Overview on Strategies and Assays for Antibiotic Discovery.

The increase in antibiotic resistance poses a major threat to global health. Actinomycetes, the Gram-positive bacteria of the order Actinomycetales, are fertile producers of bioactive secondary metabolites, including antibiotics. Nearly two-thirds of antibiotics that are used for the treatment of bacterial infections were originally isolated from actinomycetes strains belonging to the genus Streptomyces. This emphasizes the importance of actinomycetes in antibiotic discovery. However, the identification of a new antimicrobial compound and the exploration of its mode of action are very challenging tasks. Therefore, different approaches that enable the "detection" of an antibiotic and the characterization of the mechanisms leading to the biological activity are indispensable. Beyond bioinformatics tools facilitating the identification of biosynthetic gene clusters (BGCs), whole cell-screenings-in which cells are exposed to actinomycete-derived compounds-are a common strategy applied at the very early stage in antibiotic drug development. More recently, target-based approaches have been established. In this case, the drug candidates were tested for interactions with usually validated targets. This review focuses on the bioactivity-based screening methods and provides the readers with an overview on the most relevant assays for the identification of antibiotic activity and investigation of mechanisms of action. Moreover, the article includes examples of the successful application of these methods and suggestions for improvement.

Long-Term Humoral Immune Response against SARS-CoV-2 after Natural Infection and Subsequent Vaccination According to WHO International Binding Antibody Units (BAU/mL).

The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.

Facing Interpersonal Violence: Identifying the Coping Profile of Poly-Victimized Resilient Adolescents.

Coping strategies are factors that mediate the relationship between interpersonal victimizations and psychological maladjustment. The objectives are as follows: (a) to establish the coping profile of adolescents according to the number of reported interpersonal victimizations; (b) to identify the most victimized adolescents (poly-victims), detecting those with psychological symptoms (nonresilient poly-victims) and those without psychological symptoms (resilient poly-victims), and then to examine any differences in coping strategies between the two groups; (c) to determine the accumulative effect of victimizations on mental health; and (d) to test the mediating role of both approach and avoidance coping between lifetime interpersonal victimizations and symptoms. Participants were 918 community Spanish adolescents (62.7% girls) aged between 14 and 18 years. Measures used were Youth Self-Report, Juvenile Victimization Questionnaire, and Adolescent Coping Orientation for Problem Experiences. The following results were reported: (a) The most victimized adolescents used to a greater degree avoidance coping strategies than nonvictimized adolescents. (b) Resilient poly-victimized adolescents were more likely to seek family support and tended to use more positive reappraisal than nonresilient poly-victimized adolescents. (c) A clear cumulative effect of victimizations on mental health was observed: 45% of the most victimized adolescents (poly-victims) reached clinical range on Youth Self-Report in front of 2% of nonvictimized adolescents. (d) Avoidance coping and more specifically Escaping and Venting feelings strategies played a mediating role between interpersonal victimizations and psychological symptoms. Approach coping had no mediating role, except for Positive reappraisal in girls. In conclusion, the possibility of identifying the coping profile of victimized adolescents may have clinical implications in terms of both prevention and intervention.

How do adolescents with Adjustment Disorder cope with stressful situations? Relationship with suicidal risk.

OBJECTIVE: Little is known about the role of coping in relation to suicidal risk in adolescents with Adjustment Disorder (AD). The present study aimed to assess the relation between suicidal ideation and intention and coping strategies in a clinical sample of adolescents with AD, paying special attention to gender differences. MATERIAL AND METHOD: Self-reported questionnaires about suicidal ideation and intention and coping strategies were administered to 108 adolescents with an AD diagnosis. RESULTS: Compared with the normative population, adolescents with an AD diagnosis made more use of Acceptance-Resignation (an avoidance-type coping strategy) and less use of Positive Reappraisal (an approach-type coping strategy). Nevertheless, gender introduced some peculiarities. A relationship was observed between the use of certain coping strategies and suicidal ideation and intention, but with notable differences depending on gender: significant and high correlations were found between these two variables in AD boys, both in the total approach score (r=.53, p<.01) and in the total avoidant score (r=.60, p<.01), with coping strategies explaining 41% of suicidal ideation and intention; in girls, in contrast, the only significant relationship was with an avoidant strategy, Emotional Discharge (r=.25, p<.05), although it had low explanatory power. CONCLUSIONS: Coping strategies must be taken into consideration when assessing and treating adolescents with AD at risk of suicide, especially in the case of boys. The absence of association between coping strategies and suicidal risk in girls is discussed, and some therapeutic proposals are presented.

