Izhodišče: Okužbe sečil se pri novorojenčkih pojavljajo bolj pogosto kot pri starejših otrocih. V raziskavi smo želeli analizirati klinično sliko in povezavo s strukturnimi nepravilnostmi sečil ter ...pridobiti pregled nad povzročitelji in njihovo občutljivostjo za antibiotike. Metode: V retrospektivno raziskavo smo vključili novorojenčke, ki so bili zaradi okužbe sečil hospitalizirani na Kliničnem oddelku za neonatologijo Pediatrične klinike med letoma 2013 in 2021. Podat-ke smo pridobili s pomočjo bolnišničnega informacijskega sistema Clinical. Rezultati: V raziskavo je bilo vključenih 274 novorojenčkov, od tega 69 % dečkov. Delež bolnikov s pridruženimi nepravilnostmi sečil je znašal 39,8 %. Klinični znaki ob sprejemu so bili nespecifični, najpogosteje so se pojavljali vročina (37,1 %), slabše hranjenje (21,5 %) in razdražljivost oziroma neutolažljiv jok (17,1 %). Najpogosteje dokazani povzročitelj okužbe je bila Escherichia coli (60,4 %). Antibiotično zdravljenje je večinoma potekalo v parenteralni obliki (74,8 %) in je v povprečju trajalo 9,6 dneva (mediana 7 dni). Najpogosteje izbrano empirično antibiotično zdravljenje je bilo zdravljenje z ampicilinom in gentamicinom (61,3 %). V 36,5 % je bila osamljena bakterija odporna proti enemu od testiranih antibiotikov. Escherichia coli je bila najpogosteje (36,7 %) odporna proti ampicilinu in v 1,8 % proti gentamicinu. Zaključek: Okužbe sečil se pri novorojenčkih lahko kažejo z nespecifičnimi znaki. Velik delež novorojenčkov ima pridružene nepravilnosti sečil – ti običajno zbolevajo bolj zgodaj kot novorojenčki z zdravimi sečili. Pri tej skupini bolnikov je najpogostejši povzročitelj okužbe prav tako Escherichia coli, a v manjšem deležu, in je v tretjini primerov odporna proti ampicilinu in le redko proti gentamicinu.
The complete assembly of each human chromosome is essential for understanding human biology and evolution
. Here we use complementary long-read sequencing technologies to complete the linear assembly ...of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08-Mb centromeric α-satellite array, a 644-kb copy number polymorphism in the β-defensin gene cluster that is important for disease risk, and an 863-kb variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric α-satellite array is generally methylated except for a 73-kb hypomethylated region of diverse higher-order α-satellites enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. In addition, we confirm the overall organization and methylation pattern of the centromere in a diploid human genome. Using a dual long-read sequencing approach, we complete high-quality draft assemblies of the orthologous centromere from chromosome 8 in chimpanzee, orangutan and macaque to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved in the great ape ancestor with a layered symmetry, in which more ancient higher-order repeats locate peripherally to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated by more than 2.2-fold compared to the unique portions of the genome, and this acceleration extends into the flanking sequence.
Data suggest that food allergies greatly impact a child's health and growth due to inadequate nutrient intake. Our study aimed to establish the long-term outcome of children with food allergies ...compared to a control group.
This study was a retrospective cohort study with longitudinal follow-up with a mean period of 4.85 years from the diagnosis to the last study visit. The patients' nutritional intake was assessed using a three-day food diary and analysed by a dietitian. Patients (61 boys and 33 girls, mean age 6.9 years) had a single food allergy including 21 patients with cow's milk, 34 with egg, and 39 with peanut allergies. The control group included 36 children (19 boys and 17 girls, mean age 8.03 years). Blood analysis was performed on all participants.
Data from our study showed that patients with cow's milk, egg or peanut allergies had normal growth and achieved catch-up growth from the diagnosis until the last study visit. In the cow's milk allergy group, the allergy was shown to affect calcium intake (
< 0.05), while egg and peanut allergies did not impact the dietary intake of nutrients. None of the investigated food allergies affected blood results (
< 0.05).
In the present study, we showed that single food allergies do not compromise growth in children if they are provided with appropriate support and that the affected children reach catch-up growth from the diagnosis.
NaYF4 nanoparticles codoped with Yb3+ and Tm3+ exhibit upconversion fluorescence in near-infrared and visible spectral range. Consequently, such upconverting nanoparticles (UCNPs) can be used as ...contrast agents in medical diagnostics and bioassays. However, they are not chemically stable in aqueous dispersions, especially in phosphate solutions. Protective amphiphilic-polymer coatings based on poly(maleic anhydride-alt-octadec-1-ene) (PMAO) and bis(hexamethylene) triamine (BHMT) were optimised to improve the chemical stability of UCNPs under simulated physiological conditions. Morphologies of the bare and coated UCNPs was inspected with transmission electron microscopy. All samples showed intense UC fluorescence at ~800 nm, typical for Tm3+. The colloidal stability of aqueous dispersions of bare and coated UCNPs was assessed by dynamic light scattering and measurements of zeta potential. The dissolution of UCNP in phosphate-buffered saline at 37 °C, was assessed potentiometrically by measuring the concentration of the dissolved fluoride. Protection against the dissolution of UCNPs was achieved by PMAO and PMAO crosslinked with BHMT.
The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors ...(HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval CI 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to “not reached”). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).
•Panobinostat induces responses in 28% of patients with relapsed and refractory DLBCL that are typically durable off therapy.•MEF2B mutations predicted for response whereas early increase in ctDNA abundance was a strong predictor of subsequent treatment failure.
The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects ...the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.
To estimate the incidence and describe the spectrum of inflammatory and autoimmune diseases linked to SARS-CoV-2 infection and COVID-19 vaccination in children from two neighbouring south central ...European countries.
We performed a multi-centre prospective cohort study of children under 18 years diagnosed with inflammatory/autoimmune diseases linked to SARS-CoV-2 infection or COVID-19 vaccination, who were admitted to the paediatric tertiary care hospitals in Slovenia and Friuli Venezia Giulia, Italy, from January 1, 2020, to December 31, 2021. Disease incidence was calculated based on laboratory-confirmed cases only.
Inflammatory and autoimmune diseases linked to SARS-CoV-2 were diagnosed in 192 children (127 laboratory-confirmed), of whom 112 had multisystem inflammatory syndrome (MIS-C), followed by vasculitis, neurological and cardiac diseases. Calculated risk of MIS-C was 1 in 860 children after SARS-CoV-2 infection and cumulative incidence of MIS-C was 18.3/100,000 of all children. Fifteen children had severe COVID-19. Two patients with MIS-C and a patient with myositis presented after COVID-19 vaccination. All 3 had at presentation also a serologically proven recent SARS-CoV-2 infection. After MIS-C, nine patients were vaccinated against COVID-19 and 25 patients had a SARS-CoV-2 reinfection, without recurrence of MIS-C.
Autoimmune diseases following SARS-CoV-2 infection in children were 8.5 times as common as severe COVID-19. MIS-C was the most common manifestation and its incidence in this predominantly white population was higher than previously reported. MIS-C does not seem to recur after SARS-CoV-2 reinfection or COVID-19 vaccination. Autoimmune diseases were much more common after SARS-CoV-2 infection than after COVID-19 vaccination.
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