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Abstract Background Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP). Methods and Results Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median. Conclusion A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.

Background and aims: It is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state. Methods: The studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat. Results: Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups. Conclusion: This study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity.

Dual antiplatelet therapy (DAPT) for 6–12 months, followed by lifelong aspirin monotherapy is considered an effective standard therapy for the prevention of thrombo-ischemic events in patients with acute and chronic coronary syndrome (ACS, CCS) undergoing percutaneous coronary intervention (PCI) or after a primarily conservative treatment decision. In ACS patients, the stronger P2Y12-inhibitors ticagrelor or prasugrel are recommended in combination with aspirin unless the individual bleeding risk is high and shortening of DAPT is warranted or clopidogrel is preferred. However, also in patients at low individual bleeding risk, DAPT is associated with a higher risk of bleeding. In recent years, new antithrombotic treatment strategies, such as shortening DAPT followed by early P2Y12-inhibitor monotherapy and de-escalating DAPT from potent P2Y12-inhibitors to clopidogrel by maintaining DAPT duration time, have been investigated in clinical trials and shown to reduce bleeding complications in cardiovascular high-risk patients without negative effects on ischemic events. In this review, we summarize the current knowledge and discuss its implication on future antithrombotic strategies in terms of a personalized medicine.

Changes in circulating cell populations may promote ischemic events that occur soon after discontinuation of P2Y12-inhibition. The aim of the study was to track the course of thrombopoietic and erythropoietic cells in patients with coronary artery diseases (CAD) after planned and physician-driven cessation of chronic P2Y12-inhibition (clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID). Cell fractions were determined in 62 patients at baseline (the last day of P2Y12-inhibitor intake), on day-10, day-30, and day-180 thereafter. Immature platelet fraction (IPF), immature reticulocyte fraction (IRF), reticulocyte hemoglobin content (Ret-Hb) and red blood cell count (RBC) significantly increased from baseline to day-180 (IPF: p = .003; IRF: p = .013; Ret-Hb: p

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Although initial reports concentrated on severe respiratory illness, emerging literature has indicated a substantially elevated risk of thromboembolic events in patients with COVID-19 disease. Pro-inflammatory cytokine release has been linked to endothelial dysfunction and activation of coagulation pathways, as evident by elevated D-dimer levels and deranged coagulation parameters. Both macrovascular and microvascular thromboses have been described in observational cohort and post-mortem studies. Concurrently, preliminary data have suggested the role of therapeutic anticoagulation in preventing major thromboembolic complications in moderately but not critically ill patients. However, pending results from randomized controlled trials, clear guidance is lacking regarding the intensity and duration of anticoagulation in such patients. Herein, we review the existing evidence on incidence and pathophysiology of COVID-19 related thromboembolic complications and guide anticoagulation therapy based on current literature and societal consensus statements.

Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of independent predictors on long-term survival was evaluated. Results: A total of 338 patients (median age 72 years, 86.9% female) from six centers were included. Severe in-hospital complications occurred in 14.5% of patients. In multivariable analysis, high neutrophile-lymphocyte-ratio (NLR; OR 1.04 [95% CI 1.02–1.07], p = 0.009) and low LVEF (OR 0.92 [0.90–0.95] per %, p < 0.001) were significant predictors of severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were significantly associated with reduced 5-year survival. Conclusions: Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short- and long-term outcome after TTS.

Background: Coronavirus disease (COVID-19) was first described at the end of 2019 in China and has since spread across the globe. Red cell distribution width (RDW) is a potent prognostic marker in several medical conditions and has recently been suggested to be of prognostic value in COVID-19.Methods: This retrospective, observational study of consecutive patients with COVID-19 was conducted from March 12, 2020 to December 4, 2020 in the Wilhelminenhospital, Vienna, Austria. RDWlevels on admission were collected and tested for their predictive value of 28-day mortality.Results: A total of 423 eligible patients with COVID-19 were included in the final analyses and 15.4% died within 28 days (n = 65). Median levels of RDWwere significantly higher in non-survivors compared to survivors [14.6% (IQR, 13.7–16.3) vs. 13.4% (IQR, 12.7– 14.4), P < 0.001]. Increased RDW was a significant predictor of 28-day mortality [crude odds ratio (OR) 1.717, 95% confidence interval (CI) 1.462–2.017; P = < 0.001], independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (adjusted OR of the final model 1.368, 95% CI 1.126–1.662; P = 0.002). This association remained consistent upon sub-group analysis. Our study data also demonstrate that RDW levels upon admission for COVID-19 were similar to previously recorded, non-COVID-19 associated RDW levels [14.2% (IQR, 13.3–15.7) vs. 14.0% [IQR, 13.2–15.1]; P = 0.187].Conclusions: In this population, RDWwas a significant, independent prognostic marker of short-term mortality in patients with COVID-19.

