In the aftermath of the end‐Permian mass extinction, Early Triassic sediments record some of the largest Phanerozoic carbon isotopic excursions. Among them, a global Smithian‐negative carbonate ...carbon isotope excursion has been identified, followed by an abrupt increase across the Smithian–Spathian boundary (SSB; ~250.8 Myr ago). This chemostratigraphic evolution is associated with palaeontological evidence that indicate a major collapse of terrestrial and marine ecosystems during the Late Smithian. It is commonly assumed that Smithian and Spathian isotopic variations are intimately linked to major perturbations in the exogenic carbon reservoir. We present paired carbon isotopes measurements from the Thaynes Group (Utah, USA) to evaluate the extent to which the Early Triassic isotopic perturbations reflect changes in the exogenic carbon cycle. The δ13Ccarb variations obtained here reproduce the known Smithian δ13Ccarb‐negative excursion. However, the δ13C signal of the bulk organic matter is invariant across the SSB and variations in the δ34S signal of sedimentary sulphides are interpreted here to reflect the intensity of sediment remobilization. We argue that Middle to Late Smithian δ13Ccarb signal in the shallow marine environments of the Thaynes Group does not reflect secular evolution of the exogenic carbon cycle but rather physicochemical conditions at the sediment–water interface leading to authigenic carbonate formation during early diagenetic processes.
The Early Triassic is generally portrayed as a time of various, high ecological stresses leading to a delayed biotic recovery after the devastating end-Permian mass extinction. This interval is ...notably characterized by repeated biotic crises (e.g., during the late Smithian), large-scale fluctuations of the global carbon, nitrogen and sulfur cycles as well as harsh marine conditions including a combination of ocean acidification, anoxia, extreme seawater temperatures and shifting productivity. Observations from different paleolatitudes suggest that sulfidic (H2S-rich) conditions may have developed widely during the Early Triassic, possibly reaching up to ultra-shallow environments in some places. However, the existence and the spatio-temporal extent of such redox swings remain poorly constrained. In order to explore Early Triassic paleoceanographic redox changes and their potential influences on the biotic recovery, we analyzed multiple sulfur isotopes (32S, 33S, 34S, and 36S) of sedimentary pyrite and carbonate associated sulfate (δ34SCAS) from the Mineral Mountains section, Utah. Sediments from this section were mainly deposited in shallow waters and span the Smithian and lower Spathian. We report a 68‰ range of variations in δ34Spy associated with Δ33Spy varying from −0.01‰ to +0.12‰, whereas the δ34SCAS varies between +19.5‰ and + 34.8‰. We interpret the observed signal of multiple sulfur isotopes as reflecting the operation of pore-water synsedimentary microbial sulfate reduction in open system with respect to sulfates before the late Smithian, evolving to a closed system, sulfate limited, Rayleigh-type distillation across the Smithian/Spathian boundary (SSB) and immediately after the SSB. We argue that this marked change is driven by the effectiveness of the connection between the sedimentary pore waters and the overlying water column, which is, in this case, controlled by the local sedimentological conditions such as the bioturbation intensity and the sedimentation rate. Therefore, our results suggest that changes in the sulfur cycle before and across the SSB at Mineral Mountains is probably a local consequence of the loss of the mixed sedimentary layer during the late Smithian extinction event, as opposed to reflecting the development of a lethal anoxic ocean at the global scale.
Abstract Objectives Empirical literature on patient decision role preferences regarding treatment and screening was reviewed to summarize patients’ role preferences across measures, time and patient ...population. Methods Five databases were searched from January 1980 to December 2007 (1980–2007 Ovid MEDLINE, Cochrane Database of Systematic Reviews, PsychInfo, Web of Science and PubMed (2005–2007)). Eligible studies measured patient decision role preferences, described measures, presented findings as percentages or mean scores and were published in English from any country. Studies were compared by patient population, time of publication, and measure. Results 115 studies were eligible. The majority of patients preferred sharing decisions with physicians in 63% of the studies. A time trend appeared. The majority of respondents preferred sharing decision roles in 71% of the studies from 2000 and later, compared to 50% of studies before 2000. Measures themselves, in addition to patient population, influenced the preferred decision roles reported. Conclusion Findings appear to vary with the measure of preferred decision making used, time of the publication and characteristics of the population. Practice implications The role preference measure itself must be considered when interpreting patient responses to a measure or question about a patient's preference for decision roles.
