Background The purpose of this study was to examine the correlates of caregiver stress in a large sample of young people with autism spectrum disorders (ASDs). Two main objectives were to: (1) ...disentangle the effects of behaviour problems and level of functioning on caregiver stress; and (2) measure the stability of behaviour problems and caregiver stress.
Methods Parents or teachers of 293 young people with ASDs completed measures of stress, behaviour problems and social competence. Parents also completed an adaptive behaviour scale. Eighty‐one young people were rated twice at a 1‐year interval.
Results Parents and teachers did not perfectly agree on the nature and severity of behaviour problems. However, both sets of ratings indicated that behaviour problems were strongly associated with stress. Conduct problems in particular were significant predictors of stress. Adaptive skills were not significantly associated with caregiver stress. Parental reports of behaviour problems and stress were quite stable over the 1‐year interval, much more so than teacher reports. Parent ratings suggested that behaviour problems and stress exacerbated each other over time. This transactional model did not fit the teacher data.
Conclusion Results of this study suggested that it is a specific group of externalized behaviours that are the most strongly associated with both parent and teacher stress. Results were discussed from methodological and conceptual perspectives.
Abstract
Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information ...on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease IBD. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: i in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated with a particular focus on corticosteroids always with the purpose of treating active disease and maintaining remission; ii non-urgent surgeries and endoscopic procedures should be postponed for all patients; iii online consultancy should be implemented; and iv hospitalization and surgery should be limited to life-threatening situations.
Translationally relevant animal models are essential for the successful translation of basic science findings into clinical medicine. While rodent models are widely accessible, there are numerous ...limitations that prevent the extrapolation of findings to human medicine. One approach to overcome these limitations is to use animal models that are genetically diverse and naturally develop disease. For example, pet dogs spontaneously develop diseases that recapitulate the natural progression seen in humans and live in similar environments alongside humans. Thus, dogs represent a useful animal model for many areas of research. Despite the value of the canine model, species specific reagent limitations have hampered in depth characterization of canine immune cells, which constrains the conclusions that can be drawn from canine immunotherapy studies. To address this need, we used single-cell RNA sequencing to characterize the heterogeneity of circulating leukocytes in healthy dogs (n = 7) and osteosarcoma (OS) affected dogs (n = 10). We present a cellular atlas of leukocytes in healthy dogs, then employ the dataset to investigate the impact of primary OS tumors on the transcriptome of circulating leukocytes. We identified 36 unique cell populations amongst dog circulating leukocytes, with a remarkable amount of heterogeneity in CD4 T cell subtypes. In our comparison of healthy dogs and dogs with OS, we identified relative increases in the abundances of polymorphonuclear (PMN-) and monocytic (M-) myeloid-derived suppressor cells (MDSCs), as well as aberrations in gene expression within myeloid cells. Overall, this study provides a detailed atlas of canine leukocytes and investigates how the presence of osteosarcoma alters the transcriptional profiles of circulating immune cells.
The immature neonatal intestinal immune system hyperreacts to newly colonizing unfamiliar bacteria. The hypothesis that human milk oligosaccharides from colostrum (cHMOSs) can directly modulate the ...signaling pathways of the immature mucosa was tested. Modulation of cytokine immune signaling by HMOSs was measured ex vivo in intact immature (fetal) human intestinal mucosa. From the genes whose transcription was modulated by cHMOSs, Ingenuity Pathway Analysis identified networks controlling immune cell communication, intestinal mucosal immune system differentiation, and homeostasis. cHMOSs attenuate pathogen-associated molecular pattern-stimulated acute phase inflammatory cytokine protein levels (interleukin-8 (IL-8), IL-6, monocyte chemoattractant protein-1/2 and IL-1β), while elevating cytokines involved in tissue repair and homeostasis. In all, 3'-, 4-, and 6'-galactosyllactoses of cHMOSs account for specific immunomodulation of polyinosinic:polycytodylic acid-induced IL-8 levels. cHMOSs attenuate mucosal responses to surface inflammatory stimuli during early development, while enhancing signals that support maturation of the intestinal mucosal immune system.
Antiviral therapy in HCV liver cirrhosis does not prevent the onset of HCC. Even in the group with sustained virological response, HCC surveillance must be carried out with ultrasound imaging every 6 ...months.
The effect of different carbon doping techniques on the dynamic behavior of GaN-on-Si buffer was investigated. Intentional doping using a hydrocarbon precursor was compared with the more common ...autodoping technique. Breakdown and dynamic behavior of processed devices indicate that extrinsic carbon doping delivers better dynamic properties for the same blocking voltage capabilities. Modeling and simulations have revealed that charge transport across the GaN buffer is the main limiting factor during the buffer discharge process.
Glioblastoma is the most aggressive and most lethal primary brain tumor in the adulthood. Current standard therapies are not curative and novel therapeutic options are urgently required. Present ...knowledge suggests that the continued glioblastoma growth and recurrence is determined by glioblastoma stem-like cells (GSCs), which display self-renewal, tumorigenic potential, and increased radio- and chemo-resistance. The G-quadruplex ligand RHPS4 displays in vitro radiosensitizing effect in GBM radioresistant cells through the targeting and dysfunctionalization of telomeres but RHPS4 and Ionizing Radiation (IR) combined treatment efficacy in vivo has not been explored so far.
RHPS4 and IR combined effects were tested in vivo in a heterotopic mice xenograft model and in vitro in stem-like cells derived from U251MG and from four GBM patients. Cell growth assays, cytogenetic analysis, immunoblotting, gene expression and cytofluorimetric analysis were performed in order to characterize the response of differentiated and stem-like cells to RHPS4 and IR in single and combined treatments.
RHPS4 administration and IR exposure is very effective in blocking tumor growth in vivo up to 65 days. The tumor volume reduction and the long-term tumor control suggested the targeting of the stem cell compartment. Interestingly, RHPS4 treatment was able to strongly reduce cell proliferation in GSCs but, unexpectedly, did not synergize with IR. Lack of radiosensitization was supported by the GSCs telomeric-resistance observed as the total absence of telomere-involving chromosomal aberrations. Remarkably, RHPS4 treatment determined a strong reduction of CHK1 and RAD51 proteins and transcript levels suggesting that the inhibition of GSCs growth is determined by the impairment of the replication stress (RS) response and DNA repair.
We propose that the potent antiproliferative effect of RHPS4 in GSCs is not determined by telomeric dysfunction but is achieved by the induction of RS and by the concomitant depletion of CHK1 and RAD51, leading to DNA damage and cell death. These data open to novel therapeutic options for the targeting of GSCs, indicating that the combined inhibition of cell-cycle checkpoints and DNA repair proteins provides the most effective means to overcome resistance of GSC to genotoxic insults.
PDF
