Amiodarone prevents wave front-tail interactions in patients with heart failure: an in silico study.

Amiodarone (AM) is an antiarrhythmic drug whose chronic use has proved effective in preventing ventricular arrhythmias in a variety of patient populations, including those with heart failure (HF). AM has both class III [i.e., it prolongs the action potential duration (APD) via blocking potassium channels) and class I (i.e., it affects the rapid sodium channel) properties; however, the specific mechanism(s) by which it prevents reentry formation in patients with HF remains unknown. We tested the hypothesis that AM prevents reentry induction in HF during programmed electrical stimulation (PES) via its ability to induce postrepolarization refractoriness (PRR) via its class I effects on sodium channels. Here we extend our previous human action potential model to represent the effects of both HF and AM separately by calibrating to human tissue and clinical PES data, respectively. We then combine these models (HF + AM) to test our hypothesis. Results from simulations in cells and cables suggest that AM acts to increase PRR and decrease the elevation of takeoff potential. The ability of AM to prevent reentry was studied in silico in two-dimensional sheets in which a variety of APD gradients (ΔAPD) were imposed. Reentrant activity was induced in all HF simulations but was prevented in 23 of 24 HF + AM models. Eliminating the AM-induced slowing of the recovery of inactivation of the sodium channel restored the ability to induce reentry. In conclusion, in silico testing suggests that chronic AM treatment prevents reentry induction in patients with HF during PES via its class I effect to induce PRR.NEW & NOTEWORTHY This work presents a new model of the action potential of the human, which reproduces the complex dynamics during premature stimulation in heart failure patients with and without amiodarone. A specific mechanism of the ability of amiodarone to prevent reentrant arrhythmias is presented.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

Method for Using IMU-Based Experimental Motion Data in BVH Format for Musculoskeletal Simulations via OpenSim.

Biomechanical simulation allows for in silico estimations of biomechanical parameters such as muscle, joint and ligament forces. Experimental kinematic measurements are a prerequisite for musculoskeletal simulations using the inverse kinematics approach. Marker-based optical motion capture systems are frequently used to collect this motion data. As an alternative, IMU-based motion capture systems can be used. These systems allow flexible motion collection without nearly any restriction regarding the environment. However, one limitation with these systems is that there is no universal way to transfer IMU data from arbitrary full-body IMU measurement systems into musculoskeletal simulation software such as OpenSim. Thus, the objective of this study was to enable the transfer of collected motion data, stored as a BVH file, to OpenSim 4.4 to visualize and analyse the motion using musculoskeletal models. By using the concept of virtual markers, the motion saved in the BVH file is transferred to a musculoskeletal model. An experimental study with three participants was conducted to verify our method's performance. Results show that the present method is capable of (1) transferring body dimensions saved in the BVH file to a generic musculoskeletal model and (2) correctly transferring the motion data saved in the BVH file to a musculoskeletal model in OpenSim 4.4.

Postoperative Work and Activity Restrictions After Abdominal Surgery: A Systematic Review.

OBJECTIVE: This systematic review aims to assess what is known about convalescence following abdominal surgery. Through a review of the basic science and clinical literature, we explored the effect of physical activity on the healing fascia and the optimal timing for postoperative activity. BACKGROUND: Abdominal surgery confers a 30% risk of incisional hernia development. To mitigate this, surgeons often impose postoperative activity restrictions. However, it is unclear whether this is effective or potentially harmful in preventing hernias. METHODS: We conducted 2 separate systematic reviews using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The first assessed available basic science literature on fascial healing. The second assessed available clinical literature on activity after abdominal surgery. RESULTS: Seven articles met inclusion criteria for the basic science review and 22 for the clinical studies review. The basic science data demonstrated variability in maximal tensile strength and time for fascial healing, in part due to differences in layer of abdominal wall measured. Some animal studies indicated a positive effect of physical activity on the healing wound. Most clinical studies were qualitative, with only 3 randomized controlled trials on this topic. Variability was reported on clinician recommendations, time to return to activity, and factors that influence return to activity. Interventions designed to shorten convalescence demonstrated improvements only in patient-reported symptoms. None reported an association between activity and complications, such as incisional hernia. CONCLUSIONS: This systematic review identified gaps in our understanding of what is best for patients recovering from abdominal surgery. Randomized controlled trials are crucial in safely optimizing the recovery period.

