Depression and Anxiety in Times of COVID-19: How Coping Strategies and Loneliness Relate to Mental Health Outcomes and Academic Performance.

The link between depression, anxiety, and loneliness has been well established in the literature. Yet, the performance consequences of these negative mental health outcomes and the role of coping behaviors, as well as behavioral consequences such as procrastination as mediators have received far less research attention. Due to the COVID-19 social isolation restrictions, people are at risk of falling into a negative mental health spiral that can also affect their performance over time. The purpose of this longitudinal study among 881 first-year bachelor students is to explore the mechanisms by which loneliness, coping strategies in the context of COVID-19, mental health outcomes and procrastination sequentially mediate the relationship depression and anxiety on the one hand, and academic performance on the other hand. We measured mental health variables several times during the COVID-19 crisis and assessed how this translates into academic performance at the end of the academic year. By performing exploratory and confirmatory factor analyses, three high-order factors for the coping strategies in the context of the COVID-19 crisis were identified, namely maladaptive coping, adaptive coping, and supportive coping. Structural equation modeling was used to test the sequential mediational model. The results showed that maladaptive coping strategies employed at T2 during the lockdown, but not adaptive or supportive coping partially mediate the trajectories of depression (T1) and anxiety (T1). Loneliness (T2) partially mediated the trajectory of depression and anxiety (T1), and procrastination fully mediated the impact of depression (T3) on academic performance (T4). These results help understand the mechanisms that influence mental health and academic performance outcomes in response to the COVID-19 crisis. Based on the study outcomes, educational researchers can test strategies to reduce the adverse effects of stressful situations in learning environments by targeting maladaptive coping behaviors and procrastination.

From Shattered Goals to Meaning in Life: Life Crafting in Times of the COVID-19 Pandemic.

The novel COVID-19 pandemic has created an extraordinary situation for our generation, with many countries being on lockdown. With this, new situation comes many psychological challenges not only for health care workers and people suffering from COVID-19 but also for the general population. Adapting to the new situation can be demanding. Experts have suggested that emotions during this situation are very similar to grief, and people experience emptiness and sadness about the loss of their normal lives, which can even lead to a loss of meaning in life. In this paper, we argue that life crafting could offer a way to help people cope with the situation and renew their sense of meaning. A life crafting intervention is based on theoretical insights from multiple areas of research, like positive psychology, expressive writing, and the salutogenesis framework. Life-crafting interventions help people find meaning in life by focusing on their ideal future, and helping them set goals, and make concrete plans to achieve those goals and overcome obstacles. Since having a clear purpose or meaning in life has been shown to have many benefits, we propose that it can also help people to cope with the psychological effects of the pandemic. A life-crafting intervention can offer people a chance to evaluate their goals in a time of uncertainty and rediscover meaning in life to guide them through these difficult times.

Histological, immunohistochemical and transcriptomic characterization of human tracheoesophageal fistulas.

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are relatively frequently occurring foregut malformations. EA/TEF is thought to have a strong genetic component. Not much is known regarding the biological processes disturbed or which cell type is affected in patients. This hampers the detection of the responsible culprits (genetic or environmental) for the origin of these congenital anatomical malformations. Therefore, we examined gene expression patterns in the TEF and compared them to the patterns in esophageal, tracheal and lung control samples. We studied tissue organization and key proteins using immunohistochemistry. There were clear differences between TEF and control samples. Based on the number of differentially expressed genes as well as histological characteristics, TEFs were most similar to normal esophagus. The BMP-signaling pathway, actin cytoskeleton and extracellular matrix pathways are downregulated in TEF. Genes involved in smooth muscle contraction are overexpressed in TEF compared to esophagus as well as trachea. These enriched pathways indicate myofibroblast activated fibrosis. TEF represents a specific tissue type with large contributions of intestinal smooth muscle cells and neurons. All major cell types present in esophagus are present-albeit often structurally disorganized-in TEF, indicating that its etiology should not be sought in cell fate specification.

Optimizing Students' Mental Health and Academic Performance: AI-Enhanced Life Crafting.

One in three university students experiences mental health problems during their study. A similar percentage leaves higher education without obtaining the degree for which they enrolled. Research suggests that both mental health problems and academic underperformance could be caused by students lacking control and purpose while they are adjusting to tertiary education. Currently, universities are not designed to cater to all the personal needs and mental health problems of large numbers of students at the start of their studies. Within the literature aimed at preventing mental health problems among students (e.g., anxiety or depression), digital forms of therapy recently have been suggested as potentially scalable solutions to address these problems. Integrative psychological artificial intelligence (AI) in the form of a chatbot, for example, shows great potential as an evidence-based solution. At the same time, within the literature aimed at improving academic performance, the online life-crafting intervention in which students write about values and passions, goals, and goal-attainment plans has shown to improve the academic performance and retention rates of students. Because the life-crafting intervention is delivered through the curriculum and doesn't bear the stigma that is associated with therapy, it can reach larger populations of students. But life-crafting lacks the means for follow-up or the interactiveness that online AI-guided therapy can offer. In this narrative review, we propose to integrate the current literature on chatbot interventions aimed at the mental health of students with research about a life-crafting intervention that uses an inclusive curriculum-wide approach. When a chatbot asks students to prioritize both academic as well as social and health-related goals and provides personalized follow-up coaching, this can prevent -often interrelated- academic and mental health problems. Right on-time delivery, and personalized follow-up questions enhance the effects of both -originally separated- intervention types. Research on this new combination of interventions should use design principles that increase user-friendliness and monitor the technology acceptance of its participants.

