Insulin-like Growth Factor 1 and Transforming Growth Factor-β Stimulate Cystine/Glutamate Exchange Activity in Dental Pulp Cells

Introduction The growth factors insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line (Henry Schein Inc, New York, NY). Because the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-β were through the enhancement of an endogenous antioxidant mechanism. Methods We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-β, focusing on the glutathione system and the role of cystine/glutamate exchange (system xc-). Results We found that the toxicity of Durafill VS and Flow Line was attenuated by the addition of glutathione monoethylester, suggesting a specific role for the cellular antioxidant glutathione. Supporting this hypothesis, we found that IGF-1 and TGF-β were protective against the toxicity of the glutathione synthesis inhibitor buthionine sulfoximine. Because levels of cellular cystine are the limiting factor in the production of glutathione, we tested the effects of IGF-1 and TGF-β on cystine uptake. Both growth factors stimulated system xc–mediated cystine uptake. Furthermore, they attenuated the glutathione depletion induced by Durafill VS and Flow Line. Conclusions The results suggest that IGF-1 and TGF-β are protective through the stimulation of system xc–mediated cystine uptake, leading to maintenance of cellular glutathione. This novel action of growth factors on dental pulp cells has implications not only for preventing toxicity of dental materials but also for the general function of these cells

Ethnic Identity, Risk, and Protective Factors Related to Substance Abuse Among Mexican American Students

This study examines the relationship between ethnic identity, risk and protective factors for substance use and academic achievement. Risk factors include deviant behavior and susceptibility to peer influence, while the protective factor is self-reported confidence not to use substances. The sample consists of 2,370 Mexican American students enrolled in eighth, ninth, and tenth grades. Results of the analysis (MANOVA) revealed that females had more positive ethnic identity than males. Furthermore, males were significantly more susceptible to peer influence, reported higher levels of deviant behavior, used more substances and had lower grade point averages than females. There was no significant difference in their confidence not to use substances

Emotion Differentiation as a Protective Factor Against Nonsuicidal Self-Injury in Borderline Personality Disorder

Evidence that nonsuicidal self-injury (NSSI) serves a maladaptive emotion regulation function in borderline personality disorder (BPD) has drawn attention to processes that may increase risk for NSSI by exacerbating negative emotion, such as rumination. However, more adaptive forms of emotion processing, including differentiating broad emotional experiences into nuanced emotion categories, might serve as a protective factoragainst NSSI. Using an experience-sampling diary, the present study tested whether differentiation of negative emotion was associated with lower frequency of NSSI acts and urges in 38 individuals with BPD who reported histories of NSSI. Participants completed a dispositional measure of rumination and a 21-day experience-sampling diary, which yielded an index of negative emotion differentiation and frequency of NSSI acts and urges. A significant rumination by negative emotion differentiation interaction revealed that rumination predicted higher rates of NSSI acts and urges in participants with difficulty differentiating their negative emotions. The results extend research on emotion differentiation into the clinical literature and provide empirical support for clinical theories that suggest emotion identification and labeling underlie strategies for adaptive self-regulation and decreased NSSI risk in BPD

Detecting Selection Bias in Community Disseminations of Universal Family-Based Prevention Programs

The goals of the present study were to demonstrate a method for examining selection bias in large-scale implementations of community-based family skills programs, and to explore the nature of selection bias in one such implementation. We used evaluation data from a statewide dissemination of a popular substance abuse prevention program (N programs = 42; N youth = 294). The program’s evaluation measures were designed to match publicly available data on risk and protective factor scales collected in the state’s schools, which enabled us to construct a comparison sample of non-participants (N = 20,608). We then examined the risk status of adolescents in both groups to determine whether risk and protective factor scores were related to the probability of program participation. Participation was predicted by both demographics and risk and protective factor scores. Among families with younger adolescents, program attendance was associated with lower risk; among families with older adolescents, participation was associated with both higher risk (on parental management skills) and lower risk (on substance use). Selection effects must be identified and corrected for in order to calculate valid estimates of program benefits, but in community-based disseminations, the necessary supplemental comparison sample is difficult to obtain. The evaluation design and analytic approach described here can be used in program evaluations of real-world, “bottom-up” dissemination efforts to identify who attends a program, which in turn can help to inform recruitment strategies, to pinpoint possible selection influences on measured program outcomes, and to refine estimates of program costs and benefits.repeated auction; selectivity; prevention program; community-based implementation; program evaluation

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Tissue specific induction of p62/sqstm1 by farnesoid X receptor