Purpose Previous research shows that the death of a parent places children at risk for a number of negative outcomes. The role of trust in health care at the end of life has been acknowledged as ...crucial for patients and adult family members. However, the consequences of children's distrust in the care provided to their parents remain unknown. Therefore, we investigated the negative long-term outcomes of cancer-bereaved sons' and daughters' distrust in the care that was provided to a dying parent. Methods We used a population-based nationwide survey to investigate self-reported distrust in the care provided and possible negative outcomes in 622 (73%) participants who had lost a parent as a result of cancer 6 to 9 years earlier, at ages 13 to 16 years. All participants were 18 years or older at the time of the survey. Results In those who reported no or little trust (ie, distrust) in the health care provided to their dying parents, we found statistically significantly higher risks of various negative outcomes at the time of survey: bitterness toward health care professionals for not having done everything that was possible (crude risk ratio RR, 3.5; 95% CI, 2.3 to 5.1) and for having stopped treatment (RR, 3.4; 95% CI, 2.1 to 6.0), self-destructiveness (eg, self-injury RR, 1.7; 95% CI, 1.2 to 2.4), and psychological problems (eg, moderate to severe depression according to the Patient Health Questionnaire-9 RR, 2.3; 95% CI, 1.5 to 3.5). Conclusion In cancer-bereaved former adolescents, distrust in the health care provided to the dying parent is associated with a higher risk of negative long-term outcomes. The health care professionals involved in this care might play an important role in safeguarding the trust of adolescents.
The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive—binding is reduced at low ...pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA’s extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA’s adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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•H. pylori adherence is acid sensitive and fully reversed by increased pH•Diversity in BabA adhesin's acid sensitivity is driven by inflammation and disease progression•pH sensor sequences in BabA’s binding domains determine its pH responsiveness•BabA adaptation to mucosal atrophy and elevated pH can contribute to gastric cancer
Helicobacter pylori binds with high affinity to ABO/Leb blood group antigens to persist in the stomach mucosa. Bugaytsova et al. show that adherence is acid sensitive, fully reversed when acidity is decreased, and controlled by BabA adhesin protein's pH-sensors sequences changes in which are selected during chronic infection and disease.
Bladder cancer (BC) is an age-associated malignancy with increased prevalence in the elderly population. Elderly patients are a vulnerable population at increased risk for treatment-related toxicity ...secondary to medical comorbidities and geriatric syndromes. As a result, this population has been historically undertreated and suffers worse disease-specific outcomes than younger patients with BC. Recognition of this disparity has led to efforts to individualize treatment decisions based on functional status rather than chronologic age in an effort to optimize the use of curative therapies for the fit elderly and modify treatments to reduce the risk of toxicity and disease-related morbidity in vulnerable or frail patients. The comprehensive geriatric assessment is a decision framework that helps to balance underlying health considerations and risks of therapy with aggressiveness of the cancer. Development of systemic therapies with increased efficacy against BC and reduced toxicity are eagerly awaited, as are techniques and interventions to reduce the morbidity from surgery and radiation for patients with BC.
Abstract
Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical ...course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n = 5) and long-term smokers (LTS) with (LTS+, n = 4) and without COPD (LTS−, n = 8). Using mass spectrometry, we identified 57 highly confident N-glycan structures whereof 38 oligomannose, complex, and paucimannose type glycans were common to BAL samples from HNS, LTS− and LTS+ groups. Hybrid type N-glycans were identified only in the LTS+ group. Qualitatively and quantitatively, HNS had lower inter-individual variation between samples compared to LTS− or LTS+. Cluster analysis of BAL N-glycosylation distinguished LTS from HNS. Correlation analysis with clinical parameters revealed that complex N-glycans were associated with health and absence of smoking whereas oligomannose N-glycans were associated with smoking and disease. The N-glycan profile from monocyte-derived macrophages differed from the BAL N-glycan profiles. In conclusion, long-term smokers display substantial alterations of N-glycosylation in the bronchoalveolar space, and the hybrid N-glycans identified only in long-term smokers with COPD deserve to be further studied as potential biomarkers.
