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The aim of this study was to investigate how family life and marital status influence the motivations of ultramarathoners. Two-hundred-sixty-seven Polish athletes participated in the diagnostic survey during the Karkonosze Winter Ultramarathon. The Polish version of the Motivation of Marathoner Scale was used. The motivations of ultra-runners were investigated among the following groups of respondents people in a relationship/marriage; singles; people with children vs. childless people; people who run alone and with a partner; people who parted with a partner because of lack of support for running. Research results can be useful for sport managers-e.g., findings show the relative importance of modern sport for singles in the second half of life. Research has also shown how people in relationships and people with children can be realized through demanding long-distance running. We also found that running ultramarathons can pose a threat to a relationship.Pentaminomycins C-E (1-3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino acid, N5-hydroxyarginine, based on 1D and 2D NMR and mass spectroscopic analyses. The absolute configurations of the amino acid residues were assigned using Marfey's method and bioinformatics analysis of their nonribosomal peptide biosynthetic gene cluster (BGC). Detailed MMRi62 in vivo of the BGC enabled us to propose that the structural variations in 1-3 originate from the low specificity of the adenylation domain in the nonribosomal peptide synthetase (NRPS) module 1, and indicate that macrocyclization can be catalyzed noncanonically by penicillin binding protein (PBP)-type TE. Furthermore, pentaminomycins C and D (1 and 2) showed significant autophagy-inducing activities and were cytoprotective against oxidative stress in vitro.Fluorescein, and derivatives of fluorescein, are often used as fluorescent probes and sensors. In systems where pH is a variable, protonation/deprotonation of the molecule can influence the pertinent photophysics. Fluorination of the xanthene moiety can alter the molecule's pKa such as to render a probe whose photophysics remains invariant over a wide pH range. Di-fluorination is often sufficient to accomplish this goal, as has been demonstrated with compounds such as Oregon Green in which the xanthene moiety is symmetrically difluorinated. In this work, we synthesized a non-symmetrical difluorinated analog of Oregon Green which we call Athens Green. We ascertained that the photophysics and photochemistry of Athens Green, including the oxygen-dependent photophysics that results in the sensitized production of singlet oxygen, O2(a1Δg), can differ appreciably from the photophysics of Oregon Green. Our data indicate that Athens Green will be a more benign fluorescent probe in systems that involve the production and removal of O2(a1Δg). These results expand the available options in the toolbox of fluorescein-based fluorophores.Psychological distress caused by decreased physical activity (PA) is a growing concern among the elderly due to public health measures since the coronavirus disease (COVID-19). We aimed to (1) assess how public health restrictions impact PA, subjective well-being (SWB), and health-related quality of life (HRQoL) of community-dwelling elderly, and (2) investigate risk factors that lead to a decline in PA. Self-administered questionnaires assessed the changes in PA, SWB, HRQoL. Multivariate logistic regression analysis was performed to identify significant associated risk factors for decreased PA. Of 165 participants (valid response rate, 41.3%; mean age, 78.5 ± 8.0 years), 47.3% became less active, 23.0% became more active, and 29.7% maintained PA levels. There was a significant decrease in SWB at baseline and follow-up after COVID-19 restrictions in the less active group (p less then 0.01). Higher levels of moderate or strenuous exercise/sports activity at baseline (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.01-1.24), and lower mental component HRQoL scores at baseline (OR, 0.96; 95% CI, 0.93-0.99) were associated with an increased risk of decreased PA. Public health restrictions impact the PA of the elderly, especially those who had higher levels of exercise/sports activity and lower HRQoL before COVID-19. Decreased PA was strongly associated with lower SWB.More effective therapy is needed to improve the survival of patients with advanced and recurrent ovarian cancer. Preclinical and early clinical studies with single molecular targeted agents have shown limited antitumor activity in ovarian cancer, likely due to compensation by alternative growth/survival pathways. An emerging strategy in overcoming resistance is to combine inhibitors targeting multiple pathways. In this study, we used a novel strategy of combining several FDA-approved targeted drugs, including sunitinib, dasatinib, and everolimus, in human ovarian cancers. Combination of the tyrosine kinase inhibitor sunitinib with the SRC inhibitor dasatinib showed synergistic anti-tumor activity in human ovarian cancer cells. #link# The increased activity was associated