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The current study sought to characterize implicit bias toward children with autism and examine whether viewing educational materials about autism would change attitudes toward children with autism. A website developed by Sesame Street containing information about autism and resources for families was distributed to parents of children with autism ( n = 473) and parents of children without autism ( n = 707). Pre- and post-test measures of implicit bias toward children with autism; explicit attitudes and knowledge about autism; and parenting confidence, strain, and stigma were completed before and after the website was presented. Results indicated that parents of children with autism showed less implicit bias compared with those of non-autistic children during the pre-test, but the groups did not differ at the post-test. Parents without autistic children and those with more negative explicit attitudes showed a greater reduction in implicit bias from the pre- to the post-test. In addition, for parents of children with autism, a more positive change in explicit attitudes and increased knowledge from the pre- to the post-test was associated with more empowerment at the post-test. Together, our findings suggest that the online educational resources can reduce implicit bias against children with autism and help mitigate some of the psychological issues associated with parenting children with autism.

Cancer is one of the leading causes of death worldwide and requires intense and growing research investments from the public and private sectors. This is expected to lead to the development of new medicines. A determining factor in this process is the structural understanding of molecules with potential anticancer properties. Since the major compounds used in cancer therapies fail to encompass every spectrum of this disease, there is a clear need to research new molecules for this purpose. As it follows, we have studied the class of quinolinones that seem effective for such therapy. This paper describes the structural elucidation of a novel dihydroquinoline by single-crystal X-ray diffraction and spectroscopy characterization. Topology studies were carried through Hirshfeld surfaces analysis and molecular electrostatic potential map; electronic stability was evaluated from the calculated energy of frontier molecular orbitals. Additionally, in silico studies by molecular docking indicated that this dihydroquinoline could act as an anticancer agent due to their higher binding affinity with human aldehyde dehydrogenase 1A1 (ALDH 1A1). Tests in vitro were performed for VERO (normal human skin keratinocytes), B16F10 (mouse melanoma), and MDA-MB-231 (metastatic breast adenocarcinoma), and the results certified that compound as a potential anticancer agent. A Dihydroquinoline derivative was tested against three cancer cell lines and the results attest that compound as potential anticancer agent.

In obstetrics, ultrasound is used for assessment of fetal development during pregnancy. The images generated by ultrasound are used to obtain measurements of fetal head length, body size, and the analysis of fetal movements, to identify and prevent the onset of congenital disease. This work presents the development of a new method for the segmentation of two-dimensional ultrasound images of fetal skulls based on a V-Net architecture called Fully Convolutional Neural Network - Combination (VNet-c). We created a new combination of strategies using a 3D V-Net as base, such as pre-processing, use of Batch Normalization and Dropout, and evaluation of distinct activation layers, activation function, data augmentation, loss function, and network depth. The computational results reveal the feasibility of the proposal in the correct segmentation of fetal skulls and head circumference measurements, reaching up to 97.91% of correctness, overcoming states-of-the-art methods.

Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America, caused by fungi of the genus Paracoccidioides. The treatment of PCM is complex, requiring a long treatment period, which often results in serious side effects. The aim of this study was to screen for inhibitors of a specific target of the fungus that is absent in humans. Methylcitrate synthase (MCS) is a unique enzyme of microorganisms and is responsible for the synthesis of methylcitrate at the beginning of the propionate degradation pathway. This pathway is essential for several microorganisms, since the accumulation of propionyl-CoA can impair virulence and prevent the development of the pathogen. We performed the modeling and molecular dynamics of the structure of Paracoccidioides lutzii MCS (PlMCS) and performed a virtual screening on 89,415 compounds against the active site of the enzyme. The compounds were selected according to the affinity and efficiency criteria of in vitro tests. Six compounds were able to inhibit the enzymatic activity of recombinant PlMCS but only the compound ZINC08964784 showed fungistatic and fungicidal activity against Paracoccidioides spp. cells. The analysis of the interaction profile of this compound with PlMCS showed its effectiveness in terms of specificity and stability when compared to the substrate (propionyl-CoA) of the enzyme. In addition, this compound did not show cytotoxicity in mammalian cells, with an excellent selectivity index. Our results suggest that the compound ZINC08964784 may become a promising alternative antifungal against Paracoccidioides spp. Communicated by Ramaswamy H. Sarma

espanolObjetivos: Evaluar el valor predictivo del score calcico ecocardiografico (SCE). Material y metodos: Se evaluaron 96 pacientes con indicacion de coronariografia (CCG). Sindrome coronario sin supra ST 20 pacientes. Angina cronica 15 pacientes Sindrome coronario con supra ST 31 pacientes. Asintomaticos 30 pacientes. Se efectuo ecocardiograma con SCE y correlacion con coronariopatia. Dos grupos: pacientes con SCE ≤ 1 y SCE ≥ 2. Resultados: Sobre 96 pacientes, 23 sin lesiones con SCE 0,61, y 73 con lesion SCE 2,63. Entre aquellos con lesion, 16 lesion unica SCE 1,68, 57 lesion multiple SCE 2,87. De 23 sin lesiones 20 tuvieron SCE ≤ 1, y 3 SCE ≥ 2, y de 73 con lesiones 13 tuvieron SCE ≤ 1, y 60 SCE ≥ 2; asi, un SCE ≥ 2 presenta mayor frecuencia de coronariopatia vs. SCE ≤ 1 (p Conclusiones: El SCE tendria buen valor predictivo positivo para coronariopatia. EnglishObjectives: The aim of this study was to evaluate the predictive value of the echocardiographic calcium score (ECS). Methods: Ninety-six patients with coronary angiography indication were enrolled in the study: 20 with non-ST-segment elevation acute coronary syndrome, 15 with chronic angina, 31 with ST-segment elevation acute coronary syndrome and 30 asymptomatic patients. After echocardiography with ECS and correlation with coronary artery disease, patients were classified into 2 groups according to ECS ≤1 or ECS ≥2. Results: Among the total number of patients, 23 patients without lesions had ECS: 0.61 and 73 with lesions had ECS: 2.63. In patients presenting lesions, 16 had single lesion with ECS: 1.68 and 57 multiple lesions with ECS: 2.87. In the 23 patients without lesions, 20 had ECS ≤1 and 3 ECS ≥2, and among the 73 patients with lesions, 13 had ECS ≤1 and 60 ECS ≥2. Thus, ECS ≥2 presented a higher frequency of coronary artery disease vs. ECS ≤1 (p Conclusions: The ECS would have good positive predictive value to assess coronary artery disease.

