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Ney, Julia ; Heyland, Daren K. ; Amrein, Karin ; Marx, Gernot ; Grottke, Oliver ; Choudrakis, Michael ; Autschbach, Teresa ; Hill, Aileen ; Meybohm, Patrick ; Benstöm, Carina ; Goetzenich, Andreas ; Fitzner, Christina ; Stoppe, Christian
Background & aims: Recent studies indicate that vitamin D deficiency is associated with increased morbidity and mortality in critically ill patients. Knowledge about the functional role and clinical relevance of vitamin D for patients undergoing cardiac surgery is sparse. Therefore, we investigated the clinical significance of vitamin D levels on outcome of cardiac surgery patients.
Methods: 92 patients undergoing elective cardiac surgery with cardiopulmonary arrest were included in this prospective observational pilot study. 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were measured prior to surgery, immediately postoperatively as well as 6, 12 and 24 h after surgery. We assessed postoperative organ dysfunctions, infections and death until hospital discharge.
Results: The serum concentration of 1,25(OH)2D significantly decreased intraoperatively by 29.3% (p < 0.001) and was significantly lower at any postoperative time point compared to baseline values, whereas 25OHD levels did not show significant changes during the observation period. Coronary artery bypass graft (CABG) patients had significant higher baseline 1,25(OH)2D values than patients with valve surgery (39.7 ± 13.9 ng/l vs. 30.1 ± 14.1 ng/l, p = 0.010) or CABG + valve surgery (39.7 ± 13.9 ng/l vs. 32.6 ± 11.8 ng/l, p = 0.044).
Our data showed a significant odds ratio to develop postoperative organ dysfunction (OR 0.95; p = 0.009) and PCT levels ≥5 μg/l (OR 0.94; p = 0.046) for every ng/l increment in 1,25(OH)2D, when performing multivariable analysis and after adjusting for preoperative illness and demographics. In addition, multivariable-adjusted statistical analyses revealed that patients stayed significantly shorter on ICU (−0.21 h; p = 0.001) and in hospital (−2.6 days; p = 0.009) for every ng/l increment in 1,25(OH)2D.
Conclusion: Our data highlight important evidence about the clinical significance of 1,25(OH)2D levels in cardiac surgery patients. Higher levels were associated with significantly less postoperative organ dysfunctions, elevated PCT levels, death and prolonged hospital stay. 1,25(OH)2D levels decreased significantly intra- and postoperatively, while serum levels of 25OHD did not.
Trial registration: clinicaltrials.gov (NCT 02488876), registered May 1, 2015.
Brinker, Titus Josef ; Alfitian, Jonas ; Seeger, Werner ; Groneberg, Jan David Alexander ; Kalle, Christof von ; Enk, Alexander ; Herth, Felix ; Kreuter, Michael ; Bauer, Claudia M. ; Gatzka, Martina ; Suhre, Janina Leonie
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students
Minh, Truong Ngoc ; Xuan, Tran Dang ; Ahmad, Ateeque ; Elzaawely, Abdelnaser Abdelghany ; Teschke, Rolf ; Van, Truong Mai
Momilactones A and B (MA and MB, respectively) are phytoalexins and plant growth inhibitors available in rice husks. However, to date, the isolation and purification of the two compounds have been complicated, laborious, and less effective. The present study was conducted to establish a protocol to simplify and optimize quantities of MA and MB by combinations of ethyl acetate (EtOAc), distilled water, methanol (MeOH), temperature, and pressure for extractions. At a temperature of 100 °C, combined with EtOAc and MeOH 100%, MA and MB were enriched in greater quantities than non-treated rice husks, of which MB was much augmented than MA. The EtOAc extract obtained from samples dried at 100 °C for 1 h, then placed in MeOH 100% for 1 week, provided maximum yields of MA [58.76 µg/g dry weight (DW)] and MB (104.43 µg/g DW). The use of pressure effectively enhanced yields of MA (17.90–26.26 µg/g DW) and MB (40.78–71.0 µg/g DW). The actual purified amounts of MA and MB increased by 5 and 15 folds, respectively. The use of either sole distilled water or MeOH ≤ 50% at any temperature did not successfully isolate both MA and MB. The yield optimization aids to easier and more productive purification of the two compounds, and thus extends researches on biological activities of MA and MB, including pharmaceutical and medicinal properties.
Efficacy from different extractions for chemical profile and biological activities of rice husk
(2018)
Minh, Truong Ngoc ; Xuan, Tran Dang ; Ahmad, Ateeque ; Elzaawely, Abdelnaser Abdelghany ; Teschke, Rolf ; Van, Truong Mai
Rice husk is a by-product produced abundantly in rice production but it has low commercial value and causes environmental pollution. This study was conducted to examine different extracting solvents and conditions to optimize the efficacy of antioxidant and antimicrobial potentials, and chemical components in rice husk. By the use of distilled water at 100 °C, the ethyl acetate (EtOAc) extract was potent in both total phenolic content (TPC), total flavonoid content (TFC), and DPPH scavenging activity. The treatment of either ethyl acetate (100 °C, 1 h), combined with MeOH 100%, showed the highest percent of lipid peroxidation inhibition (LPI) (86%), meaning that the strongest antioxidant activity was by the β-carotene bleaching method. The treatment of distilled water at room temperature possessed the strongest antioxidant activity in the assay of the reducing power. The use of dried samples at 100 °C for 2 h, combined with methanol (MeOH) 10%, provided the most potent antimicrobial activities against Escherichia coli, Klebsiella pneumoniae, Listeria monocytogenes, Bacillus subtilis, and Proteus mirabilis. The results suggested that the EtOAc extract from rice husk could be a potential source of natural antioxidants. In general, the use of temperature 100 °C for 2 h, combined with either EtOAc or 10% MeOH, can optimize chemical components and antioxidant and antimicrobial capacities in rice husk. Principal constituents putatively identified by gas chromatography–mass spectrometry (GC–MS) revealed the presence of momilactones A and B (MA and MB, respectively), phenols, phenolic acids, and long-chain fatty acids, although yields of these compounds varied among extracts. The bioactive MA and MB were found in most of the extracts, except distilled water and MeOH ≤ 50%, at any temperature. Findings of this study provided optimal conditions for future production at an industrial scale for rice husk to exploit its potent biological properties. It thus helps to increase the economic value and reduce the disposal burden and environmental troubles caused by rice husk.