[Quality of treatment outcomes in alcohol- and substance-related disorders: an evaluation of inpatients from ten psychiatric hospitals]. / Ergebnisqualität bei alkohol- und substanzbezogenen Störungen: eine Auswertung stationär behandelter Patienten aus 10 psychiatrischen Kliniken.

AIM OF THE STUDY: Alcohol and substance-related disorders (ICD 10 F1x.x) are among the most frequent diagnoses made in hospitalized patients requiring somatic and psychiatric care. In order to assess the success of treatment, it is important to establish and implement outcome indicators in practice. METHOD: In 2016, global treatment indicators for admission and at discharge were collected at 10 Vitos clinics in Hesse (CGI and GAF). More than 10,000 patients with ICD10 F1x diagnoses were included in the evaluation. RESULTS: The evaluations show significant improvements of the clinical status as well as differences in treatment duration, remissions and gender differences. CONCLUSION: The study suggests that global indicators of outcome quality are useful in the assessment of treatment success of alcohol and substance-related disorders. Limitations of the study design, instruments and sample are critically reviewed.

A model for human action potential dynamics in vivo.

Computational modeling based on experimental data remains an important component in cardiac electrophysiological research, especially because clinical data such as human action potential (AP) dynamics are scarce or limited by practical or ethical concerns. Such modeling has been used to develop and test a variety of mechanistic hypotheses, with the majority of these studies involving the rate dependence of AP duration (APD) including APD restitution and conduction velocity (CV). However, there is very little information regarding the complex dynamics at the boundary of repolarization (or refractoriness) and reexcitability. Here, we developed a "minimal" ionic model of the human AP, based on in vivo human monophasic AP (MAP) recordings obtained during clinical programmed electrical stimulation (PES) to address the progressive decrease in AP take-off potential (TOP) and associated CV slowing seen during three tightly spaced extrastimuli. Recent voltage-clamp data demonstrating the effect of intracellular calcium on sodium current availability were incorporated and were required to reproduce large (>15 mV) elevations in take-off potential and progressive encroachment. Introducing clinically observed APD gradients into the model enabled us to replicate the dynamic response to PES in patients leading to conduction block and reentry formation for the positive, but not the negative, APD gradient. Finally, we modeled the dynamics of reentry and show that spiral waves follow a meandering trajectory with a period of ~180 ms. We conclude that our model reproduces a variety of electrophysiological behavior including the response to sequential premature stimuli and provides a basis for studies of the initiation of reentry in human ventricular tissue.NEW & NOTEWORTHY This work presents a new model of the action potential of the human which reproduces the complex dynamics during premature stimulation in patients.

[Disorder-related case groups for needs-based hospital care]. / Störungsbezogene Fallgruppen für eine bedarfsgerechte Krankenhausversorgung.

BACKGROUND: The individual needs of patients are central to hospital care. Due to the resulting complexity grouping of patients with similar therapeutic needs seems to facilitate an efficient organization of processes and the required treatment resources in hospital care. OBJECTIVE: The aim of this study was to develop a system of disorder-related, treatment-oriented case groups as a possible tool for the efficient and needs-based organization of hospital care. MATERIAL AND METHODS: The disorder-related groups were developed in a multistage, mixed-methods design. The technical content and quantitative description of the case groups and the extent of treatment included all consecutive inpatient treatment cases discharged between 1 January 2017 and 31 December 2017 from 9 psychiatric hospitals in Hesse, Germany. RESULTS: All diagnoses in chapter F of the German modification of the International Statistical Classification of Diseases 10 (ICD-10-GM) were grouped into a total of 10 disorder-related groups. Analyses included 20,252 inpatient hospital treatment cases. Substantial management-relevant differences between the case groups could be identified and the various case group-specific configurations of clinically relevant comorbidities could be demonstrated. DISCUSSION: The presented disorder-related grouping system and configuration of comorbidities suggest a modular organization of therapeutic measures and constitute a promising basis for needs-based management of patient care. Future work will show to what degree the disorder-related groups can facilitate a needs-specific treatment and align economic and therapeutic interests of psychiatric care.

