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Background: An out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) may need to be treated with airway management, emergency ventilation, invasive interventions, and post-arrest sedation. We investigated the influence of the use of midazolam for post-arrest sedation on achieving post-resuscitation care targets and the associated risk of hemodynamic complications. Methods: All emergency rescue missions of the Dresden, Gtersloh, and Lippe medical rescue services in the years 20192021 were reviewed to identify adult patients who had OHCA, unconsciousness, and sustained ROSC with spontaneous circulation until arrival at the hospital; the findings were supplemented with data from the German Resuscitation Registry. Patients who received midazolam (alone or in combination with other anesthetic agents) for post-arrest sedation were compared with those who did not. The endpoints were the regaining of a systolic blood pressure ≥100mmHg, end-tidal pCO2 3545mmHg, and oxygen saturation (SpO2) 9498%. A propensity score analysis was used to adjust for age, sex, and variables potentially affecting hemodynamic status or the targets for oxygenation and ventilation. Results: There were 2335 cases of OHCA among 391 305 emergency rescue missions. 571 patients had ROSC before arrival in the hospital (24.5%; female,33.6%; age, 6814 years). Of the 395 among them (69.2%) who were treated with post-arrest sedation, 249 (63.0%) received midazolam. Patients who received midazolam reached the guideline-recommended targets for oxygenation, ventilation, and blood pressure more frequently than those who were not sedated: the respective odds ratios and 95% confidence intervals were 2.00 [1.20; 3.34], 1.57 [0.99; 2.48], and 1.41 [0.89; 2.21]. Conclusion: The pre-hospital administration of midazolam leads to more frequent pre-hospital attainment of the oxygenation and ventilation targets in post-resuscitation care, without any evidence of an elevated risk of hemodynamic complications. [ABSTRACT FROM AUTHOR]

Objective: Following recent changes to the German Narcotics Act, this article examines prehospital analgesia by paramedics using piritramide vs. nalbuphine + paracetamol., Material and Methods: Prehospital analgesia administered by paramedics from the Fulda (piritramide) and Gütersloh (nalbuphine + paracetamol) emergency services was compared regarding pain intensity at the beginning and end of the mission, measured using the numeric rating scale (NRS). Additionally, an analysis of the resulting complications was carried out., Results: In this study 2429 administrations of analgesia were evaluated (nalbuphine + paracetamol: 1635, 67.3%, initial NRS: 8.0 ± 1.4, end of NRS: 3.7 ± 2.0; piritramide: 794, 32.7%, initial NRS: 8.5 ± 1.1, end of NRS: 4.5 ± 1.6). Factors influencing NRS change were initial NRS (regression coefficient, RC: 0.7075, 95% confidence interval, CI: 0.6503-0.7647, p < 0.001), treatment with nalbuphine + paracetamol (RC: 0.6048, 95% CI: 0.4396-0.7700, p < 0.001). Treatment with nalbuphine + paracetamol (n = 796 (48.7%)) compared to piritramide (n = 190 (23.9%)) increased the odds of achieving NRS < 4 (odds ratio, OR: 2.712, 95% CI: 2.227-3.303, p < 0.001). Complications occurred in n = 44 (5.5%) with piritramide and in n = 35 (2.1%) with nalbuphine + paracetamol. Risk factors for complications were analgesia with piritramide (OR: 2.699, 95% CI: 1.693-4.301, p < 0.001), female sex (OR: 2.372, 95% CI: 1.396-4.029, p = 0.0014), and age (OR: 1.013, 95% CI: 1.002-1.025, p = 0.0232)., Conclusion: Compared with piritramide, prehospital analgesia with nalbuphine + paracetamol has favorable effects in terms of analgesic efficacy and complication rates and should therefore be considered in future recommendations for paramedics., (© 2024. The Author(s).)

Background: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol., Methods: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored., Results: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02)., Conclusions: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia., (© 2024. The Author(s).)

