[Adults with congenital heart disease presenting to the emergency department : Potential pitfalls]. / Erwachsene mit angeborenen Herzfehlern im Notaufnahmedienst : Was ist zu beachten?

The number of adults with congenital heart disease (ACHD) already exceeds the number of children with congenital heart disease in the industrialized world. ACHD patients often show complex pathophysiology and anatomy even after reparative cardiac surgery. In case of complications patients may rapidly deteriorate and become unstable, even when they were asymptomatic or had only mild symptoms before the onset of the complication. Compared to all patients seen by emergency physicians, emergencies in ACHD patients are still rare. This review is aimed to guide management in ACHD emergency situations. Approximately two-thirds of all emergency admissions are caused by arrhythmias or acute heart failure. Sustained arrhythmias may rapidly lead to acute cardiac decompensation in ACHD patients. If medical treatment fails or patients present in hemodynamically unstable conditions, prompt electrical cardioversion is mandatory. Symptomatic bradycardia may require urgent pacemaker implantation. Depending on the underlying heart defect, placement of temporary transvenous pacemaker leads may be impossible. Acute heart failure in ACHD patients is often caused by acute right heart failure. Other more frequent emergencies are infections, syncope, thromboembolic events, and aortic dissection. It is highly recommended to contact the tertiary care center that follows the patient regularly early in case of patient presentation to the emergency room.

Lazy Sundays: role of day of the week and reactivity on objectively measured physical activity in older people.

BACKGROUND: The aim of this study was to assess the effect of day of the week and wearing a device (reactivity) on objectively measured physical activity (PA) in older people. METHODS: Walking duration as a measure for PA was recorded from 1333 German community-dwelling older people (≥65 years, 43.8% women) over 5 days using accelerometers (activPAL). Least-square means of PA with 95%-confidence intervals (95%-CI) from multi-level analysis were calculated for each day of the week and each measurement day (days after sensor attachment). RESULTS: Walking duration on Sundays was significantly lower compared to working days (Sunday vs. Monday-Friday: - 12.8 min (95%-CI: - 14.7; - 10.9)). No statistically significant difference compared to working days was present for Saturdays. The linear slope for measurement day and walking duration was marginal and not statistically significant. CONCLUSIONS: Studies using PA sensors in older people should assess Sundays and working days to adequately determine the activity level of the participants.

Inter-molecular inter-actions in a phenol-substituted benzimidazole.

Hydrogen bonding plays an important role in the design of solid-state structures and gels with desirable properties. 1-(4-Hydroxybenzyl)-2-(4-hydroxyphenyl)-5,6-dimethyl-1H-benzimidazole was isolated as the acetone disolvate, C22H20N2O2·2C3H6O. O-H⋯N hydrogen bonding between benz-imidazole mol-ecules results in chains parallel to [010]. One of the acetone solvate mol-ecules participates in O-H⋯O hydrogen bonding with the benzimidazole derivative. C-H⋯π inter-actions are observed in the extended structure. Hirshfeld surface analysis was used to explore the inter-molecular inter-actions and density functional theory was used to estimate the strength of the hydrogen bonds.

An exploration of O-H⋯O and C-H⋯π inter-actions in a long-chain-ester-substituted phenyl-phenol: methyl 10-[4-(4-hydroxyphenyl)phenoxy]decanoate.

An understanding of the driving forces resulting in crystallization vs organogel formation is essential to the development of modern soft materials. In the mol-ecular structure of the title compound, methyl 10-[4-(4-hydroxyphenyl)phen-oxy]decanoate (MBO10Me), C23H30O4, the aromatic rings of the biphenyl group are canted by 6.6 (2)° and the long-chain ester group has an extended conformation. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains along [10[Formula: see text]]. The chains are linked by C-H⋯O hydrogen bonds, forming layers parallel to the ac plane. The layers are linked by C-H⋯π inter-actions, forming a three-dimensional supra-molecular structure. The extended structure exhibits a lamellar sheet arrangement of mol-ecules stacking along the b-axis direction. Each mol-ecule has six nearest neighbors and the seven-mol-ecule bundles stack to form a columnar superstructure. Inter-action energies within the bundles are dominated by dispersion forces, whereas inter-columnar inter-actions have a greater electrostatic component.

Non-Steroidal Biphenyl Gelators: Correlation of Xerogel Structure with Solid-State Structure and Circular Dichroism Spectroscopy.

Because the factors favoring the formation of well-formed single crystals are dissimilar to those conducive to gel formation, few examples of single-crystal structural characterizations of organogelators are found in the literature. A series of biphenyl methyl and ethyl diester derivatives of varying chain length were synthesized and their gelation abilities explored. X-ray diffraction of single crystals of one of the gelators reveals a columnar extended structure. Based on XRD results for xerogels obtained from the reported organogelators, the members of the series are isostructural and so also adopt a columnar superstructure. Scanning electron microscopy (SEM) was used for the investigation of the morphology of the xerogels, which display either platelet-like morphologies or more typical entangled twisted ribbon-like aggregates. The gels exhibit chirality, which depends on the sol-gel transition history, as observed by induced circular dichroism (ICD) spectroscopy.

