Explore the vast range of titles available.

Electrification of conventionally fired chemical reactors has the potential to reduce CO₂ emissions and provide flexible and compact heat generation. Here, we describe a disruptive approach to a fundamental process by integrating an electrically heated catalytic structure directly into a steam-methane–reforming (SMR) reactor for hydrogen production. Intimate contact between the electric heat source and the reaction site drives the reaction close to thermal equilibrium, increases catalyst utilization, and limits unwanted byproduct formation.The integrated design with small characteristic length scales allows compact reactor designs, potentially 100 times smaller than current reformer platforms. Electrification of SMR offers a strong platform for new reactor design, scale, and implementation opportunities. Implemented on a global scale, this could correspond to a reduction of nearly 1% of all CO₂ emissions.

Background Although leisure-time physical activity is important for health, adherence to regular exercise is challenging for many adults. The workplace may provide an optimal setting to reach a large proportion of the adult population needing regular physical exercise. This study evaluates the effect of implementing strength training at the workplace on non-specific neck and shoulder pain among industrial workers. Methods Cluster-randomized controlled trial involving 537 adults from occupations with high prevalence of neck and shoulder pain (industrial production units). Participants were randomized to 20 weeks of high-intensity strength training for the neck and shoulders three times a week (n = 282) or a control group receiving advice to stay physically active (n = 255). The strength training program followed principles of progressive overload and periodization. The primary outcome was changes in self-reported neck and shoulder pain intensity (scale 0-9). Results 85% of the participants followed the strength training program on a weekly basis. In the training group compared with the control group, neck pain intensity decreased significantly (-0.6, 95% CI -1.0 to -0.1) and shoulder pain intensity tended to decrease (-0.2, 95% CI -0.5 to 0.1, P = 0.07). For pain-cases at baseline (pain intensity > = 3) the odds ratio - in the training group compared with the control group - for being a non-case at follow-up (pain intensity < 3) was 2.0 (95% CI 1.0 to 4.2) for the neck and 3.9 (95% CI 1.7 to 9.4) for the shoulders. Conclusion High-intensity strength training relying on principles of progressive overload can be successfully implemented at industrial workplaces, and results in significant reductions of neck and shoulder pain. Trial registration NCT01071980 .

In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing 31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.

Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as immune-responsive gene 1 [IRG1]), are upregulated during atherogenesis in mice. Deletion of Acod1 in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4-octyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis.

Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors. Modulating the host immune response during tuberculosis is an emerging and critical advance in the therapeutic approach. Here the authors present data from a first-in-human phase I/II randomised trial on the safety and immunogenicity of adjuvant therapy of the H56:IC31 vaccine and cyclooxygenase-2 inhibitors in patients with tuberculosis.

•NOCAD is a progressive condition, emphasizing the importance of early prevention.•Statins help manage NOCAD, but adherence to therapy remains suboptimal.•VICAD-RISK study is a randomized controlled study on disease visualization in NOCAD.•The study assesses the impact of image visualization on LDL reduction after 1 year.•Results may improve patient engagement and adherence to preventive therapies. With the increasing use of coronary computed tomography angiography (CTA), the prevalence of patients with nonobstructive atherosclerotic coronary artery disease (NOCAD) is growing. Presence of NOCAD is associated with an increased risk of an unfavorable clinical outcome. Therefore, guideline-directed preventive strategies such as lipid-lowering therapy with statins are important. This study aims to assess whether visualization of personal CTA images to patients with a new diagnosis of NOCAD facilitates reduction of low-density lipoprotein (LDL) cholesterol (primary endpoint), improves statin adherence, influences the perception of statin-associated side effects, and modifies the coronary atherosclerotic phenotype. The VICAD-RISK study is a Danish multicenter randomized trial including statin naïve patients suspected of chronic coronary syndrome with a new diagnosis of NOCAD determined by first-line coronary CTA. A total of 273 patients will be randomized 1:1:1 into; (1) usual care; representing current clinical practice of general practitioner follow-up; (2) low-intensity intervention; specialized nurse consultation, or (3) high-intensity intervention; similar to group 2 and presentation of the personal CTA-images. All participants, including the intervention groups, will be followed at the discretion of their general practitioner. Research follow-up including biochemistry measurements, and coronary CTA investigation will be repeated for all participants after 12 months. The VICAD-RISK study evaluates whether personal CTA image visualization in patients with a new diagnosis of NOCAD improves reduction of LDL cholesterol. ClinicalTrials.gov, NCT06413641, www.clinicaltrials.gov.

