Resilient functioning is associated with altered structural brain network topology in adolescents exposed to childhood adversity.

Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.

High expression of Toll-like receptor 7 is a survival factor in pediatric medulloblastoma.

PURPOSE: Medulloblastoma is an embryonal brain tumor that predominantly occurs in childhood with a wide histological and molecular variability. Our aim was to investigate the expression of Toll-like receptors (TLRs), their association with the infiltration of immune cells and with the histological subgroups, and, also, with the overall survival of patients. METHODS: Fifty-six paraffin-preserved biopsies from children with medulloblastoma of the classic, desmoplastic, and anaplastic subtypes were included. Microarrays of tissues were performed, and the infiltration of T and NK cells was quantified, as well as the expression of TLR7, TLR8, and TLR9. For all statistical analyses, significance was p < 0.05. RESULTS: CD4 + and CD8 + T lymphocytes and NK cells were found infiltrating the tumor. The infiltration of NK and CD4 + cells was greater in the classic and desmoplastic subtypes than in anaplastic. We found an important expression of TLRs in all medulloblastomas, but TLR7 and TLR8 were considerably higher in classic and desmoplastic subtypes than in anaplastic. Importantly, we observed that TLR7 was a prognostic factor for survival. CONCLUSIONS: Medulloblastomas present cellular infiltration and a differential expression of TLRs depending on the histological subtype. TLR7 is a prognostic factor of survival that is dependent on treatment and age.

Differences in substance use, psychiatric disorders and social factors between Mexican adolescents and young adults.

BACKGROUND AND OBJECTIVES: Substance use disorders (SUDs) have high comorbidities with psychiatric disorders. Childhood and adolescence are particularly vulnerable developmental periods for the onset of SUDs. The objective of this study was to explore the differences, if any, between Mexican adolescents and young adults with respect to the prevalences of groups of psychiatric disorders, the types of substances used and the social factors involved. METHODS: This cross-sectional study included 781 patients evaluated at the Youth Integration Center in Mexico City. The diagnostic criteria for SUDs and psychiatric disorders were defined according to the DSM-IV and ICD-10. Associations between SUDs and psychiatric disorders were evaluated via multivariate analysis using logistic regression models. RESULTS: The adolescents were more frequently substance abusers, whereas the adults had legal problems more often than the adolescents. We showed that adolescents using inhalants or cocaine were 1.62 more likely to have attention deficit hyperactivity disorder (ADHD). Moreover, adults using inhalants were 3.33 times more likely to meet the criteria for a psychotic disorder. DISCUSSION AND CONCLUSIONS: We found that adolescents diagnosed with ADHD were more likely to have problems with use or abuse of or dependence on inhalants, and an elevated prevalence of parental SUDs was found in both the adolescent and adult groups. SCIENTIFIC SIGNIFICANCE: Our findings indicate that earlier diagnosis and intervention are necessary in adolescents with ADHD and/or parental SUDs to prevent more advanced psychiatric diseases and adverse social consequences during adulthood. (Am J Addict 2018;XX:1-7).

Early adolescent perceived friendship quality aids affective and neural responses to social inclusion and exclusion in young adults with and without adverse childhood experiences.

Friendships increase mental wellbeing and resilient functioning in young people with childhood adversity (CA). However, the mechanisms of this relationship are unknown. We examined the relationship between perceived friendship quality at age 14 after the experience of CA and reduced affective and neural responses to social exclusion at age 24. Resilient functioning was quantified as psychosocial functioning relative to the degree of CA severity in 310 participants at age 24. From this cohort, 62 young people with and without CA underwent functional Magnetic Resonance Imaging to assess brain responses to social inclusion and exclusion. We observed that good friendship quality was significantly associated with better resilient functioning. Both friendship quality and resilient functioning were related to increased affective responses to social inclusion. We also found that friendship quality, but not resilient functioning, was associated with increased dorsomedial prefrontal cortex responses to peer exclusion. Our findings suggest that friendship quality in early adolescence may contribute to the evaluation of social inclusion by increasing affective sensitivity to positive social experiences and increased brain activity in regions involved in emotion regulation to negative social experiences. Future research is needed to clarify this relationship with resilient functioning in early adulthood.

Characteristics and outcomes of multisystem inflammatory syndrome in children: A multicenter, retrospective, observational cohort study in Mexico.

