S100A1's single cysteine is an indispensable redox switch for the protection against diastolic calcium waves in cardiomyocytes.

The EF-hand calcium (Ca2+) sensor protein S100A1 combines inotropic with antiarrhythmic potency in cardiomyocytes (CMs). Oxidative posttranslational modification (ox-PTM) of S100A1's conserved, single-cysteine residue (C85) via reactive nitrogen species (i.e., S-nitrosylation or S-glutathionylation) has been proposed to modulate conformational flexibility of intrinsically disordered sequence fragments and to increase the molecule's affinity toward Ca2+. Considering the unknown biological functional consequence, we aimed to determine the impact of the C85 moiety of S100A1 as a potential redox switch. We first uncovered that S100A1 is endogenously glutathionylated in the adult heart in vivo. To prevent glutathionylation of S100A1, we generated S100A1 variants that were unresponsive to ox-PTMs. Overexpression of wild-type (WT) and C85-deficient S100A1 protein variants in isolated CM demonstrated equal inotropic potency, as shown by equally augmented Ca2+ transient amplitudes under basal conditions and ß-adrenergic receptor (ßAR) stimulation. However, in contrast, ox-PTM defective S100A1 variants failed to protect against arrhythmogenic diastolic sarcoplasmic reticulum (SR) Ca2+ waves and ryanodine receptor 2 (RyR2) hypernitrosylation during ßAR stimulation. Despite diastolic performance failure, C85-deficient S100A1 protein variants exerted similar Ca2+-dependent interaction with the RyR2 than WT-S100A1. Dissecting S100A1's molecular structure-function relationship, our data indicate for the first time that the conserved C85 residue potentially acts as a redox switch that is indispensable for S100A1's antiarrhythmic but not its inotropic potency in CMs. We, therefore, propose a model where C85's ox-PTM determines S100A1's ability to beneficially control diastolic but not systolic RyR2 activity.NEW & NOTEWORTHY S100A1 is an emerging candidate for future gene-therapy treatment of human chronic heart failure. We aimed to study the significance of the conserved single-cysteine 85 (C85) residue in cardiomyocytes. We show that S100A1 is endogenously glutathionylated in the heart and demonstrate that this is dispensable to increase systolic Ca2+ transients, but indispensable for mediating S100A1's protection against sarcoplasmic reticulum (SR) Ca2+ waves, which was dependent on the ryanodine receptor 2 (RyR2) nitrosylation status.

Autologous semitendinosus meniscus graft significantly improves knee joint kinematics and the tibiofemoral contact after complete lateral meniscectomy.

PURPOSE: The purpose of this study was to investigate the potential of a doubled semitendinosus (ST) and a single gracilis tendon (GT) lateral meniscus autograft to restore the knee joint kinematics and tibiofemoral contact after total lateral meniscectomy (LMM). METHODS: Fourteen human knee joints were tested intact, after LMM and after ST and GT meniscus autograft treatment under an axial load of 200 N during full range of motion (0°-120°) and four randomised loading situations: without external moments, external rotation, valgus stress and a combination of external rotation and valgus stress using a knee joint simulator. Non-parametric statistical analyses were performed on joint kinematics and on the tibiofemoral contact mechanics. RESULTS: LMM led to significant rotational instability of the knee joints (p < 0.02), which was significantly improved after ST autograft application (p < 0.04), except for knee joint flexions > 60°. The GT autograft failed to restore the joint kinematics. LMM significantly increased the tibiofemoral contact pressure (p < 0.03), while decreasing the contact area (p < 0.05). The ST autograft was able to restore the contact mechanics after LMM (p < 0.02), while the GT replacement displayed only an improvement trend. CONCLUSION: The doubled ST lateral meniscus autograft improved the knee joint kinematics significantly and restored the tibiofemoral contact mechanics almost comparable to the native situation. Thus, from a biomechanical point of view, ST meniscus autografts might be a potential treatment alternative for patients who are indicated for meniscus allograft transplantation.

