Participants ( = 245; 93 = TH, 70 = ACC, 82 = pMDI) showed a significant difference between the groups at one-month for inhaler technique scores for TH (active 5.29 ± 1.86 vs. control = 24.4 ± 21.28), ACC (active = 3.99 ± 1.43 vs. control = 25.45 ± 22.57), and pMDI (active = 4.59 ± 0.10 vs. control = 120.55 ± 17.2), < 0.001 for all. Asthma control for active group indicated significant improvements compared to control for TH and pMDI ( < 0.001 for both), but not ACC group ( = 0.087). Retention of correct inhaler technique and improved asthma control can be enhanced by using a specialized inhaler technique label in image format. Retention of correct inhaler technique and improved asthma control can be enhanced by using a specialized inhaler technique label in image format.Germline mutations in predisposition genes account for only 20% of all familial colorectal cancers (CRC) and the remaining genetic burden may be due to rare high- to moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer-predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants a coding variant in APC downregulated 1 gene (APCDD1, p.R299H) and a non-coding variant in the 5' untranslated region (UTR) of histone deacetylase 5 gene (HDAC5). Sanger sequencing confirmed the variants segregating with the disease and Taqman assays revealed 8 additional APCDD1 variants in a cohort of 1705 familial CRC patients and no further HDAC5 variants. Proliferation assays indicated an insignificant proliferative impact for the APCDD1 variant. Luciferase reporter assays using the HDAC5 variant resulted in an enhanced promoter activity. Targeting of transcription factor binding sites of SNAI-2 and TCF4 interrupted by the HDAC5 variant showed a significant impact of TCF4 on promoter activity of mutated HDAC5. Our findings contribute not only to the identification of unrecognized genetic causes of familial CRC but also underline the importance of 5'UTR variants affecting transcriptional regulation and the pathogenesis of complex disorders.One-carbon (1C) metabolism provides methyl groups for the synthesis and/or methylation of purines and pyrimidines, biogenic amines, proteins, and phospholipids. Our understanding of how 1C pathways operate, however, pertains mostly to the (rat) liver. Here we report that transcripts for all bar two genes (i.e., BHMT, MAT1A) encoding enzymes in the linked methionine-folate cycles are expressed in all cell types within the ovarian follicle, oocyte, and blastocyst in the cow, sheep, and pig; as well as in rat granulosa cells (GCs) and human KGN cells (a granulosa-like tumor cell line). Betaine-homocysteine methyltransferase (BHMT) protein was absent in bovine theca and GCs, as was activity of this enzyme in GCs. Mathematical modeling predicted that absence of this enzyme would lead to more volatile S-adenosylmethionine-mediated transmethylation in response to 1C substrate (e.g., methionine) or cofactor provision. We tested the sensitivity of bovine GCs to reduced methionine (from 50 to 10 µM) and observed a diminished flux of 1C units through the methionine cycle. We then used reduced-representation bisulfite sequencing to demonstrate that this reduction in methionine during bovine embryo culture leads to genome-wide alterations to DNA methylation in >1600 genes, including a cohort of imprinted genes linked to an abnormal fetal-overgrowth phenotype. Bovine ovarian and embryonic cells are acutely sensitive to methionine, but further experimentation is required to determine the significance of interspecific variation in BHMT expression.There is evidence suggesting clinical progression in a subset of patients with bipolar disorder (BD). This progression is associated with worse clinical outcomes and biological changes. Molecular pathways and biological markers of clinical progression have been identified and may explain the progressive changes associated with this disorder. The biological basis for clinical progression in BD is called neuroprogression. We propose that the following intertwined pathways provide the biological basis of neuroprogression inflammation, oxidative stress, impaired calcium signaling, endoplasmic reticulum and mitochondrial dysfunction, and impaired neuroplasticity and cellular resilience. The nonlinear interaction of these pathways may worsen clinical outcomes, cognition, and functioning. Understanding neuroprogression in BD is crucial for identifying novel therapeutic targets, preventing illness progression, and ultimately promoting better outcomes.Background Nursing is a profession where staff are exposed to chronic stress. Mental resilience plays a significant role in the process of coping with these challenges. The aim of this study was to assess nurses' mental and physical wellbeing, as well as resilience, by taking into account the occurrence of risky behaviour among nurses in Poland. Methods A descriptive study was carried out between June 2017 and May 2018 among nurses (n = 1080) employed in primary healthcare or in training centres in Silesia, Poland. Data were obtained from a number of questionnaires. Results Over half of the nurses (n = 735; 68%) had an average psychophysical mood level resulting from stress, and 179 (16.6%) nurses had a low psychophysical mood. Those with a lower psychophysical mood showed a greater tendency towards developing improper eating habits (r = -0.23; p less then 0.001). Most nurses had an average (n = 649; 60.1%) or low (n = 255; 23.6%) level of resilience. Higher resilience levels were observed in nurses aged over 30 years (p = 0.004) and in those with additional employment (p = 0.008). High resilience was associated with a lower intensity of risky behaviour. Conclusion Most nurses in Poland display average and low levels of resilience, which can have unfavourable consequences for their health.Bottom ash (BA) is an industrial solid waste formed by the burning of coal. The environmental problems and storage costs caused by this waste increase with every passing day. In this study, the use of BA as an additive (clay substitute) in fired brick production was investigated. The study consisted of two stages. In the first stage, cylinder blocks were produced from clay used in brick production. The second stage was the examination of the experimental substitution of clay with 10, 20, 30 and 40% BA. Samples were fired at 900, 1000, 1100 and 1150 °C to produce fired brick samples. The unit weight, compressive strength (before and after freeze-thawing) and water absorption were analyzed for the samples. The unit weight values decreased in the samples containing BA. https://www.selleckchem.com/products/Temsirolimus.html The mechanical properties met the conditions prescribed in the relevant standards; i.e., all of the samples fired at 1100 and 1150 °C had a sufficient compressive strength over 20 MPa. The high potential of fired bricks for the construction industry was proved.