Identifying Adolescents at Risk for Emotional Disorders with Latent Profile Analysis: A Personalized, Transdiagnostic Preventive Intervention.

It can be challenging to assign patients to the appropriate intervention programs, as risk and protective factors for developing emotional disorders are multiple and shared across disorders. This study aimed to provide a theoretical and empirical approach to identify and categorise adolescents into different levels of severity. The risk of developing emotional symptoms was assessed in 1425 Spanish adolescents (M = 14.34, SD = 1.76; 59.9% women). Latent Profile Analysis (LPA) was conducted to identify subgroups based on their emotional symptom severity, risk, and resilience factors. Results revealed four profiles: at low risk (emotionally healthy), moderate risk (for selective interventions), high risk (for indicated interventions), and severe risk (for clinical referral). Older age and especially female gender were predictors of higher risk clusters, and there were differences in the levels of psychopathology and health-related quality of life across clusters. Identification of at-risk adolescents for emotional disorders by means of LPA may contribute to designing personalised and tailored prevention programs that match adolescents' specific needs.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Psychometric Properties of the Connor-Davidson Resilience Scale (CD-RISC) in Spanish Adolescents

Few studies have examined the psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a large adolescent community sample, finding a significant disparity. This study explores the psychometric properties of the CD-RISC among Spanish adolescents by means of exploratory factor analysis (EFA), Rasch analysis, and measurement invariance (MI) across sex, as well as internal consistency and criterion validity. The sample was comprised of 463 adolescents (231 girls), aged 12 to 18 years, who completed the CD-RISC and other measures on emotional status and quality of life. The EFA suggested that the CD-RISC structure presented a unidimensional model. Consequently, shorter unidimensional CD-RISC models observed in the literature were explored. Thus, the Campbell-Sills and Stein CD–RISC–10 showed the soundest psychometric properties, providing an adequate item fit and supporting MI and non-differential item functioning across sex. Item difficulty levels were biased toward low levels of resilience. Some items showed malfunctioning in lower response categories. With regard to reliability, categorical omega was. 82. Strong associations with health-related quality of life, major depressive disorder symptoms, and emotional symptoms were observed. A weak association was found between resilience and the male sex. Campbell-Sills and Stein’s CD–RISC–10 model emerges as the best to assess resilience among Spanish adolescents, as already reported in adults. Thus, independently of the developmental stage, the core of resilience may reside in the aspects of hardiness and persistence. (AU)

Psychometric Properties of the Connor-Davidson Resilience Scale (CD-RISC) in Spanish Adolescents.

Few studies have examined the psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a large adolescent community sample, finding a significant disparity. This study explores the psychometric properties of the CD-RISC among Spanish adolescents by means of exploratory factor analysis (EFA), Rasch analysis, and measurement invariance (MI) across sex, as well as internal consistency and criterion validity. The sample was comprised of 463 adolescents (231 girls), aged 12 to 18 years, who completed the CD-RISC and other measures on emotional status and quality of life. The EFA suggested that the CD-RISC structure presented a unidimensional model. Consequently, shorter unidimensional CD-RISC models observed in the literature were explored. Thus, the Campbell-Sills and Stein CD-RISC-10 showed the soundest psychometric properties, providing an adequate item fit and supporting MI and non-differential item functioning across sex. Item difficulty levels were biased toward low levels of resilience. Some items showed malfunctioning in lower response categories. With regard to reliability, categorical omega was. 82. Strong associations with health-related quality of life, major depressive disorder symptoms, and emotional symptoms were observed. A weak association was found between resilience and the male sex. Campbell-Sills and Stein's CD-RISC-10 model emerges as the best to assess resilience among Spanish adolescents, as already reported in adults. Thus, independently of the developmental stage, the core of resilience may reside in the aspects of hardiness and persistence.

A 12-Month Follow-Up of PROCARE+, a Transdiagnostic, Selective, Preventive Intervention for Adolescents At-Risk for Emotional Disorders.

