Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area

Recent evidence suggests that structural and functional abnormalities of primary cilia in kidney epithelia are associated with mouse and human autosomal dominant polycystic kidney disease. To determine whether fibrocystin/polyductin/tigmin (FPC), the protein product encoded by the PKHD1 gene that is responsible for autosomal recessive polycystic kidney disease among human subjects, is also a component of primary cilia in the kidney, antipeptide antibodies to the carboxyl-terminal intracellular domain and amino-terminal extracellular domain of FPC were generated and were characterized with immunoblotting and immuno-light and -electron microscopy. Immunolocalization in normal kidney tissue sections and cultured kidney cells demonstrated that FPC was localized to the primary cilia and concentrated on the basal bodies in both kidney tissue sections and cultured kidney cells. The FPC expression pattern was not altered in kidney cells with Pkd1 mutations. These findings suggest that FPC is a functional and/or structural component of primary cilia in kidney tubular cells. It is proposed that the pathogenesis of autosomal recessive polycystic kidney disease is linked to the dysfunction of primary cilia

Evolution of the Galapagos in the anthropocene

The Galapagos Islands inspired the theory of evolution by means of natural selection; now in the Anthropocene, the Galapagos represent an important natural laboratory to understand ecosystem resilience in the face of climate extremes and enable effective socio-ecological co-evolution under climate change

Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma

Importance: Ulceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of β-blocker therapy for IH. Objectives: To examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. Design, setting, and participants: A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. Exposures: Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (β-blocker, corticosteroids), and procedural (pulsed-dye laser). Main outcomes and measures: The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. Results: Of the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic β-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration. Conclusions and relevance: Despite the use of β-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (≤1 mg/kg/d) should be considered

Magnesium- and intermetallic alloys-based hydrides for energy storage: modelling, synthesis and properties

International audienceAbstract Hydrides based on magnesium and intermetallic compounds provide a viable solution to the challenge of energy storage from renewable sources, thanks to their ability to absorb and desorb hydrogen in a reversible way with a proper tuning of pressure and temperature conditions. Therefore, they are expected to play an important role in the clean energy transition and in the deployment of hydrogen as an efficient energy vector. This review, by experts of Task 40 ‘Energy Storage and Conversion based on Hydrogen’ of the Hydrogen Technology Collaboration Programme of the International Energy Agency, reports on the latest activities of the working group ‘Magnesium- and Intermetallic alloys-based Hydrides for Energy Storage’. The following topics are covered by the review: multiscale modelling of hydrides and hydrogen sorption mechanisms; synthesis and processing techniques; catalysts for hydrogen sorption in Mg; Mg-based nanostructures and new compounds; hydrides based on intermetallic TiFe alloys, high entropy alloys, Laves phases, and Pd-containing alloys. Finally, an outlook is presented on current worldwide investments and future research directions for hydrogen-based energy storage

Large-Scale Spatial Distribution Patterns of Echinoderms in Nearshore Rocky Habitats

This study examined echinoderm assemblages from nearshore rocky habitats for large-scale distribution patterns with specific emphasis on identifying latitudinal trends and large regional hotspots. Echinoderms were sampled from 76 globally-distributed sites within 12 ecoregions, following the standardized sampling protocol of the Census of Marine Life NaGISA project (www.nagisa.coml.org). Sample-based species richness was overall low (<1–5 species per site), with a total of 32 asteroid, 18 echinoid, 21 ophiuroid, and 15 holothuroid species. Abundance and species richness in intertidal assemblages sampled with visual methods (organisms >2 cm in 1 m(2) quadrats) was highest in the Caribbean ecoregions and echinoids dominated these assemblages with an average of 5 ind m(−2). In contrast, intertidal echinoderm assemblages collected from clearings of 0.0625 m(2) quadrats had the highest abundance and richness in the Northeast Pacific ecoregions where asteroids and holothurians dominated with an average of 14 ind 0.0625 m(−2). Distinct latitudinal trends existed for abundance and richness in intertidal assemblages with declines from peaks at high northern latitudes. No latitudinal trends were found for subtidal echinoderm assemblages with either sampling technique. Latitudinal gradients appear to be superseded by regional diversity hotspots. In these hotspots echinoderm assemblages may be driven by local and regional processes, such as overall productivity and evolutionary history. We also tested a set of 14 environmental variables (six natural and eight anthropogenic) as potential drivers of echinoderm assemblages by ecoregions. The natural variables of salinity, sea-surface temperature, chlorophyll a, and primary productivity were strongly correlated with echinoderm assemblages; the anthropogenic variables of inorganic pollution and nutrient contamination also contributed to correlations. Our results indicate that nearshore echinoderm assemblages appear to be shaped by a network of environmental and ecological processes, and by the differing responses of various echinoderm taxa, making generalizations about the patterns of nearshore rocky habitat echinoderm assemblages difficult