The prevalence of congenital hydrocephalus has been estimated at 1.1 per 1000 infants when including cases diagnosed before 1 year of age after exclusion of neural tube defects. Classification criteria are based either on CSF dynamics, pathophysiological mechanisms or associated lesions. Whereas inherited syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus either isolated or as a major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. In the past 10 years, pathogenic variants in CCDC88C have been documented but the neuropathology remains virtually unknown. We report the neuropathology of two foetuses from one family harbouring two novel compound heterozygous pathogenic variants in the CCDC88C gene: a maternally inherited indel in exon 22, c.3807_3809delinsACCT;p.(Gly1270Profs*53) and a paternally inherited deletion of exon 23, c.3967-?_c.4112-?;p.(Leu1323Argfs*10). Medical termination of pregnancy was performed at 18 and 23 weeks of gestation for severe bilateral ventriculomegaly. In both fetuses, brain lesions consisted of multifocal atresia-forking along the aqueduct of Sylvius and the central canal of the medulla, periventricular neuronal heterotopias and choroid plexus hydrops. The second fetus also presented lumbar myelomeningocele, left diaphragmatic hernia and bilateral renal agenesis. CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3. Interestingly, heterozygous variants in PARD3 result in neural tube defects by defective tight junction formation and polarization process of the neuroepithelium. Besides, during organ formation Wnt signalling is a prerequisite for planar cell polarity pathway activation, and mutations in planar cell polarity genes lead to heart, lung and kidney malformations. Hence, candidate variants in CCDC88C should be carefully considered whether brain lesions are isolated or associated with malformations suspected to result from disorders of planar cell polarity.

Aim: Computer-aided drug design approaches were applied to identify chalcones with antiplasmodial activity. Methodology: The virtual screening was performed as follows: structural standardization of in-house database of chalcones; identification of potential Plasmodium falciparum protein targets for the chalcones; homology modeling of the predicted P. falciparum targets; molecular docking studies; and in vitro experimental validation. Results: Using these models, we prioritized 16 chalcones with potential antiplasmodial activity, for further experimental evaluation. Among them, LabMol-86 and LabMol-87 showed potent in vitro antiplasmodial activity against P. falciparum, while LabMol-63 and LabMol-73 were potent inhibitors of Plasmodium berghei progression into mosquito stages. Conclusion: Our results encourage the exploration of chalcones in hit-to-lead optimization studies for tackling malaria.

Objetivos: Evaluar el valor predictivo del score calcico ecocardiografico (SCE). Material y metodos: Se evaluaron 96 pacientes con indicacion de coronariografia (CCG). Sindrome coronario sin supra ST 20 pacientes. Angina cronica 15 pacientes Sindrome coronario con supra ST 31 pacientes. Asintomaticos 30 pacientes. Se efectuo ecocardiograma con SCE y correlacion con coronariopatia. Dos grupos: pacientes con SCE ≤ 1 y SCE ≥ 2. Resultados: Sobre 96 pacientes, 23 sin lesiones con SCE 0,61, y 73 con lesion SCE 2,63. Entre aquellos con lesion, 16 lesion unica SCE 1,68, 57 lesion multiple SCE 2,87. De 23 sin lesiones 20 tuvieron SCE ≤ 1, y 3 SCE ≥ 2, y de 73 con lesiones 13 tuvieron SCE ≤ 1, y 60 SCE ≥ 2; asi, un SCE ≥ 2 presenta mayor frecuencia de coronariopatia vs. SCE ≤ 1 (p < 0,05), sensibilidad 82,2%, especificidad 87%, valor predictivo positivo: 95,2%, y negativo 60,6%. En lesion unica vs. multiple 16 presentaron lesion unica, 9 tenian SCE ≥ 2, y 57 multiple, 51 tenian SCE ≥ 2, sensibilidad: 89,5% y especificidad: 43,8% para identificar multiples vasos, valor predictivo positivo 85%, y negativo: 53,8%. Conclusiones: El SCE tendria buen valor predictivo positivo para coronariopatia.

Background Ischemia-reperfusion injury (IRI) is an antigen-independent, innate immune response to arterial occlusion and ischemia with subsequent paradoxical exacerbation after reperfusion. IRI remains a critical problem after vessel occlusion and infarction or during harvest and surgery in transplants. After transplant, liver IRI (LIRI) contributes to increased acute and chronic rejection and graft loss. Tissue loss during LIRI has been attributed to local macrophage activation and invasion with excessive inflammation together with hepatocyte apoptosis and necrosis. Inflammatory and apoptotic signaling are key targets for reducing post-ischemic liver injury. Myxomavirus is a rabbit-specific leporipoxvirus that encodes a suite of immune suppressing proteins, often with extensive function in other mammalian species. Serp-2 is a cross-class serine protease inhibitor (serpin) which inhibits the inflammasome effector protease caspase-1 as well as the apoptotic proteases granzyme B and caspases 8 and 10. In prior work, Serp-2 reduced inflammatory cell invasion after angioplasty injury and after aortic transplantation in rodents. In this report, we explore the potential for therapeutic treatment with Serp-2 in a mouse model of LIRI. Methods Wildtype (C57BL/6 J) mice were subjected to warm, partial (70%) hepatic ischemia for 90 min followed by treatment with saline or Serp-2 or M-T7, 100 ng/g/day given by intraperitoneal injection on alternate days for 5 days. M-T7 is a Myxomavirus-derived inhibitor of chemokine-GAG interactions and was used in this study for comparative analysis of an unrelated viral protein with an alternative immunomodulating mechanism of action. Survival, serum ALT levels and histopathology were assessed 24 h and 10 days post-LIRI. Results Serp-2 treatment significantly improved survival to 85.7% percent versus saline-treated wildtype mice (p = 0.0135), while M-T7 treatment did not significantly improve survival (p = 0.2584). Liver viability was preserved by Serp-2 treatment with a significant reduction in serum ALT levels (p = 0.0343) and infarct scar thickness (p = 0.0016), but with no significant improvement with M-T7 treatment. Suzuki scoring by pathologists blinded with respect to treatment group indicated that Serp-2 significantly reduced hepatocyte necrosis (p = 0.0057) and improved overall pathology score (p = 0.0046) compared to saline. Immunohistochemistry revealed that Serp-2 treatment reduced macrophage infiltration into the infarcted liver tissue (p = 0.0197). Conclusions Treatment with Serp-2, a virus-derived inflammasome and apoptotic pathway inhibitor, improves survival after liver ischemia-reperfusion injury in mouse models. Treatment with a cross-class immune modulator provides a promising new approach designed to reduce ischemia-reperfusion injury, improving survival and reducing chronic transplant damage. Electronic supplementary material The online version of this article (10.1186/s12950-019-0215-1) contains supplementary material, which is available to authorized users.