Abstract
Background
Previous research shows that many cancer-bereaved youths report unresolved grief several years after the death of a parent. Grief work hypothesis suggests that, in order to heal, ...the bereaved needs to process the pain of grief in some way. This study explored acute grief experiences and reactions in the first 6 months post-loss among cancer-bereaved teenagers. We further explored long-term grief resolution and potential predictors of having had “an okay way to grieve” in the first months post-loss.
Methods
We used a population-based nationwide, study-specific survey to investigate acute and long-term grief experiences in 622 (73% response rate) bereaved young adults (age > 18) who, 6–9 years earlier, at ages 13–16 years, had lost a parent to cancer. Associations were assessed using bivariable and multivariable logistic regression.
Results
Fifty-seven per cent of the participants reported that they did not have a way to grieve that felt okay during the first 6 months after the death of their parent. This was associated with increased risk for long-term unresolved grief (odds ratio (OR): 4.32, 95% confidence interval (CI): 2.99–6.28). An association with long-term unresolved grief was also found for those who reported to have been numbing and postponing (42%, OR: 1.73, 95% CI: 1.22–2.47), overwhelmed by grief (24%, OR: 2.02, 95% CI: 1.35–3.04) and discouraged from grieving (15%, OR: 2.68, 95% CI: 1.62–4.56) or to have concealed their grief to protect the other parent (24%, OR: 1.83, 95% CI: 1.23–2.73). Predictors of having had an okay way to grieve included being male, having had good family cohesion, and having talked about what was important with the dying parent.
Conclusion
More than half of the cancer-bereaved teenagers did not find a way to grieve that felt okay during the first 6 months after the death of their parent and the acute grief experiences and reaction were associated with their grief resolution long-term, i.e. 6–9 years post-loss. Facilitating a last conversation with their dying parent, good family cohesion, and providing teenagers with knowledge about common grief experiences may help to prevent long-term unresolved grief.
Bolus intravenous injections of phosphorothioate oligonucleotides (PS-ODN) into primates cause profound hypotension, which has been attributed to complement activation, the biochemical pathway ...leading to acute inflammatory response. Because the hypotension was not accompanied by peripheral or pulmonary edema and epinephrine was not effective, but administration of 200 ml Ringer's lactate was effective, we examined the possibility that the 15-base PS-ODN interferes with sympathetic tone. We administered doses ranging from 3.3 to 10 mg/kg of a 15-base PS-ODN as a 30-60 s iv bolus into the right atrium of conscious Macaca mulatta. Blood pressure fell to 27 mm Hg following a 5.0 mg/kg dose, but no hypotension was observed after a 3.3 mg/kg dose; 10 mg/kg was lethal. Adrenergic receptor binding was evaluated in radioligand binding assays using rat cerebral cortex membranes with radiolabeled prazosin. The 15-base PS-ODN competes with prazosin for the alpha(1)-adrenergic receptor with an IC50 of 14 microM, which favors binding over serum albumin (K(d) = 37 to 48 microM). Admixing serum albumin with 5.0 mg/kg 15-base PS-ODN prior to injection prevented hypotension, suggesting that unbound PS-ODN interferes with sympathetic tone before binding to plasma proteins. Interactions of the 15-base PS-ODN with the alpha(1)-adrenergic receptor in vivo were confirmed by a decreased response to phenylephrine. Reducing the length from 15 to 9 or 5 bases abolished alpha(1)-adrenergic receptor binding in vitro and bolus infusion of 5.0 mg/kg of 9-base PS-ODN no longer produced hypotension. In conclusion, the 15-base PS-ODN shows cooperative binding to the alpha(1)-adrenergic receptor, which produces cardiovascular effects that are oligomer length, dose, and formulation dependent.
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