Impact of hyaluronic acid injection on the knee joint friction.

PURPOSE: The purpose of this in vitro study was to investigate whether or not hyaluronic acid supplementation improves knee joint friction during osteoarthritis progression under gait-like loading conditions. METHODS: Twelve human cadaveric knee joints were equally divided into mild and moderate osteoarthritic groups. After initial conservative preparation, a passive pendulum setup was used to test the whole joints under gait-like conditions before and after hyaluronic acid supplementation. The friction-related damping properties given by the coefficient of friction µ and the damping coefficient c (in kg m2/s) were calculated from the decaying flexion-extension motion of the knee. Subsequently, tibial and femoral cartilage and meniscus samples were extracted from the joints and tested in an established dynamic pin-on-plate tribometer using synthetic synovial fluid followed by synthetic synovial fluid supplemented with hyaluronic acid as lubricant. Friction was quantified by calculating the coefficient of friction. RESULTS: In the pendulum tests, the moderate OA group indicated significantly lower c0 values (p < 0.05) under stance phase conditions and significantly lower µ0 (p = 0.01) values under swing phase conditions. No degeneration-related statistical differences were found for µend or cend. Friction was not significantly different (p > 0.05) with regard to mild and moderate osteoarthritis in the pin-on-plate tests. Additionally, hyaluronic acid did not affect friction in both, the pendulum (p > 0.05) and pin-on-plate friction tests (p > 0.05). CONCLUSION: The results of this in vitro study suggested that the friction of cadaveric knee joint tissues does not increase with progressing degeneration. Moreover, hyaluronic acid viscosupplementation does not lead to an initial decrease in knee joint friction.

[Management of chronic coronary syndrome]. / Management des chronischen Koronarsyndroms.

Coronary artery disease remains the leading cause of death in developed countries. This CME article addresses and comments on important aspects from the current guidelines for the diagnosis and management of chronic coronary syndrome of the European Society of Cardiology (ESC) and the current guidelines for the evaluation and diagnosis of chest pain of the American Heart Association (AHA)/the American College of Cardiology (ACC).

Are Knotted or Knotless Techniques Better for Reconstruction of Full-Thickness Tears of the Superior Portion of the Subscapularis Tendon? A Study in Cadavers.

