Gender disparities in pediatric research: a descriptive bibliometric study on scientific authorships.

BACKGROUND: The proportion of women in medicine, especially in pediatrics, is noticeably increasing. Yet, leadership positions are predominantly occupied by men. METHODS: Academic authorships of 156,642 pediatric original research articles were analyzed with regard to gender disparities. The evaluation included the proportion of female authorships (FAP), distributions over first-, co- and last-authorships, gender-related citation rates, a productivity analysis and investigations on journals, countries and pediatric sub-disciplines. RESULTS: In all, 46.6% of all authorships in pediatric research were held by female authors. Women held relatively more first-authorships (FAP = 52%) and had higher odds for first- (OR = 1.3) and co- (OR = 1.11) authorships, compared to men. The Prestige Index of -0.13 indicated an underrepresentation of female authors at prestigious first- and last-authorships. Citation rates were not affected by the gender of the key authors. At the country-level pronounced gender-related differences were detected. The time trend showed increasing female prospects forecasting a female-dominated Prestige Index of 0.05 in 2023. CONCLUSION: The integration of women in pediatric research has advanced. Opportunities for female authors differ at the country-level, but overall women are lacking in leadership positions. Improving career opportunities for women in pediatric research can be expected in the coming years. IMPACT: There is a measurable progress in the integration of female scientists. Gender-neutrality is partially achieved in pediatric research with yet a female underrepresentation in leading positions. Our descriptive study presents gender-related dynamics in pediatric research that forecast improving career opportunities for female scientists.

Integration of the work-related online aftercare intervention 'GSA-online plus' (healthy and without stress at the workplace) into clinical practice: study protocol for an implementation study.

BACKGROUND: In a previous RCT we established the efficacy of the psychodynamic online aftercare programme 'GSA-Online' ('Health Training Stress Management at the Workplace') for rehabilitants with work-related stress facing return to work after long-term sickness absence. The purpose of this trial is to implement it into routine care. METHODS/DESIGN: The study is performed in rehabilitation clinics with patients of different medical indications (psychosomatic, orthopedic and cardiological diseases). Rehabilitants get access to the study platform during inpatient medical rehabilitation. 'GSA-Online plus' integrates exploratory and motivational videos on the web application to familiarize potential participants and motivate them to follow through with it. In the 12-week writing intervention, patients write weekly online diary entries, answered by anonymous online therapists within 24 h. Primary outcome measures are the recommendation rate of 'GSA-Online plus' and participation rates of the rehabilitants. As secondary outcomes, psychological symptoms, overall satisfaction, helpfulness of the therapeutic feedback and utilization of 'GSA-Online plus' will be analysed exploratory along with the course of weekly ratings of well-being and work ability. DISCUSSION: Meanwhile many clinical trials and meta-analysis prove that internet-based interventions are effective. This study will add insights on the dissemination and implementation of efficacious, evidence-based online treatments into medical practice. We expect a successful implementation of 'GSA-Online plus' in the clinical routine of the rehabilitation clinics. The focus of evaluation is on acceptance of the programme, both by the physicians in charge and the patients. In the future 'GSA-Online plus' could be implemented as a routine aftercare programme for rehabilitation inpatients with occupational stress. TRIAL REGISTRATION: The trial was retrospectively registered on 6th January 2017 at ClinicalTrials.gov (Trial Registration number: ClinicalTrials Gov ID NCT03019718 ).

Psychodynamic Online Treatment Following Supportive Expressive Therapy (SET):Therapeutic Rationale, Interventions and Treatment Process.

OBJECTIVES: The feasibility of psychodynamic online treatments has remained an issue of debate. The paper presents rationale and technique of a psychodynamic online intervention discussing therapeutic process and alliance based on two case examples from an RCT. METHODS: A weekly writing task is followed by individual feedback from the online therapist. Treatment focuses on a 'Core Conflict Relationship Theme' based on relationship episodes according to the wish of the patient, reactions of the others and reactions of the self. Maladaptive interpersonal interactions are worked through by supportive and expressive therapeutic interventions. RESULTS: Case reports from our study illustrate a productive therapeutic process without immediate personal contact or nonverbal communication. CONCLUSIONS: Emotional reactions and felt concern of the online therapist promote engagement in patients. Online therapists need to detect alliance ruptures based on text messages and remedy them. We discuss psychodynamic online treatments as adjuncts to face to face psychotherapy.

Concerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence.

Expression of all Yersinia pathogenicity factors encoded on the virulence plasmid, including the yop effector and the ysc type III secretion genes, is controlled by the transcriptional activator LcrF in response to temperature. Here, we show that a protein- and RNA-dependent hierarchy of thermosensors induce LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is modest and mediated by the thermo-sensitive modulator YmoA, which represses transcription from a single promoter located far upstream of the yscW-lcrF operon at moderate temperatures. The transcriptional response is complemented by a second layer of temperature-control induced by a unique cis-acting RNA element located within the intergenic region of the yscW-lcrF transcript. Structure probing demonstrated that this region forms a secondary structure composed of two stemloops at 25°C. The second hairpin sequesters the lcrF ribosomal binding site by a stretch of four uracils. Opening of this structure was favored at 37°C and permitted ribosome binding at host body temperature. Our study further provides experimental evidence for the biological relevance of an RNA thermometer in an animal model. Following oral infections in mice, we found that two different Y. pseudotuberculosis patient isolates expressing a stabilized thermometer variant were strongly reduced in their ability to disseminate into the Peyer's patches, liver and spleen and have fully lost their lethality. Intriguingly, Yersinia strains with a destabilized version of the thermosensor were attenuated or exhibited a similar, but not a higher mortality. This illustrates that the RNA thermometer is the decisive control element providing just the appropriate amounts of LcrF protein for optimal infection efficiency.

The Csr/Rsm system of Yersinia and related pathogens: a post-transcriptional strategy for managing virulence.

This review emphasizes the function and regulation of the Csr regulatory system in the human enteropathogen Yersinia pseudotuberculosis and compares its features with the homologous Csr/Rsm systems of related pathogens. The Csr/Rsm systems of eubacteria form a complex regulatory network in which redundant non-translated Csr/Rsm-RNAs bind the RNA-binding protein CsrA/RsmA, thereby preventing its interaction with mRNA targets. The Csr system is controlled by the BarA/UvrY-type of two-component sensor-regulator systems. Apart from that, common or pathogen-specific regulators control the abundance of the Csr components. The coordinate control of virulence factors and infection-linked physiological traits by the Csr/Rsm systems helps the pathogens to adapt individually to rapidly changing conditions to which they are exposed during the different stages of an infection. As Csr/Rsm function is relevant for full virulence, it represents a target suitable for antimicrobial drug development.

Internet-based CBT for somatic symptom distress (iSOMA) in emerging adults: A randomized controlled trial.

OBJECTIVE: Persistent somatic symptom distress is common in emerging adults and is associated with adverse health outcomes and impairment. Internet-based interventions could help to prevent burden and chronicity. This randomized controlled trial tested the efficacy of a guided, cognitive-behavioral internet intervention for somatic symptom distress (iSOMA) in emerging adults at risk for somatic symptom disorder compared to a waitlist control condition. METHOD: 158 participants (N = 156 analyzed; 24.53 years, 83.3% female) with multiple somatic symptoms were recruited among German-speaking universities and randomly allocated to either receive the 8-week iSOMA intervention with psychologist support or the waitlist, both with access to treatment as usual. Primary outcomes were somatic symptom distress Patient Health Questionnaire, somatic symptom scale (PHQ-15) and psychobehavioral features of somatic symptom disorder-12 (SSD-12), assessed at baseline and 8-weeks postrandomization. Secondary outcomes included depression, anxiety, illness worries, functional impairment, and attitudes toward psychological treatment. RESULTS: Participants in the iSOMA group showed significantly greater improvements (ps < .001) in primary outcomes (PHQ-15: d = 0.70 [0.36, 1.05], SSD-12: d = 0.65 [0.30, 0.99], and secondary outcomes (ps < .05; d = 0.41-0.52) compared to the waitlist, except for attitudes toward psychological treatment (p = .944). Satisfaction with iSOMA was high (91.0%), most participants (72.8%) completed at least 4 of 7 modules and negative treatment effects were infrequent (14.9%). CONCLUSIONS: Our intervention had a substantial positive impact on somatic symptom distress across a broad range of persistent physical symptoms in a vulnerable target group, opening up promising possibilities for indicative prevention and blended care for somatic symptom disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Somatosensory amplification moderates the efficacy of internet-delivered CBT for somatic symptom distress in emerging adults: Exploratory analysis of a randomized controlled trial.