Coping and Psychopathological Profile in Nonsuicidal Self-Injurious Chilean Adolescents.

OBJECTIVE: The aims of this study were to establish the roles of coping typologies and the psychological problems associated with nonsuicidal self-injury (NSSI) and to identify adolescents who are at greater risk of engaging in this practice. METHOD: The total sample comprised 965 adolescents (57% girls, aged 12-18 years) from several Chilean schools who answered the Inventory of Statements About Self-Injury questionnaire. RESULTS: Young people with and without NSSI present different coping patterns, especially when compared by gender. Adolescents with repetitive NSSI (R-NSSI) report using escape, search for friendship, and venting feelings as coping strategies as well as a more avoidant style and less search for family support than those adolescents without NSSI. Adolescents who present avoidance coping typology are three times more likely (relative risk = 3.5) to engage in NSSI than adolescents who present approach coping typology. R-NSSI adolescents present higher scores on psychological symptomatology (within clinical ranges) than their N-NSSI counterparts. Girls were more likely to present psychological symptoms than boys. CONCLUSION: The authors highlight the usefulness of coping typologies for the detection of high-risk populations for NSSI as well as the need to consider the gender variable. Professionals who detect clinical levels of symptomatology should also assess the presence of NSSI.

Adolescents' Daily Perception of Internalizing Emotional States by Means of Smartphone-based Ecological Momentary Assessment.

This study uses ecological momentary assessment (EMA) with smartphone devices to examine community adolescents' perceptions regarding both the intensity of and variability in their daily sadness/depression, anxiety, and somatic problems over the period of one week. Participants were 90 high-school students (M age = 14.61, SD = 1.64; range 12-18). The sample was divided according to gender (61.1% girls), migratory status (68.5% Spanish nationals and 31.5% Latin American immigrants), and level of psychological symptoms (17% risk group). Sadness/depression, anxiety, and somatic problems were examined using a smartphone app, five times per day, semi-randomly, for seven days (35 possible moments). A high proportion of adolescents did not report feelings of sadness (80.0%) or worry (79.3%) or physical symptoms on a daily basis (84.9%). Girls and the risk group reported greater intensity levels for the three analyzed problems than did boys and the normal group, respectively (p .05 in all cases). Day-to-day fluctuations in mood during the week were statistically significant but not meaningful (b = 0.0004, 95% CI [0.0001, 0.0008], p = .001).

Suicidal Tendency Among Adolescents With Adjustment Disorder.

BACKGROUND: Adolescents with adjustment disorder (AD) are at risk of presenting suicidal symptoms. Certain personality traits are linked to suicidal tendencies. There is a lack of information about the link between suicide and personality patterns in adolescents with AD. AIMS: To identify the personality characteristics that predispose to or prevent the development of suicidal ideation and behavior among adolescents with AD. METHOD: We recruited 108 adolescents with AD at a public mental health center near Barcelona (Spain). They were administered the Inventario de Riesgo Suicida para Adolescentes (IRIS) to assess suicidal symptoms, as well as the Millon Adolescent Clinical Inventory (MACI) and the 16PF Adolescent Personality Questionnaire (16PF-APQ) to appraise personality features. RESULTS: Doleful personality emerged as the principal risk for suicidal symptoms. The conforming personality pattern exerted a protective effect, and emotional stability was associated with low levels of suicidal tendencies. Among the Big Five factors, anxiety had the highest explanatory power for suicidal tendencies. CONCLUSION: Certain personality characteristics are associated with heightened or reduced risk of suicidal tendencies in adolescents with AD. Their identification is important for clinicians designing treatment programs for these patients.

