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Pediatric Malaria with Respiratory Distress: Prognostic Significance of Point-of-Care Lactate
(MDPI, 2023-04-02) Mitran, Catherine; Opoka, Robert O.; Conroy, Andrea L.; Namasopo, Sophie; Kain, Kevin C.; Hawkes, Michael T.; Pediatrics, School of Medicine
Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed a pooled analysis of Ugandan children under five years of age hospitalized with malaria and RD from three past studies. In total, 1324 children with malaria and RD (median age 1.4 years, 46% female) from 21 health facilities were included. Median lactate level at admission was 4.6 mmol/L (IQR 2.6-8.5) and 586 patients (44%) had hyperlactatemia (lactate > 5 mmol/L). The mortality was 84/1324 (6.3%). In a mixed-effects Cox proportional hazard model adjusting for age, sex, clinical severity score (fixed effects), study, and site (random effects), hyperlactatemia was associated with a 3-fold increased hazard of death (aHR 3.0, 95%CI 1.8-5.3, p < 0.0001). Delayed capillary refill time (τ = 0.14, p < 0.0001), hypotension (τ = -0.10, p = 0.00049), anemia (τ = -0.25, p < 0.0001), low tissue oxygen delivery (τ = -0.19, p < 0.0001), high parasite density (τ = 0.10, p < 0.0001), and acute kidney injury (p = 0.00047) were associated with higher lactate levels. In children with malaria and RD, bedside lactate may be a useful triage tool, predictive of mortality.
Childhood Respiratory Viral Infections and the Microbiome
(Elsevier, 2023-10) Kloepfer, Kirsten M.; Kennedy, Joshua L.; Pediatrics, School of Medicine
The human microbiome associated with the respiratory tract is diverse, heterogeneous, and dynamic. The diversity and complexity of the microbiome and the interactions between microorganisms, host cells, and the host immune system are complex and multifactorial. Furthermore, the lymphatics provide a direct highway, the gut-lung axis, for the gut microbiome to affect outcomes related to respiratory disease and the host immune response. Viral infections in the airways can also alter the presence or absence of bacterial species, which might increase the risks for allergies and asthma. Viruses infect the airway epithelium and interact with the host to promote inflammatory responses that can trigger a wheezing illness. This immune response may alter the host's immune response to microbes and allergens, leading to T2 inflammation. However, exposure to specific bacteria may also tailor the host's response long before the virus has infected the airway. The frequency of viral infections, age at infection, sampling season, geographic location, population differences, and preexisting composition of the microbiota have all been linked to changes in microbiota diversity and stability. This review aims to evaluate the current reported evidence for microbiome interactions and the influences that viral infection may have on respiratory and gut microbiota, affecting respiratory outcomes in children.
Divergent trends of ecosystem-scale photosynthetic efficiency between arid and humid lands across the globe
(Wiley, 2022-09) Wei, Fangli; Wang, Shuai; Fu, Bojie; Wang, Lanhui; Zhang, Wenmin; Wang, Lixin; Pan, Ning; Fansholt, Rasmus; Earth Science, School of Science
Aim Widespread greening and an increasing global terrestrial carbon sink over recent decades have been reported. However, the spatio-temporal relationships between vegetation greenness and productivity and the factors influencing this relationship remain unclear. We define a new metric of ecosystem-scale photosynthetic efficiency (EPE) to analyse its spatio-temporal pattern and investigate how potential drivers regulate the greenness–productivity relationship. Location Global. Time period From 2001 to 2016. Major taxa studied Global terrestrial ecosystems. Methods This study used global datasets of leaf area index (LAI) and solar-induced fluorescence (SIF) as proxies of vegetation greenness and ecosystem productivity, respectively, to propose a new metric of SIF/LAI, representing ecosystem-scale photosynthetic efficiency (EPE). We identified the spatial pattern and dynamics of EPE and examined factors influencing EPE. Results The results showed a weaker increase in productivity compared with the global greening rate from 2001 to 2016, suggesting a decline in EPE at the global scale. This decline in EPE indicates a disproportionate increase in terrestrial productivity against the widespread greening. When stratified into areas following an aridity gradient, we found that EPE overall showed upward trends in arid and semi-arid areas, and downward trends in dry sub-humid and humid regions. The EPE was controlled primarily by soil moisture, which promoted or constrained the EPE in xeric and mesic ecosystems, respectively. Moreover, the increase in short vegetation cover and atmospheric water demand contributed positively or negatively to EPE changes in xeric and mesic ecosystems, respectively. Main conclusions Our study shows that greening of the Earth is associated with decreasing EPE, revealing that current rates of carbon sequestration do not increase proportionally to greening of the Earth and highlighting that soil moisture is a key controller of EPE. These results help to reduce the uncertainties in future climate change impacts on vegetation dynamics, thus having implications for sustainable ecosystem management and climate change mitigation.
Improvement of diagnosis in children with Burkitt lymphoma in Kenya: feasibility study for the implementation of fluorescence in situ hybridisation testing for MYC and the MYC/IGH translocation
(eCancer, 2023-02-08) Vance, Gail H.; Lotodo, Teresa; Kigen, Nicholas; Stohler, Ryan; Choi, Haki; Njuguna, Festus; Moormann, Ann M.; Kirwa, Erastus; Langat, Sandra; Loehrer, Patrick; Vik, Terry; Medical and Molecular Genetics, School of Medicine
Background: Indiana University (IU) initiated fluorescence in situ hybridisation (FISH) methodology for Burkitt Lymphoma (BL) to advance the accuracy and speed of diagnosis in the AMPATH Reference Laboratory at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. Standard diagnostic testing for BL at MTRH includes morphology of the biopsy specimen or aspirate and limited immunohistochemistry panels. Methods: Tumour specimens from 19 children enrolled from 2016 to 2018 in a prospective study to improve the diagnosis and staging of children with suspected BL were evaluated. Touch preps from biopsy specimens or smears from fine needle aspiration were collected, stained with Giemsa and/or H&E and reviewed by pathologists to render a provisional diagnosis. Unstained slides were stored and later processed for FISH. Duplicate slides were split between two laboratories for analysis. Flow cytometry results were available for all specimens. Results from the newly established FISH laboratory in Eldoret, Kenya were cross-validated in Indianapolis, Indiana. Results: Concordance studies found 18 of 19 (95%) of specimens studied yielded analysable FISH results for one or both probe sets (MYC and MYC/IGH) in both locations. There was 94% (17/18) concordance of results between the two FISH laboratories. FISH results were 100% concordant for the 16 specimens with a histopathological diagnosis of BL and two of three non-BL cases (one case no result in IU FISH lab). FISH was similarly concordant with flow cytometry for specimens with positive flow results with the exception of a nasopharyngeal tumour with positive flow results for CD10 and CD20 but was negative by FISH. The modal turn-around time for FISH testing on retrospective study specimens performed in Kenya ranged between 24 and 72 hours. Conclusion: FISH testing was established, and a pilot study performed, to assess the feasibility of FISH as a diagnostic tool for the determination of BL in a Kenyan paediatric population. This study supports FISH in limited resource settings to improve the accuracy and speed of diagnosis of BL in Africa.
Evaluation of Race and Ethnicity Across a Statewide System of Early Autism Evaluation
(Elsevier, 2023-03) Martin, Ann Marie; Ciccarelli, Mary R.; Swigonski, Nancy; McNally Keehn, Rebecca; Pediatrics, School of Medicine
We evaluated racial and ethnic disparities across the Early Autism Evaluation Hub system, a statewide network for autism diagnosis. Our findings suggest that this system has the potential to reduce longstanding disparities in autism spectrum disorder diagnosis for children from racial and ethnic minority backgrounds.