Background: Currently, the data regarding the impact of prehospital postcardiac arrest anesthesia on target hemodynamic and ventilatory parameters of early postresuscitation care and recommendations on its implementation are rare. The present study examines the incidence and impact of prehospital postcardiac arrest anesthesia on hemodynamic and ventilatory target parameters of postresuscitation care., Methods: In this multicentre observational study between 2019 and 2021 unconscious adult patients after out-of-hospital-cardiac arrest with the presence of a return-of-spontaneous circulation until hospital admission were included. Primary endpoint was the application of postarrest anesthesia. Secondary endpoints included the medication group used, predisposing factors to its implementation, and its influence on achieving target parameters of postresuscitation care (systolic blood pressure: ≥ 100 mmHg, etCO 2 :35-45 mmHg, SpO 2 : 94-98%) at hospital handover., Results: During the study period 2,335 out-of-hospital resuscitations out of 391,305 prehospital emergency operations (incidence: 0.58%; 95% CI 0.54-0.63) were observed with a return of spontaneous circulation to hospital admission in 706 patients (30.7%; 95% CI 28.8-32.6; female: 34.3%; age:68.3 ± 14.2 years). Postcardiac arrest anesthesia was performed in 482 patients (68.3%; 95% CI 64.7-71.7) with application of hypnotics in 93.4% (n = 451), analgesics in 53.7% (n = 259) and relaxants in 45.6% (n = 220). Factors influencing postcardiac arrest sedation were emergency care by an anesthetist (odds ratio: 2.10; 95% CI 1.34-3.30; P < 0.001) and treatment-free interval ≤ 5 min (odds ratio: 1.59; 95% CI 1.01-2.49; P = 0.04). Although there was no evidence of the impact of performing postcardiac arrest anesthesia on achieving a systolic blood pressure ≥ 100 mmHg at the end of operation (odds ratio: 1.14; 95% CI 0.78-1.68; P = 0.48), patients with postcardiac arrest anesthesia were significantly more likely to achieve the recommended ventilation (odds ratio: 1.59; 95% CI 1.06-2.40; P = 0.02) and oxygenation (odds ratio:1.56; 95% CI 1.04-2.35; P = 0.03) targets. Comparing the substance groups, the use of hypnotics significantly more often enabled the target values for etCO2 to be reached alone (odds ratio:2.79; 95% CI 1.04-7.50; P = 0.04) as well as in combination with a systolic blood pressure ≥ 100 mmHg (odds ratio:4.42; 95% CI 1.03-19.01; P = 0.04)., Conclusions: Postcardiac arrest anesthesia in out-of-hospital cardiac arrest is associated with early achievement of respiratory target parameters in prehospital postresuscitation care without evidence of more frequent hemodynamic complications., (© 2024. The Author(s).)

Background: The aim of this study was to examine the impact of COVID-19 on the response rate of community-first-responders (CFR) and other out-of-hospital-cardiac-arrest (OHCA) outcomes using the smartphone-first-responder-system (SFRS) "Mobile Retter.", Methods: All adult non-traumatic OHCA in the district of Gütersloh between 01.01.2018-31.12.2021 were included. Periods of interest were 1) prior to the first COVID-19-lockdown; to 2) both lockdowns; and 3) the time in between, as well as after the COVID-19-lockdowns (pre-COVID-19, COVID-19-lockdown and COVID-19-pandemic respectively). The primary outcome was the CFR response rate defined as proportion of CFR alerts that were accepted by a CFR and in which at least one CFR arrived on scene of the emergency out of all CFR alerts. Secondary outcomes included the rate of CFR alerts, defined as proportion of OHCA to which CFR were summoned by the emergency medical dispatcher, as well as the rate of return-of-spontaneous-circulation (ROSC) and rate of survival until hospital discharge. We also examined the incidence COVID-19-infection of CFR in context of the SFRS., Results: A total of 1064 OHCA-patients (mean age: 71.4±14.5 years; female: 33.8%) were included in the study (Pre-COVID-19: 539; COVID-19-lockdown: 109; COVID-19-pandemic: 416). The response rate was 64.0% (pre-COVID-19: 58.7%; COVID-19-lockdown: 63.5%; COVID-19-pandemic: 71.8%, P=0.002 vs. pre-COVID-19). The alert rate was 52.7% (pre-COVID-19: 56.2%; COVID-19-lockdown: 47.7%, P=0.04 vs. Pre-COVID-19; COVID-19-Pandemic: 49.5%, P=0.02 vs. pre-COVID-19). The ROSC-rate was 40.4% (pre-COVID-19: 41.0%; COVID-19-lockdown: 33.9%; COVID-19-pandemic: 41.4%) and hospital discharge rate 31.2% (Pre-COVID-19: 33.0%; COVID-19-lockdown: 36.8%; COVID-19-pandemic: 28.7%). The use of CFR was associated with favorable effects in terms of hospital admission (odds ratio [OR]: 0.654 (CI95: 0.444-0.963), P=0.03), hospital discharge (OR: 2.343 (CI95: 1.002-5.475), P=0.04). None of the CFR became infected with COVID-19., Conclusions: "Mobile-Retter" was associated with high response rates, improved outcome in OHCA patients and no COVID-19-infections of CFR during the COVID-19-pandemic and -lockdowns.