Infectious rain? Evaluation of human pathogen concentrations in stormwater in separate sewer systems.

Separate sewer systems collect and discharge rainwater directly into surface water bodies. In residential areas covering moderate traffic load these are alternative drainage routes to avoid combined sewer overflow discharge and to keep rivers clean as required by the EU Water Framework Directive. This overflow's microbial quality, however, needs to be evaluated, since stormwater run-offs are potential pathways for pathogens into river systems. Between 2010 and 2016, two separate sewer systems in North Rhine-Westphalia (Germany) were investigated. The stormwater outflow was sampled during discharge events and microbiologically analysed. The results showed high concentrations of Escherichia coli (1,100-1,100,000 CFU/100 mL) and Clostridium perfringens (20-13,000 CFU/100 mL). Campylobacter and Salmonella were detected in 97% and 43% of the samples. Giardia cysts were more often detected (31.6%) than Cryptosporidium oocysts (10.5%). The sources of human pathogens in rainwater run-off are heterogeneous. While roads have already been declared as chemical polluters via rainwater run-off, our study detected supplementary pollution of mainly faecal microorganisms. Presumably, failed connections in the sewer system itself are important sources of human pathogens. We suggest treatment of stormwater run-offs before being discharged into the river system.

[Subjective memory impairments in early detection of dementia: Relation to acceptability of lumbar puncture in memory clinic patients]. / Subjektive Gedächtnisbeeinträchtigungen in der Früherkennung von Demenzen: Beziehung zur Akzeptanz der Lumbalpunktion bei Patienten einer Gedächtnissprechstunde.

BACKGROUND: In memory clinics, biomarker-based diagnostic tools for early detection and differential diagnosis of dementia are increasingly important, even if their acceptance by patients is relatively low. OBJECTIVE: The aim of study was to examine whether sociodemographic and clinical features of memory clinic patients are associated with acceptance of lumbar puncture (LP). Of particular interest was the patients' self-perception of memory decline (subjective memory impairment, SMI) accompanied by related concerns that might affect decision to consent to LP. METHODS: Consecutive patients were examined in a day-care hospital on two consecutive days in order to implement a diagnostic procedure based on the S3 guideline "Dementia" including offer of LP. We assessed demographic and clinical variables such as depression, anxiety, neurocognitive performance and dementia severity (Clinical Dementia Rating, CDR). Furthermore, patients were interviewed about perceived memory decline and were classified on this basis - independent of their neuropsychological results - into three groups: no SMI, SMI without concerns or SMI with concerns. RESULTS: Of 44 patients (73.8 ±â€Š8.3 years; 27 f/17 m; CDR < 1: n = 16, CDR = 1: n = 28), 29 had SMI with concerns. These patients tended to be younger and had a higher level of education than those who did not report SMI (n = 7) and those perceiving SMI without concerns (n = 8). Furthermore, patients without SMI more frequently had a dementia syndrome. Patients who agreed to lumbar puncture (n = 23) were - compared to patients refusing LP (n = 17; 4 patients had to be excluded because of medical contraindication for immediate LP) - more likely male, had significantly more frequent SMI with concerns and performed poorer on declarative memory tasks. Binary regression analysis yielded SMI with concerns, a more impaired memory performance and male sex as significant predictors for consenting to LP. CONCLUSIONS: The study provides evidence that patient characteristics such as subjective and objective memory impairment as well as sex may affect the likelihood to consent to a generally less accepted biomarker-based dementia diagnostic procedure such as LP.