Teacher and child perceptions of relationship quality and ethnic minority children's behavioral adjustment in upper elementary school: A cross-lagged approach.

In this study, cross-lagged longitudinal modeling was used to examine associations between teacher-child relationship quality and children's behavioral adjustment in a sample of sixth grade ethnic minority children. In comparison to previous cross-lagged studies, children were older and cross-informant models were used. Both teachers (N = 12) and children (N = 226) reported on the relationship quality (Closeness, Conflict, and Dependency or Negative Expectations), and children's behavioral adjustment (Externalizing Problems, Internalizing Problems, and Prosocial Behavior) at the beginning and the end of the school year. Children's externalizing behavior at the beginning of the school year was consistently and positively associated with conflict at the end of the school year. Interestingly, dependency at time 1 was associated with children's behavioral adjustment at time 2, whereas for closeness and conflict associations were the other way around (i.e., children's behavior at time 1 was associated with teacher-child closeness and conflict at time 2). Taken together, our results seem to indicate that bidirectional associations between teacher-child relationships and behavioral adjustment apply to older, ethnic minority children as well.

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula.

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444_143839360)_(159119486_159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition.

A Values-Affirmation Intervention Does Not Benefit Negatively Stereotyped Immigrant Students in the Netherlands.

Previous research showed that a values-affirmation intervention can help reduce the achievement gap between African American and European American students in the US. In the present study, it was examined if these results would generalize to ethnic minority students in a country outside the US, namely the Netherlands, where there is also an achievement gap between native and ethnic minority students. This type of intervention was tested in two separate studies, the first among first-year pre-vocational students (n = 361, 84% ethnic minority), and the second among sixth grade students (n = 290, 96% ethnic minority). Most minority participants had a Turkish-Dutch or Moroccan-Dutch immigrant background. In the second study, a third condition was added to the original paradigm, in which students elaborated on either their affirmation- or a control exercise with the help of a teaching assistant. We also examined whether values affirmation affected the level of problem behavior of negatively stereotyped ethnic minority youth. Contrary to what was expected, multilevel analyses revealed that the intervention had no effect on the school achievement or the problem behavior of the ethnic minority students. Possible explanations for these findings, mainly related to contextual and cultural differences between the Netherlands and the US, are discussed.

Structural and numerical changes of chromosome X in patients with esophageal atresia.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a relatively common birth defect often associated with additional congenital anomalies such as vertebral, anal, cardiovascular, renal and limb defects, the so-called VACTERL association. Yet, little is known about the causal genetic factors. Rare case reports of gastrointestinal anomalies in children with triple X syndrome prompted us to survey the incidence of structural and numerical changes of chromosome X in patients with EA/TEF. All available (n=269) karyotypes of our large (321) EA/TEF patient cohort were evaluated for X-chromosome anomalies. If sufficient DNA material was available, we determined genome-wide copy number profiles with SNP array and identified subtelomeric aberrations on the difficult to profile PAR1 region using telomere-multiplex ligation-dependent probe amplification. In addition, we investigated X-chromosome inactivation (XCI) patterns and mode of inheritance of detected aberrations in selected patients. Three EA/TEF patients had an additional maternally inherited X chromosome. These three female patients had normal random XCI patterns. Two male EA/TEF patients had small inherited duplications of the XY-linked SHOX (Short stature HOmeoboX-containing) locus. Patients were small for gestational age at birth (

[A woman with a painful hip]. / Een vrouw met een pijnlijke heup.

A 85-year-old woman suffered persisting pain in her left hip after a fall. On X-ray no fracture was seen. Her infection parameters were high and she developed a delirium and a painful swelling on her left hip. Examination with ultrasound showed free gas in the soft tissue of the left hip. A CT-scan of the abdomen and left upper leg showed a ruptured abscess in the left kidney with free gas, spreading through the M. iliopsoas into the upper left leg. On request of the patient and her family no treatment was given.

5q11.2 deletion in a patient with tracheal agenesis.