OBJECTIVE: While studies mainly provide positive evidence for the efficacy of internet-delivered cognitive-behavioral therapy (ICBT) for various persistent somatic symptoms, it remains largely unclear for whom these interventions work or not. This exploratory analysis aimed to identify moderators for the outcome between ICBT for somatic symptom distres and a waitlist control group (WL) in a vulnerable target group of emerging adults. METHODS: Based on data from a randomized controlled trial on 156 university students with varying degrees of somatic symptom distress who were allocated to either an eight-week, therapist guided ICBT (iSOMA) or to the WL, we examined pretreatment demographic characteristics, health-related variables (e.g., somatic symptom duration), mental distress (e.g., depression, anxiety) and cognitive-emotional factors (emotional reactivity, somatosensory amplification) as candidate moderators of the outcome, somatic symptom distress (assessed by the Patient Health Questionnaire, PHQ-15) from pre- to posttreatment. RESULTS: Somatosensory amplification (assessed by the Somatosensory Amplification Scale, SSAS) moderated the outcome in favor of iSOMA (B = -0.17, SE = 0.08, p = 0.031), i.e., higher pretreatment somatosensory amplification was associated with better outcome in the active compared to the control intervention. No significant moderation effects were found among demographic characteristics, health-related variables, or mental distress. CONCLUSION: Our findings suggest that an internet-delivered CBT for somatic symptom distress should be preferred over no active treatment particularly in individuals with moderate to high levels of somatosensory amplification, which as a next step should be tested against further treatments and in clinical populations. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00014375).

Is Therapist Support Needed? Comparing Therapist- and Self-Guided Internet-Based CBT for Somatic Symptom Distress (iSOMA) in Emerging Adults.

Persistent somatic symptoms of varying etiology are very common in emerging adults and can lead to distress and impairment. Internet-delivered interventions could help to prevent the burden and chronicity of persistent somatic symptoms. This study investigated the impact of therapist guidance on the effectiveness of a cognitive-behavioral Internet intervention for somatic symptom distress (iSOMA) in emerging adults, as a secondary analysis of a two-armed randomized controlled trial. We included 149 university students (83.2% female, 24.60 yrs) with varying degrees of somatic symptom distress who were either allocated to the 8-week intervention with regular, written therapeutic guidance (iSOMA guided) or to the control group (waitlist), which was afterwards crossed over to receive iSOMA with guidance-on-demand (iSOMA-GoD). Primary outcomes were somatic symptom distress (assessed by the PHQ-15) and psychobehavioral symptoms of the somatic symptom disorder (assessed by the SSD-12) at pre- and post-treatment. Secondary outcomes included depression, anxiety, and disability. Both treatments showed statistically significant pre-post improvements in primary (iSOMA-guided: d = 0.86-0.92, iSOMA-GoD: d = 0.55-0.63) and secondary outcomes. However, intention-to-treat analysis revealed non-significant between-group effects for all outcomes (ps ≥ .335), after controlling for confounding variables, and effect sizes were marginal (d = -0.06 to 0.12). Overall, our findings indicate that Internet-delivered cognitive behavioral therapy with regular guidance is not unequivocally superior to guidance-on-demand in alleviating somatic symptom distress and associated psychopathology in emerging adults. As a next step, non-inferiority studies are needed to test the robustness of these findings and their impact on clinical populations.

