Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 863
1.
Nutrients ; 16(10)2024 May 16.
Article En | MEDLINE | ID: mdl-38794738

As the population ages, the incidence of age-related neurodegenerative diseases is rapidly increasing, and novel approaches to mitigate this soaring prevalence are sorely needed. Recent studies have highlighted the importance of gut microbial homeostasis and its impact on brain functions, commonly referred to as the gut-brain axis, in maintaining overall health and wellbeing. Nonetheless, the mechanisms by which this system acts remains poorly defined. In this review, we will explore how (poly)phenols, a class of natural compounds found in many plant-based foods and beverages, can modulate the gut-brain axis, and thereby promote neural health. While evidence indicates a beneficial role of (poly)phenol consumption as part of a balanced diet, human studies are scarce and mechanistic insight is still lacking. In this regard, we make the case that dietary (poly)phenols should be further explored to establish their therapeutic efficacy on brain health through modulation of the gut-brain axis, with much greater emphasis on carefully designed human interventions.


Aging , Brain-Gut Axis , Diet , Gastrointestinal Microbiome , Polyphenols , Humans , Aging/physiology , Polyphenols/pharmacology , Gastrointestinal Microbiome/physiology , Gastrointestinal Microbiome/drug effects , Brain-Gut Axis/physiology , Brain/physiology , Brain/metabolism , Brain/drug effects , Neurodegenerative Diseases , Animals
2.
BMC Geriatr ; 24(1): 461, 2024 May 27.
Article En | MEDLINE | ID: mdl-38797837

BACKGROUND: Fragility fractures of the pelvis (FFPs) represent a significant health burden, particularly for the elderly. The role of sarcopenia, an age-related loss of muscle mass and function, in the development and impact of these fractures is not well understood. This study aims to investigate the prevalence and impact of osteoporosis and sarcopenia in patients presenting with FFPs. METHODS: This retrospective study evaluated 140 elderly patients with FFPs. The diagnosis of sarcopenia was assessed by psoas muscle area (PMA) and the height-adjusted psoas muscle index (PMI) measured on computed tomography (CT) scans. Clinical data, radiological findings and functional outcomes were recorded and compared with the presence or absence of sarcopenia and osteoporosis. RESULTS: Our study cohort comprised 119 female (85.0%) and 21 (15.0%) male patients. The mean age at the time of injury or onset of symptoms was 82.26 ± 8.50 years. Sarcopenia was diagnosed in 68.6% (n = 96) patients using PMA and 68.8% (n = 88) using PMI. 73.6% (n = 103) of our study population had osteoporosis and 20.0% (n = 28) presented with osteopenia. Patients with sarcopenia and osteoporosis had longer hospital stays (p < 0.04), a higher rate of complications (p < 0.048) and functional recovery was significantly impaired, as evidenced by a greater need for assistance in daily living (p < 0.03). However, they were less likely to undergo surgery (p < 0.03) and the type of FFP differed significantly (p < 0.04). There was no significant difference in mortality rate, pre-hospital health status, age or gender. CONCLUSION: Our study highlights the important role of sarcopenia in FFPs in terms of the serious impact on health and quality of life in elderly patients especially when osteoporosis and sarcopenia occur together. Identifying and targeting sarcopenia in older patients may be an important strategy to reduce pelvic fractures and improve recovery. Further research is needed to develop effective prevention and treatment approaches that target muscle health in the elderly.


Sarcopenia , Humans , Sarcopenia/epidemiology , Male , Female , Retrospective Studies , Aged, 80 and over , Aged , Risk Factors , Pelvic Bones/injuries , Pelvic Bones/diagnostic imaging , Osteoporosis/epidemiology , Osteoporosis/complications , Psoas Muscles/diagnostic imaging , Osteoporotic Fractures/epidemiology , Tomography, X-Ray Computed/methods , Prevalence , Fractures, Bone/epidemiology , Fractures, Bone/complications
3.
BMC Med Educ ; 24(1): 420, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38641835

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.