Nanoscale pillar arrays for separations.

The work presented herein evaluates silicon nano-pillar arrays for use in planar chromatography. Electron beam lithography and metal thermal dewetting protocols were used to create nano-thin layer chromatography platforms. With these fabrication methods we are able to reduce the size of the characteristic features in a separation medium below that used in ultra-thin layer chromatography; i.e. pillar heights are 1-2 µm and pillar diameters are typically in the 200-400 nm range. In addition to the intrinsic nanoscale aspects of the systems, it is shown they can be further functionalized with nanoporous layers and traditional stationary phases for chromatography; hence exhibit broad-ranging lab-on-a-chip and point-of-care potential. Because of an inherent high permeability and very small effective mass transfer distance between pillars, chromatographic efficiency can be very high but is enhanced herein by stacking during development and focusing while drying, yielding plate heights in the nm range separated band volumes. Practical separations of fluorescent dyes, fluorescently derivatized amines, and anti-tumor drugs are illustrated.

Relationship between particular areas of victimization and mental health in the context of multiple victimizations in Spanish adolescents.

The main objective of this paper is to study the relationship between different areas of victimization (e.g., sexual victimization) and psychological symptoms taking into account the full range of victimizations adolescents suffer. The final aim is to contribute further evidence regarding the bias that those studies which focus on just one area of victimization may be introducing into our psychological knowledge. A total of 923 adolescents (62.4% girls) between 14 and 18 years old were recruited from seven secondary schools in Catalonia, Spain. The Youth Self-report and the Juvenile Victimization Questionnaire were employed to assess psychological problems (internalizing and externalizing symptoms) and victimization, respectively. The large majority of adolescents reported having experienced more than one area of victimization. However, Conventional Crime area was the one that was more reported in isolation. Overall, the explicative power of a particular area of victimization was greatly reduced or even lost its significance when the other areas were taken into account. However, some areas remained significant and were different by gender. Clinicians and researchers should take into account the whole range of victimizations adolescents suffer when intending to understand the psychological aftermaths of victimization. Some areas of victimization appear to be more important at explaining particular psychological symptoms, those being Peer and Sibling Victimization in the case of boys, and both Conventional Crime and Internet Victimization in the case of girls.

Superhydrophobic analyte concentration utilizing colloid-pillar array SERS substrates.

The ability to detect a few molecules present in a large sample is of great interest for the detection of trace components in both medicinal and environmental samples. Surface enhanced Raman spectroscopy (SERS) is a technique that can be utilized to detect molecules at very low absolute numbers. However, detection at trace concentration levels in real samples requires properly designed delivery and detection systems. The following work involves superhydrophobic surfaces that have as a framework deterministic or stochastic silicon pillar arrays formed by lithographic or metal dewetting protocols, respectively. In order to generate the necessary plasmonic substrate for SERS detection, simple and flow stable Ag colloid was added to the functionalized pillar array system via soaking. Native pillars and pillars with hydrophobic modification are used. The pillars provide a means to concentrate analyte via superhydrophobic droplet evaporation effects. A ≥ 100-fold concentration of analyte was estimated, with a limit of detection of 2.9 × 10(-12) M for mitoxantrone dihydrochloride. Additionally, analytes were delivered to the surface via a multiplex approach in order to demonstrate an ability to control droplet size and placement for scaled-up uses in real world applications. Finally, a concentration process involving transport and sequestration based on surface treatment selective wicking is demonstrated.

Suicidal tendency in a sample of adolescent outpatients with adjustment disorder: gender differences.