The Small Protein YmoA Controls the Csr System and Adjusts Expression of Virulence-Relevant Traits of Yersinia pseudotuberculosis.

Virulence gene expression of Yersinia pseudotuberculosis changes during the different stages of infection and this is tightly controlled by environmental cues. In this study, we show that the small protein YmoA, a member of the Hha family, is part of this process. It controls temperature- and nutrient-dependent early and later stage virulence genes in an opposing manner and co-regulates bacterial stress responses and metabolic functions. Our analysis further revealed that YmoA exerts this function by modulating the global post-transcriptional regulatory Csr system. YmoA pre-dominantly enhances the stability of the regulatory RNA CsrC. This involves a stabilizing stem-loop structure within the 5'-region of CsrC. YmoA-mediated CsrC stabilization depends on H-NS, but not on the RNA chaperone Hfq. YmoA-promoted reprogramming of the Csr system has severe consequences for the cell: we found that a mutant deficient of ymoA is strongly reduced in its ability to enter host cells and to disseminate to the Peyer's patches, mesenteric lymph nodes, liver and spleen in mice. We propose a model in which YmoA controls transition from the initial colonization phase in the intestine toward the host defense phase important for the long-term establishment of the infection in underlying tissues.

A Csr-type regulatory system, including small non-coding RNAs, regulates the global virulence regulator RovA of Yersinia pseudotuberculosis through RovM.

The MarR-type regulator RovA controls expression of virulence genes of Yersinia pseudotuberculosis in response to environmental signals. Using a genetic strategy to discover components that influence rovA expression, we identified new regulatory factors with homology to components of the carbon storage regulator system (Csr). We showed that overexpression of a CsrB- or a CsrC-type RNA activates rovA, whereas a CsrA-like protein represses RovA synthesis. We further demonstrate that influence of the Csr system on rovA is indirect and occurs through control of the LysR regulator RovM, which inhibits rovA transcription. The CsrA protein had also a major influence on the motility of Yersinia, which was independent of RovM. The CsrB and CsrC RNAs are differentially expressed in Yersinia. CsrC is highly induced in complex but not in minimal media, indicating that medium-dependent rovM expression is mediated through CsrC. CsrB synthesis is generally very low. However, overexpression of the response regulator UvrY was found to activate CsrB production, which in turn represses CsrC synthesis independent of the growth medium. In summary, the post-transcriptional Csr-type components were shown to be key regulators in the co-ordinated environmental control of physiological processes and virulence factors, which are crucial for the initiation of Yersinia infections.

Efficacy of a guided internet-based intervention (iSOMA) for somatic symptoms and related distress in university students: study protocol of a randomised controlled trial.

INTRODUCTION: Persistent and distressing somatic symptoms are common in younger age cohorts such as university students. However, the majority does not receive adequate psychosocial care. Internet-based and mobile-based interventions may represent low threshold and effective extensions to reduce somatic and associated mental symptom severity. The planned study aims to investigate the feasibility and efficacy of an internet-based intervention in reducing somatic and psychological symptoms in an international population of university students with somatic symptom burden. METHODS AND ANALYSIS: This parallel two-armed randomised controlled trial evaluates an 8-week guided intervention, including web-based consecutive modules based on cognitive behavioural therapy (CBT) principles against a waitlist control group. Guidance will be provided by trained psychologists with weekly written supportive feedback. As part of the 'Studicare' project, the present study aims to recruit n=154 university students indicating somatic symptom burden at baseline in German-speaking universities. Self-report assessments will take place at baseline and after intervention completion (8, 16 weeks after randomisation). The primary outcome will be the severity of somatic symptoms and associated mental distress. Secondary outcomes include depression, (health) anxiety, disability, intervention satisfaction and adherence. ETHICS AND DISSEMINATION: Ethics approval has been granted. Results from this study will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: DRKS00014375; Pre-results.

