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In this study, patients treated in ICUs were at high risk for new cognitive impairment during 12 months of follow-up, with 24% of patients having deficits similar in severity to those in Alzheimer's disease. A longer duration of delirium was associated with worse cognitive scores. Survivors of critical illness frequently have a prolonged and poorly understood form of cognitive dysfunction, 1 – 4 which is characterized by new deficits (or exacerbations of preexisting mild deficits) in global cognition or executive function. This long-term cognitive impairment after critical illness may be a growing public health problem, given the large number of acutely ill patients being treated in intensive care units (ICUs) globally. 5 Among older adults, cognitive decline is associated with institutionalization, 6 hospitalization, 7 and considerable annual societal costs. 8 , 9 Yet little is known about the epidemiology of long-term cognitive impairment after critical illness. Delirium, a form of acute brain . . .

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene–gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts.

In the aftermath of 2 extreme weather events in 2022, Malawi experienced a severe cholera outbreak; 59,325 cases and 1,774 deaths were reported by March 31, 2024. We generated 49 Vibrio cholerae full genomes from isolates collected during December 2022-March 2023. Phylogenetic and phylogeographic methods confirmed that the Malawi outbreak strains originated from Pakistan's 2022 cholera outbreak. That finding aligns with substantial travel between the 2 countries. The estimated most recent ancestor of this lineage was from June-August 2022, coinciding with Pakistan's floods and cholera surge. Our analysis indicates that major floods in Malawi contributed to the outbreak; reproduction numbers peaked in late December 2022. We conclude that extreme weather events and humanitarian crises in Malawi created conditions conducive to the spread of cholera, and population displacement likely contributed to transmission to susceptible populations in areas relatively unaffected by cholera for more than a decade.

Aims Lipocalin‐2 is a pro‐inflammatory molecule characterized by a highly diversified pattern of expression and structure–functional relationships. In vivo, this molecule exists as multiple variants due to post‐translational modifications and/or protein–protein interactions. Lipocalin‐2 is modified by polyamination, which enhances the clearance of this protein from the circulation and prevents its excessive accumulation in tissues. On the other hand, animal studies suggest that non‐polyaminated lipocalin‐2 (npLcn2) plays a causal role in the pathogenesis of obesity‐associated medical complications. The present study examined the presence of npLcn2 in samples from healthy volunteers or patients with cardiac abnormalities and evaluated npLcn2 as a biomarker for cardiometabolic risk assessment. Methods and results Immunoassays were developed to quantify npLcn2 in blood and urine samples collected from 100 volunteers (59 men and 41 women), or venous plasma and pericardial fluid samples obtained from 37 cardiothoracic surgery patients. In healthy volunteers, npLcn2 levels in serum are significantly higher in obese and overweight than in lean subjects. After adjustment for age, gender, smoking, and body mass index (BMI), serum npLcn2 levels are positively correlated with heart rate, circulating triglycerides, high‐sensitivity C‐reactive protein (hsCRP), and creatinine in plasma. The npLcn2 levels in urine are significantly increased in subjects with metabolic syndrome and positively correlated with BMI, heart rate, circulating triglycerides, and urinary aldosterone. In cardiothoracic surgery patients, the circulating concentrations of npLcn2 are higher (more than two‐fold) than those of healthy volunteers and positively correlated with the accumulation of this protein in the pericardial fluid. Heart failure patients exhibit excessive expression and distribution of npLcn2 in mesothelial cells and adipocytes of the parietal pericardium, which are significantly correlated with the elevated plasma levels of npLcn2, total cholesterol, and creatinine. Conclusions Quantitative and qualitative evaluation of npLcn2 in human biofluid samples and tissue samples can be applied for risk assessment of healthy individuals and disease management of patients with obesity‐related cardiometabolic and renal complications.

BackgroundStroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention.MethodsMEDLINE, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020, for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo, in patients with ischaemic stroke. Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess study quality. This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.ResultsEighteen randomised trials comprising 11 429 participants were included in this meta-analysis. Most trials possessed low risk of bias and were of low heterogeneity. Cilostazol significantly reduced the rate of ischaemic stroke recurrence (risk ratio, RR=0.69, 95% CI 0.58 to 0.81), any stroke recurrence (RR=0.64, 95% CI 0.54 to 0.74) and major adverse cardiovascular events (RR=0.67, 95% CI 0.56 to 0.81). Cilostazol did not significantly decrease mortality (RR=0.90, 95% CI 0.64 to 1.25) or increase the rate of good functional outcome (Modified Rankin Scale score of 0–1; RR=1.07, 95% CI 0.95 to 1.19). Cilostazol demonstrated favourable safety profile, significantly reducing the risk of intracranial haemorrhage (RR=0.46, 95% CI 0.31 to 0.68) and major haemorrhagic events (RR=0.49, 95% CI 0.34 to 0.70).ConclusionsCilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes. Future randomised trials can be conducted outside East Asia, or compare cilostazol with a wider range of antiplatelet agents.

