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In the following research, we specifically assessed the feasibility of a novel AS-1411-chitosan (CS)-gold nanoparticle (AuNPs) delivery system to carry methotrexate (MTX) into the cancer cells. The designed system had a spherical shape with average size of 62 ± 2.4 nm, the zeta potential of −32.1 ± 1.4 mV, and released MTX in a controlled pH- and time-dependent manner. CS-AuNPs could successfully penetrate the breast cancer cells and release the therapeutic drug, and ultimately, be accumulated by the nucleolin-AS1411 targeting mechanism within the in vivo environment. The anticancer activity of MTX was attributed to the induction of mitochondria membrane potential loss and nuclear fragmentation, which leads to apoptotic death. Moreover, the cellular internalization confirmed the high potential in the elimination of cancer cells without notable cytotoxicity on non-target cells. Therefore, it was concluded that the AS1411-CS-AuNPs with considerable in vitro and in vivo results could be utilized as a favorable system for breast cancer treatment.

Extraction from the herbs was performed using the Soxhlet method. Various formula was synthesized for niosomes containing the extracts through thin film synthesis technique, and the most efficient formulation was selected. Afterwards, physicochemical properties of niosomes, including size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficacy (EE%), extract release rate, non-interactive action between the extracts and niosomes, antibacterial potential, and cellular uptake were assessed. Finally, the toxicity level of the niosomes to breast cancer cells was compared and their impact on the expression of p53 and MCL-1 was evaluated. Our data demonstrated that the synthesized niosomes were sensitive to the temperature and pH. Also, the niosomes containing Hedera Helix extract (Nio-HHE) sized 97.7 nm, with a zeta potential of −19.9 ± 6.7 mV, PDI of 0.35, and 58 ± 2.4% encapsulation efficacy showed more toxicity to the cancer cells than the niosomes of Glycyrrhiza glabra extract (Nio-GGE) with the size of 111 ± 8.5 nm, zeta potential of −23.5 ± 4.5 mV, PDI of 0.113, and 69 ± 1.2% encapsulation efficacy. The former system proved to have more antibacterial potential, and affect the expression of the oncogenes more than the latter. Meanwhile, both niosomal systems demonstrated an acceptable cellular uptake, and no chemical interaction with the extracts was observed. Furthermore, useful function of the synthesized niosomes was confirmed by morphological assessments. Our data confirmed that encapsulation of herbal extracts improves their anticancer and antibacterial potential. We concluded that Nio-HHE has more significant antitumor effects on breast cancer cells than Nio-GGE. Consequently, applying nano drug delivery systems based on herbal therapy could mitigate the side effects resulting from chemotherapy and radiotherapy, and offer promising perspectives for treatment of breast cancer.

Assessment of human epidermal growth factor receptor-2 (HER2) tumor marker status is an impressive factor in screening, diagnosing and monitoring breast cancer (BC). The electrochemical biosensor is a revolutionary method in cancer diagnosis, which is used in this research to detect HER2+ circulating tumor cells. The electrochemical activity, size, shape, and morphology of the synthesized nanomaterials were analyzed. The hybrid nanocomposite established by the coupling of reduced graphene oxide nanosheets (rGONs) and rhodium nanoparticles (Rh-NPs) on the surface of graphite electrode resulted in improved surface area, electrochemical activity, and biocompatibility. The graphite electrode-based aptasensor (g-aptasensor) demonstrated exceptional performance against HER2-overexpressed SKBR3 cancer cells, with a linear dynamic range of 5.0 to 10.0 × 104 cells/mL, an analytical limit of detection (LOD) as low as 1.0 cell/mL, and a limit of quantification (LOQ) of 3.0 cells/mL. The G-rich DNA aptamers can fold into an intermolecular G-quadruplex, which specifically bind to the target molecule. Consequently, the advantages of this highly efficient nanocomposite platform include broad dynamic range, high specificity, selectivity, stability, reproducibility, and low cost. These characteristics indicate that the fabricated nanobiosensor has a high potential for use in detecting and monitoring HER2 level for the care of BC patients and clinical diagnosis.

