Concordance between reflectance confocal microscopy and histopathology for the diagnosis of acral lentiginous melanoma.

BACKGROUND: Acral lentiginous melanoma (ALM) is a highly malignant and invasive type of melanoma with unique locations of onset. Its incidence is increasing and early diagnosis is challenging. Reflectance confocal microscopy (RCM) is a non-invasive technique that provides an accurate image of tissue pathology. There are few reports on the use of RCM for the assessment of ALM. MATERIALS AND METHODS: In this retrospective study, data from 31 patients with a clinical diagnosis of ALM were collected. RCM image features were compared with histopathological findings to determine the concordance between the two methods. The sensitivity, specificity, positive predictive value, and negative predictive value of RCM for the diagnosis of ALM were evaluated. RESULTS: RCM and histopathology findings were concordant in 29 of 31 patients (93.5%). There were no false-negative results, although there were two false positives in RCM diagnosis. The sensitivity of RCM for diagnosing ALM was 100%, specificity was 50%, positive predictive value was 93.1%, and negative predictive value was 100%. CONCLUSIONS: RCM showed substantial concordance with histopathology in the diagnosis of ALM. It is a reliable and valuable non-invasive diagnostic tool that holds promise for the early diagnosis of ALM.

Chromosome-level genome of the transformable northern wattle, Acacia crassicarpa.

The genus Acacia is a large group of woody legumes containing an enormous amount of morphological diversity in leaf shape. This diversity is at least in part the result of an innovation in leaf development where many Acacia species are capable of developing leaves of both bifacial and unifacial morphologies. While not unique in the plant kingdom, unifaciality is most commonly associated with monocots, and its developmental genetic mechanisms have yet to be explored beyond this group. In this study, we identify an accession of Acacia crassicarpa with high regeneration rates and isolate a clone for genome sequencing. We generate a chromosome-level assembly of this readily transformable clone, and using comparative analyses, confirm a whole-genome duplication unique to Caesalpinoid legumes. This resource will be important for future work examining genome evolution in legumes and the unique developmental genetic mechanisms underlying unifacial morphogenesis in Acacia.

A widespread single amino acid mutation in AcrA reduces tigecycline susceptibility in Klebsiella pneumoniae.

IMPORTANCE: Tigecycline, a glycecycline antibiotic with broad-spectrum activity against almost all Gram-positive and Gram-negative bacteria, is a highly concerned "last-resort" antibiotic. In addition to plasmid-hosted mobile tet(X) conferring high-level resistance to tigecycline, there are many reports suggesting increased expression of AcrAB-TolC efflux pump leads to tigecycline non-susceptibility. However, the role of mutations in AcrAB-TolC on tigecycline resistance has not been identified. This study reports a novel T188A mutation of the AcrA subunit of AcrAB-TolC complex in a clinical tigecycline-resistant Klebsiella pneumoniae strain and reveals the role of AcrA mutation on tigecycline resistance in K. pneumoniae. High prevalence of A188 type AcrA in hypervirulent multidrug-resistant K. pneumoniae indicates that mutations of the AcrAB-TolC complex may play a larger role in determining bacterial pathogenesis and antibiotic susceptibility than previously expected.

Comparing organization-focused and state-focused financing strategies on provider-level reach of a youth substance use treatment model: a mixed-method study.

