Two parasitic ciliates (Protozoa: Ciliophora: Phyllopharyngea) isolated from respiratory-mucus of an unhealthy beluga whale: characterization, phylogeny and an assessment of morphological adaptations

Abstract Ciliates occur in the blowholes of marine mammals, but our understanding of their biology is poor. Consequently, we investigated an infestation of ciliates in an unhealthy, captive beluga whale that was exhibiting accelerated breathing, leukocytosis and expulsion of unusually large amounts of viscous sputum. This sputum contained ~104 ciliates mL-1 (when healthy, numbers were ten- to 100-fold lower). One known ciliate species, Planilamina ovata, is fully characterized, and a new species, Kyaroikeus paracetarius sp. nov., is here described. The new species is established based on its larger number of left kineties over its only congener. Sequences of small-subunit rDNA, large-subunit rDNA and ITS1-5.8S-ITS2 regions of these two taxa were used in phylogenetic analyses, inferring that Kyaroikeus and Planilamina have close affinity with the free-living family Dysteriidae, contradicting their morphology-based assignment to the family Kyaroikeidae. We suggest that Kyaroikeidae be relegated to subfamily status. Finally, by comparing parasitic species with free-living taxa, we suggest how these ciliates have adapted to their unique environment and how they may have initially invaded the host. We provide essential data and concepts for the continued evaluation of ciliate-parasites in whale blowholes.</jats:p

Correlation Between Bioelectrical Impedance Analysis and Chest CT-Measured Erector Spinae Muscle Area: A Cross-Sectional Study

BackgroundSkeletal muscle mass (SMM) plays an important part in diverse health and disease states. Bioelectrical impedance analysis (BIA) and computed tomography (CT) are available for its assessment. However, muscle mass assessed by BIA may be influenced by multiple factors. The erector spinae muscle area (ESA) on chest CT is recently presumed to be representative of SMM. This study aimed to derive BIA from the ESA and evaluate the magnitude of association (between ESA measured from chest CT) and BIA.MethodsSubjects hospitalized for health checkups between December 2020 and December 2021, having undergone both BIA (50 kHz, 0.8 mA) and chest CT, were included. ESA was quantified at the level of the 12th thoracic vertebra (T12-ESA) by a standardized semi-automated segmentation algorithm. Low SMM was defined using the Asian Working Group for Sarcopenia criteria. The association between T12-ESA and BIA was then evaluated. Stratified analyses by sex and BMI were also performed.ResultsAmong 606 included subjects (59.7 ± 16.6 years, 63.5% male), 110 (18.2%) had low SMM. BMI in low and normal SMM groups was 20.1 and 24.7 kg/m2, respectively. Current smoking, drinking, chronic obstructive pulmonary disease, and chronic renal dysfunction were more frequently seen in the low SMM group than in the normal SMM group. The final regression model included T12-ESA, weight, BMI, and age, and had an adjusted R2 of 0.806 with BIA. In the validation group, the correlation between T12-ESA-derived BIA and BIA remained high (Pearson correlation = 0.899). Stratified analysis disclosed a stronger correlation between T12-ESA and BIA in male subjects than in female subjects (adjusted R2 = 0.790 vs. adjusted R2 = 0.711, p &lt; 0.05), and a better correlation was observed in obese (BMI ≥ 30 kg/m2) compared with underweight (BMI &lt; 18.5 kg/m2) subjects (adjusted R2 = 0.852 vs. adjusted R2 = 0.723, p &lt; 0.05). Additional analysis revealed a significant correlation between T12-ESA and skeletal muscle cross-sectional area at the 3rd lumbar vertebra (L3-CSA) (adjusted R2 = 0.935, p &lt; 0.001).ConclusionsCT-based assessment of ESA at the T12 level is feasible and correlated well with BIA, especially in male subjects and obese subjects

Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans

It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain–containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (–7), deletions of 7q (7q–), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with –7 and 7q– developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized

Influenza A (H5N1) Viruses from Pigs, Indonesia

TOC summary: Pigs may serve as intermediate hosts in which this avian virus can adapt to mammals

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction

Background Immune checkpoint inhibitors (ICIs) have been an important therapeutic advancement in the field of cancer medicine. Recent reports provided greater insights into the cardiovascular adverse events, which prohibited the use of ICIs. Cardiovascular adverse events occur in different forms, such as myocarditis and cardiomyopathy, myocardial fibrosis, heart failure and pericardial disease. Cardiac aging overlapped with the occurrence of some cardiac diseases. Exosomes mediate cell–cell cross talk in cardiac diseases by transferring a variety of biomolecules, including microRNAs (miRs). miR-34a-5p is a well-known miR associated with the cardiac senescence. This study aimed to investigate whether cardiovascular adverse effects of the programmed cell death 1 (PD-1) inhibitor, a widely used ICI, were related to exosomal-transferred miR-34a-5p in cardiac senescence in a mouse model.Methods and results The upregulation of miR-34a-5p in cardiomyocytes induced by exosomes derived from PD-1 inhibitor–treated macrophages, accompanied by cardiac senescence, caused cardiac injury in mouse hearts. miR-34a-5p was identified as an exosomal transfer RNA to induce cardiac senescence–related injury. Inhibiting miR-34a-5p in macrophages attenuated the exosomePD-1 inhibitor-induced pro-senescent effect in cardiomyocytes. TargetScan and luciferase assay showed that miR-34a-5p targeted the serine/threonine-protein phosphatase 1 regulatory subunit 10 (PNUTS) 3′-untranslated region.Conclusions Exosomes derived from PD-1 inhibitor–treated macrophages exerted a pro-senescent effect by modulating the miR-34a-5p/PNUTS signaling pathway. The findings might supply new targets to ameliorate cardiac injury in patients with cancer receiving PD-1 inhibitor treatment

Predictor-Based Neural Dynamic Surface Control of a Nontriangular System With Unknown Disturbances

For a class of nontriangular nonlinear systems in presence of unknown disturbances, we propose a predictor-based neural dynamic surface control (PNDSC) strategy in this paper. This nontriangular system is transformed via the mean value theorem, and a predictor is then constructed. To avoid an algebraic loop problem, partial state vectors are employed as input signals of neural networks (NNs) for approximating unknown dynamics, and compensation items are designed to compensate for approximation errors from NNs. Different from the traditional NDSC, the PNDSC in this paper utilizes prediction errors to update learning parameters for improving NNs' learning behaviors with overlarge adaptive gains. On the basis of improved NNs' approximation behaviors, a predictor-based NNs disturbance observer (PNNDO) is constructed for compensation for external disturbances and approximation errors from NNs. Furthermore, with predictors, a normalization method of weights is developed to reduce the number of online learning parameters. On the basis of the aforementioned result, measurement noises are taken into account in our predictor-based neural control strategy. We employ predictor states, rather than measurement information paralyzed by noises, in design of our control strategy. This reduces high-frequency oscillations in control input. A Lyapunov-based stability analysis shows that all signals are ultimately bounded in the closed-loop system. Finally, the effectiveness of the proposed control strategy is verified by a numerical example and a permanent magnet brushless DC motor system