COVID-19 infection in children, adolescents, and young adults with Down syndrome and hematologic malignancies.

INTRODUCTION: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. METHODS: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. RESULTS: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1). CONCLUSIONS: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.

Outcomes of Referrals in Pediatric Patients With Peripheral Lymphadenopathy.

Lymphadenopathy is a common reason for referral to a subspecialist, which may result in significant anxiety for parents. Understanding which patients require a subspecialty referral for lymphadenopathy is key to streamlining health care utilization for this common clinical entity. This is an IRB-approved retrospective study examining pediatric patients consecutively referred to pediatric hematology oncology, otolaryngology, or surgery for lymphadenopathy from 2012 to 2021 at a free-standing tertiary-care children's hospital. Logistic regression was fitted to examine the association between the maximum size of the lymph nodes (LN) and a diagnosis of malignancy. The odds ratio, area under the receiver operator curve, sensitivity, and specificity were estimated. We found a significant association between LN size and cancer diagnosis. For every centimeter increase in the maximal dimension of LN, there was an estimated 2.3 times increase in the odds of malignancy (OR=2.3, 95% CI: 1.65-3.11; P<0.0001). The estimated area under the curve (0.84, 95% CI: 0.78-0.90) indicated that LN size correlated well with cancer diagnosis. A LN cut-off size of 2 cm resulted in an estimated sensitivity of 1.0 (95% CI: 0.87-1.00) and specificity of 0.54 (95% CI: 0.46-0.61). Maximum LN size may be a predictor of malignancy among pediatric patients with lymphadenopathy.

The addition of curcumin to the diet of post-weaning dairy calves: effects on ruminal fermentation, immunological, and oxidative responses.

Incorporating Curcumin into animal diets holds significant promise for enhancing both animal health and productivity, with demonstrated positive impacts on antioxidant activity, anti-microbial responses. Therefore, this study aimed to determine whether adding Curcumin to the diet of dairy calves would influence ruminal fermentation, hematologic, immunological, oxidative, and metabolism variables. Fourteen Jersey calves were divided into a control group (GCON) and a treatment group (GTRA). The animals in the GTRA received a diet containing 65.1 mg/kg of dry matter (DM) Curcumin (74% purity) for an experimental period of 90 days. Blood samples were collected on days 0, 15, 45, and 90. Serum levels of total protein and globulins were higher in the GTRA group (P < 0.05) than the GCON group. In the GTRA group, there was a reduction in pro-inflammatory cytokines (IL-1ß and IL-6) (P < 0.05) and an increase in IL-10 (which acts on anti-inflammatory responses) (P < 0.05) when compared to the GCON. There was a significantly higher (P < 0.05) concentration of immunoglobulin A (IgA) in the serum of the GTRA than the GCON. A Treatment × Day interaction was observed for haptoglobin levels, which were higher on day 90 in animals that consumed Curcumin than the GCON (P < 0.05). The catalase and superoxide dismutase activities were significantly higher (P < 0.05) in GTRA, reducing lipid peroxidation when compared to the GCONT. Hematologic variables did not differ significantly between groups. Among the metabolic variables, only urea was higher in the GTRA group when compared to the GCON. Body weight and feed efficiency did not differ between groups (meaning the percentage of apparent digestibility of dry matter, crude protein, and acid detergent fiber (ADF) and neutral detergent fiber (NDF). There was a tendency (P = 0.09) for treatment effect and a treatment x day interaction (P = 0.05) for levels of short-chain fatty acids in rumen fluid, being lower in animals that consumed curcumin. There was a treatment vs. day interaction (P < 0.05) for the concentration of acetate in the rumen fluid (i.e., on day 45, had a reduction in acetate; on day 90, values were higher in the GTRA group when compared to the GCON). We conclude that there was no evidence in the results from this preliminary trial that Curcumin in the diet of dairy calves interfered with feed digestibility. Curcumin may have potential antioxidant, anti-inflammatory, and immune effects that may be desirable for the production system of dairy calves.

A Systematic Review on Alcohol Consumption among Non-Religious and Religious Adults.