Regulatory elements implicated in the environmental control of invasin expression in enteropathogenic Yersinia.

During infections of the intestinal tract Yersinia pseudotuberculosis penetrates the epithelial cell layer through M-cells into the Peyer's patches. This early step in the infection process is primarily mediated by the outer membrane protein invasin. Expression of the invasin gene is activated by the MarR-type regulatory protein RovA in response to environmental conditions, including temperature and growth phase. In order to gain insight into the nature of the underlying control systems, mutagenesis and gene bank screens were used to identify regula components modulating the levels of invasin and RovA. We found that the inv and rovA genes were both subjected to silencing by the nucleoid-associated protein H-NS. Under inducing conditions, RovA appears to disrupt the silencer complex, through displacement of H-NS from an extended AT-rich region located upstream of the inv and rovA promoters. Furthermore, a LysR-type regulatory protein, RovM with homology to HexA/PecT of phytopathogenic Erwinia species was shown to interact specifically with the rovA regulatory region and represses rovA transcription in addition to H-NS. Disruption of the rovM gene significantly enhanced internalization of Y. pseudotuberculosis into host cells and higher numbers of the mutant bacteria were detectable in gut-associated lymphatic tissues and organs in infected mice. In addition, the histone-like protein YmoA, which has a global effect on the bacterial physiology, was found to activate rovA expression through RovM. Together, our studies showed, that H-NS, RovM and YmoA are key regulators implicated in the environmental control of virulence factors, which are important for the initiation of a Yersinia infection.

Crp induces switching of the CsrB and CsrC RNAs in Yersinia pseudotuberculosis and links nutritional status to virulence.

Colonization of the intestinal tract and dissemination into deeper tissues by the enteric pathogen Yersinia pseudotuberculosis demands expression of a special set of virulence factors important for the initiation and the persistence of the infection. In this study we demonstrate that many virulence-associated functions are coregulated with the carbohydrate metabolism. This link is mediated by the carbon storage regulator (Csr) system, including the regulatory RNAs CsrB and CsrC, and the cAMP receptor protein (Crp), which both control virulence gene expression in response to the nutrient composition of the medium. Here, we show that Crp regulates the synthesis of both Csr RNAs in an opposite manner. A loss of the crp gene resulted in a strong upregulation of CsrB synthesis, whereas CsrC levels were strongly reduced leading to downregulation of the virulence regulator RovA. Switching of the Csr RNA involves Crp-mediated repression of the response regulator UvrY which activates csrB transcription. To elucidate the regulatory links between virulence and carbon metabolism, we performed comparative metabolome, transcriptome, and phenotypic microarray analyses and found that Crp promotes oxidative catabolism of many different carbon sources, whereas fermentative patterns of metabolism are favored when crp is deleted. Mouse infection experiments further demonstrated that Crp is pivotal for a successful Y. pseudotuberculosis infection. In summary, placement of the Csr system and important virulence factors under control of Crp enables this pathogen to link its nutritional status to virulence in order to optimize biological fitness and infection efficiency through the infectious life cycle.

Circulating adhesion molecules in patients with internal carotid artery stenosis.

To study the association of plasma concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-selectin) with atheroslerotic lesions at the origin of the internal carotid artery (ICA). 179 subjects were investigated by color Doppler ultrasound of whom 133 had and 46 had no plaques at the ICA origin. Stepwise logistic regression analysis revealed that hypertension (p < 0.001), sICAM-1 concentrations (p < 0.01) and smoking (p < 0.05) were independently associated with the presence of ICA plaques. Multivariate regression analysis revealed that sICAM-1 concentrations in subjects with plaque were negatively associated with the degree of ICA stenosis (p < 0.01) and positively associated with previous cerebral ischemia (p < 0.01), coronary heart disease (p < 0.05) and peripheral artery disease (p < 0.05). In conclusion, elevated sICAM-1 concentrations are independently associated with atherosclerosis of the ICA origin and are predominantly increased in patients with low-grade lesions and with clinical manifestations of vascular disorders.