BACKGROUND: Financial barriers in substance use disorder service systems have limited the widespread adoption-i.e., provider-level reach-of evidence-based practices (EBPs) for youth substance use disorders. Reach is essential to maximizing the population-level impact of EBPs. One promising, but rarely studied, type of implementation strategy for overcoming barriers to EBP reach is financing strategies, which direct financial resources in various ways to support implementation. We evaluated financing strategies for the Adolescent Community Reinforcement Approach (A-CRA) EBP by comparing two US federal grant mechanisms, organization-focused and state-focused grants, on organization-level A-CRA reach outcomes. METHOD: A-CRA implementation took place through organization-focused and state-focused grantee cohorts from 2006 to 2021. We used a quasi-experimental, mixed-method design to compare reach between treatment organizations funded by organization-focused versus state-focused grants (164 organizations, 35 states). Using administrative training records, we calculated reach as the per-organization proportion of trained individuals who received certification in A-CRA clinical delivery and/or supervision by the end of grant funding. We tested differences in certification rate by grant type using multivariable linear regression models that controlled for key covariates (e.g., time), and tested threats to internal validity from our quasi-experimental design through a series of sensitivity analyses. We also drew on interviews and surveys collected from the treatment organizations and (when relevant) interviews with state administrators to identify factors that influenced reach. RESULTS: The overall certification rates were 27 percentage points lower in state-focused versus organization-focused grants (p = .01). Sensitivity analyses suggested these findings were not explained by confounding temporal trends nor by organizational or state characteristics. We did not identify significant quantitative moderators of reach outcomes, but qualitative findings suggested certain facilitating factors were more influential for organization-focused grants (e.g., strategic planning) and certain barrier factors were more impactful for state-focused grants (e.g., states finding it difficult to execute grant activities). DISCUSSION: As the first published comparison of EBP reach outcomes between financing strategies, our findings can help guide state and federal policy related to financing strategies for implementing EBPs that reduce youth substance use. Future work should explore contextual conditions under which different financing strategies can support the widespread implementation of EBPs for substance use disorder treatment.

Genome-wide screens reveal shared and strain-specific genes that facilitate enteric colonization by Klebsiella pneumoniae.

Gastrointestinal (GI) colonization by Klebsiella pneumoniae is a risk factor for subsequent infection as well as transmission to other patients. Additionally, colonization is achieved by many strain types that exhibit high diversity in genetic content. Thus, we aimed to study strain-specific requirements for K. pneumoniae GI colonization by applying transposon insertion sequencing to three classical clinical strains: a carbapenem-resistant strain, an extended-spectrum beta-lactamase-producing strain, and a non-epidemic antibiotic-susceptible strain. The transposon insertion libraries were screened in a murine model of GI colonization. At 3 days post-inoculation, 27 genes were required by all three strains for colonization. Isogenic deletion mutants for three genes/operons (acrA, carAB, and tatABCD) confirmed colonization defects in each of the three strains. Additionally, deletion of acrA reduced bile tolerance in vitro, while complementation restored both bile tolerance in vitro and colonization ability in vivo. Transposon insertion sequencing suggested that some genes were more important for the colonization of one strain than the others. For example, deletion of the sucrose porin-encoding gene scrY resulted in a colonization defect in the carbapenemase-producing strain but not in the extended-spectrum beta-lactamase producer or the antibiotic-susceptible strain. These findings demonstrate that classical K. pneumoniae strains use both shared and strain-specific strategies to colonize the mouse GI tract. IMPORTANCE Klebsiella pneumoniae is a common cause of difficult-to-treat infections due to its propensity to express resistance to many antibiotics. For example, carbapenem-resistant K. pneumoniae has been named an urgent threat by the United States Centers for Disease Control and Prevention. Gastrointestinal colonization in patients with K. pneumoniae has been linked to subsequent infection, making it a key process to control in the prevention of multidrug-resistant infections. However, the bacterial factors which contribute to K. pneumoniae colonization are not well understood. Additionally, individual strains exhibit large amounts of genetic diversity, begging the question of whether some colonization factors are strain dependent. This study identifies the enteric colonization factors of three classical strains using transposon mutant screens to define a core colonization program for K. pneumoniae as well as detecting strain-to-strain differences in colonization strategies.

RND pump inhibition: in-silico and in-vitro study by Eugenol on clinical strain of E. coli and P. aeruginosa.

Multidrug-resistant (MDR) gram-negative bacteria pose significant challenges to the public health. Various factors are involved in the development and spread of MDR strains, including the overuse and misuse of antibiotics, the lack of new antibiotics being developed, and etc. Efflux pump is one of the most important factors in the emergence of antibiotic resistance in bacteria. Aiming at the introduction of novel plant antibiotic, we investigated the effect of eugenol on the MexA and AcrA efflux pumps in Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). Molecular docking was performed using PachDock Server 1.3. The effect of eugenol on bacteria was determined by disk diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A cartwheel test was also performed to evaluate efflux pump inhibition. Finally, the expression of the MexA and AcrA genes was examined by real-time PCR. The results of molecular docking showed that eugenol interacted with MexA and AcrA pumps at - 29.28 and - 28.59 Kcal.mol-1, respectively. The results of the antibiogram test indicated that the antibiotic resistance of the treated bacteria decreased significantly (p < 0.05). The results of the cartwheel test suggested the inhibition of efflux pump activity in P. aeruginosa and E. coli. Analysis of the genes by real-time PCR demonstrated that the expression of MexA and AcrA genes was significantly reduced, compared to untreated bacteria (p < 0.001). The findings suggest, among other things, that eugenol may make P. aeruginosa and E. coli more sensitive to antibiotics and that it could be used as an inhibitor to prevent bacteria from becoming resistant to antibiotics.

