Antimicrobial resistance level and conjugation permissiveness shape plasmid distribution in clinical enterobacteria.

Conjugative plasmids play a key role in the dissemination of antimicrobial resistance (AMR) genes across bacterial pathogens. AMR plasmids are widespread in clinical settings, but their distribution is not random, and certain associations between plasmids and bacterial clones are particularly successful. For example, the globally spread carbapenem resistance plasmid pOXA-48 can use a wide range of enterobacterial species as hosts, but it is usually associated with a small number of specific Klebsiella pneumoniae clones. These successful associations represent an important threat for hospitalized patients. However, knowledge remains limited about the factors determining AMR plasmid distribution in clinically relevant bacteria. Here, we combined in vitro and in vivo experimental approaches to analyze pOXA-48-associated AMR levels and conjugation dynamics in a collection of wild-type enterobacterial strains isolated from hospitalized patients. Our results revealed significant variability in these traits across different bacterial hosts, with Klebsiella spp. strains showing higher pOXA-48-mediated AMR and conjugation frequencies than Escherichia coli strains. Using experimentally determined parameters, we developed a simple mathematical model to interrogate the contribution of AMR levels and conjugation permissiveness to plasmid distribution in bacterial communities. The simulations revealed that a small subset of clones, combining high AMR levels and conjugation permissiveness, play a critical role in stabilizing the plasmid in different polyclonal microbial communities. These results help to explain the preferential association of plasmid pOXA-48 with K. pneumoniae clones in clinical settings. More generally, our study reveals that species- and strain-specific variability in plasmid-associated phenotypes shape AMR evolution in clinically relevant bacterial communities.

Permissiveness and competition within and between Neurospora crassa syncytia.

A multinucleate syncytium is a common growth form in filamentous fungi. Comprehensive functions of the syncytial state remain unknown, but it likely allows for a wide range of adaptations to enable filamentous fungi to coordinate growth, reproduction, responses to the environment, and to distribute nuclear and cytoplasmic elements across a colony. Indeed, the underlying mechanistic details of how syncytia regulate cellular and molecular processes spatiotemporally across a colony are largely unexplored. Here, we implemented a strategy to analyze the relative fitness of different nuclear populations in syncytia of Neurospora crassa, including nuclei with loss-of-function mutations in essential genes, based on production of multinucleate asexual spores using flow cytometry of pairings between strains with differentially fluorescently tagged nuclear histones. The distribution of homokaryotic and heterokaryotic asexual spores in pairings was assessed between different auxotrophic and morphological mutants, as well as with strains that were defective in somatic cell fusion or were heterokaryon incompatible. Mutant nuclei were compartmentalized into both homokaryotic and heterokaryotic asexual spores, a type of bet hedging for maintenance and evolution of mutational events, despite disadvantages to the syncytium. However, in pairings between strains that were blocked in somatic cell fusion or were heterokaryon incompatible, we observed a "winner-takes-all" phenotype, where asexual spores originating from paired strains were predominantly one genotype. These data indicate that syncytial fungal cells are permissive and tolerate a wide array of nuclear functionality, but that cells/colonies that are unable to cooperate via syncytia formation actively compete for resources.

Plasmid permissiveness of wastewater microbiomes can be predicted from 16S rRNA sequences by machine learning.

MOTIVATION: Wastewater treatment plants (WWTPs) harbor a dense and diverse microbial community. They constantly receive antimicrobial residues and resistant strains, and therefore provide conditions for horizontal gene transfer (HGT) of antimicrobial resistance (AMR) determinants. This facilitates the transmission of clinically important genes between, e.g. enteric and environmental bacteria, and vice versa. Despite the clinical importance, tools for predicting HGT remain underdeveloped. RESULTS: In this study, we examined to which extent water cycle microbial community composition, as inferred by partial 16S rRNA gene sequences, can predict plasmid permissiveness, i.e. the ability of cells to receive a plasmid through conjugation, based on data from standardized filter mating assays using fluorescent bio-reporter plasmids. We leveraged a range of machine learning models for predicting the permissiveness for each taxon in the community, representing the range of hosts a plasmid is able to transfer to, for three broad host-range resistance IncP plasmids (pKJK5, pB10, and RP4). Our results indicate that the predicted permissiveness from the best performing model (random forest) showed a moderate-to-strong average correlation of 0.49 for pB10 [95% confidence interval (CI): 0.44-0.55], 0.43 for pKJK5 (0.95% CI: 0.41-0.49), and 0.53 for RP4 (0.95% CI: 0.48-0.57) with the experimental permissiveness in the unseen test dataset. Predictive phylogenetic signals occurred despite the broad host-range nature of these plasmids. Our results provide a framework that contributes to the assessment of the risk of AMR pollution in wastewater systems. AVAILABILITY AND IMPLEMENTATION: The predictive tool is available as an application at https://github.com/DaneshMoradigaravand/PlasmidPerm.