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.

There is often a large time gap between caregivers’ initial concerns and the diagnosis of autism spectrum disorder. The current study aimed to identify factors associated with missed or delayed autism spectrum disorder diagnoses among children in Colorado. In a surveillance-based sample of 8-year-old children with autism spectrum disorder ( N = 572), we examined differences between children who were identified with autism spectrum disorder by a community provider and/or were eligible for special education services under an autism eligibility (documented diagnosis) and children who were first identified with autism spectrum disorder through a systematic record review (newly identified). Compared to documented diagnosis children, newly identified children were more likely to be female, aggressive, and argumentative. They were less likely to have had a developmental regression, sleep abnormalities, or an autism screener or diagnostic measure in their records. Newly identified children also had a poorer quality of information in their records. Furthermore, among documented diagnosis children, variations in clinical presentations were associated with significantly different mean ages at autism spectrum disorder diagnosis; children who showed early delays, motor abnormalities, hyperactivity and attention deficits, and odd responses to sensory stimuli received a diagnosis much earlier than documented diagnosis children with other clinical presentations. Lay abstract Although autism can be reliably diagnosed as early as 2 years of age, many children are not diagnosed with autism until much later. We analyzed data to determine why many of the 8-year-old children who resided in Colorado and were identified as having autism through a review of their health and/or educational records did not have a documented clinical diagnosis of autism and were not eligible for special education services under an autism eligibility. We found that children who did not have a documented clinical diagnosis of autism and were not eligible for special education services under an autism eligibility were more likely to be female, aggressive, and argumentative. They had a poorer quality of information in their records and were less likely to have had a developmental regression, sleep problems, or an autism screener or diagnostic measure in their records. These results suggest that the symptoms characteristic of autism among this group of children may have been attributed to another disorder and that clinicians may be able to recognize autism more readily in children with more functional impairment and those who experience a developmental regression. We also discovered that differences in symptom presentations among children who had a documented clinical diagnosis of autism and/or were eligible for special education services under an autism eligibility were associated with different ages at autism diagnosis.

A critical step in the lifecycle of many fungal pathogens is the ability to switch between filamentous and yeast growth, a process known as dimorphism. cAMP-dependent protein kinase (PKA) controls morphological changes and the pathogenicity of several animal and plant pathogenic fungi. In this work, we report the analysis of PKA activity during the mycelium to yeast transition in the pathogenic fungus Paracoccidioides lutzii. This fungus, as well as the closely related species Paracoccidioides brasiliensis, causes paracoccidioidomycosis, a systemic mycosis that affects thousands of people in Latin America. Infection occurs when hypha fragments or spores released from mycelium are inhaled by the host, an event that triggers the morphological switch. We show here that PKA activity is regulated in the fungus phase, increasing during the mycelium to yeast transition. Also, morphological transition from mycelium to yeast is blocked by the compound H89, a specific PKA inhibitor. Nevertheless, the fungus recovers its ability to change morphology when H89 is removed from the culture media. This recovery is accompanied by a significant increase in PKA activity. Our results strongly indicate that PKA directly affects phase transition in P. lutzii.

International audience; Biogeographical studies considering the entire bacterial community may underestimate mechanisms of bacterial assemblages at lower taxonomic levels. In this context, the study aimed to identify factors affecting the spatial and temporal dynamic of the Mycobacterium, a genus widespread in aquatic ecosystems. Nontuberculous mycobacteria (NTM) density variations were quantified in the water column of freshwater lakes at the regional scale (annual monitoring of 49 lakes in the Paris area) and at the local scale (2-year monthly monitoring in Créteil Lake) by real-time quantitative PCR targeting the atpE gene. At the regional scale, mycobacteria densities in water samples ranged from 6.7 × 103 to 1.9 × 108 genome units per liter. Density variations were primarily explained by water pH, labile iron, and dispersal processes through the connection of the lakes to a river. In Créteil Lake, no spatial variation of mycobacterial densities was noticed over the 2-year monthly survey, except after large rainfall events. Indeed, storm sewer effluents locally and temporarily increased NTM densities in the water column. The temporal dynamic of the NTM densities in Créteil Lake was associated with suspended solid concentrations. No clear seasonal variation was noticed despite a shift in NTM densities observed over the 2012–2013 winter. Temporal NTM densities fluctuations were well predicted by the neutral community model, suggesting a random balance between loss and gain of mycobacterial taxa within Créteil Lake. This study highlights the importance of considering multiple spatial scales for understanding the spatio-temporal dynamic of bacterial populations in natural environments.

Malaria is a tropical infectious disease that affects over 219 million people worldwide. Due to the constant emergence of parasitic resistance to the current antimalarial drugs, the discovery of new antimalarial drugs is a global health priority. Multi-target drug discovery is a promising and innovative strategy for drug discovery and it is currently regarded as one of the best strategies to face drug resistance. Aiming to identify new multi-target antimalarial drug candidates, we developed an integrative computational approach to select multi-kinase inhibitors for Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4) and protein kinase 6 (PK6). For this purpose, we developed and validated shape-based and machine learning models to prioritize compounds for experimental evaluation. Then, we applied the best models for virtual screening of a large commercial database of drug-like molecules. Ten computational hits were experimentally evaluated against asexual blood stages of both sensitive and multi-drug resistant P. falciparum strains. Among them, LabMol-171, LabMol-172, and LabMol-181 showed potent antiplasmodial activity at nanomolar concentrations (EC50 ≤ 700 nM) and selectivity indices >15 folds. In addition, LabMol-171 and LabMol-181 showed good in vitro inhibition of P. berghei ookinete formation and therefore represent promising transmission-blocking scaffolds. Finally, docking studies with protein kinases CDPK1, CDPK4, and PK6 showed structural insights for further hit-to-lead optimization studies.

Rhombencephalosynapsis is a rare cerebellar malformation developing during embryogenesis defined by vermian agenesis or hypogenesis with fusion of the cerebellar hemispheres. It occurs either alone or in association with other cerebral and/or extracerebral anomalies. Its association with microlissencephaly is exceedingly rare and to date, only a heterozygous de novo missense variant in ADGRL2, a gene encoding Adhesion G-Protein-Coupled Receptor L2, has been identified. We report on two siblings of Roma origin presenting with severe growth retardation, fetal akinesia, microlissencephaly and small cerebellum with vermian agenesis. Neuropathological studies revealed extreme paucity in pontine transverse fibres, rudimentary olivary nuclei and rhombencephalosynapsis with vanishing spinal motoneurons in both fetuses. Comparative fetus-parent exome sequencing revealed in both fetuses a homozygous variant in exon 1 of the EXOSC3 gene encoding a core component of the RNA exosome, c.92G > C; p.(Gly31Ala). EXOSC3 accounts for 40%–75% of patients affected by ponto-cerebellar hypoplasia with spinal muscular atrophy (PCH1B). The c.92G > C variant is a founder mutation in the Roma population and has been reported in severe PCH1B. PCH1B is characterized by a broad phenotypic spectrum, ranging from mild phenotypes with spasticity, mild to moderate intellectual disability, pronounced distal muscular and cerebellar atrophy/hypoplasia, to severe phenotypes with profound global developmental delay, progressive microcephaly and atrophy of the cerebellar hemispheres. In PCH1B, the usual cerebellar lesions affect mainly the hemispheres with relative sparing of vermis that radically differs from rhombencephalosynapsis. This unusual foetal presentation expands the spectrum of PCH1B and highlights the diversity of rhombencephalosynapsis etiologies.

La consommation d’alcool au cours de la grossesse constitue une cause majeure de troubles du comportement et de handicap. Alors qu’il est possible pour un clinicien d’établir un diagnostic néonatal du syndrome d’alcoolisation fœtale, l’atteinte la plus sévère des troubles causés par l’alcoolisation fœtale (TCAF), une grande majorité des enfants échappe à un diagnostic précoce en raison de l’absence d’anomalies morphologiques évidentes. Plusieurs années de prise en charge sont alors perdues. Des avancées récentes ont permis d’établir l’existence d’un axe fonctionnel placenta-cerveau impliqué dans le contrôle de l’angiogenèse cérébrale, qui se trouve dérégulé chez les enfants exposés in utero à l’alcool. Une angiogenèse cérébrale normale étant un prérequis à l’établissement d’un neurodéveloppement correct, ces avancées ouvrent la voie à l’identification d’une nouvelle génération de biomarqueurs placentaires d’atteinte cérébrale pour le diagnostic précoce des enfants TCAF.

To promote knowledge and acceptance of autism, Sesame Workshop created an online initiative: See Amazing in All Children. This nationwide evaluation of See Amazing assessed whether it increased knowledge and acceptance, promoted community inclusion, reduced parenting strain, and enhanced parenting competence. Survey responses were collected online from parents of children (age ⩽ 6) with and without autism before (N = 1010), 1 week after (N = 510), and, for parents of autistic children, 1 month after (N = 182) they viewed the See Amazing materials. Following exposure, parents of non-autistic children showed small but significant increases in knowledge of autism and, like parents of autistic children, greater acceptance of autistic children. Parents of autistic children reported less strain, increased parenting competence, and more hope about involving their child in their community. That the See Amazing materials invoked positive changes in the general parent community and in parents of autistic children suggests that See Amazing materials have the potential to be an effective resource to increase acceptance and community inclusion, although limitations of self-selection, dropout rate, and lack of control group constrain interpretation. Implications include support for targeting acceptance as a step beyond awareness campaigns, though actual behavior change is a subject for future research.

Preterm birth is a high-risk factor for the development of gray and white matter abnormalities, referred to as "encephalopathy of prematurity," that may lead to life-long motor, cognitive, and behavioral impairments. The prevalence and clinical outcomes of encephalopathy of prematurity differ between sexes, and elucidating the underlying biological basis has become a high-priority challenge. Human studies are often limited to assessment of brain region volumes by MRI, which does not provide much information about the underlying mechanisms of lesions related to very preterm birth. However, models using KO mice or pharmacological manipulations in rodents allow relevant observations to help clarify the mechanisms of injury sustaining sex-differential vulnerability. This review focuses on data obtained from mice aged P1-P5 or rats aged P3 when submitted to cerebral damage such as hypoxia-ischemia, as their brain lesions share similarities with lesion patterns occurring in very preterm human brain, before 32 gestational weeks. We first report data on the mechanisms underlying the development of sexual brain dimorphism in rodent, focusing on the hippocampus. In the second part, we describe sex specificities of rodent models of encephalopathy of prematurity (RMEP), focusing on mechanisms underlying differences in hippocampal vulnerability. Finally, we discuss the relevance of these RMEP. Together, this review highlights the need to systematically search for potential effects of sex when studying the mechanisms underlying deficits in RMEP in order to design effective sex-specific medical interventions in human preterms.