Detection of AcrA and AcrB Efflux Pumps in Multidrug-Resistant Klebsiella pneumonia that Isolated from Wounds Infection Patients in Al-Diwaniyah Province.

Many infections produced by multidrug-resistant (MDR) Klebsiella pneumoniae are the main cause of death and treatment restrictions worldwide. In K. pneumoniae, the efflux pump system is dangerous in drug resistance. Therefore, this study was designed to investigate the involvement of the AcrA and AcrB efflux pumps in antibiotic resistance in Klebsiella pneumoniae isolated from wound patients. During June 2021-February 2022, 87 clinical isolates of Klebsiella pneumonia bacteria were obtained from wound samples patients consulted to the hospitals in AL-Diwaniyah province, Iraq. The disc diffusion method performed an antibiotic susceptibility test after microbiological/biochemical identification. The polymerase chain reaction (PCR) technique was used to examine efflux genes' prevalence (acrA and acrB). The results showed that resistance to Carbenicillin 72 (82.7%), Erythromycin 66 (75.8%), Rifampin 58 (66.6%), Ceftazidime 52 (59.7%), Cefotaxime 44 (50.5%), Novobiocin 38 (43.6%), Tetracycline 32 (36.7%), Ciprofloxacin 22 (25.2%), Gentamicin 16 (18.3%), Nitrofurantoin 6 (10.3%) in Klebsiella pneumoniae isolates. The PCR procedure revealed that the occurrence of the acrA and acrB genes is 55 (100%) and 55 (100%), respectively. The findings of this investigation show that the AcrA and AcrB efflux pumps play a crucial character in antibiotic resistance in multidrug-resistant Klebsiella pneumoniae bacterial isolates. As a result of the unintentional transmission of antimicrobial resistance genes, precise detection of resistance genes using molecular approaches is required to switch the extent of resistant strains.

Efflux Pump-Binding 4(3-Aminocyclobutyl)Pyrimidin-2-Amines Are Colloidal Aggregators.

Efflux pumps are a relevant factor in antimicrobial resistance. In E. coli, the tripartite efflux pump AcrAB-TolC removes a chemically diverse set of antibiotics from the bacterium. Therefore, small molecules interfering with efflux pump function are considered adjuvants for improving antimicrobial therapies. Several compounds targeting the periplasmic adapter protein AcrA and the efflux pump AcrB have been identified to act synergistically with different antibiotics. Among those, several 4(3-aminocyclobutyl)pyrimidin-2-amines have been shown to bind to both proteins. In this study, we intended to identify analogs of these substances with improved binding affinity to AcrA using virtual screening followed by experimental validation. While we succeeded in identifying several compounds showing a synergistic effect with erythromycin on E. coli, biophysical studies suggested that 4(3-aminocyclobutyl)pyrimidin-2-amines form colloidal aggregates that do not bind specifically to AcrA. Therefore, these substances are not suited for further development. Our study emphasizes the importance of implementing additional control experiments to identify aggregators among bioactive compounds.

Estrategias de aprendizaje y comprensión lectora en estudiantes de educación artística / Learning strategies and reading comprehension in art education students / Estratégias de aprendizagem e compreensão leitora em estudantes de arte-educação

Las estrategias de aprendizaje y la comprensión de lectura representan temas urgentes de revisión en el nivel educativo, lo es dentro de la educación básica y superior; sin embargo, con diferencias específicas, en el ámbito de la educación artística aún han sido poco exploradas. Así pues, los estudiantes de educación superior privilegian los aprendizajes relacionados al fortalecimiento de su talento o actividad artística de diversas manifestaciones artístico culturales, a la par que reciben una educación integral que permita la contribución con su perfil de egreso (pedagogos del arte). Esta situación ha determinado que se describa la relación entre dos variables de investigación para tomar acción educativa en este grupo de estudio en particular. El alcance correlacional, dentro de lo cuantitativo, ha servido para que, con la aplicación de dos instrumentos: una escala de estrategias de aprendizaje (ACRA) y una prueba que mide el nivel de comprensión lectora en 64 alumnos de arte en educación superior, se concluya que no existe relación (p ≥ 0,05) entre estas. Esto es estadísticamente significativo con un p-valor = ,617. En tal sentido, los estudiantes, si bien reciben el aprendizaje de las estrategias, no tienen relación con el desarrollo de su competencia lectora dada su escasa práctica.