Mice humanized for MHC and hACE2 with high permissiveness to SARS-CoV-2 omicron replication.

Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in "HHD-DR1" background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE22Prlmn/JAX mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine.

Butyrate Differentiates Permissiveness to Clostridioides difficile Infection and Influences Growth of Diverse C. difficile Isolates.

A disrupted "dysbiotic" gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota-accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome is short-chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known to decrease the fitness of C. difficile in vitro, and high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI than in those from healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations. IMPORTANCE Clostridioides difficile is a leading cause of infectious diarrhea in humans, and it imposes a tremendous burden on the health care system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted "dysbiotic" gut microbiota is the primary risk factor for CDI, but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.

Establishment of a Culex tarsalis (Diptera: Culicidae) Cell Line and its Permissiveness to Arbovirus Infection.

A cell line was established from Culex tarsalis Coquillett embryonated eggs and designated as CxTr. The cell line is heterogeneous, composed predominantly of small, round cells, and spindle-shaped cells with a doubling time of approximately 52-60 h. The identity of the cell line was verified as Cx. tarsalis by sequencing of cytochrome oxidase I and the cells were found to be free of contaminating cells, bacteria, fungi, and mycoplasma. The permissiveness of CxTr cells to arbovirus infection was investigated with vaccine and wildtype arboviruses from four viral families: Flaviviridae (Japanese encephalitis virus), Phenuiviridae (Rift Valley fever phlebovirus), Rhabdoviridae (vesicular stomatitis virus), and Togaviridae (Mayaro virus). All viruses were able to infect and replicate within CxTr cells.

The association between parenting styles, maternal self-efficacy, and social and emotional adjustment among Arab preschool children

Abstract Parenting styles and parental self-efficacy are major factors that affect the overall adjustment of children. The current study examined parenting styles and maternal self-efficacy and their association with social-emotional adjustment among Arab preschool children living in Israel. Parenting Styles Questionnaire , Maternal Self-Efficacy Questionnaire , and Adjustment Questionnaire were administered to 420 Arabic-speaking mothers of 3- to 4-year-old children. After employing multiple regression analyses, the results indicated that parenting styles and the overall adjustment of children were significantly correlated. More precisely, a significant association between authoritative parenting style and higher levels of social-emotional adjustment among preschool children was found. Furthermore, maternal self-efficacy was significantly correlated to the overall adjustment of children. In this regard, higher maternal self-efficacy is associated with increased social-emotional adjustment among preschool children. The findings of our study show the applicability of these constructs found relevant across numerous cultures in a unique sample of Arab children living in Israel. Lastly, this study supports intervention programs that promote authoritative parenting style and parental self-efficacy in Arab communities.

O cuidado em saúde promovido pelas religiões afro-brasileiras / Health care promoted by afro-brazilian religions / El cuidado en salud promovido por las religiones afrobrasileñas

No decorrer da história, sempre foram infindáveis os casos em que os sujeitos recorriam a centros espíritas ou terreiros de religiões de matrizes africanas em decorrência de problemas como doenças, desempregos ou amores mal resolvidos, com o objetivo de saná-los. Por conta disso, este artigo visa apresentar os resultados da pesquisa relacionados ao objetivo de mapear os processos de cuidado em saúde ofertados em três terreiros de umbanda de uma cidade do litoral piauiense. Para isso, utilizamos o referencial da Análise Institucional "no papel". Os participantes foram três líderes de terreiros e os respectivos praticantes/consulentes dos seus estabelecimentos religiosos. Identificamos perspectivas de cuidado que se contrapunham às racionalidades biomédicas, positivistas e cartesianas, e faziam referência ao uso de plantas medicinais, ao recebimento de rezas e passes e à consulta oracular. A partir desses resultados, podemos perceber ser cada vez mais necessário, portanto, que os povos de terreiros protagonizem a construção, implementação e avaliação das políticas públicas que lhe sejam específicas.(AU)