BACKGROUND: Knotted and knotless single-anchor reconstruction techniques are frequently performed to reconstruct full-thickness tears of the upper portion of subscapularis tendon. However, it is unclear whether one technique is superior to the other. QUESTIONS/PURPOSES: (1) When comparing knotless and knotted single-anchor reconstruction techniques in full-thickness tears of the upper subscapularis tendon, is there a difference in stiffness under cyclic load? (2) Are there differences in cyclic gapping between knotless and knotted reconstructions? (3) Are there differences in the maximal stiffness, yield load, and ultimate load to failure? (4) What are the modes of failure of knotless and knotted reconstruction techniques? METHODS: Eight matched pairs of human cadaveric shoulders were dissected, and a full-thickness tear of the subscapularis tendon (Grade 3 according to the Fox and Romeo classification) was created. The cadavers all were male specimens, with a median (range) age of 69 years (61 to 75). Before biomechanical evaluation, the specimens were randomized into two equal reconstruction groups: knotless single anchor and knotted single anchor. All surgical procedures were performed by a single orthopaedic surgeon who subspecializes in sports orthopedics and shoulder surgery. With a customized set up that was integrated in a dynamic material testing machine, the humeri were consecutively loaded from 10 N to 60 N, from 10 N to 100 N, and from 10 N to 180 N for 50 cycles. Furthermore, the gapping behavior of the tear was analyzed using a video tracking system. Finally, the stiffness, gapping, maximal stiffness, yield loads, and maximum failure loads of both reconstruction groups were statistically analyzed. Failure was defined as retearing of the reconstructed gap threshold due to rupture of the tendon and/or failure of the knots or anchors. After biomechanical testing, bone quality was measured at the footprint of the subscapularis using microCT in all specimens. Bone quality was equal between both groups. To detect a minimum 0.15-mm difference in gap formation between the two repair techniques (with a 5% level of significance; α = 0.05), eight matched pairs (n = 16 in total) were calculated as necessary to achieve a power of at least 90%. RESULTS: The first study question can be answered as follows: for stiffness under cyclic load, there were no differences with the numbers available between the knotted and knotless groups at load stages of 10 N to 60 N (32.7 ± 3.5 N/mm versus 34.2 ± 5.6 N/mm, mean difference 1.5 N/mm [95% CI -6.43 to 3.33]; p = 0.55), 10 N to 100 N (45.0 ± 4.8 N/mm versus 45.2 ± 6.0 N/mm, mean difference 0.2 N/mm [95% CI -5.74 to 6.04]; p = 0.95), and 10 N to 180 N (58.2 ± 10.6 N/mm versus 55.2 ± 4.7 N/mm, mean difference 3 N/mm [95% CI -5.84 to 11.79]; p = 0.48). In relation to the second research question, the following results emerged: For cyclic gapping, there were no differences between the knotted and knotless groups at any load levels. The present study was able to show the following with regard to the third research question: Between knotted and knotless repairs, there were no differences in maximal load stiffness (45.3 ± 8.6 N/mm versus 43.5 ± 10.2 N/mm, mean difference 1.8 [95% CI -11.78 to 8.23]; p = 0.71), yield load (425.1 ± 251.4 N versus 379.0 ± 169.4 N, mean difference 46.1 [95% CI -276.02 to 183.72]; p = 0.67), and failure load (521.1 ± 266.2 N versus 475.8 ± 183.3 N, mean difference 45.3 [95% CI -290.42 to 199.79]; p = 0.69). Regarding the fourth question concerning the failure modes, in the knotted repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 6 of 8, and no suture slipped from the eyelet; in the knotless repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 3 of 8, and the threads slipped from the eyelet in 3 of 8. CONCLUSION: With the numbers available, we found no differences between single-anchor knotless and knotted reconstruction techniques used to repair full-thickness tears of the upper portion of subscapularis tendon. CLINICAL RELEVANCE: The reconstruction techniques we analyzed showed no differences in terms of their primary stability and biomechanical properties at the time of initial repair and with the numbers available. In view of these experimental results, it would be useful to conduct a clinical study in the future to verify the translationality of the experimental data of the present study.

E4 Transfer (E=P, As) to Ni Complexes.

The use of [Cp''2 Zr(η1:1 -E4 )] (E=P (1 a), As (1 b), Cp''=1,3-di-tert-butyl-cyclopentadienyl) as phosphorus or arsenic source, respectively, gives access to novel stable polypnictogen transition metal complexes at ambient temperatures. The reaction of 1 a/1 b with [CpR NiBr]2 (CpR =CpBn (1,2,3,4,5-pentabenzyl-cyclopentadienyl), Cp''' (1,2,4-tri-tert-butyl-cyclopentadienyl)) was studied, to yield novel complexes depending on steric effects and stoichiometric ratios. Besides the transfer of the complete En unit, a degradation as well as aggregation can be observed. Thus, the prismane derivatives [(Cp'''Ni)2 (µ,η3:3 -E4 )] (2 a (E=P); 2 b (E=As)) or the arsenic containing cubane [(Cp'''Ni)3 (µ3 -As)(As4 )] (5) are formed. Furthermore, the bromine bridged cubanes of the type [(CpR Ni)3 {Ni(µ-Br)}(µ3 -E)4 ]2 (CpR =Cp''': 6 a (E=P), 6 b (E=As), CpR =CpBn : 8 a (E=P), 8 b (E=As)) can be isolated. Here, a stepwise transfer of En units is possible, with a cyclo-E4 2- ligand being introduced and unprecedented triple-decker compounds of the type [{(CpR Ni)3 Ni(µ3 -E)4 }2 (µ,η4:4 -E'4 )] (CpR =CpBn , Cp'''; E/E'=P, As) are obtained.