In this paper, we reviewed the recent advances in nanoscale modifications and evaluated their potential for dental implant applications. Surfaces at the nanoscale provide remarkable features that can be exploited to enhance biological activities. Herein, titanium and its alloys are considered as the main materials due to their background as Ti-based implants, which have been yielding satisfactory results over long-term periods. At first, we discussed the survivability and the general parameters that have high impacts on implant failure and the necessities of nanoscale modification. Afterward, fabrication techniques that can generate nanostructures on the endosseous implant body are categorized as mechanical, chemical, and physical methods. These techniques are followed by biomimetic nanotopographies (e.g., nanopillars, nanoblades, etc.) and their biological mechanisms. Alongside the nanopatterns, the applications of nanoparticles (NPs) including metals, ceramics, polymers, etc., as biofunctional coating or delivery systems are fully explained. Finally, the biophysiochemical impacts of these modifications are discussed as essential parameters for a dental implant to provide satisfactory information for future endeavors.

To date, the use of nanocarriers has been developed in various fields, especially in cancer treatment. Graphene oxide (GO) is a novel drug delivery system that eagerly attracts the attention of many researchers due to its unique features. For the first time, a biocompatible AS1411 APT-GO-COOH was synthesized for the co-delivery of chemotherapeutics and herbal drugs. Here, a human gastric adenocarcinoma cell line (AGS) was targeted with aptamer-carboxylated graphene oxide (APT-CGO) containing anticancer drugs (curcumin (CUR) and doxorubicin (DOX)). The current study aimed to assess the anti-cancer effect of combination therapy, as well as target genes and proteins interfering in the development of gastric cancer. After attachment of APT to CGO, the drugs (CUR and DOX) were loaded on the carrier, establishing a co-delivery system. Then, physical characteristics, release profile, cytotoxicity assay, cellular uptake, expression rates of the genes (RB1, CDK2, AKT, and NF-KB) and proteins (RB1, CDK2), and the apoptosis rate were determined. The designed co-delivery system for the drugs (CUR and DOX) and APT showed a thermo- and pH-sensitive drug release behavior that successfully reduced the expression of CDK2, AKT, and NF-KB while it enhanced RB1 expression at the gene and protein levels. Also, APT-CGO-drugs were successfully targeted to the AGS cell line, leading to a highly inhibitory property against this cell line compared to CGO-drugs. It seems that the co-delivery of CUR and DOX along with APT as a targeting agent was more effective than CGO-drugs, suggesting a promising candidate for the treatment of gastric cancer. The results showed that this biofunctionalized nanocarrier could reduce the cytotoxicity of the drugs in normal cells and could increase efficiency.

Cancer treatment is challenging due to late-stage diagnosis, drug resistance and systemic toxicity of chemotherapeutic agents. The formulation of the drug into nanoparticles (NPs) can enhance the treatment efficacy and effectiveness. Therefore, a new cationic niosomal formulation, which contains Tween 80, Tween 60, cholesterol and lysine amino acid as a platform model to enhance transfection efficacy and reach more acceptable stability, and curcumin (Cur) as a biological anti-cancer drug, are introduced. Here, the authors focused on the design and synthesis of novel lysine-mediated niosomal NPs for the effectual and controlled release of the antitumor agent, Cur, and turned to optimize niosome formulations, concerning the volume of cholesterol and surfactant to implement these anticancer agents, simultaneously. The characterization of NPs s was carried out and the results showed the successful synthesis of Cur-entrapped niosomal NPs with high efficacy, sufficient positive charges and a favorable size (95/33 nm). The in vitro studies have been performed to investigate the cytotoxicity, cellular uptake and apoptosis of normal and cancer cells treated by black niosome, free Cur and niosom-loaded Cur. The results showed that implementing agents by niosome caused enhanced cytotoxicity, uptake and anticancer activity in cancer cells in comparison with normal cells. Furthermore, the effect of this nanodrug was surveyed on the 4T1 xenografted Balb/C mouse tumor model. Cur delivery to cancer models caused a higher tumor inhibition rate than in other groups.