Coronavirus disease-19 (COVID-19) emerged late December 2019 in the city of Wuhan, China and has since spread rapidly all over the world causing a global pandemic. While the respiratory system is the primary target of disease manifestation, COVID-19 has been shown to also affect several other organs, making it a rather complex, multi-system disease. As such, cardiovascular involvement has been a topic of discussion since the beginning of the COVID-19 pandemic, primarily due to early reports of excessive myocardial injury in these patients. Treating physicians are faced with multiple challenges in the management and early triage of patients with COVID-19, as disease severity is highly variable ranging from an asymptomatic infection to critical cases rapidly deteriorating to intensive care treatment or even fatality. Laboratory biomarkers provide important prognostic information which can guide decision making in the emergency department, especially in patients with atypical presentations. Several cardiac biomarkers, most notably high-sensitive cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have emerged as valuable predictors of prognosis in patients with COVID-19. The purpose of this review was to offer a concise summary on prognostic cardiac biomarkers in COVID-19 and discuss whether routine measurements of these biomarkers are warranted upon hospital admission.

Background: The rapid and reliable differentiation of myocardial infarction (MI) due to atherothrombosis (T1MI) from MI due to supply-demand mismatch (T2MI) or acute myocardial injury is of major clinical relevance due to very different treatments, but still a major unmet clinical need. This study aimed to investigate whether copeptin, a stress hormone produced in the hypothalamus, helps to differentiate between T1MI versus T2MI or injury., Methods: In a retrospective analysis, 1271 unselected consecutive patients presenting with symptoms suggestive of MI to the emergency department were evaluated. Patients diagnosed with ST-elevation MI were excluded. All patients with elevated cardiac troponin I (cTnI) concentration possibly indicating MI were classified into T1MI, T2MI, or acute myocardial injury using detailed clinical assessment and coronary imaging. Copeptin plasma concentration was measured in a blinded fashion. A multicenter diagnostic study with central adjudication of the final diagnosis served as external validation cohort (n = 1390)., Results: Among 1161 patients, 154 patients had increased cTnI concentration. Of these, 78 patients (51%) were classified as T1MI and 76 (49%) as T2MI or myocardial injury. Patients with T2MI or myocardial injury had significantly higher copeptin plasma concentration between patients versus T1MI (21,4 pmol/l versus 8,1 pmol/l, p = 0,001). A multivariable regression analysis revealed that higher concentrations of copeptin and C-reactive protein, higher heart rate at presentation and lower frequency of smoking remained significantly associated with T2MI and myocardial injury. Findings were largely confirmed in the external validation cohort., Conclusion: In patients without ST-segment elevation, copeptin concentration was higher in T2MI and myocardial Injury versus T1MI and may help in their differential diagnosis., Competing Interests: Declaration of competing interest Dr. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the University of Basel, the University Hospital Basel, Abbott, Astra Zeneca, Beckman Coulter, Brahms, Idorsia, LSI-Medience, Novartis, Ortho Clinical Diagnostics, Quidel, Roche, Siemens, Singulex, Sphingotec, as well as speaker honoraria/consulting honoraria from Amgen, Astra Zeneca, Bayer, Beckman Coulter, Boehringer Ingelheim, BMS, Idorsia, Novartis, Osler, Roche, Sanofi, Siemens, and Singulex. Dr. Huber has received speaker honoraria/consulting honoraria from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Chiesi, Daiichi Sankyo, Ferrer, Novartis, NovoNordisk, and Sanofi Aventis. All other authors have no COIs. This study received no grant support. No conflicts of interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We endeavored to create an evidence-based curriculum to improve general surgery resident fund of knowledge. Global and resident-specific interventions were employed to this end. These interventions were monitored via multiple choice question results on a weekly basis and American Board of Surgery In-Training Examination (ABSITE) performance., Methods: This study was performed in a prospective manner over a 2-year period. A structured textbook review with testing was implemented for all residents. A focused textbook question-writing assignment and a Surgical Council on Resident Education (SCORE)-based individualized learning plan (ILP) were implemented for residents scoring below the 35th percentile on the ABSITE., Results: Curriculum implementation resulted in a statistically significant reduction in the number of residents scoring below the 35th percentile, from 50% to 30.8% ( P = .023). One hundred percent of residents initially scoring below the 35th percentile were successfully remediated over the study period. Average overall program ABSITE percentile scores increased from 38.5% to 51.4% over a 2-year period., Conclusion: Structured textbook review and testing combined with a question-writing assignment and a SCORE-focused ILP successfully remediated residents scoring below the 35th percentile and improved general surgery residency ABSITE performance., Competing Interests: Conflicts of Interest: The authors declare they have no conflicts of interest., (© 2024 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Laser shock peening (LSP) is a mechanical surface treatment process to modify near-surface material properties. Compared to conventional shot peening (SP) the process parameters can be finely adjusted with greater precision and a higher penetration depth of compressive residual stresses could be reached. However, high process times of LSP leads to high production costs. In this study, ultrafast LSP (U-LSP) with an ultrafast laser source (pulse time in the picosecond range) was applied on specimens made of X5CrNiCu15-5 and AlZnMgCu1.5. The surface characteristics (surface roughness) and surface-near properties (microstructure, residual stresses, and phase composition) were compared to the as-delivered condition, to conventional laser shock peening (C-LSP), and to SP, whereas metallographic analyses and X-ray and synchrotron radiation techniques were used. The process time was significantly lower via U-LSP compared to C-LSP. For X5CrNiCu15-5, no significant compressive residual stresses were induced via U-LSP. However, for AlZnMgCu1.5, similar compressive residual stresses were reached via C-LSP and U-LSP; however, with a lower penetration depth. A change in the phase portions in the surface layer of X5CrNiCu15-5 after C-LSP compared to SP were determined.

