DIGEP-Pred 2.0: A web application for predicting drug-induced cell signaling and gene expression changes.

The analysis of drug-induced gene expression profiles (DIGEP) is widely used to estimate the potential therapeutic and adverse drug effects as well as the molecular mechanisms of drug action. However, the corresponding experimental data is absent for many existing drugs and drug-like compounds. To solve this problem, we created the DIGEP-Pred 2.0 web application, which allows predicting DIGEP and potential drug targets by structural formula of drug-like compounds. It is based on the combined use of structure-activity relationships (SARs) and network analysis. SAR models were created using PASS (Prediction of Activity Spectra for Substances) technology for data from the Comparative Toxicogenomics Database (CTD), the Connectivity Map (CMap) for the prediction of DIGEP, and PubChem and ChEMBL for the prediction of molecular mechanisms of action (MoA). Using only the structural formula of a compound, the user can obtain information on potential gene expression changes in several cell lines and drug targets, which are potential master regulators responsible for the observed DIGEP. The mean accuracy of prediction calculated by leave-one-out cross validation was 86.5 % for 13377 genes and 94.8 % for 2932 proteins (CTD data), and it was 97.9 % for 2170 MoAs. SAR models (mean accuracy-87.5 %) were also created for CMap data given on MCF7, PC3, and HL60 cell lines with different threshold values for the logarithm of fold changes: 0.5, 0.7, 1, 1.5, and 2. Additionally, the data on pathways (KEGG, Reactome), biological processes of Gene Ontology, and diseases (DisGeNet) enriched by the predicted genes, together with the estimation of target-master regulators based on OmniPath data, is also provided. DIGEP-Pred 2.0 web application is freely available at https://www.way2drug.com/digep-pred.

Navigating pharmacophore space to identify activity discontinuities: a case study with BCR-ABL.

The exploration of chemical space is a fundamental aspect of chemoinformatics, particularly when one explores a large compound data set to relate chemical structures with molecular properties. In this study, we extend our previous work on chemical space visualization at the pharmacophoric level. Instead of using conventional binary classification of affinity (active vs inactive), we introduce a refined approach that categorizes compounds into four distinct classes based on their activity levels: super active, very active, active, and inactive. This classification enriches the color scheme applied to pharmacophore space, where the color representation of a pharmacophore hypothesis is driven by the associated compounds. Using the BCR-ABL tyrosine kinase as a case study, we identified intriguing regions corresponding to pharmacophore activity discontinuities, providing valuable insights for structure-activity relationships analysis.

Advancements in inhibitors of crucial enzymes in the cysteine biosynthetic pathway: Serine acetyltransferase and O-acetylserine sulfhydrylase.

Infectious diseases have been jeopardized problem that threaten public health over a long period of time. The growing prevalence of drug-resistant pathogens and infectious cases have led to a decrease in the number of effective antibiotics, which highlights the urgent need for the development of new antibacterial agents. Serine acetyltransferase (SAT), also known as CysE in certain bacterial species, and O-acetylserine sulfhydrylase (OASS), also known as CysK in select bacteria, are indispensable enzymes within the cysteine biosynthesis pathway of various pathogenic microorganisms. These enzymes play a crucial role in the survival of these pathogens, making SAT and OASS promising targets for the development of novel anti-infective agents. In this comprehensive review, we present an introduction to the structure and function of SAT and OASS, along with an overview of existing inhibitors for SAT and OASS as potential antibacterial agents. Our primary focus is on elucidating the inhibitory activities, structure-activity relationships, and mechanisms of action of these inhibitors. Through this exploration, we aim to provide insights into promising strategies and prospects in the development of antibacterial agents that target these essential enzymes.

Estimating the prevalence and clinical causality of obstructive sleep apnea in paediatric narcolepsy patients.