Assessment of coronary vasomotor responses to acetylcholine in German and Japanese patients with epicardial coronary spasm-more similarities than differences?

Coronary spasm is an established cause for angina pectoris. Ethnic differences have been suggested among Asian compared to Caucasian patients regarding prevalence, gender distribution, and angiographic patterns of coronary spasm. The aim of this study was to compare contemporary German and Japanese patients with coronary spasm. Between 2011 and 2015, 149 patients with resting angina and unobstructed coronary arteries with acetylcholine-induced epicardial spasm were enrolled in Stuttgart, Germany (n = 69) and Sendai, Japan (n = 80). All patients underwent intracoronary acetylcholine testing according to a standardized protocol. Comprehensive analysis included type of spasm (focal/diffuse), dose of acetylcholine leading to spasm, and frequency of multivessel spasm. Patients in this study were 61 ± 11 years old, predominantly female (54%), and had normal left ventricular ejection fraction (73 ± 9%). Diffuse spasm was the most prevalent type of spasm (85%) whereas focal spasm was found in the remaining 15% of patients. 31% of patients had multivessel spasm. Comparing the German with the Japanese patients, distribution of spasm type (focal/diffuse, p = 0.19) and frequency of multivessel spasm (p = 0.22) were comparable. Moreover, when Japanese patients were compared with German patients and diffuse spasm with focal spasm patients, respectively, no significant differences were observed regarding the acetylcholine dose required to induce spasm (p = 0.078 and p = 0.46, respectively). In conclusion, diffuse epicardial coronary spasm is the most frequent finding among German and Japanese patients with resting angina, unobstructed coronary arteries, and epicardial spasm on acetylcholine testing. Japanese and German patients share several similarities including comparable types of spasm and frequency of multivessel spasm.

[Detection of ECG alterations typical for myocardial ischemia : New methods 2021]. / Erkennung ischämietypischer EKG-Veränderungen : Neue Methoden 2021.

BACKGROUND: The electrocardiogram (ECG) represents an essential diagnostic tool in cardiology and beyond. Classical ECG devices enable the registration of up to 12 leads, whereas modern ECG systems enable additional leads even with a reduced number of electrodes. Additionally, "smart" devices even enable patients to record an ECG at home. OBJECTIVE: Evaluation of a potential additional benefit of using various modern ECG systems for the detection of ECG alterations typical for myocardial ischemia. MATERIAL AND METHODS: Presentation of various signs of ischemia in the ECG according to the latest guidelines. Demonstration of modern ECG systems and their potential advantage in the detection of signs of ischemia in the ECG based on current study results. RESULTS: Modern ECG systems with vector-based electrocardiography can facilitate and optimize the detection of ischemic ECG alterations. Smart nonvector-based devices for patients are primarily useful for detection of arrhythmias and do not replace the 12-lead ECG for detection of ischemia, even though they can be useful for documentation of temporary ECG alterations also within the ST-segment. CONCLUSION: The ECG systems based on vector electrocardiography can improve the detection of ECG alterations typical for ischemia compared to the conventional 12-lead ECG.

Newly Defined ATP-Binding Cassette Subfamily B Member 5 Positive Dermal Mesenchymal Stem Cells Promote Healing of Chronic Iron-Overload Wounds via Secretion of Interleukin-1 Receptor Antagonist.

In this study, we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of nonhealing wounds. Local administration of dermal ABCB5+ -derived mesenchymal stem cells (MSCs) attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wounds in the iron-overload mouse model mimicking the nonhealing state of human venous leg ulcers. The observed beneficial effects were due to interleukin-1 receptor antagonist (IL-1RA) secreted by ABCB5+ -derived MSCs, which dampened inflammation and shifted the prevalence of unrestrained proinflammatory M1 macrophages toward repair promoting anti-inflammatory M2 macrophages at the wound site. The beneficial anti-inflammatory effect of IL-1RA released from ABCB5+ -derived MSCs on human wound macrophages was conserved in humanized NOD-scid IL2rγ null mice. In conclusion, human dermal ABCB5+ cells represent a novel, easily accessible, and marker-enriched source of MSCs, which holds substantial promise to successfully treat chronic nonhealing wounds in humans. Stem Cells 2019;37:1057-1074.

Chondral lesions at the medial femoral condyle, meniscal degeneration, anterior cruciate ligament insufficiency, and lateral meniscal tears impair the middle-term results after arthroscopic partial meniscectomy.

PURPOSE: The aim of the present study was to analyse which clinical, radiological and arthroscopic findings are able to predict the postoperative outcome after arthroscopic partial meniscectomy. Furthermore, the present study aimed to investigate the postoperative outcome after partial meniscectomy in patients with degenerative meniscal lesions. METHODS: A total of 91 patients with a follow-up period of 34.7 ± 11.4 months after arthroscopic partial meniscectomy were included in this retrospective study. Clinical, radiological, and arthroscopic data were analysed at the time of follow-up. The multivariable linear regression analysis for postoperative outcome, based on the Western Ontario Meniscal Evaluation Tool (WOMET), included age, gender, body mass index, physical activity, presence of cartilage lesions, leg alignment, grade of radiographic osteoarthritis, location of meniscal lesions, meniscal extrusion, meniscal degeneration, presence of an anterior cruciate ligament tears as well as bone marrow lesions. RESULTS: WOMET and WOMAC scores showed a significant improvement of 45.0 ± 48.1 points (CI 34.9-55.1; p ≤ 0.0001) and 75.1 ± 69.3 points (CI 60.6-89.6; p = 0.001) within the follow-up period. Multivariable linear regression analysis showed that poor preoperative WOMET scores (p = 0.001), presence of cartilage lesions at the medial femoral condylus (p = 0.001), meniscal degeneration (p = 0.008), the presence of an anterior cruciate ligament lesion (p = 0.005), and lateral meniscal tears (p = 0.039) were associated with worse postoperative outcomes. Patients with femoral bone marrow lesions had better outcome (p = 0.038). CONCLUSION: Poor preoperative WOMET scores, presence of cartilage lesions at the medial femoral condylus, meniscal degeneration, concomitant anterior cruciate ligament lesions as well as lateral meniscal tears are correlated with worse postoperative outcomes after arthroscopic partial meniscectomy. Patients with femoral bone marrow lesions femoral are more likely to gain benefit from arthroscopic partial meniscectomy in the middle term. Despite justified recent restrictions in indication, arthroscopic partial meniscectomy seems to effectively reduce pain and alleviate symptoms in carefully selected patients with degenerative meniscal tears. LEVEL OF EVIDENCE: III.

Impact of caffeine on myocardial perfusion reserve assessed by semiquantitative adenosine stress perfusion cardiovascular magnetic resonance.

BACKGROUND: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. METHODS: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. RESULTS: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p <  0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p <  0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92). CONCLUSION: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.

Biomechanical considerations are crucial for the success of tendon and meniscus allograft integration-a systematic review.