α-Pyrrolidinohexiophenone (α-PHP) is a derivative of the class of α-pyrrolidinophenones, a subgroup of synthetic cathinones. These substances are the second most abused drugs of new psychoactive substances. Here, we report the toxicological investigation of a series of 29 authentic forensic and clinical cases with analytically confirmed intake of α-PHP including two cases of drug testing in newborns using meconium. The age range of subjects where serum samples were available was 23-51 years (median 39.5), and 90% were male. Serum α-PHP concentrations, determined by a validated LC-MS-MS method, showed a high variability ranging from 1 to 83 ng/mL (mean, 40 ng/mL; median, 36 ng/mL). Comprehensive toxicological analysis revealed co-consumption of other psychotropic drugs in almost all cases with frequent occurrence of opiates (60%), benzodiazepines (35%), cannabinoids (30%), and cocaine (20%). Hence, forensic and clinical symptoms like aggressive behavior, sweating, delayed physical response, and impaired balance could not be explained by the abuse of α-PHP alone but rather by poly-intoxications. Liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry were used to investigate the metabolism of α-PHP in vivo using authentic human urine samples. Altogether, 11 phase I metabolites and 5 phase II glucuronides could be identified by this approach. Apart from the parent drug, most abundant findings in urine were the metabolites dihydroxy-pyrrolidinyl-α-PHP and dihydro-α-PHP and, to a lesser extent, 2'-oxo-dihydro-α-PHP and 2'-oxo-α-PHP. Monitoring of these metabolites along with the parent drug in forensic and clinical toxicology could unambiguously prove the abuse of the novel designer drug α-PHP., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is an increasing amount of evidence suggesting multiple fatal complications in takotsubo syndrome; however, findings on the long-term outcome are scarce and show inconsistent evidence., Methods: This is a single center study of long-term prognosis in takotsubo patients admitted to the Klinik Ottakring, Vienna, Austria, from September 2006 to August 2019. We investigated the clinical features, prognostic factors and outcome of patients with takotsubo syndrome. Furthermore, survivors and non-survivors and patients with a different cause of death were compared., Results: Overall, 147 patients were included in the study and 49 takotsubo patients (33.3%) died during the follow-up, with a median of 126 months. The most common cause of death was a non-cardiac cause (71.4% of all deaths), especially malignancies (26.5% of all deaths). Moreover, non-survivors were older and more often men with more comorbidities (chronic kidney disease, malignancy). Patients who died because of cardiovascular disease were older and more often women than patients who died due to non-cardiovascular cause. Adjusted analysis showed no feature of an independent predictor of cardiovascular mortality for takotsubo patients. Female gender (HR = 0.32, CI: 0.16-0.64, p < 0.001), cancer (HR = 2.35, CI: 1.15-4.8, p = 0.019) and chronic kidney disease (HR = 2.61, CI: 1.11-6.14, p = 0.028) showed to be independent predictors of non-cardiovascular mortality., Conclusion: Long-term prognosis of takotsubo patients is not favorable, mainly due to noncardiac comorbidities. Hence, consequent outpatient care in regular intervals after a takotsubo event based on risk factor control and early detection of malignancies seems justified., (© 2021. Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Repeated episodes of trauma, particularly in older adults, result in increased morbidity and mortality. This study investigates trauma recidivism in our adult population to identify which patients in our region are more likely to become recidivists., Materials and Methods: This 4 year retrospective study (2013 to 2017) examines all patients 18 years of age or older with multiple hospital admissions for trauma, comparing patients ages 65 and older (older adults) to those ages 18 to 64 (younger adults). Exclusion criteria consisted of those younger than 18 and/or had a home zip code outside of the study region. Data included admission demographics, injury characteristics and other clinical metrics., Results: There were 240 younger adult and 182 older adult trauma recidivists included. In total, 4% of all patients were recidivists with significantly higher rates of recidivism among older adults (OR: 1.94 [1.59-2.36], p <0.001). Older adult recidivists were more likely to be female (OR: 4.28 [2.82-6.51], p <0.001) and suffer blunt trauma secondary to a fall (OR: 5.36 [3.91-7.35], p <0.001). Trauma recidivism in older adults also correlated with a higher Injury Severity Score, longer length of stay and an increased proportion of patients requiring to be discharged home with organizational help or to a rehabilitation facility., Conclusions: Trauma can be recurrent and associated with poor health outcomes, particularly in older adults. Recidivists in the studied region were significantly older with the most at-risk population consisting of females suffering blunt injury secondary to a fall. Improved prevention strategies are needed for this population., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2021 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