Background: The aim of this study was to examine the effectiveness and safety of prehospital analgesia with nalbuphine and/or paracetamol by paramedics., Methods: In this retrospective trial, following the implementation of a standard-operating-procedure for pain requiring treatment as defined as a score ≥4 on the 0-10 Numeric Rating Scale for pain, all emergency operations in the district of Gütersloh between January 1, 2020, and June 30, 2022, with analgesic administration by paramedics in patients ≥18 years were included in the study. Analgesic agents employed by the paramedics included nalbuphine and/or paracetamol, butylscopolamine for abdominal colic, and esketamine in case of failure of the other analgesics. The primary endpoint was the patients' rating of their pain on the Numeric Rating Scale at the end of the operation. Additional covariates included sex, cause of pain, analgesics used, Numeric Rating Scale at beginning and analgesic-associated complications (reduced level of consciousness, hypotension, desaturation, a- or bradypnea)., Results: A total of 1931 emergency operations (female: N.=1039 [53.8%]) with pain requiring treatment (non-traumatic cause: N.=1106 [57.3%]; initial Numeric Rating Scale: 8.0±1.4). Analgesics applied were nalbuphine + paracetamol (50.6%), paracetamol (38.7%), butylscopolamine (13.4%), nalbuphine (7.7%), and esketamine (4.9%). Mean pain reduction was 4.3±2.3 (nalbuphine + paracetamol: 5.0±2.1; nalbuphine: 4.7±2.3) and paracetamol: 3.3±2.2, respectively. Factors influencing a change in the Numeric Rating Scale were trauma (regression-coefficient: -0.308, 95% CI: -0.496 - -0.119, P=0.0014 vs. non-trauma; nalbuphine [yes vs. no]: regression-coefficient 0.684, 95% CI 0.0774-1.291, P=0.03; nalbuphine + paracetamol: regression-coefficient 0.763, 95% CI 0.227-1.299, P=0.005). At the end of the operation, 49.7% had a Numeric Rating Scale <4, 34.3% had a Numeric Rating Scale 4-5, and 16.0% had a Numeric Rating Scale ≥6. Factors influencing a Numeric Rating Scale <4 at end of use were trauma vs. non-trauma: odds ratio 0.788, 95% CI 0.649-0.957, P=0.02. The Numeric Rating Scale at beginning reported: odds ratios 0.754, 95% CI 0.700-0.812, P<0.0001. Analgesic-associated complications were not observed., Conclusions: Prehospital analgesia by paramedics with nalbuphine as monotherapy or in combination with paracetamol allows for sufficient analgesia without the occurrence of complications.

Hypertension has been shown to have long-term cardiovascular effects if left untreated. Hypertension also has been shown to affect women during pregnancy, which can be detrimental not only to the patient but also to the fetus. Early identification and treatment are paramount to prevent adverse outcomes. This article details the epidemiology, clinical presentation, diagnosis, and treatment of essential hypertension in women, gestational hypertension, preeclampsia, and eclampsia., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A series of new metallophores, referred to as frankobactins, were extracted from cultures of the symbiotic and nitrogen-fixing actinobacterium Frankia sp. CH37. Structure elucidation revealed a 2-hydroxyphenyl-substituted oxazoline core and a chain composed of five proteinogenic and nonproteinogenic amino acids, suggesting nonribosomal peptide synthesis as the biosynthetic origin. By whole-genome sequencing, bioinformatic analysis, and comparison with other Frankia strains, the genetic locus responsible for the biosynthesis was detected. Spectrophotometric titration of frankobactin with Fe(III) and Cu(II) and mass spectrometry established the 1:1 (metal:frankobactin) coordination. Uptake experiments suggested that frankobactin A 1 ( 1 ) did not serve to recruit iron, but to detoxify Cu(II). As frankobactin A 1 prevents the cellular entry of Cu(II), it could play a crucial role in the symbiosis of Frankia sp. and its host in the reclamation of copper-contaminated soil.