Computer-Assisted Instruction , Humans , Ventilator Weaning , Learning , Health Personnel/education , Critical Care
4.
Phys Chem Chem Phys ; 26(15): 11988-12002, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38573315

Ionic liquid crystals (ILCs) combine the ion mobility of ionic liquids with the order and self-assembly of thermotropic mesophases. To understand the role of the anion in ILCs, wedge-shaped arylguanidinium salts with tetradecyloxy side chains were chosen as benchmark systems and their liquid crystalline self-assembly in the bulk phase as well as their electrochemical behavior in solution were studied depending on the anion. Differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS, SAXS) experiments revealed that for spherical anions, the phase width of the hexagonal columnar mesophase increased with the anion size, while for non-spherical anions, the trends were less clear cut. Depending on the anion, the ILCs showed different stability towards electrochemical oxidation and reduction with the most stable being the PF6 based compound. Cyclic voltammetry (CV) and density functional theory (DFT) calculations suggest a possible contribution of the guanidinium cation to the oxidation processes.

6.
J Biol Chem ; 300(5): 107243, 2024 May.
Article En | MEDLINE | ID: mdl-38556086

Sterols are ubiquitous membrane constituents that persist to a large extent in the environment due to their water insolubility and chemical inertness. Recently, an oxygenase-independent sterol degradation pathway was discovered in a cholesterol-grown denitrifying bacterium Sterolibacterium (S.) denitrificans. It achieves hydroxylation of the unactivated primary C26 of the isoprenoid side chain to an allylic alcohol via a phosphorylated intermediate in a four-step ATP-dependent enzyme cascade. However, this pathway is incompatible with the degradation of widely distributed steroids containing a double bond at C22 in the isoprenoid side chain such as the plant sterol stigmasterol. Here, we have enriched a prototypical delta-24 desaturase from S. denitrificans, which catalyzes the electron acceptor-dependent oxidation of the intermediate stigmast-1,4-diene-3-one to a conjugated (22,24)-diene. We suggest an α4ß4 architecture of the 440 kDa enzyme, with each subunit covalently binding an flavin mononucleotide cofactor to a histidyl residue. As isolated, both flavins are present as red semiquinone radicals, which can be reduced by stigmast-1,4-diene-3-one but cannot be oxidized even with strong oxidizing agents. We propose a mechanism involving an allylic radical intermediate in which two flavin semiquinones each abstract one hydrogen atom from the substrate. The conjugated delta-22,24 moiety formed allows for the subsequent hydroxylation of the terminal C26 with water by a heterologously produced molybdenum-dependent steroid C26 dehydrogenase 2. In conclusion, the pathway elucidated for delta-22 steroids achieves oxygen-independent hydroxylation of the isoprenoid side chain by bypassing the ATP-dependent formation of a phosphorylated intermediate.


Bacterial Proteins , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Molybdenum/metabolism , Molybdenum/chemistry , Mixed Function Oxygenases/metabolism , Mixed Function Oxygenases/chemistry
7.
ASAIO J ; 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38446867

When determining extracorporeal oxygen transfer (V ML O 2 ) during venovenous extracorporeal membrane oxygenation (VV ECMO) dissolved oxygen is often considered to play a subordinate role due to its poor solubility in blood plasma. This study was designed to assess the impact of dissolved oxygen on systemic oxygenation in patients with acute respiratory distress syndrome (ARDS) on VV ECMO support by differentiating between dissolved and hemoglobin-bound extracorporeal oxygen transfer. We calculated both extracorporeal oxygen transfer based on blood gas analysis using the measuring energy expenditure in extracorporeal lung support patients (MEEP) protocol and measured oxygen uptake by the native lung with indirect calorimetry. Over 20% of V ML O 2 and over 10% of overall oxygen uptake (VO 2 total ) were realized as dissolved oxygen. The transfer of dissolved oxygen mainly depended on ECMO blood flow (BF ML ). In patients with severely impaired lung function dissolved oxygen accounted for up to 28% of VO 2 total . A clinically relevant amount of oxygen is transferred as physically dissolved fraction, which therefore needs to be considered when determining membrane lung function, manage ECMO settings or guiding the weaning procedure.

