Revealing novel biomarkers for diagnosing chronic kidney disease in pediatric patients.

Pediatric chronic kidney disease (CKD) is a clinical condition characterized by progressive renal function deterioration. CKD diagnosis is based on glomerular filtration rate, but its reliability is limited, especially at the early stages. New potential biomarkers (citrulline (CIT), symmetric dimethylarginine (SDMA), S-adenosylmethionine (SAM), n-butyrylcarnitine (nC4), cis-4-decenoylcarnitine, sphingosine-1-phosphate and bilirubin) in addition to creatinine (CNN) have been proposed for early diagnosis. To verify the clinical value of these biomarkers we performed a comprehensive targeted metabolomics study on a representative cohort of CKD and healthy pediatric patients. Sixty-seven children with CKD and forty-five healthy children have been enrolled in the study. Targeted metabolomics based on liquid chromatography-triple quadrupole mass spectrometry has been used for serum and plasma samples analysis. Univariate data analysis showed statistically significant differences (p < 0.05) in the concentration of CNN, CIT, SDMA, and nC4 among healthy and CKD pediatric patients. The predictive ability of the proposed biomarkers was also confirmed through specificity and sensitivity expressed in Receiver Operating Characteristic curves (AUC = 0.909). In the group of early CKD pediatric patients, AUC of 0.831 was obtained, improving the diagnostic reliability of CNN alone. Moreover, the models built on combined CIT, nC4, SDMA, and CNN allowed to distinguish CKD patients from healthy control regardless of blood matrix type (serum or plasma). Our data demonstrate potential biomarkers in the diagnosis of early CKD stages.

Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos / Natural history of mucopolysaccharidosis type III in a series of Colombian patients

Introducción: La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos: Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones: La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.(AU)

Introduction: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. Case reports: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. Conclusions: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.(AU)

[Natural history of mucopolysaccharidosis type III in a series of Colombian patients]. / Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. CASE REPORTS: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. CONCLUSIONS: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.

TITLE: Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.Introducción. La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos. Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones. La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.

Athletes and superstitious rituals.

Superstitious rituals are common in sports and can play a role in athletes' optimism, sense of control, and confidence in performance. Superstitious rituals have characteristics rooted in tradition and need for perfection. While superstitious rituals vary in type of activity, it is necessary to consider their impact on players and the team, and to guide athletes into positive forms of expression to optimize their performance and overall well-being when engaged in their athletic activities. This paper explores the potential benefits and challenges of superstitious rituals, and the ways in which positive alternative pathways can contribute to peak performance in athletes.

Emerging Technologies in Edge Computing and Networking.

The global evolution of the Internet is experiencing a notable and inevitable change towards a convergent scenario known as the Internet of Things (IoT), where a large number of devices with heterogeneous characteristics and requirements have to be interconnected to serve different verticals, such as smart cities, intelligent transportation systems, smart grids, (ITS) or e-health [...].

Autonomic nervous system function before and after trauma-focused psychotherapy in youth with (partial) posttraumatic stress disorder.

While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous system (ANS) associated with PTSD, remains incompletely understood. During neutral and personalized trauma script imagery heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) were recorded in youth aged 8-18 with PTSD or partial PTSD (n = 76) and trauma-exposed controls (TEC) (n = 27) to determine ANS activity and stress reactivity. Within the patient group, 77.6% met the full DSM-IV diagnostic criteria for PTSD, the remaining 22.4% met the criteria for partial PTSD. Youth with (partial) PTSD were subsequently treated with eight sessions of either trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing. PTSD severity was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide patients into responders and non-responders. Youth with (partial) PTSD relative to TEC had higher overall HR during both neutral and trauma imagery (p = .05). Youth with (partial) PTSD showed RSA decrease during trauma imagery relative to neutral imagery, the reverse of TEC (p = .01). Relative to non-responders, responders demonstrated a significant baseline to posttreatment increase of RSA response to stress only when employing a ≥ 50% response criterion (p = .05) and not with the primary ≥ 30% criterion (p = .12). Our results suggest overall higher HR and sympathetic nervous system activity as well as vagal withdrawal in response to stress in youth with (partial) PTSD and only provide partial support for normalization of the latter with successful trauma-focused psychotherapy.

Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial.