Background: Research has suggested that religiosity is a protective factor in alcohol use, but this is an area that could be further explored. Objective: To undertake a systematic review of the literature on drinking patterns and their relationship with religiosity and non-religiosity in adult populations. Methods: We searched for relevant studies using the PubMed, LILACS, Web of Science, Scopus, and Psych-INFO databases. This review included only studies of people aged 18 and over which had a non-religious group as a comparison measure. Results: Fifty-one studies met the inclusion criteria. The present review showed that religious people tend to have lower alcohol consumption compared to those with no religion. However, this difference appears only when religions are analyzed together without differentiating between religious affiliations (Catholicism, Buddhism, Evangelicalism, etc.). Some religious affiliations, such as Buddhism, Catholicism and Lutheranism, appear to be risk factors for alcohol consumption. Definitions of risk consumption showed high heterogeneity, ranging from eight to 21 or more doses per week, a difference of 13 doses of alcohol between studies. Conclusions: The present review showed that religious people tend to have lower alcohol consumption compared to non-religious people. However, the results are contradictory when religious affiliations are analyzed separately and compared with non-religious participants. Adequately understanding which dimensions of religiosity and non-religiosity (e.g., group processes, engagement, meaning, rules of behavior) are protective in adulthood is fundamental to the construction of more effective interventions in this age group.

Mother-infant bonding in the first nine months postpartum: the role of mother's attachment style and psychological flexibility.

INTRODUCTION: Mother's bond to the infant in the postpartum period plays an important role in the subsequent mother-infant relationship and the infant's socio-emotional functioning. Several maternal characteristics, such as attachment style and psychological flexibility, may contribute to the quality of mother-infant bonding, though literature examining these variables is still scarce. The present study aimed to examine the impact of mother's attachment on mother-infant bonding in the first month postpartum and the mediating role of psychological flexibility on that association. METHODS: Participants were 226 mothers of an infant up to 9 months old, who reported on their own attachment style (in terms of anxiety, comfort with proximity, trust in others), psychological flexibility (in terms of openness to experience, behavioural awareness, valued action) and mother-infant bonding. RESULTS: Results showed that mother's attachment anxiety predicted a bond with the infant directly and indirectly via mother's psychological flexibility, specifically through behavioural awareness and valued action. Trust in others had an impact on mother-infant bonding through behavioural awareness, whereas comfort with proximity influenced mother-infant bond indirectly, via valued action. Finally, mothers' civil status, schooling and number of children were relevant to better understand the variance of our mediating and dependent variables. DISCUSSION: Our findings highlight the importance of mother's attachment and psychological flexibility in promoting the quality of mother-infant bonding, which can inform future intervention programmes targeting modifiable factors, such as psychological flexibility, to promote early positive parent-infant relationships, particularly for single, first-time mothers, with higher levels of education.

Immunohistochemical identification of a malignant catarrhal fever virus in cattle with renal diseases from Paraná state, Southern Brazil: a retrospective epidemiological study.

Malignant catarrhal fever (MCF) is a viral infectious disease caused by specific members of the Macavirus genus that are referred to as the MCF virus (MCFV) complex group. This study determined the prevalence of MCFV-associated infections in cattle within the mesoregions of the state of Paraná, Southern Brazil, by analyzing the histopathologic patterns of renal lesions in association with positive immunoreactivity to intralesional antigens of MCFV. Intracytoplasmic MCFV antigens were identified in 41.7% (48/115) of the kidneys of cattle evaluated. Lymphocytic interstitial nephritis, vascular degeneration, and ballooning degeneration of the renal tubules were the principal histopathological findings associated with positive immunoreactivity to MCFV. The results indicate that MCFV infections are endemic within the state of Paraná and suggest that the kidney can be of diagnostic value in suspected cases of MCF-associated infections in cattle. Furthermore, the utilization of an in situ diagnostic technique resulted in the detection of a greater number of cases of infections by MCFV than previously identified using other diagnostic methods. Additionally, degenerative vascular lesions of the kidney should be considered during the establishment of a histological diagnosis of MCFV-induced infections in cattle in the absence of fibrinoid change or necrotizing vasculitis.

Impact of sociodemographic factors on early mortality in acute promyelocytic leukemia in the United States: A time-trend analysis.