Among the increasing number of new psychoactive substances, 3',4'-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) belongs to the group of synthetic cathinones, which are the derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant. Currently, only limited data are available for MDPHP, and no information is available on its human metabolism. We describe the toxicological investigation of nine cases associated with the use of MDPHP during the period February-June 2019. Serum MDPHP concentrations showed a high variability ranging from 3.3 to 140 ng/mL (mean 30.3 ng/mL and median 16 ng/mL). Intoxication symptoms of the described cases could not be explained by the abuse of MDPHP alone because in all cases the co-consumption of other psychotropic drugs with frequent occurrence of opiates and benzodiazepines could be verified. Therefore, the patients showed different clinical symptoms, including aggressive behaviour, delayed physical response, loss of consciousness and coma. Liquid chromatography-high-resolution mass spectrometry was successfully used to investigate the human in vivo metabolism of MDPHP using authentic human urine samples. The metabolism data for MDPHP were further substantiated by the analysis of human urine using gas chromatography-mass spectrometry (GC-MS, a widely used systematic toxicological analysis method appropriate for the toxicological detection of MDPHP intake), which revealed the presence of seven phase I metabolites and three phase II metabolites as glucuronides. GC-MS spectral data for MDPHP and metabolites are provided. The identified metabolite pattern corroborates the principal metabolic pathways of α-pyrrolidinophenones in humans., (© 2020 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Suspension trauma is a potentially dangerous outcome of the body's normal physiological response to motionless vertical suspension from a rope. All who use a safety harness are at risk, and the growing need for occupational work at extreme heights in addition to the interest in caving and mountaineering worldwide has led to an increased number of individuals wearing protective harnesses for work and recreation. It has been described as the cause of death in many climbing incidents and has been demonstrated in multiple studies for improvement of employee fall protection. Although suspension trauma is potentially life-threatening, there is a lack of scientific data to define an exact mechanism of injury, and there is little conclusive evidence about the proper management of victims. This has led to controversy surrounding the topic of postsuspension management. The discussion of suspension trauma has historically been led by nonmedical experts, but the recent push for more evidence-based research has created a better understanding of the condition. Further investigation of the pathophysiological mechanism of suspension trauma and more complete collection of data from individual cases will increase our understanding of the topic and lead to better decision making in the management of victims., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Weber et al.)

Aims: The combination of oral anticoagulation with a P2Y12 inhibitor and aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is associated with a high bleeding risk. Dual antithrombotic therapy (DAT) with omission of aspirin is a promising option to reduce bleedings, but carries a yet unknown risk of ischaemic events. We therefore sought to systematically review and analyse randomized controlled trials investigating DAT vs. triple antithrombotic therapy (TAT) in patients with AF following PCI and/or acute coronary syndrome (ACS)., Methods and Results: We included four trials with overall 9317 patients (5039 DAT, 4278 TAT) in our analysis. Dual antithrombotic therapy was associated with a significant reduction in thrombolysis in myocardial infarction major bleeding [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.42-0.65; P = 0.0001], while the composite trial-defined ischaemic endpoint did not differ significantly between DAT and TAT (HR 0.98, 95% CI 0.79-1.22; P = 0.88). There was also no difference regarding the occurrence of myocardial infarction (MI; HR 1.16, 95% CI 0.92-1.46; P = 0.21) or stent thrombosis (HR 1.25, 95% CI 0.69-2.26; P = 0.46). Absolute numbers for MI were 131/4278 (3.1%) with TAT and 182/5039 (3.6%) with DAT, and for stent thrombosis 32/4278 (0.75%) and 52/5039 (1%), respectively. A post hoc power calculation based on the size and event rate of this meta-analysis revealed 80% power to detect a 37% and 100% increase in MI and stent thrombosis, respectively., Conclusion: Dual antithrombotic therapy significantly reduces bleedings compared with TAT and seems to have a similar effect in preventing ischaemic endpoints in AF patients post-PCI or ACS. Future investigations are needed to determine its applicability specifically in patients at high risk of ischaemic outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Popliteal artery injuries (PAIs) remain a challenging entity and carry the greatest risk of limb loss among traumatic lower extremity vascular injuries. Operative management of traumatic popliteal vascular injuries continues to evolve. Improved diagnostic imaging and the introduction of endovascular techniques offered alternative modalities to traditional surgical management. Despite major efforts in establishing protocols and guidelines in the management of vascular trauma, optimal strategies of traumatic PAIs are still under investigation. Herein, we discussed the role of multidisciplinary team, involving trauma and endovascular surgeons, emergency department personnel, and interventional radiologists in the management of complex PAIs., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Comprehensive screening procedures for psychoactive agents in body fluids are an essential task in clinical and forensic toxicology. With the continuous emergence and adaption of new psychoactive substances (NPS) keeping a screening method up to date is challenging. To meet these demands, hyphenated high-resolution mass spectrometry has gained interest as extensive and expandable screening approach. Here we present a comprehensive method for systematic toxicological analysis of serum by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) with data independent acquisition. The potential of this method was demonstrated by analysis of 247 authentic serum- and 12 post-mortem femoral blood samples. Thus 950 compounds, comprising 185 different drugs and metabolites could be identified. For the detected substances, including pharmaceutical substances, illicit drugs as well as NPS, serum concentrations were confirmed ranging from traces to toxic values indicating the capability for forensic toxicological requirements. Positive identification of drugs was achieved by accurate mass measurement (±5ppm for [M+H] + ; ±10ppm for [M-H] - ), retention time (±0.35min), isotopic pattern match (less than 10 m/z RMS [ppm]), isotope match intensity (less than 20% RMS) and the presence of at least two fragment ions. The LC-QTOF-MS procedure was shown to be superior to serum screening by GC-MS, since 240% (335 versus 141) more drugs were identified in serum samples compared to GC-MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Anthroposophic therapeutic speech (ATS) has been shown to positively influence heart rate variability (HRV) and cardiorespiratory coordination in healthy volunteers. This prospective, exploratory, pre-post study was performed to investigate ATS effects on baroreflex sensitivity (BRS), heart rate (HR), HRV by standard deviation of beat to beat intervals (SDNN), blood pressure (BP), and mood in hypertensive patients., Design: Patients received three ATS treatments, alternating with three sham interventions (control). During the sessions, BP and electrocardiography were continuously recorded. BRS and SDNN were analyzed from those measurements. Changes in mood score were assessed by a questionnaire. All data were compared before and after intervention (ATS and control)., Results: Thirty-one patients participated, the majority diagnosed with arterial hypertension (22 out of 31). Pre-post analysis of the data revealed immediate and significant changes in hypertensive patients during control and ATS with respect to BRS (control: 6.57 to 6.92 msec/mmHg, p = 0.0349; ATS: 6.03 to 7.27 msec/mmHg, p < 0.0001), SDNN (control: 39 to 42 msec, p = 0.0058; ATS: 38 to 43 msec, p = 0.0003), and HR (control: 74 to 71 beats per minute [bpm], p < 0.0001; ATS: 74 to 70 bpm, p < 0.0001). In normotensive patients, those changes were generally less pronounced and less significant with respect to BRS (control: 8.13 to 8.56 msec/mmHg, p = 0.1102; ATS: 8.20 to 8.98 msec/mmHg, p = 0.0273), SDNN (control: 36 to 40 msec, p = 0.0002; ATS: 35 to 38 msec, p = 0.0556), and HR (control: 80 to 77 bpm, p < 0.0001; ATS: 80 to 78 bpm, p < 0.0011). Only in hypertensive patients significant long-term changes were observed for BRS (6.6 to 7.7 msec/mmHg, p = 0.0070), SDNN (39.1 to 45.5 msec, p = 0.0074), and HR (75.8 to 67.2 bpm, p = 0.0001). No significant long-term changes were observed in normotensive patients. The mean systolic BP did not change significantly during this study. Both ATS and control also yielded improvements in the mood summary score, which again were more apparent for ATS than for sham interventions, but these were more pronounced among normotensive patients (3.5 to 4.2) than for hypertensive patients (2.9 to 3.9)., Conclusion: The results indicate that ATS has the potential to improve cardiovascular parameters which play an important role in BP regulation capability.