Objective: American Indian and Alaska Native (AI/AN) populations experience greater health disparities in alcohol use outcomes compared with the general population. This secondary data analysis examines cultural factors related to alcohol use in reservation-based American Indian (AI) adults ( N = 65; 41 males; mean age = 36.7 years) in a randomized controlled trial of a culturally tailored contingency management (CM) program. It was hypothesized that individuals with higher rates of cultural protective factors would have lower rates of alcohol use, whereas individuals with higher rates of risk factors would have higher rates of alcohol use. It was also hypothesized that enculturation would moderate the relationship between treatment group and alcohol use., Method: Generalized linear mixed modeling was used to calculate odds ratios (ORs) for the repeated measure, biweekly urine tests of the biomarker, ethyl glucuronide (EtG), across 12 weeks. The relationships between alcohol use (abstinence [EtG < 150 ng/ml]) or heavy drinking [EtG > 500 ng/ml]) and culturally relevant protective (enculturation, years lived on the reservation) and risk factors (discrimination, historical loss, historical loss symptoms) were examined., Results: There was a negative association between enculturation and probability of submitting a heavy drinking urine sample (OR = 0.973; 95% CI [0.950, 0.996], p = .023), indicating that enculturation may serve as a protective factor against heavy drinking., Conclusions: Cultural factors (e.g., enculturation) may be important constructs to assess and incorporate into treatment planning with AI adults engaged in alcohol treatment., Competing Interests: Michael McDonell has received funding from a tribally owned for-profit medical clinic to evaluate clinic outcomes; that Tribe and clinic were not involved in the current study. The other authors report no conflicts of interest. The views expressed do not necessarily represent the views of any participating Tribe or partnering organization.

Aims: Achieving an effective biocompatible system for siRNAs delivery to the tumor site remains a significant challenge. Materials & methods: Selenium nanoparticles (SeNPs) modified by chitosan (CS) and hyaluronic acid (HA) were fabricated for PLK1 siRNAs ( siPLK1 ) delivery to the bladder cancer cells. The HA-CS-SeNP@siPLK1 efficacy was evaluated using in vitro and in vivo models. Results: HA-CS-SeNP@siPLK1 was selectively internalized into T24 cells through clathrin-mediated endocytosis. Treatment with HA-CS-SeNP@siPLK1 successfully silenced the PLK1 gene, inhibited cell proliferation and induced cell cycle arrest in vitro . HA-CS-SeNP@siPLK1 could also inhibit tumor growth in vivo without causing systemic toxicity. Conclusion: Our results suggest that HA-CS-SeNPs may provide a good vehicle for delivering siPLK1 to the bladder tumor site.

Doxorubicin (DOX) is a common chemotherapy agent that is used in clinics for the treatment of a wide spectrum of cancers. Herein, a novel approach for improving doxorubicin loading on nanoparticles and also controlled release is suggested using crosslinking doxorubicin molecules with glutaraldehyde. We investigated the loading efficiency of doxorubicin on CoFe 2 O 4 nanoparticles in the absence and presence of glutaraldehyde. Based on the feasible, one-pot, and time-saving approach suggested here, the crosslinked DOX showed loading efficiency about twice more in comparison with the non-crosslinked DOX. In vitro doxorubicin release of three formulations including DOX crosslinked with glutaraldehyde (DOXGA), DOX loaded on CoFe 2 O 4 (CFDOX) and DOX loaded on CoFe 2 O 4 using glutaraldehyde (CFDOXGA) yielded a sustained release. The kinetic models such as first-order, Sahlin-Peppas, and Higuchi were employed for further exploration of DOX release profile. Our suggested method might extend to other nanomaterial-based drug delivery formulations to promote drug delivery efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Approximately 25% of patients with staphylococcus aureus bacteremia (SAB) develop infective endocarditis (IE), which has a consequent mortality of 25-46%. Current guidelines recommend routine transthoracic echocardiography (TTE) for patients with SAB; transesophageal echocardiogram (TEE) is reserved for those in whom initial TTE is negative and clinical suspicion for IE remains high. We sought to elucidate high risk features of SAB associated with the development of IE that warrant a TEE after a negative TTE. This retrospective study included 213 patients who were diagnosed with SAB at the University of New Mexico Hospital between 2010-2020. A pre-determined list of clinical risk factors along with TTE and TEE status was extracted from the electronic medical record. The primary outcome was development of IE in patients with SAB. Multivariate logistic regression analysis was used to identify clinical risk factors for IE. Moreover, sensitivity and specificity of TTE and TEE was calculated. Out of 213 patients with SAB, 68 patients met diagnostic criteria for IE. Most patients (n = 209) underwent TTE and 171 patients underwent subsequent TEE. The overall sensitivity of TTE was 63% and overall sensitivity of TEE was 88%. Multivariate analysis showed significantly increased risk of IE in patients who had implanted permanent pacemaker (aOR 32.3, CI 5.23 - 281, p < 0.001) and persistent fever (aOR 6.97, CI 2.42 - 21.0 P < 0.001). Based on our analysis, we recommend that TEE should be strongly considered after negative TTE in SAB patients with intracardiac prosthetics or persistent fever despite appropriate antibiotic therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo , the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shahidi, Abazari, Dayati, Haghiralsadat, Oroojalian and Tofighi.)

