal response. The impact of anxiety before surgery can have an impact on the operation so that it must be postponed. Action is needed to overcome the anxiety experienced by the patient. One that can by givingSelf relaxound therapy, that is by providing a combination of relaxation interventionsmaybeandnature sound developed by researchers which is done by perception and self-suggestion while listening to natural sounds and deep breathing exercises. The aim of this research is to determine the effect of relaxationself relaxound on patient anxiety before laparotomy surgery. This type of research uses quantitative research, by designquasi experiment using a non planequivalent without control group. This research was carried out in the surgical inpatient room on 32 respondents. Anxiety measurement uses a questionnaireZung Self Rating Scale. Data analysis usingPaired Sample T test with a significance limit of 0.05. The results of the analysis obtained a p value = 0.000 (α 0.05), which shows that there is a significant effect between therapyself relaxound with patient anxiety. Psychological problems are closely related to surgery, for this the researchers suggestSelf relaxound therapy can be considered as a nursing procedure for every preoperative patient.

The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus.

GDF9His209GlnfsTer6/S428T and GDF9Q321X/S428T bi-allelic variants caused female subfertility with defective follicle enlargement

BackgroundAntral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined.MethodsWhole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients.ResultsTwo probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement.ConclusionsGDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration

BackgroundLate-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. Material and methodsA group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. ResultsEight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48–0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0–0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. ConclusionsOur study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Neuromarkers in addiction: definitions, development strategies, and recent advances.

Substance use disorders (SUDs) are the most costly and prevalent psychiatric conditions. Recent calls emphasize a need for biomarkers-measurable, stable indicators of normal and abnormal processes and response to treatment or environmental agents-and, in particular, brain-based neuromarkers that will advance understanding of the neurobiological basis of SUDs and clinical practice. To develop neuromarkers, researchers must be grounded in evidence that a putative marker (i) is sensitive and specific to the psychological phenomenon of interest, (ii) constitutes a predictive model, and (iii) generalizes to novel observations (e.g., through internal cross-validation and external application to novel data). These neuromarkers may be used to index risk of developing SUDs (susceptibility), classify individuals with SUDs (diagnostic), assess risk for progression to more severe pathology (prognostic) or index current severity of pathology (monitoring), detect response to treatment (response), and predict individualized treatment outcomes (predictive). Here, we outline guidelines for developing and assessing neuromarkers, we then review recent advances toward neuromarkers in addiction neuroscience centering our discussion around neuromarkers of craving-a core feature of SUDs. In doing so, we specifically focus on the Neurobiological Craving Signature (NCS), which show great promise for meeting the demand of neuromarkers.

Computational simulation of impact perforation of polymeric-foam core sandwiched composites with different skin–face configurations

The normal and oblique impact perforation responses of composite sandwich panels based on a Rohacell polymeric-foam core are numerically investigated at high impact energies (>60 J). A cylindrical form factor with a diameter of 140 mm and a thickness of 15 mm is selected for the sandwich specimens. Four different stacking sequences of 1 mm carbon/epoxy face sheets are considered (i.e., quasi-isotropic, cross-ply, angle-ply, and unidirectional stacking). A computational model was constructed using LS-DYNA finite element software and an inverse perforation testing scheme adapted with a split Hopkinson bar and confirmed by comparing these results with those obtained using the free shooting projectile-target testing schemes published in the literature. The effects of impact energy, failure modes, impact angles, and damage key parameters are analyzed. The results reveal the contact force versus displacement curves are highly influenced by the impact energy increases. The stacking sequence of the face sheets does not influence the energy absorption capacity. However, the maximum absorbed energy increases with an increasing impact angle up to 20°. Using Hopkinson bars in conjunction with the virtual inverse perforation testing approach is effective for examining the response of sandwich composites at high impact energies.

