Evidence of the Role of Inflammation and the Hormonal Environment in the Pathogenesis of Adrenal Myelolipomas in Congenital Adrenal Hyperplasia.

Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis. We aimed to evaluate the role of the immune system and hormones that accumulate in poorly controlled CAH in the development of AML. When compared to normal adrenal tissue, CAH-affected adrenal tissue and myelolipomas showed an increased expression of inflammatory cells (CD68, IL2Rbeta), stem cells (CD117) B cells (IRF4), and adipogenic markers (aP2/FABP4, AdipoQ, PPARγ, Leptin, CideA), and immunostaining showed nodular lymphocytic accumulation. Immunohistochemistry staining revealed a higher density of inflammatory cells (CD20, CD3, CD68) in CAH compared to non-CAH myelolipomas. In vitro RNA-sequencing studies using NCI-H295R adrenocortical cells with exogenous exposure to ACTH, testosterone, and 17-hydroxyprogesterone hormones, showed the differential expression of genes involved in cell cycle progression, phosphorylation, and tumorigenesis. Migration of B-lymphocytes was initiated after the hormonal treatment of adrenocortical cells using the Boyden chamber chemotaxis assay, indicating a possible hormonal influence on triggering inflammation and the development of myelolipomas. These findings demonstrate the important role of inflammation and the hormonal milieu in the development of AML in CAH.

Correlation between aggression at the veterinary clinic and problem behaviors at home for cats in the USA.

OBJECTIVES: The aim of the study was to determine whether cats that exhibit aggression during veterinary visits are more likely to have behavior problems at home. METHODS: An online, anonymous, cross-sectional survey was developed and distributed to residents in the USA who were aged over 18 years and who were the primary owners of at least one cat. The survey collected information about cat and household factors, and utilized a validated questionnaire instrument for obtaining behavioral information of pet cats. RESULTS: Aggression at the veterinary clinic was reported in 42.6% of the cats. The frequency of aggression exhibited at the veterinary clinic was lower in cats that lived in multi-cat households. Most cats did not receive medications intended to reduce fear, anxiety and/or pain before veterinary visits. Aggression at the veterinary clinic was positively associated with behavior problems at home, including stranger-directed aggression, owner-directed aggression, resistance to restraint, familiar cat aggression, dog-directed aggression, house-soiling, separation-related behaviors and scratching claws on inappropriate surfaces indoors. CONCLUSIONS AND RELEVANCE: Cats that exhibit aggression at the veterinary clinic are more likely to exhibit aggression and anxiety-related behaviors at home. Veterinarians should screen cats that exhibit aggression at the veterinary clinic for behavior problems at home to institute prompt diagnosis and treatment.

TGF-ß and BMP signaling are associated with the transformation of glioblastoma to gliosarcoma and then osteosarcoma.

Background: Gliosarcoma, an isocitrate dehydrogenase wildtype (IDH-WT) variant of glioblastoma, is defined by clonal biphasic differentiation into gliomatous and sarcomatous components. While the transformation from a glioblastoma to gliosarcoma is uncommon, the subsequent transformation to osteosarcoma is rare but may provide additional insights into the biology of these typically distinct cancers. We observed a patient initially diagnosed with glioblastoma, that differentiated into gliosarcoma at recurrence, and further evolved to osteosarcoma at the second relapse. Our objective was to characterize the molecular mechanisms of tumor progression associated with this phenotypic transformation. Methods: Tumor samples were collected at all 3 stages of disease and RNA sequencing was performed to capture their transcriptomic profiles. Sequential clonal evolution was confirmed by the maintenance of an identical PTEN mutation throughout the tumor differentiation using the TSO500 gene panel. Publicly available datasets and the Nanostring nCounter technology were used to validate the results. Results: The glioblastoma tumor from this patient possessed mixed features of all 3 TCGA-defined transcriptomic subtypes of an IDH-WT glioblastoma and a proportion of osteosarcoma signatures were upregulated in the original tumor. Analysis showed that enhanced transforming growth factor-ß (TGF-ß) and bone morphogenic protein signaling was associated with tumor transformation. Regulatory network analysis revealed that TGF-ß family signaling committed the lineage tumor to osteogenesis by stimulating the expression of runt-related transcription factor 2 (RUNX2), a master regulator of bone formation. Conclusions: This unusual clinical case provided an opportunity to explore the modulators of longitudinal sarcomatous transformation, potentially uncovering markers indicating predisposition to this change and identification of novel therapeutic targets.

