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APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort.
Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m
] and slow/non-progressors (eGFR > 30 mL/min/1.73 m
through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy.
Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-ris-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.It is extremely difficult to stratify bronchiolitis and predict the need for admission to the pediatric intensive care unit (PICU). We aimed to evaluate the capacity of a new lung ultrasound score (LUSBRO) to predict the need for admission to the PICU compared to a clinical score. This was a prospective observational single-center study that includes infants less then 6 month of age admitted to a hospital due to acute bronchiolitis. Both scores were calculated at admission. The main outcome was PICU admission. Second endpoints were the need for mechanical ventilation, respiratory support duration, and the length of stay in the hospital. Eighty patients were included, with a median age of 53 days (IQR 29-115). Forty-four patients (55%) required PICU admission. LUSBRO score showed a better AUC compared to the clinical score to predict PICU admission 0.932 (95% CI 0.873-0.990) vs. 0.675 (95% CI 0.556-0.794) and a positive correlation with the hospital length of stay. The best cut-off point for predicting the need for PICU admission for LUSBRO score was 6, showing a sensitivity of 90.91% and a specificity of 88.89%.Conclusions The LUSBRO score is a useful tool to predict the need for admission to the PICU. What is Known • It is extremely difficult to stratify which patients affected by bronchiolitis should be precociously transferred to a third level hospital and will require pediatric intensive care unit (PICU) admission. • Clinical scores have been created but neither of them is accurate. What is New • The LUSBRO score is a useful tool to predict the need for admission to the PICU of patients with bronchiolitis and, consequently, to predict the patients who should be transferred to a tertiary hospital to optimize respiratory support.Screening for hypo- or hyperthyroidism in adults is generally done by measuring the serum thyrotropin (thyroid-stimulating hormone, TSH) concentration. This is an efficient approach in case of suspected acquired thyroid disease. However, in infants and children, congenital hypothalamus-pituitary-thyroid (HPT) axis disorders also need to be considered, including primary and central congenital hypothyroidism, and even rarer thyroid hormone receptor and transporter defects. In primary congenital hypothyroidism, TSH will be elevated, but in the other congenital HPT axis disorders, TSH is usually within the normal range. Free thyroxine (FT4) assessment is essential for the diagnosis in these conditions.Conclusion Here we discuss a number of rare congenital HPT axis disorders in which TSH is normal, but FT4 is low, and provide a clinical algorithm to distinguish between these disorders. What is Known • A single thyroid-stimulating hormone (TSH) measurement is an appropriate screening method for primary hypothyroidism. • For central hypothyroidism and rare thyroid hormone receptor and transporter defects a free thyroxine (FT4) measurement is essential for the diagnosis because TSH is usually normal. What is New • Here we present a new problem-oriented clinical algorithm including a diagnostic flow-chart for low FT4 and normal TSH in infants and children.HIV-associated neurocognitive disorder (HAND) is characterized by cognitive and behavioral deficits in people living with HIV. HAND is still common in patients that take antiretroviral therapies, although they tend to present with less severe symptoms. The continued prevalence of HAND in treated patients is a major therapeutic challenge, as even minor cognitive impairment decreases patient's quality of life. Therefore, modern HAND research aims to broaden our understanding of the mechanisms that drive cognitive impairment in people with HIV and identify promising molecular pathways and targets that could be exploited therapeutically. Recent studies suggest that HAND in treated patients is at least partially induced by subtle synaptodendritic damage and disruption of neuronal networks in brain areas that mediate learning, memory, and executive functions. Although the causes of subtle neuronal dysfunction are varied, reversing synaptodendritic damage in animal models restores cognitive function and thus highlights a promising therapeutic approach. OT-82 datasheet In this review, we examine evidence of synaptodendritic damage and disrupted neuronal connectivity in HAND from clinical neuroimaging and neuropathology studies and discuss studies in HAND models that define structural and functional impairment of neurotransmission. Then, we report molecular pathways, mechanisms, and comorbidities involved in this neuronal dysfunction, discuss new approaches to reverse neuronal damage, and highlight current gaps in knowledge. Continued research on the manifestation and mechanisms of synaptic injury and network dysfunction in HAND patients and experimental models will be critical if we are to develop safe and effective therapies that reverse subtle neuropathology and cognitive impairment.Since 1987, a group of behavior geneticists have been teaching an annual methodology workshop on how to use state-of-the-art methods to analyze genetically informative data. In the early years, the focus was on analyzing twin and family data, using information of their known genetic relatedness to infer the role of genetic and environmental factors on phenotypic variation. With the rapid evolution of genotyping and sequencing technology and availability of measured genetic data, new methods to detect genetic variants associated with human traits were developed and became the focus of workshop teaching in alternate years. Over the years, many of the methodological advances in the field of statistical genetics have been direct outgrowths of the workshop, as evidence by the software and methodological publications authored by workshop faculty. We provide data and demographics of workshop attendees and evaluate the impact of the methodology workshops on scientific output in the field by evaluating the number of papers applying specific statistical genetic methodologies authored by individuals who have attended workshops.
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