A Tetracarbene Iron(II) Complex with a Long-lived Triplet Metal-to-ligand Charge Transfer State due to a Triplet-Triplet Barrier.

Mixed N-heterocyclic carbene (NHC) / pyridyl iron(II) complexes have attracted a great deal of attention recently because of their potential as photocatalysts and light sensitizers made from Earth-abundant elements. The most decisive challenge for their successful implementation is the lifetime of the lowest triplet metal-to-ligand charge transfer state (3MLCT), which typically decays via a triplet metal-centered (3MC) state back to the ground state. We reveal by variable-temperature ultrafast transient absorption spectroscopy that the tripodal iron(II) bis(pyridine) complex isomers trans- and cis-[Fe(pdmi)2]2+with four NHC donors show 3MLCT→3MC population transfers with very different barriers and rationalize this by computational means. While trans-[Fe(pdmi)2]2+possesses an unobservable activation barrier, the cis isomer exhibits a barrier of 492 cm-1, which leads to a nanosecond 3MLCT lifetime at 77 K. The kinetic and quantum chemical data were analyzed in the context of semi-classical Marcus theory revealing a high reorganization energy and small electronic coupling between the two triplet states. This highlights the importance of detailed structural control and kinetic knowledge for the rational design of photosensitizers from first row transition metals such as iron.

Pediatric Conjunctivitis: A Review of Clinical Manifestations, Diagnosis, and Management.

Conjunctivitis is a common pediatric problem and is broadly divided into infectious and non-infectious etiologies. Bacterial conjunctivitis makes up the majority of cases in children and often presents with purulent discharge and mattering of the eyelids. Treatment is supportive with an individual approach to antibiotic use in uncomplicated cases since it may shorten symptom duration, but is not without risks. Viral conjunctivitis is the other infectious cause and is primarily caused by adenovirus, with a burning, gritty feeling and watery discharge. Treatment is supportive. Allergic conjunctivitis is largely seasonal and presents with bilateral itching and watery discharge. Treatment can include topical lubricants, topical antihistamine agents, or systemic antihistamines. Other causes of conjunctivitis include foreign bodies and non-allergic environmental causes. Contact lens wearers should always be treated for bacterial conjunctivitis and referred to evaluate for corneal ulcers. Neonatal conjunctivitis requires special care with unique pathogens and considerations. This review covers essential information for the primary care pediatric provider as they assess cases of conjunctivitis.

Janus-type emission from a cyclometalated iron(III) complex.

Although iron is a dream candidate to substitute noble metals in photoactive complexes, realization of emissive and photoactive iron compounds is demanding due to the fast deactivation of their charge-transfer states. Emissive iron compounds are scarce and dual emission has not been observed before. Here we report the FeIII complex [Fe(ImP)2][PF6] (HImP = 1,1'-(1,3-phenylene)bis(3-methyl-1-imidazol-2-ylidene)), showing a Janus-type dual emission from ligand-to-metal charge transfer (LMCT)- and metal-to-ligand charge transfer (MLCT)-dominated states. This behaviour is achieved by a ligand design that combines four N-heterocyclic carbenes with two cyclometalating aryl units. The low-lying π* levels of the cyclometalating units lead to energetically accessible MLCT states that cannot evolve into LMCT states. With a lifetime of 4.6 ns, the strongly reducing and oxidizing MLCT-dominated state can initiate electron transfer reactions, which could constitute a basis for future applications of iron in photoredox catalysis.

Higher MLCT lifetime of carbene iron(II) complexes by chelate ring expansion.

Combining strong σ-donating N-heterocyclic carbene ligands and π-accepting pyridine ligands with a high octahedricity in rigid iron(ii) complexes increases the 3MLCT lifetime from 0.15 ps in the prototypical [Fe(tpy)2]2+ complex to 9.2 ps in [Fe(dpmi)2]2+12+. The tripodal CNN ligand dpmi (di(pyridine-2-yl)(3-methylimidazol-2-yl)methane) forms six-membered chelate rings with the iron(ii) centre leading to close to 90° bite angles and enhanced iron-ligand orbital overlap.