Children's literacy about the genetics of late-onset hereditary breast/ovarian cancer (HBOC) often develops through conversations with parents about BRCA gene testing and adults' cancer diagnoses. These conversations may promote early understanding of HBOC, but the long-term impact on children's psychosocial adjustment remains unclear. We investigated cancer genetic health communication in BRCA-tested families to consider benefits, risks, and moderating influences on children's understanding and well-being. Adolescent and young adult children (ages 12-24) of mothers who underwent BRCA testing 1+ years previously completed qualitative interviews that were transcribed, coded (intercoder K ≥ .70), and content-analyzed (N = 34). Children readily recalled conversations about BRCA testing and HBOC (100%) that they considered important (94%), but implications for children were ambiguous and obfuscated their concerns. Psychosocial impacts were muted, multifaceted, and displayed a range of favorable (82%), neutral (71%), and unfavorable (59%) response-frequently co-occurring within the same child over different aspects (e.g., medical, concern for self and others). Children verbalized active (50%) and avoidant (38%) coping strategies: about 1:5 endorsed transient thoughts about vulnerability to HBOC, 1:3 had not further considered it, and all reported specific actions they had or would undertake to remain healthy (e.g., diet/exercise). A majority (94%) of children had or would consider genetic testing for themselves, usually later in life (59%). Long-term outcomes highlighted benefits (awareness of HBOC, psychological hardiness, healthier lifestyle behaviors), as well as some psychosocial concerns that could be managed through interventions promoting genetic health literacy.

Cerebral lesions acquired in the perinatal period can induce cerebral palsy (CP), a multifactorial pathology leading to lifelong motor and cognitive deficits. Several risk factors, including perinatal hypoxia-ischemia (HI), can contribute to the emergence of CP in preterm infants. Currently, there is no international consensus on treatment strategies to reduce the risk of developing CP. A meta-analysis showed that magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery reduces the risk of developing CP ( Crowther et al., 2017 ). However, only a few studies have investigated the long-term effects of MgSO4 and it is not known whether sex would influence MgSO4 efficacy. In addition, the search for potential deleterious effects is essential to enable broad use of MgSO4 in maternity wards. We used a mouse model of perinatal HI to study MgSO4 effects until adolescence, focusing on cognitive and motor functions, and on some apoptosis and inflammation markers. Perinatal HI at postnatal day 5 (P(5)) induced (1) sensorimotor deficits in pups; (2) increase in caspase-3 activity 24 h after injury; (3) production of proinflammatory cytokines from 6 h to 5 days after injury; (4) behavioral and histological alterations in adolescent mice with considerable interindividual variability. MgSO4 prevented sensorimotor alterations in pups, with the same efficacy in males and females. MgSO4 displayed anti-apoptotic and anti-inflammatory effects without deleterious side effects. Perinatal HI led to motor coordination impairments in female adolescent mice and cognitive deficits in both sexes. MgSO4 tended to prevent these motor and cognitive deficits only in females, while it prevented global brain tissue damage in both sexes. Moreover, interindividual and intersexual differences appeared regarding the lesion size and neuroprotection by MgSO4 in a region-specific manner. These differences, the partial prevention of disorders, as well as the mismatch between histological and behavioral observations mimic clinical observations. This underlines that this perinatal HI model is suitable to further analyze the mechanisms of sex-dependent perinatal lesion susceptibility and MgSO4 efficacy.

It is well documented that adults with intellectual disability (ID) experience higher rates of a series of health conditions compared to their peers without disability. These health conditions include cardiovascular disease, obesity, diabetes, gastrointestinal disorders, and psychiatric and behavioral disorders. With life expectancy approximating the general population, adults with ID are also now experiencing health conditions related to aging, further increasing their risk for diminished function and well-being. This increased morbidity poses new challenges in geriatric healthcare planning for this population. Relatively simple health prevention practices, such as the implementation of a health screening tool, can substantially increase disease detection and clinical activities directed toward improved health outcomes for people with ID. This study examines data collected from the District of Columbia Developmental Disabilities Administration's (DC DDA's) health screening component of its Health and Wellness Standards. Findings are presented, along with recommendations and implications for improving preventive health screening practices in the ID population.

Hysterectomy is the most common surgical gynecologic procedure, which is frequently related to the treatment of leiomyoma. The laparoscopic hysterectomy is associated with a shorter hospital stay, fewer infection rates, and a faster return to daily activities. Most gynecologists do not recommend a hysterectomy via the vagina or a laparoscopic-assisted vaginal hysterectomy (LAVH) in the case of a uterus weighing more than 300 g. This case report presents the case of an LAVH undertaken in a 43-year-old patient with a uterus weighing 2,800 g. There are no definite guidelines concerning the procedure for a large uterus, and the literature is vague regarding the best surgical procedure for these cases. The size of the uterus does not seem to be an absolute contraindication for endoscopic surgery. This procedure relies entirely on the surgeon's ability.

Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumor. Pharmacological treatment of this malignance is limited by the selective permeability of the blood-brain barrier (BBB) and relies on a single drug, temozolomide (TMZ), thus making the discovery of new compounds challenging and urgent. Therefore, aiming to discover new anti-glioma drugs, we developed robust machine learning models for predicting anti-glioma activity and BBB penetration ability of new compounds. Using these models, we prioritized 41 compounds from our in-house library of compounds, for further in vitro testing against three glioma cell lines and astrocytes. Subsequently, the most potent and selective compounds were resynthesized and tested in vivo using an orthotopic glioma model. This approach revealed two lead candidates, 4m and 4n, which efficiently decreased malignant glioma development in mice, probably by inhibiting thioredoxin reductase activity, as shown by our enzymological assays. Moreover, these two compounds did not promote body weight reduction, death of animals, or altered hematological and toxicological markers, making then good candidates for lead optimization as anti-glioma drug candidates.

Few Zika virus (ZIKV) outbreaks had been reported since its first detection in 1947, until the recent epidemics occurred in South America (2014/2015) and expeditiously became a global public health emergency. This arbovirus reached 0.5-1.3 million cases of ZIKV infection in Brazil in 2015 and rapidly spread in new geographic areas such as the Americas. Despite the mild symptoms of the Zika fever, the major concern is related to the related severe neurological disorders, especially microcephaly in newborns. Advances in ZIKV drug discovery have been made recently and constitute promising approaches to ZIKV treatment. In this review, we summarize current computational drug discovery efforts and their applicability to discovery of anti-ZIKV drugs. Lastly, we present successful examples of the use of computational approaches to ZIKV drug discovery.

