Lipid Changes During Endocrine Therapy in Breast Cancer Patients: The Results of a 5-Year Real-World Retrospective Analysis

BackgroundThe aim of this study was to investigate the status of serum lipids during endocrine therapy.MethodsWe retrospectively analysed lipid profiles during the 5-year treatment of 1487 consecutive postoperative BC patients. Lipid parameters included triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C). Those biomarkers were measured at baseline and 1, 2, 3, 4 and 5 years following the initiation of endocrine therapy.ResultsFor premenopausal BC patients, LDL levels rapidly decreased at 1 year in the tamoxifen (TAM) group compared with baseline levels (p<0.05), and this decline remained for the following 4 years. Additionally, LDL levels were significantly lower in the TAM group than in the nonendocrine group at all assessment time points (p<0.05). Similarly, TC levels also decreased in the TAM group compared with baseline levels at all assessment time points (p<0.05), and compared with the levels in the nonendocrine group, TC levels were also lower for the first 4 years. For postmenopausal BC patients, there was no significant difference in the lipid profiles (TG, TC, LDL and HDL) in the letrozole (LET), anastrozole (ANA) or exemestane (EXE) groups compared with the nonendocrine group. For patients who received TAM, compared with the nonendocrine group, TC levels decreased at 1 year, and LDL levels decreased at 1 and 2 years.ConclusionsTAM may improve LDL and TC levels in premenopausal BC patients. In postmenopausal BC patients, aromatase inhibitors (AIs) may have no adverse effects on lipid profiles, and TAM may have limited beneficial effects on serum lipids.

Can Body Mass Index Affect Height Growth at Menarche among Girls Receiving Treatment for Early Puberty? A Retrospective Study in Korean Girls

Gonadotropin-releasing hormone agonist (GnRHa) therapy is used to control puberty progression and it preserves height potential in patients with idiopathic central precocious puberty (ICPP). This study evaluated the correlation between weight and height gain at menarche following GnRHa treatment among girls with ICPP and relatively central early puberty (EP). We investigated height/weight trends and changes in height from diagnosis to menarche in girls with ICPP and EP treated with GnRHa. The mean difference in height (Δheight) from treatment cessation to menarche was 9.79 ± 3.53 cm. Girls were divided into girls with Δheight ≥ 9.79 cm (Group 1) and girls with Δheight < 9.79 cm (Group 2). Although near adult height was significantly higher in Group 1, the mean body mass index (BMI) and weight were significantly lower at diagnosis, treatment discontinuation, and menarche. The BMI and weight at the three time points were negatively correlated with height. Girls with higher BMI at all three time points had slower growth rates during the study period. Considering that BMI and body weight were closely related to Δheight, proper management of BMI and body weight of girls receiving early puberty treatment might contribute to growth during and after GnRHa treatment.

Adverse childhood experiences and other risk factors associated with adolescent and young adult vaping over time: a longitudinal study

Background Vaping among adolescents and young adults is a significant public health concern worldwide. Understanding which risk factors are associated with vaping is important to help inform evidence-based prevention and intervention strategies. There are several gaps in the current literature examining these associations such as limited longitudinal research. We examined the association between parental smoking/vaping, adolescent sex, mental disorders in adolescence, 13 adverse childhood experiences (ACEs) and a) any vaping and b) course of vaping across two time points among adolescents and young adults. Methods Data were from Waves 1 and 2 of the longitudinal Well-Being and Experiences Study (The WE Study) in Manitoba, Canada which collected data from a community sample of adolescents (14 to 17 years) and their parent/caregiver in Wave 1 in 2017–18 and the adolescents/young adults only in Wave 2 in 2019. A total of 752 adolescents/young adults (72.4% of the original cohort) completed both waves of the study. Binary and multinomial logistic regressions were conducted to understand the relationship between the 16 risk factors and the two vaping outcomes. Results Vaping prevalence was 45.5% for any vaping, 2.7% for Wave 1 vaping only, 19.7% for new onset Wave 2 vaping, and 21.2% for vaping at both waves. After adjusting for covariates, the majority of risk factors examined were associated with any adolescent or young adult vaping, including: parental smoking or vaping, emotional abuse, emotional neglect, exposure to verbal intimate partner violence, household substance use, household mental illness, parental separation/divorce, parental problems with police, foster care or contact with a child protective organization, an unsafe neighbourhood, and peer victimization. The majority of these risk factors, as well as adolescent mental health and parental gambling, were associated with different courses of vaping across the two time points. Conclusions The findings emphasize the need for early vaping prevention and identified several ACEs and other factors that were associated with adolescent and young adult vaping and course of vaping. These identified ACEs and risk factors can help inform programs, strategies, and potential groups to target for vaping interventions.

Case Report: Variety of Target Antigens During 1 Year Follow-Up of a Patient Initially Diagnosed With Bullous Pemphigoid

Autoimmune bullous diseases (AIBDs), presenting cutaneous and/or mucosal bullous lesions, are classified into pemphigus and pemphigoid diseases. A longtime observation for complicated AIBD cases is rarely reported. In this study, serum samples of one AIBD patient were collected at seven different time points during the disease course including a relapse, which were examined by our conventional and newly developed methods for the detection of autoantibodies. Interestingly, we found changes of both the presence and the titers of various autoantibodies in accordance with the changes of clinical features during the whole disease course, which indicated that the patient started as bullous pemphigoid and relapsed as concurrence of bullous pemphigoid and mucosal-dominant-type pemphigus vulgaris.

