Objective
Evidence suggests that intima–media thickness (IMT) and plasma homocysteine (Hcy) levels are associated with one another, and both appear to be related to cognitive dysfunction. However, no ...connection between both factors taken together and mild cognitive impairment (MCI) has been established. This study analysed potential relationships between IMT, Hcy and MCI.
Methods
We included 105 patients with MCI and 76 controls with no history of vascular disease. All participants underwent laboratory analyses, a carotid ultrasound, and clinical and neuropsychological assessment. We used the Mantel–Haenszel test (MHT), ANCOVA and multiple linear regression models (MLRM) to examine any associations between IMT, Hcy and cognitive state.
Results
The MHT revealed a significant association between IMT and risk of MCI (z = 4.285, P < 0.0001). The OR for the upper quartile vs the lower quartile was 5.12 (95% CI: 2.12–12.36). MHT also showed a clear association between Hcy levels and risk of MCI (z = 3.01, P = 0.003). OR for the upper vs the lower quartile was 3.39 (95% CI: 1.41–8.12). Additionally, we found a correlation between IMT and Hcy (r = 0.162, P = 0.032).
Conclusions
Our results suggest that there is a connection between IMT, Hcy levels and presence of amnestic MCI in a population with no history of clinically manifest atherosclerosis. Furthermore, there is also a connection between the IMT and Hcy levels themselves.
The interest on magnesium (Mg) has grown since clinical studies have shown the efficacy of Mg-containing phosphate binders. However, some concern has arisen for the potential effect of increased ...serum Mg on parathyroid hormone (PTH) secretion. Our objective was to evaluate the direct effect of Mg in the regulation of the parathyroid function; specifically, PTH secretion and the expression of parathyroid cell receptors: CaR, the vitamin D receptor (VDR) and FGFR1/Klotho.
The work was performed in vitro by incubating intact rat parathyroid glands in different calcium (Ca) and Mg concentrations.
Increasing Mg concentrations from 0.5 to 2 mM produced a left shift of PTH-Ca curves. With Mg 5 mM, the secretory response was practically abolished. Mg was able to reduce PTH only if parathyroid glands were exposed to moderately low Ca concentrations; with normal-high Ca concentrations, the effect of Mg on PTH inhibition was minor or absent. After 6-h incubation at a Ca concentration of 1.0 mM, the expression of parathyroid CaR, VDR, FGFR1 and Klotho (at mRNA and protein levels) was increased with a Mg concentration of 2.0 when compared with 0.5 mM.
Mg reduces PTH secretion mainly when a moderate low calcium concentration is present; Mg also modulates parathyroid glands function through upregulation of the key cellular receptors CaR, VDR and FGF23/Klotho system.
Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID‐19 disease, caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) virus. Here, we examine ...the levels of various plasma species of the SARS‐CoV‐2 host receptor, the angiotensin‐converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C‐terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full‐length ACE2 species were also examined in serum samples derived from humanized K18‐hACE2 mice challenged with a lethal dose of SARS‐CoV‐2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full‐length forms (95, 100, 130, and 170 kDa). COVID‐19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full‐length species, while a truncated 70‐kDa form was marginally higher compared with non‐disease controls (n = 26). Levels of ACE2 full‐length species were in the normal range in patients after a recovery period with an interval of 58‐70 days (n = 29), while the 70‐kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS‐CoV‐2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID‐19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS‐CoV‐2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.
Purpose
The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic ...characteristics of a cohort of patients with CNO.
Methods
A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)–confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR).
Results
One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (
p
< 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s,
p
< 0.001; 0.80 vs 1.00,
p
< 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%,
p
= 0.051).
Conclusion
The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.
Background and purpose
Recently, brain and vascular imaging have been added to clinical variables to identify patients with transient ischaemic attack (TIA) with a high risk of stroke recurrence. The ...aim of our study was to externally validate the ABCD3‐I score and the same score taking into account intracranial circulation.
Methods
We analyzed data from 1137 patients with TIA from the PROMAPA study who underwent diffusion‐weighted magnetic resonance imaging (DWI) within 7 days of symptom onset. Clinical variables and diagnostic work‐up were recorded prospectively. The end‐points were subsequent stroke at 7 and 90 days follow‐up.
Results
A total of 463 (40.7%) subjects fulfilled all inclusion criteria. During follow‐up, eight patients (1.7%) had a stroke within 7 days, and 14 (3.1%) had a stroke within 3 months. In the Cox proportional hazard multivariate analyses, the combination of large‐artery atherosclerosis and positive DWI remained as independent predictors of stroke recurrence at 7‐ and 90‐day follow‐up HR 8.23, 95% confidence interval (CI) 2.89–23.46, P < 0.001. The ABCD3‐I score was a powerful predictor of subsequent stroke. The area under the receiver operating characteristic curve was 0.83 (95% CI 0.72–0.93) at 7 days and 0.69 (95% CI 0.53–0.85) at 90 days. When we include intracranial vessel disease in the score, the area under the curve increases but the difference observed was non‐significant.
Conclusion
The inclusion of vascular and neuroimaging information to clinical scales (ABCD3‐I score) provides important prognostic information and also helps management decisions, although it cannot give a complete distinction between high‐risk and low‐risk groups.
Eighty‐four HCV/HIV‐coinfected and 252‐matched HCV‐monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty‐six (43%) HCV/HIV‐coinfected and 75 (30%) ...HCV‐monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42–64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420–3.413 p < 0.001). Multivariate analysis of only the HCV/HIV‐coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32–6.76), donor risk index (HR, 9.48; 95% CI, 2.75–32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03–0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV‐infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5‐year prognosis (69%95% CI, 54–80) to that of HCV‐monoinfected recipients. In conclusion, 5‐year survival in HCV/HIV‐coinfected liver recipients was lower than in HCV‐monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.
Taken as a whole, HCV/HIV‐coinfected liver transplant recipients have lower posttransplant survival than matched HCV‐monoinfected liver transplant recipients, although an important subset of coinfected patients with survival similar to that of HCV‐monoinfected patients can be identified retrospectively.
Background. There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety ...of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. Methods. The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). Results. The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. Conclusions. Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.
Cryo‐electron microscopy (cryoEM) has become a well established technique to elucidate the 3D structures of biological macromolecules. Projection images from thousands of macromolecules that are ...assumed to be structurally identical are combined into a single 3D map representing the Coulomb potential of the macromolecule under study. This article discusses possible caveats along the image‐processing path and how to avoid them to obtain a reliable 3D structure. Some of these problems are very well known in the community. These may be referred to as sample‐related (such as specimen denaturation at interfaces or non‐uniform projection geometry leading to underrepresented projection directions). The rest are related to the algorithms used. While some have been discussed in depth in the literature, such as the use of an incorrect initial volume, others have received much less attention. However, they are fundamental in any data‐analysis approach. Chiefly among them, instabilities in estimating many of the key parameters that are required for a correct 3D reconstruction that occur all along the processing workflow are referred to, which may significantly affect the reliability of the whole process. In the field, the term overfitting has been coined to refer to some particular kinds of artifacts. It is argued that overfitting is a statistical bias in key parameter‐estimation steps in the 3D reconstruction process, including intrinsic algorithmic bias. It is also shown that common tools (Fourier shell correlation) and strategies (gold standard) that are normally used to detect or prevent overfitting do not fully protect against it. Alternatively, it is proposed that detecting the bias that leads to overfitting is much easier when addressed at the level of parameter estimation, rather than detecting it once the particle images have been combined into a 3D map. Comparing the results from multiple algorithms (or at least, independent executions of the same algorithm) can detect parameter bias. These multiple executions could then be averaged to give a lower variance estimate of the underlying parameters.
Single‐particle analysis (SPA) by cryo‐electron microscopy comprises the estimation of many parameters along its image‐processing pipeline. Overfitting observed in SPA is normally due to misestimated parameters, and the only way to identify these is by comparing the estimates of multiple algorithms or, at least, multiple executions of the same algorithm.
The use of polymer matrix composite materials in the armor industry has rapidly increased. In the present work, the ballistic efficiency of body armor manufactured using a polymer-based composite, ...with a laminar configuration, was tested. For the composite, a synthesized polyamide 6 reinforced with 37% weight of fiberglass (GF) and an aramid fabric, were used. The laminar configuration of the composite, like a sandwich form with a size of 30 cm × 30 cm, was made with two panels of composite material (PA6 + 37 wt % GF) and an intermediate aramid fabric layer. It was tested in ballistic environments with available firearms. The results showed that the manufactured body armor prevents the penetration of a 9 mm bullet enabling its potential use as an urban armor level III-A, according to NIJ-Standard-0101.04. However, after testing with weapons larger than 9 mm in caliber, it was permanently deformed (5.56 mm and 7.62 mm weapons), which is why the level IV is not recommended.
Because of climate change and the scarce availability of natural resources there is a need to develop sustainable intensification strategies intended for optimizing water use in vineyards. In this ...study, water regime, fertilization and soil management practices were assessed in terms of vineyard water use, by evaluating the inter-row and crop line evapotranspiration (ET) components using the Mapping EvapoTranspiration at high Resolution with Internalized Calibration (METRIC) model in combination with unmanned aerial vehicle multispectral and thermal images taken on five dates throughout the growing season. The application of the METRIC-UAV using high-resolution imagery was proven as a useful tool for evaluating the effects of sustainable intensification strategies on water use of crops where vegetation does not completely cover the soil, identifying the most efficient site-specific strategies for water conservation purposes. Moreover, METRIC-UAV allowed evaluating separately their effects on the inter-row and the crop line. Among the assessed sustainable intensification strategies, the application of mulching provided the highest water savings (- 28%) when compared to traditional soil tillage management, reducing inter-row soil evaporation by 63%, while increasing crop-line ET by 14%. In spite of this, the mulching application did not affect yield, but significantly enhanced water use efficiency (WUE) in terms of grape yield compared to tillage. The adoption of deficit irrigation (DI) strategies did not result in vine water stress that was severe enough to significantly affect crop line ET when compared with fully irrigated (FI) vines. Both DI and FI strategies increased vine water use by 18% and 27%, respectively, as compared to the rainfed regime, with no differences found in the inter-row water consumption. DI and FI, in turn, significantly increased yield as compared to rainfed crops, leading to significant improvements in WUE. In the short term, the application of supplemental inorganic fertilizers did not modify either the vineyard water use or vine performance.
•Surface energy balance models with high-resolution imagery for water use evaluation.•METRIC-UAV allowed evaluating separately the inter row and crop line responses.•Mulching and full irrigation strategies increased vineyard water use efficiency.
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