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1.
NPJ Clim Atmos Sci ; 7(1): 215, 2024.
Article in English | MEDLINE | ID: mdl-39281887

ABSTRACT

During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

2.
Toxicol Lett ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39276811

ABSTRACT

The therapy of intoxication with distinct organophosphorus (OP) compounds is still limited today. Especially chemical warfare agents like tabun and soman as well as novichok intoxications are difficult to address using established oxime therapeutics. These neurotoxins inhibit acetylcholinesterase (AChE), a pivotal enzyme in the synaptic cleft. The following accumulation of acetylcholine in the synaptic cleft leads to a dysfunctional, desensitized state of nicotinic acetylcholine receptors (nAChR). Without adequate treatment, the resulting cholinergic crisis leads to death by respiratory arrest. Consequently, the research approach for new therapeutic options needs to be expanded. A promising option would be substances interacting directly with nAChRs. Therefore, screening methods for new drug candidates are needed, with affinity assays playing an important role. In the present work, a saturation and competition scintillation proximity assay (SPA) for binding studies at [3H]epibatidine binding sites, conventionally classified as orthosteric binding sites of the muscle type nAChR was developed. This method offers several advantages over other assay technologies because no separation as well as washing steps are required to remove unbound ligands. Assay precision and solvent tolerance were validated according to the guidelines for validation of bioanalytical methods of the Food and Drug Administration (FDA) and European Medicines Agency (EMA). The newly developed binding assay was successfully implemented on an automated pipetting platform and is suitable for high-throughput-screening receptor-ligand interactions at the nAChR. Furthermore, it allows countering the affinity at the orthosteric binding site in the presence of highly toxic agents such as nerve agents or structurally similar pesticides. Related to further pharmacological results, the affinity to [3H]epibatidine binding sites can provide additional information on whether potential drug candidates would be suitable for treatment of nerve agent poisoning.

3.
Sci Rep ; 14(1): 20804, 2024 09 06.
Article in English | MEDLINE | ID: mdl-39242729

ABSTRACT

In a randomized, controlled study, whole-body electromyostimulation (WB-EMS) was investigated as a promising alternative treatment technique compared to conventional strength training for the management of knee osteoarthritis (OA). Seventy-two overweight participants with symptomatic knee OA were randomly assigned to WB-EMS (n = 36) or a usual care group (UCG, n = 36). For seven months, the WB-EMS group received three times per fortnight a WB-EMS training, while the UCG was prescribed six-times physiotherapeutic treatments. We observed significant effects for the primary outcome "pain", as determined by the Knee injury and Osteoarthritis Outcome Score (KOOS), with more favourable changes in the WB-EMS group vs UCG (between-group difference 9.0 points, 95%CI 2.9-15.1, p = 0.004). Secondary outcomes, including the other KOOS subscales (symptoms, function in daily living, function in sports/recreational activities and quality of life), 7 day pain diary, hip/leg extensor strength and lower limb function (30s sit-to-stand test), were also statistically significant in favour of the WB-EMS group. Overall, WB-EMS was found to be effective in relieving knee pain symptoms and improving physical function in individuals with symptomatic knee OA compared to usual care treatment. WB-EMS could be used as an alternative therapy in the management of knee OA; particularly for patients that cannot be motivated for conventional training.


Subject(s)
Electric Stimulation Therapy , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/rehabilitation , Female , Male , Middle Aged , Electric Stimulation Therapy/methods , Aged , Treatment Outcome , Quality of Life , Knee Joint/physiopathology , Pain Management/methods , Pain/physiopathology , Pain/etiology
4.
J Clin Microbiol ; 62(9): e0062824, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39158309

ABSTRACT

Nanopore sequencing has shown the potential to democratize genomic pathogen surveillance due to its ease of use and low entry cost. However, recent genotyping studies showed discrepant results compared to gold-standard short-read sequencing. Furthermore, although essential for widespread application, the reproducibility of nanopore-only genotyping remains largely unresolved. In our multicenter performance study involving five laboratories, four public health-relevant bacterial species were sequenced with the latest R10.4.1 flow cells and V14 chemistry. Core genome MLST analysis of over 500 data sets revealed highly strain-specific typing errors in all species in each laboratory. Investigation of the methylation-related errors revealed consistent DNA motifs at error-prone sites across participants at read level. Depending on the frequency of incorrect target reads, this either leads to correct or incorrect typing, whereby only minimal frequency deviations can randomly determine the final result. PCR preamplification, recent basecalling model updates and an optimized polishing strategy notably diminished the non-reproducible typing. Our study highlights the potential for new errors to appear with each newly sequenced strain and lays the foundation for computational approaches to reduce such typing errors. In conclusion, our multicenter study shows the necessity for a new validation concept for nanopore sequencing-based, standardized bacterial typing, where single nucleotide accuracy is critical.