Structural characterization, gelation ability, and energy-framework analysis of two bis(long-chain ester)-substituted 4,4'-biphenyl compounds.

There are few examples of single-crystal structure determinations of gelators, as gel formation requires that the dissolved gelator self-assemble into a three-dimensional network structure incorporating solvent via noncovalent interactions rather than self-assembly followed by crystallization. In the solid-state structures of the isostructural compounds 4,4'-bis[5-(methoxycarbonyl)pentyloxy]biphenyl (BBO6-Me), C26H34O6, and 4,4'-bis[5-(ethoxycarbonyl)pentyloxy]biphenyl (BBO6-Et), C28H38O6, the molecules sit on a crystallographically imposed center of symmetry, resulting in strictly coplanar phenyl rings. BBO6-Me behaves as an organogelator in various alcohol solvents, whereas BBO6-Et does not. The extended structure reveals bundles of molecules that form a columnar superstructure. Framework-energy calculations reveal much stronger interaction energies within the columns (-52 to -78 kJ mol-1) than between columns (-2 to -16 kJ mol-1). The intracolumnar interactions are dominated by a dispersion component, whereas the intercolumnar interactions have a substantial electrostatic component.

Heterodimerization of AML1/ETO with CBFß is required for leukemogenesis but not for myeloproliferation.

The AML1/Runx1 transcription factor and its heterodimerization partner CBFß are essential regulators of myeloid differentiation. The chromosomal translocation t(8;21), fusing the DNA binding domain of AML1 to the corepressor eight-twenty-one (ETO), is frequently associated with acute myeloid leukemia and generates the AML1/ETO (AE) fusion protein. AE represses target genes usually activated by AML1 and also affects the endogenous repressive function of ETO at Notch target genes. In order to analyze the contribution of CBFß in AE-mediated leukemogenesis and deregulation of Notch target genes, we introduced two point mutations in a leukemia-initiating version of AE in mice, called AE9a, that disrupt the AML1/CBFß interaction (AE9aNT). We report that the AE9a/CBFß interaction is not required for the AE9a-mediated aberrant expression of AML1 target genes, while upregulation/derepression of Notch target genes does require the interaction with CBFß. Using retroviral transduction to express AE9a in murine adult bone marrow-derived hematopoietic progenitors, we observed that both AE9a and AE9aNT lead to increased myeloproliferation in vivo. However, both development of leukemia and long-term replating capacity are only observed with AE9a but not with AE9aNT. Thus, deregulation of both AML1 and Notch target genes is required for the development of AE9a-driven leukemia.

Synthesis and characterization of a novel long-alkyl-chain ester-substituted benzimidazole gelator and its octan-1-ol solvate.

The synthesis of a novel benzimidazole derivative with a long-chain-ester substituent, namely methyl 8-[4-(1H-benzimidazol-2-yl)phenoxy]octanoate, (3), is reported. Ester (3) shows evidence of aggregation in solution and weak gelation ability with toluene. The octan-1-ol solvate, methyl 8-[4-(1H-benzimidazol-2-yl)phenoxy]octanoate octan-1-ol monosolvate, C22H26N2O3·C8H18O, (4), exhibits a four-molecule hydrogen-bonded motif in the solid state, with N-H...O hydrogen bonds between benzimidazole molecules and O-H...N hydrogen bonds between the octan-1-ol solvent molecules and the benzimidazole unit. The alkyl chains of the ester and the octan-1-ol molecules are in unfolded conformations. The phenylene ring is canted by 10.27 (6)° from the plane of the benzimidazole ring system. H...C contacts make up 20.7% of the Hirshfeld surface coverage. Weak C-H...π interactions involving the benzimidazole alkyl chain and three aromatic rings are observed.

The Political Future of Social Medicine: Reflections on Physicians as Activists.

The academic discipline of social medicine has always had a political and policy advocacy component, in addition to its core functions of research and teaching. Its origins lie in the 18th and 19th centuries, in the work of Johann Peter Frank and Rudolph Virchow, among others. Virchow's dictum that "politics is nothing else but medicine on a large scale" highlights that most social determinants of health are politically determined and shape population health. Yet despite intense epidemiological and sociological research on the social determinants of health, less attention has been paid to this political and policy dimension.During the 1960s, the author and many other clinicians were directly involved in attempts to use health care institutions to foster structural change. However, the author argues that efforts to assist individual patients and more effectively manage their interactions with the health care system, as described in the articles in this issue's special collection on "structural competency," while worthy and useful, do not confront root causes. Going forward, efforts to effect structural change must take place outside the arena of the clinical encounter and involve interprofessional teams and collaborations with nongovernmental organizations. They should intervene directly on the structures that contribute to illness such as poor housing, income and wealth inequality, inferior education, racism and residential segregation, and toxic concentrations of extreme poverty in urban areas. Collectively, these efforts-within and outside the spheres of medicine-represent the real operative form of structural competency.