Introduction: Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. Methods: This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis (LCA) to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. Results: The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysms were found in 5.7% and 13.2% of the patients in whom coronary artery diameter was measured, respectively. Any cause in-hospital mortality was 5.4%. Hospitalization after ten days of symptoms was associated with coronary artery abnormalities (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0). Age ≥10 years (OR: 5.6, 95% CI: 1.4-2.04), severe underlying condition (OR: 9.3, 95% CI: 2.8-31.0), platelet count <150,000 /mm3 (OR: 4.2, 95% CI: 1.2-14.7), international normalized ratio >1.2 (OR: 3.8, 95% CI: 1.05-13.9), and serum ferritin concentration >1,500 mg/dl at admission (OR: 52, 95% CI: 5.9-463) were risk factors for death. Discussion: Mortality in patients with MIS-C was higher than reported in other series, probably because of a high rate of cases with serious underlying diseases.

Characteristics and Outcomes of Cases of Children and Adolescents With Pediatric Inflammatory Multisystem Syndrome in a Tertiary Care Center in Mexico City.

Background: Pediatric inflammatory multisystem syndrome (PIMS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that resembles Kawasaki syndrome and places them at high risk of cardiorespiratory instability and/or cardiac damage. This study aims to describe the clinical presentation and outcomes of patients with PIMS in Mexico City. Methods: This was an observational study of children hospitalized for PIMS based on the Centers for Disease Control and Prevention case definition criteria, in a single tertiary care pediatric center in Mexico City between May 1, 2020, and September 30, 2021. Demographic characteristics, epidemiological data, medical history, laboratory tests, cardiologic evaluations, treatment, and clinical outcomes were analyzed. Results: Seventy-five cases fulfilled the case definition criteria for PIMS [median age: 10.9 years, Interquartile range (IQR): 5.6-15.6]. Fifteen (20%) patients had a severe underlying disease, 48 (64%) were admitted to the intensive care unit, 33 (44%) required invasive mechanical ventilation and 39 (52%) received vasopressor support. The patients were clustered through latent class analysis based on identified symptoms: Cluster 1 had rash or gastrointestinal symptoms (n = 60) and cluster 2 were those with predominantly respiratory manifestations (n = 15). Two patients (2.7%) died, and both had severe underlying conditions. Five patients (6.7%), all from cluster 1, developed coronary aneurysms. Conclusion: There were a high proportion of patients with severe respiratory involvement and positive RT-PCR SARS-CoV-2 and very few cases of coronary aneurysms in our study which suggests that a high proportion of the children had severe acute COVID-19. The clinical manifestations and outcomes are comparable to previously reported international studies.

Tracing COVID-19 Source of Infection Among Health Personnel in a Pediatric Hospital.

Health personnel (HP) have been universally recognized as especially susceptible to COVID-19. In Mexico, our home country, HP has one of the highest death rates from the disease. From the beginning of the SARS-CoV-2 pandemic, an office for initial attention for HP and a call center were established at a COVID-19 national reference pediatric hospital, aimed at early detection of COVID-19 cases and stopping local transmission. The detection and call center implementation and operation, and tracing methodology are described here. A total of 1,042 HP were evaluated, with 221 positive cases identified (7.7% of all HP currently working and 26% of the HP tested). Community contagion was most prevalent (46%), followed by other HP (27%), household (14%), and hospitalized patients (13%). Clusters and contact network analysis are discussed. This is one of the first reports that address the details of the implementation process of contact tracing in a pediatric hospital from the perspective of a hybrid hospital with COVID-19 and non-COVID-19 areas.

Covid-19 Incidence and Mortality by Age Strata and Comorbidities in Mexico City: A Focus in the Pediatric Population.

Background: SARS-COV2 appears less frequently and less severely in the pediatric population than in the older age groups. There is a need to precisely estimate the specific risks for each age group to design health and education policies suitable for each population. Objective: This study aimed to describe the risk of death in SARS-COV2 infected subjects by age group and according to the presence of comorbidities. Methods: We analyzed data of confirmed SARS-COV2 infection cases where symptoms began between February 22th, 2020, and April 18th, 2021, as published by the General Epidemiology Direction (DGE) of the Mexican Ministry of Health. We calculated COVID-19 incidence and mortality by age group using population data from the Statistics and Population National Institute (INEGI), and estimated the association between risk of death and the presence of comorbidities. Results: Mortality in SARS-COV2 infected people varied considerably, between 7 and 155 deaths per million per year in the under-20 age groups compared to 441 to 15,929 in the older age groups. Mortality in pediatric populations is strongly associated with comorbidities (OR: 4.6-47.9) compared to the milder association for older age groups (OR: 3.16-1.23). Conclusion: The risk of death from SARS-COV2 infection in children is low and is strongly associated with comorbidities.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates.

Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder.

Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been associated with an increase in inflammation and oxidative stress. This review presents an overview of findings following antioxidant treatment for ADHD and describes the potential amelioration of inflammation and oxidative stress using antioxidants that might have a future as multi-target adjuvant therapy in ADHD. The use of antioxidants against inflammation and oxidative conditions is an emerging field in the management of several neurodegenerative and neuropsychiatric disorders. Thus, antioxidants could be promising as an adjuvant ADHD therapy.

Default Mode Network Efficiency Is Correlated With Deficits in Inhibition in Adolescents With Inhalant Use Disorder.

It is well established that alterations in cognitive function and damage to brain structures are often found in adolescents who have substance use disorder (SUD). However, deficits in executive cognitive functioning in adolescents related to the vulnerability and consumption of such substances are not well known. In this study, we use graph theoretic analysis to compare the network efficiency in the resting state for three networks-default mode network (DMN), salience network (SN) and fronto-parietal network (FPN)-between inhalant-consuming adolescents and a control group (12 to 17 years old). We analyzed whether the efficiency of these functional networks was related to working memory, mental flexibility, inhibition of response, and sequential planning. We found that, when compared to the control group, inhalant-consuming adolescents presented with important deficits in communication among brain regions that comprise the DMN, SN, and FPN networks. DMN is the most affected network by inhalant abuse during adolescence. The mediation analyses suggested that the relationship between inhalant abuse and inhibitory control and sequential planning was partly mediated by DMN efficiency.

fMRI Mapping of Brain Activity Associated with the Vocal Production of Consonant and Dissonant Intervals.

The neural correlates of consonance and dissonance perception have been widely studied, but not the neural correlates of consonance and dissonance production. The most straightforward manner of musical production is singing, but, from an imaging perspective, it still presents more challenges than listening because it involves motor activity. The accurate singing of musical intervals requires integration between auditory feedback processing and vocal motor control in order to correctly produce each note. This protocol presents a method that permits the monitoring of neural activations associated with the vocal production of consonant and dissonant intervals. Four musical intervals, two consonant and two dissonant, are used as stimuli, both for an auditory discrimination test and a task that involves first listening to and then reproducing given intervals. Participants, all female vocal students at the conservatory level, were studied using functional Magnetic Resonance Imaging (fMRI) during the performance of the singing task, with the listening task serving as a control condition. In this manner, the activity of both the motor and auditory systems was observed, and a measure of vocal accuracy during the singing task was also obtained. Thus, the protocol can also be used to track activations associated with singing different types of intervals or with singing the required notes more accurately. The results indicate that singing dissonant intervals requires greater participation of the neural mechanisms responsible for the integration of external feedback from the auditory and sensorimotor systems than does singing consonant intervals.

Neural activity related to discrimination and vocal production of consonant and dissonant musical intervals.

BACKGROUND: Relationships between musical pitches are described as either consonant, when associated with a pleasant and harmonious sensation, or dissonant, when associated with an inharmonious feeling. The accurate singing of musical intervals requires communication between auditory feedback processing and vocal motor control (i.e. audio-vocal integration) to ensure that each note is produced correctly. The objective of this study is to investigate the neural mechanisms through which trained musicians produce consonant and dissonant intervals. METHODOLOGY: We utilized 4 musical intervals (specifically, an octave, a major seventh, a fifth, and a tritone) as the main stimuli for auditory discrimination testing, and we used the same interval tasks to assess vocal accuracy in a group of musicians (11 subjects, all female vocal students at conservatory level). The intervals were chosen so as to test for differences in recognition and production of consonant and dissonant intervals, as well as narrow and wide intervals. The subjects were studied using fMRI during performance of the interval tasks; the control condition consisted of passive listening. RESULTS: Singing dissonant intervals as opposed to singing consonant intervals led to an increase in activation in several regions, most notably the primary auditory cortex, the primary somatosensory cortex, the amygdala, the left putamen, and the right insula. Singing wide intervals as opposed to singing narrow intervals resulted in the activation of the right anterior insula. Moreover, we also observed a correlation between singing in tune and brain activity in the premotor cortex, and a positive correlation between training and activation of primary somatosensory cortex, primary motor cortex, and premotor cortex during singing. When singing dissonant intervals, a higher degree of training correlated with the right thalamus and the left putamen. CONCLUSIONS/SIGNIFICANCE: Our results indicate that singing dissonant intervals requires greater involvement of neural mechanisms associated with integrating external feedback from auditory and sensorimotor systems than singing consonant intervals, and it would then seem likely that dissonant intervals are intoned by adjusting the neural mechanisms used for the production of consonant intervals. Singing wide intervals requires a greater degree of control than singing narrow intervals, as it involves neural mechanisms which again involve the integration of internal and external feedback.