In history, there have always been endless cases of people turning to spiritual centers or terreiros of religions of African matrices due to problems such as illnesses, unemployment, or unresolved love affairs. Therefore, this article aims to present the research results related to the objective of mapping the health care processes offered in three Umbanda terreiros of a city on the Piauí Coast. For this, we use the Institutional Analysis reference "on Paper." The participants were three leaders of terreiros and the respective practitioners/consultants of their religious establishments. We identified perspectives of care that contrasted with biomedical, positivist, and Cartesian rationalities and referred to the use of medicinal plants, the prescript of prayers and passes, and oracular consultation. From these results, we can see that it is increasingly necessary, therefore, that the peoples of the terreiros lead the construction, implementation, and evaluation of public policies that are specific to them.(AU)

A lo largo de la historia, siempre hubo casos en los cuales las personas buscan en los centros espíritas o terreros de religiones africanas la cura para sus problemas, como enfermedades, desempleo o amoríos mal resueltos. Por este motivo, este artículo pretende presentar los resultados de la investigación con el objetivo de mapear los procesos de cuidado en salud ofrecidos en tres terreros de umbanda de una ciudad del litoral de Piauí (Brasil). Para ello, se utiliza el referencial del Análisis Institucional "en el Papel". Los participantes fueron tres líderes de terreros y los respectivos practicantes / consultivos de los establecimientos religiosos que los mismos conducían. Se identificaron perspectivas de cuidado que se contraponían a las racionalidades biomédicas, positivistas y cartesianas, y hacían referencia al uso de plantas medicinales, al recibimiento de rezos y pases y a la consulta oracular. Los resultados permiten concluir que es cada vez más necesario que los pueblos de terreros sean agentes protagónicos de la construcción, implementación y evaluación de las políticas públicas destinadas específicamente para ellos.(AU)

(In)tolerância como política: os discursos de direita e de esquerda no facebook / (In)tolerance as policy: the rightist and leftist discourses on facebook / (In)tolerancia como política: los discursos de la derecha y la izquierda en facebook

Este estudo tem como objetivo analisar traços da mentalidade potencialmente autoritária a partir do discurso de usuários do Facebook vinculados a páginas de cunho político autodeclarado de direita e de esquerda no Brasil. A Netnografia é utilizada como aporte metodológico para imersão on-line nas páginas "Eu era Direita e não sabia" e "Jovens de Esquerda", selecionadas por meio do Facebook Audience Insights, ferramenta disponibilizada pelo Facebook. Delas, foram extraídas oito postagens com maior engajamento (número de comentários, curtidas e compartilhamentos), identificadas pelo Netvizz. Foram coletados 3.489 comentários, os quais foram organizados em um corpus textual submetido ao software IRAMUTEQ e analisados sob a perspectiva da análise crítica imanente da teoria crítica. Como resultado, apresenta-se a forma como o pensamento autoritário se manifesta na racionalização da sociedade contemporânea e nas práticas discursivas em redes sociais on-line, enraizada no âmbito sociopolítico brasileiro, ameaçando o processo democrático e a construção de uma sociedade plural e liberta.(AU)

This study aims to analyze traits of the potentially authoritarian mentality from the speech of Facebook users linked to political pages self-declared as rightist and leftist in Brazil. Netnography is used as a methodological contribution for online immersion in the pages "Eu era Direita e não sabia" and "Jovens de Esquerda" selected via Facebook Audience Insights, a tool provided by Facebook. From these, eight posts with greater engagement (number of comments, likes and shares), identified by Netvizz, were extracted. We collected 3,489 comments, which were organized in a textual corpus submitted to IRAMUTEQ software and analyzed from the perspective of immanent critical analysis of Critical Theory. As a result, we present the way in which authoritarian thinking manifests itself in the rationalization of contemporary society and in discursive practices in online social networks, rooted in the Brazilian socio-political sphere, threatening the democratic process and the construction of a plural and free society.(AU)

