Relationship-Contingent Self-Esteem As A Moderator Of Borderline Personality Features And Mate Retention

The current study examined the relationship between borderline personality features, relationship-contingent self-esteem, and mate retention behaviors. Participants were recruited through Amazon’s Mechanical Turk. They completed the Personality Inventory for the DSM-5, the Rosenberg Self-Esteem Scale, the Relationship-Contingent Self- Esteem Scale, and the Mate Retention Inventory-Short Form. Participants then received feedback through the modified Future Alone Manipulation, where they were randomly assigned to one of three feedback conditions: positive, negative, or negative control. After the feedback, participants completed the Mate Retention Inventory-Short Form to assess their response to feedback. Contrary to our predictions, borderline personality features (BPF) were not correlated with relationship-contingent self-esteem (RCSE), and RCSE and threat did not moderate the relationship between BPF and mate retention behaviors (MRB). Consistent with our hypotheses, BPF predicted the used of cost-inflicting MRB. Interestingly, RCSE predicted the use of benefit-provisioning MRB. This research is the first to address the relationship between BPF and RCSE and provides insight into individuals differences in relationship behaviors

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

Cartilage matrix homeostasis involves a dynamic balance between numerous signals that modulate chondrocyte functions. This study aimed at elucidating the role of the extracellular glucose concentration in modulating anabolic and catabolic gene expression in normal and osteoarthritic (OA) human chondrocytes and its ability to modify the gene expression responses induced by pro-anabolic stimuli, namely Transforming Growth Factor-β (TGF). For this, we analyzed by real time RT-PCR the expression of articular cartilage matrix-specific and non-specific genes, namely collagen types II and I, respectively. The expression of the matrix metalloproteinases (MMPs)-1 and -13, which plays a major role in cartilage degradation in arthritic conditions, and of their tissue inhibitors (TIMP) was also measured. The results showed that exposure to high glucose (30 mM) increased the mRNA levels of both MMPs in OA chondrocytes, whereas in normal ones only MMP-1 increased. Collagen II mRNA was similarly increased in normal and OA chondrocytes, but the increase lasted longer in the later. Exposure to high glucose for 24 h prevented TGF-induced downregulation of MMP-13 gene expression in normal and OA chondrocytes, while the inhibitory effect of TGF on MMP-1 expression was only partially reduced. Other responses were not significantly modified. In conclusion, exposure of human chondrocytes to high glucose, as occurs in vivo in diabetes mellitus patients and in vitro for the production of engineered cartilage, favors the chondrocyte catabolic program. This may promote articular cartilage degradation, facilitating OA development and/or progression, as well as compromise the quality and consequent in vivo efficacy of tissue engineered cartilage

Differential effects of the essential oils of Lavandula luisieri and Eryngium duriaei subsp. juresianum in cell models of two chronic inflammatory diseases

CONTEXT: Effective drugs to treat osteoarthritis (OA) and inflammatory bowel disease (IBD) are needed. OBJECTIVE: To identify essential oils (EOs) with anti-inflammatory activity in cell models of OA and IBD. MATERIALS AND METHODS: EOs from Eryngium duriaei subsp. juresianum (M. Laínz) M. Laínz (Apiaceae), Laserpitium eliasii subsp. thalictrifolium Sennen & Pau (Apiaceae), Lavandula luisieri (Rozeira) Rivas-Martínez (Lamiaceae), Othantus maritimus (L.) Hoff. & Link (Asteraceae), and Thapsia villosa L. (Apiaceae) were analyzed by GC and GC/MS. The anti-inflammatory activity of EOs (5-200 μg/mL) was evaluated by measuring inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) activation (total and phosphorylated IκB-α), in primary human chondrocytes and the intestinal cell line, C2BBe1, stimulated with interleukin-1β (IL-1β) or interferon-γ (IFN-γ), IL-1β and tumor necrosis factor-α (TNF-α), respectively. RESULTS: The EO of L. luisieri significantly reduced iNOS (by 54.9 and 81.0%, respectively) and phosphorylated IκB-α (by 87.4% and 62.3%, respectively) in both cell models. The EO of E. duriaei subsp. juresianum caused similar effects in human chondrocytes, but was inactive in intestinal cells, even at higher concentrations. The EOs of L. eliasii subsp. thalictrifolium and O. maritimus decreased iNOS expression by 45.2 ± 8.7% and 45.2 ± 6.2%, respectively, in C2BBe1 cells and were inactive in chondrocytes. The EO of T. villosa was inactive in both cell types. DISCUSSION AND CONCLUSION: This is the first study showing anti-inflammatory effects of the EOs of L. luisieri and E. duriaei subsp. juresianum. These effects are specific of the cell type and may be valuable to develop new therapies or as sources of active compounds with improved efficacy and selectivity towards OA and IBD

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

Osteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpenes, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti-catabolic and pro-anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1β-induced nitric oxide production (IC50=37.3μg/ml and 85.3µg/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and -3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1β-treated cells. None of the compounds tested was able to increase the expression of cartilage matrix-specific genes (collagen II and aggrecan), but both compounds prevented the increased expression of the non-cartilage specific, collagen I, induced by IL-1β. These data show that myrcene has significant anti-inflammatory and anti-catabolic effects in human chondrocytes and, thus, its ability to halt or, at least, slow down cartilage destruction and osteoarthritis progression warrants further investigation

Reliability and Predictive Validity of Screener/Assessment Tools in Nebraska Juvenile Diversion

