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The purpose of this pilot study was to examine the feasibility of a fundamental motor skills (FMS) intervention with two groups on the acquisition of FMS of children with autism spectrum disorders (ASD). We randomly assigned families (n = 15) of children with ASD aged 4–11 years into two groups (a workshop or a home-based group) focused on FMS development. Both groups participated in a 10-week intervention and were given the same instructional manual and adapted physical activity equipment. The workshop group also attended four in-person workshops targeting the needs of children with ASD and their parents. Children were tested on their FMS using the third edition of the Test of Gross Motor Development at the start and end of the intervention and then three months following the intervention. The recruitment rate was 50%, and the retention rate was 80% for all participants. The intervention for groups was safe and accepted by the participants as evaluated by post-program interviews. The outcomes of this pilot study suggest that parents can facilitate the acquisition of FMS of their children with ASD. Although these results are positive, there is a need to further identify effective interventions for FMS development in children with ASD.

Research supports that dance provides physical and psychological benefits to individuals with and without disabilities (Masunah, 2016). Students with disabilities can specifically benefit from dance because it can be easily modified and encourages self-expression. Therefore, general physical educators and adapted physical educators can play a key role in introducing dance to students. Confidence in teaching dance as part of the physical education curriculum is positively associated with experience in dance (Maclean, 2007), experience that many physical educators may not have. Thus, the purpose of this paper is to provide strategies that might assist teachers and physical activity professionals to confidently implement adapted dance fitness classes or programs in schools or communities. This article can serve as a framework for teachers to increase comfort level and improve the success of students during adapted dance fitness classes. Keywords: Adapted dance, aerobic dance, dance fitness, disability, physical activity, physical education

A major hallmark of cancer is successful evasion of regulated forms of cell death. Ferroptosis is a recently discovered type of regulated necrosis which, unlike apoptosis or necroptosis, is independent of caspase activity and receptor-interacting protein 1 (RIPK1) kinase activity. Instead, ferroptotic cells die following iron-dependent lipid peroxidation, a process which is antagonised by glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1). Importantly, tumour cells escaping other forms of cell death have been suggested to maintain or acquire sensitivity to ferroptosis. Therefore, therapeutic exploitation of ferroptosis in cancer has received increasing attention. Here, we systematically review current literature on ferroptosis signalling, cross-signalling to cellular metabolism in cancer and a potential role for ferroptosis in tumour suppression and tumour immunology. By summarising current findings on cell biology relevant to ferroptosis in cancer, we aim to point out new conceptual avenues for utilising ferroptosis in systemic treatment approaches for cancer.

The recently finalized research project “ZRR for municipal waste” aimed at testing and evaluating the automation of municipal waste sorting plants by supplementing or replacing manual sorting, with sorting by a robot with artificial intelligence (ZRR). The objectives were to increase the current recycling rates and the purity of the recovered materials; to collect additional materials from the current rejected flows; and to improve the working conditions of the workers, who could then concentrate on, among other things, the maintenance of the robots. Based on the empirical results of the project, this paper presents the main results of the training and operation of the robotic sorting system based on artificial intelligence, which, to our knowledge, is the first attempt at an application for the separation of bulky municipal solid waste (MSW) and an installation in a full-scale waste treatment plant. The key questions for the research project included (a) the design of test protocols to assess the quality of the sorting process and (b) the evaluation of the performance quality in the first six months of the training of the underlying artificial intelligence and its database.

Lurbinectedin is an oncogenic transcription inhibitor indicated for the treatment of small cell lung cancer (SCLC), which has also shown activity against other malignancies. In this work, two independent cohorts of 180 (discovery cohort) and 719 (validation cohort) cancer patients receiving lurbinectedin in Phases I, II, or III clinical trials were enrolled. Using a population pharmacokinetic (popPK) model of the discovery cohort, patients with extremely high (n = 10, cohort 1) and low (n = 10, cohort 2) etaCL values (i.e., a variable used as a surrogate of unexplained CL interindividual variability) were identified. They were sequenced for 42 candidate genes involved in lurbinectedin pharmacokinetics. A total of 34 variants located in 20 genes were significantly associated with lurbinectedin etaCL; the best nine hits (located in CYP3A5, CYP3A4, ABCB1, ARNT, NR5A2, NR1H4, and FOXA3) were subsequently genotyped in the validation cohort. A strong additive association between CYP3A4 and CYP3A5 genotypes (informed as a CYP3A activity score [AS] variable) and lurbinectedin clearance (CL) and exposure was confirmed, for example, patients with an AS of 3, 2, or 1 showed a 2.3‐, 1.6‐, and 1.5‐fold higher total lurbinectedin CL compared to those with an AS of 0 and 2.3‐, 1.8‐, and 1.6‐fold higher unbound lurbinectedin CL. In conclusion, preemptive CYP3A genotyping may offer a valuable approach for personalizing treatment with lurbinectedin in cancer patients.

Background Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case–control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. Methods A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes’ sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. Results Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p -values > 0.05; beta-diversity: PERMANOVA, both R 2  < 0.0007, p -values > 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p -values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes’ sequence reads were not significantly different between groups (all FDR p -values > 0.05). Conclusions Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.