Subject(s)
Bacteria , Genotyping Techniques , Nanopore Sequencing , Nanopore Sequencing/methods , Reproducibility of Results , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Humans , Genotyping Techniques/methods , Genotype , Multilocus Sequence Typing/methods , DNA, Bacterial/genetics , Genome, Bacterial/genetics , Sequence Analysis, DNA/methods
5.
Article in English | MEDLINE | ID: mdl-39115878

ABSTRACT

OBJECTIVES: Adequate theoretical and practical training of prospective clinical perfusionists is essential for maintaining clinical standards and ensuring patient safety during cardiac surgery procedures. Perfusion schools play a crucial role in establishing and maintaining higher education and training standards in clinical perfusion. The aim of this study is to obtain a comprehensive overview of European training standards in clinical perfusion in 2023. METHODS: For this study, 53 perfusion schools in Europe were found and contacted, of which 30 (56.6%) responded, giving a sample size of n = 30, which were then included in the data analysis. The quantitative data of the survey are analysed using descriptive methods. RESULTS: The university and training standards in clinical perfusion in Europe vary in many respects. Starting with the entry criterion for studies (most frequently a required bachelor's degree 36.7% or 2nd most common an university entrance qualification 30%), the duration [from <12 months (13.3%) up to 36 months (13.3%)] and regarding the content of the teaching in clinical perfusion [<30 European Credit Transfer System (ECTS) (33.3%) and more than 180 ECTS (6.7%)]. The mean value for teaching in clinical perfusion content is 62.63 ECTS credits. CONCLUSIONS: The obtained results show important differences between countries and schools. As such, they form a valuable database for future discussions establishing a common European curriculum and training standards for perfusionists. For the generalizability of the results, further evaluations and larger samples are needed.

6.
BMC Musculoskelet Disord ; 25(1): 579, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048996

ABSTRACT

BACKGROUND: Although patients with shoulder complaints are frequently referred to physiotherapy, putative predictive factors for outcomes are still unclear. In this regard, only a limited amount of scientific data for patients with subacromial pain syndrome exist, with inconsistent results. An improved knowledge about the ability of baseline variables to predict outcomes could help patients make informed treatment decisions, prevent them from receiving ineffective treatments, and minimize the risk of developing chronic pain. AIM: The aims of this secondary longitudinal analysis are threefold: First, to investigate baseline differences between patients with and without successful long-term outcomes following physiotherapy. Second, to compare the predictive ability of two sets of putative predictive variables on outcomes, one based on the literature and one based on the data of the original trial. Third, to explore the contribution of short-term follow-up data to predictive models. METHODS: Differences between responders and nonresponders were calculated. The predictive ability of variables defined through literature and of variables based on the Akaike Information Criterion (AIC) from the original trial dataset on the Shoulder Pain and Disability Index and the Patients' Global Impression of Change at the one-year follow-up were analyzed. To test the robustness of the results, different statistical models were used. To investigate the contribution of follow-up data to prediction, short-term data were included in the analyses. RESULTS: A sample of 87 patients with subacromial pain syndrome was analyzed. 77% (n = 67) of these participants were classified as responders. Higher expectations and short-term change scores were positive, and higher fear avoidance beliefs, greater baseline disability and pain levels were negative predictors of long-term outcomes in patients with subacromial pain syndrome. CONCLUSIONS: Although our results are in line with previous research and support the use of clinical factors for prediction, our findings suggest that psychological factors, especially patient expectations and fear avoidance beliefs, also contribute to long-term outcomes and should therefore be considered in the clinical context and further research. However, the hypotheses and recommendations generated from our results need to be confirmed in further studies due to their explorative nature. TRIAL REGISTRATION: The original trial was registered at Current Controlled Trials under the trial registration number ISRCTN86900354 on March 17, 2010.


