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Mirabegron has promising results for OAB symptoms in adults, although the potential for cardiovascular side effects has caused concern. Efficacy and tolerability in children have not been extensively studied. Effectiveness, tolerability, and side effects of Mirabegron are reported in children with refractory OAB. A retrospective review of children receiving Mirabegron between February 2014 and November 2018 was completed. Frequency, urgency, nocturnal (NE), and daytime incontinence (DI) were analyzed at baseline and 6 months. 70 children (50 females), median age 15 [range 8–16] years, commenced Mirabegron 25 mg (n = 29) or 50 mg (n = 41). 37 (53%) were still receiving treatment at 6 months: monotherapy n = 30, and combination therapy n = 7 (Solifenacin n = 4, Desmopressin n = 2, both n = 1). Where undertaken, blood pressure monitoring and ECGs were normal. For patients on monotherapy, 6 of 17 (35%) had improvement in NE, 11 of 19 (58%) in DI, 12 of 20 (60%) in frequency, and 8 of 21 (38%) in urgency symptoms. For patients receiving combination therapy, 2 of 6 (33%) had improvement in NE, 2 of 4 in DI (50%), 2 of 4 (50%) in frequency, and 4 of 6 (67%) had improvement in urgency. Reasons for treatment discontinuation (entire cohort) were: ineffectiveness (n = 28), worse symptoms (n = 4) and/or adverse reactions (n = 7), including dry mouth (n = 2), headaches (n = 4), dizziness (n = 1), nausea/vomiting (n = 3), increased seizures (n = 1), and rash (n = 1). Mirabegron improved symptoms in 70% of patients with refractory OAB. A prospective RCT should be the next step to establish the role of Mirabegron for the treatment of OAB in children. Level II. [ABSTRACT FROM AUTHOR]

Objective: To measure plasma levels of vascular endothelial growth factor (VEGF) and several cytokines (Interleukin [IL]-6 IL-8, IL-10) during the first week of life to examine the relationship between protein expression and likelihood of developing respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD).Study Design: Levels of IL-6, IL-8, IL-10, and VEGF were measured from plasma obtained from preterm patients during the first week of life. Newborns were recruited from a single center between April 2009 and April 2019. Criteria for the study included being inborn, birth weight of less than 1500 grams, and a gestational age of less than 32 weeks at birth.Results: The development of RDS in preterm newborns was associated with lower levels of VEGF during the first week of life. Higher plasma levels of IL-6 and IL-8 plasma were associated with an increased likelihood and increased severity of BPD at 36 weeks postmenstrual age. In contrast, plasma levels of VEGF, IL-6, IL-8, and IL-10 obtained during the first week of life were not associated with respiratory symptoms and acute care use in young children with BPD in the outpatient setting.Conclusions: During the first week of life, lower plasma levels of VEGF was associated with the diagnosis of RDS in preterm infants. Preterm infants with higher levels of IL-6 and IL-8 during the first week of life were also more likely to be diagnosed with BPD. These biomarkers may help to predict respiratory morbidities in preterm newborns during their initial hospitalization. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of pulmonary hypertension (PH) biomarkers in children with Down syndrome, an independent risk factor for PH, in whom biomarker performance may differ compared with other populations.Study Design: Serum endostatin, interleukin (IL)-1 receptor 1 (ST2), galectin-3, N-terminal pro hormone B-natriuretic peptide (NT-proBNP), IL-6, and hepatoma-derived growth factor (HDGF) were measured in subjects with Down syndrome and PH (n = 29), subjects with Down syndrome and resolved PH (n = 13), subjects with Down syndrome without PH (n = 49), and subjects without Down syndrome with World Symposium on Pulmonary Hypertension group I pulmonary arterial hypertension (no Down syndrome PH group; n = 173). Each biomarker was assessed to discriminate PH in Down syndrome. A classification tree was created to distinguish PH from resolved PH and no PH in children with Down syndrome.Results: Endostatin, galectin-3, HDGF, and ST2 were elevated in subjects with Down syndrome regardless of PH status. Not all markers differed between subjects with Down syndrome and PH and subjects with Down syndrome and resolved PH. NT-proBNP and IL-6 levels were similar in the Down syndrome with PH group and the no Down syndrome PH group. A classification tree identified NT-proBNP and galectin-3 as the best markers for sequentially distinguishing PH, resolved PH, and no PH in subjects with Down syndrome.Conclusions: Proteomic markers are used to improve the diagnosis and prognosis of PH but, as demonstrated here, can be altered in genetically unique populations such as individuals with Down syndrome. This further suggests that clinical biomarkers should be evaluated in unique groups with the development of population-specific nomograms. [ABSTRACT FROM AUTHOR]

Abstract: Indigenous forests are declining throughout southern Africa, partly because of exogenous disturbances such as harvesting of forest resources. We evaluate the influence of colonial logging and present-day harvesting of pole-size trees (2–15cmdbh), used for construction and fuelwood, on the structure and composition of iGxalingenwa forest in KwaZulu-Natal, South Africa. This forest has a distinctive physiognomy, with a thicket-like understorey and an emergent layer of primarily coniferous Podocarpus spp. These emergent trees represent individuals that were too small to be harvested during the colonial period. We argue that the dense angiosperm-dominated understorey arose in gaps created by logging, which allowed greater light levels at the forest floor. The understorey has since been intensively harvested (36% of available stems) for pole-sized stems, including canopy species, effectively suppressing the advanced regeneration as well as the replacement of the senescing canopy and emergent tree populations. The harvesting intensity of pole-sized stems is related to the species, size, and availability of trees. Few straight pole-sized stems are available among the understorey species and typically straight-stemmed canopy species are opportunistically harvested. Examination of community composition further suggests that, without management intervention, this forest will have a reduced stature, a thicket-like physiognomy, and be less diverse and less dominated by conifers. To rescue iGxalingenwa forest from this successional path requires a reduction in harvesting pressure on seedlings and saplings of species that normally dominate the canopy layer, many of which (Podocarpus falcatus, Ptaeroxylon obliquum and Calodendrum capense) appear to have declining populations. The effects of commercial logging a century ago still persist and are being compounded by subsistence harvesting with significant changes to forest physiognomy and composition and the possibility of arrested succession. [Copyright &y& Elsevier]

Objective: To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH).Study Design: IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n = 175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n = 61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis.Results: In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P = .037).Conclusions: IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Objectives: To determine if children with congenital heart disease (CHD) have lower newborn T-cell receptor excision circles (TREC) levels than the general population and to evaluate if low TREC levels in newborns with CHD are associated with clinical complications such as hospitalization for infection.Study Design: The Connecticut Newborn Screening Program reported TREC levels for newborns with CHD delivered between October 2011 and September 2016 at 2 major Connecticut children's hospitals. TREC levels for children with CHD were compared with the general population. TREC levels and outcome measures, including hospitalization for infection, were compared.Results: We enrolled 575 participants with CHD in the study. The median TREC level for newborns with CHD was lower than the general population (180.1 copies/μL vs 312.5 copies/μL; P < .01). patients with CHD requiring hospitalization for infection had lower median TREC levels than their counterparts (143.0 copies/μL vs 186.7 copies/μL; P < .01). The combination of prematurity and low TREC level had a strong relationship to hospitalization for infection (area under the receiver operative characteristic curve of 0.89). There was no association between TREC level and CHD severity.Conclusions: Newborns with CHD demonstrated lower TREC levels than the general population. Low TREC levels were associated with hospitalization for infection in preterm children with CHD. Study limitations include that this was a retrospective chart review. These findings may help to identify newborns with CHD at highest risk for infection, allowing for potential opportunities for intervention. [ABSTRACT FROM AUTHOR]

In fragmented landscapes, tree recruitment is critical for forest persistence. We examined the effects of disturbance and environmental factors, isolation distance, and forest area on the spatial scale (grain) of regeneration of tree species in Afromontane forest fragments in South Africa. A species’ grain is defined by whether it typically regenerates within its own canopy shadow (fine-grained) or over a larger spatial scale (coarse-grained). Species richness did not differ between small and large forest fragments but there were proportionately more coarse-grained species and fewer fine-grained species in small than in large fragments. While coarse-grained species richness increased with decreasing disturbance and increasing fragment isolation, fine-grained species richness increased with increasing fragment area. Fine-grained species are vulnerable to area-dependent fragmentation pressures. Although they regenerate in their canopy shadow, fine-grained species do not dominate disturbed fragments as expected. While able to survive in small fragments, fine-grained species are potentially dispersal limited and are not good colonisers and depend for their persistence on establishment in large forests. Conversely, because coarse-grained species have effective dispersal mechanisms they can colonise small fragments and are important for the maintenance of tree diversity in fragmented Afromontane forests. Thus, consideration of species grain of regeneration is necessary in conserving Afromontane tree diversity. Fine-grained species are conserved by protecting large forests while coarse-grained species are effectively conserved by maintaining small forest fragments often assumed to be ecologically unviable. [Copyright &y& Elsevier]

Standardized biodegradation testing methods, like the OECD 308 Aerobic and Anaerobic Transformation in Aquatic Sediment Systems, generate data on biodegradation required during environmental risk and hazard assessment of chemicals under different European and international regulations. However, difficulties arise when applying the OECD 308 guideline for testing hydrophobic volatile chemicals. Especially the use of a co-solvent (like acetone) as a measure to facilitate the application of the test chemical in combination with a closed setup to reduce losses due to volatilization tend to deplete/restrict the amount of oxygen in the test system. The result is a low oxygen or even anoxic water column in the water-sediment system. Thus, the degradation half-lives of the chemical generated from such tests are not directly comparable to the regulatory half-life values for Persistence assessment of the test chemical. The aim of this work was to further develop the closed setup to improve and maintain aerobic conditions in the water phase of the water-sediment systems for testing slightly volatile hydrophobic test chemicals. This improvement was attained by optimizing the test system geometry and agitation technique to maintain aerobic conditions in the water phase in a closed test setup, investigating appropriate co-solvent application strategy, and trialing the resulting test setup. This study shows that when using a closed test setup for OECD 308 tests, agitation of the water phase overlaying the sediment and the test item application using low co-solvent volume is critical for maintaining an aerobic water layer. [Display omitted] • Agitation of the water-sediment sample without/limited sediment resuspension. • Use of co-solvent for application should be limited while testing volatiles using closed setup. • Improved closed setup results in stable aerobic conditions and higher degradation. [ABSTRACT FROM AUTHOR]