INTRODUCTION: The peritoneum is the second most affected organ for the dissemination of colorectal cancer (CRC). Patients with colorectal peritoneal metastases (CPM) face a poor prognosis, despite the majority of patients being treated with palliative systemic therapy. The efficacy of palliative systemic therapy is limited due to the plasma-peritoneum barrier. The poor prognosis of unresectable CPM patients has resulted in the development of new treatment strategies where systemic therapy is combined with local, intraperitoneal chemotherapy. In the recently published phase I study, the maximum tolerated dose and thus the recommended phase II dose of intraperitoneal irinotecan was investigated and determined to be 75 mg. In the present study, the overall survival after treatment with 75 mg irinotecan with concomitant mFOLFOX4 and bevacizumab will be investigated. MATERIALS AND METHODS: In this single-arm phase II study in two Dutch tertiary referral centres, 85 patients are enrolled. Eligibility criteria are an adequate performance status and organ function, histologically confirmed microsatellite stable and unresectable CPM, no previous palliative therapy for CRC, no systemic therapy<6 months for CRC prior to enrolment and no previous cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). Patients will undergo a diagnostic laparoscopy as standard work-up for CPM and if the peritoneal disease is considered unresectable (eg, Peritoneal Cancer Index (PCI)>20, too extensive small bowel involvement), a peritoneal access port and a port-a-cath are placed for administration of intraperitoneal and intravenous chemotherapy, respectively. Patients may undergo up to 12 cycles of study treatment. Each cycle consists of intravenous mFOLFOX4 with bevacizumab and concomitant intraperitoneal irinotecan (75 mg), which is repeated every 2 weeks, with a maximum of 12 cycles. Modified FOLFOX-4 regimen consists of 85 mg/m2 oxaliplatin plus 200 mg/m2 LV and 5-FU 400 mg/m2 bolus on day 1 followed by 1600 mg/m2 5-FU as a 46 hours infusion. Study treatment ends after the 12th cycle, or earlier in case of disease progression or unacceptable toxicity. The primary outcome is overall survival and key secondary outcomes are progression-free survival, safety (measured by the amount of grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0)), patient-reported outcomes and pharmacokinetics of irinotecan. It is hypothesised that the trial treatment will lead to a 4 month increase in overall survival; from a median of 12.2 to 16.2 months. ETHICS AND DISSEMINATION: This study is approved by the Dutch Authority (CCMO, the Hague, the Netherlands), by a central medical ethics committee (MEC-U, Nieuwegein, the Netherlands) and by the institutional research boards of both research centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. TRIAL REGISTRATION NUMBER: NCT06003998.

Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials.

BACKGROUND: Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators. METHODS: This was an individual participant data meta-analysis of published and unpublished randomised studies in young people aged 6-18 years exposed to trauma. We included studies identified by the latest UK National Institute of Health and Care Excellence guidelines (completed on Jan 29, 2018) and updated their search. The search strategy included database searches restricted to publications between Jan 1, 2018, and Nov 12, 2019; grey literature search of trial registries ClinicalTrials.gov and ISRCTN; preprint archives PsyArXiv and bioRxiv; and use of social media and emails to key authors to identify any unpublished datasets. The primary outcome was post-traumatic stress symptoms after treatment (<1 month after the final session). Predominantly, one-stage random-effects models were fitted. This study is registered with PROSPERO, CRD42019151954. FINDINGS: We identified 38 studies; 25 studies provided individual participant data, comprising 1686 young people (mean age 13·65 years [SD 3·01]), with 802 receiving CBTs-TF and 884 a control condition. The risk-of-bias assessment indicated five studies as low risk and 20 studies with some concerns. Participants who received CBTs-TF had lower mean post-traumatic stress symptoms after treatment than those who received the control conditions, after adjusting for post-traumatic stress symptoms before treatment (b=-13·17, 95% CI -17·84 to -8·50, p<0·001, τ2=103·72). Moderation analysis indicated that this effect of CBTs-TF on post-traumatic stress symptoms post-treatment increased by 0·15 units (b=-0·15, 95% CI -0·29 to -0·01, p=0·041, τ2=0·03) for each unit increase in pre-treatment post-traumatic stress symptoms. INTERPRETATION: This is the first individual participant data meta-analysis of young people exposed to trauma. Our findings support CBTs-TF as the first-line treatment, irrespective of age, gender, trauma characteristics, or carer involvement in treatment, with particular benefits for those with higher initial distress. FUNDING: Swiss National Science Foundation.

A Longitudinal Study in Worrisome Sexual Behavior Following Sexual Abuse in Infancy or Early Childhood: The Amsterdam Sexual Abuse Case.