Simultaneous Upregulation of Elastolytic and Elastogenic Factors Are Necessary for Regulated Collateral Diameter Expansion

Background: During arteriogenesis, outward remodeling of the arterial wall expands luminal diameter to produce increased conductance in developing collaterals. We have previously shown that diameter expansion without loss of internal elastic lamina (IEL) integrity requires both degradation of elastic fibers and LOX-mediated repair. The aim of this study was to investigate the expression of genes involved in remodeling of the extracellular matrix (ECM) using a model of arteriogenesis.Methods: Sprague-Dawley rats underwent femoral artery ligation with distal arteriovenous fistula (FAL + AVF) placement. Profunda femoral arteries (PFA) were harvested for analysis at various time points. Serum desmosine, an amino acid found exclusively in elastin, was evaluated with enzyme-linked immunosorbent assay (ELISA) as a marker of tissue elastolysis. Tissue mRNA isolated from FAL + AVF exposed PFAs was compared to the contralateral sham-operated using qPCR. HCAECs were cultured under low shear stress (8 dyn·s/cm2) for 24 h and then exposed to high shear stress (40 dyn·s/cm2) for 2–6 h. Primers used included FBN-1, FBN-2, Timp-2, LOX-1, Trop-E, Cath-K, Cath-S, MMP-2, MMP-9, FBLN-4, and FBLN-5 and were normalized to GAPDH. mRNA fold changes were quantified using the 2-ΔΔCq method. Comparisons between time points were made with non-parametric ANOVA analysis with Bonferroni adjustment.Results: PFAs showed IEL reorganization during arteriogenesis. Serum desmosine levels are significantly elevated at 2 days and one week, with a return to baseline thereafter (p &lt; 0.01). Expression of ECM structural proteins (FBN-1, FBN-2, FBLN-4, FBLN-5, Tropoelastin, TIMP-2, LOX-1) and elastolytic proteins (MMP-2, MMP-9, Cathepsin S, Cathepsin K) exhibited an early peak (p &lt; 0.05) relative to sham PFAs. After two weeks, expression returned to baseline. HCAECs demonstrated upregulation of FBN-2, FBLN-5, LOX-1 and Trop-E at 4 h of high shear stress, as well as elastolytic protein MMP-2.Conclusions: Elastin degradation begins early in arteriogenesis and is mediated by local upregulation of elastolytic genes. Elastolysis appears to be simultaneously balanced by production of elastic fiber components which may facilitate stabilization of the IEL. Endothelial cells are central to initiation of arteriogenesis and begin ECM remodeling in response to altered shear stress.

Understanding Memories of the Past in the Context of Different Complex Neural Network Architectures

Deep learning (primarily using backpropagation) and neuroevolution are the preeminent methods of optimizing artificial neural networks. However, they often create black boxes that are as hard to understand as the natural brains they seek to mimic. Previous work has identified an information-theoretic tool, referred to as R, which allows us to quantify and identify mental representations in artificial cognitive systems. The use of such measures has allowed us to make previous black boxes more transparent. Here we extend R to not only identify where complex computational systems store memory about their environment but also to differentiate between different time points in the past. We show how this extended measure can identify the location of memory related to past experiences in neural networks optimized by deep learning as well as a genetic algorithm.

Children Use Non-referential Gestures in Narrative Speech to Mark Discourse Elements Which Update Common Ground

While recent studies have claimed that non-referential gestures (i.e., gestures that do not visually represent any semantic content in speech) are used to mark discourse-new and/or -accessible referents and focused information in adult speech, to our knowledge, no prior investigation has studied the relationship between information structure (IS) and gesture referentiality in children’s narrative speech from a developmental perspective. A longitudinal database consisting of 332 narratives performed by 83 children at two different time points in development was coded for IS and gesture referentiality (i.e., referential and non-referential gestures). Results revealed that at both time points, both referential and non-referential gestures were produced more with information that moves discourse forward (i.e., focus) and predication (i.e., comment) rather than topical or background information. Further, at 7–9 years of age, children tended to use more non-referential gestures to mark focus and comment constituents than referential gestures. In terms of the marking of the newness of discourse referents, non-referential gestures already seem to play a key role at 5–6 years old, whereas referential gestures did not show any patterns. This relationship was even stronger at 7–9 years old. All in all, our findings offer supporting evidence that in contrast with referential gestures, non-referential gestures have been found to play a key role in marking IS, and that the development of this relationship solidifies at a period in development that coincides with a spurt in non-referential gesture production.

Latent Markov Factor Analysis: A Mixture Modeling Approach for Evaluating Within- and Between-Person Measurement Model Differences in Intensive Longitudinal Data

SUMMARY DOCTORAL DISSERTATION: Experience sampling methodology, in which participants are repeatedly questioned via smartphone apps, is popular for studying psychological constructs or “factors” (e.g., well-being or depression) within persons over time. The validity of such studies (e.g., concerning treatment decisions) may be hampered by distortions of the measurement of the relevant constructs due to response styles or item interpretations that change over time and differ across persons. In this PhD project, we developed a new approach to evaluate person- and time-point-specific distortions of the construct measurements, taking into account the specific characteristics of (time-intensive) longitudinal data inherent to experience sampling studies. Our new approach, latent Markov factor analysis, extends mixture factor analysis and clusters time-points within persons according to their factor model. The factor model describes how well items measure the constructs. With the new approach, researchers can examine how many and which factor models underlie the data, for which persons and time-points they apply, and thus which observations are validly comparable. Such insights can also be interesting in their own right. In personalized healthcare, for example, detecting changes in response styles is critical for accurate decisions about treatment allocation over time, as response styles may be related to the occurrence of depressive episodes.

Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers

Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load. Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II). Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6. Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.