Este estudio tiene como objetivo analizar las huellas de la mentalidad potencialmente autoritaria a partir de los discursos de usuarios en Facebook vinculados a páginas políticas autodeclaradas de derecha y de izquierda en Brasil. La netnografía se utiliza como marco metodológico para la inmersión en línea en las páginas "Eu era Direita e não sabia" y "Jovens de Esquerda", seleccionadas por Facebook Audience Insights, herramienta proporcionada por Facebook. Se extrajeron las ocho publicaciones con mayor compromiso (número de comentarios, gustos y compartidas), identificadas por Netvizz. Se recogieron 3.489 comentarios, los cuales fueron organizados en un corpus textual sometido al software IRAMUTEQ y analizado bajo la perspectiva del análisis crítico inmanente de la teoría crítica. Los resultados presentan la forma en que el pensamiento autoritario se manifiesta en la racionalización de la sociedad contemporánea y en prácticas discursivas en redes sociales en línea, arraigada en el ámbito sociopolítico brasileño, que amenazan el proceso democrático y la construcción de una sociedad plural y liberada.(AU)

IL-33 Induces an Antiviral Signature in Mast Cells but Enhances Their Permissiveness for Human Rhinovirus Infection.

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.

Identification of CD98 as a Novel Biomarker for HIV-1 Permissiveness and Latent Infection.

Human immunodeficiency virus type 1 (HIV-1) can integrate viral DNA into host cell chromosomes to establish a long-term stable latent reservoir, which is a major obstacle to cure HIV-1 infection. The characteristics of the HIV-1 latent reservoir have not been fully understood. Here, we identified 126 upregulated plasma membrane proteins in HIV-1 latently infected cells by a label-free liquid chromatography-tandem mass spectrometry analysis. The higher levels of CD98 expression in multiple HIV-1 latently infected cell lines and primary CD4+ T cells compared to uninfected cells were further confirmed by quantitative reverse transcription PCR (RT-qPCR) and flow cytometry analyses. In addition, CD98high CD4+ T cells displayed hyper-permissiveness to HIV-1 infection and possessed distinct immune phenotypic profiles associated with Th17 and peripheral follicular T helper (pTFH) characteristics. Notably, the CD98high resting memory CD4+ T cells harbored significantly higher cell-associated viral RNA and intact provirus than CD98low counterparts in HIV-1-infected individuals receiving combined antiretroviral therapy. Furthermore, CD98high CD4+ T cells exhibited a robust proliferative capacity and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. Our study demonstrates that CD98 can be used as a novel biomarker of HIV-1 latently infected cells to indicate the effect of various strategies to reduce the viral reservoir. IMPORTANCE Identification of cellular biomarkers is the crucial challenge to eradicate the HIV-1 latent reservoir. In our study, we identified CD98 as a novel plasma membrane biomarker for HIV-1 permissiveness and latent infection. Importantly, CD98high CD4+ T cells exhibited a hyper-permissiveness to HIV-1 infection and significantly contributed to the clonal expansion of the HIV-1 latent reservoir. CD98 could be targeted to develop therapeutic strategies to reduce the HIV-1 latent reservoir in further research.

Dietary Carbohydrate as Glycemic Load, Not Fat, Coupled with Genetic Permissiveness Favoring Rapid Growth and Extra Calories, Dictate Metabolic Syndrome and Diabetes Induction in Nile Rats (Arvicanthis niloticus).