Macroalgal microbiomes have core functions related to biofilm formation, growth, and morphogenesis of seaweeds. In particular, the growth and development of the sea lettuce Ulva spp. (Chlorophyta) depend on bacteria releasing morphogenetic compounds. Under axenic conditions, the macroalga Ulva mutabilis develops a callus-like phenotype with cell wall protrusions. However, co-culturing with Roseovarius sp. (MS2) and Maribacter sp. (MS6), which produce various stimulatory chemical mediators, completely recovers morphogenesis. This ecological reconstruction forms a tripartite community which can be further studied for its role in cross-kingdom interactions. Hence, our study sought to identify algal growth- and morphogenesis-promoting factors (AGMPFs) capable of phenocopying the activity of Maribacter spp. We performed bioassay-guided solid-phase extraction in water samples collected from U. mutabilis aquaculture systems. We uncovered novel ecophysiological functions of thallusin, a sesquiterpenoid morphogen, identified for the first time in algal aquaculture. Thallusin, released by Maribacter sp., induced rhizoid and cell wall formation at a concentration of 11 pmol l-1. We demonstrated that gametes acquired the iron complex of thallusin, thereby linking morphogenetic processes with intracellular iron homeostasis. Understanding macroalgae-bacteria interactions permits further elucidation of the evolution of multicellularity and cellular differentiation, and development of new applications in microbiome-mediated aquaculture systems., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Frankia spp. are widespread nitrogen-fixing soil bacteria, which often live in symbiosis with a broad range of hosts. Metal homeostasis plays a crucial role in the success of the symbiosis regarding the acquisition of essential trace metals and detoxification of potentially toxic elements. We have hypothesised that Frankia releases many organic ligands with a broad spectrum of affinity for essential and toxic metals. We coined the term 'ligandosphere' to describe the entirety of excreted metal complexing agents and ligands derived from the dissolved organic matter. Using metal isotope-coded profiling (MICP); metallophores of physiological important and toxic trace metals were identified by the addition of stable metal isotope pairs such as 54Fe/58Fe, 63Cu/65Cu, 66Zn/68Zn or 95Mo/98Mo. Liquid chromatography coupled to a mass spectrometer revealed strong variations of the metallophore profile in between the 14 test-strains. In total, about 83 organic ligands were identified as binding to one of the tested metals. The predicted sum formula of the major Fe binding ligands and MS/MS experiments suggested that several metallophore candidates have a similar molecular backbone. Growth experiments with a hyper-producer of metallophores revealed a positive relationship between metallophore production and the concentration of Cu in the growth medium. The present study provides the first comprehensive overview of the complexity of Frankia's ligandosphere. It opens a path to a deeper understanding of mechanisms that regulate metal homeostasis in frankiae. Deciphering these mechanisms is important since the fitness of actinorhizal plants and their potential in ecological restoration relies heavily on their symbiosis with frankiae.

Introduction: Stable isotopic labeling experiments are powerful tools to study metabolic pathways, to follow tracers and fluxes in biotic and abiotic transformations and to elucidate molecules involved in metal complexing., Objective: To introduce a software tool for the identification of isotopologues from mass spectrometry data., Methods: DeltaMS relies on XCMS peak detection and X 13 CMS isotopologue grouping and then analyses data for specific isotope ratios and the relative error of these ratios. It provides pipelines for recognition of isotope patterns in three experiment types commonly used in isotopic labeling studies: (1) search for isotope signatures with a specific mass shift and intensity ratio in one sample set, (2) analyze two sample sets for a specific mass shift and, optionally, the isotope ratio, whereby one sample set is isotope-labeled, and one is not, (3) analyze isotope-guided perturbation experiments with a setup described in X 13 CMS., Results: To illustrate the versatility of DeltaMS, we analyze data sets from case-studies that commonly pose challenges in evaluation of natural isotopes or isotopic signatures in labeling experiment. In these examples, the untargeted detection of sulfur, bromine and artificial metal isotopic patterns is enabled by the automated search for specific isotopes or isotope signatures., Conclusion: DeltaMS provides a platform for the identification of (pre-defined) isotopologues in MS data from single samples or comparative metabolomics data sets.