PURPOSE: This systematic review intends to give an overview of the current knowledge on how allografts used for the reconstruction of cruciate ligaments and menisci are integrated and specifically perform regarding their biomechanical function. METHODS: Two reviewers reviewed the PubMed and Central Cochrane library with focus on the biomechanical integration of tendon ligament and meniscus allografts. The literature search was conducted in accordance with the PRISMA statement for reporting systematic reviews and meta-analyses. RESULTS: The analysed literature on tendon allografts shows that they are more vulnerable to overstretching in the phase of degradation compared to autografts as the revascularization process starts later and takes longer. Therefore, to avoid excessive graft loads, allografts for cruciate ligament replacement should be selected that exhibit much higher failure loads than the native ligaments to counteract the detrimental effect of degradation. Further, placement techniques should be considered that result in a minimum of strain differences during knee joint motion, which is best achieved by near-isometric placement. The most important biomechanical parameters for meniscus allograft transplantation are secure fixation and proper graft sizing. Allograft attachment by bone plugs or by a bone block is superior to circumferential suturing and enables the allograft to restore the chondroprotective biomechanical function. Graft sizing is also of major relevance, because too small grafts are not able to compensate the knee joint incongruity and too large grafts may fail due to extrusion. Only adequate sizing and fixation together can lead to a biomechanically functioning allograft. The objective assessment of the biomechanical quality of allografts in a clinical setting is challenging, but would be highly desirable for monitoring the remodelling and incorporation process. CONCLUSIONS: Currently, indicators like ap-stability after ACL reconstruction or meniscal extrusion represent only indirect measures for biomechanical graft integration. These parameters are at best clinical indicators of allograft function, but the overall integration properties comprising e.g. fixation and graft stiffness remain unknown. Therefore, future research should e.g. focus on advanced imaging techniques or other non-invasive methods allowing for in vivo assessment of biomechanical allograft properties.

Release of the medial collateral ligament is mandatory in medial open-wedge high tibial osteotomy.

PURPOSE: The purpose of this study was to quantify the effect of clinically relevant open-wedge high tibial osteotomies on medial collateral ligament (MCL) strain and the resultant tibiofemoral contact mechanics during knee extension and 30° knee flexion. METHODS: Six human cadaveric knee joints were axially loaded (1 kN) in knee extension and 30° knee flexion. Strains at the anterior and posterior regions of the MCL were determined using strain gauges. Tibiofemoral contact mechanics (contact area, mean and maximum contact pressure) were investigated using pressure-sensitive sensors. Open-wedge osteotomy was performed using biplanar cuts and osteotomy angles of 5° and 10° were maintained using an external fixator. Tests were performed first with intact and then with dissected MCL. RESULTS: Nonparametric statistical analyses indicated a significant strain increase (p < 0.01) in the anterior and posterior fibres of the MCL with increasing osteotomy angle of up to 8.3% and 6.0%, respectively. Only after releasing the MCL the desired lateralisation of the mechanical axis was achieved, indicating a significant decrease in the maximum contact pressure in knee extension of - 25% (p = 0.028) and 30° knee flexion of - 21% (p = 0.027). CONCLUSIONS: The results of the present biomechanical study suggest, that an open-wedge high tibial osteotomy is most effective in reducing the medial contact pressure when spreading the osteotomy to 10° and concomitantly releasing the MCL. To transfer the results of this biomechanical study to the clinical day-to-day practice, it is necessary to factor in the individual ligamentous laxity of each patient into the treatment options e.g. particularly for patients with distinct knee ligament laxity or medial ligamentary instability, the release of the MCL should be performed with care. LEVEL OF EVIDENCE: Controlled laboratory study.

Transfer Reagent for Bonding Isomers of Iron Complexes.