Metallic interconnects in solid oxide fuel cells are exposed to a dual environment: fuel on one side (i.e., H2 gas) and oxidizer on the other side (i.e., air). It has been observed that the oxidation behavior of thin stainless steel sheet in air is changed by the presence of H2 on the other side of the sheet. The resulting dual-environment scales are flaky and more friable than the single-environment scales. The H2 disrupts the scale on the air side. A model to explain some of the effects of a dual environment is presented where hydrogen diffusing through the stainless steel sheet reacts with oxygen diffusing through the scale to form water vapor, which has sufficient vapor pressure to mechanically disrupt the scale. Experiments on preoxidized 316L stainless steel tubing exposed to air-air, H2-air, and H2-Ar environments are reported in support of the model.[PUBLICATION ABSTRACT]

Although technological change is a hallmark of health care worldwide, relatively little evidence exists on whether changes in health care differ across the very different health care systems of developed countries. We present new comparative evidence on heart attack care in seventeen countries showing that technological change--changes in medical treatments that affect the quality and cost of care--is universal but has differed greatly around the world. Differences in treatment rates are greatest for costly medical technologies, where strict financing limits and other policies to restrict adoption of intensive technologies have been associated with divergences in medical practices over time. Countries appear to differ systematically in the time at which intensive cardiac procedures began to be widely used and in the rate of growth of the procedures. The differences appear to be related to economic and regulatory incentives of the health care systems and may have important economic and health consequences.

This study examines the effectiveness of various waterflooding strategies to recover pooled dense nonaqueous phase liquid (DNAPL) from the subsurface at an industrial facility. The relative influence of horizontal injection/recovery well configuration, established hydraulic gradient, and fluid properties is investigated for a site characterized by a homogeneous silty sand underlain by an impermeable clay layer. The top of the clay layer is located 5 m below the water table and supports a laterally extensive 2 m deep DNAPL pool. The sensitivity study employs a two-phase flow numerical model that simulates both DNAPL infiltration and redistribution, including the formation of immobilized DNAPL residual. This is accomplished with constitutive relations featuring hysteretic capillary pressure-saturation pathways in which the local amount of residual formed is a function of the maximum nonwetting saturation attained during infiltration. Sixteen simulations, performed in two-dimensional vertical cross-section, demonstrate that strategies effecting increased wetting phase gradients, namely increasing drawdown at the recovery drain, adding injection wells, and reducing their distance to the recovery drain, result in an increased DNAPL volume recovered with time at the expense of increased volumes of ground water removed per unit volume of DNAPL recovered. Strategies which do not increase wetting phase gradients result in DNAPL recovery with a minimum volume of produced contaminated ground water. Three pulsed pumping simulations indicate that increasing the length of pump shut-down time decreases the recovery of DNAPL with time but increases efficiency with respect to ground water pumped. Decreased nonwetting density and increased interfacial tension result in poorer DNAPL recovery with respect to both time and volume of ground water removed, while reduced nonwetting viscosity corresponds to dramatically increased efficiency in both respects

The development of Wilms' tumor, a pediatric nephroblastoma, has been associated with a deletion in the p13 region of chromosome 11. The structure and function or functions of this deleted genetic material are unknown. The role of this deletion in the process of malignant transformation was investigated by introducing a normal human chromosome 11 into a Wilms' tumor cell line by means of the microcell transfer technique. These variant cells, derived by microcell hybridization, expressed similar transformed traits in culture as the parental cell line. Furthermore, expression of several proto-oncogenes by the parental cells was unaffected by the introduction of this chromosome. However, the ability of these cells to form tumors in nude mice was completely suppressed. Transfer of other chromosomes, namely X and 13, had no effect on the tumorigenicity of the Wilms' tumor cells. These studies provide support for the existence of genetic information on chromosome 11 which can control the malignant expression of Wilms' tumor cells.

To investigate nitrogen assimilation and translocation in Zea mays L. colonized by the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus fasciculatum (Thax. sensu Gerd.), we measured key enzyme activities, 15N incorporation into free amino acids, and 15N translocation from roots to shoots. Glutamine synthetase and nitrate reductase activities were increased in both roots and shoots compared with control plants, and glutamate dehydrogenase activity increased in roots only. In the presence of [15N]ammonium, glutamine amide was the most heavily labeled product. More label was incorporated into amino acids in VAM plants. The kinetics of 15N labeling and effects of methionine sulfoximine on distribution of 15N-labeled products were entirely consistent with the operation of the glutamate synthase cycle. No evidence was found for ammonium assimilation via glutamate dehydrogenase. 15N translocation from roots to shoots through the xylem was higher in VAM plants compared with control plants. These results establish that, in maize, VAM fungi increase ammonium assimilation, glutamine production, and xylem nitrogen translocation. Unlike some ectomycorrhizal fungi, VAM fungi do not appear to alter the pathway of ammonium assimilation in roots of their hosts