Objective: Whether dietary carbohydrate (CHO) or fat is more involved in type 2 diabetes (T2DM) induction uncomplicated by dietary fiber was addressed in a spontaneous diabetic model, the diurnal Nile rat that mimics the human condition. Methods: A total of 138 male Nile rats were fed plant-based and animal-based saturated fat where 10% energy as CHO and fat were exchanged across 5 diets keeping protein constant, from 70:10:20 to 20:60:20 as CHO:fat:protein %energy. Diabetes induction was analyzed by: 1. diet composition, i.e., CHO:fat ratio, to study the impact of diet; 2. quintiles of average caloric intake per day to study the impact of calories; 3. quintiles of diabetes severity to study the epigenetic impact on diabetes resistance. Results: High glycemic load (GLoad) was most problematic if coupled with high caloric consumption. Diabetes severity highlighted rapid growth and caloric intake as likely epigenetic factors distorting glucose metabolism. The largest weanling rats ate more, grew faster, and developed more diabetes when the dietary GLoad exceeded their gene-based metabolic capacity for glucose disposal. Diabetes risk increased for susceptible rats when energy intake exceeded 26 kcal/day and the GLoad was >175/2000 kcal of diet and when the diet provided >57% energy as CHO. Most resistant rats ate <25 kcal/day independent of the CHO:fat diet ratio or the GLoad adjusted to body size. Conclusion: Beyond the CHO:fat ratio and GLoad, neither the type of fat nor the dietary polyunsaturated/saturated fatty acid (P/S) ratio had a significant impact, suggesting genetic permissiveness affecting caloric and glucose intake and glucose disposition were key to modulating Nile rat diabetes. Fat became protective by limiting GLoad when it contributed >40% energy and displaced CHO to <50% energy, thereby decreasing the number of diabetic rats and diabetes severity.

A single amino acid residue in bank vole prion protein drives permissiveness to Nor98/atypical scrapie and the emergence of multiple strain variants.

Prions are infectious agents that replicate through the autocatalytic misfolding of the cellular prion protein (PrPC) into infectious aggregates (PrPSc) causing fatal neurodegenerative diseases in humans and animals. Prions exist as strains, which are encoded by conformational variants of PrPSc. The transmissibility of prions depends on the PrPC sequence of the recipient host and on the incoming prion strain, so that some animal prion strains are more contagious than others or are transmissible to new species, including humans. Nor98/atypical scrapie (AS) is a prion disease of sheep and goats reported in several countries worldwide. At variance with classical scrapie (CS), AS is considered poorly contagious and is supposed to be spontaneous in origin. The zoonotic potential of AS, its strain variability and the relationships with the more contagious CS strains remain largely unknown. We characterized AS isolates from sheep and goats by transmission in ovinised transgenic mice (tg338) and in two genetic lines of bank voles, carrying either methionine (BvM) or isoleucine (BvI) at PrP residue 109. All AS isolates induced the same pathological phenotype in tg338 mice, thus proving that they encoded the same strain, irrespective of their geographical origin or source species. In bank voles, we found that the M109I polymorphism dictates the susceptibility to AS. BvI were susceptible and faithfully reproduced the AS strain, while the transmission in BvM was highly inefficient and was characterized by a conformational change towards a CS-like prion strain. Sub-passaging experiments revealed that the main strain component of AS is accompanied by minor CS-like strain components, which can be positively selected during replication in both AS-resistant or AS-susceptible animals. These findings add new clues for a better comprehension of strain selection dynamics in prion infections and have wider implications for understanding the origin of contagious prion strains, such as CS.

Relationship between childhood sexual abuse and attitudes toward premarital sexual permissiveness among middle school students in Luzhou, China.

BACKGROUND: In recent years, the number of adolescents engaging in premarital sex has increased, and an increasing number of childhood sexual abuse (CSA) cases have been reported in China. Many studies have indicated that CSA has a well-established association with risky sexual activities. However, only a limited number of studies have explored possible reasons for this association among middle school students, a population that may engage in premarital sex, which is critical for the development of interventions to prevent risky sexual behavior. Based on random samples of middle school students from a Chinese city, this article investigated the relationship between CSA and students' premarital sexual permissiveness (PSP). METHODS: In a cross-sectional study conducted between 2016 and 2017 in Luzhou, China, 2292 middle school and high school students aged 12-18 years were recruited by multistage random sampling. All students were administered anonymous questionnaires. Multiple linear regression and binary logistic regression analyses were conducted to analyze the relationship between CSA and PSP. RESULTS: The prevalence of CSA was 15.4% (354/2292; 95% CI: 14-16.9%). A higher percentage of male respondents (18.2%) than female respondents (12.9%) had experienced CSA. A positive association between CSA and PSP was found among students. Respondents who had suffered CSA exhibited greater PSP, and this relationship was observed in the male sample, female sample and the total student sample in Luzhou (ß = - 3.76, P < 0.05; ß = - 2.79, P < 0.05; and ß = - 2.84, P < 0.05, respectively). Respondents who had suffered CSA were also more likely to express a double standard about premarital sex (odds ratio [OR] =1.41, P < 0.05), especially among male students (odds ratio [OR] =1.63, P < 0.05). CONCLUSIONS: Sex differences in CSA and the relationship between CSA and PSP were significant among this large sample of middle school students in Luzhou (China). The findings suggest that experiencing CSA may be closely related to youth attitudes toward premarital sex, especially among males. Therefore, it is important to emphasize the prevention of CSA and provide adolescent reproductive health programs to reduce the impact of CSA on sexual cognition and attitude, prevent premarital sex and promote positive attitudes toward sexual equality for middle school students.

FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication.

The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is known about the factors regulating this process in infected cells. Here we show that HCV is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an iron-dependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2). Genetic depletion and ectopic expression experiments show FADS2 is a key determinant of cellular sensitivity to ferroptosis. Inhibiting FADS2 markedly enhances HCV replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Our results identify FADS2 as a rate-limiting factor in ferroptosis, and suggest the possibility of pharmacologically manipulating the ferroptosis pathway to attenuate viral replication.

Does parental permissiveness toward cigarette smoking and alcohol use influence illicit drug use among adolescents? A longitudinal study in seven European countries.

PURPOSE: Adolescents' perceptions of parental norms may influence their substance use. The relationship between parental norms toward cigarette and alcohol use, and the use of illicit substances among their adolescent children is not sufficiently investigated. The purpose of this study was to analyze this relationship, including gender differences, using longitudinal data from a large population-based study. METHODS: The present study analyzed longitudinal data from 3171 12- to 14-year-old students in 7 European countries allocated to the control arm of the European Drug Addiction Prevention trial. The impact of parental permissiveness toward cigarettes and alcohol use reported by the students at baseline on illicit drug use at 6-month follow-up was analyzed through multilevel logistic regression models, stratified by gender. Whether adolescents' own use of cigarette and alcohol mediated the association between parental norms and illicit drug use was tested through mediation models. RESULTS: Parental permissive norms toward cigarette smoking and alcohol use at baseline predicted adolescents' illicit drug use at follow-up. The association was stronger among boys than among girls and was mediated by adolescents' own cigarette and alcohol use. CONCLUSION: Perceived parental permissiveness toward the use of legal drugs predicted adolescents' use of illicit drugs, especially among boys. Parents should be made aware of the importance of norm setting, and supported in conveying clear messages of disapproval of all substances.

Tolerancia al triclosán en cepas de Klebsiella pneumoniae y Escherichia coli de origen clínico / Triclosan tolerance in Klebsiella pneumoniae and Escherichia coli strains of clinical origin / Tolerância a Triclosan em cepas de Klebsiella pneumoniae e Escherichia coli de origem clínica

Introducción: Los biocidas son compuestos químicos que se emplean comúnmente para inhibir o eliminar el crecimiento microbiano. El triclosán es un agente biocida que afecta la estructura y función microbiana. Es am-pliamente utilizando como desinfectante y antiséptico en suturas quirúrgicas, exfoliantes, implantes y dispositivos médicos, pero se ha observado el desarrollo de múltiples mecanismos de tolerancia bacteriana a este agente. Objetivo: Determinar la tolerancia al triclosán en cepas de Escherichia coli y Klebsiella pneumoniae. Materiales y métodos: Se llevó a cabo un estudio descriptivo de corte transversal, de tipo observacional, a partir de cepas de origen clínico que presentaran algunos genotipos de resistencia a los antibióticos como blaTEM, blaCTXM1 y blaSHV. Se determinó la concentración mínima inhibitoria (C1, C2, C3, C4 y C5) al triclosán. Resultados: De los 32 aislamientos recuperados, 17 fueron de E. coli y 15 de K. pneumoniae. Se evidenció que el 25 % de los aislamientos evaluados presentó tolerancia a concentraciones más bajas C1 (0,00025 %) de triclosán y que el 12 % fue tolerante a la concentración más alta C1 (1 %). Adicionalmente, un mayor número de cepas de E. coli presentó mayor tolerancia al triclosán que las cepas de K. pneumoniae. Así mismo, se evidenció que la mayoría de las cepas fueron tolerantes a las concentraciones evaluadas más bajas. Conclusiones: El 37 % de los aislados presentaron tolerancia al triclosán, con predominio de la E. coli. Palabras clave: triclosán; tolerancia; bacterias; gramnegativas

