Determination of dipole coupling constants using heteronuclear multiple quantum NMR

The problem of extracting dipole couplings from a system of N spins I = 1/2 and one spin S by NMR techniques is analyzed. The resolution attainable using a variety of single quantum methods is reviewed. The theory of heteronuclear multiple quantum (HMQ) NMR is developed, with particular emphasis being placed on the superior resolution available in HMQ spectra. Several novel pulse sequences are introduced, including a two-step method for the excitation of HMQ coherence. Experiments on partially oriented [1−13C] benzene demonstrate the excitation of the necessary HMQ coherence and illustrate the calculation of relative line intensities. Spectra of high order HMQ coherence under several different effective Hamiltonians achievable by multiple pulse sequences are discussed. A new effective Hamiltonian, scalar heteronuclear recoupled interactions by multiple pulse (SHRIMP), achieved by the simultaneous irradiation of both spin species with the same multiple pulse sequence, is introduced. Experiments are described which allow heteronuclear couplings to be correlated with an S-spin spreading parameter in spectra free of inhomogeneous broadening

A preliminary investigation for accidental load design of a submerged floating tube bridges

Submerged floating tunnels are more and more considered as a suitable solution to cross water channels limiting environmental impact on the visual landscape and ensuring large ship passage while crossing large distances between coasts. The design of this kind of strategical infrastructures must deal not only with live loads and particular loading conditions coming from the floating situation, but needs also to carefully consider accidental actions that concur to the global safety of the infrastructure. The construction of the new E39 highway along the Norwegian coast asks for crossing several fjords and this solution is seriously taken into consideration. For this reason, a comprehensive research program was aimed at the analysis of accidental load design of the infrastructure. This paper aims to present a comprehensive overview of an ad-hoc experimental investigation on the behavior of reinforced concrete (RC) circular slabs (60 cm diameter) under exposure to fire, blast, or a combination of both actions. Additionally, it seeks to draw design-driven conclusions that could be valuable for the design of critical infrastructure in scenarios involving fire and blast. The presented experimental campaign was intended to provide a benchmark for assessing the reliability of the design approaches to be adopted in the design of the global infrastructure. First of all, the concrete mechanical characterization at normal conditions and at high temperatures was performed referring both to uniaxial compression and uniaxial tension. The structural behavior of simply supported RC slabs has also been investigated by considering slabs exposed to a hydrocarbon fire curve at different exposure times and by considering the post-fire application of static or dynamic loading condition. In particular, the fire curve was applied by a gas burner while the dynamic load was reproduced by a shock tube equipment that was used to apply two different blast-like pressure histories

Tracking neuroinflammatory biomarkers in Alzheimer’s disease: a strategy for individualized therapeutic approaches?

Background: Recent trials of anti-amyloid-beta (A beta) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. Main body: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of A beta reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain A beta deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of A beta ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I"). Conclusions: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients

Sudden Death in End Stage Renal Disease : Comparing Hemodialysis versus Peritoneal Dialysis

Background/Aims: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). Methods: This is a multicenter retrospective cohort study. Results: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) \ue2\u89\ua435%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF \ue2\u89\ua435% (p < 0.05). Conclusions: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=464347

Increased Plasma Aldosterone Concentrations in Patients with Clinical Depression

BACKGROUND: Clinical depression has been increasingly recognized as an independent risk factor for adverse cardiovascular events, but the biological mechanisms of this association remain unclear. Recent evidence for renin system dysregulation in patients with depression led us to hypothesize that aldosterone--a well-recognized contributor to vascular injury--could be increased in depressed patients. The present study was designed, therefore, to be a cross-sectional investigation of plasma renin and aldosterone levels in depressed patients as compared with healthy controls with no history of psychiatric illness. METHODS: A total of 65 depressed patients and 65 age- and gender-matched control subjects were enrolled. Following a fixed sodium and potassium diet, venous blood samples were obtained at 9:00 a.m. to avoid the influence of circadian rhythms. RESULTS: Although there were no significant differences in plasma level of renin among subjects with depression and controls (7.9 +/- 5.8 vs. 6.4 +/- 4.3 pg/mL, respectively; p=0.10), depressed subjects exhibited greater mean aldosterone levels as compared with control subjects (157.2 +/- 67.5 vs. 125.7 +/- 38.1 pg/mL, respectively; p=0.0014). After adjusting for potential confounders, multivariate logistic regression analysis showed that subjects with depression had 2.77 times higher odds of elevated aldosterone levels compared with healthy control subjects (95% confidence interval, 1.30-5.92, p=0.008). CONCLUSIONS: Our present findings support the hypothesis that hyperaldosteronism could be a common feature among depressed patients, thereby suggesting that increased aldosterone levels may act as a mediator in the pathway linking depression to unfavorable vascular events