Nowadays, radiotherapy is one of the most effective treatments for breast cancer. In order to overcome the radioresistance of cancer cells, radio-sensitizing agents can be used combined with irradiation to increase the therapeutic efficiency. Curcumin can enhance the radiosensitivity of cancer cells and decrease their viability by the accumulation of these cells in the G2 phase. The encapsulation of curcumin in a nanoniosomal delivery system increases aqueous solubility and bioavailability, resulting in increased radio sensitivity. The present study aimed to enhance the radio-sensitizing effect of the curcumin-containing nanoniosome (Cur-Nio) when combined with irradiation. Thus, curcumin (0.5 mg ml -1 ) was loaded on a PEGylated nanoniosome containing Tween 60, cholesterol, DOTAP, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (at ratios of 70:30:10:5, respectively) by the thin-film hydration method. The particle size, zeta potential, entrapment efficiency, and drug-release rate of formulated nanoniosomes were determined. In order to assess cytotoxicity and apoptosis, different doses of irradiation along with various concentrations of free curcumin and Cur-Nio (single or in combination with irradiation) were treated with breast cancer cells. The particle size and zeta potential of Cur-Nio were reported to be 117.5 nm and -15.1 mV, respectively. The entrapment efficiency (EE%) and loading capacities were 72.3% and 6.68%, respectively. The drug-release rate during 6 h was 65.9%. Cell survival in the presence of curcumin at doses of 1 and 3 Gy showed a significant reduction compared with cells irradiated at 48 h and 72 h ( p < 0.000). Also, the rate of cytotoxicity and apoptosis was significantly higher in cells treated with the combination of curcumin-containing nanoniosomes and irradiation in comparison with those treated with free curcumin. These findings indicate that the efficacy of pre-treatment with Cur-Nio as a radiosensitizer during radiotherapy enhances irradiation-induced breast cancer cell apoptosis and is a useful strategy to increase the effectiveness of breast cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Afereydoon, Haghiralsadat, Hamzian, Shams, Hemati, Naghib, Shabani, Zandieh-doulabi and Tofighi.)

Bladder cancer is one of the concerning urological malignant diseases in the world, which has a clinical need for effective targeted therapy. The development of nanotechnology-based gene delivery to bladder tumor sites is an effective strategy for targeted cancer therapy with low/no toxicity. With this view, in the present work, the mesoporous silica nanoparticles (MSNs) modified with c(RGDfK)-PLGA-PEG [c(RGDfK)-MSN NPs] were constructed for co-delivery of miR-34a and siPD-L1 within bladder cancer cells and tissues. Our findings showed that miR-34a is downregulated while PD-L1 is up-regulated in cell lines and animal studies. This nano-carrier is biocompatible in the serum environment and effectively protects miR-34a and siPD-L1 against serum degradation. However, we showed that c(RGDfK)-MSN NPs could simultaneously downregulate PD-L1 expression and up-regulate miR-34a in the T24 cells and T24 mice model and enhance anti-tumor effects both in vivo and in vitro . In conclusion, these findings presented new suggestions for improving targeted therapeutic strategies with specified molecular objectives for bladder cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shahidi, Abazari, Dayati, Bakhshi, Zavarreza, Modarresi, Haghiralsadat, Rahmanian, Naghib and Tofighi.)