Worrisome sexual behavior (WSB) is often described as an outcome specific to child sexual abuse (CSA). Therefore, it is highly relevant to study WSB in relation to sexual abuse, especially in very young children, as it is hard to recognize sexual abuse in children who have limited verbal capacities of disclosing. Over time, literature describing WSB following CSA has gradually broadened. However, a gap remains regarding the long-term development of WSB in children who were sexually abused during infancy or very early childhood. To our knowledge, our study is the first to examine developmentally-related sexual behavior versus sexual abuse-specific behavior longitudinally in children who were sexually abused at a very young age. In total, we examined the sexual behavior, as reported by parents of 45 children who experienced early-age sexual abuse for a period of more than five years. Overall, we found that WSB is likely to be a CSA-specific and potentially long-term outcome for children who were sexually abused at a very young age. Despite the decrease in sexual abuse-specific behavior over time, the level of this behavior was still significantly high 8 years after the sexual abuse. This finding supports long-term monitoring and assessment and intervention for WSB over time. Despite these findings, it is important to note that WSB does not serve as proof of sexual abuse in children; likewise, when a child does not present with WSB, it does not indicate the absence of a substantiated history of sexual abuse.

Treatment Responsivity in Adolescents With Disruptive Behavior Problems: Co-Creation of a Virtual Reality-Based Add-On Intervention.

BACKGROUND: We developed Street Temptations (ST) as an add-on intervention to increase the treatment responsivity of adolescents with disruptive behavior problems. ST's primary aim is to improve adolescents' mentalizing abilities in order to help them engage in and benefit from psychotherapy. Additionally, virtual reality (VR) is used to work in a more visual, less verbal, fashion. OBJECTIVE: By recapping the lessons learned while developing ST so far, we aim to design the following study on ST. Furthermore, we aim to enhance the development and study of new health care interventions in clinical practice, together with adolescents as their end users. METHODS: We followed an iterative co-creation process to develop a prototype of ST, in collaboration with adolescents and professionals from a secured residential facility in Amsterdam, the Netherlands. The prototype was tested during a pilot phase, involving 2 test runs, in which 4 adolescents and 4 professionals participated. Qualitative data were collected through interviews with the adolescents and by conducting a group interview with the professionals, in order to gain first insights into ST's usability, feasibility, and its added value to clinical practice. In between the first and second test runs, the prototype was enhanced. On the basis of the complete pilot phase, we reflected on the future development and implementation of ST to design a subsequent study. RESULTS: Over the course of 6 months, ST's first prototype was developed during multiple creative sessions. Included was the development of a short 360° VR video, to serve as a base for the mentalization exercises. The final version of ST consisted of 7 individual therapy sessions, incorporating both the VR video and a VR StreetView app. On the basis of the qualitative data collected during the pilot phase, we found preliminary signs of ST's potential to support adolescents' perspective-taking abilities specifically. Additionally, using VR to focus on real-life situations that adolescents encounter in their daily lives possibly helps to facilitate communication. However, several challenges and requests concerning the VR hardware and software and the implementation of ST emerged, pointing toward further development of ST as an add-on intervention. These challenges currently limit large-scale implementation, resulting in specific requirements regarding a subsequent study. CONCLUSIONS: In order to gather more extensive information to shape further development and study treatment effects, a small-scale and individually oriented research design seems currently more suitable than a more standard between-subjects design. Using the reflection on the lessons learned described in this report, a research protocol for a forthcoming study on ST has been developed. By presenting our co-creation journey thus far, we hope to be of inspiration for a more co-creative mindset and in that way contribute to the mutual reinforcement of science and clinical practice.

Correction to "Chemical Synthesis of La0.75Sr0.25CrO3 Thin Films for p-Type Transparent Conducting Electrodes".

[This corrects the article DOI: 10.1021/acs.chemmater.2c03831.].

p90RSK2, a new MLCK mediates contractility in myosin light chain kinase null smooth muscle.