Attitudes and practices toward feral cats of male and female dog or cat owners and non-owners in Seoul, South Korea.

The number of pet cats in South Korea has sharply increased since 2010. Problems have arisen with feral or stray cats, creating conflict among residents, to such an extent that the government provides some sites for people to offer feeding stations for the stray cats. This study investigated hypotheses on people's attitudes toward feral cats in Seoul, South Korea: (i) dog and cat owners would show more positive attitudes than non-owners toward feral cats; (ii) females would have more positive attitudes toward feral cats than males; (iii) the number of Seoul-provided feeding stations by district would be correlated with people's positive attitudes toward feral cats. Responses from 7,394 participants were used for the final analyses with 3,179 males, 3,607 females, and 599 others (includes "decline to state"). Cat owners reported more extremely positive attitudes toward feral cats than people who had no cats. Females more often had cats than males, and they were more extremely positive toward pet and feral cats than males, and strongly opposed to culling as a management strategy. The attitudes toward feral cats of people with only dogs were intermediate between people with cats and people without pets, more resembling those of people without pets. There was a correlation between the number of city-provided feeding stations and people's attitudes toward feral cats, but only in the areas with at least 40 feeder stations; having many city-provided feeding stations was associated with very negative attitudes to feral cats. Whether the very large number of feeding stations were provided in the two neighborhoods due to a previously excessive number of feral cats in those neighborhoods, vs. those feeding stations attracting or provisioning an ever-growing number of feral cats, is unknown. These results show sharp differences in attitudes between cat owners and non-owners, and between males and females. Results resemble findings in other studies, perhaps with more extreme differences between sub-groups. The study revealed that attitudes toward pet and feral cats in Seoul were complex and varied with pet ownership, with sex, and with neighborhood context.

Unveiling the genomic landscape of possible metastatic malignant transformation of teratoma secondary to cisplatin-chemotherapy: a Tempus gene analysis-based case report literature review.

In this case report, we describe a patient who developed metastatic liver cancer of unknown primary origin one year following the surgical removal of a retroperitoneal adenocarcinoma. The retroperitoneal adenocarcinoma is considered a malignant transformation of teratoma (MTT), given the patient's distant history of testicular tumor excised 25 years prior and treated with chemotherapy. Despite no primary tumor being identified, the leading primary hypothesis is that the liver metastasis stemmed from the resected retroperitoneal adenocarcinoma from one year prior. We theorize that the patient's cisplatin-based chemotherapy 25 years ago may have triggered the MTT, as documented in the existing literature. Using TEMPUS gene testing on both the retroperitoneal adenocarcinoma and the recently discovered liver metastasis, we identified several genes with variants of unknown significance (VUS) that could potentially be linked to cisplatin chemotherapy resistance. While we cannot conclude that this patient definitively underwent MTT, it remains the most plausible explanation. Future research should investigate both the validity of the genes we have uncovered with respect to cisplatin resistance, as well as other genes associated with cisplatin resistance to further understand the pathogenesis of cisplatin resistance for better prediction of treatment response. As the world of medicine shifts towards individualized therapies and precision medicine, reporting and analyzing genetic mutations derived from tumors remains imperative. Our case report aims to contribute to the growing database of defined mutations and underscores the immense potential of genetic analysis in directing personalized treatment options.

Urban-Rural Differences in the Prevalence of Depressive Symptoms in Korean Adults.

This study aimed to investigate the prevalence of depression among Koreans living in urban and rural areas, stratified by socioeconomic status. The study included 216,765 participants from the 2017 Korean Community Health Survey. Depressive symptoms were assessed using the PHQ-9, with a score of 10 or higher indicating depressive symptoms. Residences with the words Eup and Myeon in their addresses were categorized as rural areas, and residences with Dong in their addresses as urban areas. Socioeconomic status was evaluated by household income and education level. A Poisson regression analysis with sampling weights was conducted and adjusted for demographic, lifestyle, socioeconomic status, and comorbidity. The adjusted prevalence rate of depressive symptoms was 3.33% (95% CI, 3.21-3.45) in urban areas and 2.59% (95% CI, 2.43-2.74) in rural areas. The prevalence of depressive symptoms in urban areas was 1.29 times (95% CI, 1.20-1.38) higher than in rural areas. The prevalence rate ratio for depressive symptoms in urban areas compared to rural areas sorted by monthly incomes was 1.39 (95% CI, 1.28-1.51) for less than 2 million won, 1.22 (95% CI, 1.06-1.41) for 2 to 3.99 million won, and 1.09 (95% CI, 0.90-1.32) for more than 4 million won, and the urban-rural difference was more evident in lower household income subjects (p for interaction=0.033). However, urban-rural differences did not differ according to sex, age, or education level. In conclusion, we found urban-rural differences in depressive symptoms in a representative sample of Koreans, and revealed that these differences may vary according to income level. These results suggest that mental health policy must consider the health disparities according to residence and income.