BACKGROUND: Although Adjustment Disorder (AD) is a prevalent diagnosis in adolescent mental health services and linked to suicidal tendency in adolescence, little research exists examining prevalence and gender differences of suicidal symptoms among AD patients using standardized instruments. AIMS: The present study aims to assess the presence of suicidal tendency in a clinical sample of Spanish adolescents with AD analyzing gender differences. METHOD: Ninety-seven adolescents with AD were recruited at a public mental health center and included in the AD sample; they were administered the Inventario de Riesgo Suicida para Adolescentes (Suicide Risk Inventory for Adolescents-IRIS) and the Millon Adolescent Clinical Inventory (MACI). Ninety-nine community adolescents were recruited and administered the IRIS inventory. The community sample works as a contrast group. RESULTS: Girls with AD show higher levels of suicidal symptoms than boys on both the IRIS Suicidal Ideation and Intention scale (t=8.15, p<.001) and the MACI Suicidal Tendency scale (t=6.6, p<.001). Girls with AD scored significantly higher than girls from the community contrast group sample in the IRIS Suicidal Ideation and Intention scale, but boys with AD presented no differences with regard to boys form the community contrast group sample. Compared with normative clinical samples of the MACI, no differences in the Suicidal Tendency scale scores were found between AD and normative girls, but AD boys showed significantly lower mean scores than normative boys. Suicidal symptoms were presented by 27% of girls and 18% of boys, although only 6% of the girls and none of the boys presented clear suicidal tendencies. CONCLUSIONS: Considering suicidal tendencies in adolescents with Adjustment Disorder is important-especially in girls, who present high suicidal tendencies in relation both to boys and to community peers and the normative clinical population.

Post-traumatic stress problems among poly-victimized Spanish youth: time effect of past vs. recent interpersonal victimizations.

The cumulative effect of lifetime interpersonal victimization experiences (e.g., child maltreatment, sexual victimizations, conventional crime, witnessing indirect victimization, peer and sibling victimizations) on posttraumatic stress (PTS) symptoms is an important topic in the scientific literature. The objectives of the present study were: (a) to analyze the relationship between lifetime interpersonal victimizations and PTS symptoms, (b) to determine the most prevalent specific PTS symptoms among poly-victimized adolescents, and (c) to establish the time-based effect of interpersonal victimization experiences that occurred in the last year versus those that occurred years before on current level of PTS symptoms. Gender differences were taken into account for each of these objectives. Participants were 823 Spanish adolescents (63% girls and 37% boys) between 14 and 18 years of age recruited from May 2010 to November 2011 from schools in Barcelona, Spain. The majority (87.6%) was of Spanish nationality. The results highlighted the cumulative effect of interpersonal victimizations on PTS symptoms. Among poly-victims adolescents, the most prevalent PTS symptom was intrusive thoughts, but some differences were observed according to gender. The time-based effect of interpersonal victimizations showed a different pattern for girls and boys. For girls, the victimizing events occurring in past years had more explanatory power of the current PTS symptoms than those that occurred more recently. In boys, the interpersonal victimizing events occurring in the last year had the greater explanatory power. These results may have clinical and therapeutic value.

Predicción de conducta autodestructiva en adolescentes mediante tipologías de afrontamiento / Predicting Self-Destructive Behavior in Adolescents by Means of Coping Typologies

La conducta autodestructiva es un fenómeno prevalente en la adolescencia. El propósito principal del estudio es establecer la asociación entre conducta autodestructiva y tipologías de afrontamiento en adolescentes, detectando los perfiles de mayor riesgo. Un propósito previo y adicional es determinar la presencia de conducta autodestructiva en un rango subclínico/clínico, según género. A partir de una muestra total de 1.400 alumnos de Enseñanza General Básica con edades entre 12 y 16 años y utilizando un diseño transversal, los resultados indican que un 15% de los adolescentes refiere conductas autodestructivas dentro de un rango subclínico y/o clínico, no existiendo diferencias de género. Los adolescentes con mayor probabilidad de referir conducta autodestructiva son los pertenecientes a la tipología evitadora, caracterizada por sobreutilizar las estrategias de evitación en detrimento de las de aproximación. Las tipologías de afrontamiento se han mostrado más útiles en la predicción de conductas autodestructivas que la clásica dicotomía aproximación/evitación. Los resultados de este estudio pueden tener implicaciones a nivel de prevención y de tratamiento.