BACKGROUND: Numerous risk factors in paediatric narcolepsy may predispose them to obstructive sleep apnea (OSA). The concurrent presence of OSA in these patients might lead to underdiagnosing narcolepsy. This research investigates the prevalence and potential causality between OSA and paediatric narcolepsy. METHODS: A case-control study coupled with a two-sample Mendelian randomization (MR) analysis was employed to explore the prevalence and causal link between paediatric narcolepsy and OSA risk. RESULTS: The case-control study revealed that paediatric narcolepsy patients are at an increased risk of OSA, with an Odds ratio (OR) of 4.87 (95% CI: 2.20-10.71; P < 0.001). The inverse-variance weighted (IVW) model further suggests a potential causal link between narcolepsy and OSA (IVW OR: 4.671, 95% CI: 1.925-11.290; P < 0.001). Additionally, sensitivity analysis confirmed these findings' reliability. CONCLUSION: The findings highlight an elevated prevalence and genetic susceptibility to OSA among paediatric narcolepsy patients, underscoring the necessity for clinical screening of OSA. Continued research is essential to clarify the pathogenic mechanisms and develop potential treatments.

Comparing the stability and reproducibility of brain-behavior relationships found using canonical correlation analysis and partial least squares within the ABCD sample.

Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset (N > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV1 for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, p < .001). LV1 for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

Clinical neuroscience research is going through a translational crisis largely due to the challenges of producing meaningful and generalizable results. Two critical limitations within clinical neuroscience research are the use of univariate statistics and between-study methodological variation. Univariate statistics may not be sensitive enough to detect complex relationships between several variables, and methodological variation poses challenges to the generalizability of the results. We compared two widely used multivariate statistical approaches, canonical correlations analysis (CCA) and partial least squares correlation (PLS), to determine the generalizability and stability of their solutions. We show that the properties of the measures inputted into the analysis likely play a more substantial role in the generalizability and stability of results compared to the specific approach applied (i.e., CCA or PLS).

Plastome evolution of Engelhardia facilitates phylogeny of Juglandaceae.

BACKGROUND: Engelhardia (Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of Engelhardia, the maternal genome evolution and phylogeny of Engelhardia in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight Engelhardia species and the outgroup Rhoiptelea chiliantha, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of Engelhardia and the whole Juglandaceae family. RESULTS: The 13 Engelhardia plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (TrnK-rps16, ndhF-rpl32, and ycf1) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only rpl22 and psaI genes showed positive selection (Ka/Ks > 1). Phylogenetic results fully supported Engelhardia as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The Engelhardia originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn't support rapid radiation occurred in the evolution history of Engelhardia. CONCLUSION: Our study fully supported the taxonomic treatment of at the section for Engelhardia species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of Engelhardia and the whole Juglandaceae family.

Stigma and its associations with self-confidence and sexual relations in 4 types of premature ejaculation.

BACKGROUND: Although men with premature ejaculation (PE) always show more negative emotions, including embarrassment, guilt and worry, this may be related to the stigma of PE. To investigated stigma and its associations with self-confidence and sexual relations in 4 PE syndromes, a survey was conducted in our hospital from December 2018 to December 2019 among 350 men with self-reported PE and 252 men without self-reported PE. The stigma, self-confidence and sexual relations were assessed by the Social Impact Scale (SIS) and Self-Esteem and Relationship questionnaire (SEAR), respectively. Ejaculation control, sexual life satisfaction and distress caused by PE were evaluated by the Index of PE. RESULTS: Men with self-reported PE had higher internalized shame and social isolation scores and lower SEAR scores than control subjects. The highest score of internalized shame and social isolation and the lowest score of SEAR appeared in men with lifelong PE (LPE). After age adjustment, the positive relationships were stronger between distress about PE and internalized shame. Whereas, the stronger negative associations were found between social isolation and sexual satisfaction. The strongest association was observed between social isolation and sexual relationship. Therefore, the stigma associated with PE adversely affects the self-confidence, self-esteem, and sexual relationships of men with PE. CONCLUSION: Men with PE, especially LPE, have a high level of stigma and disharmonious sexual relations, and often lack self-confidence and self-esteem, which have a certain negative impact on their physical and mental health and life. These will be the key issues to be considered when we formulate a personalized treatment plan for PE.