Stress regulation begins to develop in the first year of life through interactions with caregivers, particularly in the presence of stressors. High quality caregiving, characterized by maternal sensitivity and responsiveness to the infant's emotional cues, is particularly important in the development of infant stress regulation. The purpose of this study was to assess the longitudinal stability of, and associations between, maternal interactive behavior and infant stress regulation (indexed by positive infant affect and cortisol reactivity) in response to the Still Face paradigm (SF) in a cohort of infants born preterm (< 32 weeks gestation, N = 22) at four months and nine months (adjusted age). The percent of time mothers spent using specific interaction styles (contingent maternal interaction (CMI), attention seeking, and watching) during Play/baseline, Reunion#1, and Reunion#2 SF episodes was calculated To assess infant stress regulation, two indices were obtained at both 4 and 9 months during the SF paradigm: the percent of positive affect displayed over each SF episode (0-100%) and a neuroendocrine stress response score based on salivary cortisol reactivity. We found three non-significant but medium-large effect size differences between 4 and 9 month variables, with more positive findings at 9 months. Regarding stability within the 4 month and 9 month episodes, maternal behavior and positive infant affect were non-significantly but moderately stable, with maternal watching behavior being particularly stable. Positive infant affect stability between Reunion#1 and Reunion#2 at 4 months was significantly greater than positive infant affect stability across these two episodes at 9 months. Regarding stability across 4 and 9 month (same) episodes, CMI and positive infant affect showed modest but non-significant stability across (same) 4 and 9 month episodes. Finally, with positive infant affect at Reunion#2 as the "outcome" of the Still Face, CMI at both 4 month Play and Reunion#1 episodes were significantly correlated with this "outcome." Further, positive infant affect at Reunion#2 was more strongly correlated with CMI at both Play and Reunion#1 for 4 month old compared with 9 month old infants. Thus, sensitive care appears particularly important for younger infants born preterm, and mothers' behavior early in a repeated stress exposure paradigm may be particularly important in maintaining positive infant affect and in the development of infants' stress regulation more generally. Identifying the longer-term effects of early stress on infant stress regulation, and its relationship with maternal interaction, has important implications for understanding trajectories of regulatory patterns and deficits. A greater understanding of these relationships is particularly important given that greater emotion and neuroendocrine stress regulation in infancy have been directly associated with numerous positive outcomes throughout childhood., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mechanisms of behavior change are the processes through which interventions are hypothesized to cause changes in outcomes. Latent growth curve mediation models (LGCMM) are recommended for investigating the mechanisms of behavior change because LGCMM models establish temporal precedence of change from the mediator to the outcome variable. The Correlated Augmented Mediation Sensitivity Analyses (CAMSA) App implements sensitivity analysis for LGCMM models to evaluate if a mediating path (mechanism) is robust to potential confounding variables. The CAMSA approach is described and applied to simulated data, and data from a research study exploring a mechanism of change in the treatment of substance use disorder., Competing Interests: Disclosure statement. The authors do not have any conflicts of interest.

Mediation analysis relies on an untestable assumption of the no omitted confounders, which posits that an omitted variable that confounds the relationships between the antecedent, mediator, and outcome variables cannot exist. One common model in alcohol addiction studies is a nonrandomized latent growth curve mediation model (LGCMM), where the antecedent variable is not randomized, the two covarying mediators are latent intercept and slope modeling longitudinal effect of the repeated measures mediator, and an outcome variable that measures alcohol use. An important gap in the literature is lack of sensitivity analysis techniques to assess the effect of the violation of the no omitted confounder assumption in a nonrandomized LGCMM. We extend a sensitivity analysis technique, termed correlated augmented mediation sensitivity analysis (CAMSA), to a nonrandomized LGCMM. We address several unresolved issues in conducting CAMSA for the nonrandomized LGCMM and present: (a) analytical results showing how confounder correlations model a confounding bias, (b) algorithms to address admissible values for confounder correlations, (c) accessible R code within an SEM framework to conduct our proposed sensitivity analysis, and (d) an empirical example. We conclude that conducting sensitivity analysis to ascertain robustness of the mediation analysis is critical., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tofighi.)