Assay of Fe(III) Chelate Reductase Activity in Arabidopsis thaliana Root.

A sensitive FerroZine assay is used to measure the membrane-bound ferric-chelate reductase activity in the Arabidopsis thaliana roots. In Arabidopsis, FRO2 (FERRIC CHELATE REDUCTASE 2) encodes the Fe(III) chelate reductase and its expression is induced by iron deficiency. As FRO2 reduces Fe(III) to soluble Fe(II), the resulting Fe(II) forms a purple-colored complex with the dye FerroZine. The concentration of the Fe(II)-FerroZine is directly proportional to the absorbance at 562 nm.

Defining Terms Used for Animals Working in Support Roles for People with Support Needs.

The nomenclature used to describe animals working in roles supporting people can be confusing. The same term may be used to describe different roles, or two terms may mean the same thing. This confusion is evident among researchers, practitioners, and end users. Because certain animal roles are provided with legal protections and/or government-funding support in some jurisdictions, it is necessary to clearly define the existing terms to avoid confusion. The aim of this paper is to provide operationalized definitions for nine terms, which would be useful in many world regions: "assistance animal", "companion animal", "educational/school support animal", "emotional support animal", "facility animal", "service animal", "skilled companion animal", "therapy animal", and "visiting/visitation animal". At the International Society for Anthrozoology (ISAZ) conferences in 2018 and 2020, over 100 delegates participated in workshops to define these terms, many of whom co-authored this paper. Through an iterative process, we have defined the nine terms and explained how they differ from each other. We recommend phasing out two terms (i.e., "skilled companion animal" and "service animal") due to overlap with other terms that could potentially exacerbate confusion. The implications for several regions of the world are discussed.

Structural Priming and Inverse Preference Effects in L2 Grammaticality Judgment and Production of English Relative Clauses.

This study investigated inverse preference effects in L2 structural priming of English relative clauses and their potential influences on subsequent learning of target structures. One hundred fourteen Chinese learners of English at a low-to-intermediate proficiency level participated in a structural priming experiment with a pretest-posttest design. The experimental group underwent a priming task in which they orally produced syntactic structures immediately after viewing English object or passive relative clauses as primes, whereas the control group only read sentences unrelated to English relative clauses. A grammaticality judgment task and a sentence completion task were used to measure the inverse preference effect and its subsequent effects on L2 learning. The results showed the presence of structural priming and inverse preference effects in immediate production, which extended to subsequent learning of L2. In subsequent grammaticality judgments and production, L2 learners performed better with English object relative clauses than with English passive relative clauses in comparison with the pretest. The results are discussed in terms of the structural frequency in both L1 and L2 as well as the implicit learning mechanisms of structural priming.

Animal Welfare Assessment in 16 Zoos in South Korea Using the Modified Animal Welfare Assessment Grid.

Various assessment tools that have been proposed thus far have disadvantages in that they are complex, time-consuming, non-objective, and not convenient for assessing multiple zoos. This study aimed to develop a simple, objective, and reliable welfare assessment tool, the modified Animal Welfare Assessment Grid (AWAG), that can be applied in South Korea, where there is no licensing system for zoos. The AWAG has four main sections: physical, psychological, environmental, and procedural. These four sections include 23 welfare factors like general conditions, behaviors, housing, and restraints, for which each individual or group of animals is given a score. The modified AWAG system was applied by converting the 10-point rating scale of the original AWAG to a 6-point Likert scale. Sixteen zoos in Korea were selected based on the zoos with the most animals. Three inspectors assessed the scores of each animal and then averaged the results. The total data surveyed included 16,065 items. Zoos were largely classified into four grades based on the size of the zoo, animal species, and operating organization. In a relatively short period of 14 days, all the zoos were successfully assessed. Despite the shortened and modified assessment tool, the inter-rater reliability among inspectors was 0.942 with high objectivity. The modified AWAG could identify welfare differences between grades of Korean zoos. There were large differences between zoos in most environmental sections and some zoos were evaluated as having inadequate welfare levels. The modified AWAG showed high usability and objectivity. In addition, it was possible to determine which environmental or procedural sections could potentially help improve physical and psychological scores. The modified AWAG is an objective method that could set the direction for the improvement of zoo welfare in the future.