Few studies have reported long-term follow-up data on selective preventive interventions for adolescents. No follow-up selective preventive transdiagnostic studies for adolescents at-risk for emotional disorders, such as anxiety and depression, have been reported. To fill this gap, this study aims to provide the first follow-up assessment of a randomized controlled trial (RCT) studying selective transdiagnostic prevention in at-risk adolescents. A 12-month follow-up assessment was conducted with subjects who originally received either PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), PROCARE+, which includes the PROCARE protocol along with personalized add-on modules or an active control condition (ACC) based on emotional psychoeducation, and their respective booster session for each experimental condition. 80 subjects (47.5% girls) aged between 12 and 18 years (M = 14.62; SD 1.43) who completed these treatment conditions were available for the 12-month follow-up. The results demonstrate the superior long-term efficacy of the PROCARE+ intervention in mitigating emotional symptoms and obsessive-compulsive symptomatology compared to the PROCARE and ACC conditions, with effect sizes notably exceeding those commonly observed in preventive programs. While the three treatments demonstrated beneficial impacts, the pronounced results associated with PROCARE+ at the 12-month follow-up emphasized the importance of personalized treatment modules and the sustained benefits of booster sessions in the realm of preventive psychological interventions. The findings also highlight the potential role of add-on modules in enhancing the effects of the PROCARE+ condition.

Randomized controlled trial for selective preventive transdiagnostic intervention for adolescents at risk for emotional disorders.

Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents' risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 208 adolescents (48.5% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Data from 153 adolescents who completed all assessments in the different phases of the study were analyzed. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6 month follow-up was carried out, together with a 1 month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE + in the short and long term. Interventions were acceptable in terms of acceptability, with good satisfaction rates. Tailored targeted selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.

Randomized controlled trial for selective preventive transdiagnostic intervention for adolescents at risk for emotional disorders.

Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, online-delivered, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session, to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents' risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 286 adolescents (53.3% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6-month follow-up was carried out, together with a 1-month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE +. Interventions were excellent in terms of acceptability, with good satisfaction rates. Tailored selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.

The state of psychological treatments for social anxiety disorder in children and adolescents: An Umbrella Review / Estado de los tratamientos psicológicos para el Trastorno de Ansiedad Social en población infanto-juvenil: Revisión de revisiones

Social Anxiety Disorder (SAD) is a very common disorder in childhood and adolescence. Many studies have examined various types of CognitiveBehavioral Therapy (CBT), meaning there is a need for a study exploring the efficacy of CBT. The objectives of this study are to determine whattreatments and factors can improve treatment outcomes for SAD. We performed an umbrella review of the effectiveness of psychological interventions in treating SAD in children and adolescents. Nine databases were searched using a combination of keywords. Risk of bias was assessed usingAMSTAR-2. Six systematic reviews and meta-analysis were selected and reported. All of those studies assessed the efficacy of CBT in children andadolescents with SAD, demonstrating its short- and long-term effectiveness. The components that seem to be most effective are exposure in anymodality and social skills training. Other considerations to take into account are addressed in the discussion. (AU)

El Trastorno de Ansiedad Social (TAS) es un trastorno muy común en la infancia y adolescencia. Muchos estudios han analizado los diferentes tipos de TerapiaCognitivo-Conductual (TCC) para dicho trastorno, pero ello hace necesario estudiar la eficacia de TCC. El objetivo de esta revisión de revisioneses determinar que tratamientos y que factores son más eficaces para el TAS en población infanto-juvenil. Se realizó una revisión de revisiones sobrela efectividad de las intervenciones psicológicas para tratar el TAS en niños y adolescentes. Para ello, se realizó una búsqueda en nueve bases dedatos utilizando una combinación de palabras clave. El riesgo de sesgo se evaluó mediante la herramienta AMSTAR-2. Se seleccionaron y analizaronseis revisiones sistemáticas y meta-análisis. Todos los estudios seleccionados evaluaron la eficacia de la TCC en niños y adolescentes con SAD,demostrando su efectividad a corto y largo plazo. Los componentes que parecen ser más efectivos son la exposición en cualquier modalidad y elentrenamiento en habilidades sociales. Otras consideraciones a tener en cuenta se abordan en la discusión. (AU)

Cumulative Risk Exposure and Social Isolation as Correlates of Carer and Child Mental Health During the COVID-19 Pandemic: An Online Study with Families from Various Europeans Countries.