Inhibitory control, the ability to suppress irrelevant thoughts or actions, is central to cognitive and social development. Protracted maturation of frontal brain networks has been reported as a major restraint for this ability, yet, young children, when motivated, successfully inhibit delayed responses. A better understanding of the age-dependent neural inhibitory mechanism operating during the awaiting-to-respond window in children may elucidate this conundrum. We recorded ERPs from children and parental adults to a visual-spatial working memory task with delayed responses. Cortical activation elicited during the first 1000 ms of the awaiting-to-respond window showed, as predicted by prior studies, early inhibitory effects in prefrontal ERPs (P200, 160-260 ms) associated with top-down attentional-biasing, and later effects in parietal/occipital ERPs (P300, 270-650 ms) associated with selective inhibition of task-irrelevant stimuli/responses and recurrent memory retrieval. Children successfully inhibited delayed responses and performed with a high level of accuracy (often over 90%), although, the prefrontal P200 displayed reduced amplitude and uniformly delayed peak latency, suggesting low efficacy of top-down attentional-biasing. P300, however, with no significant age-contrasts in latency was markedly elevated in children over the occipital/inferior parietal regions, with effects stronger in younger children. These results provide developmental evidence supporting the sensorimotor recruitment model of visual-spatial working memory relying on the occipital/parietal regions of the early maturing dorsal-visual network. The evidence is in line with the concept of age-dependent variability in the recruitment of cognitive inhibitory networks, complementing the former predominant focus on frontal lobes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Latent class mediation modeling is designed to estimate the mediation effect when both the mediator and the outcome are latent class variables. We suggest using an adjusted one-step approach in which the latent class models for the mediator and the outcome are estimated first to decide on the number of classes, then the latent class models and the mediation model are jointly estimated. We present both an empirical demonstration and a simulation study to compare the performance of this one-step approach to a standard three-step approach with modal assignment (modal) and four different modern three-step approaches. Results from the study indicate that unadjusted modal, which ignores the classification errors of the latent class models, produced biased mediation effects. On the other hand, the adjusted one-step approach and the modern three-step approaches performed well with respect to bias for estimating mediation effects, regardless of measurement quality (i.e., model entropy) and latent class size. Among the three-step approaches we investigated, the maximum likelihood method with modal assignment and the BCH correction with robust standard error estimators are good alternatives to the adjusted one-step approach, given their unbiased standard error estimations.

Infants who experience sensitive caregiving are at lower risk for numerous adverse outcomes. This is especially true for infants born preterm, leading them to be more susceptible to risks associated with poorer quality caregiving. Some research suggests that preterm and full-term infants differ on temperament, which may contribute to these findings. This study aimed to investigate associations between infant temperament (negative emotionality, positive affectivity/surgency, and orienting/regulatory capacity) and maternal sensitivity among infants born preterm (M = 30.2 weeks) and full term. It was hypothesized that mothers of infants born preterm and mothers of infants with more difficult temperaments would display lower sensitivity, indicated by lower responsiveness to nondistress, lower positive regard, and higher intrusiveness. Videotaped play interactions and a measure of temperament (Infant Behavior Questionnaire) were coded for 18 preterm and 44 full-term infants at 9 months (corrected) age. Results suggest that mothers of preterm and full-term infants differed significantly in responding to their infants, but these results cannot be explained by infant temperament. Preterm status and sociodemographic risk emerged as correlates of maternal behavior, such that mothers of infants born preterm and mothers with greater sociodemographic risk displayed lower levels of maternal sensitivity., (© 2021 Michigan Association for Infant Mental Health.)

Mediation analysis is an important approach for investigating causal pathways. One approach used in mediation analysis is the test of an indirect effect, which seeks to measure how the effect of an independent variable impacts an outcome variable through 1 or more mediators. However, in many situations the proposed tests of indirect effects, including popular confidence interval-based methods, tend to produce poor Type I error rates when mediation does not occur and, more generally, only allow dichotomous decisions of "not significant" or "significant" with regards to the statistical conclusion. To remedy these issues, we propose a new method, a likelihood ratio test (LRT), that uses nonlinear constraints in what we term the model-based constrained optimization (MBCO) procedure. The MBCO procedure (a) offers a more robust Type I error rate than existing methods; (b) provides a p value, which serves as a continuous measure of compatibility of data with the hypothesized null model (not just a dichotomous reject or fail-to-reject decision rule); (c) allows simple and complex hypotheses about mediation (i.e., 1 or more mediators; different mediational pathways); and (d) allows the mediation model to use observed or latent variables. The MBCO procedure is based on a structural equation modeling framework (even if latent variables are not specified) with specialized fitting routines, namely with the use of nonlinear constraints. We advocate using the MBCO procedure to test hypotheses about an indirect effect in addition to reporting a confidence interval to capture uncertainty about the indirect effect because this combination transcends existing methods. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Complex mediation models, such as a two-mediator sequential model, have become more prevalent in the literature. To test an indirect effect in a two-mediator model, we conducted a large-scale Monte Carlo simulation study of the Type I error, statistical power, and confidence interval coverage rates of 10 frequentist and Bayesian confidence/credible intervals (CIs) for normally and nonnormally distributed data. The simulation included never-studied methods and conditions (e.g., Bayesian CI with flat and weakly informative prior methods, two model-based bootstrap methods, and two nonnormality conditions) as well as understudied methods (e.g., profile-likelihood, Monte Carlo with maximum likelihood standard error [MC-ML] and robust standard error [MC-Robust]). The popular BC bootstrap showed inflated Type I error rates and CI under-coverage. We recommend different methods depending on the purpose of the analysis. For testing the null hypothesis of no mediation, we recommend MC-ML, profile-likelihood, and two Bayesian methods. To report a CI, if data has a multivariate normal distribution, we recommend MC-ML, profile-likelihood, and the two Bayesian methods; otherwise, for multivariate nonnormal data we recommend the percentile bootstrap. We argue that the best method for testing hypotheses is not necessarily the best method for CI construction, which is consistent with the findings we present.

