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Bullying is a persistent social and behavioral problem in the United States. Bullying victimization and perpetration are linked to a host of negative physical, social, and emotional outcomes. Research suggests that a key risk factor for bullying behaviors is adverse childhood experiences (ACEs). On the other hand, positive childhood experiences (PCEs) may counter some of the negative effects of ACEs. This study (a) assesses the independent effects of ACEs and PCEs on adolescent bullying victimization and perpetration, and (b) examines whether ACEs and PCEs interact to affect bullying victimization and perpetration.We use data from the 2020 to 2021 National Survey of Children's Health, a nationally representative survey of children ages 0 to 17 in the United States. The analytic sample was limited to children who were 6 years old or older at the time of the survey ( N  = 60,809). Using caregiver reports of bullying victimization and perpetration, we created a cumulative ACEs scale comprised of 10 items and a cumulative PCEs scale comprised of eight measures. We then estimated a set of logistic regression models to predict bullying behaviors. The results showed that ACEs are associated with a higher likelihood of both bullying victimization and perpetration. Although PCEs have a slight mitigating effect, ACEs and PCEs interact such that even in the presence of PCEs, children with many ACEs still have a higher likelihood of both bullying victimization and perpetration. This highlights the considerable impact of ACEs on bullying behaviors. These findings suggest that enhancing ACE-aware care and ACE prevention is important because even promoting PCEs is unlikely to decrease bullying levels on their own., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Recent research suggests that bullying victimization increases the risk of handgun carrying among adolescents. Yet, little to no research has considered whether different types of bullying victimization (i.e., physical, verbal, cyber) shape handgun-carrying behaviors among youth. Understanding these relationships can, however, inform intervention efforts addressing youths' access to and motives for carrying handguns. The purposes of this study are twofold. First, we establish whether there is a relationship between bullying victimization and youth handgun carrying. Second, we seek to determine whether certain types of bullying victimization are associated more strongly with handgun carrying than others, using data from the 2022 Florida Youth Substance Abuse Survey (FYSAS, n = 47,572), a statewide representative sample of Florida middle school and high school students. The results from multinomial regression models indicate that physical bullying and cyberbullying victimization were associated with an elevated risk of carrying a handgun in the past 12 months. Interventions that underscore the importance of comprehensive anti-bullying interventions that not only address traditional physical aggression among adolescents but also mitigate the evolving challenges posed by unsupervised digital spaces may reduce the risk of handgun carrying., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: Many studies have investigated the effects of adverse childhood experiences (ACEs) on the health, development, and well-being of children and adolescents. However, most studies have failed to examine whether childhood adversity and ecological factors interact to influence relevant health outcomes., Objective: We used pooled data from the 2018-19 National Survey of Children's Health (n = 24,817) to assess the relationship between ACEs, neighborhood quality, and three domains of adolescent health and well-being: mental health (i.e., symptoms of anxiety problems and depression), neurodevelopmental health, and behavioral problems., Methods: Nine types of ACEs were captured in the NSCH data. Logistic regression models were employed to explore the relationship between ACEs, neighborhood quality, and adolescent health and well-being., Results: Our results indicate that ACEs are associated with each of these domains, with higher ACE scores associated with a higher risk of detrimental outcomes. Neighborhood disorder is also associated with several outcomes. Consistent with our expectations, in the presence of neighborhood disorder the association between higher ACEs exposure and behavior/conduct problems or neurodevelopmental disorders is larger., Conclusions: Our results have important implications for understanding how individual and contextual factors may combine to influence child health and behaviors, as well as offering policy recommendations that might help children who experience traumatic events., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lung tissue resident memory (TRM) cells are thought to play crucial roles in lung host defense. We have recently shown that immunization with the adjuvant LTA1 (derived from the A1 domain of E. coli heat labile toxin) admixed with OmpX from K. pneumoniae can elicit antigen specific lung Th17 TRM cells that provide serotype independent immunity to members of the Enterobacteriaceae family. However, the upstream requirements to generate these cells are unclear. Single-cell RNA-seq showed that vaccine-elicited Th17 TRM cells expressed high levels of IL-1R1, suggesting that IL-1 family members may be critical to generate these cells. Using a combination of genetic and antibody neutralization approaches, we show that Th17 TRM cells can be generated independent of caspase-1 but are compromised when IL-1α is neutralized. Moreover IL-1α could serve as a molecular adjuvant to generate lung Th17 TRM cells independent of LTA1. Taken together, these data suggest that IL-1α plays a major role in vaccine-mediated lung Th17 TRM generation., (© 2024. The Author(s).)