RéSUMé: CONTEXTE: Bien que les hommes atteints d'éjaculation précoce (EP) montrent plus d'émotions négatives toujours, notamment de l'embarras, de la culpabilité et de l'inquiétude, cela peut être lié à la stigmatisation de l'EP. Afin d'étudier la stigmatisation et ses associations avec la confiance en soi et les relations sexuelles dans 4 syndromes d'EP, une enquête a été menée dans notre hôpital de décembre 2018 à décembre 2019 auprès de 350 hommes atteints d'EP autodéclarée et de 252 hommes sans EP autodéclarée. La stigmatisation, la confiance en soi et les relations sexuelles ont été évaluées respectivement à l'aide de l'échelle d'impact social (SIS) et du questionnaire sur l'estime de soi et les relations (SEAR). Le contrôle de l'éjaculation, la satisfaction de la vie sexuelle et la détresse causée par l'EP ont été évalués par l'indice d'EP. RéSULTATS: Les hommes ayant une EP autodéclarée avaient des scores de honte intériorisée et d'isolement social plus élevés, et des scores SEAR inférieurs, à ceux des sujets témoins. Le score le plus élevé de honte intériorisée et d'isolement social, et le score le plus bas de SEAR, sont apparus chez les hommes atteints d'EP à vie (EPL). Après ajustement sur l'âge, les relations positives étaient plus fortes entre la détresse due à l'EP et la honte intériorisée. Les associations négatives les plus fortes ont été trouvées entre l'isolement social et la satisfaction sexuelle. Par conséquent, la stigmatisation associée à l'EP affecte négativement la confiance en soi, l'estime de soi et les relations sexuelles des hommes atteints d'EP. CONCLUSION: Les hommes atteints d'EP, en particulier ceux atteints d'EPL, ont un niveau élevé de stigmatisation et de relations sexuelles disharmonieuses, et ils manquent souvent de confiance en soi et d'estime de soi; ce qui a un impact négatif certain sur leur santé physique et mentale, et sur leur vie. Ce seront les questions clés à prendre en compte lorsque nous formulerons un plan de traitement personnalisé pour l'EP.

Network analysis of occupational stress and job satisfaction among radiologists.

Background: Occupational stress and job satisfaction significantly impact the well-being and performance of healthcare professionals, including radiologists. Understanding the complex interplay between these factors through network analysis can provide valuable insights into intervention strategies to enhance workplace satisfaction and productivity. Method: In this study, a convenience sampling method was used to recruit 312 radiologists for participation. Data on socio-demographic characteristics, job satisfaction measured by the Minnesota job satisfaction questionnaire revised short version (MJSQ-RSV), and occupational stress assessed using the occupational stress scale. Network analysis was employed to analyze the data in this study. Results: The network analysis revealed intricate patterns of associations between occupational stress and job satisfaction symptoms among radiologists. Organizational management and occupational interests emerged as crucial nodes in the network, indicating strong relationships within these domains. Additionally, intrinsic satisfaction was identified as a central symptom with high connectivity in the network structure. The stability analysis demonstrated robustness in the network edges and centrality metrics, supporting the reliability of the findings. Conclusion: This study sheds light on the complex relationships between occupational stress and job satisfaction in radiologists, offering valuable insights for targeted interventions and support strategies to promote well-being and job satisfaction in healthcare settings.

Pressure to not feel bad among (different-sex) romantic partners: prevalence, and correlates.

Western society generally highly values happiness. As a result, people sometimes experience pressure not to feel negative emotions. In this study, we comprehensively investigated this pressure, and how it manifests itself, in adult romantic relationships. Specifically, we first examined when, how often and how intensely people experience pressure not to feel bad from their romantic partners (94 different-sex couples). Additionally, we investigated (both between- and within-person) how this pressure is related to context (presence of, contact and or conflict with a partner), emotional processes (i.e. experienced sadness and anxiety, emotion suppression, and how their partner perceived their affect), and relationship well-being. Using experience sampling methodology data (6/14 reports per day over one week) we found that although participants generally did not experience strong pressure from their partner, they experienced some feelings of pressure about 50% of the time. Furthermore, within-person predictors associated with negative processes/emotions (i.e. negative emotions, conflict, emotion suppression) were related to the momentary frequency (odds) and/or intensity of perceived pressure not to feel bad. At the between-person level, individuals who experience more sadness, anxiety and reported suppressing their emotions more often tended to experience more and/or stronger pressure. Only weak associations with relationship well-being were found.

How Feminist Heterosexual Men Navigate Their Sexual Desire While Following Feminist Principles.

