The coronavirus disease (COVID-19) affected virtually all countries. Uncertain about the health risk and an increasing financial loss will contribute to widespread emotional distress and an increased risk of psychiatric disorders shortly. Posttraumatic, anxiety, and depression disorders are expected during and aftermath of the pandemic. Some groups, like children, have more susceptibility to having long term consequences in mental health. Herein, we made a comprehensive and non-systematic search in four databases (PubMed, Scopus, SciELO, and Google Scholars) to answer the question: What are children's and adolescents' mental health effects of the pandemic? Furthermore, which features are essential for mental health in a pandemic? Results: Seventy-seven articles were selected for full text read, and 51 were included. Children answer stress differently, depending on the development stage. High rates of anxiety, depression, and post-traumatic symptoms were identified among children. Discussion: Symptoms were as expected. New supportive strategies have appeared during this pandemic, but there is no measure of its effectiveness. Some groups seem to be more vulnerable to the mental health burden of the COVID-19 pandemic, and the mitigation actions should prioritize them. The school's role appears to be revalued by society. This review seems to pick good targets to prioritize mitigation actions aiming to spare children not only from the severe cases of COVID-19 but also to help them to deal with the mental health burden of the pandemics.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3, and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

No abstract

Previously the Slit and Trk-like family member 1 (SLITRK1) gene was identified as a candidate gene for Gilles de la Tourette Syndrome (GTS) based on a patient that carried a chromosomal inversion on 13q, as well as the identification of two rare DNA variants in the SLITRK1 gene. Since that report, studies have tested for the two rare variants in GTS and either did not find them, or when found, they did not segregate with the disorder in families, casting doubt on the relationship of this gene to GTS. We tested for these two rare variants and genotyped three polymorphisms that tag the currently identified major haplotypes of this gene in a sample of 154 nuclear families with GTS. In addition, the entire coding region was screened for novel DNA variants. We did not find the two reported rare variants in any of the probands or siblings in these families. We did however find significant evidence for association of a single polymorphism and of haplotypes of the three tagging polymorphisms. These findings provide the first support for the original finding indicating SLITRK1 as a susceptibility gene for GTS and indicate that further study of this gene in GTS is warranted.

No abstract

Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.

Renal tubular acidosis (RTA) is characterized by metabolic acidosis due to renal impaired acid excretion. Hyperchloremic acidosis with normal anion gap and normal or minimally affected glomerular filtration rate defines this disorder. RTA can also present with hypokalemia, medullary nephrocalcinosis and nephrolitiasis, as well as growth retardation and rickets in children, or short stature and osteomalacia in adults. In the past decade, remarkable progress has been made in our understanding of the molecular pathogenesis of RTA and the fundamental molecular physiology of renal tubular transport processes. This review summarizes hereditary diseases caused by mutations in genes encoding transporter or channel proteins operating along the renal tubule. Review of the molecular basis of hereditary tubulopathies reveals various loss-of-function or gain-of-function mutations in genes encoding cotransporter, exchanger, or channel proteins, which are located in the luminal, basolateral, or endosomal membranes of the tubular cell or in paracellular tight junctions. These gene mutations result in a variety of functional defects in transporter/channel proteins, including decreased activity, impaired gating, defective trafficking, impaired endocytosis and degradation, or defective assembly of channel subunits. Further molecular studies of inherited tubular transport disorders may shed more light on the molecular pathophysiology of these diseases and may significantly improve our understanding of the mechanisms underlying renal salt homeostasis, urinary mineral excretion, and blood pressure regulation in health and disease. The identification of the molecular defects in inherited tubulopathies may provide a basis for future design of targeted therapeutic interventions and, possibly, strategies for gene therapy of these complex disorders.

Brief cognitive tests are widely used in neuropsychology and related areas, in order to assess and diagnose develop mental, neurological, and psychiatric conditions. The Clock Drawing Test (CDT) is also adopted as a screening tool for cognitive impairment in several conditions such as dementia, stroke, schizophrenia, mild cognitive impairment and mood disorders¹. The CDT basically consists of the drawing of dif ferent elements of a clock, including the clock face, numbers, and arrow-hands. The instructions and scoring methods vary according to each version. Influences of aging and education are also related to test performance, where children and the elderly perform worse than adults and lower education asso ciates with worse performance².Different versions of the CDT were developed. Although very similar and highly correlated³, they differ in diagnosis accuracy 4 and probably on the cognitive processes involved ABSTRACTThe Clock Drawing Test (CDT) is a cognitive screening tool used in clinical and research settings. Despite its role on the assessment of global cognitive functioning, the specific cognitive components required for test performance are still unclear. We aim to assess the role of executive functioning, global cognitive status, visuospatial abilities, and semantic knowledge on Shulman's CDT performance. Fifty-three mild cognitive impairment, 60 Alzheimer's dementia, and 57 normal elderly controls performed the CDT, the Frontal Assessment Battery, the Mini-Mental State Examination, the Stick Design Test, and a naming test (TN-LIN). An ordinal regression assessed specific neuropsychological in fluences on CDT performance. All the cognitive variables were related to the CDT, accounting for 53% of variance. The strongest association was between the CDT and executive functions, followed by global cognitive status, visuospatial processing, and semantic knowledge. Our result confirms the multidimensional nature of the test and the major role of executive functions on performance.Keywords: clock drawing test, executive functions, visuospatial abilities, semantic knowledge, dementia. Palavras-chave: teste do desenho do relógio, funções executivas, habilidades visioespaciais, conhecimento semântico, demência. RESUMO