BACKGROUND: The survival of patients with acute promyelocytic leukemia (APL) has dramatically improved with the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, because of the complexity of the initial management, early mortality (EM) remains a major contributor to treatment failure. It is less known whether advances in treatment, urgent access to specialized care, and broad availability of ATRA/ATO have reduced EM in the last 2 decades. Furthermore, the influence of sociodemographic factors on the risk of EM also remains unclear. METHODS: This study used the Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on the rates of EM and overall survival (OS) in patients with APL diagnosed between 1992 and 2015. RESULTS: In all, 2224 cases were identified (895 who were younger than 40 years and 1329 who were 40 years old or older); 47.9% had a county-level median household income of $59,630 or higher, 49.0% belonged to counties where more than 31% of adults held at least a bachelor's degree, and 86.0% resided in urban areas. The rate of EM declined from 31.5% in 1992-1995 to 15.9% in 2012-2015 for all patients. It improved for patients younger than 40 years (27.4% in 1992-1995 vs 5.4% in 2012-2015; P < .001) and for patients 40 years old or older but not to the same extent (35.2% in 1992-1995 vs 22.2% in 2012-2015; P = .02). Importantly, improvements in EM were not seen among patients residing in rural areas, with the rate remaining higher than 20% in 2012-2015. The 3-year OS rate was 49.2% for patients with APL diagnosed in 1992-1995 and 76.4% for patients diagnosed in 2012-2015. CONCLUSIONS: These findings confirm consistent improvements in EM and OS for patients with APL and point to the challenge of further extending these improvements in EM rates to older patients and to those living in rural areas.

Detection of bovine gammaherpesvirus 6 in tissues of aborted fetuses from dairy cows concomitantly infected by Histophilus somni.

Bovine gammaherpesvirus 6 (BoGHV6), formerly known as bovine lymphotropic virus, is a member of the Macavirus genus, subfamily Gammaherpesvirinae, family Herpesviridae, that was initially associated with proliferative diseases in cattle. While the Macavirus genus contains agents, including alcelaphine gammaherpesvirus 1 (AlGHV1), ovine gammaherpesvirus 2 (OvGHV2), and caprine gammaherpesvirus-2 (CpGHV2), known to cause malignant catarrhal fever (MCF), and are collectively referred to as MCF virus (MCFV) group of organisms, diseases and/or clinical syndromes have not been associated with BoGHV6 and porcine lymphotropic herpesvirus (PLHV). This report investigated the occurrence of BoGHV6 in tissues of aborted dairy fetuses known to be infected by Histophilus somni to identify possible disease patterns associated with infection by this Macavirus. A nested-PCR (nPCR) assay was used to amplify the BoGHV6 polymerase gene from multiple tissues of 13 fetuses and the cow of one of these which were derived from seven dairy herds located in three geographical regions of Brazil. Direct sequencing confirmed the results of the nPCR assays. Additionally, all fetal tissues were previously investigated for the presence of H. somni, Listeria monocytogenes, Neospora caninum, Brucella abortus, Leptospira spp., bovine alphaherpesvirus 1, and bovine viral diarrhea virus (BVDV) by PCR and/or RT-PCR assays. The nPCR assay amplified BoGHV6 DNA from fetuses of most dairy herds (85.7%; 6/7) investigated, resulting in the amplification of BoGHV6 from 76.9% (10/13) of all fetuses evaluated from two geographical and important cattle-producing regions of Brazil. Furthermore, only BoGHV6 was identified in the spleen (n = 3), myocardium, and kidney (n = 2) of five fetuses, and BoGHV6 was the only agent associated with myocarditis in one of these. Nevertheless, dual, triple, and quadruple infections (including BVDV, B. abortus, and N. caninum) were identified in fetuses that were concomitantly infected by H. somni. Phylogenetic analysis revealed that the strain herein identified has 100% nucleotide (nt) sequence identity with wild type strains of BoGHV6 circulating in ruminants from Brazil and 99.8% nt identity with the reference strain of BoGHV6 but was 72.2-73.3% and 67.4-68.2% different from members of the MCFV group and PLHV, respectively. These results demonstrated that 76.9% of the fetuses evaluated were infected by BoGHV6, most likely via vertical infection resulting in transplacental transmission. Considering that most fetuses were concomitantly infected by BoGHV6 and H. somni the real impact of this viral infection cannot be efficiently determined. However, since BoGHV6 was the only pathogen identified in the myocardium of one fetus with myocarditis by histopathology, the possible participation of this Macavirus in the etiopathogenesis of the myocardial disease observed in this fetus cannot be ignored or discarded. However, the mere amplification of BoGHV6 DNA from the myocardium is not enough to establish a definite association between cause and effect, since in situ evaluations and experimental studies would be needed to confirm this agent in the etiopathogenesis of fetal diseases and/or abortions in cattle. Consequently, additional studies are needed to determine the exact role, if any, of BoGHV6 in the development of fetal disease, and possibly fetal mortality.

Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

Impact of insurance status on the survival of younger patients diagnosed with acute promyelocytic leukemia in the United States.

BACKGROUND: Survival among patients diagnosed with acute promyelocytic leukemia (APL) has significantly improved with the use of all-trans retinoic acid and arsenic trioxide. However, the need for immediate diagnosis and access to specialized care and the cost associated with APL management can potentially act as barriers for disadvantaged patients. The influence of sociodemographic factors on the outcomes of patients with APL remains unclear. METHODS: The authors used the National Cancer Institute's Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on survival in patients younger than 65 years with APL. RESULTS: The authors identified 1787 cases: 816 who were younger than 40 years and 971 who were 40 years old or older. Insured patients who were younger than 40 years had an improved 5-year overall survival (OS) rate in comparison with patients without insurance. Among patients who were 40 years or older, having insurance (other than Medicaid) was associated with better survival than being a Medicaid beneficiary or being uninsured, whereas patients with Medicaid had improved 5-year OS in comparison with uninsured patients. In a multivariate analysis of patients younger than 40 years, a higher risk of death was associated with being male, being diagnosed in earlier years, and being uninsured. For patients who were 40 years old or older, mortality increased with increasing age and for both Medicaid and uninsured patients in comparison with insured patients. CONCLUSIONS: Despite the high cure rate experienced by patients with APL, patients younger than 65 years without insurance and those 40 years old or older with Medicaid are at a significant disadvantage in comparison with patients with insurance. These findings point to an opportunity to improve survival in APL by addressing access to care.

Ovine gammaherpesvirus-2 infection associated with chronic interstitial pneumonia in a sheep.

Sheep Associated-Malignant Catarrhal Fever (SA-MCF) is severe, frequently lethal, lymphoproliferative disease predominantly of ruminants, that is caused by ovine gammaherpesvirus-2 (OvHV-2), a member of the MCF virus (MCFV) complex. However, SA-MCF in sheep is a rare entity with few demonstrations of natural diseases worldwide. This report documents the clinical, radiographical, pathological, immunohistochemical, and molecular findings of SA-MCF in a sheep. A 4-year-old, female, mixed-breed sheep with progressive emaciation for at least one month was humanely euthanized due to poor prognosis. Clinically, the animal had tachypnea, ruminal hypomotility, productive coughing with bilateral muffling sounds during pulmonary auscultation. Radiographical evaluation revealed alveolar opacity of the cranioventral pulmonary region. Grossly, there were distinct rib impressions on the pleural surface of the lungs, suggestive of interstitial pneumonia. Histopathologic evaluation of the lungs revealed several disease patterns including 1) chronic interstitial pneumonia with vasculitis and proliferating vascular lesions, and thrombosis; 2) pulmonary abscesses associated with embolic dissemination of Corynebacterium pseudotuberculosis from superficial lymph node due to caseous lymphadenitis, CLA; 3) granulomatous pneumonia associated with pulmonary nematodes; and 4) chronic pleuritis, probably due to caseous lymphadenitis. Additional significant histologic findings included widespread lymphocytic vasculitis and proliferating vascular lesions in multiple tissues, atrophic enteritis, segmental degeneration of myocardial fibers with lymphocytic pericarditis, lymphocytic interstitial nephritis, and non-suppurative encephalitis. An immunohistochemistry (IHC) assay, based on the monoclonal antibody 15A (MAb-15A), that is specific to all MCFV known to cause MCF, revealed positive, intracytoplasmic, intralesional immunoreactivity, predominantly within bronchial and bronchiolar epithelial cells of the lungs and cryptal epithelial cells of the small intestine, followed by the renal tubular epithelium, cardiomyocytes, and with patchy immunolabelling within neurons of the cerebral cortex. Molecular testing done to detect a wide range of bacterial and viral agents of ruminant diseases, only amplified OvHV-2 DNA from fresh tissue fragments of the lungs, kidney, liver, spleen, and cerebrum. Direct sequencing confirmed that the PCR amplicon derived from the pulmonary fragments had 99.2-99.7% nucleotide sequence identity with OvHV-2 reference strains and strains of OvHV-2 from Brazil. The clinical, radiographical, gross, histopathologic, IHC, and molecular findings in the lungs are consistent with chronic interstitial pneumonia associated with infection by OvHV-2. Furthermore, the non-detection of other viral agents associated with pulmonary diseases in ruminants suggest that OvHV-2 was directly associated with the development of chronic pneumonia in this sheep. Additionally, the dental alterations, CLA, and the pulmonary nematode may have contributed towards the reduced immunological statue of the animal and facilitated the occurrence of SA-MCF. These findings may indicate that OvHV-2 may be a major participant in the pathogenesis of pulmonary disease of sheep under special conditions. Moreover, the proliferating vascular lesions identified in multiple tissues are additional evidence of chronic manifestations of OvHV-2 infections as described in chronic SA-MCF of cattle, while the widespread vasculitis is consistent with SA-MCF. Additionally, the IHC findings using the MAb-15A confirmed that this diagnostic approach is efficient to identify intralesional antigens of OvHV-2.