Ground- and Excited-State Properties of Iron(II) Complexes Linked to Organic Chromophores.

Two new bichromophoric complexes, [Fe(bim-ant)2]2+ and [Fe(bim-pyr)2]2+ ([H2-bim]2+ = 1,1'-(pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium); ant = 9-anthracenyl; pyr = 1-pyrenyl), are investigated to explore the possibility of tuning the excited-state behavior in photoactive iron(II) complexes to design substitutes for noble-metal compounds. The ground-state properties of both complexes are characterized thoroughly by electrochemical methods and optical absorption spectroscopy, complemented by time-dependent density functional theory calculations. The excited states are investigated by static and time-resolved luminescence and femtosecond transient absorption spectroscopy. Both complexes exhibit room temperature luminescence, which originates from singlet states dominated by the chromophore (1Chrom). In the cationic pro-ligands and in the iron(II) complexes, the emission is shifted to red by up to 110 nm (5780 cm-1). This offers the possibility of tuning the organic chromophore emission by metal-ion coordination. The fluorescence lifetimes of the complexes are in the nanosecond range, while triplet metal-to-ligand charge-transfer (3MLCT) lifetimes are around 14 ps. An antenna effect as in ruthenium(II) polypyridine complexes connected to an organic chromophore is found in the form of an internal conversion within 3.4 ns from the 1Chrom to the 1MLCT states. Because no singlet oxygen forms from triplet oxygen in the presence of the iron(II) complexes and light, efficient intersystem crossing to the triplet state of the organic chromophore (3Chrom) is not promoted in the iron(II) complexes.

Vertebral Body Osteolysis 6 Years After Cervical Disk Arthroplasty.

Cervical arthroplasty is an accepted and widely performed surgical intervention with usually favorable outcomes. We report a rare case of a 37-year-old woman who presented with vertebral body osteolysis, 6 years after two-level cervical arthroplasty (C5-C6 and C6-C7). The patient showed no initial complications, but at year 6 she presented with neck and radicular arm pain. Diagnostic imaging revealed osteolysis of the vertebral body C6. The patient subsequently underwent removal of the two prostheses and C6 corpectomy, followed by bridging C5 to C7 and anterior fixation. During surgery, the mantle of the prostheses appeared broken, with the core expulsed anteriorly and embedded in granulomatous scar tissue. Pathologic evaluation of the samples showed partially proliferating fibroblasts, giant cell reaction, and textile particles. Postoperatively, clinical symptoms resolved with no residual deficits. Additional research should be performed to assess the long-term complications of this procedure that should be included in the patient informed consent materials.

Phase space methods for non-linear analysis of pedalling forces in cycling.

INTRODUCTION: From the perspective of dynamic systems theory, stability and variability of biological signals are both understood as a functional adaptation to variable environmental conditions. In the present study, we examined whether this theoretical perspective is applicable to the pedalling movement in cycling. Non-linear measures were applied to analyse pedalling forces with varying levels of subjective load. MATERIALS AND METHODS: Ten subjects completed a 13-sector virtual terrain profile of 15 km total length on a roller trainer with varying degrees of virtual terrain inclination (resistance). The test was repeated two times with different instructions on how to alter the bikes gearing. During the experiment, pedalling force and heart rate were measured. Force-time curves were sequenced into single cycles, linearly interpolated in the time domain, and z-score normalised. The established time series was transferred into a two-dimensional phase space with limit cycle properties given the applied 25% phase shift. Different representations of the phase space attractor were calculated within each sector and used as non-linear measures assessing pedalling forces. RESULTS AND DISCUSSION: A contrast analysis showed that changes in pedalling load were strongly associated to changes in non-linear phase space attractor variables. For the subjects investigated in this study, this association was stronger than that between heart rate and resistance level. The results indicate systematic changes of the pedalling movement as an adaptive response to an externally determined increase in workload. Future research may utilise the findings from this study to investigate possible relationships between subjective measures of exhaustion, comfort, and discomfort with biomechanic characteristics of the pedalling movement and to evaluate connections with dynamic stability measures.