Subject(s)
Physical Therapy Modalities , Shoulder Impingement Syndrome , Humans , Female , Male , Middle Aged , Treatment Outcome , Shoulder Impingement Syndrome/rehabilitation , Shoulder Impingement Syndrome/therapy , Adult , Longitudinal Studies , Pain Measurement , Shoulder Pain/therapy , Shoulder Pain/psychology , Shoulder Pain/diagnosis , Shoulder Pain/rehabilitation , Aged , Follow-Up Studies , Time Factors , Predictive Value of Tests , Disability Evaluation
8.
Commun Biol ; 7(1): 640, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796645

ABSTRACT

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common autosomal dominant muscle disorders, yet no cure or amelioration exists. The clinical presentation is diverse, making it difficult to identify the actual driving pathomechanism among many downstream events. To unravel this complexity, we performed a meta-analysis of 13 original omics datasets (in total 171 FSHD and 129 control samples). Our approach confirmed previous findings about the disease pathology and specified them further. We confirmed increased expression of former proposed DUX4 biomarkers, and furthermore impairment of the respiratory chain. Notably, the meta-analysis provides insights about so far not reported pathways, including misregulation of neuromuscular junction protein encoding genes, downregulation of the spliceosome, and extensive alterations of nuclear envelope protein expression. Finally, we developed a publicly available shiny app to provide a platform for researchers who want to search our analysis for genes of interest in the future.


Subject(s)
Muscular Dystrophy, Facioscapulohumeral , Neuromuscular Junction , Nuclear Envelope , Spliceosomes , Humans , Muscular Dystrophy, Facioscapulohumeral/genetics , Muscular Dystrophy, Facioscapulohumeral/metabolism , Muscular Dystrophy, Facioscapulohumeral/pathology , Nuclear Envelope/metabolism , Nuclear Envelope/genetics , Spliceosomes/metabolism , Spliceosomes/genetics , Neuromuscular Junction/metabolism , Neuromuscular Junction/genetics , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Gene Expression Regulation
9.
Brief Bioinform ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38436559

ABSTRACT

A wide range of approaches can be used to detect micro RNA (miRNA)-target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies and applied them to three distinct rare disease datasets that comprise smallRNA-Seq and RNA-Seq data obtained from the same samples, obtaining mTPs related to the disease pathology. All datasets were preprocessed using a standardized, freely available computational workflow, DEG_workflow. This workflow includes coRmiT, a method to compare multiple strategies for mTP detection. We used it to investigate the overlap of the detected mTPs with predicted and validated mTPs from 11 different databases. Results show that there is no clear best strategy for mTP detection applicable to all situations. We therefore propose the integration of the results of the different strategies by selecting the one with the highest odds ratio for each miRNA, as the optimal way to integrate the results. We applied this selection-integration method to the datasets and showed it to be robust to changes in the predicted and validated mTP databases. Our findings have important implications for miRNA analysis. coRmiT is implemented as part of the ExpHunterSuite Bioconductor package available from https://bioconductor.org/packages/ExpHunterSuite.


Subject(s)
MicroRNAs , Consensus , Databases, Factual , MicroRNAs/genetics , Odds Ratio , RNA-Seq
10.
Front Physiol ; 15: 1349750, 2024.
Article in English | MEDLINE | ID: mdl-38455842

ABSTRACT

Hypertension is a frequent condition in untrained middle-aged to older adults, who form the core group of whole-body electromyostimulation (WB-EMS) applicants. So far, the acute effects of varying impulse intensities on blood pressure responses have not been evaluated in normo- and hypertensive people. Thirteen hypertensive and twelve normotensive overweight WB-EMS novices, 40-70 years old, conducted the same WB-EMS protocol (20 min, bipolar, 85 Hz, 350 µs, 4 s impulse-4 s rest; combined with easy movements) with increasing impulse intensity (low, moderate, advanced) per session. Mean arterial blood pressure (MAP) as determined by automatic sphygmomanometry rose significantly (p < .001) from rest, 5 min pre-WB-EMS to immediately pre-WB-EMS assessment. Of importance, a 20-min WB-EMS application does not increase MAP further. In detail, maximum individual MAP does not exceed 128 mmHg (177 mmHg systolic or 110 mmHg diastolic) in any case. Two-min post-WB-EMS, MAP was significantly lower (p = .016) compared to immediately pre-WB-EMS. In contrast, heart rate increased significantly from immediately pre to immediately post-exercise (p < .001), though individual peak values did not exceed 140 beats/min-1 and heart rate decreased rapidly (p < .001) post-exercise. No significant differences in MAP and HR kinetics were observed for impulse intensity categories or hypertensive status. In summary, largely independently of impulse intensity and status, the acute effect of WB-EMS on MAP in novice applicants seem to be largely negligible. Although definite evidence might not have been provided by the present study, we conclude that hypertension, at least under treatment, should not be considered as a barrier for WB-EMS application in moderately old or older cohorts.