This study adopted a cumulative risk approach to examine the relations between various domains of risk factors (i.e., social isolation and home confinement, other pandemic-related risk factors, and pre-existing psychosocial risk factors) and carers' and children's mental health during the first wave of the COVID-19 pandemic in Europe. The sample consisted of 1475 carers of 6- to 16-year-old children and adolescents residing in five European countries (Portugal, United Kingdom, Romania, Spain, and The Netherlands) who completed an online survey. The results showed that each of the three domains of adversity accounted for unique variation in carers' and children's mental health outcomes. Also, the results indicated that pre-existing psychosocial risk factors moderated the relationship between pandemic-related risk factors and children and carers' anxiety and between social isolation and confinement and carers' well-being. Simple slopes analysis suggested a stronger relationship between these domains of adversities and mental health outcomes in already more vulnerable families. It is important to consider the implications of social isolation measures and confinement for families' mental health, paying special attention to families with pre-existing psychosocial vulnerabilities.

Maternal diet in pregnancy and acute leukemia in infants: a case-control study in Mexico City.

Introduction: Epidemiological studies around the world on acute leukemia (AL) and risk factors in infants are scarce. Infant AL has been proposed to originate in utero, which facilitates its study by establishing a short exposure time in pregnant women to environmental and dietary factors that could contribute to the risk of or protection against leukemia. We hypothesized that maternal diet during pregnancy may be an important factor involved in AL in offspring. Methods: We conducted a hospital-based case-control study from 2010 to 2019 on maternal diet during pregnancy in nine high-specialty public hospitals of different health institutions that diagnose and offer treatment to children with AL in Mexico City. Cases (n=109) were children ≤24 months of age with de novo diagnosis of AL, and controls (n=252) were children obtained in hospitals from second-level medical care matched for age, sex, and health institution. Maternal diet during pregnancy was obtained by a semiquantitative food frequency questionnaire. Unconditional logistic regression models were used to assess the association between food groups and infant AL. Potential confounders were assessed by constructing directed acyclic graphs (DAGs) with Dagitty software in which adjusted options were identified for the construction of unconditional logistic regression models. Results: Cases were slightly predominantly female (52.3%). The years of education of the mother in cases and controls was 0-9 on average, and those who reported smoking cigarettes and consuming alcohol during pregnancy did so at a low frequency. Regarding the mother's diet, the main findings were that the consumption of allium vegetables during pregnancy was inversely associated with AL for medium and high consumption (OR=0.26, 95% CI 0.14-0.46; P-trend< 0.001). In contrast, the high consumption of high-fat dairy products had a positive association with AL (OR=2.37, 95% CI 1.30-4.34; P-trend<0.001). No association was found between consumption of topoisomerase II inhibitor foods during pregnancy and AL. Conclusion: The results suggest that maternal intake during pregnancy of allium vegetables, specifically garlic, is inversely associated with the development of AL in children ≤24 months old. On the other hand, consumption of high-fat dairy products is positively associated with AL in children ≤24 months old.

Emotion Dysregulation as a Mediator of the Relationship between Anxiety, Compulsive Exercise and Eating Disorder Symptoms in Adolescents.

Anxiety has been suggested to be a key contributing factor for compulsive exercise, however, existing literature has demonstrated contradictory relationships between anxiety and compulsive exercise among adolescents. According to the Emotional Cascade Model (ECM), factors such as rumination and emotional suppression may mediate the association between affect and exercise. The current study therefore aimed to investigate whether rumination and emotional suppression mediate the relationship between anxiety and compulsive exercise in predicting ED symptoms in adolescents. Questionnaires assessing compulsive exercise, anxiety, depressive rumination, emotional suppression, and ED symptoms were completed by 212 adolescent males (Mage = 13.39, SD = 1.22) and 189 adolescent females (Mage = 13.64, SD = 1.29). The structural equation model showed indirect effects between anxiety and compulsive exercise through rumination and emotional suppression in males but not in females. Moreover, anxiety had an indirect effect on eating disorder symptoms through rumination, emotional suppression and compulsive exercise in both males and females. In line with ECM, the results suggest that rumination and emotional suppression may have a key role in the association between anxiety, compulsive exercise and eating disorder symptoms in adolescents. These findings suggest that compulsive exercise may be used as a dysfunctional coping mechanism to escape from a negative emotional cascade generated by the interaction of anxiety, rumination and emotional suppression. Future longitudinal studies to test the role of compulsive exercise as a dysfunctional behaviour in the ECM are needed.

Screening Social Anxiety in Adolescents Through the Eyes of Their Carers.

Despite the availability of efficacious treatment and screening protocols, social anxiety disorder (SAD) in adolescents is considerably under-detected and undertreated. Our main study objective was to examine a brief, valid, and reliable social anxiety measure already tested to serve as self-report child measure but administered via Internet aimed at listening to the ability of his or her parent to identify social anxiety symptomatology in his or her child. This parent version could be used as a complementary measure to avoid his or her overestimation of children of social anxiety symptomatology using traditional self-reported measures. We examined the psychometric properties of brief and valid social anxiety measure in their parent format and administered via the Internet. The sample included 179 parents/legal guardians of adolescents (67% girls) with a clinical diagnosis of SAD (mean age: 14.27; SD = 1.33). Findings revealed good factor structure, internal consistency, and construct validity. Data support a single, strength-based factor on the SPAIB-P, being structure largely invariant across age and gender. The limited number of adolescents with a performance-only specifier prevented examining the utility of scale to screen for this recently established specifier. It is crucial to evaluate if these results generalize to different cultures and community samples. The findings suggest that the SPAIB-P evidences performance comparable with child-reported measure. Parents can be reliable reports of the social anxiety symptomatology of the adolescent. The SPAIB-P may be useful for identifying clinically disturbed socially anxious adolescents.

Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population. METHODS: A multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5'exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software. RESULTS: miR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05-2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23-23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04-298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found. CONCLUSION: Our findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.

Validation of the Structured Interview for the Assessment of Expressed Emotion (E5) in a Sample of Adolescents and Young Adults From the General Population.

Expressed emotion (EE) is an index of significant others' attitudes, feelings, and behavior toward an identified patient. EE was originally conceptualized as a dichotomous summary index. Thus, a family member is rated low or high on how much criticism, hostility, and emotional overinvolvement (EOI) s/he expresses toward an identified patient. However, the lack of brief, valid measures is a drawback to assess EE. To cover this gap, the E5 was designed. The objective of this study is to provide psychometric properties of a recent measured in adolescents to be used to tap perceived high levels of EE. The sample was composed by 2,905 adolescents aged from 11-19years; 57% girls. Results demonstrate good factor structure, reliability, construct validity and invariance across gender and age revealed a good fit. As a result, E5 is a brief, valid and reliable measure for assessing expressed emotion in parents of adolescent children.

Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children. Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis. Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21-1.93), rs1799929 (OR 1.96, 95% CI 1.55-2.49), and rs1208 (OR 1.44, 95% CI 1.14-1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30-1.71, OR 3.87, 95% CI 2.20-6.80, and OR 2.26, 95% CI 1.32-3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed. Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

Maternal and paternal ages at conception of index child and risk of childhood acute leukaemia: A multicentre case-control study in Greater Mexico City.

BACKGROUND: The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults. METHODS: A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category. RESULTS: In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was <20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83). CONCLUSION: In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages.

Mediators in psychological and psychoeducational interventions for the prevention of depression and anxiety. A systematic review.

Although efforts have been undertaken to determine how psychological interventions exert their effects, research on mediators and mechanisms of change remains limited, especially in the field of prevention. We aimed to assess available evidence on mediators of psychological and psychoeducational interventions for the prevention of depression and anxiety in varied populations. A systematic review using PubMed, PsycINFO, Web of Science, Embase, OpenGrey, and the Cochrane Central Register of Controlled Trials was performed. Two independent reviewers assessed the eligibility criteria of all articles, extracted data, determined the risk of bias in randomized controlled trials, and the requirements for mediators. The outcomes were mediators of the incidence of depression or anxiety and/or the reduction of symptoms of depression or anxiety. We identified 28 nested mediator studies within randomized controlled trials involving 7442 participants. Potential cognitive, behavioral, emotional and interpersonal mediators were evaluated in different psychological and psychoeducational interventions to prevent depression and anxiety. The effects were mediated mainly by cognitive variables, which were the most commonly assessed factors. For depression, the mediator with the strongest empirical support was negative thinking in adults. Cognitive change is an important mediator in preventive psychological and psychoeducational interventions for both anxiety and depression. REGISTRATION DETAILS: Registration number (PROSPERO): CRD42018092393.

Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia.