Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the ...characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia.
A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared.
Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group.
MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.
Growth Arrest-Specific 1 (Gas1) is a pleiotropic protein with different functions, in the adult kidney Gas1 acts as an endogenous inhibitor of cell proliferation but it is also necessary for the ...maintenance and proliferation of Renal Progenitor Cells (RPC) during early development, thus it fulfills important functions in the adult kidney. However, it is not known whether or not Gas1 is expressed during postnatal development, a critical stage for renal maturation. For this reason, the main objective of this work was to characterize the expression pattern of Gas1 in the different regions of the kidney by immunofluorescence and Western blot analysis during the postnatal development of the rat. We found that Gas1 is present and has a differential expression pattern in the various regions of the nephron during postnatal development. We observed that the highest levels of expression of Gas1 occur in the adult, however, Gas1 is also expressed in RPC and interestingly, the expression of RPC markers such as the Neural cell adhesion molecule (NCAM) and Cluster of differentiation 24 (CD24) were found to have an inverse pattern of expression to Gas1 (decreases as the kidney matures) during postnatal renal maturation, this indicates a role for Gas1 in the regulation of renal cell proliferation at this stage of development.
A eutectic mixture of L‐menthol and malonic acid, Me/MA (4 : 1), was characterized by calorimetry and other physical measurements. The new deep eutectic solvent (m.p. 6 °C) solvates 338 mg of ...ibuprofen per mL, and the solution is stable in a wide temperature range. Strategies of NMR titration used in supramolecular chemistry were employed to explore binding forces between the eutectic constituents as well as solute‐solvent interaction in ibuprofen solution. Even in acetonitrile, Me4MA is formed through a hydrogen‐bonding network, where the constituents act as hydrogen donors and acceptors at the same time. The estimated association constant is around 30 M−1; the binding forces are enough to build the eutectic mixture at high concentrations. The aggregate Me4MA forms a molecular complex with ibuprofen in acetonitrile as a result of the cooperative effect of the constituents. In addition, van der Waals interactions are operative between ibuprofen and menthol in the saturated IB‐Me/MA (4 : 1) solution.
The type and strength of the non‐covalent interactions that take place in a solution of ibuprofen in a new natural deep eutectic solvent (NADES), based on L‐menthol, were investigated through NMR methods. Even in acetonitrile, a hydrogen‐bonding network is formed between the components of the solvent. As a result of the cooperative effect of the constituents, a molecular complex is also formed with ibuprofen.
•Dravet syndrome (DS) is a severe disease with high unmet needs.•DS is associated with important burden for patients and the healthcare system.•Fenfluramine provides greater value than alternatives ...in DS.•Multicriteria Decision Analysis is useful to assess value contribution in DS.
Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles.
Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients’ Quality of Life (QoL).
Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA.
A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology.
Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine’s therapeutic impact on patients with DS is considered high and supported by high-quality evidence.
Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.
An underlying diagnosis of keratoconus (KC) can complicate cataract surgery. In this study, the results of a focused review of the literature pertaining to cataract surgery in patients with KC are ...detailed. Topics essential for the appropriate management of this patient population are discussed. First, the individual and shared epidemiology and pathophysiology of cataract and KC are reviewed. Then, the theory and approach to intraocular lens power calculation are discussed, highlighting particularities and pitfalls of this exercise when performed in patients with KC. Finally, several special-although not uncommon-management scenarios and questions are addressed, such as surgical planning in cases where corneal stabilization or tissue replacement interventions are also necessitated.
