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Water column dissolved inorganic carbon and total alkalinity were measured during five hydrographie sections in the Atlantic Ocean and Drake Passage. The work was funded through the Strategic Funding Initiative of the UK's Oceans2025 programme, which ran from 2007 to 2012. The aims of this programme were to establish the regional budgets of natural and anthropogenic carbon in the North Atlantic, the South Atlantic, and the Atlantic sector of the Southern Ocean, as well as the rates of change of these budgets. This paper describes the dissolved inorganic carbon and total alkalinity data collected along east-west sections at 55-60° N (Arctic Gateway), 24.5° N, and 24° S in the Atlantic and across two Drake Passage sections. Other hydrographic and biogeochemical parameters were measured during these sections, yet are not covered in this paper. Over 95 % of samples taken during the 24.5° N, 24° S, and the Drake Passage sections were analysed onboard and subjected to a 1st level quality control addressing technical and analytical issues. Samples taken during Arctic Gateway were analysed and subjected to quality control back in the laboratory. Complete post-cruise 2nd level quality control was performed using cross-over analysis with historical data in the vicinity of measurements, and data are available through the Carbon Dioxide Information Analysis Center (CDIAC) and are included in the Global Ocean Data Analyses Project, version 2 (GLODAP 2). [ABSTRACT FROM AUTHOR]

Background: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making., Material and Methods: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis., Results: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents., Discussion: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers., (© 2024. The Author(s).)

In polar regions, global warming has accelerated the melting of glacial and buried ice, resulting in meltwater run-off and the mobilization of surface nutrients. Yet, the short-term effects of altered nutrient regimes on the diversity and function of soil microbiota in polyextreme environments such as Antarctica, remains poorly understood. We studied these effects by constructing soil microcosms simulating augmented carbon, nitrogen, and moisture. Addition of nitrogen significantly decreased the diversity of Antarctic soil microbial assemblages, compared with other treatments. Other treatments led to a shift in the relative abundances of these microbial assemblages although the distributional patterns were random. Only nitrogen treatment appeared to lead to distinct community structural patterns, with increases in abundance of Proteobacteria (Gammaproteobateria) and a decrease in Verrucomicrobiota (Chlamydiae and Verrucomicrobiae).The effects of extracellular enzyme activities and soil parameters on changes in microbial taxa were also significant following nitrogen addition. Structural equation modeling revealed that nutrient source and extracellular enzyme activities were positive predictors of microbial diversity. Our study highlights the effect of nitrogen addition on Antarctic soil microorganisms, supporting evidence of microbial resilience to nutrient increases. In contrast with studies suggesting that these communities may be resistant to change, Antarctic soil microbiota responded rapidly to augmented nutrient regimes., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Plasmepsins IX (PMIX) and X (PMX) are essential aspartyl proteases for Plasmodium spp. egress, invasion, and development. WM4 and WM382 inhibit PMIX and PMX in Plasmodium falciparum and P. vivax. WM4 inhibits PMX, while WM382 is a dual inhibitor of PMIX and PMX. To understand their function, we identified protein substrates. Enzyme kinetic and structural analyses identified interactions responsible for drug specificity. PMIX and PMX have similar substrate specificity; however, there are distinct differences for peptide and protein substrates. Differences in WM4 and WM382 binding for PMIX and PMX map to variations in the S' region and engagement of the active site S3 pocket. Structures of PMX reveal interactions and mechanistic detail of drug binding important for development of clinical candidates against these targets., Competing Interests: Declaration of interests A.F.C., M.d.L.R., P.F., Z.G., J.A.M., D.O., B.E.S., and T.T. have a patent for Antimalarial Agents (PCT/CN2019/100781) based on compounds in this manuscript. M.d.L.R., D.O., Z.G., N.M., and J.A.M. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA) and may own stock or hold stock options in Merck & Co., Inc., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To estimate the incidence of anemia in pregnancy and compare the maternal and perinatal outcomes of women with and without anemia., Methods: We conducted a population-based retrospective cohort study on all pregnant women in British Columbia who had a live birth or stillbirth at or after 20 weeks of gestation between 2004 and 2016. Women were diagnosed with anemia based on two criteria: third-trimester hemoglobin value or a delivery admission diagnosis of anemia (made before delivery). Anemia was categorized into no anemia (hemoglobin 11 g/dL or greater), mild (9-10.9 g/dL), moderate (7-8.9 g/dL), severe (less than 7 g/dL), or anemia of unspecified severity (with diagnosis made before delivery). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs expressing the association between anemia and maternal and perinatal outcomes., Results: Of 515,270 women in the study population, 65,906 (12.8%) had anemia: 11.8%, 0.43%, and 0.02% had mild, moderate, and severe anemia, respectively, and 0.58% had anemia of unspecified severity. Anemic women had longer hospitalization duration and more antenatal admissions, and rates of preeclampsia, placenta previa and cesarean delivery were higher among women with anemia. The intrapartum-postpartum blood transfusion rate was 5.1 per 1,000 among women without anemia, and higher among women with anemia (aOR 2.45, 95% CI 1.74-3.45 for mild anemia; 21.3, 95% CI 12.2-37.3 for moderate anemia; not analyzable for severe anemia; and 48.3, 95% CI 6.60-353.9 for anemia of unspecified severity). Anemia was associated with preterm birth (mild anemia, aOR 1.09, 95% CI 1.05-1.12; moderate anemia, aOR 2.26, 95% CI 2.02-2.54; anemia of unspecified severity, aOR 2.27, 95% CI 2.06-2.50), small-for-gestational-age live birth, low 5-minute Apgar score, neonatal death, and perinatal death., Conclusion: Maternal anemia in pregnancy represents a common and potentially reversible risk factor associated with antepartum, intrapartum, and postpartum maternal morbidity and perinatal morbidity and mortality.