Aim: The shape-based virtual screening was used for the identification of new compounds anti-paracoccidioidomycosis (PCM). Materials & methods: The study was performed according to the following steps: collection and curation of a dataset of quinolinyl N-oxide chalcones with anti-PCM activity, development and validation of shape-based models, application of the best model for virtual screening, and experimental validation. Results & Conclusion: Among 31 computational hits, eight compounds showed potent antifungal activity and low cytotoxicity for mammalian cells. The checkerboard assay showed that most promising hit (compound 3) displayed additive effects with the antifungal cotrimoxazole and amphotericin B. Therefore, the shape-based virtual screening allowed us to discover promising compounds in prospective hit-to-lead optimization studies for tackling PCM.

Background Drug repurposing has been an interesting and cost-effective approach, especially for neglected diseases, such as Chagas disease. Methods In this work, we studied the activity of the antidepressant drug sertraline against Trypanosoma cruzi trypomastigotes and intracellular amastigotes of the Y and Tulahuen strains, and investigated its action mode using cell biology and in silico approaches. Results Sertraline demonstrated in vitro efficacy against intracellular amastigotes of both T. cruzi strains inside different host cells, including cardiomyocytes, with IC50 values between 1 to 10 μM, and activity against bloodstream trypomastigotes, with IC50 of 14 μM. Considering the mammalian cytotoxicity, the drug resulted in a selectivity index of 17.8. Sertraline induced a change in the mitochondrial integrity of T. cruzi, resulting in a decrease in ATP levels, but not affecting reactive oxygen levels or plasma membrane permeability. In silico approaches using chemogenomic target fishing, homology modeling and molecular docking suggested the enzyme isocitrate dehydrogenase 2 of T. cruzi (TcIDH2) as a potential target for sertraline. Conclusions The present study demonstrated that sertraline had a lethal effect on different forms and strains of T. cruzi, by affecting the bioenergetic metabolism of the parasite. These findings provide a starting point for future experimental assays and may contribute to the development of new compounds. Electronic supplementary material The online version of this article (10.1186/s40409-018-0165-8) contains supplementary material, which is available to authorized users.

Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium, affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum (PfdUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target. Using a combi-QSAR (quantitative structure-activity relationship) approach followed by virtual screening and in vitro experimental evaluation, we report herein the discovery of novel chemical scaffolds with in vitro potency against asexual blood stages of both P. falciparum multidrug-resistant and sensitive strains and against sporogonic development of P. berghei. We developed 2D- and 3D-QSAR models using a series of nucleosides reported in the literature as PfdUTPase inhibitors. The best models were combined in a consensus approach and used for virtual screening of the ChemBridge database, leading to the identification of five new virtual PfdUTPase inhibitors. Further in vitro testing on P. falciparum multidrug-resistant (W2) and sensitive (3D7) parasites showed that compounds LabMol-144 and LabMol-146 demonstrated fair activity against both strains and presented good selectivity versus mammalian cells. In addition, LabMol-144 showed good in vitro inhibition of P. berghei ookinete formation, demonstrating that hit-to-lead optimization based on this compound may also lead to new antimalarials with transmission blocking activity. publishersversion published

Five bis-arylimidamides were assayed as anti- Trypanosoma cruzi agents by in vitro , in silico , and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. In silico target fishing suggested DNA as the main target, but ultrastructural data did not match.

There is a lack of research examining differences in functioning in autism spectrum disorder (ASD) across ethnicity, particularly among those without intellectual disability (ID). This study investigated ethnic differences in parent-reported impairment in executive function, adaptive behavior, and social–emotional functioning. White and Black youth (n = 64; ages 6–17) with ASD without ID were compared on each of these domains. Black youth had significantly lower levels of impairment on all three domains. Findings may reflect better daily functioning among Black youth with ASD and/or cultural differences in parent response to questionnaires. Regardless, these findings raise concern about the sensitivity of commonly used measures for Black children with ASD and the impact of culture on daily functioning and symptom manifestation.

Summary Since the 1990s, stroke units have emerged as core elements in effective acute stroke treatment. Consistent adherence to key processes of stroke care, primarily based on effic ient organisational structures, has been the cornerstone of success. On the basis of huge datasets of high quality there is now conclusive evidence of the signific ant contribution of stroke unit care to diminished mortality and functional dependency in the long term. In the subjective awareness of the affected individuals quality of life has improved considerably. Meanwhile the concept has emerged as a platform for new ideas and research promoting stroke care and early neurorehabilitation. This dynamic process includes exploring specifi c treatment of comorbidities and the prevention of early recurrence of stroke, as well as the contribution of occupational and speech and language therapy in the acute phase and their interaction with long-term outcome. Current issues include strategies in assessment and treatment of atrial fi brillation, hypertension and diabetes mellitus at hyperacute and acute stage, models of prognostic value in dysphagia used to prevent its inherent risks, and concepts of early language and speech therapy to enhance functional communication. In neurorehabilitation, targeted treatment referred to pathophysiological mechanisms and perception of idiosyncratic in addition to common aspects of functional impairment are major concerns.

Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

Both Sweet’s syndrome (SS), also known as acute febrile neutrophilic dermatosis, and Pyoderma Gangrenosum (PG) are rare syndromes that have been associated with malignancy, autoimmune disease and c...

Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants.

Leishmaniasis are infectious diseases caused by parasites of genus Leishmania that affect affects 12 million people in 98 countries mainly in Africa, Asia, and Latin America. Effective treatments for this disease are urgently needed. In this study, we present a computer-aided approach to investigate a set of 32 recently synthesized chalcone and chalcone-like compounds to act as antileishmanial agents. As a result, nine most promising compounds and three potentially inactive compounds were experimentally evaluated against Leishmania infantum amastigotes and mammalian cells. Four compounds exhibited EC50 in the range of 6.2-10.98μM. In addition, two compounds, LabMol-65 and LabMol-73, exhibited cytotoxicity in macrophages >50μM that resulted in better selectivity compared to standard drug amphotericin B. These two compounds also demonstrated low cytotoxicity and high selectivity towards Vero cells. The results of target fishing followed by homology modeling and docking studies suggest that these chalcone compounds could act in Leishmania because of their interaction with cysteine proteases, such as procathepsin L. Finally, we have provided structural recommendations for designing new antileishmanial chalcones.

Chagas disease is a neglected tropical disease, caused by the protozoan parasite Trypanosoma cruzi, which affects more than eight million people in Tropical and Subtropical countries especially in Latin America. Current treatment is limited to nifurtimox and benznidazole, both with reduced effectiveness and high toxicity. In this work, the n-hexane extract from leaves of Nectandra leucantha (Lauraceae) displayed in vitro antitrypanosomal activity against T. cruzi. Using several chromatographic steps, four related neolignans were isolated and chemically characterized as dehydrodieugenol B (1), 1-(8-propenyl)-3-[3′-methoxy-1′-(8-propenyl)-phenoxy]-4,5-dimethoxybenzene (2), 1-[(7S)-hydroxy-8-propenyl]-3-[3′-methoxy-1′-(8′-propenyl)-phenoxy]-4-hydroxy-5-methoxybenzene (3), and 1-[(7S)-hydroxy-8-propenyl]-3-[3′-methoxy-1′-(8′-propenyl)-phenoxy]-4,5-dimethoxybenzene (4). These compounds were tested against intracellular amastigotes and extracellular trypomastigotes of T. cruzi and for mammalian cytotoxicity. Neolignan 4 showed the higher selectivity index (SI) against trypomastigotes (>5) and amastigotes (>13) of T. cruzi. The investigation of the mechanism of action demonstrated that neolignan 4 caused substantial alteration of the plasma membrane permeability, together with mitochondrial dysfunctions in trypomastigote forms. In silico studies of pharmacokinetics and toxicity (ADMET) properties predicted that all compounds were non-mutagenic, non-carcinogenic, non-genotoxic, weak hERG blockers, with acceptable volume of distribution (1.66–3.32 L/kg), and low rodent oral toxicity (LD50 810–2200 mg/kg). Considering some clinical events of cerebral Chagas disease, the compounds also demonstrated favorable properties, such as blood-brain barrier penetration. Unfavorable properties were also predicted as high promiscuity for P450 isoforms, high plasma protein binding affinity (>91%), and moderate-to-low oral bioavailability. Finally, none of the isolated neolignans was predicted as interference compounds (PAINS). Considering the promising chemical and biological properties of the isolated neolignans, these compounds could be used as starting points to develop new lead compounds for Chagas disease.

Most children with in utero alcohol exposure do not exhibit all features of fetal alcohol syndrome (FAS), and a challenge for clinicians is to make an early diagnosis of fetal alcohol spectrum disorders (FASD) to avoid lost opportunities for care. In brain, correct neurodevelopment requires proper angiogenesis. Since alcohol alters brain angiogenesis and the placenta is a major source of angiogenic factors, we hypothesized that it is involved in alcohol-induced brain vascular defects. In mouse, using in vivo repression and overexpression of PLGF, we investigated the contribution of placenta on fetal brain angiogenesis. In human, we performed a comparative molecular and morphological analysis of brain/placenta angiogenesis in alcohol-exposed fetuses. Results showed that prenatal alcohol exposure impairs placental angiogenesis, reduces PLGF levels and consequently alters fetal brain vasculature. Placental repression of PLGF altered brain VEGF-R1 expression and mimicked alcohol-induced vascular defects in the cortex. Over-expression of placental PGF rescued alcohol effects on fetal brain vessels. In human, alcohol exposure disrupted both placental and brain angiogenesis. PLGF expression was strongly decreased and angiogenesis defects observed in the fetal brain markedly correlated with placental vascular impairments. Placental PGF disruption impairs brain angiogenesis and likely predicts brain disabilities after in utero alcohol exposure. PLGF assay at birth could contribute to the early diagnosis of FASD. Electronic supplementary material The online version of this article (doi:10.1186/s40478-017-0444-6) contains supplementary material, which is available to authorized users.

Objective We studied brain structure abnormalities in adolescents and young adults who had undergone the neonatal arterial switch operation for transposition of the great arteries and related them to the neurologic and psycho-intellectual outcomes. Methods In a prospective longitudinal study, 60 unselected adolescents and young adults who had undergone surgery with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were re-evaluated at a mean age of 16.9 ± 1.7 years to determine their clinical neurologic status, intellectual development, and psychological condition. The results were related to population norms and anatomic structural abnormalities assessed by brain magnetic resonance imaging, with consideration of the risk factors in the preoperative and perioperative periods. Results Neurologic impairment was more frequent (10%) than in the normal population. Although the average full-scale, verbal, and performance intelligence quotients were not reduced, scores >2 standard deviations less than the expected mean were increased. Above average scores were found for analytical thinking, but the orthography testing results were reduced. The self-rated psychological condition was better than expected. Magnetic resonance imaging demonstrated moderate or severe structural brain abnormalities in 32% of the patients. Periventricular leukomalacia was detected in >50%; its severity correlated with the grade of neurologic impairment, which correlated significantly with reduced intelligence, analytical thinking, and orthography. Preoperative acidosis and hypoxia were the only independent patient-related risk factors for neurologic dysfunction, reduced intelligence, periventricular leukomalacia, and reduced brain volume. Conclusions Despite encouraging overall neurodevelopmental outcomes, a significant minority had performances below the expected level, emphasizing the need for ongoing surveillance. Considering the high frequency of structural brain abnormalities, prospective long-term studies are needed to define their prognostic value with respect to the neuropsychological outcomes in childhood and adolescence.