Inactivation of VRK1 sensitizes ovarian cancer to PARP inhibition through regulating DNA-PK stability

Ovarian cancer is the leading cause of gynecologic cancer death. Among the most innovative anti-cancer approaches, the genetic concept of synthetic lethality is that mutations in multiple genes work synergistically to effect cell death. Previous studies found that although vaccinia-related kinase-1 (VRK1) associates with DNA damage repair proteins, its underlying mechanisms remain unclear. Here, we found high VRK1 expression in ovarian tumors, and that VRK1 depletion can significantly promote apoptosis and cell cycle arrest. The effect of VRK1 knockdown on apoptosis was manifested by increased DNA damage, genomic instability, and apoptosis, and also blocked non-homologous end joining (NHEJ) by destabilizing DNA-PK. Further, we verified that VRK1 depletion enhanced sensitivity to a PARP inhibitor (PARPi), olaparib, promoting apoptosis through DNA damage, especially in ovarian cancer cell lines with high VRK1 expression. Proteins implicated in DNA damage responses are suitable targets for the development of new anti-cancer therapeutic strategies, and their combination could represent an alternative form of synthetic lethality. Therefore, normal protective DNA damage responses are impaired by combining olaparib with elimination of VRK1 and could be used to reduce drug dose and its associated toxicity. In summary, VRK1 represents both a potential biomarker for PARPi sensitivity, and a new DDR-associated therapeutic target, in ovarian cancer.

Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients.

After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Fixed width confidence interval estimation for general continuous responses under a response adaptive design

. A fixed width confidence interval for the treatment difference is obtained under heteroscedastic normal responses following a response adaptive allocation targeting Neyman optimum allocation. The developed procedure is further extended for general location-scale model based responses under a compound response adaptive allocation. The developed procedures are studied theoretically and are supported empirically assuming various response models. A real data study is also provided following the proposed procedure for the purpose of illustration.

Usability of myocardial work parameters to demonstrate subclinical myocardial involvement in normotensive individuals with exaggerated hypertensive response in treadmill exercise testing.

Early determination of changes in myocardial functions is essential for the protection of cardiovascular diseases. This study aimed to evaluate myocardial work parameters in healthy individuals who developed an exaggerated hypertensive response during the treadmill exercise test procedure. The study included a total of 64 patients for whom an exercise electrocardiography test was planned for functional capacity evaluation. The study population was divided according to the presence of exaggerated hypertensive response to exercise (EBPRE) (SBP/DBP ≥210/105mmHg in males ≥190/105mmHg in females) and normal blood pressure response to exercise (NBPRE). Patients' echocardiographic evaluations were made at rest, and myocardial work parameters were calculated. There was no statistical difference between the groups (NBPRE vs. EBPRE, respectively) in terms of left ventricular 2,3 and 4 chamber strains and global longitudinal strain (GLS) values (-20.6±-2.3, -19.7±-1.9, p:.13; -21.3±-2.7, -21±-2.4, p:.68; -21.2±-2.2, -21.2±-2.3, p:.93; and -20.8±-1.5, -20.4±-1.5, p:.23, respectively). Global constrictive work (GCW), global waste work (GWW), and global work efficiency (GWE) were not statistically different between the two groups (2374±210, 2465±204, p:.10; 142±64, 127±42, p:.31; 94.3±2.5, 95.1±1.5, p:.18, respectively). In contrast, global work index (GWI) parameters were different between the two groups (2036±149, 2147±150, p<.001). The GWI was independently associated with EBPRE (odds ratio with 95% 3.32 (1.02-11.24), p=.03). The partial effect plots were used for GWI to predict EBPRE, according to the results, an increase in GWI predicts probability of exaggerated hypertensive response. In conclusion, Myocardial work analyses might be used to identify early signs of myocardial involvement in normotensive patients with EBPRE.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Abnormal Feather Phenotype Associated with a Fatal Stress Response and Unusual Tolerance to Human Contact in the Zebra Finch (Taeniopygia castanotis).

The zebra finch (Taeniopygia castanotis) is a songbird sold in the pet trade and commonly used in research. In this report, we describe a set of partially overlapping traits shared by 3 birds in 2 broods from the same nest box that included atypical morphologic, developmental, and behavioral characteristics. The most obvious feature of this novel phenotype was feathers exhibiting a clumped appearance, which was accompanied by slow growth, delayed expression of adult plumage traits, and tameness, which we define as a lack of escape response upon handling without behavioral indicators of stress such as rapid breathing. Surprisingly, these birds also displayed a fatal response to nonhuman stressors. In one brood, a male expressed all of these characteristics, 2 females were wild-type, and a male sibling expressed only a hyperactive stress response but was otherwise normal. This indicates that the stress response could be inherited independently of the other abnormalities found in the male nest mate. In a second brood, a male bearing the abnormal feather phenotype behaved similarly to the male in the first brood, supporting the possibility that tameness is genetically associated with the unusual feather phenotype. The 2 other male and 2 female nest mates from this brood were behaviorally and visually normal, although the females developed slowly. Although similar traits have appeared in the aviary previously, such as slow development and small size, these are the first cases documented in detail. This correlated suite of traits suggests a linkage among altered feather growth, developmental rate, and brain and/or physiologic traits influencing normal fear and stress responses in the zebra finch. Awareness and study of the mechanism(s) linking these traits by examination of underlying genetic or environmental factors will allow a better understanding of the relationship between physical and behavioral traits in domesticated laboratory animals.

Factors Affecting Perceived Stress-Cortisol Responses in Young Adults

Background: This study examined the distribution of stress-cortisol responses and risk factors affecting perceived stress and cortisol responses among 187 university students in South Korea.Methods: Perceived stress, depressive symptoms, and health-promoting lifestyle were assessed using structured questionnaires. Blood analyses and anthropometrics were used to determine cortisol and cardiometabolic risks. Multinomial logistic regression analysis was used to examine the factors affecting stress-cortisol responses.Results: Four groups of stress-cortisol responses were found, including normal (39.0%), high stress (34.8%), high stress-cortisol (13.9%), and high cortisol group (12.3%). Age, systolic blood pressure, high-density lipoprotein cholesterol, depressive symptoms, and physical activity were associated with stress-cortisol responses.Conclusions: Multidimensional interventions are needed to reduce stress levels and promote normal stress-cortisol responses.

Exercise-induced Hypertension and Carotid Intima-media Thickness in Male Marathon Runners.

This study aimed to identify the relationship between exercise-induced hypertension and carotid artery intima-media thickness in long-distance runners. Sixty healthy male runners aged 40 to 60 years were assigned to the following three groups based on resting blood pressure and maximal systolic blood pressure during a maximal exercise test: normal blood pressure response, exercise-induced hypertension, and complex hypertension. An exaggerated systolic blood pressure response was defined as a maximal systolic blood pressure+≥+210 mmHg during the maximal exercise test, while carotid intima-media thickness was measured using B-mode ultrasonography. The carotid intima-media thickness mean values were the highest in the complex hypertension group (0.72±0.11 mm), followed by exercise-induced hypertension (0.62±0.12 mm) and normal blood pressure groups (0.55±0.13 mm), with a significant difference between the groups (p+<+0.002). In linear regression analysis, the mean intima-media thickness was independently associated with age (p=0.015) and maximal systolic blood pressure (p=0.046) but not with resting systolic blood pressure. These results suggest that exercise-induced hypertension is associated with carotid intima-media thickness, a surrogate marker of cardiovascular disease, in long-distance runners. Therefore, evaluating the blood pressure response during exercise is important for the early detection of potential cardiovascular disease risks in long-distance runners.

Identification of the cytochrome P450 gene AccCYP6A13 in Apis cerana cerana and its response to environmental stress

Cytochrome P450 plays a crucial role in regulating insect growth, development, and resisting a variety of stresses. Insect metamorphosis and response to external stress are altered by deleting CYP450 genes. In this study, we identified and analyzed a novel gene of CYP450 family, AccCYP6A13, from Apis cerana cerana, and explored its role in the response of Apis cerana cerana to adverse external stressors. It was found that the expression of AccCYP6A13 was spatiotemporal specificity. The expression level increased with age and reached its highest value in the adult stage. The primarily expressiong location were legs, brain, and epidermis of honeybees. Stress conditions can affect the expression of AccCYP6A13 depending on treatment times. RNA interference experiments have shown that knocking down AccCYP6A13 reduces antioxidant activity and deactivates detoxification enzymes, resulting in oxidative damage accumulation and a decline in detoxification capability in bees, as well as inhibiting numerous antioxidant genes. Additionally, knockdown of the AccCYP6A13 gene in Apis cerana cerana resulted in increased sensitivity to pesticides and increased mortality when treated with neonicotinoid pesticides such as thiamethoxam. AccCYP6A13 overexpression in a prokaryotic system further confirmed its role in resistance to oxidative stress. To summarize, AccCYP6A13 may play an essential role in the normal development and response to environmental stress in Apis cerana cerana. Furthermore, this study contributed to the theoretical understanding of bee resistance biology.

Shear and shear-induced normal responses of origami cylinders relate to their structural asymmetries

Origami cylinders have been studied extensively under compression, however, their normal force response under shear deformation is still ill-understood. We experimentally studied the shear-induced normal force of these systems and provided a simple model to predict this response in Yoshimura and Kresling origami cylinders in the range of small deformations. Besides that, the effect of disorder is little understood in those origami patterns. Therefore, we investigate the disorder effect and show it can lead to diverse normal responses perpendicular to shear deformation in crumpled Yoshimura, with slopes of the force perpendicular to torsion that can be positive, zero, or negative depending on the disordered pattern of folds. The disorder leads to an asymmetry concerning the shearing direction, which we quantified via an asymmetry index from the 2D Fast Fourier transform spectrum of the crease pattern images. This asymmetry index is found to be linearly related to the slope of the normal force-torsion relationship.

Roxadustat and transfusional iron overload induced hypothyroidism in a hemodialysis patient: a case report with a literature review

BackgroundAlthough roxadustat has been reported to cause central hypothyroidism, the details of the mechanisms and clinical characteristics of patients who are prone to developing hypothyroidism with roxadustat are uncertain.Case presentationA 53-year-old man with a 3-year history of hemodialysis due to diabetic kidney disease who had been treated with roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, for 2 years was admitted to the hospital because of worsening gait disturbance and impaired consciousness. He had also acquired pure red cell aplasia associated with T-cell large granular lymphocytic leukemia and received multiple blood transfusions. Because his serum concentration of thyroid hormones was low, we diagnosed him with hypothyroidism, and his consciousness level recovered to normal with thyroid hormone replacement therapy. Computed tomography revealed a high-intensity atrophic thyroid gland, and magnetic resonance imaging showed diffusely reduced T2 and T1 signals of the pituitary anterior gland. These findings confirmed the accumulation of iron in the pituitary and thyroid glands. Combined pituitary stimulation tests with thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and corticotropin-releasing hormone revealed that the patient had pan-hypopituitarism. After discontinuation of roxadustat, the patient was treated with another hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat. One month after switching medication, a stimulation test with thyrotropin-releasing hormone showed normal responses to thyroid-stimulating hormone. The patient was treated with levothyroxine 50 μg daily without any significant symptoms and is currently under follow-up observation as an outpatient.ConclusionsWe encountered a dialysis patient with roxadustat-induced hypothyroidism associated with transfusion iron overload. To our knowledge, this is the first case to clearly show that roxadustat can impair thyroid-stimulating hormone secretion in repeated thyrotropin-releasing hormone stimulation tests. Because the present patient had received roxadustat for more than 2 years before hypothyroidism became apparent, regular monitoring of the thyroid function may be needed in patients with renal anemia who have been treated with roxadustat, especially those at high risk of thyroid dysfunction.

Abstract 1432: Development of transparent transgenic zebrafish model to study CNS microglia and NF-kB activity in glioblastoma

Abstract Microglia are resident macrophages of the central nervous system (CNS) and have crucial roles in normal brain homeostasis, function, and immune response. Microglia play key roles in the healthy brain, ranging from phagocytosis of dying neurons and CNS debris to modulating adaptability. The role of microglia has been well documented but their specific contributions to the development and progression of cancers, such as glioblastoma, have recently garnered wide attention. The zebrafish have proven novel tool for modeling innate immune responses. A macrophage-specific marker mpeg1 and its promoter are used in mpeg1-driven transgenes. mpeg1-driven transgenes mpeg1:mCherryFP are expressed in macrophage-lineage cells that do not express neutrophil-marking transgenes. These zebrafish transgenes contribute to the fields of inflammation, infection, and leukocyte biology. We have recently developed a novel transparent transgenic homozygous strain Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−) of zebrafish to the in-vivo study of NF-kB activity under normal and inflammation stage at the cellular, organ-specific and whole organism level. To perform an in-vivo study of microglial function, we are developing Casper;mpeg1:mCherryFP microglia specific strain and integrating with newly developed Tg(6xNF-kB:EGFP); Casper(roy−/−, nacre−/−) strain through crossbreeding of Casper and transgenic zebrafish. We have generated F1 generation of newly developed strains of Casper;mpeg1:mCherryFP and Tg(6xNF-kB:EGFP);Casper. The presence of fluorescence mCherry and GFP, in crossbred progeny was identified through the screening of larvae at 72 HPF stage. The expression of these fluorescent proteins determines the presence of the reporter genes. F1 generation confirmed heterozygous and allowed them to grow into adults to breed transparent transgenic strain to get F2 generation. This process will be continued to F2, F3, F4, and F5 generation until achieving homozygous progeny. This model allows for in-vivo examination of microglia functional morphology by using fluorescent and confocal microscopy. This novel transgenic model will be applied to identify novel anti-inflammatory drug inhibitors in NF-kB pathophysiology for glioblastoma and cardio-oncology experimental therapeutics. Citation Format: Surendra K. Rajpurohit, Sai Nasanally, Simran Hotwani, Taitum Gossman, Keshu Bhatt, Aiden Van Derhei, Rohan Pasi, Devan-Anmol Manhiani, Kirk Kimmerling, Balakrishna L. Lokeshwar. Development of transparent transgenic zebrafish model to study CNS microglia and NF-kB activity in glioblastoma [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 1432.

The Effect of Supine Versus Upright Positioning on Eyelid Height in the Nonsurgical Patient.

To directly compare margin-reflex distance 1, margin-reflex distance 2, and palpebral fissure in the upright versus supine positions in nonsurgical patients. A total of 43 patients (31 female, 12 male, and age range 26-96) were enrolled. Photos were taken in the clinic in the upright and supine position with a ruler placed vertically in the same plane as the eyelid, and the above computer-analyzed measurements were obtained. Among the 86 eyes observed, the average upright margin-reflex distance 1 was 2.97 mm (95% confidence interval [CI], 2.70-3.24), while the average supine margin-reflex distance 1 was 2.38 mm (95% CI, 2.13-2.63). These differences were statistically significant (p < 0.001). Similarly, statistically significant differences were seen with margin-reflex distance 2 (p < 0.001), where upright measurements averaged 5.57 mm (95% CI, 5.33-5.81), and supine measurements averaged 5.01 mm (95% CI, 4.73-5.28). Finally, palpebral fissure showed similar significance (p < 0.001). Upright measurements averaged 8.54 mm (95% CI, 8.19-8.90), while supine measurements averaged 7.38 mm (95% CI, 7.00-7.76). Supine positioning provides a decrease in margin-reflex distance 1, margin-reflex distance 2, and palpebral fissure when compared with upright positioning in nonsurgical patients. This contradicts a previous study on intraoperative patients when lidocaine with epinephrine was used. This study helps us better understand the normal physiologic response to position changes with regard to eyelid height in the nonsurgical patient. As such, this study may function as a control for future studies comparing anesthetic/surgical parameter effects on intra- and post-operative eyelid heights.