Based on a detailed geological map and stratigraphy aided by new 230Th/238U and 206P/238U age determinations we established the eruptive chronology of the Tres Vírgenes Volcanic Complex (TVVC). The ...complex consists of three northeast-southwest aligned stratovolcanoes, which from older to younger are El Viejo, El Azufre, and La Virgen and associated cinder cones and domes. The alignment was fed from fissures that mark the southern trace of the left-lateral Cimarron Fault. The TVVC was built upon the basement rocks of the Peninsular Ranges Batholith (~99 Ma), the Santa Lucia Formation (21.6 Ma), the Esperanza basalt (7.6 Ma), and the 1.1 Ma ignimbrite of El Aguajito caldera. The TVVC began its formation at ca. 300 ka mainly with dacitic lava flows and domes that formed El Viejo volcano (4.2 km3). At around 173 ka, activity migrated to the southwest to build El Azufre volcano (3.8 km3) with the emission of dacitic lavas and several phases of dome construction and destruction with the generation of pyroclastic density currents. El Azufre's activity ended ~128 ka with the extrusion of the summit dome. At about 112 ka, volcanism migrated 4.2 km to the southwest to begin the construction of La Virgen Volcano through the emission of andesitic and dacitic lavas that built the largest cone of the complex until ~22 ka (31.2 km3). This volcano was built upon several stages of cone construction with the emission of lava flows and peripheral dacitic domes and cinder cones. Between 128 and 112 ka six cinder cones vented along the Cimarron Fault between the La Virgen and El Azufre volcanoes. By assuming a constant emission of magma the total volume of the TVVC (39 km3) was erupted at an average rate of 0.13 km3/kyr. Of this volume, effusive eruptions dominated the evolution of the complex (89%) of which 62% are dacites and 38% andesites. The TVVC rocks have compositions of 50–67 wt% in silica, and low-medium K (0.5–2.5 wt% K2O). Trace element signatures of the TVVC rocks (Sr/Y <40, La/Yb <10, Nb-Ti negative anomalies and relative enrichments of LILE and LREE) suggest a post-subduction mixture between adakitic and calc-alkaline magmas. Xenoliths of granodiorites hosted in lavas and La Virgen tephra suggest that magma chambers feeding the complex have stagnated at depths >2 km within the Peninsular Ranges Batholith as confirmed by geobarometry, aeromagnetic data, and the drill-holes of the geothermal field. Today, the Tres Vírgenes geothermal field generates 10 MW of electricity although future exploration of several nearby areas may increase such capacity.
•The Tres Vírgenes Volcanic Complex lies along a left-lateral fault system caused by a transtensional stress regime.•The ~300 ka Tres Vírgenes Volcanic Complex emplaced 39 km3 of magma over an area of 120 km2.•The volcanic complex has emitted andesitic to dacitic magmas from 300 to 22 ka.•Shallow intrusive bodies located about >1.2 km deep could provide a potential geothermal source.
The growth of health care spending on older adults with chronic diseases faces major concerns that require effective measures to be adopted worldwide. Among the main concerns is whether recent ...technological advances now offer the possibility of providing remote health care for the aging population. The benefits of suitable prevention and adequate monitoring of chronic diseases by using emerging technological paradigms such as wearable devices and the Internet of Things (IoT) can increase the detection rates of health risks to raise the quality of life for the elderly. Specifically, on the subject of remote health monitoring in older adults, a first approach is required to review devices, sensors, and wearables that serve as tools for obtaining and measuring physiological parameters in order to identify progress, limitations, and areas of opportunity in the development of health monitoring schemes. For these reasons, a review of articles on wearable devices was presented in the first instance to identify whether the selected articles addressed the needs of aged adults. Subsequently, the direct review of commercial and prototype wearable devices with the capability to read physiological parameters was presented to identify whether they are optimal or usable for health monitoring in older adults.
MicroRNAs (miRNAs) are small RNA molecules recognized as important regulators of gene expression. Although plant miRNAs have been extensively studied in model systems, less is known in other plants ...with limited genome sequence data. We are interested in the identification of miRNAs in Phaseolus vulgaris (common bean) to uncover different plant strategies to cope with adverse conditions and because of its relevance as a crop in developing countries. Here we present the identification of conserved and candidate novel miRNAs in P. vulgaris present in different organs and growth conditions, including drought, abscisic acid treatment, and Rhizobium infection. We also identified cDNA sequences in public databases that represent the corresponding miRNA precursors. In addition, we predicted and validated target mRNAs amongst reported EST and cDNAs for P. vulgaris. We propose that the novel miRNAs present in common bean and other legumes, are involved in regulation of legume-specific processes including adaptation to diverse external cues.
We present a new 1:80,000-scale geologic map of the Acoculco caldera (Ac) located between the states of Puebla and Hidalgo in eastern México. The map, encompassing an area of 856 km
2
, is grounded ...on an ArcMap data set and is supported by nine new
40
Ar/
39
Ar dates. The caldera lies upon Cretaceous limestones and Miocene to Pliocene volcanic rocks (13-3 Ma). The caldera consists of 31 lithostatrigraphic units formed between 2.7 and 0.06 Ma that include a wide variety of volcanic landforms (cinder cones, lava domes). The caldera has a semi-circular shape (18-16 km) bounded by the Atotonilco scarp to the north, the NW-SE Manzanito fault to the west, and scattered vents to the east and southern parts. The distribution of the Acoculco ignimbrite, the lithic breccia, and lacustrine sediments define the caldera ring fault. Late Pleistocene activity and pervasive hydrothermal alteration suggest a high geothermal potential in the area.
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