Self-destructive behavior is a phenomenon that is becoming increasingly prevalent among adolescents. The main objective of this study is to establish in Spanish communitarian adolescents the association between self-destructive behavior and coping typologies, detecting higher risk profiles. A previous and additional objective is to determine the presence of self-destructive behavior in a subclinical/clinical range according to gender. From a sample of 1400 high school students between 12 and 16 years the results of this cross-sectional study indicate that 15% of adolescents reports self-destructive behavior in a subclinical or clinical level. No gender differences were observed. The adolescents with higher risk of self-destructive behavior are those belonging to the avoidance typology, characterized by the overuse of avoidance coping responses at the expense of those of approach. Coping typologies are more useful in predicting the risk of self-destructive behavior than the typical approach/avoidance dichotomy. The results of this study may have important implications for the prevention and treatment of self-destructive behaviors in adolescents at risk.

Polyvictimization and risk for suicidal phenomena in a community sample of Spanish adolescents.

This study aims to provide data regarding the association between reported degree of victimization and suicidal phenomena, with special emphasis on gender differences. There were 923 adolescents recruited from eight secondary schools in Catalonia, Spain. The Youth Self-Report (YSR) and the Juvenile Victimization Questionnaire (JVQ) were used to assess suicidal phenomena and victimization, respectively. Participants were divided into three groups (nonvictim, victim, and polyvictim groups) according to the total number of different kinds of victimization reported. Results showed that the polyvictim group reported significantly more suicidal phenomena than did the victim and nonvictim groups in both boys and girls. Furthermore, although no gender differences in reported suicidal phenomena were found in the nonvictim group, girls reported significantly more suicidal phenomena in both the victim and the polyvictim groups. In conclusion, the results suggest that victimization may play an important role in generating gender differences with respect to reported suicidal phenomena. In addition, this study highlights the importance of taking into account the whole range of victimizations suffered by adolescents when seeking to design suicide prevention and intervention policies.

Factor structure of the adolescent coping orientation for problem experiences in Spanish adolescents.

The present study aimed to identify the best structure of the Adolescent Coping Orientation for Problem Experiences when applied to Spanish adolescents. A confirmatory factor analysis of five previous factor structures was conducted. As the data did not fit previous factor models, two exploratory factor analyses (first- and second-order) were carried out to identify the structure for Spanish adolescents and to analyse its criterion validity in relation to mental health, which was assessed by means of the Youth Self-Report. A first-wave sample of 1,152 secondary education pupils (645 boys, 56%; 507 girls, 44%; M age = 14.4 yr., SD = 1.4) was involved in the confirmatory and exploratory factor analyses. A second-wave sample of = 374 secondary education pupils (188 boys, 50.5%; 186 girls, 49.5%; M age = 15.4 yr., SD = 1.1) was used to assess criterion validity. The results yielded eight first-order factors with Cronbach's alpha ranging from .63 to .79, and two second-order factors that replicated the Approach and Avoidance focus of coping. The paper discusses both the content of the extracted factors and mental health issues.

Highly ordered silicon pillar arrays as platforms for planar chromatography.

Unlike HPLC, there has been sparse advancement in the stationary phases used for planar chromatography. Nevertheless, modernization of planar chromatography platforms can further highlight the technique's ability to separate multiple samples simultaneously, utilize orthogonal separation formats, image (detect) separations without rigorous temporal demands, and its overall simplicity. This paper describes the fabrication and evaluation of ordered pillar arrays that are chemically modified for planar chromatography and inspected by fluorescence microscopy to detect solvent development and analyte bands (spots). Photolithography, in combination with anisotropic deep reactive ion etching, is used to produce uniform high aspect ratio silicon pillars. The pillar heights, diameters, and pitch variations are approximately 15-20 µm, 1-3 µm, and 2-6 µm, respectively, with the total pillar array size typically 1 cm × 3 cm. The arrays are imaged using scanning electron microscopy in order to measure the pillar diameter and pitch as well as analyze the pillar sidewalls after etching and stationary phase functionalization. These fluidic arrays will enable exploration of the impact on mass transport and chromatographic efficiency caused by altering the pillar array morphology. A C18 reverse stationary phase (RP), common RP solvents that are transported by traditional but uniquely rapid capillary flow, and Rhodamine 6G (R6G) as the preliminary analyte are used for this initial evaluation. The research presented in this article is aimed at understanding and overcoming the unique challenges in developing and utilizing ordered pillar arrays as a new platform for planar chromatography: focusing on fabrication of expansive arrays, studies of solvent transport, methods to create compatible sample spots, and an initial evaluation of band dispersion.