Introduction: Biocides are chemical compounds that are commonly used to inhibit or eliminate mi-crobial growth. Triclosan is a biocidal agent that affects microbial structure and function. It is widely used as a disinfectant and antiseptic in surgical sutures, exfoliants, implants and medical devices. The development of multiple mechanisms of bacterial tolerance to this agent has been observed. Target. To determine the tolerance to triclosan in strains of Escherichia coli and Klebsiella pneumoniae. Materials and methods: A descriptive, cross-sectional, observational study was carried out using strains of clinical origin, which presented some genotypes of resistance to antibiotics such as blaTEM, blaCTXM1, and blaSHV. The Minimum Inhibitory Concentration (C1, C2, C3, C4, and C5) to triclosan was determined. Results: Of the 32 isolates recovered, 17 were E. coli and 15 were K. pneumoniae. It was evidenced that 25% of the evaluated isolates presented tolerance to lower concentrations C1 (0.00025%) of triclosan and 12% were tolerant to the highest concentration C1 (1%). Additionally, a greater number of E. coli strains presented greater tolerance to triclosan than the K. pneumoniae strains, likewise, it was evidenced that most of the strains were tolerant to the lowest concentrations evaluated.

Introdução: Os biocidas são compostos químicos comumente usados para inibir ou eliminar o cres-cimento microbiano. O Triclosan é um agente biocida que afeta a estrutura e função microbiana. É amplamente utilizado como desinfetante e anti-séptico em suturas cirúrgicas, esfoliantes, implantes e dispositivos médicos, mas foram observados múltiplos mecanismos de tolerância bacteriana a este agente. Objetivo: Determinar a tolerância ao Triclosan nas cepas Escherichia coli e Klebsiella pneumoniae. Materiais e métodos: Foi realizado um estudo descritivo, transversal, observacional, em cepas de origem clínica com alguns genótipos de resistência a antibióticos como blaTEM, blaCTXM1 e blaSHV. A concentração inibitória mínima (C1, C2, C3, C4 e C5) de Triclosan foi determinada. Resultado: Dos 32 isolados recuperados, 17 eram E. coli e 15 eram K. pneumoniae. Verificou-se que 25% dos isolados testados eram tolerantes a menores concentrações de C1 (0,00025%) de Triclosan e 12% eram tolerantes à maior concentração C1 (1%). Além disso, um maior número de cepas de E. coli foram tolerantes a Triclosan, do que às cepas de K. pneumoniae. Foi também evidente que a maioria das cepas foi tolerante às menores concentrações testadas

The Mediating Role of Parental Factors in the Social Patterning of Smoking among Adolescents in Urban Indonesia.

INTRODUCTION: Parental factors may explain part of the social patterning of smoking among adolescents. This study aims at assessing the association between adolescent smoking and family characteristics (parental education, family wealth, and religion) and the mediating role of parental factors (smoking, control, and permissiveness towards smoking). METHODS: In 2017, a cross-sectional survey was conducted in eight Indonesian cities among 2,393 students aged 13-18 years. Multilevel logistic regression analysis estimated the associations between family characteristics and adolescent smoking. Generalized Structural Equation Models (GSEM) quantified mediation of these associations by parental factors. Analyses were stratified by gender. RESULTS: Smoking prevalence was 35.8% among boys and 2.6% among girls. Odds of smoking were higher among those with lower parental education among boys (low vs. high: OR:1.57, 95%CI:1.01-2.43), but not girls (OR:0.91, 95%CI:0.24-3.43). The association among boys was partially mediated by father's smoking status, parental control, and parental permissiveness towards smoking. High family wealth was associated with higher odds of smoking among girls (poorer vs. wealthier: OR:0.39, 95%CI:0.15-0.99), but not boys (OR:0.76, 95%CI:0.52-1.10). This association among girls was not clearly mediated by parental factors. Religion was not associated with smoking among boys or girls. CONCLUSIONS: In Indonesia's urban settings, inequalities in boys' smoking by educational background may be addressed by measures aimed at supporting lower educated parents to improve parental control and to reduce permissiveness towards smoking.