Introduction: Phosphorylation of smooth muscle (SM) myosin regulatory light chain (RLC20) is a critical switch leading to SM contraction. The canonical view held that only the short isoform of myosin light chain kinase (MLCK1) catalyzed this reaction. It is now accepted that auxiliary kinases may contribute to vascular SM tone and contractility. We have previously reported that p90 ribosomal S6 kinase (RSK2) functions as such a kinase, in parallel with MLCK1, contributing ∼25% of the maximal myogenic force in resistance arteries. Thus, RSK2 may be instrumental in the regulation of basal vascular tone and blood pressure. Here, we take advantage of a MLCK1 null mouse (mylk1 -/-) to further test our hypothesis that RSK2 can function as an MLCK, playing a significant physiological role in SM contractility. Methods: Using fetal (E14.5-18.5) SM tissues, as embryos die at birth, we investigated the necessity of MLCK for contractility and fetal development and determined the ability of RSK2 kinase to compensate for the lack of MLCK and characterized its signaling pathway in SM. Results and Discussion: Agonists induced contraction and RLC20 phosphorylation in mylk1 -/- SM was attenuated by RSK2 inhibition. The pCa-tension relationships in permeabilized strips of bladder showed no difference in Ca2+ sensitivity in WT vs mylk1 -/- muscles, although the magnitude of force responses was considerably smaller in the absence of MLCK. The magnitude of contractile responses was similar upon addition of GTPγS to activate the RhoA/ROCK pathway or calyculinA to inhibit the myosin phosphatase. The Ca2+-dependent tyrosine kinase, Pyk2, contributed to RSK2-mediated contractility and RLC20 phosphorylation. Proximity-ligation and immunoprecipitation assays demonstrated an association of RSK2, PDK1 and ERK1/2 with MLCK and actin. RSK2, PDK1, ERK1/2 and MLCK formed a signaling complex on the actin filament, positioning them for interaction with adjacent myosin heads. The Ca2+-dependent component reflected the agonist mediated increases in Ca2+, which activated the Pyk2/PDK1/RSK2 signaling cascade. The Ca2+-independent component was through activation of Erk1/2/PDK1/RSK2 leading to direct phosphorylation of RLC20, to increase contraction. Overall, RSK2 signaling constitutes a new third signaling pathway, in addition to the established Ca2+/CaM/MLCK and RhoA/ROCK pathways to regulate SM contractility.

ß-Peptides incorporating polyhydroxylated cyclohexane ß-amino acid: synthesis and conformational study.

We describe the synthesis of trihydroxylated cyclohexane ß-amino acids from (-)-shikimic acid, in their cis and trans configuration, and the incorporation of the trans isomer into a trans-2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of trans-2-aminocyclohexanecarboxylic acid. This means that the high degree of substitution of the cyclohexane ring of the new residue is compatible with the adoption of a stable helical secondary structure and opens opportunities for the design of more elaborate peptidic foldamers with oriented polar substituents at selected positions of the cycloalkane residues.

Treatment of multiple traumatized adolescents by enhancing regulation skills and reducing trauma related symptoms: rationale, study design, and methods of randomized controlled trial (the Mars-study).

BACKGROUND: There is ongoing debate regarding the treatment of severe and multiple traumatized children and adolescents with post-traumatic stress disorder (PTSD). Many clinicians favor a phase-based treatment approach (i.e., a stabilization phase prior to trauma-focused therapy) over immediate trauma-focused psychological treatment, despite the lack of scientific evidence. Research on the effects of different treatment approaches is needed for children and adolescents with (symptoms of complex) PTSD resulting from repeated sexual and/or physical abuse during childhood. OBJECTIVE: This paper describes the rationale, study design, and methods of the MARS-study, a two-arm randomized controlled trial (RCT) that aims to compare the results of phase-based treatment with those of immediate trauma-focused treatment and determine whether immediate trauma-focused treatment is not worse than phase-based treatment in reducing PTSD symptoms. METHODS: Participants are individuals between 12 and 18 years who meet the diagnostic criteria for PTSD due to repeated sexual abuse, physical abuse, or domestic violence during childhood. Participants will be blindly allocated to either the phase-based or immediate trauma-focused treatment condition. In the phase-based treatment condition, participants receive 12 sessions of the Dutch version of Skill Training in Affective and Interpersonal Regulation (STAIR-A), followed by 12 sessions of EMDR therapy. In the immediate trauma-focused condition, the participants receive 12 sessions of EMDR therapy. The two groups are compared for several outcome variables before treatment, mid-treatment (only in the phase-based treatment condition), after 12 trauma-focused treatment sessions (post-treatment), and six months post-treatment (follow-up). The main parameter is the presence and severity of PTSD symptoms (Clinician-Administered PTSD Scale for Children and Adolescents, CAPS-CA). The secondary outcome variables are the severity of complex PTSD symptoms (Interpersonal Problems as measured by the Experiences in Close Relationship-Revised, ECR-RC; Emotion Regulation as measured by the Difficulties in Emotion Regulation Scale, DERS; Self Esteem as measured by the Rosenberg Self Esteem Scale, RSES), changes in anxiety and mood symptoms (Revised Anxiety and Depression Scale; RCADS), changes in posttraumatic cognitions (Child Posttraumatic Cognitions Inventory, CPTCI), changes in general psychopathology symptoms (Child Behavior Checklist, CBCL), and Quality of Life (Youth Outcome Questionnaire, Y-OQ-30). Furthermore, parental stress (Opvoedingsvragenlijst, OBVL) and patient-therapist relationship (Feedback Informed Treatment, FIT) will be measured, whereas PTSD symptoms will be monitored in each session during both treatment conditions (Children's Revised Impact of Event Scale, CRIES-13). DISCUSSION: Treating (symptoms of complex) PTSD in children and adolescents with a history of repeated sexual and/or physical abuse during childhood is of great importance. However, there is a lack of consensus among trauma experts regarding the optimal treatment approach. The results of the current study may have important implications for selecting effective treatment options for clinicians working with children and adolescents who experience the effects of exposure to multiple interpersonal traumatic events during childhood. TRIAL REGISTRATIONS: The study was registered on the "National Trial Register (NTR)" with the number NTR7024. This registry was obtained from the International Clinical Trial Registry Platform (ICTRP) and can be accessed through the ICTRP Search Portal ( https://trialsearch.who.int/ ).