De Sousa Fernandes Perna, Elizabeth B. ; Theunissen, Eef L. ; Dolder, Patrick ; Mason, Natasha L. ; Hutten, Nadia R. P. W. ; Tönnes, Stefan W. ; Kuypers, Kim P. C. ; Ramaekers, Johannes G.
Availability of novel psychoactive substances (NPS) exponentially increased over the last years. Risk evaluations of NPS are hampered by the lack of pharmacological studies in humans on health parameters. The aim of the present study was to evaluate safety and neurocognitive function of healthy volunteers (N = 12) who received single doses of 100 and 150 mg 4-fluoroamphetamine (4-FA), a phenethylamine that has been associated with severe cardiovascular and cerebrovascular complications. The study was set-up as a placebo controlled, within subject, phase 1 trial as it was the first to administer 4-FA to humans under controlled conditions. Overall, 4-FA produced a strong elevation in blood pressure up until 4-5 h after administration that was followed by a sustained increase in heart rate. After an interim review of safety data from five participants, a decision was taken to cancel administration of 150 mg. We subsequently obtained complete datasets for placebo and 100 mg 4-FA treatments only. Effects of 4-FA on mood and neurocognitive function were most distinct at 1 h post drug and included significant elevations of vigor, friendliness, elation, arousal, positive mood, as well as improvements in attention and motor performance. Negative affect was also reported as time progressed in the acute phase and even more so during the subacute phase. Overall, the influence of 4-FA on vital signs, mood, and neurocognition was similar to that observed with other stimulants. Present findings confirm clinical observations of acute toxicity among 4-FA users and warrant warnings about potential health risks associated with 4-FA use.
Wörtge, Dennis ; Moll, Jochen ; Krozer, Viktor ; Bazrafshan, Babak ; Hübner, Frank ; Park, Clara ; Vogl, Thomas J.
Hemispherical and cylindrical antenna arrays are widely used in radar-based and tomography-based microwave breast imaging systems. Based on the dielectric contrast between healthy and malignant tissue, a three-dimensional image could be formed to locate the tumor. However, conventional X-ray mammography as the golden standard in breast cancer screening produces two-dimensional breast images so that a comparison between the 3D microwave image and the 2D mammogram could be difficult. In this paper, we present the design and realisation of a UWB breast imaging prototype for the frequency band from 1 to 9 GHz. We present a refined system design in light of the clinical usage by means of a planar scanning and compare microwave images with those obtained by X-ray mammography. Microwave transmission measurements were processed to create a two-dimensional image of the breast that can be compared directly with a two-dimensional mammogram. Preliminary results from a patient study are presented and discussed showing the ability of the proposed system to locate the tumor.
Banning, Antje ; Babuke, Tanja ; Kurrle, Nina Susanne ; Meister, Melanie ; Ruonala, Mika O. ; Tikkanen, Ritva
Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.
Bonham, James R. ; Carling, Rachel S. ; Lindner, Martin ; Franzson, Leifur ; Zetterstrom, Rolf ; Boemer, Francois ; Cerone, Roberto ; Eyskens, Francois ; Vilarinho, Laura ; Hougaard, David Michael ; Schielen, Peter C. J. I.
While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.
Laina, Ageliki ; Gatsiou, Aikaterini ; Georgiopoulos, Georgios ; Stamatelopoulos, Kimon ; Stellos, Konstantinos
Since our knowledge on structure and function of messenger RNA (mRNA) has expanded from merely being an intermediate molecule between DNA and proteins to the notion that RNA is a dynamic gene regulator that can be modified and edited, RNA has become a focus of interest into developing novel therapeutic schemes. Therapeutic modulation of RNA molecules by DNA- and RNA-based therapies has broadened the scope of therapeutic targets in infectious diseases, cancer, neurodegenerative diseases and most recently in cardiovascular diseases as well. Currently, antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), and microRNAs are the most widely applied therapeutic strategies to target RNA molecules and regulate gene expression and protein production. However, a number of barriers have to be overcome including instability, inadequate binding affinity and delivery to the tissues, immunogenicity, and off-target toxicity in order for these agents to evolve into efficient drugs. As cardiovascular diseases remain the leading cause of mortality worldwide, a large number of clinical trials are under development investigating the safety and efficacy of RNA therapeutics in clinical conditions such as familial hypercholesterolemia, diabetes mellitus, hypertriglyceridemia, cardiac amyloidosis, and atrial fibrillation. In this review, we summarize the clinical trials of RNA-targeting therapies in cardiovascular disease and critically discuss the advances, the outcomes, the limitations and the future directions of RNA therapeutics in precision transcriptomic medicine.
The development of genome editing tools capable of modifying specific genomic sequences with unprecedented accuracy has opened up a wide range of new possibilities in targeted gene manipulation. In particular, the CRISPR/Cas9 system, a repurposed prokaryotic adaptive immune system, has been widely adopted because of its unmatched simplicity and flexibility.
In this review we discuss achievements and current limitations of CRISPR/Cas9 genome editing in hematopoietic cells with special emphasis on its potential use in ex vivo gene therapy of monogenic blood disorders, HIV and cancer.