3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone belonging to the class of α-pyrrolidinophenones that become increasingly popular as a designer psychostimulant. Here, we report a comprehensive collection of MDPV exposure with quantitative serum level confirmation in Germany. During the years 2014-2016, we could proof consumption of MDPV in 23 cases where urine and blood samples were submitted to our laboratory by the police of Lower Saxony. Most of the samples underwent systematic toxicological analysis by gas chromatography-mass spectrometry (GC-MS), where MDPV could be detected in urine and/or serum samples. The determined concentrations of MDPV in serum showed a high variability, ranging from traces (<10ng/mL) up to 576ng/mL with a mean concentration of 118ng/mL and median of 47ng/mL. The majority of MDPV users were men (87%) and the age ranged from 23 to 49 years (mean 35.9, median 37 years). For most of the analytically confirmed MDPV cases we could prove co-consumption of other psychotropic drugs with frequent occurrence of opiates and cannabinoids in 22% of the cases, followed by benzodiazepines and cocaine in 17%. Analysis of urine samples by GC-MS disclosed the presence of MDPV and its metabolites 2'-oxo-MDPV, demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-oxo-MDPV, demethylenyl-methyl-oxo-MDPV and demethylenyl-methyl-N,N-bisdealkyl-MDPV. The metabolite pattern substantiates previous suggestions for principle metabolic pathways of MDPV in humans., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this study, promising electrolytes for use in Li-ion batteries are studied in terms of interacting and wetting polyethylene (PE) and particle-coated PE separators. The electrolytes are characterized according to their physicochemical properties, where the flow characteristics and the surface tension are of particular interest for electrolyte-separator interactions. The viscosity of the electrolytes is determined to be in a range of η = 4-400 mPa∙s and surface tension is finely graduated in a range of γL = 23.3-38.1 mN∙m(-1). It is verified that the technique of drop shape analysis can only be used in a limited matter to prove the interaction, uptake and penetration of electrolytes by separators. Cell testing of Li|NMC half cells reveals that those cell results cannot be inevitably deduced from physicochemical electrolyte properties as well as contact angle analysis. On the other hand, techniques are more suitable which detect liquid penetration into the interior of the separator. It is expected that the results can help fundamental researchers as well as users of novel electrolytes in current-day Li-ion battery technologies for developing and using novel material combinations.

