A survey on lifestyle restrictions in children with asthma: A comparison with Quality of Life (QoL)

Objectives: To describe the Quality of Life and the restrictions imposed by parents and caregivers of asthmatic children aged 7-15 years.Methods: This comparative cross sectional study was conducted at outpatient clinics of two hospitals in Colombo. Children with physician diagnosed bronchial asthma, aged 7-15 years were recruited by systematic random sampling. The QoL was assessed using Mini Paediatric Asthma Quality of Life Questionnaire (MPAQoLQ). QoL was categorized as good (score=1.00-3.00) moderate (3.01-5.00) and poor (5.01-7.00).Results: A total of 254 completed questionnaires were returned. The mean MPAQoLQ score was 4.9. Six (2.4%) had poor, 116(45.7%) had moderate and 132(52%) had good scores. There were significant restrictions to food items, such as cold/chilled food (n=202; 79.5%), eggs (n=159; 62.6%), fresh milk (n=159; 62.6%) and soya bean products (n=127; 50.0%). Furthermore physical activity (n=23; 9.1%) and playing with pets (n=197; 77.6%) were restricted. There was a statistically significant association between MPAQoLQ score and restrictions on cold/chilled food (p=0.000), soya bean products (p=0.001), physical activity (p=0.000) and bathing (p=0.001).Conclusions: Quality of life of children with asthma is affected and it is in par with statistics of developed countries. However, dietary restrictions were highly prevalent (93.3%). These restrictions may be related to myths and beliefs in our society. Caregiver education on diet and lifestyle should be an integral part of out-patient management

Employing epigenetic memory and native instructive stimuli to stimulate iPS-NLC differentiation

Notochordal cells (NCs) are linked to a healthy intervertebral disc (IVD), and are considered a promising candidate for cell-based therapies. However, NCs are scarcely available as they are lost early in life, and attempts at in vitro expansion have failed because NCs lose their specific phenotype. The production of notochordal-like cells (NLCs) from human induced pluripotent stem cells (hiPSCs) is a viable alternative. Therefore, this study aimed to build on the tissue-specific epigenetic memory of hiPSCs derived from IVD-progenitor cells (TIE2+-cells) and the instructive capacity of decellularized notochordal cell-derived matrix (dNCM)2 to improve hiPSC differentiation towards mature, healthy matrix-producing NLCs. hiPSCs were generated from TIE2+-IVD cells of three adult donors. As a comparison donor-matched minimally invasive peripheral blood mononuclear (PBM)-derived iPSCs were used. Firstly, hiPSCs were differentiated into mesendodermal progenitors by Wnt pathway activation (N2B27 medium + 3µM CHIR99021)1 for 2 days. Thereafter, the cells were further driven towards the NC-lineage by transfection with synthetic NOTO mRNA1 and matured by switching to a 3D-cell pellet culture in discogenic medium containing 10ng/mL TGF-β1 or 3mg/mL dNCM until day 28. Read-outs included cell morphology, gene and protein expression and matrix deposition. Both TIE2+- and PBM-cell derived hiPSC showed successful differentiation towards mesendodermal progenitors following Wnt-activation on day 2, indicated by the cells moving out of the colonies after CHIR stimulation. Accordingly, a decreased gene expression of pluripotency markers (OCT4, SOX2, NANOG), and upregulation of Wnt and Nodal signaling (LEF1, NODAL) and mesendodermal markers (FOXA2, TBXT) was detected, compared to mTeSR1 controls. This was confirmed by immuno-stains for FOXA2 and TBXT. On day 3, we detected a significant increase in NOTO mRNA levels in all donor lines after transfection compared to untransfected cell pellets. 3D-pellets of all donor lines showed glycosaminoglycan (GAG)- and collagen type II-rich areas after dNCM- but not TGF-β1-treatment on day 28. This was confirmed with the DMMB-assay, showing a significantly increased GAG content in the 3D-pellets treated with dNCM compared to TGF-β1. Next to that, TIE2+-cell derived iPSC pellets contained a significantly higher GAG content after dNCM-treatment compared to the PBM-cell derived hiPSC pellets. Immunohistochemical evaluation showed a heterogeneous cell population including cells positive for chondrogenic- (ACAN, SOX9), NPC/NC- (panKRT, T), and IVD progenitor- markers (CD24, TIE2). In conclusion, using tissue-specific TIE2+-cell derived hiPSCs combined with dNCM-treatment may allow for an improved differentiation capacity indicated by the increased deposition of GAG and collagen type II-rich matrix. However, the obtained cell population is still very heterogeneous and further transcriptome analysis could unravel whether the 3D-pellets contain cells which were successfully driven towards the notochordal-lineage and how these can be enriched based on unique NC-specific markers. Next to that, delineating which epigenetic features are retained after reprogramming of these two cell lines, could shed light on the observed differences in their differentiation capacity. These insights could be used for further optimization of iPS-NLC differentiation and allow for a more purified population of mature, healthy matrix-producing NLCs. This work was funded by Horizon 2020 (no. 825925) and the Dutch Arthritis Society (LLP22). References 1Colombier, P. et al. (2020). NOTO transcription factor directs human induced pluripotent stem cell-derived mesendoderm progenitors to a notochordal fate. Cells, 9(2), 509. 2Bach, Frances C., et al. "Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside." Oncotarget 9.41 (2018): 26507