Out-of-hospital cardiac arrest is a leading cause of death worldwide. Establishing vascular access is critical for administering guideline-recommended drugs during cardiopulmonary resuscitation. Both the intraosseous route and the intravenous route are used routinely, but their comparative effectiveness remains unclear. We conducted a randomized clinical trial to compare the effectiveness of initial attempts at intraosseous or intravenous vascular access in adults who had nontraumatic out-of-hospital cardiac arrest. The primary outcome was a sustained return of spontaneous circulation. Key secondary outcomes were survival at 30 days and survival at 30 days with a favorable neurologic outcome, defined by a score of 0 to 3 on the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability). Among 1506 patients who underwent randomization, 1479 were included in the primary analysis (731 in the intraosseous-access group and 748 in the intravenous-access group). The successful establishment of vascular access within two attempts occurred in 669 patients (92%) assigned to the intraosseous-access group and in 595 patients (80%) assigned to the intravenous-access group. Sustained return of spontaneous circulation occurred in 221 patients (30%) in the intraosseous-access group and in 214 patients (29%) in the intravenous-access group (risk ratio, 1.06; 95% confidence interval [CI], 0.90 to 1.24; P = 0.49). At 30 days, 85 patients (12%) in the intraosseous-access group and 75 patients (10%) in the intravenous-access group were alive (risk ratio, 1.16; 95% CI, 0.87 to 1.56); a favorable neurologic outcome at 30 days occurred in 67 patients (9%) and 59 patients (8%), respectively (risk ratio, 1.16; 95% CI, 0.83 to 1.62). Prespecified adverse events were uncommon. There was no significant difference in sustained return of spontaneous circulation between initial intraosseous and intravenous vascular access in adults who had out-of-hospital cardiac arrest. (Funded by the Novo Nordisk Foundation and others; IVIO EU Clinical Trials Register number, 2022-500744-38-00; ClinicalTrials.gov number, NCT05205031.).

Introduction Coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated. Aim To test whether lipid lowering therapy is associated with significant improvement in FFRCT, and whether there is a dose–response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery. Methods Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first‐line CTA, and FFRCT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFRCT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18‐month difference in FFRCT using (1) the FFRCT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study. Conclusion The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.

The interplay between systemic metabolism and immune responses is increasingly recognized as a significant factor in the dysregulation of glucose homeostasis associated with diabetes and obesity. Immune metabolites play crucial roles in mediating this crosstalk, with itaconate emerging as an important immune metabolite involved in the inflammatory response of macrophages. Recent studies have highlighted the role of itaconate as a regulator of glucose metabolism, particularly in the context of obesity, although the underlying mechanisms remain poorly understood. In this study, we identified itaconate as one of the metabolites that significantly increase in the liver during fasting compared to fed conditions. Mechanistically, we found that itaconate enhances glucagon-induced liver gluconeogenesis independently of insulin signaling. Notably, itaconate upregulates the expression of gluconeogenic genes both under basal conditions and in the presence of palmitic acid. Furthermore, our data indicate that the effects of itaconate occur independently of CREB activation. Instead, we demonstrate that these potentiating effects are mediated through the induction of nuclear factor erythroid 2-related factor 2 (NRF2). Our findings demonstrate that itaconate has a glucagon-potentiating effects in the liver, suggesting that itaconate may play a significant role in the pathogenesis of metabolic-associated liver diseases.