ObjectivesGiant cell arteritis (GCA) is a complex systemic vasculitis mediated by the interplay between both genetic and epigenetic factors. Monocytes are crucial players of the inflammation occurring in GCA. Therefore, characterisation of the monocyte methylome and transcriptome in GCA would be helpful to better understand disease pathogenesis.MethodsWe performed an integrated epigenome-and transcriptome-wide association study in CD14+ monocytes from 82 patients with GCA, cross-sectionally classified into three different clinical statuses (active, in remission with or without glucocorticoid (GC) treatment), and 31 healthy controls.ResultsWe identified a global methylation and gene expression dysregulation in GCA monocytes. Specifically, monocytes from active patients showed a more proinflammatory phenotype compared with healthy controls and patients in remission. In addition to inflammatory pathways known to be involved in active GCA, such as response to IL-6 and IL-1, we identified response to IL-11 as a new pathway potentially implicated in GCA. Furthermore, monocytes from patients in remission with treatment showed downregulation of genes involved in inflammatory processes as well as overexpression of GC receptor-target genes. Finally, we identified changes in DNA methylation correlating with alterations in expression levels of genes with a potential role in GCA pathogenesis, such as ITGA7 and CD63, as well as genes mediating the molecular response to GC, including FKBP5, ETS2, ZBTB16 and ADAMTS2.ConclusionOur results revealed profound alterations in the methylation and transcriptomic profiles of monocytes from GCA patients, uncovering novel genes and pathways involved in GCA pathogenesis and in the molecular response to GC treatment.

The purpose of this study was to determine the mean propulsive velocity (MVP) at various percentages of one repetition maximum (1RM) in the full squat and chest press exercises. A total of 96 young women and 256 young men (recreational athletes) performed an incremental test (50–60–70–80% 1RM) comprising the bench press and full squat exercises in two different sessions. The individual load and velocity ratios were established through the MPV. Data were analyzed using SPSS software version 25.0, with the significance level set at 5%. The following findings were revealed: highly linear load-velocity relationships in the group of women (r = 0.806 in the squat, and r = 0.872 in the bench press) and in the group of men (r = 0.832 and r = 0.880, respectively); significant differences (p < 0.001) in the MPV at 50–70–80% 1RM between the bench press and the full squat in men and at 70–80% 1RM in women; and a high variability in the MPV (11.49% to 22.63) in the bench press and full squat (11.58% to 25.15%) was observed in women and men (11.31% to 21.06%, and 9.26% to 24.2%) at the different percentages of 1RM evaluated. These results suggest that the load-velocity ratio in non-strength-trained subjects should be determined individually to more precisely establish the relative load to be used in a full squat and bench press training program.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed. Yet, how this is regulated and whether it is involved in ferroptotic cell death has remained unexplored. Here, we provide evidence that Drp1 is activated upon experimental induction of ferroptosis and promotes cell death execution and mitochondrial fragmentation. Using time-lapse microscopy, we found that ferroptosis induced mitochondrial fragmentation and loss of mitochondrial membrane potential, but not mitochondrial outer membrane permeabilization. Importantly, Drp1 accelerated ferroptotic cell death kinetics. Notably, this function was mediated by the regulation of mitochondrial dynamics, as overexpression of Mitofusin 2 phenocopied the effect of Drp1 deficiency in delaying ferroptosis cell death kinetics. Mechanistically, we found that Drp1 is phosphorylated and activated after induction of ferroptosis and that it translocates to mitochondria. Further activation at mitochondria through the phosphatase PGAM5 promoted ferroptotic cell death. Remarkably, Drp1 depletion delayed mitochondrial and plasma membrane lipid peroxidation. These data provide evidence for a functional role of Drp1 activation and mitochondrial fragmentation in the acceleration of ferroptotic cell death, with important implications for targeting mitochondrial dynamics in diseases associated with ferroptosis.

The COVID-19 pandemic has posed a huge challenge to healthcare systems and their personnel worldwide. The study of the impact of SARS-CoV-2 infection among healthcare workers (HCW), through prevalence studies, will let us know viral expansion, individuals at most risk and the most exposed areas in healthcare organizations. The aim of this study is to gauge the impact of SARS-CoV-2 pandemic in our hospital workforce and identify groups and areas at increased risk. This is a cross-sectional and incidence study carried out on healthcare workers based on molecular and serological diagnosis of SARS-CoV-2 infection. Of the 3013 HCW invited to participate, 2439 (80.9%) were recruited, including 674 (22.4%) who had previously consulted at the Occupational Health Service (OHS) for confirmed exposure and/or presenting symptoms suggestive of COVID-19. A total of 411 (16.9%) and 264 (10.8%) healthcare workers were SARS-CoV-2 IgG and rRT-PCR positive, respectively. The cumulative prevalence considering all studies (IgG positive HCW and/or rRT-PCR positive detection) was 485 (19.9%). SARS-CoV-2 IgG-positive patients in whom the virus was not detected were 221 (9.1%); up to 151 of them (68.3%) did not report any compatible symptoms nor consult at the OHS for this reason. Men became more infected than women (25% vs 18.5%, p = 0.0009), including when data were also classified by age. COVID-19 cumulative prevalence among the HCW assigned to medical departments was higher (25.2%) than others, as well as among medical staff (25.4%) compared with other professional categories (p<0.01). The global impact of the COVID-19 pandemic on HCW of our centre has been 19.9%. Doctors and medical services personnel have had the highest prevalence of SARS-CoV-2 infection, but many of them have not presented compatible symptoms. This emphasizes the performance of continuous surveillance methods of the most exposed health personnel and not only based on the appearance of symptoms.