A Comparative Study of Three Measurement Methods of Chinese Character Recognition for L2 Chinese Learners.

Measuring Chinese character recognition ability is essential in research on character learning among learners of Chinese as a second language (CSL). Three methods are typically used to evaluate character recognition competence by investigating the following properties of a given character: (a) pronunciation (phonological method), (b) meaning (semantic method), and (c) pronunciation and meaning (phonological and semantic or PS method). However, no study has explored the similar or dissimilar outcomes that these three measurements might yield. The current study examined this issue by testing 162 CSL learners with various L1 backgrounds and Chinese proficiency levels. Participants' performance in character recognition measured using a phonological method, a semantic method, and a PS method was compared, which led to two major findings. In terms of similarity, participants' performance in character recognition and the influence of L1 background and Chinese proficiency level on character recognition was similar across the three methods. As for differences, the semantic method could yield a character recognition test with better quality than the other two methods, and the three methods yielded different best fitting models and showed different predictions for Chinese proficiency across different L1 groups. Theoretical and practical implications of these findings are proposed.

Measles susceptibility of marriage migrant women in Korea.

International migrants could be considered a risk group susceptible to vaccine-preventable diseases. We conducted a measles seroprevalence study among 419 marriage migrant women living in Sinan-gun and Wando-gun, South Jeolla Province, located in the southwestern part of Korea. The overall seroimmunity was 92.8%. The seroimmunity varied considerably according to the country of origin and increased with age. Our current analysis could be valuable in the context of discussions concerning vaccination policies for immigrants in Korea.

Effects of trazodone on behavioral and physiological signs of stress in dogs during veterinary visits: a randomized double-blind placebo-controlled crossover clinical trial.

OBJECTIVE: To determine whether a single dose of trazodone administered to dogs before a veterinary visit reduced their behavioral and physiologic signs of stress and owners' stress during veterinary visits. SAMPLE: 20 dogs and their owners. PROCEDURES: In this randomized double-blinded placebo-controlled crossover clinical trial, dogs with a history of anxiety during veterinary visits were scheduled for 2 veterinary visits 1 week apart and randomly assigned to receive a single oral dose of either trazodone (9 to 12 mg/kg) or a placebo 90 minutes before transport to the veterinary clinic for alternate visits between September 21 and November 3, 2019. For each visit, we collected and assessed owner-completed surveys of dog stress score (DSS) and owner stress score; various investigator-reported scores, including from video-recorded behavior analyses; and patient-related physiologic data. RESULTS: Dogs treated with trazodone versus placebo had lower mean DSSs, assessed by owners for physical examination and assessed by video analysis for time spent in the examination room; lower mean SD of normal-to-normal intervals, root mean square of successive heartbeat interval difference, and respiratory rate; and higher mean heart rate. No meaningful differences were observed in other behavioral or physiologic outcomes, including serum cortisol concentrations. CLINICAL RELEVANCE: A single dose of trazodone before transport reduced signs of stress during veterinary visits for dogs in the present study and may be useful as an anti-anxiety medication for similarly affected dogs, potentially resulting in higher-quality clinical examinations and improved patient welfare.

GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.

BACKGROUND: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear. METHOD: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication. RESULTS: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery. CONCLUSION: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.

5-HT1A and 5-HT2A Signaling, Desensitization, and Downregulation: Serotonergic Dysfunction and Abnormal Receptor Density in Schizophrenia and the Prodrome.

The significant role of serotonin (5-hydroxytryptamine [5-HT]) in the pathogenesis and early development of schizophrenia has been established by contemporary research through the assessment of structural and pharmacological neuroimaging, blood metabolites, cerebrospinal fluid, genome polymorphisms, and other valid indicators of abnormal serotonergic activity in prodromal, ultra-high-risk, and schizophrenic patient groups. A modern approach toward understanding the complex psychophysiology behind schizophrenia will be outlined through the demonstration of 5-HT1A and 5-HT2A receptors as key modulators within the spectrum of negative symptoms associated with schizoaffective disorders, including a variety of disturbances in cognition, behavior, mood, social function, perception of reality, and hormonal response to stressors. This paper will review the evidence for attributing the risk of schizophrenia onset to early defects in serotonergic neurotransmission and explore the perspective of selective serotonin receptor inhibitor (SSRI) pharmacotherapy as a method of treatment and intervention for prodromal and ultra-high-risk patients by increasing 5-HT1A receptor sensitivity levels and modifying the transcription of 5-HT1A receptor-associated gene expression in these groups.

Development and application of a couple-centered antenatal education program in Korea.

Purpose: This study was conducted to develop a couple-centered antenatal education program and to test the program's feasibility. Methods: With a preliminary-experimental study design, 33 pregnant couples who were expecting their first child participated in this study. The program consisted of four sessions (1 hour/session/week) of education and counseling. Data were collected before and after the intervention from September 2018 to April 2019 at a women's hospital in Daejeon, Korea, with demographic data forms, the Edinburgh Postnatal Depression Scale, Perceived Stress Scale, Maternal-Fetal Attachment Scale, Korean Newborn Care Confidence Scale, Wijma Delivery Expectancy/Experience Questionnaire, and Dyadic Adjustment Scale-10. Results: The pregnant women and their husbands were on average 32.30±3.10 and 33.21±6.25 years old, respectively. The mean marriage duration was 2.34±1.63 years, the gestational age was 31.30±2.66 weeks, and 78.8% of the couples had a planned pregnancy. After the program, both the pregnant women and their husbands showed significant improvements in attachment to the fetus and confidence in providing infant care. Prenatal depression, prenatal stress, and fear of childbirth in pregnant women significantly decreased after completing the program. However, the dyadic adjustment score did not change significantly either in the pregnant women or their husbands. Conclusion: A couple-centered antenatal education program seems to be effective for couples adjusting to parenthood, but further studies should explore ways to have a positive impact on couples' relationships.

Relationship of breastfeeding duration with joint pain and knee osteoarthritis in middle-aged Korean women: a cross-sectional study using the Korea National Health and Nutrition Examination Survey.

BACKGROUND: The effect of joint health on the quality of life of middle-aged and older women is becoming more widely recognized with the aging of the world's population. However, the association of long-term breastfeeding with joint pain and knee osteoarthritis has not been fully examined. The aim of this study was to determine the association of prior breastfeeding duration with current joint pain and knee osteoarthritis in middle-aged Korean women. METHODS: This cross-sectional study was conducted among 3454 women aged ≥50 years who underwent knee radiography and answered a questionnaire on breastfeeding and joint pain for the 5th Korea National Health and Nutrition Examination Survey (2010-2011). After adjusting for confounding sociodemographic, medical history, and obstetric and gynecologic variables, logistic regression analysis was conducted to analyze the prevalence of joint pain and knee osteoarthritis according to breastfeeding and its duration. RESULTS: Among the 3454 participants, 298 had not breastfed and 1042, 815, and 1299 had breastfed for 1-24, 25-48, and ≥ 49 months, respectively. Of all participants, 1731 had joint pain and 739 were diagnosed with knee osteoarthritis after radiography. Using the non-breastfeeding group as a reference, the odds ratio (OR) for joint pain among women who breastfed ≥1 month was 1.49 (95% confidence interval [CI] 1.01-2.21). As the breastfeeding duration increased, the OR of joint pain prevalence also increased (p for trend; p = 0.002). For knee osteoarthritis, the OR was 2.30 in the 25-48 months group (95% CI 1.09-4.86). The OR of knee osteoarthritis in the ≥49 months group was 2.17 (95% CI 1.01-4.64). Sensitivity analysis after selecting only participants aged ≥60 years showed that the prevalence of joint pain and knee osteoarthritis was more positively correlated with extended breastfeeding duration (joint pain, p for trend; p = 0.005) (knee osteoarthritis, p for trend; p = 0.012). CONCLUSIONS: Long-term feeding for more than 25 months was associated with an increased prevalence of joint pain and degenerative arthritis in Korean women aged ≥50 years.