Screening children to determine risk for Autism Spectrum Disorders has become more common, although some question the advisability of such a strategy. The purpose of this systematic review is to identify autism screening tools that have been adapted for use in cultures different from that in which they were developed, evaluate the cultural adaptation process, report on the psychometric properties of the adapted instruments, and describe the implications for further research and clinical practice. A total of 21 articles met criteria for inclusion, reporting on the cultural adaptation of autism screening in 19 countries and in 10 languages. The cultural adaptation process was not always clearly outlined and often did not include the recommended guidelines. Cultural/linguistic modifications to the translated tools tended to increase with the rigor of the adaptation process. Differences between the psychometric properties of the original and adapted versions were common, indicating the need to obtain normative data on populations to increase the utility of the translated tool.

Glutamate excitotoxicity is a consolidated hypothesis in neonatal brain injuries and tissue plasminogen activator (t-PA) participates in the processes through proteolytic and receptor mediated effects. In brain microvascular endothelial cell (nBMEC) cultures from neonates, t-PA content and release upon glutamate are higher than in adult (aBMECs) cultures. Owing to the variety of t-PA substrates and receptor targets, the study was aimed at determining the putative roles of endothelial t-PA in the neonatal brain parenchyma under glutamate challenge. Basal t-PA release was 4.4 fold higher in nBMECs vs aBMECs and glutamate was 20 fold more potent to allow Evans blue vascular permeability in neonate microvessels indicating that, under noxious glutamate (50 μM) exposure, high amounts of endothelial t-PA stores may be mobilized and may access the nervous parenchyma. Culture media from nBMECS or aBMECs challenged by excitotoxic glutamate were applied to neuron cultures at DIV 11. While media from adult cells did not evoke more LDH release in neuronal cultures that under glutamate alone, media from nBMECs enhanced 2.2 fold LDH release. This effect was not observed with media from t-PA(-/-) nBMECs and was inhibited by hr-PAI-1. In Cortical slices from 10 day-old mice, hrt-PA associated with glutamate evoked neuronal necrosis in deeper (more mature) layers, an effect reversed by NMDA receptor GluN1 amino-terminal domain antibody capable of inhibiting t-PA potentiation of the receptor. In superficial layers (less mature), hrt-PA alone inhibited apoptosis, an effect reversed by the EGF receptor antagonist AG1478. Applied to immature neurons in culture (DIV5), media from nBMEC rescued 85.1% of neurons from cell death induced by serum deprivation. In cortical slices, the anti-apoptotic effect of t-PA fitted with age dependent localization of less mature neurons. These data suggest that in the immature brain, propensity of vessels to release high amounts of t-PA may not only impact vascular integrity but may also influence neuronal fate, via regulation of apoptosis in immature cells and, as in adult by potentiating glutamate toxicity in mature neurons. The data point out putative implication of microvessels in glutamate neurotoxicity in the development, and justify research towards vessel oriented neuroprotection strategies in neonates.

Preterm infants born before 29 gestation weeks incur major risk of subependymal/intracerebral/intraventricular hemorrhage. In mice, neonate brain endothelial cells are more prone than adult cells to secrete proteases under glutamate challenge, and invalidation of the Serpine 1 gene is accompanied by high brain hemorrhage risk up to five days after birth. We hypothesized that the structural and functional states of microvessels might account for age-dependent vulnerability in mice up to five days after birth and might represent a pertinent paradigm to approach the hemorrhage risk window observed in extreme preterms. Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways. Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways. Both approaches pointed towards extracellular matrix, cell adhesion and junction pathways, indicating delayed microvascular strengthening after P5. Furthermore, glutamate receptors, proteases and their inhibitors exhibited convergent evolutions towards excitatory aminoacid sensitivity and low proteolytic control likely accounting for vascular vulnerability in P5 mice. Thus, age vascular specificities must be considered in future therapeutic interventions in preterms. Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870).

The cancer is a painful disease that kill too many people. Skin cancer is among the most frequent types of tumors in the world, and melanoma is the most worrying type of skin cancer due to its high metastasis chances. Its global occurrence index is close to 133.000 people per year.

Low-income and ethnic minority families continue to face critical disparities in access to diagnostic and treatment services for neurodevelopmental conditions, such as autism spectrum disorder and attention deficit hyperactivity disorder. Despite the growing cultural diversity of the United States, ethnic minority children and families continue to be substantially underrepresented across research on neurodevelopmental disorders, and there is a particularly concerning lack of research on the treatment of these conditions in low-income and ethnic minority communities. Of note, there are currently no published studies on adapting autism spectrum disorder treatment for low-income Latino communities and relatively few studies documenting adapted treatments for children with attention deficit hyperactivity disorder in these communities. This article describes methodological considerations and adaptations made to research procedures using a Diffusion of Innovation framework in order to effectively recruit and engage low-income, ethnic minority, particularly Latino, families of children with neurodevelopmental disorders, in a comparative effectiveness trial of two school-based interventions for executive dysfunction.

Background: Although acute respiratory infections (ARIs) are the global leading cause of pediatric morbidity and mortality, the relative impact of viral pathogens on pediatric ARIs is still poorly understood, especially in equatorial settings. Long-term studies of multiple viruses concurrently circulating in these regions are still lacking. Here, we report the results of a systematic prospective surveillance of multiple respiratory viruses conducted every weekday for nearly a decade in an equatorial city in Brazil. Methods: We analyzed the relative burden of influenza, parainfluenza, respiratory syncytial virus (RSV), adenovirus, and metapneumovirus, their seasonality, and their association with climatic and demographic factors, ARI diagnosis, and pediatric mortality. Results and Conclusions: RSV was the primary driver of severe childhood respiratory infections, including pneumonia. RSV was also the virus most strongly associated with respiratory-associated deaths, with RSV circulation and pediatric mortality being in phase. Annual circulation of influenza peaked much earlier than annual mortality due to respiratory causes. The results also show that viral circulation can be strongly seasonal even in equatorial regions, which lack seasons with low temperatures: RSV and influenza were concentrated in the rainy season, whereas parainfluenza predominantly circulated in the dry season. The consistent epidemiologic patterns observed can be used for an effective adjustment of the timing of therapeutic and prophylactic interventions in this and potentially in other equatorial regions.