Learning strategies and reading comprehension represent urgent review issues at the educational level, it is within basic and higher education; however, with specific differences, in the field of artistic education they have still been little explored. Thus, higher education students privilege learning related to strengthening their talent or artistic activity of various cultural artistic manifestations, while receiving a comprehensive education that allows the contribution to their graduation profile (art pedagogues). This situation has determined that the relationship between two research variables is described in order to take educational action in this particular study group. The correlational scope, within the quantitative, has served so that, with the application of two instruments: a scale of learning strategies (ACRA) and a test that measures the level of reading comprehension in 64 art students in higher education, conclude that there is no relationship (p ≥ 0.05) between them. This is statistically significant with a p-value = .617. In this sense, the students, although they receive the learning of the strategies, are not related to the development of their reading competence given their little practice.

Estratégias de aprendizagem e compreensão de leitura representam questões urgentes de revisão no nível educacional, seja na educação básica e superior; porém, com diferenças específicas, no campo da educação artística ainda são pouco exploradas. Assim, os estudantes do ensino superior privilegiam as aprendizagens relacionadas com o reforço do seu talento ou atividade artística de diversas manifestações artísticas culturais, ao mesmo tempo que recebem uma formação integral que permite contribuir para o seu perfil de formação (pedagogos da arte). Essa situação determinou que a relação entre duas variáveis de pesquisa seja descrita para a ação educativa nesse grupo de estudo específico. O escopo correlacional, dentro do quantitativo, serviu para que, com a aplicação de dois instrumentos: uma escala de estratégias de aprendizagem (ACRA) e um teste que mede o nível de compreensão leitora em 64 estudantes de arte do ensino superior, concluímos que há nenhuma relação (p ≥ 0,05) entre eles. Isso é estatisticamente significativo com um valor de p = 0,617. Nesse sentido, os alunos, embora recebam o aprendizado das estratégias, não se relacionam com o desenvolvimento de sua competência leitora dada sua pouca prática.

TolC-AcrA complex formation monitored by time dependent single-channel electrophysiology.

Characterizing protein-protein interaction on a single molecular level is a challenge, experimentally as well as interpretation of the data. For example, Gram-negative bacteria contain protein complexes spanning the outer and inner cell wall devoted to efflux effectively cell toxic substances. Recent seminal work revealed the high-resolution structure of such a tripartic composition TolC-AcrA-AcrB suggesting to design inhibitors preventing efflux of antibiotics. To show that electrophysiology can provide supporting information here, we reconstitute single TolC homotrimer into a planar lipid membrane, apply a transmembrane voltage and follow the assembly of AcrA to TolC using the modulation of the ion current through TolC channel during binding. In particular, the presence of AcrA in solution increases the average ionic current through TolC and, moreover, reduces the ion-current fluctuations caused by flickering of TolC. Here, we show that statistical properties of ion-current fluctuations (the power spectral density) provide a complementary measure of the interaction of the TolC-AcrA complex in presence of putative efflux pump inhibitors. Both characteristics, the average ion current across TolC and the current noise, taken into consideration together, point to a stiffening of the tip of TolC which might reduce the formation of the complex.

Estrategias de aprendizaje y comprensión lectora en estudiantes de educación artística

Las estrategias de aprendizaje y la comprensión de lectura representan temas urgentes de revisión en el nivel educativo, lo es dentro de la educación básica y superior; sin embargo, con diferencias específicas, en el ámbito de la educación artística aún han sido poco exploradas. Así pues, los estudiantes de educación superior privilegian los aprendizajes relacionados al fortalecimiento de su talento o actividad artística de diversas manifestaciones artístico culturales, a la par que reciben una educación integral que permita la contribución con su perfil de egreso (pedagogos del arte). Esta situación ha determinado que se describa la relación entre dos variables de investigación para tomar acción educativa en este grupo de estudio en particular. El alcance correlacional, dentro de lo cuantitativo, ha servido para que, con la aplicación de dos instrumentos: una escala de estrategias de aprendizaje (ACRA) y una prueba que mide el nivel de comprensión lectora en 64 alumnos de arte en educación superior, se concluya que no existe relación (p ≥ 0,05) entre estas. Esto es estadísticamente significativo con un p-valor = ,617. En tal sentido, los estudiantes, si bien reciben el aprendizaje de las estrategias, no tienen relación con el desarrollo de su competencia lectora dada su escasa práctica.