In mediation analysis, conditions necessary for commonly recommended tests, including the confidence interval (CI)-based tests, to produce an accurate Type I error, do not generally hold for finite sample sizes and non-normally distributed model residuals. This is typically the case because of the complexity of testing a null hypothesis about indirect effects. To remedy these issues, we propose two extensions of the recently developed asymptotic Model-based Constrained Optimization (MBCO) likelihood ratio test (LRT), a promising new model comparison method for testing a general function of indirect effects. The proposed tests, semi-parametric and parametric bootstrap MBCO LRT are shown to yield a more accurate Type I error rate in smaller sample sizes and under various degrees of non-normality of the model residuals compared to the asymptotic MBCO LRT and the CI-based methods. We provide R script in the Supplemental Materials to perform all three MBCO LRTs., (Copyright © 2020 Tofighi.)

The development and evaluation of mindfulness-based interventions for a variety of psychological and medical disorders has grown exponentially over the past 20 years. Yet, calls for increasing the rigor of mindfulness research and recognition of the difficulties of conducting research on the topic of mindfulness have also increased. One of the major difficulties is the measurement of mindfulness, with varying definitions across studies and ambiguity with respect to the meaning of mindfulness. There is also concern about the reproducibility of findings given few attempts at replication. The current secondary analysis addressed the issue of reproducibility and robustness of the construct of self-reported mindfulness across two separate randomized clinical trials of mindfulness-based relapse prevention (MBRP), as an aftercare treatment for substance use disorder. Specifically, we tested the robustness of our previously published findings, which identified a latent construct of mindfulness as a significant mediator of the effect of MBRP on reducing craving following treatment. First, we attempted to replicate the findings in a separate randomized clinical trial of MBRP. Second, we conducted sensitivity analyses to test the assumption of the no-omitted confounder bias in a mediation model. The effect of MBRP on self-reported mindfulness and overall mediation effect failed to replicate in a new sample. The effect of self-reported mindfulness in predicting craving following treatment did replicate and was robust to the no-omitted confounder bias. The results of this work shine a light on the difficulties in the measurement of mindfulness and the importance of examining the robustness of findings., Competing Interests: Conflict of Interests: None.

Latent growth curve mediation models are increasingly used to assess mechanisms of behavior change. For latent growth mediation model, like any another mediation model, even with random treatment assignment, a critical but untestable assumption for valid and unbiased estimates of the indirect effects is that there should be no omitted variable that confounds indirect effects. One way to address this untestable assumption is to conduct sensitivity analysis to assess whether the inference about an indirect effect would change under varying degrees of confounding bias. We developed a sensitivity analysis technique for a latent growth curve mediation model. We compute the biasing effect of confounding on point and confidence interval estimates of the indirect effects in a structural equation modeling framework. We illustrate sensitivity plots to visualize the effects of confounding on each indirect effect and present an empirical example to illustrate the application of the sensitivity analysis.

Objective: Few studies have found support for coping as a mechanism of behavior change (MOBC) following coping skills training interventions for alcohol use disorder (AUD). One potential reason for null findings is heterogeneity in the patterns of coping skills acquired during treatment. This study sought to identify latent classes of coping and to test the latent class variable as a mediator of the effect of a combined behavioral intervention for AUD., Method: Secondary analyses of data from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study (N = 1,124; mean age = 44.4 years; 69.1% male; 23.2% non-White), a multisite study of medication and behavioral treatments for individuals with AUD. Latent class mediation models were estimated to test whether patterns of alcohol-specific coping mediated the effect of combined behavioral intervention with medication management, as compared with medication management only, on drinking outcomes 12 months following treatment., Results: Three classes were identified, which differed in repertoire broadness, or the degree in which a wide range of different skills were used. Coping repertoire class was a significant mediator of the effect of the combined behavioral intervention on drinking outcomes. Receiving the combined behavioral intervention, in addition to medication management, predicted a greater likelihood of expected classification in the broad coping repertoire class, which in turn was associated with significant improvements in drinking outcomes., Conclusions: Using the novel methodological approach of latent class mediation, this study identified coping repertoire as a significant mediator of behavioral intervention efficacy for AUD. Future work examining heterogeneity in mediators and outcomes may help refine AUD treatment to be maximally effective.