Objectives: Develop pricing models for bundled payments that draw inputs from clinician-defined best practice standards and benchmarks set from regional variations in utilization., Data: Health care utilization and claims data for a cohort of incident Ontario ischemic and hemorrhagic stroke episodes. Episodes of care are created by linking incident stroke hospitalizations with subsequent health service utilization across multiple datasets., Study Design: Costs are estimated for episodes of care and constituent service components using setting-specific case mix methodologies and provincial fee schedules. Costs are estimated for five areas of potentially avoidable utilization, derived from best practice standards set by an expert panel of stroke clinicians. Alternative approaches for setting normative prices for stroke episodes are developed using measures of potentially avoidable utilization and benchmarks established by the best performing regions., Principal Findings: There are wide regional variations in the utilization of different health services within episodes of stroke care. Reconciling the best practice standards with regional utilization identifies significant amounts of potentially avoidable utilization. Normative pricing models for stroke episodes result in increasingly aggressive redistributions of funding., Conclusions: Bundled payment pilots to date have been based on the costs of historical service patterns, which effectively 'bake in' unwarranted and inefficient variations in utilization. This study demonstrates the feasibility of novel clinically informed episode pricing approaches that leverage these variations to target reductions in potentially avoidable utilization., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

MurG is an essential bacterial glycosyltransferase enzyme in Pseudomonas aeruginosa performing one of the key membrane steps of peptidoglycan synthesis catalyzing the transfer of N-acetyl glucosamine (GlcNAc) from its donor substrate, UDP-GlcNAc, to the acceptor substrate Lipid I. We have solved the crystal structure of the complex between Pseudomonas aeruginosa MurG and UDP-GlcNAc and compared it with the previously solved complex from E. coli. The structure reveals a large-scale conformational change in the relative orientations of the N- and C-terminal domains, which has the effect of widening the cofactor binding site and displacing the UDP-GlcNAc donor. These results suggest new opportunities to design potent inhibitors of peptidoglycan biosynthesis.

Bacillus anthracis is a Gram-positive spore-forming bacterium that is the causative agent of anthrax disease. The use of anthrax as a bioweapon has increased pressure for the development of an effective treatment. Dihydrodipicolinate synthase (DHDPS) catalyses the first committed step in the biosynthetic pathway yielding two essential bacterial metabolites, meso-diaminopimelate (DAP) and (S)-lysine. DHDPS is therefore a potential antibiotic target, as microbes require either lysine or DAP as a component of the cell wall. This paper is the first biochemical description of DHDPS from B. anthracis. Enzyme kinetic analyses, isothermal titration calorimetry (ITC), mass spectrometry and differential scanning fluorimetry (DSF) were used to characterise B. anthracis DHDPS and compare it with the well characterised Escherichia coli enzyme. B. anthracis DHDPS exhibited different kinetic behaviour compared with E. coli DHDPS, in particular, substrate inhibition by (S)-aspartate semi-aldehyde was observed for the B. anthracis enzyme (K(si(ASA))=5.4+/-0.5 mM), but not for the E. coli enzyme. As predicted from a comparison of the X-ray crystal structures, the B. anthracis enzyme was not inhibited by lysine. The B. anthracis enzyme was thermally stabilised by the first substrate, pyruvate, to a greater extent than its E. coli counterpart, but has a weaker affinity for pyruvate based on enzyme kinetics and ITC studies. This characterisation will provide useful information for the design of inhibitors as new antibiotics targeting B. anthracis.

At the Alzheimer's Day Center in Columbia, South Carolina, staff, families, and volunteers comprise the A-team. The team offers persons with Alzheimer's disease a homelike environment full of laughter and love, while providing respite for family caregivers.