Learning strategies and reading comprehension represent urgent review issues at the educational level, it is within basic and higher education; however, with specific differences, in the field of artistic education they have still been little explored. Thus, higher education students privilege learning related to strengthening their talent or artistic activity of various cultural artistic manifestations, while receiving a comprehensive education that allows the contribution to their graduation profile (art pedagogues). This situation has determined that the relationship between two research variables is described in order to take educational action in this particular study group. The correlational scope, within the quantitative, has served so that, with the application of two instruments: a scale of learning strategies (ACRA) and a test that measures the level of reading comprehension in 64 art students in higher education, conclude that there is no relationship (p ≥ 0.05) between them. This is statistically significant with a p-value = .617. In this sense, the students, although they receive the learning of the strategies, are not related to the development of their reading competence given their little practice.

Estratégias de aprendizagem e compreensão de leitura representam questões urgentes de revisão no nível educacional, seja na educação básica e superior; porém, com diferenças específicas, no campo da educação artística ainda são pouco exploradas. Assim, os estudantes do ensino superior privilegiam as aprendizagens relacionadas com o reforço do seu talento ou atividade artística de diversas manifestações artísticas culturais, ao mesmo tempo que recebem uma formação integral que permite contribuir para o seu perfil de formação (pedagogos da arte). Essa situação determinou que a relação entre duas variáveis de pesquisa seja descrita para a ação educativa nesse grupo de estudo específico. O escopo correlacional, dentro do quantitativo, serviu para que, com a aplicação de dois instrumentos: uma escala de estratégias de aprendizagem (ACRA) e um teste que mede o nível de compreensão leitora em 64 estudantes de arte do ensino superior, concluímos que há nenhuma relação (p ≥ 0,05) entre eles. Isso é estatisticamente significativo com um valor de p = 0,617. Nesse sentido, os alunos, embora recebam o aprendizado das estratégias, não se relacionam com o desenvolvimento de sua competência leitora dada sua pouca prática.

Comparing two federal financing strategies on penetration and sustainment of the adolescent community reinforcement approach for substance use disorders: protocol for a mixed-method study.

BACKGROUND: Sustained, widespread availability of evidence-based practices (EBPs) is essential to address the public health and societal impacts of adolescent substance use disorders (SUD). There remains a particularly significant need to identify effective financing strategies, which secure and direct financial resources to support the costs associated with EBP implementation and sustainment. This protocol describes a new project comparing two types of U.S. federal grant mechanisms (i.e., a type of financing strategy), which supported the implementation of the Adolescent Community Reinforcement Approach (A-CRA) EBP for SUD, through either organization-focused or state-focused granting of funds. The Exploration-Preparation-Implementation-Sustainment (EPIS) framework will guide our study aims, hypotheses, and selection of measures. METHOD: We will employ a longitudinal, mixed-method (i.e., web surveys, semi-structured interviews, document review, focus groups, administrative data), quasi-experimental design to compare the grant types' outcomes and examine theoretically informed mediators and moderators. Aim 1 will examine the proportion of eligible clinicians certified in A-CRA with adequate fidelity levels (i.e., penetration outcomes) at the end of grant funding. Aim 2 will examine the sustainment of A-CRA up to 5 years post-funding, using a 10-element composite measure of treatment delivery and supervision activities. We will integrate the new data collected from state-focused grant recipients (~85 organizations in 19 states) with previously collected data from organization-focused grant recipients (Hunter et al., Implement Sci 9:104, 2014) (82 organizations in 26 states) for analysis. We will also use sensitivity analyses to characterize the effects of observed and unobserved secular trends in our quasi-experimental design. Finally, aim 3 will use comparative case study methods (integrating diverse quantitative and qualitative measures) to identify and disseminate policy implications about the roles of state- and organization-focused federal grants in efforts to promote adolescent SUD EBP implementation and sustainment. DISCUSSION: The proposed research will have direct, practical implications for behavioral health administrators, policymakers, implementation experts, and the public. It will offer new knowledge that can directly inform financing strategies to support large-scale, sustained EBP delivery in behavioral health-while advancing implementation science through the use of novel methods to study financing strategies and sustainment.

Hfq Regulates Efflux Pump Expression and Purine Metabolic Pathway to Increase Trimethoprim Resistance in Aeromonas veronii.

Aeromonas veronii (A. veronii) is a zoonotic pathogen. It causes clinically a variety of diseases such as dysentery, bacteremia, and meningitis, and brings huge losses to aquaculture. A. veronii has been documented as a multiple antibiotic resistant bacterium. Hfq (host factor for RNA bacteriophage Qß replication) participates in the regulations of the virulence, adhesion, and nitrogen fixation, effecting on the growth, metabolism synthesis and stress resistance in bacteria. The deletion of hfq gene in A. veronii showed more sensitivity to trimethoprim, accompanying by the upregulations of purine metabolic genes and downregulations of efflux pump genes by transcriptomic data analysis. Coherently, the complementation of efflux pump-related genes acrA and acrB recovered the trimethoprim resistance in Δhfq. Besides, the accumulations of adenosine and guanosine were increased in Δhfq in metabonomic data. The strain Δhfq conferred more sensitive to trimethoprim after appending 1 mM guanosine to M9 medium, while wild type was not altered. These results demonstrated that Hfq mediated trimethoprim resistance by elevating efflux pump expression and degrading adenosine, and guanosine metabolites. Collectively, Hfq is a potential target to tackle trimethoprim resistance in A. veronii infection.

Proteomic profiling of Klebsiella pneumoniae carbapenemase (KPC)-producer Klebsiella pneumoniae after induced polymyxin resistance.

Aim: To elucidate the changes in protein expression associated with polymyxin resistance in Klebsiella pneumoniae, we profiled a comparative proteomic analysis of polymyxin B-resistant mutants KPC-2-producing K. pneumoniae, and of its susceptible counterparts. Material & methods: Two-dimensional reversed phase nano ultra-performance liquid chromatography mass spectrometry was used for proteomic analysis. Results: Our results showed that the proteomic profile involved several biological processes, and we highlight the downregulation of outer membrane protein A (OmpA) and the upregulation of SlyB outer membrane lipoprotein (conserved protein member of the PhoPQ regulon) and AcrA multidrug efflux pump in polymyxin B-resistant strains. Conclusion: Our results highlight the possible participation of the SlyB, AcrA and OmpA proteins in the determination of polymyxin B heteroresistance in KPC-2-producing K. pneumoniae.

Measuring Small Molecule Binding to Escherichia coli AcrB by Surface Plasmon Resonance.

Antimicrobial resistance (AMR) is rapidly becoming one of the great healthcare challenges. A common mechanism employed by pathogenic bacteria to avoid the action of certain antibiotics is to overexpress efflux pumps that can extrude these drugs from the cell rendering them ineffective. Small molecule inhibitors that target bacterial efflux pumps provide a route toward reversing AMR. Here, we describe the application of surface plasmon resonance (SPR) technology to characterize protein:small molecule interactions between the inner membrane protein AcrB subunit of the Escherichia coli AcrA-AcrB-TolC efflux pump and its substrates and novel inhibitors. The SPR assay provides quantitative data about the kinetics of binding that can help guide the development of new chemotherapies to combat AMR.

Retention and Treatment Outcome of Youth with Cannabis Use Disorder Referred By the Legal System.