Feminist considerations have influenced how women and men view sex, affecting not only women's perspectives but also men's feelings about sexual desire with regard to gender equity. This might be especially the case among men who self-identify as feminist. However, how men should manage their sexual desire or communicate about it within relationships with women is not always clear in this evolving social climate. Thus, the current study aimed to explore the successes and/or struggles feminist heterosexual men experience while navigating their desires alongside feminist considerations. To explore this, we recruited feminist-identified heterosexual men in long-term relationships. We asked participants (N = 30) a series of questions regarding their sexual desire, considering the context of their long-term relationships and evolving gender norms, during a one-on-one interview via Zoom. Using thematic analysis, we identified 11 themes from the interview data. We found that, though the feminist men in this study were all aware of negative societal perceptions of heterosexual men's sexual desire, most men in this study did not feel conflicts between their feminist principles and their own sexual desires. This is because they reported already following feminist principles; those who felt ambivalent navigated this by communicating with their partners. Findings demonstrate the usefulness and positive impact men report feminism having on them, their sexuality, and their long-term relationships, by allowing them to better engage with their sexuality and partners.

Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

Childhood adversity and suicidal ideation in older Korean adults: unraveling the mediating mechanisms of mental health, physical health, and social relationships.

BACKGROUND: Suicide rates in older adults are much higher than those in younger age groups. Given the rapid increase in the proportion of older adults in Korea and the high suicide rate of this age group, it is worth investigating the mechanism of suicidal ideation for older adults. Generally, adverse childhood experiences are positively associated with suicidal ideation; however, it is not fully understood what mediating relationships are linked to the association between these experiences and current suicidal ideation. METHODS: The data from 685 older Korean adults were analyzed utilizing logistic regression, path analyses, and structural equation modeling. Based on our theoretical background and the empirical findings of previous research, we examined three separate models with mental health, physical health, and social relationship mediators. After that, we tested a combined model including all mediators. We also tested another combined model with mediation via mental health moderated by physical health and social relationships. RESULTS: The univariate logistic regression results indicated that childhood adversity was positively associated with suicidal ideation in older adults. However, multivariate logistic regression results demonstrated that the direct effect of childhood adversity became nonsignificant after accounting all variables. Three path models presented significant mediation by depression and social support in the association between childhood adversity and suicidal ideation. However, combined structural equation models demonstrated that only mediation by a latent variable of mental health problems was statistically significant. Social relationships moderated the path from mental health problems to suicidal ideation. CONCLUSIONS: Despite several limitations, this study has clinical implications for the development of effective strategies to mitigate suicidal ideation. In particular, effectively screening the exposure to adverse childhood experiences, early identification and treatment of depressive symptoms can play a crucial role in weakening the association between childhood adversity and suicidal ideation in older adults.

Impact of the COVID-19 pandemic on psychosocial health in rheumatic patients: A longitudinal study.

AIM: To describe the impact of the COVID-19 on the psychosocial health of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and systemic lupus erythematosus (SLE). DESIGN: Longitudinal observational study of a series of patients with rheumatic disease. METHODS: The main outcome measure was impairment of the ability to participate in social activities, as measured using the PROMIS-APS instrument Short Form-8a. We evaluated social activities in various settings and performed a multivariate analysis to study the association between worsening of social participation during the COVID-19 pandemic and implicated factors. RESULTS: One hundred and twenty-five patients had completed the prospective follow-up: 40 with AR (32%), 42 with SpA (33.6%), and 43 with SLE (34.4%). Overall, poorer mean PROMIS scores were recorded after the COVID-19 pandemic for: satisfaction with social roles (p=0.029), depression (p=0.039), and ability to participate in social activities (p=0.024). The factors associated with ability to participate in social activities after the COVID-19 pandemic were older age (ß=-0.215; p=0.012), diagnosis of SLE (ß=-0.203; p=0.015), depression (ß=-0.295; p=0.003) and satisfaction with social roles (ß=0.211; p=0.037). CONCLUSION: The ability to participate in social activities after the COVID-19 pandemic is affected in patients with rheumatic disease, especially in SLE.

A cross-omics data analysis strategy for metabolite-microbe pair identification.