Tracheal agenesis (TA) is a rare congenital anomaly of the respiratory tract. Many patients have associated anomalies, suggesting a syndromal phenotype. In a cohort of 12 patients, we aimed to detect copy number variations. In addition to routine cytogenetic analysis, we applied oligonucleotide array comparative genomic hybridization. Our patient cohort showed various copy number variations, of which many were parentally inherited variants. One patient had, in addition to an inherited 16p12.1 deletion, a 3.6 Mb deletion on chromosomal locus 5q11.2. This patient had a syndromic phenotype, including vertebral, anal, cardiovascular and tracheo-oesophageal associated anomalies, and other foregut-related anomalies, such as cartilage rings in the oesophagus and an aberrant right bronchus. No common deletions or duplications are found in our cohort, suggesting that TA is a genetically heterogeneous disorder.

Polyalanine expansion in the ZIC3 gene leading to X-linked heterotaxy with VACTERL association: a new polyalanine disorder?

BACKGROUND: The VACTERL association is a non-random association of congenital defects with an unknown aetiology in the majority of patients. METHODS: A male newborn is reported with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of this patient overlaps with that of X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced. RESULTS: In a patient with the VACTERL association a 6-nucleotide insertion was found in the GCC repeat of the ZIC3 gene, which is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. The polyalanine expansion is a novel ZIC3 mutation which was not found in 336 chromosomes from 192 ethnically matched controls. The mutation was also not present in the mother, suggesting it occurred de novo in the patient and is therefore a pathogenetic mutation. CONCLUSION: It is hypothesized that this novel and de novo polyalanine expansion in ZIC3 contributes to the VACTERL association in this patient. A newborn male is described with features of the VACTERL association, including anal atresia, laryngeal and oesophageal atresia with tracheo-oesophageal fistula, dextroposition of the heart with persistent left superior vena cava, and unilateral multicystic kidney. As the clinical picture of the VACTERL association overlaps with X-linked heterotaxy caused by ZIC3 mutations, the ZIC3 coding region was sequenced, and a 6-nucleotide insertion was found that is predicted to expand the amino-terminal polyalanine repeat from 10 to 12 polyalanines. This novel mutation was not present in the mother, nor in 336 chromosomes from 192 ethnically matched controls. It is hypothesised that this novel and de novo polyalanine expansion in the ZIC3 gene contributes to the VACTERL association in this patient.

Etiology of esophageal atresia and tracheoesophageal fistula: "mind the gap".

Esophageal atresia and tracheoesophageal fistula (EA/TEF) are major congenital malformations affecting 1:3500 live births. Current research efforts are focused on understanding the etiology of these defects. We describe well-known animal models, human syndromes, and associations involving EA/TEF, indicating its etiologically heterogeneous nature. Recent advances in genotyping technology and in knowledge of human genetic variation will improve clinical counseling on etiologic factors. This review provides a clinical summary of environmental and genetic factors involved in EA/TEF.

Improved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1.

CONTEXT: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. OBJECTIVE: Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. DESIGN AND RESULTS: We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. CONCLUSION: This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders.

Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: an overview of the current concepts.

Esophageal atresia and/or tracheoesophageal fistula (EA/TEF) are severe congenital anomalies. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of these defects is lagging. Many genes and genetic pathways have been implicated in the development of EA/TEF, but only a few genes have been shown to be involved in humans, in animals, or in both. Extrapolating data from animal models to humans is not always straightforward. Environmental factors may also carry a risk, but the mechanisms are yet to be elucidated. This review gives an overview of the current state of knowledge about both genetic and environmental risk factors in the etiology of EA/TEF.

Non-VACTERL-type anomalies are frequent in patients with esophageal atresia/tracheo-esophageal fistula and full or partial VACTERL association.

BACKGROUND: The VACTERL association is the nonrandom co-occurrence of Vertebral anomalies, Anal atresia, Cardiovascular malformations, Tracheo-esophageal fistula (TEF) and/or Esophageal atresia (EA), Renal anomalies, and/or Limb-anomalies. The full phenotype of patients with EA/TEF and other anomalies of the VACTERL spectrum of defects association is not well described in the literature. METHODS: Data on patients with EA/TEF seen in two pediatric surgical centers in the Netherlands between January 1988 and August 2006 were evaluated for defects of the VACTERL spectrum as well as non-VACTERL-type defects. The presence of two or more defects of the VACTERL spectrum in addition to EA/TEF was the criterion for inclusion in this study. A detailed description was made of all defects. RESULTS: Of 463 patients with EA and/or TEF, 107 (23.1%) fulfilled the inclusion criterion, of which seventeen cases had a recognized etiology and were excluded, leaving 90 cases (19.4%) for analysis. Other than the esophagus and the trachea, the vertebrae/ribs and the cardiovascular system were most commonly affected (68.9 and 65.6%, respectively). Interestingly, 70% of cases had additional non-VACTERL-type defects, with high occurrences for single umbilical artery (20%), genital defects (23.3%), and respiratory tract anomalies (13.3%). CONCLUSIONS: Many patients with EA/TEF and at least two other defects of the VACTERL spectrum also display non-VACTERL-type congenital anomalies.