Laser desorption vs. electrospray of polyyne-threaded rotaxanes: Preventing covalent cross-linking and promoting noncovalent aggregation.

Laser-induced cross-linking of polyynes is successfully hindered when the polyyne is encapsulated as part of a rotaxane and therefore protected by a surrounding macrocycle. When the rotaxane is electrosprayed, however, noncovalent aggregate ions are efficiently formed. Aggregates of considerable size (including more than 50 rotaxane molecules with masses beyond 100k Da) and charge states (up to 13 charges and beyond) have been observed. Either protons or sodium cations act as the charge carriers. These aggregates are not formed when the individual components of the rotaxane, i.e., the macrocycle or the polyyne, are separately electrosprayed. This underlines the structural importance of the rotaxane for the aggregate formation. Straightforward force field calculations indicate that the polyyne thread hinders the folding of the macrocycles, which facilitates the bonding interaction between the two components.

Polyyne Rotaxanes: Stabilization by Encapsulation.

Active metal template Glaser coupling has been used to synthesize a series of rotaxanes consisting of a polyyne, with up to 24 contiguous sp-hybridized carbon atoms, threaded through a variety of macrocycles. Cadiot-Chodkiewicz cross-coupling affords higher yields of rotaxanes than homocoupling. This methodology has been used to prepare [3]rotaxanes with two polyyne chains locked through the same macrocycle. The crystal structure of one of these [3]rotaxanes shows that there is extremely close contact between the central carbon atoms of the threaded hexayne chains (C···C distance 3.29 Å vs 3.4 Å for the sum of van der Waals radii) and that the bond-length-alternation is perturbed in the vicinity of this contact. However, despite the close interaction between the hexayne chains, the [3]rotaxane is remarkably stable under ambient conditions, probably because the two polyynes adopt a crossed geometry. In the solid state, the angle between the two polyyne chains is 74°, and this crossed geometry appears to be dictated by the bulk of the "supertrityl" end groups. Several rotaxanes have been synthesized to explore gem-dibromoethene moieties as "masked" polyynes. However, the reductive Fritsch-Buttenberg-Wiechell rearrangement to form the desired polyyne rotaxanes has not yet been achieved. X-ray crystallographic analysis on six [2]rotaxanes and two [3]rotaxanes provides insight into the noncovalent interactions in these systems. Differential scanning calorimetry (DSC) reveals that the longer polyyne rotaxanes (C16, C18, and C24) decompose at higher temperatures than the corresponding unthreaded polyyne axles. The stability enhancement increases as the polyyne becomes longer, reaching 60 °C in the C24 rotaxane.

A population-based study comparing laparoscopic and robotic outcomes in colorectal surgery.

BACKGROUND: Current data addressing the role of robotic surgery for the management of colorectal disease are primarily from single-institution and case-matched comparative studies as well as administrative database analyses. The purpose of this study was to compare minimally invasive surgery outcomes using a large regional protocol-driven database devoted to surgical quality, improvement in patient outcomes, and cost-effectiveness. METHODS: This is a retrospective cohort study from the prospectively collected Michigan Surgical Quality Collaborative registry designed to compare outcomes of patients who underwent elective laparoscopic, hand-assisted laparoscopic, and robotic colon and rectal operations between July 1, 2012 and October 7, 2014. We adjusted for differences in baseline covariates between cases with different surgical approaches using propensity score quintiles modeled on patient demographics, general health factors, diagnosis, and preoperative co-morbidities. The primary outcomes were conversion rates and hospital length of stay. Secondary outcomes included operative time, and postoperative morbidity and mortality. RESULTS: A total of 2735 minimally invasive colorectal operations met inclusion criteria. Conversion rates were lower with robotic as compared to laparoscopic operations, and this was statistically significant for rectal resections (colon 9.0 vs. 16.9%, p < 0.06; rectum 7.8 vs. 21.2%, p < 0.001). The adjusted length of stay for robotic colon operations (4.00 days, 95% CI 3.63-4.40) was significantly shorter compared to laparoscopic (4.41 days, 95% CI 4.17-4.66; p = 0.04) and hand-assisted laparoscopic cases (4.44 days, 95% CI 4.13-4.78; p = 0.008). There were no significant differences in overall postoperative complications among groups. CONCLUSIONS: When compared to conventional laparoscopy, the robotic platform is associated with significantly fewer conversions to open for rectal operations, and significantly shorter length of hospital stay for colon operations, without increasing overall postoperative morbidity. These findings and the recent upgrades in minimally invasive technology warrant continued evaluation of the role of the robotic platform in colorectal surgery.