Comparison of Near-Infrared Spectroscopy with Needle Indentation and Histology for the Determination of Cartilage Thickness in the Large Animal Model Sheep.

The suitability of near-infrared spectroscopy (NIRS) for non-destructive measurement of cartilage thickness was compared with the gold standard needle indentation. A combination of NIRS and biomechanical indentation (NIRS-B) was used to address the influence of varying loads routinely applied for hand-guided NIRS during real-life surgery on the accuracy of NIRS-based thickness prediction. NIRS-B was performed under three different loading conditions in 40 osteochondral cylinders from the load-bearing area of the medial and lateral femur condyle of 20 cadaver joints (left stifle joints; female Merino sheep; 6.1 ± 0.6 years, mean ± standard error of the mean). The cartilage thickness measured by needle indentation within the region analyzed by NIRS-B was then compared with cartilage thickness prediction based on NIRS spectral data using partial least squares regression. NIRS-B repeat measurements yielded highly reproducible values concerning force and absorbance. Separate or combined models for the three loading conditions (the latter simulating load-independent measurements) resulted in models with optimized quality parameters (e.g., coefficients of determination R2 between 92.3 and 94.7) and a prediction accuracy of < 0.1 mm. NIRS appears well suited to determine cartilage thickness (possibly in a hand-guided, load-independent fashion), as shown by high reproducibility in repeat measurements and excellent reliability compared with tissue-destructive needle indentation. This may provide the basis for non-destructive, intra-operative assessment of cartilage status quo and fine-tuning of repair procedures.

Restoration of cellular integrity following "ballistic" pronuclear exchange during Tetrahymena conjugation.

During sexual reproduction or conjugation, ciliates form a specialized cell adhesion zone for the purpose of exchanging gametic pronuclei. Hundreds of individual membrane fusion events transform the adhesion zone into a perforated membrane curtain, the mating junction. Pronuclei from each mating partner are propelled through this fenestrated membrane junction by a web of short, cris-crossing microtubules. Pronuclear passage results in the formation of two breaches in the membrane junction. Following pronuclear exchange and karyogamy (fertilization), cells seal these twin membrane breaches thereby re-establishing cellular independence. This would seem like a straightforward problem: simply grow membrane in from the edges of each breach in a fashion similar to how animal cells "grow" their cytokinetic furrows or how plant cells construct a cell wall during mitosis. Serial section electron microscopy and 3-D electron tomography reveal that the actual mechanism is less straightforward. Each of the two membrane breaches transforms into a bowed membrane assembly platform. The resulting membrane protrusions continue to grow into the cytoplasm of the mating partner, traverse the cytoplasm in anti-parallel directions and make contact with the plasma membrane that flanks the mating junction. This investigation reveals the details of a novel, developmentally-induced mechanism of membrane disruption and restoration associated with pronuclear exchange and fertilization in the ciliate, Tetrahymena thermophila.

Stress echocardiography for risk stratification of asymptomatic patients with type 2 diabetes mellitus.

BACKGROUND: The purpose of this study was to assess stressechocardiography (SE) for risk stratification of asymptomatic type 2 diabetic patients (DM2) without known coronary artery disease CAD. METHODS: A total of 211 consecutive, asymptomatic DM2 patients underwent exercise (n=177) or dobutamine (n=34) SE and were followed up for 11+/-2 months. Primary endpoint was a major cardiac or vascular event (MACCE; all-cause-death, non-fatal myocardial infarction, coronary revascularization procedures, cerebrovascular event, acute limb-ischemia). RESULTS: During follow-up 39 of these patients suffered a MACCE. SE correctly identified 33 of these 39 patients by demonstrating silent ischemia in advance. In a multivariate logistic regression analysis a positive SE turned out to be an independent predictor for the occurrence of a MACCE during 11+/-2 months. CONCLUSIONS: SE represents an effective tool for risk stratification of asymptomatic DM2 patients.

Risk of exercise-induced hypoglycaemia in patients with type 2 diabetes on intensive insulin therapy: comparison of insulin glargine with NPH insulin as basal insulin supplement.