11.
Sensors (Basel) ; 24(3)2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38339689

ABSTRACT

Whole-body electromyostimulation (WB-EMS) can be considered as a time-efficient, joint-friendly, and highly customizable training technology that attracts a wide range of users. The present evidence map aims to provide an overview of different non-athletic cohorts addressed in WB-EMS research. Based on a comprehensive systematic search according to PRISMA, eighty-six eligible longitudinal trials were identified that correspond with our eligibility criteria. In summary, WB-EMS research sufficiently covers all adult age categories in males and females. Most cohorts addressed (58%) were predominately or exclusively overweight/obese, and in about 60% of them, diseases or conditions were inclusion criteria for the trials. Cohorts specifically enrolled in WB-EMS trials suffer from cancer/neoplasm (n = 7), obesity (n = 6), diabetes mellitus (n = 5), metabolic syndrome (n = 2), nervous system diseases (n = 2), chronic heart failure (n = 4), stroke (n = 1), peripheral arterial diseases (n = 2), knee arthrosis (n = 1), sarcopenia (n = 3), chronic unspecific low back pain (n = 4), and osteopenia (n = 3). Chronic kidney disease was an eligibility criterion in five WB-EMS trials. Finally, three studies included only critically ill patients, and two further studies considered frailty as an inclusion criterion. Of importance, no adverse effects of the WB-EMS intervention were reported. In summary, the evidence gaps in WB-EMS research were particular evident for cohorts with diseases of the nervous and cerebrovascular system.


Subject(s)
Electric Stimulation Therapy , Humans , Male , Female , Electric Stimulation Therapy/methods , Longitudinal Studies , Adult , Obesity , Middle Aged , Aged , Neoplasms/therapy , Sarcopenia/therapy , Sarcopenia/physiopathology
12.
BMC Geriatr ; 24(1): 141, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38326734

ABSTRACT

BACKGROUND: Osteosarcopenia is a common geriatric syndrome with an increasing prevalence with age, leading to secondary diseases and complex consequences such as falls and fractures, as well as higher mortality and frailty rates. There is a great need for prevention and treatment strategies. METHODS: In this analysis, we used magnetic resonance imaging (MRI) data from the randomised controlled FrOST trial, which enrolled community-dwelling osteosarcopenic men aged > 72 years randomly allocated to 16 months of twice-weekly high-intensity resistance training (HIRT) or a non-training control group. MR Dixon imaging was used to quantify the effects of HIRT on muscle fat infiltration in the paraspinal muscles, determined as changes in muscle tissue, fat faction and intermuscular adipose tissue (IMAT) in the erector spinae and psoas major muscles. Intention-to-treat analysis with multiple imputation was used to analyse the data set. RESULTS: After 16 months of intervention, 15 men from the HIRT and 16 men from the CG were included in the MRI analysis. In summary, no positive effects on the fat infiltration of the erector spinae and psoas major muscles were observed. CONCLUSIONS: The previously reported positive effects on lumbar spine bone mineral density (BMD) suggest that mechanotransduction induces tropic effects on bone, but that fat infiltration of the erector spinae and psoas major muscles are either irreversible or, for some unknown reason, resistant to exercise. Because of the beneficial effects on spinal BMD, HIRT is still recommended in osteosarcopenic older men, but further research is needed to confirm appropriate age-specific training exercises for the paraspinal muscles. The potential of different MRI sequences to quantify degenerative and metabolic changes in various muscle groups must be better characterized. TRIAL REGISTRATIONS: FrOST was approved by the University Ethics Committee of the Friedrich-Alexander University of Erlangen-Nürnberg (number 67_15b and 4464b) and the Federal Office for Radiation Projection (BfS, number Z 5-2,246,212 - 2017-002). Furthermore, it fully complies with the Declaration of Helsinki and is registered at ClinicalTrials.gov: NCT03453463 (05/03/2018). JAMA 310:2191-2194, 2013.