Objective: This study was performed to characterize the physiologic effects of rhythmical massage (RM), an anthroposophic therapy whose effectiveness is supported by empirical observations and a prospective observational study., Methods: Patients referred to RM at the Paracelsus Hospital Richterswil for any indication were continuously enrolled. They received an average of 10 RM sessions, which included not only the massage but also therapeutic rest in the supine position immediately thereafter. Effects of RM on surface temperature and on heart rate variability (HRV) were determined with infrared imaging (IRI) and electrocardiography (ECG), respectively. IRI of the patients' dorsal region was performed without clothes, in standing position, at the start and at the end of two waiting periods before and after RM. ECG was performed from the beginning of the first waiting period until the end of the second one., Results: Results on IRI from 9 and ECG from 11 patients could be analyzed. RM led to an immediate increase in dorsal temperature. Furthermore, comparison of the IRI images for consecutive RM sessions showed a tendency toward improved warmth distribution as a progressive therapy effect. Analysis of the EGC results recorded during the waiting periods-in the sitting position--showed a significant increase of HRV after RM, as detected by the standard deviation of the beat-to-beat periods and a relative increase of low-frequency power. During the course of the RM sessions, the change in HRV during the therapeutic rest period depended on the initial value: Low initial values were enhanced, whereas high ones were reduced., Conclusions: RM led to an immediate increase in the patient's dorsal surface temperature, as well as increased HRV and sympathetic stimulation. In the long term, RM resulted in a progressive improvement of warmth distribution and regulation of the resting HRV.

Ikaros is a critical regulator of lymphocyte development and homeostasis; thus, understanding its transcriptional regulation is important from both developmental and clinical perspectives. Using a mouse transgenic reporter approach, we functionally characterized a network of highly conserved cis-acting elements at the Ikzf1 locus. We attribute B-cell and myeloid but not T-cell specificity to the main Ikzf1 promoter. Although this promoter was unable to counter local chromatin silencing effects, each of the 6 highly conserved Ikzf1 intronic enhancers alleviated silencing. Working together, the Ikzf1 enhancers provided locus control region activity, allowing reporter expression in a position and copy-independent manner. Only 1 of the Ikzf1 enhancers was responsible for the progressive upregulation of Ikaros expression from hematopoietic stem cells to lymphoid-primed multipotent progenitors to T-cell precursors, which are stages of differentiation dependent on Ikaros for normal outcome. Thus, Ikzf1 is regulated by both epigenetic and transcriptional factors that target its enhancers in both redundant and specific fashions to provide an expression profile supportive of normal lymphoid lineage progression and homeostasis. Mutations in the Ikzf1 regulatory elements and their interacting factors are likely to have adverse effects on lymphopoiesis and contribute to leukemogenesis.

The melting point of triacylglycerides (TAGs) under atmospheric pressure depends on both the fatty acid composition and crystalline structure of the polymorphic state, which are influenced by the temperature treatment history of the TAG. In this contribution, the additional effect of high hydrostatic pressure is described. Samples were placed in a temperature-controlled cell and pressurized up to 450 MPa. The phase transition was investigated either by perpendicular light scattering and transmission or with a polarized-light microscope. The high-pressure polarized-light microscope allows a precise determination of the melting point. The investigated TAGs showed a significant nonlinear increase of the melting point with pressure. Light scattering and transmission were used to observe the phase change in the high-pressure cell. Similar to supercooling in temperature-induced phase transition, we found a dramatic increase of the delay time in our pressure-induced solidification. Even the dependency of this induction time on the control parameter pressure was similar to that in temperature-driven crystallization. We propose that different crystalline structures may be obtained by superpressuring instead of supercooling.