AIM: Hypoglycaemia is the most common adverse event associated with intensive conventional insulin therapy (ICT). This study compared the risk of exercise-related hypoglycaemia in type 2 diabetes patients receiving either basal insulin glargine or NPH insulin. METHODS: In a prospective trial, 122 ICT patients (glargine n=60, NPH n=62) had a standardized treadmill test, monitored by capillary lactate concentration. Blood glucose (BG) profiles were performed the day before, during and the day after the exercise test, with the patients on a strict carbohydrate-defined diet. All patients had been on a stable ICT scheme for at least three months and had an HbA1c below 7.5%. RESULTS: BG at the beginning of the exercise test, BG decline and lowest BG during the test were comparable between the two groups. The episodes of mild hypoglycaemia (BG<3.3 mmol/l) and amounts of additional carbohydrate intake due to mild symptoms of hypoglycaemia (BG 3.3-5.0 mmol/l) were not significantly different. No episodes of hypoglycaemia occurred during several hours after the exercise. CONCLUSIONS: Moderate physical activity can be recommended for well-controlled type 2 diabetes patients receiving ICT, independently of glargine or NPH as basal insulin and without risk of exercise-induced hypoglycaemia.

Disseminated hyperkeratotic and granulomatous nodules in a child with fatal Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis is a rare and potentially fatal syndrome associated with a variety of genetic, malignant, autoimmune, or infectious conditions. The importance of cutaneous presentations of this syndrome has only recently been brought forward. We report the first case of Epstein-Barr-virus-associated hemophagocytic lymphohistiocytosis presenting with papulonodular and granulomatous skin lesions. A girl of African origin developed several umbilicated papules on her extremities and face at the age of 18 months. She was born in Germany, had never visited Africa, and was otherwise healthy. Over the next 5 months the lesions progressed in size and number and became hyperkeratotic. Histopathologic analysis of early lesions revealed a superficial lympho- and plasmacellular dermatitis with some features of panniculitis. Later biopsy specimens from nodular lesions showed the formation of tuberculoid granulomas in the deep dermis. At the age of 23 months she became severely ill, rapidly developing high fever, hepatosplenomegaly, icterus, pancytopenia, and ascites. On the basis of bone marrow and lymph node biopsies, the diagnosis of hemophagocytic lymphohistiocytosis was established. However, this phenomenon could not be detected in any of the skin specimens. An active Epstein-Barr virus infection was diagnosed by polymerase chain reaction in blood, lymphoid tissue, and skin. Despite chemotherapy with etoposide and cortisone, the girl expired 14 days after clinical onset of her systemic disease.

Platelet degranulation is associated with progression of intima-media thickness of the common carotid artery in patients with diabetes mellitus type 2.

BACKGROUND: Platelets play a key role in atherogenesis and thromboembolic complications in patients with type 2 diabetes. METHODS AND RESULTS: We prospectively examined the relationship between systemic platelet activation and progression of carotid wall thickness within 1 year in 105 patients with type 2 diabetes. The intima-media thickness (IMT) of the common carotid artery was measured bilaterally at study entry and after 1 year. Platelet activation was assessed with the use of immunologic markers of platelet activation (CD62P, CD63, and CD40L) and flow cytometry. The prevalence for progression of atherosclerotic carotid disease in this population was 55.2%. We found that platelet degranulation (CD63 and CD40L) correlated with progression of IMT within 1 year (CD63: r=0.231, P=0.022; CD40L: r=0.230, P=0.029). Diabetic patients with progression of IMT had a significantly increased expression of CD63 compared with patients with stable carotid disease (mean intensity of immunofluorescence; median, interquartile range: 17.1 [12.4, 25.8] versus 11.9 [7.7, 19.8]; P=0.004). Multivariate logistic regression analysis revealed that degranulation of platelet CD63 is a predictor for progression of IMT independently of classical cardiovascular risk factors and hemoglobin A1c in diabetic patients (P=0.017). CONCLUSIONS: Enhanced systemic platelet degranulation is associated with progression of carotid artery disease in type 2 diabetes.