Subject(s)
Mechanotransduction, Cellular , Paraspinal Muscles , Aged , Male , Humans , Paraspinal Muscles/diagnostic imaging , Paraspinal Muscles/physiology , Bone Density , Adipose Tissue/diagnostic imaging , Research Design , Magnetic Resonance Imaging/methods
13.
Eur J Med Res ; 29(1): 42, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38212823

ABSTRACT

BACKGROUND: The established therapy of asthma might be supported by additional non-pharmaceutical measures, such as the Buteyko breathing technique (BBT); however, the available data are mixed. To clarify the effects of BBT in patients with asthma, we investigated whether it led to clinical improvements with correlation to functional parameters. METHODS: Using a randomized, controlled design, we studied two groups (n = 30 each) of patients with asthma under either BBT or usual therapy (UT) w/o BBT over a period of 3 months. The primary outcome comprised the voluntary control pause (CP) after 3 months, secondary outcomes an additional breathhold parameter, forced expiratory volume in 1 s (FEV1), capnovolumetry, exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ) and Nijmegen Questionnaire (NQ), and the use of medication (ß2-agonists; inhaled corticosteroids, ICS). RESULTS: CP showed significant time-by-group interaction [F(1,58.09) = 28.70, p < 0.001] as well as main effects for study group [F(1,58.27) = 5.91, p = 0.018] and time [F(1,58.36) = 17.67, p < 0.001]. ACQ and NQ scores were significantly (p < 0.05 each) improved with BBT. This was associated with reductions in the use of ß2-agonists and ICS (p < 0.05 each) by about 20% each. None of these effects occurred in the UT group. While FEV1 and the slopes of the capnovolumetric expiratory phases 2 and 3 did not significantly change, the capnovolumetric threshold volume at tidal breathing increased (p < 0.05) with BBT by about 10 mL or 10%, compared to baseline, suggesting a larger volume of the central airways. No significant changes were seen for FeNO. CONCLUSIONS: BBT was clinically effective, as indicated by the fact that the improvement in symptom scores and the small increase in bronchial volume occurred despite the significant reduction of respiratory pharmacotherapy. As the self-controlled Buteyko breathing therapy was well-accepted by the participants, it could be considered as supporting tool in asthma therapy being worth of wider attention in clinical practice. Trial registration Retrospectively registered on 10 March 2017 at ClinicalTrials.gov (NCT03098849).


Subject(s)
Asthma , Adult , Humans , Asthma/drug therapy , Asthma/chemically induced , Adrenal Cortex Hormones/therapeutic use
14.
J Integr Complement Med ; 30(4): 394-402, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37815790

ABSTRACT

Background: Antibiotic use in neonatal intensive care units (NICUs) remains high. Low antibiotic prescribing has been documented among physicians trained in complementary medicine. This study sought to identify if an NICU integrating complementary medicine has low antibiotic prescribing. Methods: We conducted a retrospective analysis at the level-2 NICU of the Filderklinik, an integrative medicine hospital in Southern Germany, to compare antibiotic use locally and internationally; to compare neonates with suspected infection, managed with and without antibiotics; and to describe use and safety of complementary medicinal products. Results: Among 7778 live births, 1086 neonates were hospitalized between 2014 and 2017. Two hundred forty-six were diagnosed with suspected or confirmed infection, their median gestational age was 40.3 weeks (range 29-42), 3.25% had a birthweight <2500 g, 176 were treated with antibiotics for a median duration of 4 days, 6 had culture-proven infection (0.77 per 1000 live births), and 2.26% of live births were started on antibiotics. A total of 866 antibiotic treatment days corresponded to 111 antibiotic days per 1000 live births and 8.8 antibiotic days per 100 hospital days. Neonates managed with antibiotics more often had fever and abnormal laboratory parameters than those managed without. Complementary medicinal products comprising 71 different natural substances were used, no side effect or adverse event were described. A subanalysis using the inclusion criteria of a recent analysis of 13 networks in Europe, North America, and Australia confirmed this cohort to be among the lowest prescribing networks. Conclusions: Antibiotic use was low in this NICU in both local and international comparison, while the disease burden was in the mid-range, confirming an association between integrative medicine practice and low antibiotic prescribing in newborns. Complementary medicinal products were widely used and well tolerated. Clinical Trial Registration number: NCT04893343.


Subject(s)
Anti-Bacterial Agents , Integrative Medicine , Humans , Infant, Newborn , Infant , Anti-Bacterial Agents/adverse effects , Intensive Care Units, Neonatal , Retrospective Studies , Gestational Age
15.
Nanomedicine ; 55: 102724, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38007066

ABSTRACT

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS. DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described. Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Nanopores , Ethanolamine/analysis , Ethanolamine/chemistry , Ethanolamines , DNA/chemistry , Base Sequence , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods
16.
J Clin Med ; 12(17)2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37685707

ABSTRACT

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten the time for antibiotic administration in the emergency department. We retrospectively evaluated all patients above 18 years of age who were diagnosed with sepsis or severe infection in our emergency department between 2018 and 2020. We recorded the suspected diagnosis at the time of presentation, the type of referring healthcare provider, and the time until initiation of antibiotic treatment. Differences between groups were calculated using the Kruskal-Wallis rank sum test. Of the 277 patients who were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients, and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well-described outcome benefits of early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce the time to antibiotic administration and improve patient outcomes.