9.
Appl Microbiol Biotechnol ; 108(1): 250, 2024 Mar 02.
Article En | MEDLINE | ID: mdl-38430417

The fungal diglycosidase α-rhamnosyl-ß-glucosidase I (αRßG I) from Acremonium sp. DSM 24697 catalyzes the glycosylation of various OH-acceptors using the citrus flavanone hesperidin. We successfully applied a one-pot biocatalysis process to synthesize 4-methylumbellipheryl rutinoside (4-MUR) and glyceryl rutinoside using a citrus peel residue as sugar donor. This residue, which contained 3.5 % [w/w] hesperidin, is the remaining of citrus processing after producing orange juice, essential oil, and peel-juice. The low-cost compound glycerol was utilized in the synthesis of glyceryl rutinoside. We implemented a simple method for the obtention of glyceryl rutinoside with 99 % yield, and its purification involving activated charcoal, which also facilitated the recovery of the by-product hesperetin through liquid-liquid extraction. This process presents a promising alternative for biorefinery operations, highlighting the valuable role of αRßG I in valorizing glycerol and agricultural by-products. KEYPOINTS: • αRßG I catalyzed the synthesis of rutinosides using a suspension of OPW as sugar donor. • The glycosylation of aliphatic polyalcohols by the αRßG I resulted in products bearing a single rutinose moiety. • αRßG I catalyzed the synthesis of glyceryl rutinoside with high glycosylation/hydrolysis selectivity (99 % yield).


Acremonium , Hesperidin , Hesperidin/chemistry , Glycerol
10.
Respir Res ; 25(1): 69, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38317197

BACKGROUND: Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. METHODS: This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). RESULTS: A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p = 0.025), Charlson Comorbidity Index (OR 1.2, p = 0.027), pH (OR 2.7, p < 0.001) and duration of IMV before admission (OR 1.01, p < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p = 0.007). CONCLUSION: Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.


Methicillin-Resistant Staphylococcus aureus , Respiration, Artificial , Humans , Male , Respiration, Artificial/adverse effects , Retrospective Studies , Ventilator Weaning , Bacteria , Anti-Bacterial Agents/therapeutic use
11.
Resusc Plus ; 17: 100564, 2024 Mar.
Article En | MEDLINE | ID: mdl-38328746

Background: Since 2021, international guidelines for cardiopulmonary resuscitation recommend the implementation of so-called "life-saving systems". These systems include smartphone alerting systems (SAS), which enable dispatch centres to alert first responders via smartphone applications, who are in proximity of a suspected out-of-hospital cardiac arrest (OHCA). However, the effect of SAS on survival remains unknown. Aim: The aim is to assess the rate of survival to hospital discharge in adult patients with OHCA not witnessed by emergency medical services (EMS): before and after SAS implementation. Design: Multicentre, prospective, observational, intention-to-treat, pre-post design clinical trial. Population: Adults (aged ≥ 18 years), OHCA not witnessed by EMS, no traumatic cause for cardiac arrest, cardiopulmonary resuscitation initiated or continued by EMS. Setting: Dispatch-centre-based. Outcomes: Primary: survival to hospital discharge. Secondary: time to first compression, rate of basic life support measures before EMS arrival, rate of patients with shockable rhythm at EMS arrival, Cerebral Performance Category at hospital discharge, and duration of hospital stay. Sample size: Assuming an absolute difference in survival rates to hospital discharge of 4% in the two groups (11% before implementation of the SAS versus 15% after) and 80% power, and a type 1 error rate of 0.05, the required sample size is N = 1,109 patients per group (at least N = 2,218 evaluated patients in total). Conclusions: The HEROES trial will investigate the effects of a SAS on the survival rate after OHCA. Trial registration: German Clinical Trials Register (DRKS, ID: DRKS00032920).

12.
Drug Metab Dispos ; 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38408868

Fluorination of organic compounds plays an important role in the chemical and pharmaceutical industry and is often applied in order to improve physicochemical parameters or modify pharmacological properties. While oxidative and reductive defluorination have been shown to be responsible for the metabolic degradation of organofluorine compounds, the involvement of hydrolytic mechanisms catalyzed by human enzymes has not been reported so far. Here, we investigated the enzymatic defluorination of terminally monofluorinated aliphates with [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-methanone (AM-2201) as a model substance. We performed in vitro biotransformation using pooled human liver microsomes (pHLM) and human recombinant cytochrome P450 (CYP) assays. In order to elucidate the underlying mechanisms, modified incubation conditions were applied including the use of deuterium labeled AM-2201 (d2 -AM-2201). Identification of the main metabolites and analysis of their isotopic composition was performed by liquid-chromatography coupled to time-of-flight-mass-spectrometry (LC-QToF-MS). Quantification of the metabolites was achieved with a validated method based on liquid-chromatography-tandem-mass-spectrometry (LC-MS/MS). CYP 1A2 mediated defluorination of d2 -AM-2201 revealed an isotopic pattern of the defluorinated 5-hydroxypentyl metabolite (5-HPM) indicating a redox mechanism with an aldehyde as a plausible intermediate. In contrast, formation of 5-HPM by pHLM was observed independently of the presence of atmospheric oxygen or co-factors regenerating the redox system. pHLM incubation of d2 -AM-2201 confirmed the hypothesis of a non-oxidative mechanism involved in the defluorination of the 5-fluoropentyl moiety. So far, enzymatically catalyzed, hydrolytic defluorination was only described in bacteria and other prokaryotes. The presented data prove the involvement of a hydrolytic mechanism catalyzed by human microsomal enzymes other than CYP. Significance Statement Elucidating the mechanisms involved in the enzymatic detoxification of organofluorine compounds is crucial for enhancing our understanding and facilitating the design and development of drugs with improved pharmacokinetic profiles. The carbon-fluorine bond possesses a high binding energy, which suggests that non-activated fluoroalkanes would not undergo hydrolytic cleavage. However, our study provides evidence for the involvement of a non-oxidative mechanism catalyzed by human liver enzymes. It is important to consider CYP-independent, hydrolytic defluorination, when investigating the pharmacokinetic properties of fluorinated xenobiotics.

13.
Respir Res ; 25(1): 60, 2024 Jan 27.
Article En | MEDLINE | ID: mdl-38281006

BACKGROUND: Long-term invasive mechanical ventilation (IMV) is a major burden for those affected and causes high costs for the health care system. Early risk assessment is a prerequisite for the best possible support of high-risk patients during the weaning process. We aimed to identify risk factors for long-term IMV within 96 h (h) after the onset of IMV. METHODS: The analysis was based on data from one of Germany's largest statutory health insurance funds; patients who received IMV ≥ 96 h and were admitted in January 2015 at the earliest and discharged in December 2017 at the latest were analysed. OPS and ICD codes of IMV patients were considered, including the 365 days before intubation and 30 days after discharge. Long-term IMV was defined as evidence of invasive home mechanical ventilation (HMV), IMV ≥ 500 h, or readmission with (re)prolonged ventilation. RESULTS: In the analysis of 7758 hospitalisations, criteria for long-term IMV were met in 38.3% of cases, of which 13.9% had evidence of HMV, 73.1% received IMV ≥ 500 h and/or 40.3% were re-hospitalised with IMV. Several independent risk factors were identified (p < 0.005 each), including pre-diagnoses such as pneumothorax (OR 2.10), acute pancreatitis (OR 2.64), eating disorders (OR 1.99) or rheumatic mitral valve disease (OR 1.89). Among ICU admissions, previous dependence on an aspirator or respirator (OR 5.13), and previous tracheostomy (OR 2.17) were particularly important, while neurosurgery (OR 2.61), early tracheostomy (OR 3.97) and treatment for severe respiratory failure such as positioning treatment (OR 2.31) and extracorporeal lung support (OR 1.80) were relevant procedures in the first 96 h after intubation. CONCLUSION: This comprehensive analysis of health claims has identified several risk factors for the risk of long-term ventilation. In addition to the known clinical risks, the information obtained may help to identify patients at risk at an early stage. Trial registration The PRiVENT study was retrospectively registered at ClinicalTrials.gov (NCT05260853). Registered at March 2, 2022.


Noninvasive Ventilation , Pancreatitis , Humans , Respiration, Artificial/adverse effects , Respiration, Artificial/methods , Longitudinal Studies , Acute Disease , Risk Factors
14.
Org Lett ; 26(5): 1051-1055, 2024 Feb 09.
Article En | MEDLINE | ID: mdl-38285916

Two unprecedented fluorescent nucleosides that feature BN-doped polycyclic aromatic hydrocarbons are presented. One of them, having a BN-modified phenanthrene moiety incorporated, shows blue fluorescence but suffers from poor stability under aqueous conditions. The other nucleoside comprises an internally BN-doped pyrene as the chromophore. It shows green fluorescence in various solvents and is stable under aqueous and alkaline conditions.