Biological nitrogen fixation can be catalysed by three isozymes of nitrogenase: molybdenum (Mo)-nitrogenase, vanadium (V)-nitrogenase and iron-only (Fe)-nitrogenase. The activity of these isozymes strongly depends on their metal cofactors, molybdenum, vanadium and iron, and their bioavailability in ecosystems. Here, we show how metal bioavailability can be affected by the presence of tannic acid (organic matter), and the subsequent consequences on diazotrophic growth of the soil bacterium Azotobacter vinelandii. In the presence of tannic acids, A. vinelandii produces a higher amount of metallophores, which coincides with an active, regulated and concomitant acquisition of molybdenum and vanadium under cellular conditions that are usually considered not molybdenum limiting. The associated nitrogenase genes exhibit decreased nifD expression and increased vnfD expression. Thus, in limiting bioavailable metal conditions, A. vinelandii takes advantage of its nitrogenase diversity to ensure optimal diazotrophic growth., (© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Metal isotope coded profiling (MICP) introduces a universal discovery platform for metal chelating natural products that act as metallophores, ion buffers or sequestering agents. The detection of cation and oxoanion complexing ligands is facilitated by the identification of unique isotopic signatures created by the application of isotopically pure metals.

Metallophores are a unique class of organic ligands released, for example, by nitrogen fixing bacteria in their environment in order to recruit the micronutrients molybdenum (Mo) and iron (Fe). Mo and Fe are essential cofactors of nitrogenase that reduces atmospheric nitrogen into bioavailable ammonium. Upon release, these bacterial metallophores bind to both metal cations and oxo-anions in the extracellular medium increasing the bioavailability of the metals to the nitrogen fixers, which can subsequently recruit the complexes. The efficient quantification of those metal complexes is crucial for the understanding of the homeostasis of the metal cofactors of nitrogenase (e.g., Fe and Mo), the dynamics of nitrogen fixation and the nitrogen cycle. A novel direct ultra-high-performance liquid chromatography coupled to a time-of-flight mass spectrometer (UHPLC-ToF-MS) was developed to quantify and monitor the production of Fe and Mo complexes of the catecholate metallophores protochelin (Prot) and azotochelin (Azo) in the growth medium of the nitrogen fixer and model organism Azotobacter vinelandii. Chromatographic separations were carried on a reversed C18-phase with a mobile phase ramped from water to acetonitrile spiked with 1 mmol/L ammonium acetate (pH 6.6) to achieve stability of the metal complexes. Linearity for Mo-protochelin and Fe-protochelin was found at the concentration range between 5.0×10(-8) and 9.0×10(-7) mol/L with a limit of detection of 2.0×10(-8) and 3.0×10(-8) mol/L, respectively. The coefficient of variation of the procedure is in the range from 1.5 to 3.4%. The validation has hence demonstrated that the UHPLC-ToF-MS methodology is a fast, precise, specific, robust, and sensitive approach allowing the direct measurement of metallophores in growth medium without any sample preparation. The UHPLC-ToF-MS methodology was applied to the analysis of metallophores in our laboratory. Under lower Mo concentration, the Mo-protochelin concentration peaks in the middle lag phase, while the Fe-protochelin concentration rises to two maxima at the beginning of the exponential phase and during the stationary phase. The results indicate that the production of metallophores is highly dynamic throughout the growth and has to be monitored with high sensitivity and temporal resolution., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The purpose of this study was to determine if facial or dentoalveolar growth takes place after the occurrence of the radiographic handwrist stage R-J (completed fusion of the proximal epiphysis and diaphysis of the radius), which generally defines the completion of facial growth. Handwrist roentgenograms and lateral head films (LHFs) from 56 subjects (31 male and 25 female) aged 14 to 21 years were examined. Eight cephalometric distances (3 sagittal, 4 vertical, and 1 diagonal) and their changes during 2 different examination periods (from 1 year before to 2 years after the occurrence of R-J) were assessed. The investigation revealed that after the occurrence of R-J vertical dentoalveolar growth changes between 0.5 and 1.75 mm took place in the mandible and in the maxilla in 20% and 10% of the subjects, respectively. Comparing the 2 periods the frequency of the measured growth changes before and after R-J was, on average, almost equal. Because chronological age cannot be used for the assessment of facial growth termination, a reliable indicator for the assessment of facial growth termination is of major importance. After the occurrence of the handwrist stage R-J, most subjects revealed growth changes of less than 1 mm. Especially in the field of tooth implantology, it is important to forecast even small vertical dentoalveolar growth changes. The detected amount of growth after the insertion of an implant can cause esthetic and functional problems.