Impact of poly-victimization on mental health: the mediator and/or moderator role of self-esteem.

The current study examines the relationship between the total kinds of victimization (TKV) experienced, self-esteem, and internalizing symptoms (IS) and externalizing symptoms (ES). It also explores the mediator and/or moderator role of two self-esteem facets: self-liking (SL) and self-competence (SC). The sample comprised 736 adolescents recruited from eight secondary schools in Catalonia, Spain. The Rosenberg Self-Esteem Scale, the Youth Self Report, and the Juvenile Victimization Questionnaire were used to assess self-esteem facets (SL and SC), psychological distress (IS and ES), and the TKV suffered. This article has several innovative features. On one hand, it considers that self-esteem is comprised of two different but related factors: SL and SC. On the other hand, it is the first study to provide evidence for the mediator/moderator role of SL and SC between victimization and psychological symptoms, taking account of the TKV experienced. Results suggest that SL is more relevant to mental health than SC. A low sense of being a worthy social being (SL) is more closely related to both victimization and poor mental health than a low sense of personal efficacy (SC). Moreover, SL seems to partially mediate the relationship between TKV and both IS and ES, whereas SC only acts as a partial mediator for the TKV-IS relationship in girls. At the same time, SL acts as a partial moderator of the TKV-IS relationship in boys. These findings support the importance of self-esteem in buffering the impact of victimization on mental health and may indicate that proper prevention and treatment policies should focus on adolescents' sense of being a good person, according to their own criteria of worth.

Surface enhanced Raman scattering imaging of developed thin-layer chromatography plates.

A method for hyphenating surface enhanced Raman scattering (SERS) and thin-layer chromatography (TLC) is presented that employs silver-polymer nanocomposites as an interface. Through the process of conformal blotting, analytes are transferred from TLC plates to nanocomposite films before being imaged via SERS. A procedure leading to maximum blotting efficiency was established by investigating various parameters such as time, pressure, and type and amount of blotting solvent. Additionally, limits of detection were established for test analytes malachite green isothiocyanate, 4-aminothiophenol, and Rhodamine 6G (Rh6G) ranging from 10(-7) to 10(-6) M. Band broadening due to blotting was minimal (∼10%) as examined by comparing the spatial extent of TLC-spotted Rh6G via fluorescence and then the SERS-based spot size on the nanocomposite after the blotting process. Finally, a separation of the test analytes was carried out on a TLC plate followed by blotting and the acquisition of distance × wavenumber × intensity three-dimensional TLC-SERS plots.

Effects of poly-victimization on self-esteem and post-traumatic stress symptoms in Spanish adolescents.

This study aims to provide evidence concerning the effects of experiencing multiple forms of victimization (poly-victimization) on self-esteem and post-traumatic stress symptoms in Spanish adolescents. A total of 722 adolescents were recruited from seven secondary schools in Catalonia, Spain. The Rosenberg Self-Esteem Scale, the Youth Self Report and the Juvenile Victimization Questionnaire were employed to assess self-esteem, post-traumatic stress symptoms and victimization, respectively. Participants were divided into three groups (non-victim, victim and poly-victim groups) according to the total number of different kinds of victimization experienced. Results showed that 88.4 % of adolescents had been exposed to at least one kind of victimization. Poly-victimization was associated with a higher number of post-traumatic stress symptoms in both boys and girls. Also, self-liking was significantly lower in the poly-victim group, whereas self-competence was equivalent across the three victimization groups. Girls were approximately twice as likely to report child maltreatment (OR = 1.92) and sexual victimization (OR = 2.41) as boys. In conclusion, the present study adds evidence on the importance of taking account of the full burden of victimizations suffered when studying victimization correlates. Also, it highlights the importance of prevention policies to focus particularly on preserving adolescents' sense of social worth.