Impact of sharing Alzheimer's disease biomarkers with individuals without dementia:A systematic review and meta-analysis of empirical data

Introduction: We conducted a systematic literature review and meta-analysis of empirical evidence on expected and experienced implications of sharing Alzheimer's disease (AD) biomarker results with individuals without dementia. Methods: PubMed, Embase, APA PsycInfo, and Web of Science Core Collection were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results from included studies were synthesized, and quantitative data on psychosocial impact were meta-analyzed using a random-effects model. Results: We included 35 publications. Most personal stakeholders expressed interest in biomarker assessment. Learning negative biomarker results led to relief and sometimes frustration, while positive biomarkers induced anxiety but also clarity. Meta-analysis of five studies including 2012 participants (elevated amyloid = 1324 [66%], asymptomatic = 1855 [92%]) showed short-term psychological impact was not significant (random-effect estimate = 0.10, standard error = 0.23, P = 0.65). Most professional stakeholders valued biomarker testing, although attitudes and practices varied considerably. Discussion: Interest in AD biomarker testing was high and sharing their results did not cause psychological harm. Highlights: Most personal stakeholders expressed interest in Alzheimer's disease biomarker assessment. Personal motivations included gaining insight, improving lifestyle, or preparing for the future. There was no short-term psychological impact of sharing biomarker status, implying it can be safe. Most professional stakeholders valued biomarker testing, believing the benefits outweigh the risk. Harmonized guidelines on biomarker testing and sharing results are required.</p

Direct simulation of ion beam induced stressing and amorphization of silicon

Using molecular dynamics (MD) simulation, we investigate the mechanical response of silicon to high dose ion-irradiation. We employ a realistic and efficient model to directly simulate ion beam induced amorphization. Structural properties of the amorphized sample are compared with experimental data and results of other simulation studies. We find the behavior of the irradiated material is related to the rate at which it can relax. Depending upon the ability to deform, we observe either the generation of a high compressive stress and subsequent expansion of the material, or generation of tensile stress and densification. We note that statistical material properties, such as radial distribution functions are not sufficient to differentiate between different densities of amorphous samples. For any reasonable deformation rate, we observe an expansion of the target upon amorphization in agreement with experimental observations. This is in contrast to simulations of quenching which usually result in denser structures relative to crystalline Si. We conclude that although there is substantial agreement between experimental measurements and most simulation results, the amorphous structures being investigated may have fundamental differences; the difference in density can be attributed to local defects within the amorphous network. Finally we show that annealing simulations of our amorphized samples can lead to a reduction of high energy local defects without a large scale rearrangement of the amorphous network. This supports the proposal that defects in amorphous silicon are analogous to those in crystalline silicon.Comment: 13 pages, 12 figure

Perfusion patterns in patients with chronic limb-threatening ischemia versus control patients using near-infrared fluorescence imaging with indocyanine green

In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform(R) (Middenmeer, The Netherlands). The time-intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage.Cardiovascular Aspects of Radiolog

Perfusion parameters in near-infrared fluorescence imaging with indocyanine green: a systematic review of the literature

(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Antimicrobial susceptibility of organisms causing community-acquired urinary tract infections in Gauteng Province, South Africa

BACKGROUND: Patients with community-acquired urinary tract infections (UTIs) frequently present to healthcare facilities in South Africa (SA). AIM: To provide information on UTI aetiology and antimicrobial susceptibility of pathogens. METHODS: We recruited women with UTI-related symptoms, who tested positive for ≥2 urine dipstick criteria (proteinuria, blood, leucocytes or nitrites) at 1 public and 5 private primary healthcare facilities in 2011. Demographic and clinical data were recorded and mid-stream urine (MSU) specimens were cultured. UTI pathogens were Gram-stained and identified to species level. Etest-based antimicrobial susceptibility testing was performed for amoxicillin/clavulanic acid, cefixime, cefuroxime, ciprofloxacin, fosfomycin, levofloxacin, nitrofurantoin, norfloxacin and trimethoprim/sulphamethoxazole. RESULTS: Of the 460 women recruited, 425 MSU samples were processed and 204 UTI pathogens were identified in 201 samples. Most pathogens were Gram-negative bacilli (GNB) (182; 89.2%) and 22 (10.8%) were Gram-positive cocci (GPC). Escherichia coli was the most frequent GNB (160; 79.6%), while Enterococcus faecalis was the predominant GPC (8; 4.0%). The UTI pathogens had similar susceptibility profiles for fosfomycin (95.5%; 95% confidence interval (CI) 92.6 - 98.4), the 3 fluoroquinolones (94.1%; 95% CI 90.8 - 97.4), nitrofurantoin (91.7%; 95% CI 87.8 - 95.6), cefuroxime (90.1%; 95% CI 86.0 - 94.3) and cefixime (88.2%; 95% CI 83.7 - 92.6). UTI pathogens were less susceptible to amoxicillin/clavulanic acid (82.8%; 95% CI 77.5 - 88.0) when compared with fluoroquinolones and fosfomycin. Trimethoprim/ sulphamethoxazole was the least efficacious antimicrobial agent (44.3% susceptible; 95% CI 37.4 - 51.2). CONCLUSION: This study provides relevant data for the empirical treatment of community-acquired UTIs in SA

The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis

MIR139 is a tumor suppressor and is commonly silenced in acute myeloid leukemia (AML). However, the tumor-suppressing activities of miR-139 and molecular mechanisms of MIR139-silencing remain largely unknown. Here, we studied the poorly prognostic MLL-AF9 fusion protein-expressing AML. We show that MLL-AF9 expression in hematopoietic precursors caused epigenetic silencing of MIR139, whereas overexpression of MIR139 inhibited in vitro and in vivo AML outgrowth. We identified novel miR-139 targets that mediate the tumor-suppressing activities of miR-139 in MLL-AF9 AML. We revealed that two enhancer regions control MIR139 expression and found that the polycomb repressive complex 2 (PRC2) downstream of MLL-AF9 epigenetically silenced MIR139 in AML. Finally, a genome-wide CRISPR-Cas9 knockout screen revealed RNA Polymerase 2 Subunit M (POLR2M) as a novel MIR139-regulatory factor. Our findings elucidate the molecular control of tumor suppressor MIR139 and reveal a role for POLR2M in the MIR139-silencing mechanism, downstream of MLL-AF9 and PRC2 in AML. In addition, we confirmed these findings in human AML cell lines with different oncogenic aberrations, suggesting that this is a more common oncogenic mechanism in AML. Our results may pave the way for new targeted therapy in AML.Proteomic

The role of reactive oxygen species in apoptosis of the diabetic kidney

Increased levels of reactive oxygen species (ROS) by hyperglycemia can induce apoptosis of renal cells and diabetic nephropathy. The redox balance in the renal cell seems, therefore, of the utmost importance. ROS-mediated apoptosis may be further aggravated by an inadequate cytoprotective response against ROS. When there are insufficient cytoprotective and ROS scavenging molecules, ROS lead to considerable cellular damage and to a point of no return in apoptosis. Induction of cytoprotective proteins may prevent or attenuate apoptosis, renal cell injury, and finally diabetic nephropathy. Here, we discuss some mechanisms of apoptosis and several strategies that have been probed to ameliorate, or to prevent apoptosis in the diabetic kidney