International heterogeneity in coronavirus disease 2019 pediatric mortality rates / Heterogeneidad internacional en las tasas de mortalidad pediátrica por COVID-19

Abstract Background: Severe coronavirus disease 2019 (COVID-19) is infrequent in children and shows a mortality rate of around 0.08%. This study aims to explore international differences in the pediatric mortality rate. Methods: We analyzed several countries with populations over 5 million that report disaggregated data of COVID-19 deaths by quinquennial or decennial age groups. Data were extracted from COVID-19 cases and deaths by age database, National Ministeries of Health, and the World Health Organization. Results: We included 23 countries in the analysis. Pediatric mortality varied from 0 to 12.1 deaths per million children of the corresponding age group, with the highest rate in Peru. In most countries, deaths were more frequent in the 0-4-year-old age group, except for Brazil. The pediatric/general COVID-19 mortality showed a great variation and ranged from 0% (Republic of Korea) to 10.4% (India). Pediatric and pediatric/general COVID mortality correlates strongly with 2018 neonatal mortality (r = 0.77, p < 0.001; and r = 0.88, p < 0.001, respectively), while shows a moderate or no correlation (r = 0.47, p = 0.02; and r = 0.19, p = 0.38, respectively) with COVID-19 mortality in the general population. Conclusions: International heterogeneity in pediatric COVID-19 mortality importantly parallels historical neonatal mortality. Neonatal mortality is a well-known index of the quality of a country's health system, which points to the importance of social determinants of health in pediatric COVID-19 mortality disparities. This issue should be further explored.

Resumen Introducción: La COVID-19 grave es poco frecuente en la infancia. El objetivo de este estudio fue explorar las diferencias en la tasa de mortalidad internacional por COVID-19 en la población pediátrica. Método: Se analizaron países con poblaciones superiores a 5 millones de habitantes que reporten muertes por COVID-19 con datos desglosados por grupos de edad quinquenales o decenales. Los datos se extrajeron de la base de datos COVerAge-DBs, de los ministerios nacionales de salud y de la Organización Mundial de la Salud. Resultados: Se incluyeron 23 países. La mortalidad pediátrica varió de 0 a 12.1 muertes por millón de personas del grupo de edad correspondiente, con la tasa más alta en Perú. En la mayoría de los países, las muertes fueron más frecuentes en el grupo de 0 a 4 años, excepto en Brasil. La mortalidad pediátrica/general por COVID-19 mostró una gran variación entre países y osciló entre el 0% (República de Corea) y el 10.4% (India). La mortalidad pediátrica y pediátrica/general por COVID-19 se correlaciona fuertemente con la mortalidad neonatal de 2018, mientras que tiene una moderada o nula correlación con la mortalidad por COVID-19 en la población general. Conclusiones: Existe una importante heterogeneidad internacional en la mortalidad pediátrica por COVID-19, que es paralela a la mortalidad neonatal histórica, la cual es un indicador de la calidad de los sistemas de salud y señala la importancia de los determinantes sociales de la salud en las disparidades de mortalidad pediátrica por COVID-19. Este tema debe explorarse a fondo.

Effects of rTMS on Parkinson's disease: a longitudinal fMRI study.

Parkinson's disease is a movement disorder whose principal symptoms are tremor, rigidity, bradykinesia and postural instability. Initially, drugs like L: -dopa or dopaminergic agonists are able to control these symptoms, but with the progress of the disease these drugs become less effective. Previous studies have reported that repetitive transcranial magnetic stimulation (rTMS) can improve these motor symptoms. The objective of this study was to investigate the neural mechanisms through which 25 Hz rTMS may improve motor symptoms in Parkinson's disease. In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz. rTMS in 10 Parkinson's disease patients. Fifteen rTMS sessions were performed over the primary cortex on both hemispheres (one after the other) during a 12-week period. The patients were studied using functional magnetic resonance imaging during performance of a simple tapping and a complex tapping task, 1 week before the administration of the first rTMS session and just after the last session. rTMS improved bradykinesia, while functional magnetic resonance imaging showed different cortical patterns in prefrontal cortex when patients performed the complex tapping test. Furthermore, the improvement in bradykinesia is associated with caudate nucleus activity increases in simple tapping. Finally, we observed a relative change in functional connectivity between the prefrontal areas and the supplementary motor area after rTMS. These results show a potential beneficial effect of repetitive transcranial magnetic stimulation on bradykinesia in Parkinson's disease which is substantiated by neural changes observed in functional magnetic resonance imaging.