A large literature demonstrates that social capital has positive effects on outcomes for children, but we know little about whether social capital is durable, i.e., whether its effects persist long after its creation. We use two nationally representative data sets of U.S. high school students and structural equation modeling designed for binomial outcomes to examine the durability of returns to social capital created in the family on both college enrollment and college completion. Controlling for selected school characteristics, race, family, SES and other factors, results suggest that family social capital continues to have strong associations with outcomes increasingly distant from its creation. Family SES has a smaller but positive effect on both college enrollment and college completion. These findings suggest that social capital can be a durable good if formed in the family, and that family SES is also influential., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dufur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Craniofacial and dentoalveolar abnormalities are present in all types of osteogenesis imperfecta (OI). Mouse models of the disorder are critical to understand these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. The Brtl/+ and G610c/+ are moderately severe and mild-type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT-scanned heads of 3-wk-old, 3-mo-old, and 6-mo-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT ( P  < .05), whereas G610c/+ skulls are similar in length to their WT counterparts. The Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible ( P  < .05). By contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 mo ( P  < .05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars ( P  < .05), which are similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in the craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Immune responses to antigens, including innocuous, self, tumor, microbial, and vaccine antigens, differ between males and females. The quest to uncover the mechanisms for biological sex differences in the immune system has intensified, with considerable literature pointing toward sex hormonal influences on immune cell function. Sex steroids, including estrogens, androgens, and progestins, have profound effects on immune function. As such, drastic changes in sex steroid concentrations that occur with aging (e.g., after puberty or during the menopause transition) or pregnancy impact immune responses and the pathogenesis of immune-related diseases. The effect of sex steroids on immunity involves both the concentration of the ligand and the density and distribution of genomic and nongenomic receptors that serve as transcriptional regulators of immune cellular responses to affect autoimmunity, allergy, infectious diseases, cancers, and responses to vaccines. The next frontier will be harnessing these effects of sex steroids to improve therapeutic outcomes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Adverse childhood experiences (ACEs) are associated with several negative health and behavioral outcomes during adolescence, but most of the extant research has employed ACEs scores at one or two time points. Studies have not assessed whether latent class ACEs trajectories affect adolescent problem behaviors and conditions., Objectives: We used longitudinal data from the Fragile Families and Child Wellbeing Study (FFCWS, n = 3444) to assess ACEs at several time points and empirically developed latent class trajectories. We then examined the sociodemographic characteristics of youth who belonged to each trajectory group. We next evaluated whether the ACEs trajectories during childhood were associated with delinquent behavior, substance use, and symptoms of anxiety or depression. Finally, we explored whether closeness to mother buffered the impact of ACEs on these outcomes., Methods: Eight types of ACEs were captured in the FFCWS data. ACE scores were assessed at year one, three, five, and nine, along with the outcomes during year 15. Trajectories were estimated with a semiparametric latent class models., Results: The analysis revealed three latent trajectories during childhood: a low/none ACEs group, a medium exposure group, and a high exposure group. Adolescents in the high exposure group manifested a heightened risk of involvement in delinquent behaviors and substance use. They also reported more symptoms of anxiety and depression than their peers in the low/none and medium exposure groups., Conclusions: Repeated exposure to ACEs during childhood can have serious negative repercussions in the lives of adolescents, but maternal closeness may buffer their effects. Scholars should continue to examine the dynamics of ACEs exposure during childhood by using empirical approaches appropriate for identifying age-graded trajectories., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There is an urgent need for new treatment options for carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), which is a common cause of life-threatening hospital- and community-acquired infections. Prophylactic or therapeutic vaccination may offer an approach to control these infections, however, none has yet been approved for human use. Here, we report the chemical synthesis of an outer core tetra- and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae. The oligosaccharides were equipped with an aminopentyl linker, which facilitated conjugation to the carrier proteins CRM 197 and BSA. Mice immunized with the glycoconjugate vaccine candidates elicited antibodies that recognized isolated LPS as well as various strains of K. pneumoniae. The successful preparation of the oligosaccharides relied on the selection of monosaccharide building blocks equipped with orthogonal hydroxyl and amino protecting groups. It allowed the differentiation of three types of amines of the target compounds and the installation of a crowded 4,5-branched Kdo moiety., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Here, we describe the continued synthetic molecular evolution of a lineage of host-compatible antimicrobial peptides (AMP) intended for the treatment of wounds infected with drug-resistant, biofilm-forming bacteria. The peptides tested are variants of an evolved AMP called d-amino acid CONsensus with Glycine Absent (d-CONGA), which has excellent antimicrobial activities in vitro and in vivo . In this newest generation of rational d-CONGA variants, we tested multiple sequence-structure-function hypotheses that had not been tested in previous generations. Many of the peptide variants have lower antibacterial activity against Gram-positive or Gram-negative pathogens, especially variants that have altered hydrophobicity, secondary structure potential, or spatial distribution of charged and hydrophobic residues. Thus, d-CONGA is generally well tuned for antimicrobial activity. However, we identified a variant, d-CONGA-Q7, with a polar glutamine inserted into the middle of the sequence, that has higher activity against both planktonic and biofilm-forming bacteria as well as lower cytotoxicity against human fibroblasts. Against clinical isolates of Klebsiella pneumoniae , innate resistance to d-CONGA was surprisingly common despite a lack of inducible resistance in Pseudomonas aeruginosa reported previously. Yet, these same isolates were susceptible to d-CONGA-Q7. d-CONGA-Q7 is much less vulnerable to AMP resistance in Gram-negative bacteria than its predecessor. Consistent with the spirit of synthetic molecular evolution, d-CONGA-Q7 achieved a critical gain-of-function and has a significantly better activity profile.

Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans-specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C. albicans)-reactive Th17 cells from the intestine to the liver. The antifungal agent nystatin decreased C. albicans-specific Th17 cells in the liver and reduced ethanol-induced liver disease in mice. Transgenic mice expressing T cell receptors (TCRs) reactive to Candida antigens developed more severe ethanol-induced liver disease than transgene-negative littermates. Adoptively transferring Candida-specific TCR transgenic T cells or polyclonal C. albicans-primed T cells exacerbated ethanol-induced liver disease in wild-type mice. Interleukin-17 (IL-17) receptor A signaling in Kupffer cells was required for the effects of polyclonal C. albicans-primed T cells. Our findings indicate that ethanol increases C. albicans-specific Th17 cells, which contribute to alcohol-associated liver disease., Competing Interests: Declaration of interests B.S. has been consulting for Ambys Medicines, Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, and Takeda. B.S.’s institution UC San Diego has received research support from Artizan Biosciences, Axial Biotherapeutics, BiomX, CymaBay Therapeutics, NGM Biopharmaceuticals, Prodigy Biotech, and Synlogic Operating Company. B.S. is the founder of Nterica Bio. UC San Diego has filed several patents with B.S. and Y.D. as inventors related to this work. P.S. received grant support from Gilead Sciences Belgium., (Published by Elsevier Inc.)