The cothermolysis of As4 and [Cp″2Zr(CO)2] (Cp″ = η5-C5H3tBu2) results in the formation of [Cp″2Zr(η1:1-As4)] (1) in high yields and the arsenic-rich complex [(Cp″2Zr)(Cp″Zr)(µ,η2:2:1-As5)] (2) as a minor product. In contrast to yellow arsenic, 1 is a light-stable, weighable and storable arsenic source for subsequent reactions. The transfer reaction of 1 with [Cp‴Fe(µ-Br)]2 (Cp‴ = η5-C5H2tBu3) yields the unprecedented bond isomeric complexes [(Cp‴Fe)2(µ,η4:4-As4)] (3a) and [(Cp‴Fe)2(µ,η4:4-cyclo-As4)] (3b). In contrast, the analogous reaction with the CpBn derivative [CpBnFe(µ-Br)]2 (CpBn = η5-C5(CH2(C6H5)5) leads exclusively to the triple decker complex [(CpBnFe)2(µ,η4:4-As4)] (4) possessing the tetraarsabutadiene-type ligand analogous to 3a. To elucidate the stability of the bonding isomers 3a and 3b, DFT calculations were performed. The oxidation of 4 with AgBF4 affords [(CpBnFe)2(µ,η5:5-As5)][BF4] (5), which is a product expanded by one arsenic atom, instead of the expected complex [(CpBnFe)2(µ,η4:4-cyclo-As4)]+.

Coordination Behavior of [Cp''2 Zr(η1:1 -P4 )] towards Different Lewis Acids.

A detailed method for the preparation of [Cp''2 Zr(η1:1 -P4 )] (1) is presented. The coordination behavior of 1 towards Lewis acidic transition metal complexes of tungsten, manganese, and iron, respectively, and main group compounds (AlMe3 , AlEt3 ) was investigated in detail by computational and experimental studies. In doing so, a series of unprecedented complexes with different coordination modes and multiple coordination numbers of the tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as well as the starting materials, were comprehensively characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray structural analysis.

Effects of caffeine on the detection of ischemia in patients undergoing adenosine stress cardiovascular magnetic resonance imaging.

BACKGROUND: Adenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR. METHODS: Thirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden. RESULTS: Despite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p < 0.001 each). Moreover, no relevant ischemia (≥2 segments in a 16-segment model) was missed by prior ingestion of caffeine. CONCLUSIONS: Although differences were small and no relevant myocardial ischemia had been missed, prior consumption of caffeine led to significant reduction of ischemic burden, and might lower the high diagnostic and prognostic value of adenosine stress CMR. Therefore, we suggest that patients should still refrain from caffeine prior adenosine stress CMR tests.

ACL double-bundle reconstruction with one tibial tunnel provides equal stability compared to two tibial tunnels.

PURPOSE: The purpose of this study was to investigate whether an anterior cruciate ligament (ACL) double-bundle reconstruction with one tibial tunnel displays the same in vitro stability as a conventional double-bundle reconstruction with two tibial tunnels when using the same tensioning protocol. METHODS: In 11 fresh-frozen cadaveric knees, ACL double-bundle reconstruction with one and two tibial tunnels was performed. The two grafts were tightened using 80 N in different flexion angles (anteromedial-bundle at 60° and posterolateral-bundle at 15°). Anterior tibial translation (134 N) and translation with combined rotatory and valgus loads (10 Nm valgus stress and 4 Nm internal tibial torque) were determined at 0°, 30°, 60° and 90° flexion. Measurements were taken in intact ACL, resected ACL, three-tunnel reconstruction and four-tunnel reconstruction. Additionally, the tension on the grafts was determined. Student's t test was performed for statistical analysis of the related samples. Significance was set at p < 0.017 according to Bonferroni correction. RESULTS: The two reconstructive techniques displayed no significant differences in comparison with the intact ACL in anterior tibial translation at 0°, 60° and 90° of flexion. The same results were obtained for the anterior tibial translation with a combined rotatory load at 60° and 90°. When directly comparing both reconstructive techniques, there were no significant differences for the anterior tibial translation and combined rotatory load at all flexion angles. The measured tension on grafts displayed similar load sharing between both bundles. Except at full extension, both grafts displayed a significantly different tension increase under anterior tibial translation for both techniques (p = 0.0086). CONCLUSIONS: Tightening both bundles in ACL double-bundle reconstruction with one or two tibial tunnels in different flexion angles achieved comparable restoration of stability, although there was different load sharing on the bundles. With regard to individualized ACL reconstruction, the double-bundle technique with one tibial tunnel offers a possibility to address small tibial insertion sites without compromising the advantages of a double-bundle procedure.