Given the pivotal roles of metabolomics and microbiomics, numerous data mining approaches aim to uncover their intricate connections. However, the complex many-to-many associations between metabolome-microbiome profiles yield numerous statistically significant but biologically unvalidated candidates. To address these challenges, we introduce BiOFI, a strategic framework for identifying metabolome-microbiome correlation pairs (Bi-Omics). BiOFI employs a comprehensive scoring system, incorporating intergroup differences, effects on feature correlation networks, and organism abundance. Meanwhile, it establishes a built-in database of metabolite-microbe-KEGG functional pathway linking relationships. Furthermore, BiOFI can rank related feature pairs by combining importance scores and correlation strength. Validation on a dataset of cesarean-section infants confirms the strategy's validity and interpretability. The BiOFI R package is freely accessible at https://github.com/chentianlu/BiOFI.

Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents.

Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.

A wingless fly on a winged mammal: host-parasite dynamics between Basilia travassosi (Diptera: Nycteribiidae) and Myotis lavali (Chiroptera: Vespertilionidae).

Nycteribiidae encompasses a specialized group of wingless blood-sucking flies that parasitize bats worldwide. Such relationships are frequently species- or genus-specific, indicating unique eco-evolutionary processes. However, despite this significance, comprehensive studies on the relationships of these flies with their hosts, particularly in the New World, have been scarce. Here, we provide a detailed description of the parasitological patterns of nycteribiid flies infesting a population of Myotis lavali bats in the Atlantic Forest of northeastern Brazil, considering the potential influence of biotic and abiotic factors on the establishment of nycteribiids on bat hosts. From July 2014 to June 2015, we captured 165 M. lavali bats and collected 390 Basilia travassosi flies. Notably, B. travassosi displayed a high prevalence and was the exclusive fly species parasitizing M. lavali in the surveyed area. Moreover, there was a significant predominance of female flies, indicating a female-biased pattern. The distribution pattern of the flies was aggregated; most hosts exhibited minimal or no parasitism, while a minority displayed heavy infestation. Sexually active male bats exhibited greater susceptibility to parasitism compared to their inactive counterparts, possibly due to behavioral changes during the peak reproductive period. We observed a greater prevalence and abundance of flies during the rainy season, coinciding with the peak reproductive phase of the host species. No obvious correlation was observed between the parasite load and bat body mass. Our findings shed light on the intricate dynamics of nycteribiid-bat interactions and emphasize the importance of considering various factors when exploring bat-parasite associations.

Biomechanical, biochemical, and histological characterization of sacroiliac joint cartilage in the Yucatan minipig.

Although the sacroiliac (SI) joint can be a source of lower back and buttock pain, no comprehensive characterization studies on SI cartilage have been conducted. Using the minipig as a large animal model, this study conducted the first biomechanical, biochemical, and histological characterization of SI joint cartilage. Because previous literature has reported that sacral cartilage and iliac cartilage within the SI joint are histologically distinct, concomitantly it was expected that functional properties of the sacral cartilage would differ from those of the iliac cartilage. Creep indentation, uniaxial tension, biochemical, and histological analyses were conducted on the sacral and iliac cartilage of skeletally mature female Yucatan minipigs (n = 6-8 for all quantitative tests). Concurring with prior literature, the iliac cartilage appeared to be more fibrous than the sacral cartilage. Glycosaminoglycan content was 2.2 times higher in the sacral cartilage. The aggregate modulus of the sacral cartilage was 133 ± 62 kPa, significantly higher than iliac cartilage, which only had an aggregate modulus of 51 ± 61 kPa. Tensile testing was conducted in both cranial-caudal and ventral-dorsal axes, and Young's modulus values ranged from 2.5 ± 1.5 MPa to 13.6 ± 1.5 MPa, depending on anatomical structure (i.e., sacral vs. iliac) and orientation of the tensile test. The Young's modulus of sacral cartilage was 5.5 times higher in the cranial-caudal axis and 2.0 times higher in the ventral-dorsal axis than the iliac cartilage. The results indicate that the sacral and iliac cartilages are functionally distinct from each other. Understanding the distinct differences between sacral and iliac cartilage provides insight into the structure and function of the SI joint, which may inform future research aimed at repairing SI joint cartilage.

Adult Child Financial Disadvantage and the Cognitive Trajectories among Older Parents in the United States.