Juvenile diversion is offered in most counties throughout Nebraska to eligible youth; and although state guidelines require the use of a screening or assessment tool, the tools utilized are not standardized or uniform statewide. This report quantifies whether the various tools are being reliably administered and are effectively predicting diversion completion and future system involvement. The Juvenile Justice Institute gathered item-level risk/needs screener and assessment data from all juvenile diversion programs receiving Community-based Aid (CBA) funds. Overall, 3,916 youth were assessed for a juvenile diversion program between July 1st, 2015 and June 30th, 2017. The Youth Level of Service Inventory/Case Management Inventory (YLS) comprised the largest number of completed assessments (n = 2,193), followed by the Nebraska Youth Screen (NYS; n = 1,512), and the Arizona Risk-Needs Assessment (ARNA; n = 211). First, we tested the reliability of each tool, which is how well it is consistently performing at predicting risk (i.e., less error in measurement). Reliability analyses revealed the YLS/CMI had the strongest internal consistency of the three measures, which means the items are grouped well together to measure the construct (i.e., risk level). The items within the NYS, however, demonstrated the strongest item-total correlations, which means these items were most related to the overall construct (i.e., risk level). Both the NYS and ARNA had poor internal consistency. Second, we performed Receiver Operating Curve (ROC) analyses to determine the predictive validity of each tool, utilizing both unsuccessful discharge from diversion and future system involvement as outcomes. Results revealed all three tools had predictive validity for unsuccessful diversion completion with large effect sizes (i.e., measure of strength of the relationship). Furthermore, while all three tools demonstrated predictive validity for future system involvement with small to moderate effect sizes, when we tested predictive validity by both gender and race/ethnicity, only the YLS accurately predicted future system involvement for girls, none of the tools accurately predicted future system involvement for Black/African American youth, and only the ARNA accurately predicted future system involvement for Hispanic youth. While it is always recommended to screen and/or assess youth, the tools currently being utilized in Nebraska juvenile diversion programs are not reliably and validly measuring risk for all youth assessed. The most problematic items within each tool were those relating to prior convictions or prior contacts with the legal system. Because this is a diversion population, presumably with little to no prior juvenile justice system involvement, these items poorly capture risk in this population, which in turn contributes to lower reliability and predictive validity. While these findings do not provide definitive results for us to whole-heartedly recommend a tool for juvenile diversion programs at this time, our recommendation is to explore creating/utilizing a risk assessment tool that removes items that measure previous legal system involvement or norming current tools without those items. Future research and practice should continue to explore gender and racial/ethnic differences within youth assessment

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin

OBJECTIVE: Chondrocytes respond to insulin, but the presence and role of the specific high affinity insulin receptor (InsR) has never been demonstrated. This study determined whether human chondrocytes express the InsR and compared its abundance and function in normal and osteoarthritis (OA) human chondrocytes. DESIGN: Cartilage sections were immunostained for detection of the InsR. Non-proliferating chondrocyte cultures from normal and OA human cartilage were treated with 1nM or 10nM insulin for various periods. InsR, insulin-like growth factor receptor (IGFR), aggrecan and collagen II mRNA levels were assessed by real time RT-PCR. InsR, glucose transporter (GLUT)-1, phospho-InsRbeta and phospho-Akt were evaluated by western blot and immunofluorescence. Glucose transport was measured as the uptake of [3H]-2-Deoxy-d-Glucose (2-DG). RESULTS: Chondrocytes staining positively for the InsR were scattered throughout the articular cartilage. The mRNA and protein levels of the InsR in OA chondrocytes were approximately 33% and 45%, respectively, of those found in normal chondrocytes. Insulin induced the phosphorylation of the InsRbeta subunit. Akt phosphorylation and 2-DG uptake increased more intensely in normal than OA chondrocytes. Collagen II mRNA expression increased similarly in normal and OA chondrocytes while aggrecan expression remained unchanged. The Phosphoinositol-3 Kinase (PI3K)/Akt pathway was required for both basal and insulin-induced collagen II expression. CONCLUSIONS: Human chondrocytes express functional InsR that respond to physiologic insulin concentrations. The InsR seems to be more abundant in normal than in OA chondrocytes, but these still respond to physiologic insulin concentrations, although some responses are impaired while others appear fully activated. Understanding the mechanisms that regulate the expression and function of the InsR in normal and OA chondrocytes can disclose new targets for the development of innovative therapies for OA

Expression and function of K(ATP) channels in normal and osteoarthritic human chondrocytes: possible role in glucose sensing.

ATP-sensitive potassium [K(ATP)] channels sense intracellular ATP/ADP levels, being essential components of a glucose-sensing apparatus in various cells that couples glucose metabolism, intracellular ATP/ADP levels and membrane potential. These channels are present in human chondrocytes, but their subunit composition and functions are unknown. This study aimed at elucidating the subunit composition of K(ATP) channels expressed in human chondrocytes and determining whether they play a role in regulating the abundance of major glucose transporters, GLUT-1 and GLUT-3, and glucose transport capacity. The results obtained show that human chondrocytes express the pore forming subunits, Kir6.1 and Kir6.2, at the mRNA and protein levels and the regulatory sulfonylurea receptor (SUR) subunits, SUR2A and SUR2B, but not SUR1. The expression of these subunits was no affected by culture under hyperglycemia-like conditions. Functional impairment of the channel activity, using a SUR blocker (glibenclamide 10 or 20 nM), reduced the protein levels of GLUT-1 and GLUT-3 by approximately 30% in normal chondrocytes, while in cells from cartilage with increasing osteoarthritic (OA) grade no changes were observed. Glucose transport capacity, however, was not affected in normal or OA chondrocytes. These results show that K(ATP) channel activity regulates the abundance of GLUT-1 and GLUT-3, although other mechanisms are involved in regulating the overall glucose transport capacity of human chondrocytes. Therefore, K(ATP) channels are potential components of a broad glucose sensing apparatus that modulates glucose transporters and allows human chondrocytes to adjust to varying extracellular glucose concentrations. This function of K(ATP) channels seems to be impaired in OA chondrocytes