Monitoring micropollutants in the Swist river basin.

Micropollutant pathways were studied for the Swist river basin (Western Germany). The aim was to verify the effectiveness of a monitoring approach to detect micropollutants entering the river. In a separate sewer system, water was frequently found to be contaminated with micropollutants. Improper connections of sewage canals to the stormwater network seemed to be the cause of pollution. Wastewater treatment plants (WWTPs) exerted the largest influence on micropollutants for the receiving river. During a flu outbreak, antibiotics in the Swist stemming from WWTPs increased remarkably. Elevated levels of pharmaceuticals were measured in discharges from a combined sewer overflow (CSO). The study showed that the pharmaceutical load of a CSO was significantly reduced by advanced treatment with a retention soil filter. Painkillers, an anticonvulsant and beta blockers were the most often detected pharmaceuticals in the sewage of urban areas. Herbicides, flame retardants and industrial compounds were also observed frequently. On cropland, Chloridazon and Terbuthylazine compounds were often found in landscape runoff. Fungicides and insecticides were the most frequent positive findings in runoff from orchards. The paper shows that a coherent approach to collecting valid information regarding micropollutants and to addressing relevant pathways as a basis for appropriate management strategies could be established.

Nonsteroidal Anti-inflammatory Drugs: Do They Increase the Risk of Anastomotic Leaks Following Colorectal Operations?

BACKGROUND: Nonsteroidal anti-inflammatory drugs have become an important component of narcotic-sparing postoperative pain management protocols. However, conflicting evidence exists regarding the adverse association of nonsteroidal anti-inflammatory drug use with intestinal anastomotic healing in colorectal surgery. OBJECTIVE: This study compares patients receiving nonsteroidal anti-inflammatory drugs on postoperative day 1 with patients who did not receive nonsteroidal anti-inflammatory drugs with regard to the occurrence of anastomotic leaks. DESIGN: This is a retrospective study from a protocol-driven prospectively collected statewide database. A propensity score model was used to adjust for differences between the groups in patient demographics, characteristics, comorbidities, and laboratory values. SETTINGS: The multicenter data set used in this analysis represents a variety of academic and community hospitals within the state of Michigan from July 2012 through February 2014. PATIENTS: Nonpregnant patients over the age of 18 who underwent colon and rectal surgery with bowel anastomosis were selected. MAIN OUTCOME MEASURES: Occurrence of anastomotic leak, composite surgical site infection, sepsis, and death within 30 days of surgery were the primary outcomes measured. RESULTS: A total of 4360 patients met inclusion criteria, of which 1297 (29.7%) received nonsteroidal anti-inflammatory drugs and 3063 (70.3%) did not receive nonsteroidal anti-inflammatory drugs. There was no statistically significant difference between the 2 groups in the proportion of cases with anastomotic leak (OR, 1.33; CI, 0.86-2.05; p = 0.20), composite surgical site infection (OR, 1.26; CI, 0.96-1.66; p = 0.09), or death within 30 days (OR, 0.58; CI, 0.28-1.19; p = 0.14). There was a significantly greater risk of sepsis for patients given nonsteroidal anti-inflammatory drugs than for those patients not given nonsteroidal anti-inflammatory drugs (OR, 1.47; CI, 1.05-2.06; p = 0.03). LIMITATIONS: This is a nonrandomized study performed retrospectively, and it is based on data collected only within a subset of hospitals in the state of Michigan. CONCLUSIONS: No statistically significant increase in the proportion of patients with anastomotic leak was observed when prescribing nonsteroidal anti-inflammatory drugs for analgesia in the early postoperative period for patients undergoing elective colorectal surgery. Unexpectedly, there was an increased risk of sepsis that warrants further investigation (see video, Supplemental Digital Content 1, http://links.lww.com/DCR/A192, for a synopsis of this study).