To draw valid inference about an indirect effect in a mediation model, there must be no omitted confounders. No omitted confounders means that there are no common causes of hypothesized causal relationships. When the no-omitted-confounder assumption is violated, inference about indirect effects can be severely biased and the results potentially misleading. Despite the increasing attention to address confounder bias in single-level mediation, this topic has received little attention in the growing area of multilevel mediation analysis. A formidable challenge is that the no-omitted-confounder assumption is untestable. To address this challenge, we first analytically examined the biasing effects of potential violations of this critical assumption in a two-level mediation model with random intercepts and slopes, in which all the variables are measured at Level 1. Our analytic results show that omitting a Level 1 confounder can yield misleading results about key quantities of interest, such as Level 1 and Level 2 indirect effects. Second, we proposed a sensitivity analysis technique to assess the extent to which potential violation of the no-omitted-confounder assumption might invalidate or alter the conclusions about the indirect effects observed. We illustrated the methods using an empirical study and provided computer code so that researchers can implement the methods discussed.

Multilevel mediation analysis examines the indirect effect of an independent variable on an outcome achieved by targeting and changing an intervening variable in clustered data. We study analytically and through simulation the effects of an omitted variable at level 2 on a 1-1-1 mediation model for a randomized experiment conducted within clusters in which the treatment, mediator, and outcome are all measured at level 1. When the residuals in the equations for the mediator and the outcome variables are fully orthogonal, the two methods of calculating the indirect effect (ab, c - c') are equivalent at the between- and within-cluster levels. Omitting a variable at level 2 changes the interpretation of the indirect effect and will induce correlations between the random intercepts or random slopes. The equality of within-cluster ab and c - c' no longer holds. Correlation between random slopes implies that the within-cluster indirect effect is conditional, interpretable at the grand mean level of the omitted variable., (© 2012 The British Psychological Society.)

This article describes the RMediation package,which offers various methods for building confidence intervals (CIs) for mediated effects. The mediated effect is the product of two regression coefficients. The distribution-of-the-product method has the best statistical performance of existing methods for building CIs for the mediated effect. RMediation produces CIs using methods based on the distribution of product, Monte Carlo simulations, and an asymptotic normal distribution. Furthermore, RMediation generates percentiles, quantiles, and the plot of the distribution and CI for the mediated effect. An existing program, called PRODCLIN, published in Behavior Research Methods, has been widely cited and used by researchers to build accurate CIs. PRODCLIN has several limitations: The program is somewhat cumbersome to access and yields no result for several cases. RMediation described herein is based on the widely available R software, includes several capabilities not available in PRODCLIN, and provides accurate results that PRODCLIN could not.

This study presents formulae for the covariances between parameter estimates in a single mediator model. These covariances are necessary to build confidence intervals (CI) for effect size measures in mediation studies. We first analytically derived the covariances between the parameter estimates in a single mediator model. Using the derived covariances, we computed the multivariate-delta standard errors, and built the 95% CIs for the effect size measures. A simulation study evaluated the accuracy of the standard errors as well as the Type I error, power, and coverage of the CIs using various parameter values and sample sizes. Finally, we presented a numerical example and a SAS MACRO that calculates the CIs for the effect size measures.

Appropriately centering Level 1 predictors is vital to the interpretation of intercept and slope parameters in multilevel models (MLMs). The issue of centering has been discussed in the literature, but it is still widely misunderstood. The purpose of this article is to provide a detailed overview of grand mean centering and group mean centering in the context of 2-level MLMs. The authors begin with a basic overview of centering and explore the differences between grand and group mean centering in the context of some prototypical research questions. Empirical analyses of artificial data sets are used to illustrate key points throughout. The article provides a number of practical recommendations designed to facilitate centering decisions in MLM applications., (Copyright 2007 APA, all rights reserved.)