Uvod: Enteralno hranjenje provodi se kod bolesnika koji imaju poremećaj gutanja (disfagija). Hranjenje uporabom perkutane gastrostome (engl. PEG) indicirano je kod bolesnika koji duže od 4 tjedna ...nisu u sposobnosti uzimati hranu peroralnim putem, dok je za bolesnike kod kojih se očekuje oporavak sposobnosti gutanja u periodu kraćem od 4 tjedna preporučeno hranjenje uporabom
nazogastrične sonde (engl. NGS). Uspostavljanje ponovne peroralne prehrane ovisi o različitim čimbenicima, zahtijeva individualni pristup bolesniku u koji su uključeni svi članovi interdisciplinarnog zdravstvenog tima.
Cilj: Svrha rada je prikazati uzorak bolesnika koji su imali poremećaj gutanja, a tijekom liječenja uporabljene su metode NGS i PEG u odnosu na ukupan broj bolesnika, koji su se nalazili na medicinskoj rehabilitaciji, i to poslije traumatske ozljede mozga. Opisuje skupinu ispitanika kod kojih je došlo do oporavka sposobnosti gutanja na završetku medicinske rehabilitacije u odnosu na uporabljene metode zdravstvene njege. Rezultati omogućavaju usporedbu krajnjih ishoda liječenja bolesnika prilikom otpusta, koja se odnosi na sposobnost gutanja, te su statistički mjerljivi i komparabilni.
Zaključak: Enteralno hranjenje bolesnika indicirano je za osiguravanje nutritivnog balansa bolesnika koji su pretrpjeli traumu mozga te kod kojih je verificirano postojanje poremećaja akta gutanja. Hranjenje uporabom PEG-sonde danas je standard u liječenju bolesnika s dugotrajnim poremećajem akta gutanja i znatna je učestalost uporabe metode hranjenja tijekom medicinske rehabilitacije. Cilj osiguravanja nutritivne sigurnosti u bolesnika je smanjenje stope mortaliteta i rizik od nastanka neželjenih komplikacija dekubitus, i skraćenje
duljine vremenskog trajanja hospitalizacije te posljedično znatnog smanjenja troškova liječenja.
People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability ...explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down.
Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids.
Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage.
Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies.
Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements".
Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) ...amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established “biological-ageing-clock”) in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4–19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. Funding: Main funding came from the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the “Acknowledgements”.