Postoperative hyperglycemia and adverse outcomes in patients undergoing colorectal surgery: results from the Michigan surgical quality collaborative database.

PURPOSE: Our objective was to assess the relationship between high blood glucose levels (BG) in the early postoperative period and the incidence of surgical site infections (SSIs), sepsis, and death following colorectal operations. METHODS: The Michigan Surgical Quality Collaborative database was queried for colorectal operations from July 2012 to December 2013. Normoglycemic (BG < 180 mg/dL) and hyperglycemic (BG ≥ 180 mg/dL) groups were defined by using the highest BG within the first 72 h postoperatively. Outcomes of interest included the incidence of superficial, deep, and organ/space SSIs, sepsis, and death within 30 days. Initial unadjusted analysis was followed by propensity score matching and multiple logistic regression modeling after adjusting for significant predictors. Separate analyses were performed for previously diagnosed diabetic and non-diabetic patients. RESULTS: A total of 5145 cases met inclusion criteria, of which 1072 were diabetic. For diabetic patients, there was a marginally significant association between high BG and superficial SSI in the unadjusted analysis (OR = 1.75, p = 0.056), but not in the adjusted analysis (OR = 1.35, p = 0.39). There was no significant relationship between elevated BG and deep SSI, organ/space SSI, sepsis, or death among diabetic patients. For non-diabetic patients, there was a significant association between high BG and superficial SSI (OR = 1.53, p = 0.03), sepsis (OR = 1.61, p < 0.01), and death (OR = 2.26, p < 0.01), but not deep or organ/space SSI. CONCLUSIONS: Following colorectal operations, superficial SSI, sepsis, and death are associated with postoperative serum hyperglycemia in patients without diabetes, but not those with diabetes. Vigilant postoperative BG monitoring is critical for all patients undergoing colorectal surgery.

Cumulene rotaxanes: stabilization and study of [9]cumulenes.

The stabilization of long [n]cumulenes has traditionally been achieved by placing sterically bulky "protecting groups" at the termini, which shield the reactive carbon chain from unwanted reactions. Herein, we present an alternative strategy: stabilization through threading the sp-hybridized carbon chain through a phenanthroline-based macrocycle. The result is stable [9]cumulene rotaxanes that enable the study of properties as a function of length for [n]cumulenes in unprecedented detail, including by quantitative UV/Vis spectroscopy, cyclic voltammetry, and differential scanning calorimetry. The experimental results are supported by DFT calculations.

Drug-induced post-repolarization refractoriness as an antiarrhythmic principle and its underlying mechanism.

AIMS: We hypothesized that amiodarone (AM), unlike d-sotalol (DS) (a 'pure' Class III agent), not only prolongs the action potential duration (APD) but also causes post-repolarization refractoriness (PRR), thereby preventing premature excitation and providing superior antiarrhythmic efficacy. METHODS AND RESULTS: We tested this hypothesis in 31 patients with inducible ventricular tachycardia (VT) during programmed stimulation with the use of the 'Franz' monophasic action potential (MAP) catheter with simultaneous pacing capability. We determined the effective refractory period (ERP) for each of three extrastimuli (S2-S4) and the corresponding MAP duration at 90% repolarization (APD90), both during baseline and on randomized therapy with either DS (n = 15) or AM (n = 16). We defined ERP > APD90 as PRR and ERP < APD90 as 'encroachment' on repolarization. A revised computer action potential model was developed to help explain the mechanisms of these in-vivo human-heart phenomena. Encroachment but not PRR was present in all patients at baseline and during DS treatment (NS vs. baseline), and VT was non-inducible in only 2 of 15 DS patients. In contrast, in 12 of 16 AM patients PRR was present (P < 0.001 vs. baseline), and VT was no longer inducible. Our model (with revised sodium channel kinetics) reproduced encroachment and drug-induced PRR. CONCLUSION: Both, AM and DS, prolonged APD90 but only AM produced PRR and prevented encroachment of premature extrastimuli. Our computer simulations suggest that PRR is due to altered kinetics of the slow inactivation of the rapid sodium current. This may contribute to the high antiarrhythmic efficacy of AM.