17.
J Osteoporos ; 2023: 5570030, 2023.
Article in English | MEDLINE | ID: mdl-37588008

ABSTRACT

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813.

19.
Front Physiol ; 14: 1135663, 2023.
Article in English | MEDLINE | ID: mdl-36994417

ABSTRACT

Introduction: Aquatic or water-based exercise is a very popular type of exercise in particular for people with physical limitations, joint problems and fear of falling. The present systematic review and meta-analysis aimed to provide evidence for the effect of aquatic exercise on Bone Mineral Density (BMD) in adults. Methods: A systematic literature search of five electronic databases (PubMed/MEDLINE, Cochrane Library, Scopus, Web of Science and CINAHL) according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted until 2022/01/30, with an update to 2022/10/07. We included controlled trials with a duration of more than 6 months and at least two study groups, aquatic exercise (EG) versus non-training controls (CG) with no language restrictions. Outcome measures were standardized mean differences (SMD) with 95%-confidence intervals (95%-CI) for BMD changes at the lumbar spine (LS) and femoral neck (FN). We applied a random-effects meta-analysis and used the inverse heterogeneity (IVhet) model to analyze the data. Results: Excluding an outlier study with an exceptionally high effect size for LS-BMD, we observed a statistically significant (p = .002) effect (EG vs. CG) of aquatic exercise for the LS-BMD (n = 10; SMD: 0.30; 95%-CI: 0.11-0.49). In parallel, the effect of aquatic exercise on FN-BMD was statistically significant (p = .034) compared to the CG (n = 10; SMD: 0.76, 95%-CI: 0.06-1.46). Of importance, heterogeneity between the trial results was negligible for LS (I2: 7%) but substantial for FN-BMD (I2: 87%). Evidence for risks of small study/publication bias was low for LS-BMD and considerable for FN-BMD. Discussion: In summary, the present systematic review and meta-analysis provides further evidence for the favorable effect of exercise on bone health in adults. Due to its safety and attractiveness, we particularly recommend water-based exercise for people unable, afraid or unmotivated to conduct intense land-based exercise programs.

20.
J Clin Microbiol ; 61(4): e0163122, 2023 04 20.
Article in English | MEDLINE | ID: mdl-36988494

ABSTRACT

Next-generation whole-genome sequencing is essential for high-resolution surveillance of bacterial pathogens, for example, during outbreak investigations or for source tracking and escape variant analysis. However, current global sequencing and bioinformatic bottlenecks and a long time to result with standard technologies demand new approaches. In this study, we investigated whether novel nanopore Q20+ long-read chemistry enables standardized and easily accessible high-resolution typing combined with core genome multilocus sequence typing (cgMLST). We set high requirements for discriminatory power by using the slowly evolving bacterium Bordetella pertussis as a model pathogen. Our results show that the increased raw read accuracy enables the description of epidemiological scenarios and phylogenetic linkages at the level of gold-standard short reads. The same was true for our variant analysis of vaccine antigens, resistance genes, and virulence factors, demonstrating that nanopore sequencing is a legitimate competitor in the area of next-generation sequencing (NGS)-based high-resolution bacterial typing. Furthermore, we evaluated the parameters for the fastest possible analysis of the data. By combining the optimized processing pipeline with real-time basecalling, we established a workflow that allows for highly accurate and extremely fast high-resolution typing of bacterial pathogens while sequencing is still in progress. Along with advantages such as low costs and portability, the approach suggested here might democratize modern bacterial typing, enabling more efficient infection control globally.


Subject(s)
Bacteria , Genome, Bacterial , Genotyping Techniques , Multilocus Sequence Typing , Nanopore Sequencing , Antigens, Bacterial/genetics , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/pathogenicity , Bacterial Vaccines/genetics , Bordetella pertussis/genetics , Bordetella pertussis/isolation & purification , Bordetella pertussis/pathogenicity , Drug Resistance, Bacterial/genetics , Environmental Monitoring , High-Throughput Nucleotide Sequencing/methods , Multilocus Sequence Typing/methods , Nanopore Sequencing/methods , Phylogeny , Reproducibility of Results , Virulence Factors/genetics
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