Pediatric Hodgkin Lymphoma, Version 3.2021.

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

Racial disparities in the survival of patients with indolent non-Hodgkin lymphomas in the United States.

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68 059 adult patients with follicular lymphoma (FL, n = 41 943), marginal zone lymphoma (MZL, n = 22 485), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM, n = 3631) who were diagnosed in the US between 2000 and 2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. The RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; p < .001], corresponding to a difference of 55 (95% CI, 24-86) excess deaths per 10 000 person-years. For MZL, Black patients had a 40% higher excess mortality rate compared to White patients (aEHR 1.40; 95% CI, 1.18-1.66; p < .001), corresponding to a difference of 62 (95% CI, 26-98) excess deaths per 10 000 person-years. No significant racial differences were detected for patients with WM. The greatest disparity was seen for younger Black patients with FL. Our findings highlight the need for interventions to improve the outcomes of Black patients with iNHLs, particularly younger Black patients with FL.

Novel CUBN Mutation in a Young Child With Megaloblastic Anemia.

Inherited disorders of cobalamin (Cbl, vitamin B12) metabolism are rare causes of megaloblastic anemia and neurologic abnormalities. More prevalent in certain ethnic groups, these disorders occur despite adequate Cbl intake and usually result from abnormal vitamin cell transport or processing. Cubilin (CUBN, intrinsic factor-cobalamin receptor) is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. Its gene is localized to chromosome 10p13 and mutations involving CUBN have been described in patients with congenital megaloblastic anemia. In this report, we describe a novel CUBN pathogenic variant in a child with megaloblastic anemia.

Regional Frequency Analysis applied to extreme rainfall events: Evaluating its conceptual assumptions and constructing null distributions.

Besides increasing the amount of data that can be used in a fitting process, the Regional Frequency Analysis (RFA) also assesses the quality of weather station networks. This technique assumes that it is possible to form homogeneous groups of meteorological series presenting independent and identically distributed data. Based on the hypothesis that such homogeneous groups can be formed under tropical-subtropical conditions, this study applied the RFA to assess the probability of one-day annual maximum rainfall in the State of São Paulo, Brazil. Critical limits used in previous studies to declare a region/group as 'acceptable homogeneous' (H≤1.00) or to select a distribution (|Z|≤1.64) were evaluated through Monte Carlo simulations. While the limit H≤1 is appropriate, the limit |Z|≤1.64 may lead to unacceptably high rates of rejecting a true null hypothesis. This statement is particularly true for the general logistic distribution. A computational algorithm allowing the selection of critical limits corresponding to pre-specified probabilities of rejecting a true null hypothesis is provided. Considering the new critical limits, data from one of the largest weather station networks of the State have been pooled into four homogeneous groups. Both generalized logistic and extreme value distributions are recommended for the probabilistic assessment of such groups.

Genomic imbalances in craniofacial microsomia.

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation-dependent probe amplification (MLPA) for all individuals. The CMA was performed only for individuals with additional major features. MLPA revealed pathogenic CNVs at the 22q11 region in 3/54 (5.6%) individuals. CMA revealed pathogenic CNVs in 4/17 (23.5%) individuals, including the three CNVs at the 22q11 region also detected by MLPA, and CNVs classified as variants of unknown significance (VOUS) in 4/17 (23.5%) individuals. Pathogenic alterations were found at the 2p12, 5p15, 13q13, and 22q11 regions. VOUS were found at 3q29, 5q22.2, 5q22.1, and 9p22 regions. All individuals with pathogenic alterations presented additional major features, including congenital heart disease (CHD). The literature review revealed pathogenic CNVs in 17/193 (8.8%) individuals and most of them also presented additional major features, such as CHD, renal anomalies, or developmental delay. In conclusion, CNVs should be investigated in patients with CFM and additional major features.

Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

Impact of mining activities on areas of environmental protection in the southwest of the Amazon: A GIS- and remote sensing-based assessment.

The southwest Brazilian Amazon state of Rondônia has a relatively recent non-indigenous occupation, which subsequently develops a variety of human pressures and conflicts of interest presently identified in the region. Given such framework, it is worthwhile to note that there are 57 Conservation Units that must guarantee the biodiversity protection of Amazonia biome. However, due to the need for electricity and the international high demand for minerals, the highlighted scenario has dramatically changed in recent years. Official data from mining processes in the studied area demonstrated the existence of high interest for minerals, especially cassiterite and gold. Mining is indeed an essential activity for the nation mainly due to the generation of jobs and income. On the other hand, it produces several environmental and social impacts that vary accordingly to the peculiarities of the mining and with respect to the type of ore. Therefore, this research work investigated the concentration of mining projects in the state of Rondônia and complementarily evaluated the impact of such activities on areas of environmental protection. Landsat 8 OLI imageries were employed to map the diversity of land covers across the study area and also to evaluate the corresponding impact of mining activities. More than 500 processes have been identified within the Conservation Units. A significant part of the mining areas, covering about 26 km2, was observed inside one of the three types of evaluated areas (Integral Protection Sustainable Use Conservation Units and Damping Zone), clearly showing the development of the illegal activity, as defined in terms of the National System of Conservation Units. If deforestation is considered in this analysis, the area increases to about 6110 km2, representing more than 5.2% of the Conservation Units. In addition, we proposed the creation of the Mining Pressure Index (MPI), which allows classifying a Conservation Unit by the degree of pressure from mining activities. The proposed index revealed to be very efficient since it predicted high values over Conservation Units where it was expected a greater vulnerability. The index is a promising tool for public policy formulation and management of protected areas, as well as for enforcement action. The results provide a new horizon in terms of the perspective of importance and applicability of geotechnologies in the evaluation of environmental impacts, not restricted to mining activity.

Monozygotic twins with neuroblastoma MS have a similar molecular profile: a case of twin-to-twin metastasis.

Fetoplacental neuroblastoma metastasis has been postulated as a mechanism accounting for concordant cases where one twin develops a primary tumour and the second twin manifests the disease without an identifiable primary site. These tumours may originate and spread concomitantly due to the same genetic background shared by monozygotic twins. This study investigated the molecular profile of stage MS neuroblastoma presenting concomitantly in monozygotic twins. Comparative genomic hybridisation (aCGH) was done for each of the twin liver tumour and peripheral blood samples at diagnosis. Comparison of copy-number variation (CNV) regions revealed a set of CNVs that were common to both tumour specimens and not apparent in the blood. The CNV signature in both twins' tumours was highly similar, suggesting a common clonal origin. Additional findings included large deletion of chromosome 10 and amplification of chromosome 17. Notably, both liver samples had amplification of a short region involving DEIN (chromosome 4q34.1). Similar CNVs strongly support a common clonal origin and metastatic spread from one twin to the other. DEIN is a long-coding RNA (IncRNA) that has been found highly expressed in stage MS neuroblastoma and is likely involved in biological processes such as cell migration and metastasis.

Treatment and prognosis of mature (non-anaplastic) T- and NK-cell lymphomas in childhood, adolescents, and young adults.

Paediatric non-Hodgkin lymphomas (pNHL) are a diverse group of malignancies characterised by nodal and/or extranodal involvement. Less common pNHL forms include those derived from mature T- and natural killer (NK) cells. Much of our current understanding of paediatric mature (non-anaplastic) T/NK-cell lymphomas with respect to pathogenesis, diagnosis and treatment is extrapolated from adult literature. At the Sixth International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma, convened September 26-29, 2018 in Rotterdam, The Netherlands, some important aspects on diagnosis and outcomes of mature (non-anaplastic) T/NK-cell lymphoma in children and adolescents were discussed and will be reviewed in here.