Influence of the substitution position on spin communication in photoexcited perylene-nitroxide dyads.

By virtue of the modularity of their structures, their tunable optical and magnetic properties, and versatile applications, photogenerated triplet-radical systems provide an ideal platform for the study of the factors controlling spin communication in molecular frameworks. Typically, these compounds consist of an organic chromophore covalently attached to a stable radical. After formation of the chromophore triplet state by photoexcitation, two spin centres are present in the molecule that will interact. The nature of their interaction is governed by the magnitude of the exchange interaction between them and can be studied by making use of transient electron paramagnetic resonance (EPR) techniques. Here, we investigate three perylene-nitroxide dyads that only differ with respect to the position where the nitroxide radical is attached to the perylene core. The comparison of the results from transient UV-vis and EPR experiments reveals major differences in the excited state properties of the three dyads, notably their triplet state formation yield, excited state deactivation kinetics, and spin coherence times. Spectral simulations and quantum chemical calculations are used to rationalise these findings and demonstrate the importance of considering the structural flexibility and the contribution of rotational conformers for an accurate interpretation of the data.

Joining forces for pathology diagnostics with AI assistance: The EMPAIA initiative.

Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces. The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA Platform and successfully integrated 14 AI-based image analysis apps from eight different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes. Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future.

Reversibility of abdominal wall atrophy and fibrosis after primary or mesh herniorrhaphy.

OBJECTIVE: To determine whether primary or mesh herniorrhaphy reverses abdominal wall atrophy and fibrosis associated with hernia formation. BACKGROUND: We previously demonstrated that hernia formation is associated with abdominal wall atrophy and fibrosis after 5 weeks in an animal model. METHODS: A rat model of chronic incisional hernia was used. Groups consisted of uninjured control (UC, n = 8), sham repair (SR, n = 8), unrepaired hernia (UR, n = 8), and 2 repair groups: primary repair (PR, n = 8) or tension-free polypropylene mesh repair (MR, n = 8) hernia repair on postoperative day (POD) 35. All rats were killed on POD 70. Intact abdominal wall strips were cut perpendicular to the wound for tensiometric analysis. Internal oblique muscles were harvested for fiber type and size determination. RESULTS: No hernia recurrences occurred after PR or MR. Unrepaired abdominal walls significantly demonstrated greater stiffness, increased breaking and tensile strengths, yield load and yield energy, a shift to increased type IIa muscle fibers than SR (15.9% vs 9.13%; P < 0.001), and smaller fiber cross-sectional area (CSA, 1792 vs 2669 µm(2); P < 0.001). PR failed to reverse any mechanical changes but partially restored type IIa fiber (12.9% vs 9.13% SR; P < 0.001 vs 15.9% UR; P < 0.01) and CSA (2354 vs 2669 µm(2) SR; P < 0.001 vs 1792 µm(2) UR; P < 0.001). Mesh-repaired abdominal walls demonstrated a trend toward an intermediate mechanical phenotype but fully restored type IIa muscle fiber (9.19% vs 9.13% SR; P > 0.05 vs 15.9% UR; P < 0.001) and nearly restored CSA (2530 vs 2669 µm(2) SR; P < 0.05 vs 1792 µm(2) UR; P < 0.001). CONCLUSIONS: Mesh herniorrhaphy more completely reverses atrophic abdominal wall changes than primary herniorrhaphy, despite failing to restore normal anatomic muscle position. Techniques for hernia repair and mesh design should take into account abdominal wall muscle length and tension relationships and total abdominal wall compliance.