Cardiopulmonary function, quality of life and effects of exercise in children and adolescents with Fontan circulation

Background Survival of children and adolescents with Fontan circulation has increased over the last decades, and today a large majority survive to adult age. There is increasing concern regarding these children’s impaired physical performance and quality of life. Little is known about the impact of exercise on cardiopulmonary function and quality of life in this patient group compared with the impact on healthy children. Aim The aims of this thesis were to study activity, physical capacity, lung function, quality of life, and sleep before and after an exercise intervention in patients with Fontan circulation and healthy matched controls. A follow-up, one year after the training programme, was also performed. We wanted to evaluate if physical exercise could improve cardiopulmonary function and also, most importantly, quality of life in this patient group. Method Patients with Fontan circulation (n = 30) and healthy controls (n = 25) performed measurements and/or assessments of physical activity including accelerometer recordings, submaximal and maximal exercise capacity, lung function, sleep, and quality of life. All examinations were done prior to and after an individualised endurance training programme for 12 weeks, and also after one year. Results Patients with Fontan circulation reported less time in regular physical exercise than healthy controls, though the objectively measured activity was similar. Quality of life was reported significantly lower by the patients and by their parents compared with the controls. After the exercise intervention, submaximal exercise capacity had increased and quality of life was improved for the patients. However, the exercise intervention did not have an impact on maximal exercise capacity for the patients. After one year, patients showed further improvement of submaximal exercise capacity and quality of life was still improved, as after the exercise intervention. Moreover, children with Fontan circulation had impaired lung function and a reduced pulmonary diffusing capacity. Diffusing capacity increased with age in the patients, but less than in the control subjects. Moreover, endurance training improved vital capacity in the patient group. Fontan patients seemed to have a prolonged latency to sleep onset compared with healthy children. Increased time in physical activities seemed to be correlated with better sleep quality in patients with Fontan circulation. Conclusions Structured individualized training programmes may improve submaximal exercise capacity, lung function, and quality of life in children with Fontan circulation. Also, the improvement of quality of life appears to remain, one year after the intervention. Increased amount of physical activity may also be beneficial for sleep quality for these patients. The clinical importance of our results is that increased physical activity is likely to be beneficial for cardiopulmonary function, quality of life, and sleep quality in this patient group. Thus, patients with Fontan palliation should be encouraged to regularly engage in individually designed sports and activities. Rehabilitation programmes should include structured individualised endurance training for improved outcome in this group of patients. Impaired health-related quality of life is most likely multifactorial and further research is needed to more fully understand the effects of exercise on cardiopulmonary function, sleep, and quality of life in this patient group. Also, more research is needed on how to individualise recommendations and find optimal regimens for exercise prescriptions from early age for these patients. The important message is, though, to encourage physical exercise for these patients for better health and well-being

Large Steel Tank Fails and Rockets to Height of 30 meters - Rupture Disc Installed Incorrectly

AbstractAt a brewery, the base plate-to-shell weld seam of a 90-m3 vertical cylindrical steel tank failed catastrophically. The 4 ton tank “took off” like a rocket leaving its contents behind, and landed on a van, crushing it. The top of the tank reached a height of 30 m. The internal overpressure responsible for the failure was an estimated 60 kPa. A rupture disc rated at < 50 kPa provided overpressure protection and thus prevented the tank from being covered by the European Pressure Equipment Directive. This safeguard failed and it was later discovered that the rupture disc had been installed upside down. The organizational root cause of this incident may be a fundamental lack of appreciation of the hazards of large volumes of low-pressure compressed air or gas. A contributing factor may be that the standard piping and instrumentation diagram (P&ID) symbol for a rupture disc may confuse and lead to incorrect installation. Compressed air systems are ubiquitous. The medium is not toxic or flammable. Such systems however, when operated at “slight overpressure” can store a great deal of energy and thus constitute a hazard that ought to be addressed by safety managers

New records of the Paleotropical migrant Hemianax ephippiger in the Caribbean and a review of its status in the Neotropics

Tropical America is currently experiencing the establishment of a new apex insect predator, the Paleotropical dragonfly Hemianax ephippiger (Odonata: Aeshnidae). H. ephippiger is migratory and is suggested to have colonised the eastern Neotropics by chance Trans-Atlantic displacement. We report the discovery of H. ephippiger at three new locations in the Caribbean, the islands of Bonaire, Isla de Coche (Venezuela), and Martinique, and we review its reported distribution across the Neotropics. We discuss the establishment of H. ephippiger as a new apex insect predator in the Americas, both in terms of ecological implications and the possible provision of ecosystem services. We also provide an additional new species record for Bonaire, Pantala hymenaea (Odonata: Libellulidae).Peer reviewe

Modeling Motor Neuron Resilience in ALS Using Stem Cells

Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry, and RNA sequencing, that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. We also show that in vitro-generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro that display a resilience similar to that seen in vivo.</p

Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations

[EN] Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified. We show that the full-length form of MORC2 is highly expressed in both embryonic and adult human neural tissues and that Morc2 expression is dynamically regulated in both the developing and the maturing murine nervous system. To determine the effect of the most common MORC2 mutations, p.S87L and p.R252W, we used several in vitro cell culture paradigms. Both mutations induced transcriptional changes in patient-derived fibroblasts and when expressed in rodent sensory neurons. These changes were more pronounced and accompanied by abnormal axonal morphology, in neurons expressing the MORC2 p.S87L mutation, which is associated with a more severe clinical phenotype. These data provide insight into the neuronal specificity of the mutated MORC2-mediated phenotype and highlight the importance of neuronal cell models to study the pathophysiology of CMT2Z.Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (PI15/00187 to C. E. and PI16/00403 to T. S.), co-funded with FEDER funds; Ramon Areces Foundation (CIVP17A2810 to C. E.); Generalitat Valenciana (PROMETEO/2018/135 to C. E. and T. S.); AFM-Telethon (21500 to C. E. and R. C.); National Health and Medical Research Council of Australia Grant (APP1046680 to M. K.); Czech Health Research Council (AZV16-30206A to P. L.); Swedish StratNeuro program grant; Swedish Research Council (2015-02394 to R. C.). C. E. had a 'Miguel Servet' contract funded by the ISCIII and the Centro de Investigacion Principe Felipe (CPII14/00002). P. S. is the recipient of a FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Sancho, P.; Bartesaghi, L.; Miossec, O.; García-García, F.; Ramírez-Jiménez, L.; Siddell, A.; Ajkesson, E.... (2019). Characterization of molecular mechanisms underlying the axonal Charcot-Marie-Tooth neuropathy caused by MORC2 mutations. Human Molecular Genetics. 28(10):1629-1644. https://doi.org/10.1093/hmg/ddz00616291644281

Description of two cultivated and two uncultivated new Salinibacter species, one named following the rules of the bacteriological code: Salinibacter grassmerensis sp. nov.; and three named following the rules of the SeqCode: Salinibacter pepae sp. nov., Salinibacter abyssi sp. nov., and Salinibacter pampae sp. nov.

Current -omics methods allow the collection of a large amount of information that helps in describing the microbial diversity in nature. Here, and as a result of a culturomic approach that rendered the collection of thousands of isolates from 5 different hypersaline sites (in Spain, USA and New Zealand), we obtained 21 strains that represent two new Salinibacter species. For these species we propose the names Salinibacter pepae sp. nov. and Salinibacter grassmerensis sp. nov. (showing average nucleotide identity (ANI) values < 95.09% and 87.08% with Sal. ruber M31T, respectively). Metabolomics revealed species-specific discriminative profiles. Sal. ruber strains were distinguished by a higher percentage of polyunsaturated fatty acids and specific N-functionalized fatty acids; and Sal. altiplanensis was distinguished by an increased number of glycosylated molecules. Based on sequence characteristics and inferred phenotype of metagenome-assembled genomes (MAGs), we describe two new members of the genus Salinibacter. These species dominated in different sites and always coexisted with Sal. ruber and Sal. pepae. Based on the MAGs from three Argentinian lakes in the Pampa region of Argentina and the MAG of the Romanian lake Fără Fund, we describe the species Salinibacter pampae sp. nov. and Salinibacter abyssi sp. nov. respectively (showing ANI values 90.94% and 91.48% with Sal. ruber M31T, respectively). Sal. grassmerensis sp. nov. name was formed according to the rules of the International Code for Nomenclature of Prokaryotes (ICNP), and Sal. pepae, Sal. pampae sp. nov. and Sal. abyssi sp. nov. are proposed following the rules of the newly published Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). This work constitutes an example on how classification under ICNP and SeqCode can coexist, and how the official naming a cultivated organism for which the deposit in public repositories is difficult finds an intermediate solution.This study was funded by the Spanish Ministry of Science, Innovation and Universities projects PGC2018-096956-B-C41, RTC-2017-6405-1 and PID2021-126114NB-C42, which were also supported by the European Regional Development Fund (FEDER). RRM acknowledges the financial support of the sabbatical stay at Georgia Tech and HelmholzZentrum München by the grants PRX18/00048 and PRX21/00043 respectively also from the Spanish Ministry of Science, Innovation and Universities. This research was carried out within the framework of the activities of the Spanish Government through the “Maria de Maeztu Centre of Excellence” accreditation to IMEDEA (CSIC-UIB) (CEX2021-001198). KTK’s research was supported, in part, by the U.S. National Science Foundation (Award No. 1831582 and No. 2129823). IMG. AC and HLB were financially supported by a grant of the Ministry of Research, Innovation and Digitization, CNCS/CCCDI – UEFISCDI, project number PN-III-P4-ID-PCE-2020-1559, within PNCDI III. HLB acknowledges Ocna Sibiului City Hall (Sibiu County, Romania) for granting the access to Fără Fund Lake and A. Baricz and D.F. Bogdan for technical support during sampling and sample preparation. MBS thanks Dominion Salt for their assistance in sample Lake Grassmere. MELL acknowledges the financial support of the Argentinian National Scientific and Technical Research Council (Grant CONICET-NSFC 2017 N° IF-2018-10102222-APN-GDCT-CONICET) and the National Geographic Society (Grant # NGS 357R-18). BPH was supported by NASA (award 80NSSC18M0027). TV acknowledges the “Margarita Salas” postdoctoral grant, funded by the Spanish Ministry of Universities, within the framework of Recovery, Transformation and Resilience Plan, and funded by the European Union (NextGenerationEU), with the participation of the University of Balearic Islands (UIB)