with inhibition of the STAT3, SRC, and MAPK signaling pathways, but not AKT signaling. To inhibit the PI3K/AKT/mTOR pathway, we added the mTOR inhibitor everolimus, which further increased anti-tumor activity in cells. Combined treatment with sunitinib, dasatinib, and everolimus also resulted in greater inhibition of human ovarian tumor growth in mice. Furthermore, the triple combination also synergistically increased the anti-tumor activity of paclitaxel, both in vitro and in vivo. Taken together, our results demonstrate that simultaneous inhibition of several signaling pathways results in better anti-tumor activity compared to inhibiting any of these signaling pathways alone.Although up to 8% of European youngsters carry out high-intensity care for a family member, adolescent young carers (AYCs), especially those caring for their grandparents (GrPs), remain an under-researched group. This study aimed at addressing the current knowledge gap by carrying out an online survey in Italy, the Netherlands, Slovenia, Sweden, Switzerland, and the United Kingdom. The analysis included a final sample of 817 AYCs aged 15-17 years old. AYCs of grandparents (GrPs) were compared to AYCs of other care recipients (OCRs), in order to identify any difference in positive and negative caregiving outcomes and exposure factors between the two groups. Linear or logistic regression models were built, and multivariate analyses were repeated, including a fixed effect on the country variable. AYCs of GrPs experienced more positive caregiving outcomes than AYCs of OCRs across all six countries. Being female or non-binary, and having a migration background, were associated with more negative outcomes, regardless of the relationship with the care recipient. Further research on intergenerational caregiving outcomes is recommended for shaping measures and policies, which preserve the intergenerational emotional bonds, whilst protecting AYCs from inappropriate responsibilities, undermining their mental health and well-being.The delivery of small interfering RNAs (siRNA) is an efficient method for gene silencing through the induction of RNA interference (RNAi). It critically relies, however, on efficient vehicles for siRNA formulation, for transfection in vitro as well as for their potential use in vivo. While polyethylenimines (PEIs) are among the most studied cationic polymers for nucleic acid delivery including small RNA molecules, polypropylenimines (PPIs) have been explored to a lesser extent. link2 Previous studies have shown the benefit of the modification of small PEIs by tyrosine grafting which are featured in this paper. Additionally, we have now extended this approach towards PPIs, presenting tyrosine-modified PPIs (named PPI-Y) for the first time. In this study, we describe the marked improvement of PPI upon its tyrosine modification, leading to enhanced siRNA complexation, complex stability, siRNA delivery, knockdown efficacy and biocompatibility. Results of PPI-Y/siRNA complexes are also compared with data based on tyrosine-modified linear or branched PEIs (LPxY or PxY). Taken together, this establishes tyrosine-modified PPIs or PEIs as particularly promising polymeric systems for siRNA formulation and delivery.Nanomedicine, the application of nanotechnology at the level of one billionth of a millimeter to medicine, has inspired great interest in the last twenty years, leading to the commercialization of successful products both from a clinical and an economic point of view [...].Life-sustaining treatments (LSTs) and end-of-life (EOL) care's goal for prolonging one's life are defined as aggressive EOL care among critically ill patients. They have limited effects and add unnecessary financial burden to advanced cancer patients. link3 A questionnaire survey was conducted to collect information on demographics, disease conditions, preference for LSTs, and goal of EOL care among advanced cancer patients of comprehensive grade-A tertiary hospitals in Wuhan, mainland China. Most patients preferred to accept LSTs when they were in a critical condition, including cardiopulmonary resuscitation (89.9%), mechanical ventilation support (85.7%), nasogastric tube feeding (84.1%), blood transfusion (89.8%), general surgery (87.5%), and hemodialysis (85.8%). Most (88%) preferred prolonging life as the goal of EOL care. Logistic regression showed common influencing factors were participants who completed junior high/high school or below and were financially adequate had higher reference for aggressive EOL care. Patients whose physician had accurately disclosed prognosis; however, showed a decrease trend for aggressive EOL care. Most advanced cancer patients preferred to accept aggressive EOL care. Discussions about prognosis disclosure among physicians and patients should be improved. Education about LSTs' limitations and comfort-oriented care's benefits should be promoted among the advanced cancer patients in mainland China.Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1β in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia.
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