Background: Psychoactive substance use is a transient behavior among many adolescents and diminishes as they mature, but some engage in heavy forms of substance use, which increases their risk of health and behavioral challenges. A consistent predictor of substance use among youth is family structure, with adolescents living in single-parent, stepparent, or no-parent families at higher risk than others of several forms of substance use. The objective of this research was to investigate whether unstructured socializing mediated the association between family structure and heavy alcohol or substance use., Methods: Data from 30 nations ( n = 65,737) were used to test the hypothesis using a generalized structural equation model and tests of mediation., Results: The analysis furnished clear support for a mediation effect among adolescents living with a single parent but less support among those living with a stepparent or neither parent., Conclusion: The association between living in a single-parent household and heavy alcohol or other substance use was mediated largely by time spent outside the home with friends in unsupervised activities. Additional research that uses longitudinal data and more nuanced measures of family structure is needed to validate this finding.

The aim of this review is to assess empirical studies from the last 2 decades that have examined the association between cumulative stressors and adolescent substance use. Cumulative stressors were measured in these studies with adverse childhood experiences or adolescent stressful life events inventories. The 109 articles meeting the eligibility criteria that emerged from the review demonstrated a consistent, yet modest, association between cumulative stressors and adolescent substance use. Of note, several studies found that the associations were moderated or mediated by genetic factors related to cortisol regulation, intrapersonal factors such as low self-control, or interpersonal factors such as peer substance use. The review's findings thus suggest that efforts to reduce the effects of cumulative stressors on substance use could gainfully identify and target these risk moderators and mediators.

The rapid development of COVID-19 vaccines was the result of decades of research to establish flexible vaccine platforms and understand pathogens with pandemic potential, as well as several novel changes to the vaccine discovery and development processes that partnered industry and governments. And while vaccines offer the potential to drastically improve global health, low-and-middle-income countries around the world often experience reduced access to vaccines and reduced vaccine efficacy. Addressing these issues will require novel vaccine approaches and platforms, deeper insight how vaccines mediate protection, and innovative trial designs and models. On June 28-30, 2021, experts in vaccine research, development, manufacturing, and deployment met virtually for the Keystone eSymposium "Innovative Vaccine Approaches" to discuss advances in vaccine research and development., (© 2022 New York Academy of Sciences.)

Tissue-resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from Klebsiella pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both T H 1 and T H 17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae . Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4 + T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4 + T cells from OmpX+LTA1–immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited T H 17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with T H 1 cells, and T H 17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a promising vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.

Background: Biofilms are microbial communities surrounded by a self-produced extracellular matrix which protects them from environmental stress. Bacteria within biofilms are 10- to 1000-fold more resistant to antibiotics, making it challenging but imperative to develop new therapeutics that can disperse biofilms and eradicate infection. Gram-negative bacteria produce outer membrane vesicles (OMV) that play critical roles in communication, genetic exchange, cargo delivery, and pathogenesis. We have previously shown that OMVs derived from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi., Results: Here, we examine the antibiofilm activity of Burkholderia thailandensis OMVs against the oral biofilm-forming pathogen Streptococcus mutans. We demonstrate that OMV treatment reduces biofilm biomass, biofilm integrity, and bacterial cell viability. Both heat-labile and heat-stable components, including 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline and long-chain rhamnolipid, contribute to the antibiofilm activity of OMVs. When OMVs are co-administered with gentamicin, the efficacy of the antibiotic against S. mutans biofilms is enhanced., Conclusion: These studies indicate that bacterial-derived OMVs are highly effective biological nanoparticles that can inhibit and potentially eradicate biofilms., (© 2021. The Author(s).)

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections., 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 © 2021 Hoffmann, Kolls and McCombs.)

Objectives: The aim of this study was to examine whether three theories of adolescent substance use-social learning, social bonding, and self-control-were useful for predicting adolescent nicotine vaping. Methods : The analysis utilized data on U.S. 8th and 10th grade students from the 2017 and 2018 Monitoring the Future (MTF) studies, repeated cross-sectional surveys that included 11,624 youth who responded to questions about past 12-month nicotine vaping. Measures from each of the three theories were used to predict the outcome using a zero-inflated negative binomial model. Results : The results demonstrated that variables from social learning and self-control theories were key predictors of nicotine vaping. Friends' substance use appeared as the most consequential predictor, followed by low self-control or higher risk-taking propensities. An interaction effect also suggested that friends' substance use had a stronger association with nicotine vaping among youth who reported higher self-control. Conclusions/Importance : The findings suggested that adolescent nicotine vaping is a consequence of social learning influences and low self-control. Future research should explore these and similar factors in more detail.

Gram-negative bacteria secrete outer membrane vesicles (OMVs) that play critical roles in intraspecies, interspecies, and bacteria-environment interactions. Some OMVs, such as those produced by Pseudomonas aeruginosa, have previously been shown to possess antimicrobial activity against competitor species. In the current study, we demonstrate that OMVs from Burkholderia thailandensis inhibit the growth of drug-sensitive and drug-resistant bacteria and fungi. We show that a number of antimicrobial compounds, including peptidoglycan hydrolases, 4-hydroxy-3-methyl-2-(2-non-enyl)-quinoline (HMNQ) and long-chain rhamnolipid are present in or tightly associate with B. thailandensis OMVs. Furthermore, we demonstrate that HMNQ and rhamnolipid possess antimicrobial and antibiofilm properties against methicillin-resistant Staphylococcus aureus (MRSA). These findings indicate that B. thailandensis secretes antimicrobial OMVs that may impart a survival advantage by eliminating competition. In addition, bacterial OMVs may represent an untapped resource of novel therapeutics effective against bio-film-forming and multidrug-resistant organisms.

Novel classes of antibiotics and new strategies to prevent and treat infections are urgently needed because the rapid rise in drug-resistant bacterial infections in recent decades has been accompanied by a parallel decline in development of new antibiotics. Membrane permeabilizing antimicrobial peptides (AMPs) have long been considered a potentially promising, novel class of antibiotic, especially for wound protection and treatment to prevent the development of serious infections. Yet, despite thousands of known examples, AMPs have only infrequently proceeded as far as clinical trials, especially the chemically simple, linear examples. In part, this is due to impediments that often limit their applications in vivo. These can include low solubility, residual toxicity, susceptibility to proteolysis, and loss of activity due to host cell, tissue, and protein binding. Here we show how synthetic molecular evolution can be used to evolve potentially advantageous antimicrobial peptides that lack these impediments from parent peptides that have at least some of them. As an example of how the antibiotic discovery pipeline can be populated with more promising candidates, we evolved and optimized one family of linear AMPs into a new generation with high solubility, low cytotoxicity, potent broad-spectrum sterilizing activity against a panel of gram-positive and gram-negative ESKAPE pathogens, and antibiofilm activity against gram-positive and gram-negative biofilms. The evolved peptides have these activities in vitro even in the presence of concentrated host cells and also in vivo in the complex, cell- and protein-rich environment of a purulent animal wound model infected with drug-resistant bacteria., Competing Interests: Competing interest statement: Authors C.G.S., J.G., S.G., and W.C.W. are inventors on a US Patent application filed by Tulane University.

Increased prevalence of antibiotic resistance in skin and soft tissue infections is a concerning public health challenge currently facing medical science. A combinatory, broad spectrum biocidal antiseptic has been developed ("ASP") as a topically applied solution to potential resistant and polymicrobial infected wounds that may be encountered in this context. The ASP-105 designate was evaluated in vitro by determining the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), against different strains of methicillin-resistant Staphylococcus aureus (MRSA), resulting estimates of which approximated the positive control (bacitracin). To evaluate in vivo microbicide efficacy, we utilized a murine full thickness wound model to study bacterial infection and wound healing kinetics. Mice were experimentally wounded dorsally and infected with bioluminescent MRSA. The infected wound was splinted, dressed and treated topically with either ASP-105, vehicle (-control), or bacitracin. Bacterial burden and wound healing was monitored using an in vivo imaging system and evaluation of biofilm formation using scanning electron microscopy of wound dressing. Treatment with ASP-105 significantly reduced bacterial burdens in the first 3 days of infection and inhibited MRSA biofilm formation on the surgical dressing. Notably, treatment with ASP-105 resulted in a sterilizing effect of any detectable MRSA in nearly all (80%; 4/5) of treatment group. All mice receiving vehicle control developed highly MRSA-luminescent and purulent wound beds as a result of experimental infection. The ASP-105 therapy facilitated natural healing in the absence of MRSA infection. Results of this study suggests that that the novel "ASP" combinatory topical antiseptic can be used directly in wounds as a potent, broad-spectrum microbicide against drug resistant S. aureus without injury to the wound bed and impediment of natural restorative processes associated with wound healing. Further studies are warranted to test the effectiveness of this biocidal formulation against other recalcitrant bacterial and fungal pathogens in the context of serious wound infections, and to assess utility of use in both clinical and self-treat scenarios., (Copyright © 2020 Hoffmann, Friedman, Wang, McLachlan, Sammarco, Morici and Roy.)

Background: Research on the association between cohabitation and substance use has been inconsistent, with some studies indicating an elevated risk among cohabiters and others finding either no difference in risk or a reduced risk of substance use. However, studies of this association have not utilized a causal modeling empirical framework., Objectives: The purpose of this research was to assess whether cohabitation has a causal effect on two forms of substance use among young adults: marijuana and heavy alcohol use., Methods: Three waves of data from the National Survey of Youth and Religion (n = 2,202; 2002-2008), a representative sample of young adults in the United States, and an augmented inverse probability weighting (AIPW) model designed for multivalued treatment effects estimation, were used to assess the association between cohabitation and substance use., Results: The findings indicated that cohabitation was associated with more frequent marijuana use only among females. Much of the effect of cohabitation, though, was due to previous factors, including substance use, that affected whether young adults cohabit or not. Moreover, there was no evidence that cohabitation had a causal impact on heavy alcohol use. Conclusions/Importance: There is little evidence that cohabitation has a causal impact on substance use in general. However, among young women, those who cohabited reported higher levels of marijuana use than those who remained single. Future research should address why this group is at particular risk of substance use.