Background: Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily and is a ligand-activated transcription factor essential for maintaining liver and intestinal homeostasis. FXR is protective against carcinogenesis and inflammation in liver and intestine as demonstrated by the development of inflammation and tumors in the liver and intestine of FXR knock-out mice. However, mechanisms for the protective effects of FXR are not completely understood. This study reports a novel role of FXR in regulating expression of Sqstm1, which encodes for p62 protein. p62 plays an important role in maintaining cellular homeostasis through selective autophagy and activating signal transduction pathways, such as NF-κB to support cell survival and caspase-8 to initiate apoptosis. FXR regulation of Sqstm1 may serve as a protective mechanism. Methods and Results: This study showed that FXR bound to the Sqstm1 gene in both mouse livers and ileums as determined by chromatin immunoprecipitation. In addition, FXR activation enhanced transcriptional activation of Sqstm1 in vitro. However, wild-type mice treated with GW4064, a synthetic FXR ligand, showed that FXR activation induced mRNA and protein expression of Sqstm1/p62 in ileum, but not in liver. Interestingly, FXR-transgenic mice showed induced mRNA expression of Sqstm1 in both liver and ileum compared to wild-type mice. Conclusions: Our current study has identified a novel role of FXR in regulating the expression of p62, a key factor in protein degradation and cell signaling. Regulation of p62 by FXR indicates tissue-specific and gene-dosage effects. Furthermore, FXR-mediated induction of p62 may implicate a protective mechanism of FXR. © 2012 Williams et al

Incidence and public health burden of sunburn among beachgoers in the United States.

The beach environment creates many barriers to effective sun protection, putting beachgoers at risk for sunburn, a well-established risk factor for skin cancer. Our objective was to estimate incidence of sunburn among beachgoers and evaluate the relationship between sunburn incidence and sun-protective behaviors. A secondary analysis, of prospective cohorts at 12 locations within the U.S. from 2003 to 2009 (n&nbsp;=&nbsp;75,614), were pooled to evaluate sunburn incidence 10-12&nbsp;days after the beach visit. Behavioral and environmental conditions were cross-tabulated with sunburn incidence. Multivariable logistic regression was used to estimate the association between new sunburn and sun-protective behaviors. Overall, 13.1% of beachgoers reported sunburn. Those aged 13-18&nbsp;years (16.5%), whites (16.0%), and those at beach locations along the Eastern Seaboard (16.1%), had the highest incidence of sunburn. For those spending ≥5&nbsp;h in the sun, the use of multiple types of sun protection reduced odds of sunburn by 55% relative to those who used no sun protection (Odds Ratio&nbsp;=&nbsp;0.45 (95% Confidence Interval:0.27-0.77)) after adjusting for skin type, age, and race. Acute health effects of sunburn tend to be mild and self-limiting, but potential long-term health consequences are more serious and costly. Efforts to encourage and support proper sun-protective behaviors, and increase access to shade, protective clothing, and sunscreen, can help prevent sunburn and reduce skin cancer risk among beachgoers

Administration of Interleukin-15 Peptide Improves Cardiac Function in a Mouse Model of Myocardial Infarction.

Interleukin-15 is a pleotropic factor, capable of modulating metabolism, survival, proliferation, and differentiation in many different cell types. The rationale behind this study relates to previous work demonstrating that IL-15 is a major factor present in stem cell extracts, which protects cardiomyocytes subjected to hypoxic stress in vitro. The objective of this current study was to assess whether administration of IL-15 peptide will also show protective effects in vivo. The data indicate that administration of IL-15 reduces cell death, increases vascularity, decreases scar size, and significantly improves left ventricular ejection fraction in a mouse model of myocardial infarction

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

Reported associations between asthma and acute lymphoblastic leukemia: insights from a hybrid simulation study.

Numerous studies have reported a protective association between asthma and acute lymphoblastic leukemia (ALL), but the causal structure of this association remains unclear. We present a hybrid simulation to examine the compatibility of this association with uncontrolled confounding by infection or another unmeasured factor. We generated a synthetic cohort using inputs on the interrelations of asthma, ALL, infections, and other suggested risk factors from the literature and the Danish National Birth Cohort. We computed odds ratios (ORs) between asthma and ALL in the synthetic cohort with and without adjustment for infections and other (including unmeasured) confounders. Only if infection was an extremely strong risk factor for asthma (OR of 10) and an extremely strong protective factor against ALL (OR of 0.1) was the asthma-ALL association compatible with the literature (OR of 0.78). Similarly, strong uncontrolled confounding by an unmeasured factor could downwardly bias the asthma-ALL association, but not enough to replicate findings in the literature. This investigation illustrates that the reported protective association between asthma and ALL is unlikely to be entirely due to uncontrolled confounding by infections or an unmeasured confounder alone. Simulation can be used to advance our understanding of risk factors for rare outcomes as demonstrated by this study