Different Reactivity of As4 towards Disilenes and Silylenes.

The activation of yellow arsenic is possible with the silylene [PhC(NtBu)2 SiN(SiMe3 )2 ] (1) and the disilene [(Me3 Si)2 N(η1 -Me5 C5 )Si=Si(η1 -Me5 C5 )N(SiMe3 )2 ] (3). The reaction of As4 with 1 leads to the unprecedented As10 cage compound [(LSiN(SiMe3 )2 )3 As10 ] (2; L=PhC(NtBu)2 ) with an As7 nortricyclane core stabilized by arsasilene moieties containing silicon(II)bis(trimethylsilyl)amide substituents. In contrast, the compound [Cp*{(SiMe3 )2 N}SiAs]2 (4) containing a butterfly-like diarsadisilabicyclo[1.1.0]butane unit is formed by the reaction of As4 with the disilene 3. Both compounds were characterized by single-crystal X-ray diffraction analysis, NMR spectroscopy, and mass spectrometry. The reaction outcomes demonstrate the different reaction behavior of yellow arsenic (As4 ) compared to white phosphorus (P4 ) in the reactions with the corresponding silylenes and disilenes.

Pnictogen-Silicon Analogues of Benzene.

Since the discovery of the first "inorganic benzene" (borazine, B3N3H6), the synthesis of other noncarbon derivatives is an ongoing challenge in Inorganic Chemistry. Here we report on the synthesis of the first pnictogen-silicon congeners of benzene, the triarsa- and the triphospha-trisilabenzene [(PhC(NtBu)2)3Si3E3] (E = P (1a), As (1b)) by a simple metathesis reaction. These compounds are formed by the reaction of [Cp″2Zr(η(1:1)-E4)] (E = P, As; Cp″ = C5H3tBu2) with [PhC(NtBu)2SiCl] in toluene at room temperature along with the silicon pnictogen congeners of the cyclobutadiene, [(PhC(NtBu)2)2Si2E2] (E = P (2a), As (2b)), which is unprecedented for the arsenic system 2b. All compounds were comprehensively characterized, and density functional theory calculations were performed to verify the stability and the aromatic character of the triarsa- and the triphospha-trisilabenzene.

S100A1 DNA-based Inotropic Therapy Protects Against Proarrhythmogenic Ryanodine Receptor 2 Dysfunction.

Restoring expression levels of the EF-hand calcium (Ca(2+)) sensor protein S100A1 has emerged as a key factor in reconstituting normal Ca(2+) handling in failing myocardium. Improved sarcoplasmic reticulum (SR) function with enhanced Ca(2+) resequestration appears critical for S100A1's cyclic adenosine monophosphate-independent inotropic effects but raises concerns about potential diastolic SR Ca(2+) leakage that might trigger fatal arrhythmias. This study shows for the first time a diminished interaction between S100A1 and ryanodine receptors (RyR2s) in experimental HF. Restoring this link in failing cardiomyocytes, engineered heart tissue and mouse hearts, respectively, by means of adenoviral and adeno-associated viral S100A1 cDNA delivery normalizes diastolic RyR2 function and protects against Ca(2+)- and ß-adrenergic receptor-triggered proarrhythmogenic SR Ca(2+) leakage in vitro and in vivo. S100A1 inhibits diastolic SR Ca(2+) leakage despite aberrant RyR2 phosphorylation via protein kinase A and calmodulin-dependent kinase II and stoichiometry with accessory modulators such as calmodulin, FKBP12.6 or sorcin. Our findings demonstrate that S100A1 is a regulator of diastolic RyR2 activity and beneficially modulates diastolic RyR2 dysfunction. S100A1 interaction with the RyR2 is sufficient to protect against basal and catecholamine-triggered arrhythmic SR Ca(2+) leak in HF, combining antiarrhythmic potency with chronic inotropic actions.