Purpose: Fractures, occlusal adjustments, or marginal corrections after removing excess composite cements result in rough surfaces of all-ceramic FPDs. These have to be polished to prevent damage of the surrounding tissues. The aim of this study was to evaluate the roughness of zirconia, silicate-ceramic, and composite after polish with different systems for intraoral use., Materials and Methods: Each set of 50 plates was made of zirconia, silicate-ceramic, and composite. All plates were ground automatically and were divided into 15 groups according to the treatment. Groups Zgrit, Sgrit, and Cgrit received no further treatment. Groups Zlab and Slab received glaze-baking, and group Clab was polished with a polishing device. In the experimental groups Zv, Sv, Cv, Zk, Sk, Ck, Zb, Sb, and Cb, the specimens were polished with ceramic-polishing systems "v", "k", and "b" for intraoral use. Roughness was measured using profilometry. Statistical analysis was performed with ANOVA and Scheffé-procedure with the level of significance set at P =.05., Results: All systems reduced the roughness of zirconia, but the differences from the controls Zgrit and Zlab were not statistically significant ( P >.907). Roughness of silicate ceramic was reduced only in group Sv, but it did not differ significantly from both controls ( P >.580). Groups Cv, Ck, and Cb had a significantly rougher surface than that of group Clab ( P <.003)., Conclusion: Ceramic materials can be polished with the tested systems. Polishing of interface areas between ceramic and composite material should be performed with polishing systems for zirconia first, followed by systems for veneering materials and for composite materials.

Background: Numerous studies indicate that family structure is a key correlate of adolescent substance use. Yet there are some important limitations to this research. Studies have been conducted mainly in the United States, with relatively few studies that have compared family structure and youth substance use across nations. There is also a lack of recognition of the complexity of family types prevalent in contemporary global society. Moreover, there remains a need to consider personal, interpersonal, and macro-level characteristics that may help account for the association between family structure and youth substance use., Objective: This study uses data from 37 countries to examine several models that purport to explain the association between family structure and substance use., Methods: The data are from the 2005-2006 WHO-sponsored Health Behaviour in School-Aged Children (HBSC) (n = 193,202). Multilevel models, including linear, probit, and structural equation models (SEMs), were used to test several hypotheses., Results: The results suggest that time spent with friends largely accounted for the association between specific types of family structures and frequency of alcohol use and getting drunk, but that cannabis use was negatively associated with living with both biological parents irrespective of other factors.

Research indicates that conservative Protestants are highly supportive of corporal punishment. Yet, Americans' support for this practice has waned during the past several decades. This study aggregates repeated cross-sectional data from the General Social Surveys (GSS) to consider three models that address whether attitudes toward spanking among conservative Protestants shifted relative to those of other Americans from 1986 to 2014. Although initial results reveal a growing gap between conservative Protestants and the broader American public, we find that average levels of support have remained most robust among less educated conservative Protestants, with some erosion among more highly educated conservative Protestants. Moreover, trends in variability suggest that conservative Protestants exhibit more cohesive support for this practice than do others. These results provide a window into the cultural contours of religious change and the social factors that facilitate such change., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A growing body of literature suggests that social capital is a valuable resource for children and youth, and that returns to that capital can increase academic success. However, relatively little is known about whether youth from different backgrounds build social capital in the same way and whether they receive the same returns to that capital. We examine the creation of and returns to social capital in family and school settings on academic achievement, measured as standardized test scores, for white boys, black boys, white girls, and black girls who were seniors in high school in the United States. Our findings suggest that while youth in different groups build social capital in largely the same way, differences exist by race and sex as to how family social capital affects academic achievement. Girls obtain greater returns to family social capital than do boys, but no group receives significant returns to school social capital after controlling for individual- and school-level characteristics.

Objective: The purpose of this research was to examine the associations of parenting style, religiosity, and peer alcohol use with alcohol use and heavy drinking., Method: Structural equation modeling was used to estimate direct and indirect associations among 5,419 adolescents ages 12-14 years from the National Longitudinal Study of Youth 1997., Results: Adolescents whose parents were authoritative were less likely to drink heavily than adolescents who experienced neglectful or indulgent parenting styles. Religiosity was negatively associated with heavy drinking after other relevant variables were controlled for., Conclusions: Authoritative parenting appears to have both direct and indirect negative associations with the risk of heavy drinking among adolescents. Authoritative parenting, where monitoring and support are above average, and religiosity might help deter adolescents from heavy drinking, even when adolescents experience peer environments where alcohol use is common. Authoritarian parenting, although it was not associated with heavy drinking, was positively associated with alcohol use and peer alcohol use, thus placing adolescents at some risk.

The risks of early adolescent substance use on health and well-being are well documented. In recent years, several experts have claimed that a simple preventive measure for these behaviors is for families to share evening meals. In this study, we use data from the 1997 National Longitudinal Study of Youth (n = 5,419) to estimate propensity score models designed to match on a set of covariates and predict early adolescent substance use frequency and initiation. The results indicate that family dinners are not generally associated with alcohol or cigarette use or with drug use initiation. However, a continuous measure of family dinners is modestly associated with marijuana frequency, thus suggesting a potential causal impact. These results show that family dinners may help prevent one form of substance use in the short term but do not generally affect substance use initiation or alcohol and cigarette use.

We use a reaction diffusion equation, together with a genetic algorithm approach for model selection to develop a general modeling framework for biological invasions. The diffusion component of the reaction diffusion model is generalized to include dispersal and advection. The reaction component is generalized to include both linear and non-linear density dependence, and Allee effect. A combination of the reaction diffusion and genetic algorithm is able to evolve the most parsimonious model for invasive species spread. Zebra mussel data obtained from Lake Champlain, which demarcates the states of New York and Vermont, is used to test the appropriateness of the model. We estimate the minimum wave spread rate of Zebra mussels to be 22.5 km/year. In particular, the evolved models predict an average northward advection rate of 60.6 km/year (SD ± 1.9), which compares very well with the rate calculated from the known hydrologic residence time of 60 km/year. A combination of a reaction diffusion model and a genetic algorithm is, therefore, able to adequately describe some of the hydrodynamic features of Lake Champlain and the spread of a typical invasive species--Zebra mussels within the lake.

Objective: The purpose of this research was to examine whether authoritative, authoritarian, indulgent, and neglectful parenting styles were associated with adolescent alcohol use and heavy drinking, after controlling for peer use, religiosity, and other relevant variables., Method: Structural equation modeling was used to estimate direct and indirect associations of parenting style with alcohol use and heavy drinking among 4,983 adolescents in Grades 7-12., Results: Adolescents whose parents were authoritative were less likely to drink heavily than adolescents from the other three parenting styles, and they were less likely to have close friends who used alcohol. In addition, religiosity was negatively associated with heavy drinking after controlling for other relevant variables., Conclusions: Authoritative parenting appears to have both direct and indirect associations with the risk of heavy drinking among adolescents. Authoritative parenting, where monitoring and support are above average, might help deter adolescents from heavy alcohol use, even when adolescents have friends who drink. In addition, the data suggest that the adolescent's choice of friends may be an intervening variable that helps explain the negative association between authoritative parenting and adolescent heavy drinking.

Using data from the National Immunization Surveys (2003 and 2004), the authors model the influence of child, maternal, and state- or metropolitan-level factors on the initiation, duration, and exclusivity of breastfeeding to determine the characteristics of groups meeting the Healthy People 2010 targets. Analyses indicate that only children of college graduates meet the targets for breastfeeding at initiation, 6 months, and 12 months; no groups meet the target for exclusive breastfeeding. Results indicate a low prevalence of breastfeeding among children of single mothers, less educated mothers, participants in the Women, Children, and Infants program, and those living in nonwestern states and in areas of high newborn risk. Hispanic children, children of college graduates, and children living in the West consistently have higher odds of breastfeeding. Only the prevalence of breastfeeding early postpartum is near the Healthy People 2010 target of 75%, the percentages for 6 or 12 months and exclusive breastfeeding are well below.

In order to evaluate the feasibility of a combined evolutionary algorithm-information theoretic approach to select the best model from a set of candidate invasive species models in ecology, and/or to evolve the most parsimonious model from a suite of competing models by comparing their relative performance, it is prudent to use a unified model that covers a myriad of situations. Using Schnute's postulates as a starting point [Schnute, J., 1981. A versatile growth model with statistically stable parameters, Can. J. Fish Aquat. Sci. 38, 1128-1140], we present a single, unified model for growth that can be successfully utilized for model selection in evolutionary computations. Depending on the parameter settings, the unified equation can describe several growth mechanisms. Such a generalized model mechanism, which encompasses a suite of competing models, can be successfully implemented in evolutionary computational algorithms to evolve the most parsimonious model that best fits ground truth data. We have done exactly this by testing the effectiveness of our reaction-diffusion-advection (RDA) model in an evolutionary computation model selection algorithm. The algorithm was validated (with success) against field data sets of the Zebra mussel invasion of Lake Champlain in the United States.

This research investigates the effects of extracurricular activities on alcohol use among male (n = 4,495) and female (n = 5,398) adolescents who participated in the 1990-92 National Education Longitudinal Study. Previous studies have assessed the association between extracurricular activities and alcohol use, but none have explored whether the association depends on the school context. Using a multilevel model, I examine whether school-level factors affect the relationship between involvement in athletic or nonathletic activities and changes in adolescent alcohol use from 1990 to 1992. The results indicate that the negative association between nonathletic activities and alcohol use is stronger among males in low-minority-population schools. Moreover the positive association between athletic involvement and alcohol use is stronger among females in lower-socioeconomic-status schools and males in higher-socioeconomic-status schools. I propose that these results reflect variation in high school cultures and in the resources available to schools.

Using a probability sample of 4,230 adolescents from grades 7-12, we used negative binomial regression to estimate the effects of peer and six family variables on the risk of adolescent drug use. Peer drug use had relatively strong effects of adolescent drug use. Parental drug attitudes, sibling drug use, and adult drug use had significant direct effects net of peer influences. In addition, they had significant indirect effects that were mediated by peer drug use. The influences of parental monitoring, attachment to mother, and attachment to father were statistically significant but relatively small. The findings applied to alcohol, binge drinking, cigarettes, marijuana, and other illicit drugs. Editors' Strategic Implications: The authors interpret their findings as being more consistent with social learning than social control theory. This research, although cross-sectional and limited to adolescents' self-reports, contributes to a growing literature on the direct and indirect influences of parents on their teens' substance use rates. It speaks to the need for school- and community-based prevention efforts to focus on families as well as peers.

Drawing on the family process literature, child health models, and recent studies of macro-level effects on health, we examine the effects of household structure, resources, care-giving, reproduction, and communication on child nutritional status and infant mortality. Using Demographic and Health Surveys, we analyze the influence of these factors across 42 countries in Latin America, Africa, and Asia. We also consider country-level including nontraditional family structure, level of economic development and expenditures on health care. Our results underscore the importance of family resources, decision-making, and health and feeding practices on child well-being in less developed countries. Although there is cross-national variability, the size of the variability was small relative to the overall effect. The country-level measures had modest effects on infant mortality and child nutritional status.

Objectives: To examine the association between parental affective disorders and psychoactive substance use disorders and the onset of major depressive disorder (MDD) among adolescents and young adults and to determine whether this association is affected by stressful life events, family cohesion, self-esteem, or gender., Method: Prospective cohort study of 804 adolescents, aged 11-17 years, and their parents who were followed for seven consecutive years. The sample was drawn from the Minneapolis-St. Paul metropolitan area. Parental diagnoses were based on Structured Clinical Interview for administered during study screening stage. Diagnoses of MDD and age of onset were based on Composite International Diagnostic Interview 2.1 administered during final year of data collection., Results: Of the correlates examined, only parental affective disorders, low self-esteem, and gender were significantly related to the onset of MDD. Females were twice as likely as males to experience MDD., Conclusions: The direct association between parental affective disorders and MDD onset was not affected by family cohesion, self-esteem, or stressful life events; thus more research is needed on other factors that may affect this association, such as genetic factors or other family- and intrapersonal-based variables.

A common observation in the research literature is that children of drug-dependent parents are at significantly heightened risk of adolescent drug use, abuse, and dependence. Recent research indicates that several psychological and interpersonal factors may affect the association between parents' psychoactive substance use disorder (PSUD) and drug use risks among adolescents, yet studies have failed to examine explicitly whether these factors moderate the association between PSUD and adolescent substance abuse. This paper explores these potential relationships using longitudinal data from a study that has followed three cohorts of adolescents and their families over a 7-year period. The cohorts are defined by parental diagnoses of PSUD, affective disorders, or no diagnosable disorder. The results indicate that PSUD is positively associated with adolescent drug abuse, yet this association is attenuated by strong family cohesion. Affective disorders among parents are associated with a higher risk of alcohol, but not drug, abuse. The associations are stronger in the presence of lower stress and higher self-esteem. PSUD is also associated more strongly with offspring drug and alcohol abuse when levels of use are lower. Hence, some unobserved mechanism that may involve physiological sensitivities to drugs and alcohol appears to put children of parents with drug problems at particular risk of drug and alcohol abuse. Limitations of the data and analysis are discussed.

Background and Objective: The determination of parathyroid hormone (PTH) is of great clinical relevance in the assessment of calcium metabolic disorders. Although PTH was one of the first hormones measured by immunoassays, there are still many difficulties in its determination due to the low concentration of the hormone in blood and due to the heterogeneity of PTH resulting from different circulating hormone fragments. The aim of our multicenter-study was to evaluate the technical performance and the clinical validity of a new immunoassay for intact PTH measurement on the Elecsys Systems 2010 and 1010., Methods and Results: The multicenter evaluation was performed in 11 clinical laboratories. The Elecsys PTH assay is a one step sandwich electrochemiluminescence immunoassay based upon the streptavidin-biotin technology. Two monoclonal antibodies are used in the assay providing detection of intact PTH. The imprecision study yielded within-run and between-days coefficients of variation of 3.1% - 6.6% and 3.4% - 15.6%, respectively using a three level control (PreciControl Bone, Roche Diagnostics) and human pool sera at two different concentrations (HS-low: 20 - 60 pg/ml, HS-high > 65 pg/ml). The analytical sensitivity calculated as the mean value plus 2 standard deviations of a within-run imprecision was below 2.70 pg/ml using zero calibrator matrix. Dilution linearity was observed up to 4890 pg/ml using zero calibrator matrix or human pool sera. Recoveries ranged between 85% - 115%. Serum, EDTA- and heparin plasma were evaluated for PTH measurement. Due to a better analyte stability (48h at 21 degrees C; 3d at 4 degrees C) EDTA plasma was recommended for PTH measurement. Results of the Elec sys PTH immunoassay correlated well (r = 0.926 - 0.994) with three different immunoradiometric assays (N-tact PTH SP, DiaSorin; Nichols Allegro Intact PTH, Nichols Institute Diagnostics; ELSA-PTH, CISBio International) and two different immunochemiluminometric assays (PTH-Intact-Immulite, DPC Biermann; Nichols Advantage Intact PTH, Nichols Institute Diagnostics) in technical and clinical method comparisons. The Passing/Bablok regression analysis yielded slopes of 0.692 - 1.729 and intercepts of -13.982 - +15.763 pg/ml. Deviations from slope 1.0 and intercept 0.0 were not unexpected due to differences in immunoassay standardization and probably due to the presence of different PTH fragments and a variable affinity of the used antibodies to these PTH fragments. Highly similar PTH concentration pattern of the Elecsys immunoassay and the Quick-Intraoperative Intact PTH immunoassay (Nichols Institute Diagnostics) obtained from specimens taken intraoperatively support the applicability of the Elecsys immunoassay to monitor the success of parathyroid resection. A reference range of 12.3 - 56.0 pg/ml calculated from PTH values of 43 apparently healthy individuals confirms reference limits published in the literature. The partition of collectives according to age showed, that individuals > 50 years have slightly higher PTH concentrations, independently of gender. This shift could be due to age itself or to an increased prevalence of individuals without obvious calcium metabolic disorders in this collective., Conclusion: The Elecsys PTH assay is a useful and reliable tool for determination of intact PTH. Our data support the intended use of the assay in clinical applications related to disorders of calcium metabolism.

Using nationally representative data for 16,454 8th graders and 13,840 10th graders, we explore racial/ethnic differences in "daily cigarette initiation," beginning to smoke on a daily basis between baseline interviews and reinterviews conducted two years later. In both samples, the initiation rate among whites is more than double the rate among blacks and higher than rates among Asian/Pacific Islanders and Hispanics. Risk factors at the individual, family, and peer-group levels of analysis do not explain most racial/ethnic differences. We develop alternative hypotheses by extending theories of cigarette use to the school level, and we test them using multilevel models: Consistent with social learning theory, cigarette risk among blacks and Hispanics decreases as the percentage of racial/ethnic minority students in the school increases. Consistent with strain theory, cigarette risk increases with the academic competitiveness of the school--especially among females--after controlling for the adolescent's academic performance.

Few studies have examined gender-specific factors associated with the nonuse of condoms among homeless and runaway youths (HRYs)-a population at high risk for HIV infection. In this article, we evaluate these factors and explore gender differences in background experiences, psychosocial functioning, and risk behaviors among HRYs from four U.S. metropolitan areas. Of 879 sexually active HRYs sampled, approximately 70% reported unprotected sexual intercourse during a 6-month period, and nearly a quarter reported never using condoms in the same period. Among males and females, having only one sex partner in the previous 6 months had the strongest association with nonuse of condoms. Among males, nonuse was also associated with having ever caused pregnancy, frequent marijuana use, prior physical victimization, and low self-control and sociability. Among females, nonuse was associated with knowledge of HIV status, prior sexual victimization, low social support, and infrequent marijuana use. These findings highlight the ongoing need for HIV prevention services for HRYs. Implications for the scope and content of these services are discussed.

The purpose of this paper is to describe and examine one pathway by which adolescent drug use increases during early and mid-adolescence. It draws upon recent research on adolescent stress, drug use, and family processes to describe an important stage of the life course. A chief principle underlying the proposed pathway is that the cumulative effect of stressful life experiences over time can lead to a steeper escalation of drug use in adolescence. Furthermore, based on previous stress research, we propose that this effect may be moderated by factors such as sex, income, family attachment, self-esteem, and mastery. Using 4 years of panel data from the Family Health Study (n = 651 adolescents ages 11-14 during Year 1), we estimate a hierarchical growth curve model that examines the time-varying effects of stressful life events and peer relations on drug use. The results indicate that experiencing a high number of life events over time is related to a significant "growth" of drug use, even after controlling for "growth" due to age or peer relations. In addition, this relationship is moderated by family attachment; high levels of attachment serve to diminish this growth significantly.

Stressful life circumstances have myriad influences on human health and behavior. Early research focused on the variable distribution of stress and its effects by socioeconomic status, race, and gender. More recent research indicates that variation by age is also an important consideration. For example, adolescent reactions to stressful life events are often inconsistent with adult reactions to similar life situations and transitions. Moreover, since most studies assess only a single outcome--usually depression--they risk classification bias since analyses exclude other potential stress-related outcomes. This paper assesses the gender distinct effects of stressful life events on two outcomes among adolescents, substance use and depressive symptoms. The results of a second-order regression model indicate that life events affect female, but not male, depressive symptoms, especially when self-esteem is low or mastery is high. Furthermore, life events affect substance use when peer drug use is high, or when parental support is low, but this latter effect is limited to female adolescents.

Aims: To develop and test a non-recursive model that examines the effects of parental psychoactive substance use disorder (PSUD) on the reciprocal relationships among stressful life events, family attachment, peer drug use and adolescent drug use., Design: A 3-year prospective cohort study followed adolescents from three types of families defined by a parental diagnosis of a psychiatric disorder., Setting: A large metropolitan area in the upper Midwestern United States., Participants: Seven hundred and seventy-seven 10-16-year-old adolescents from three groups of families: 214 who resided in families in which a parent was diagnosed with PSUD, 181 who resided in families in which a parent was diagnosed with an affective disorder (but no co-morbid PSUD), and 382 who resided in families in which both parents were free of any diagnosable disorder., Measurements: Psychiatric disorder was defined by the Structured Clinical Interview for DSM-III-R (SCID). Two follow-up interviews of adolescent respondents were used to measure stressful life events via the Junior High Life Experiences Survey, family attachment via FACES-III and a child-parent strain index, peer drug use, and two self-reported drug use scales designed to measure past-year alcohol use and illicit drug use (e.g. marijuana, cocaine, inhalants)., Findings: Nested structural equation models with latent variables revealed that adolescents from PSUD families were at heightened risk of stressful life events, peer drug use, attenuated family attachments and drug use during the first follow-up period. In turn, peer drug use was strongly associated with drug use during the second follow-up period. However, drug use during the first follow-up also led to greater peer drug use and attenuated family attachment during the second follow-up period. The findings support a non-recursive model describing relations among adolescent drug use, peer drug use and family attachment., Conclusions: Parental psychoactive substance use disorder puts adolescents at significant risk of becoming embedded in a cycle of drug use, associations with drug using peers, and poor family relations.

Studies indicate that HIV risk behaviors vary greatly among injection drug users (IDUs). The source of such variation is often ascribed to individual differences, but much of it is due to how IDUs are grouped into social networks. Nevertheless, given the turbulent and uncertain lives led by many IDUs, it would not be surprising if their social networks changed substantially over time. We used data from a study of the social networks of IDUs in Chicago and Washington, DC, to examine changes in individual behavior and network characteristics over time. The results indicated few changes in standard network measures, such as density of ties or network size, over time. However, specific network change measures, that is, indicators of movement into and out of networks, showed significant movement of network members over time. Moreover, movement of members into a network significantly predicted a higher likelihood of risky injection drug use over time. We suggest that these movements are indicative of a lack of a stable resource base among IDU networks.

The role of family structure in adolescence has been linked to a host of problem behaviors, including marijuana use. This paper investigates the relationship between family structure and marijuana use, and elaborates previous research by 1) exploring several intervening mechanisms that affect the relationship, and 2) examining the effects of a variety of family forms. Analyses of data from the National Youth Survey (1977-79) indicate that 1) a parental divorce or living with a stepparent decreases family attachment among adolescents; 2) attenuated family attachment and involvement increase the likelihood of associating with drug-using peers; and 3) less family involvement and increased associations with drug-using peers increase the probability of initiating marijuana use and elevate frequency of use.