OBJECTIVES: Adult child socioeconomic status (SES) has been identified as a predictor of older parents' cognitive aging. However, studies have primarily relied on educational attainment as the sole measure of adult child SES. We evaluated the relationship between adult children's financial disadvantage and cognitive outcomes of older parents in the United States. METHODS: We used data from U.S. Health and Retirement Study (2000-2014, n = 15,053 respondents > 50 years with at least one adult child). Adult child financial disadvantage was measured with three indicators of extremely low income, unemployment, and lack of home ownership. We used linear mixed models to estimate the association between adult child financial disadvantage and the rate of decline in verbal memory scores, controlling for respondents' socio-demographic characteristics. RESULTS: Having at least one adult child (vs. no adult children) with extremely low income was found to be associated with lower verbal memory (b = -0.041, 95% CI: -0.043, -0.039) at baseline. There was a small but significant association with the rate of decline in verbal memory z-scores (b = 0.004, 95% CI: 0.000, 0.008) and some evidence of heterogeneity by parent gender, marital status, and SES. DISCUSSION: Offspring financial disadvantage may be influential for older parents' initial level of memory function, although evidence of associations with memory decline was weak. Public policy interventions aimed at improving the economic conditions of adult children may indirectly benefit the late-late cognitive performance of disadvantaged parents.

Phenotypic Relationships Between Meat Quality Parameters And Residual Feed Intake In Japanese Black Wagyu Cattle.

Japanese black Wagyu cattle are renowned for producing some of the world's most highly valued and recognized beef with exceptional marbling. Therefore, the primary focus of genetic selection for Wagyu cattle has historically been on meat quality, particularly achieving high marbling levels. However, even when the price of the final product is high, production costs also remain high, especially considering that most of the feed has to be imported. The objective of this study was to evaluate phenotypic relationships between feed efficiency, specifically residual feed intake, as the most utilized efficiency index in cattle, and various meat quality parameters in Japanese black cattle in order to determine if a common phenotypic selection for these parameters could be feasible. For this, a total of 39 Wagyu cattle were evaluated for feed efficiency over their entire fattening period (900 days), with a focus on RFI as a key indicator. Animals were fed high-starch diets with vitamin A deprivation to achieve the desired marbling. Results revealed positive correlations between feed efficiency and meat quality in Wagyu cattle. Specifically, animals with higher feed efficiency exhibited superior meat quality traits, including firmness, marbling, and overall meat rating. When comparing the 20 most extreme RFI individuals (10 most and 10 least efficient), we observed that efficient RFI animals showed increased marbling levels (+13.2%, P=0.05) and ranking quality (+12%, P=0.06) of the meat. In conclusion, this research contributes to understanding the interplay between feed efficiency and meat quality in Japanese black Wagyu cattle. Phenotypic correlations observed suggest the possibility of incorporating RFI criteria into genetic selection programs without compromising the prized meat quality traits of Wagyu beef.

Validation of the Interpersonal Relationships in Eating Disorders (IR-ED) Scale in an Eating Disorder Sample.

OBJECTIVE: Interpersonal problems have been identified as a plausible mechanism underlying the onset and maintenance of eating disorders. The Interpersonal Relationships in Eating Disorders (IR-ED) scale is the first eating disorders-specific measure of interpersonal problems, which was developed in a nonclinical sample. The aims of the current study were to (a) confirm the factor structure of the IR-ED within a large clinical sample, (b) investigate measurement invariance of the IR-ED across nonclinical and clinical samples, (c) examine the convergent validity of the IR-ED using a generic measure of interpersonal problems, and (d) investigate the incremental clinical utility of the IR-ED in uniquely predicting eating disorder symptomatology. METHOD: Treatment-seeking individuals (N = 437) completed the IR-ED at their initial assessment appointment at a specialist eating disorder outpatient service. RESULTS: A multiple-group confirmatory factor analysis supported an invariant bifactor structure comprising a general interpersonal problems factor and two group factors-Avoidance of Body Evaluation and Food-Related Interpersonal Tension. Convergent validity was demonstrated by a large, statistically significant correlation with a generic measure of interpersonal problems (r = 0.62, p < 0.001). A series of structural equation models further revealed unique incremental predictive utility of the IR-ED for eating disorder symptomatology. DISCUSSION: The IR-ED has strong psychometric properties and may prove beneficial in the assessment, formulation, and treatment of eating-specific interpersonal problems among patients with eating disorders.