15.
JMIR Form Res ; 8: e47572, 2024 Jan 25.
Article En | MEDLINE | ID: mdl-38271087

BACKGROUND: Medical photography plays a pivotal role in modern health care, serving multiple purposes ranging from patient care to medical documentation and education. Specifically, it aids in wound management, surgical planning, and medical training. While digital cameras have traditionally been used, smartphones equipped with specialized apps present an intriguing alternative. Smartphones offer several advantages, including increased usability and efficiency and the capability to uphold medicolegal standards more effectively and consistently. OBJECTIVE: This study aims to assess whether implementing a specialized smartphone app could lead to more frequent and efficient use of medical photography. METHODS: We carried out this study as a comprehensive single-center panel investigation at a level 1 trauma center, encompassing various settings including the emergency department, operating theaters, and surgical wards, over a 6-month period from June to November 2020. Using weekly questionnaires, health care providers were asked about their experiences and preferences with using both digital cameras and smartphones equipped with a specialized medical photography app. Parameters such as the frequency of use, time taken for image upload, and general usability were assessed. RESULTS: A total of 65 questionnaires were assessed for digital camera use and 68 for smartphone use. Usage increased significantly by 5.4 (SD 1.9) times per week (95% CI 1.7-9.2; P=.005) when the smartphone was used. The time it took to upload pictures to the clinical picture and archiving system was significantly shorter for the app (mean 1.8, SD 1.2 min) than for the camera (mean 14.9, SD 24.0 h; P<.001). Smartphone usage also outperformed the digital camera in terms of technical failure (4.4% vs 9.7%; P=.04) and for the technical process of archiving (P<.001) pictures to the picture archiving and communication system (PACS) and display images (P<.001) from it. No difference was found in regard to the photographer's intent (P=.31) or reasoning (P=.94) behind the pictures. Additionally, the study highlighted that potential concerns regarding data security and patient confidentiality were also better addressed through the smartphone app, given its encryption capabilities and password protection. CONCLUSIONS: Specialized smartphone apps provide a secure, rapid, and user-friendly platform for medical photography, showing significant advantages over traditional digital cameras. This study supports the notion that these apps not only have the potential to improve patient care, particularly in the realm of wound management, but also offer substantial medicolegal and economic benefits. Future research should focus on additional aspects such as patient comfort and preference, image resolution, and the quality of photographs, as well as seek to corroborate these findings through a larger sample size.

16.
Nutr Neurosci ; : 1-14, 2024 Jan 03.
Article En | MEDLINE | ID: mdl-38170169

Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the 'microbiota-gut-brain axis', the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.

17.
Chembiochem ; 25(1): e202300409, 2024 01 02.
Article En | MEDLINE | ID: mdl-37948327

Cofactor regeneration systems are of major importance for the applicability of oxidoreductases in biocatalysis. Previously, geranylgeranyl reductases have been investigated for the enzymatic reduction of isolated C=C bonds. However, an enzymatic cofactor-regeneration system for in vitro use is lacking. In this work, we report a ferredoxin from the archaea Archaeoglobus fulgidus that regenerates the flavin of the corresponding geranylgeranyl reductase. The proteins were heterologously produced, and the regeneration was coupled to a ferredoxin reductase from Escherichia coli and a glucose dehydrogenase from Bacillus subtilis, thereby enabling the reduction of isolated C=C bonds by purified enzymes. The system was applied in crude, cell-free extracts and gave conversions comparable to those of a previous method using sodium dithionite for cofactor regeneration. Hence, an enzymatic approach to the reduction of isolated C=C bonds can be coupled with common systems for the regeneration of nicotinamide cofactors, thereby opening new perspectives for the application of geranylgeranyl reductases in biocatalysis.


Coenzymes , Ferredoxins , Coenzymes/metabolism , Ferredoxins/metabolism , Oxidoreductases/metabolism , Escherichia coli/metabolism , Oxidation-Reduction
18.
Angew Chem Int Ed Engl ; 63(13): e202314740, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-37924279

The asymmetric reduction of double bonds using NAD(P)H-dependent oxidoreductases has proven to be an efficient tool for the synthesis of important chiral molecules in research and on industrial scale. These enzymes are commercially available in screening kits for the reduction of C=O (ketones), C=C (activated alkenes), or C=N bonds (imines). Recent reports, however, indicate that the ability to accommodate multiple reductase activities on distinct C=X bonds occurs in different enzyme classes, either natively or after mutagenesis. This challenges the common perception of highly selective oxidoreductases for one type of electrophilic substrate. Consideration of this underexplored potential in enzyme screenings and protein engineering campaigns may contribute to the identification of complementary biocatalytic processes for the synthesis of chiral compounds. This review will contribute to a global understanding of the promiscuous behavior of NAD(P)H-dependent oxidoreductases on C=X bond reduction and inspire future discoveries with respect to unconventional biocatalytic routes in asymmetric synthesis.


NAD , Oxidoreductases , NAD/chemistry , Oxidation-Reduction , Oxidoreductases/metabolism , Catalysis , Biocatalysis
19.
J Pain Symptom Manage ; 67(4): 279-289.e6, 2024 Apr.
Article En | MEDLINE | ID: mdl-38154625

CONTEXT: Leading oncology societies recommend monitoring symptoms and support needs through patient-reported outcome measures (PROMs), but their use for assessing specialist palliative care (SPC) need has not yet been explored. Research on SPC integration has focused on staff-assessed screening tools, which are time-consuming. OBJECTIVES: This study aimed to assess the diagnostic validity of the Integrated Palliative Outcome Scale (IPOS) and NCCN Distress Thermometer (NCCN DT) in identifying need for SPC in patients with incurable cancer. METHODS: In a cross-sectional study, patients with incurable cancer (prognosis <2 years) completed PROMs. In an independent process, the palliative care consultation service (PCCS) assessed the need for SPC in each patient through multiprofessional case review, and this was used as the reference standard. ROC analyses were employed to determine diagnostic validity. RESULTS: Of the 208 participants, 71 (34.1 %) were classified as having SPC need by the PCCS. Aiming for a minimum sensitivity of 80%, a cut-off of ≥2 items with high/very high burden in the IPOS resulted in a 90.2% sensitivity (specificity = 50; AUC = 0.791; CI 95%= 0.724-0.858). A cut-off of ≥5 resulted in a sensitivity of 80 % for NCCN DT (specificity = 49.5 %; AUC = 0.687; CI 95% = 0.596-0.777). CONCLUSION: PROMs are useful for identifying SPC need in cancer patients. Their implementation might facilitate timely integration of SPC. Future research should focus on an integrated assessment approach with PROMs that combines the requirements of the different specialties to save patient and staff resources.


Neoplasms , Palliative Care , Humans , Palliative Care/methods , Cross-Sectional Studies , Neoplasms/diagnosis , Neoplasms/therapy , Patient Reported Outcome Measures
20.
Resusc Plus ; 17: 100510, 2024 Mar.
Article En | MEDLINE | ID: mdl-38076389

Aim: Smartphone alerting systems (SAS) alert volunteers in close vicinity of suspected out-of-hospital cardiac arrest. Some systems use sophisticated algorithms to select those who will probably arrive first. Precise estimation of departing times and travel times may help to further improve algorithms. We developed a global positioning system (GPS) based method for automatic measurements of departing times. The aim of this pilot study was to evaluate feasibility and precision of the method. Methods: Region of Lifesavers alerting app (iOS/ Android, version 3.0, FirstAED ApS, Denmark) was used in this study. 27 experiments were performed with 9 students, who were instructed to stay in their flats during the study days. A geofence was set for each alarm in the alerting system with a radius of 10 m (8 cases), 15 m (10 cases), and 20 m (9 cases) around the GPS position at which the alarm was accepted in the app. The system logged responders as being departed when the smartphone position was registered outside the geofence. The students were instructed to manually start a stopwatch at the time of the alert and to stop the stopwatch once they had entered the street in front of their flat. Results: The median difference between automatically and manually retrieved times were -16 seconds [interquartile range IQR 50 seconds] (geofence 10 m), 30 seconds [IQR 25 seconds] (15 m), and 20 seconds [IQR 13 seconds] (20 m), respectively. The 20 m geofence was associated with the smallest interquartile range. Conclusion: Departing times of volunteer responders in SAS can be retrieved automatically using GPS and a geofence.

...