BACKGROUND: Youth with Substance Use Disorders (SUDs) referred to treatment from the Juvenile Justice System (JJS) account for approximately half of the treatment admissions nationwide. The objective of this paper is to report a comparison of retention and outcomes for JJS referrals to those from the general community. METHODS: A total of 172 adolescents, 13-18 years of age, 83% males, 70% JJS referrals, diagnosed with DSM-IV Cannabis Use Disorder (CUD), enrolled in this outpatient, randomized, continued care study. Following a 7-session weekly motivational enhancement and cognitive behavioral therapy intervention (MET/CBT-7), only poor responders were randomized into a 10-week second phase of either an individualized enhanced CBT or an Adolescent Community Reinforcement Approach (ACRA) intervention. RESULTS: JJS referrals' retention rates were significantly higher than those of non-JJS referrals (X 2 (1) = 11.21, p < .01) at the end of Phase I (i.e. week 7). However, there was no difference in abstinence rates between the groups at the end of phase I or II and any of the quarterly additional follow-up assessments up to one year from treatment onset. CONCLUSIONS: Additional research examining how to capitalize on improved retention rates among youth JJS referrals is necessary in order to advance abstinence.

Factors associated with an evidence-based measure of implementation for the Adolescent Community Reinforcement Approach.

BACKGROUND: An evidence-based measure of implementation (EBMI) is an implementation outcome measure shown to have predictive validity with one or more future-measured constructs of importance. The current study sought to identify correlates and predictors of an EBMI called procedure exposure. Garner et al. (2016) found procedure exposure to be an EBMI for the Adolescent Community Reinforcement Approach (A-CRA). METHODS: The dataset included 76 community-based substance use treatment organizations located across the United States. Organizational-level regression analyses, which were framed within the context of Chaudoir et al. (2013) framework for predicting implementation outcomes, were used to examine predictors of A-CRA procedure exposure RESULTS: The Washington Circle's treatment initiation performance measure (B=5.05 [SE=1.60], p=0.002), as well as session exposure (B=0.18 [SE=0.06], p=0.003), were significant predictors of A-CRA procedure exposure in the backward stepwise regression analysis (Adjusted R-square=0.55). The Washington Circle's treatment engagement performance measure (B=7.93 [SE=0.77], p<0.001), as well as time-to-proficiency (B=-0.04 [SE=0.02], p=0.02), each had significant bivariate relationships with A-CRA procedure exposure but were not retained in the final model. CONCLUSIONS: Organizations implementing A-CRA are encouraged to make the following high priorities: (a) scheduling and completing a subsequent treatment session within 14days of their index session (treatment initiation) and (b) providing a targeted number of treatment sessions to each client (session exposure). To the extent organizations do this, they may be more likely to achieve higher levels of A-CRA procedure exposure.

An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump.

Bacterial efflux pumps confer multidrug resistance by transporting diverse antibiotics from the cell. In Gram-negative bacteria, some of these pumps form multi-protein assemblies that span the cell envelope. Here, we report the near-atomic resolution cryoEM structures of the Escherichia coli AcrAB-TolC multidrug efflux pump in resting and drug transport states, revealing a quaternary structural switch that allosterically couples and synchronizes initial ligand binding with channel opening. Within the transport-activated state, the channel remains open even though the pump cycles through three distinct conformations. Collectively, our data provide a dynamic mechanism for the assembly and operation of the AcrAB-TolC pump.

Ordering of convex polyhedra and the Fedorov algorithm.

A method of naming any convex polyhedron by a numerical code arising from the adjacency matrix of its edge graph has been previously suggested. A polyhedron can be built using its name. Classes of convex n-acra (i.e. n-vertex polyhedra) are strictly (without overlapping) ordered by their names. In this paper the relationship between the Fedorov algorithm to generate the whole combinatorial variety of convex polyhedra and the above ordering is described. The convex n-acra are weakly ordered by the maximum extra valencies of their vertices. Thus, non-simple n-acra follow the simple ones for any n.

Expression of the Fluoroquinolones Efflux Pump Genes acrA and mdfA in Urinary Escherichia coli Isolates.

Escherichia coli is one of the most frequent causes of urinary tract infections. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. Our aim in this study was to investigate the relation between antibiotic resistance and the expression of the efflux pump genes acrA and mdfA in E. coli by real-time reverse transcription-PCR. We tested the in vitro susceptibilities to 12 antibiotics in 28 clinical isolates of E. coli obtained from urine samples. We also determined the minimum inhibitory concentrations of levofloxacin to these samples. We then revealed significant correlations between the overexpression of both mdfA and acrA and MICs of levofloxacin. In conclusion, we demonstrated that the increased expression of efflux pump genes such as mdfA and acrA can lead to levofloxacin resistance in E. coli. These findings contribute to further understanding of the molecular mechanisms of efflux pump systems and how they contribute to antibiotic resistance.