Weak charge form factor and radius of 208Pb through parity violation in electron scattering

We use distorted wave electron scattering calculations to extract the weak charge form factor F_W(q), the weak charge radius R_W, and the point neutron radius R_n, of 208Pb from the PREX parity violating asymmetry measurement. The form factor is the Fourier transform of the weak charge density at the average momentum transfer q=0.475 fm$^{-1}$. We find F_W(q) =0.204 \pm 0.028 (exp) \pm 0.001 (model). We use the Helm model to infer the weak radius from F_W(q). We find R_W= 5.826 \pm 0.181 (exp) \pm 0.027 (model) fm. Here the exp error includes PREX statistical and systematic errors, while the model error describes the uncertainty in R_W from uncertainties in the surface thickness \sigma of the weak charge density. The weak radius is larger than the charge radius, implying a "weak charge skin" where the surface region is relatively enriched in weak charges compared to (electromagnetic) charges. We extract the point neutron radius R_n=5.751 \pm 0.175 (exp) \pm 0.026 (model) \pm 0.005 (strange) fm$, from R_W. Here there is only a very small error (strange) from possible strange quark contributions. We find R_n to be slightly smaller than R_W because of the nucleon's size. Finally, we find a neutron skin thickness of R_n-R_p=0.302\pm 0.175 (exp) \pm 0.026 (model) \pm 0.005 (strange) fm, where R_p is the point proton radius.Comment: 5 pages, 1 figure, published in Phys Rev. C. Only one change in this version: we have added one author, also to metadat

Maternal Responses in the Face of Infection Risk

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of infection risk on maternal responses, we exposed healthy female Japanese quail to either an immune-challenged (lipopolysaccharide [LPS] treated) mate or to a healthy (control) mate. We first assessed how females responded behaviorally to these treatments. Exposure to an immune-challenged or control male was immediately followed by exposure to a healthy male, to determine whether treatment affected paternity allocation. We predicted that females paired with immune-challenged males would avoid and show aggression towards those males, and that paternity would be skewed towards the healthy male. After mating, we collected eggs over a 5-day period. As an additional control, we collected eggs from immune-challenged females mated to healthy males. We tested eggs for fertilization status, embryo sex ratio, as well as albumen corticosterone, lysozyme activity, and ovotransferrin, and yolk antioxidant capacity. We predicted that immune-challenged females would show the strongest changes in the egg and embryo metrics, and that females exposed to immune-challenged males would show intermediate responses. Contrary to our predictions, we found no avoidance of immune-challenged males and no differences in terms of paternity allocation. Immune-challenged females laid fewer eggs, with an almost bimodal distribution of sex ratio for embryos. In this group, albumen ovotransferrin was the lowest, and yolk antioxidant capacity decreased over time, while it increased in the other treatments. No differences in albumen lysozyme were found. Both females that were immune-challenged and those exposed to immune-challenged males deposited progressively more corticosterone in their eggs over time, a pattern opposed to that shown by females exposed to control males. Our results suggest that egg-laying Japanese quail may be able to respond to infection risk, but that additional or prolonged sickness symptoms may be needed for more extensive maternal responses

Species diversity and forage value of herbage in a neglected coconut land proposed for livestock integration

The proposed coconut land is situated in the southern province. belongs to the land suitability class S4which is moderately suitable for coconut. Therefore, managing coconut as rnonoculture is unprofitableand steps have been taken to optimize the land use through livestock integration. Therefore, objectiveof this study was to investigate the species diversity and forage value of understory vegetation in thecoconut land before introducing cattle. Stratified quadrate sampling technique was adopted and 4samples each from 6 paddocks (approx 0.4 ha) were randomly taken. Each stratum contained morethan 80% of edible species while the non edible species found in all strata were common uplandweeds Axonopus affinus (carpet grass), Axonopus compressus (narrow carpet grass) andDesmodium trifolium were dominant prostate grass and legume species found in 0-5 em strataabove ground level. In addition to above species Pueraria phasioloides (Centro) was found to bedominant in 5-15 em strata. Crysopogen ariculatus and Pueraria phasioloides were dominant in15-25 cm strata while Seteria anceps (fox tail grass) found to be dominant above 25 em height. Thecommon non-edible species found in the lower two strata's were Urena lobota, Hemidcsmus indicumand Ocimum tenuiflorum while Lantana camara and Ocimum tenuiflorum were dominant in uppertwo strata's. The dry matter (DM) and crude protein (CP) content of edible herbage increased frombottom to top layers ranged from 390 gkg' to 480 gkg' and 75 gkg' to 100 gkg' respectively.The results of this study reveal that the species diversity and forage value are in an acceptablestandard to initiate cattle grazing. However, crop and cattle management strategies are important inorder to improve coconut and livestock performance.

Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization

Objective: VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis. Approach and Results: We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4. Conclusions: We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies