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Barron Bonner opublikował 1 rok, 3 miesiące temu
We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer’s disease (AD) patients in a phase 2b/3 trial (Alzheimer’s Management by Albumin Replacement [AMBAR] study).
Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14.
The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes>100%; P-values .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes 94%to>100%; P-values .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values .04 to .008).
PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.
PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.
Besides angiotensin converting enzyme 2 (ACE2), an active involvement of proteases (FURIN and/or TMPRSS2) is important for cellular entry of SARS-CoV-2. Therefore, a simultaneous expression profiling of entry proteins in a tissue might provide a better risk assessment of SARS-CoV-2 infection as compared to individual proteins. In an attempt to understand the relative susceptibility of oral squamous cell carcinoma (OSCC) lesions as compared to the normal oral mucosa (NOM) for SARS-CoV-2 attachment/entry, this study examined the mRNA and protein expression profiles of ACE2, FURIN, and TMPRSS2 in the corresponding tissues using public transcriptomic and proteomics datasets.
Public transcriptomic and proteomics datasets (the Cancer Genome Atlas (TCGA)/the Genotype-Tissue Expression (GTEx), the Human Protein Atlas (HPA), and two independent microarray datasets) were used to examine the expression profiles of ACE2, TMPRSS2 and FURIN in NOM and OSCC.
ACE2, TMPRSS2, and FURIN mRNAs were detected in NOM, however, at lower levels as compared to other body tissues. Except for moderate up-regulation of FURIN, expression levels of ACE2 and TMPRSS2 mRNA were unchanged/down-regulated in OSCC as compared to the NOM.
These results indicate that NOM may serve as a possible site for SARS-CoV-2 attachment, however, to a lesser extent as compared to organs with higher expression levels of the SARS-CoV-2 entry proteins. However, the evidence is lacking to suggest that expression status of entry proteins predisposes OSCC lesions to additional risk for SARS-CoV-2 attachment/entry as compared to NOM.
These results indicate that NOM may serve as a possible site for SARS-CoV-2 attachment, however, to a lesser extent as compared to organs with higher expression levels of the SARS-CoV-2 entry proteins. However, the evidence is lacking to suggest that expression status of entry proteins predisposes OSCC lesions to additional risk for SARS-CoV-2 attachment/entry as compared to NOM.
The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF.
Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP-proBNP]/total BNP)×100. We retrospectively identified the patients with reduced EF (≤40%, on admission) ssociated with future ventricular contractile recovery.
The ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.
In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known.
A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34mL/m
) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3 hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P=0.0006] and dilated left atria (Groups 2 and 4 HR 0.93, 95% CI 0.91-0.96; P<0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4 HR 1.018, 95% CI 1.011-1.024; P<0.00001) but not in those with normal PALS (Groups 1 and 2 HR 1.023, 95% CI 0.99-1.057; P=0.1).
Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.
Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.
Differential counts of leukocytes are frequent, and often several automated blood cell counters are needed in contemporary laboratories. However, these modules are often individually quality assured. Our aim was therefore to validate the interchangeability of five hematology modules in a large modern laboratory and to compare them with our gold standard (GS) manual white blood cell differential count.
At Copenhagen University Hospital, we compared five Sysmex XN-modules for neutrophils, lymphocytes, monocytes, eosinophils, basophils, and immature granulocytes (IG). We analyzed control samples in three levels to evaluate intra- and intermodular precision. Bias between modules was evaluated by analyzing 93 random patient samples within reference intervals. XN-modules’ mean counts were compared with GS.
We found acceptable intramodular CV% (0.92%-8.76%), only neutrophils and eosinophils exceeded state-of-the-art imprecision or desirable specifications for medium control levels. Intermodular CV% showed significance difference for only monocytes (ANOVA, P<.0001). For patient samples, there were significant differences between XN-modules regarding four WBC types (ANOVA); however, proportional bias ranged from 1.7% to 3.8%, being within desirable specifications except basophils and IG (bias=13.3% and 24.9%, respectively). Comparisons with GS, XN-modules exceeded desirable bias for basophils (lower than GS); monocytes and IG (higher than GS).
This multimodule comparison shows acceptable intermodular imprecision and bias for clinical purposes, which is important for patient safety. Similar multimodule study should be performed with samples out of reference range in large-scale laboratories to confirm the interchangeability.
This multimodule comparison shows acceptable intermodular imprecision and bias for clinical purposes, which is important for patient safety. Similar multimodule study should be performed with samples out of reference range in large-scale laboratories to confirm the interchangeability.
Both left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO
. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial emptying fraction (LAEF).
We analysed echocardiographic measurements, cardiopulmonary exercise testing (CPET), and isokinetic muscle function in 55 subjects with HF and controls [17 heart failure with preserved ejection fraction (HFpEF), 18 heart failure with reduced ejection fraction (HFrEF), and 20 healthy controls]. Patients with reduced LAEF showed reduced peak VO
14.3±3.5 vs. 18.5±3.5mL/min/kg, P=0.003, and reduced muscle endurance (RME) 64.3±23.9 vs. 88.5±32.3Nm/kg, P=0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) was associated withtions of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful.Mechanisms of soil organic carbon (SOC) stabilization have been widely studied due to their relevance in the global carbon cycle. No-till (NT) has been frequently adopted to sequester SOC; however, limited information is available regarding whether sequestered SOC will be stabilized for long term. Thus, we reviewed the mechanisms affecting SOC stability in NT systems, including the priming effects (PE), molecular structure of SOC, aggregate protection, association with soil minerals, microbial properties, and environmental effects. Although a more steady-state molecular structure of SOC is observed in NT compared with conventional tillage (CT), SOC stability may depend more on physical and chemical protection. On average, NT improves macro-aggregation by 32.7%, and lowers SOC mineralization in macro-aggregates compared with CT. Chemical protection is also important due to the direct adsorption of organic molecules and the enhancement of aggregation by soil minerals. Higher microbial activity in NT could also produce binding agents to promote aggregation and the formation of metal-oxidant organic complexes. Thus, microbial residues could be stabilized in soils over the long term through their attachment to mineral surfaces and entrapment of aggregates under NT. On average, NT reduces SOC mineralization by 18.8% and PE intensities after fresh carbon inputs by 21.0% compared with CT (p less then .05). Although higher temperature sensitivity (Q10 ) is observed in NT due to greater Q10 in macro-aggregates, an increase of soil moisture regime in NT could potentially constrain the improvement of Q10 . This review improves process-based understanding of the physical and chemical mechanism of protection that can act, independently or interactively, to enhance SOC preservation. It is concluded that SOC sequestered in NT systems is likely to be stabilized over the long term.