The effects of COVID-19 on child mental health: Biannual assessments up to April 2022 in a clinical and two general population samples.

Background: The COVID-19 pandemic has had an acute impact on child mental and social health, but long-term effects are still unclear. We examined how child mental health has developed since the start of the COVID-19 pandemic up to 2 years into the pandemic (April 2022). Methods: We included children (age 8-18) from two general population samples (N = 222-1333 per measurement and N = 2401-13,362 for pre-covid data) and one clinical sample receiving psychiatric care (N = 334-748). Behavioral questionnaire data were assessed five times from April 2020 till April 2022 and pre-pandemic data were available for both general population samples. We collected parent-reported data on internalizing and externalizing problems with the Brief Problem Monitor and self-reported data on Anxiety, Depressive symptoms, Sleep-related impairments, Anger, Global health, and Peer relations with the Patient-Reported Outcomes Measurement Information System (PROMIS®). Results: In all samples, parents reported overall increased internalizing problems, but no increases in externalizing problems, in their children. Children from the general population self-reported increased mental health problems from before to during the pandemic on all six PROMIS domains, with generally worst scores in April 2021, and scores improving toward April 2022 but not to pre-pandemic norms. Children from the clinical sample reported increased mental health problems throughout the pandemic, with generally worst scores in April 2021 or April 2022 and no improvement. We found evidence of minor age effects and no sex effects. Conclusions: Child mental health in the general population has deteriorated during the first phase of the COVID-19 pandemic, has improved since April 2021, but has not yet returned to pre-pandemic levels. Children in psychiatric care show worsening of mental health problems during the pandemic, which has not improved since. Changes in child mental health should be monitored comprehensively to inform health care and policy.

Increased grey wolf diurnality in southern Europe under human-restricted conditions.

Wolves have been the archetype of wildlife persecution by humans for centuries all over the world, and still are heavily persecuted in some regions. Facultative diurnal/nocturnal wild mammals are known to become more nocturnal when persecuted. Conversely, little is known regarding the possibility of wolves becoming more diurnal if not persecuted. We took advantage of a 9-year natural experiment of restricted human access to a restored coal mine debris dump to study the daily activity patterns of wolves under conditions of infrequent human presence. Results were compared with a paired control site with frequent human use. Circadian wolf activity was monitored using camera traps (3 years in human-restricted site; 2 years in control). Additionally, data from two GPS-GSM-collared wolves monitored in a second control site were also analyzed. In our control sites, wolves were nearly inactive during daylight hours. In contrast, in the human-restricted site wolves extended their activity toward noon, with a daily activity peak between 10:00 and 12:00, and showed some activity throughout the entire circadian 2-h interval cycle considered. Wolves clearly had higher diurnality in the human-restricted area with 78% greater incidence of capture with remote cameras during the day than in the control site. We suggest that the shift toward increased diurnality was related to the loss of fear of humans. Evidence in support of this hypothesis comes from flight initiation distance (FID) data. Wolves showed relatively short FIDs when faced with a human observer (range 70-183 m) in broad daylight at the human-restricted site, but were so afraid of humans in the control site that we were unable to conduct FID trials there. Based on these results, we suggest that wolves may increase their diurnality in those European countries with currently increasing movement of human populations from rural to urban areas and that do not conduct lethal control of wolves. This would represent a historical landmark for a species that has been persecuted for many centuries. However, such behavioral shifts could bring new human-wolf conflicts that would require new policies.

The effect of functional calibration methods on gait kinematics in adolescents with idiopathic rotational deformity of the femur.

BACKGROUND: Due to anatomical deviations, assumptions of the conventional calibration method for gait analysis may be violated in individuals with rotational deformities of the femur. Functional calibration methods were compared with conventional methods in this group for 1) localization of the hip joint center and orientation of the knee axis, and 2) gait kinematics. METHODS: Twenty-four adolescents with idiopathic rotational deformity of the femur underwent gait analysis and a CT scan. During standing, distance between hip joint centers and knee axis orientation were compared between calibration methods, with CT serving as reference for hip joint center estimation. Gait kinematics were compared using statistical parametric mapping. FINDINGS: The conventional calibration method estimated the hip joint center closer to the CT reference (4±12 mm more lateral) than the functional calibration method (26 ± 20 mm more lateral). Orientation of the knee joint axis was 2.6° less internal in the functional calibration method. During gait, statistical parametric mapping revealed significantly more hip flexion, less external hip rotation during the swing phase, less knee varus-valgus motion, and larger knee flexion angles when applying the functional method. INTERPRETATION: Functional calibration methods were less accurate in determining the hip joint center location than the conventional calibration method and resulted in a knee joint axis that was less internally rotated. Importantly, there was less knee joint angle crosstalk during gait when using the functional method. Although differences between methods on gait kinematics were within clinically acceptable limits for the sagittal plane, relatively larger differences on transversal hip kinematics may hold clinical importance.

Victims of Child Abuse Dropping Out of Trauma-Focused Treatment: A Meta-Analysis of Risk Factors.

A substantial number of children who experienced child maltreatment drop out of evidence-based trauma-focused treatments (TF-CBT). Identifying child, family, and treatment-related factors associated with treatment dropout is important to be able to prevent this from happening and to effectively treat children's trauma-related symptoms. Methods: A quantitative review was performed based on a systematic synthesis of the literature on potential risk factors for dropout of trauma-focused treatment in maltreated children. Results: Eight studies were included, that examined TF-CBT, reporting on 139 effects of potential risk factors for dropout. Each factor was classified into one of ten domains. Small but significant effects were found for the "Demographic and Family" risk domain (r = .121), with factors including being male, child protective services involvement or placement, and minority status, and for the "Youth Alliance" risk domain (r = .207), with factors including low therapist-child support and low youth perception of parental approval. Moderator analyses suggested that family income and parental education may better predict the risk for TF-CBT dropout than other variables in the "Demographic and Family" domain. Conclusions: Our results provide a first overview of risk factors for dropout of trauma-focused treatments (TF-CBT) after child maltreatment, and highlight the role of the therapeutic relationship in this. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-022-00500-2.

Chemical Synthesis of La0.75Sr0.25CrO3 Thin Films for p-Type Transparent Conducting Electrodes.

The imperative need for highly performant and stable p-type transparent electrodes based on abundant metals is stimulating the research on perovskite oxide thin films. Moreover, exploring the preparation of these materials with the use of cost-efficient and scalable solution-based techniques is a promising approach to extract their full potential. Herein, we present the design of a chemical route, based on metal nitrate precursors, for the preparation of pure phase La0.75Sr0.25CrO3 (LSCO) thin films to be used as a p-type transparent conductive electrode. Different solution chemistries have been evaluated to ultimately obtain dense, epitaxial, and almost relaxed LSCO films. Optical characterization of the optimized LSCO films reveals promising high transparency with ∼67% transmittance while room temperature resistivity values are 1.4 Ω·cm. It is suggested that the presence of structural defects, i.e., antiphase boundaries and misfit dislocations, affects the electrical behavior of LSCO films. Monochromated electron energy loss spectroscopy allowed changes in the electronic structure in LSCO films to be determined, revealing the creation of Cr4+ and unoccupied states at the O 2p upon Sr-doping. This work offers a new venue to prepare and further investigate cost-effective functional perovskite oxides with potential to be used as p-type transparent conducting electrodes and be easily integrated in many oxide heterostructures.