Objectives: This study sought to determine the clinical course and predictors of long-term outcome in patients with documented amiodarone-induced thyrotoxicosis (AIT)., Background: Amiodarone-induced thyrotoxicosis is a condition that is difficult to manage, in particular because of the long half-life of amiodarone. Data on optimal treatment for AIT are scarce., Methods: We performed a retrospective review among patients with documented AIT at a tertiary care center. Baseline characteristics, treatment received, laboratory parameters, and events during follow-up were evaluated. The predefined composite end point consisted of the following AIT-associated complications: death, heart transplantation, hospitalization for heart failure, myocardial infarction, stroke, hospitalization for arrhythmia management, or hospitalization for treatment complications., Results: Eighty-four patients were included in the present analysis; 27 patients received prednisone for AIT. There was no difference in time to normalization of free thyroxine between those receiving and those not receiving prednisone. Long-term follow-up showed high morbidity and mortality; 47 patients (56%) reached the primary end point. Patients receiving prednisone had a worse outcome than those not receiving prednisone (p = 0.003). Although patients received prednisone for 84 +/- 65 days, curves started to separate only 12 months after the initial diagnosis., Conclusions: Patients with AIT have a high event rate during follow-up. Prednisone had no effect on time to normalization of thyroxine levels and was associated with an increased event rate. Importantly, AIT-related problems must be expected late, at a time when thyroid function is under control.

Questions Under Study: CardioCard is a CDROM of credit card size containing medical information on cardiac patients. Patient data acquired during hospital stay are stored in PDF format and secured by a password known to patients only. In a consecutive series of patients, we assessed acceptance and utility of this new information medium., Methods and Results: A questionnaire was sent to all patients who had received CardioCard over a one-year period. The questionnaire was returned by 392 patients (73%). 44% of patients had the card with them all the time. The majority of patients (73%) considered the CardioCard useful (8% not useful, 19% no statement) and most (78%) would even agree to bear additional costs. Only 5% worried about data security. In contrast, 44% would be concerned of data transmission via internet. During an observation period of 6 (SD 3) months, data were accessed by 27% of patients and 12% of their physicians. The proportion of card users was lower among older patients: < or = 50 years (y), 39%; 51.60 y, 38%; 61.70 y, 26%; >70 y, 16% and particularly among older women: 61.70 y, 9%; >70 y, 5%. Technical problems during data access occurred in 34%, mostly due to incorrect handling., Conclusions: A majority of patients considered CardioCard as useful and safe. Lack of hardware equipment or insufficient computer knowledge, but not safety issues were the most important limitations. As patients expressed concerns regarding protection of privacy if data were accessible via internet, this would remain a strong limiting factor for online use.

Regulated expression of Ikaros is critical for normal hemopoiesis and lymphocyte development. To elucidate the mechanisms underlying transcription of Ikaros, tissue-specific DNase I-hypersensitive sites (DHS) were mapped throughout the Ikaros locus, and several promoters were identified. The activity of these regulatory regions was elucidated using an enhanced green fluorescent protein (EGFP) reporter in transgenic mice. Two genomic fragments, each containing a distinct promoter and its associated DHS cluster, were found to be active in the myeloid (DHS-C2 and DHS-C3) and B-cell (DHS-C3) lineages. Although neither of these regulatory regions was active within the majority of differentiating thymocytes and mature T cells, the DHS-C3 region was active at the earliest stages (DN1-DN3) of T-cell differentiation. However, when the DHS-C3 region was combined with the downstream intronic DHS-C6 cluster, its activity was maintained and raised to higher levels at subsequent stages of T-cell differentiation. This combination of regulatory elements provided reporter expression that closely resembles that of endogenous Ikaros during hemo-lymphopoiesis, and it decreased (but did not alleviate) position effect variegation within the expressing cell types.