Structure determination of three furan-substituted benzimidazoles and calculation of π-π and C-H···π interaction energies.

The synthesis and structural characterization of 2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzimidazole [C16H12N2O2, (I)], 2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzimidazol-3-ium chloride monohydrate [C16H13N2O2(+)·Cl(-)·H2O, (II)] and the hydrobromide salt 5,6-dimethyl-2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzimidazol-3-ium bromide [C18H17N2O2(+)·Br(-), (III)] are described. Benzimidazole (I) displays two sets of aromatic interactions, each of which involves pairs of molecules in a head-to-tail arrangement. The first, denoted set (Ia), exhibits both intermolecular C-H···π interactions between the 2-(furan-2-yl) (abbreviated as Fn) and 1-(furan-2-ylmethyl) (abbreviated as MeFn) substituents, and π-π interactions involving the Fn substituents between inversion-center-related molecules. The second, denoted set (Ib), involves π-π interactions involving both the benzene ring (Bz) and the imidazole ring (Im) of benzimidazole. Hydrated salt (II) exhibits N-H···OH2···Cl hydrogen bonding that results in chains of molecules parallel to the a axis. There is also a head-to-head aromatic stacking of the protonated benzimidazole cations in which the Bz and Im rings of one molecule interact with the Im and Fn rings of adjacent molecules in the chain. Salt (III) displays N-H···Br hydrogen bonding and π-π interactions involving inversion-center-related benzimidazole rings in a head-to-tail arrangement. In all of the π-π interactions observed, the interacting moieties are shifted with respect to each other along the major molecular axis. Basis set superposition energy-corrected (counterpoise method) interaction energies were calculated for each interaction [DFT, M06-2X/6-31+G(d)] employing atomic coordinates obtained in the crystallographic analyses for heavy atoms and optimized H-atom coordinates. The calculated interaction energies are -43.0, -39.8, -48.5, and -55.0 kJ mol(-1) for (Ia), (Ib), (II), and (III), respectively. For (Ia), the analysis was used to partition the interaction energies into the C-H···π and π-π components, which are 9.4 and 24.1 kJ mol(-1), respectively. Energy-minimized structures were used to determine the optimal interplanar spacing, the slip distance along the major molecular axis, and the slip distance along the minor molecular axis for 2-(furan-2-yl)-1H-benzimidazole.

Synthesis and spectroscopic characterization of chiral biphenyl-cholesterol gels.

The synthesis of 4-(3-cholesteroxycarbonylpropyloxy)biphenyl (BO4-chol), 4-(7-cholesteroxycarbonylheptyloxy)biphenyl (BO8-chol), and 4,4'-bis(7-cholesteroxycarbonyl heptyloxy)biphenyl (BBO8-chol) is reported. These gelators form 1% and 2% (w/w) stable gels in n-octanol. The gels formed from single cholesterol gelators (BO4-chol and BO8-chol) exhibit lower phase transition temperatures (Tg) (62-65, 68-69 °C) than the gel obtained from the bischolesterol gelator BBO8-chol (96-98 °C). All three gelators form chiral gels in n-octanol as observed by induced circular dichroism (ICD) spectroscopy. The effect of two cholesterol moieties versus one cholesterol unit linked to a biphenyl molecule by a flexible chain, and the effect of the chain length on the gelation ability of these three novel gelators was investigated by circular dichroism (CD), absorption, and fluorescence spectroscopies. The gels obtained from BO4-chol and BO8-chol exhibit biphasic circular dichroism spectra with opposite chirality. The ICD spectra of both BO8-chol and BBO8-chol gels show a positive ICD band followed by a negative band at room temperature. However, while BO8-chol gel ICD absorptions decrease equally as temperature increases, BBO8-chol gel shows an inversion of the Cotton effect bands between 50 and 60 °C until completely disappearing above the phase transition temperature. SEM was used for the investigation of the morphology of the xerogels. On the basis of XRD data and molecular modeling, we propose packing modes for the formation of the organogelator aggregates.

4-Bromo-2-(5-bromo-thio-phen-2-yl)-1-[(5-bromo-thio-phen-2-yl)meth-yl]-5,6-dimethyl-1H-benzimidazole.

The title compound, C18H13Br3N2S2, was obtained via the reaction of N-bromo-succinamide with 5,6-dimethyl-2-(thio-phen-2-yl)-1-[(thio-phen-2-yl)meth-yl]-1H-benzimidazole. The compound exhibits rotational disorder of the 5-bromo-thio-phen-2-yl substituent with a refined major:minor occupancy ratio of 0.876 (7):0.124 (7). The 5-bromo-thio-phen-2-yl mean plane is canted to the benzimidazole plane by 20.0 (4) and 21 (4)° in the major and minor components, respectively. In the crystal, weak C-H⋯N inter-actions link the mol-ecules into infinite C(7) chains along the 21 axes.

[Changing spectrum of renal disease in HIV infection]. / Veränderungen im Spektrum der Nierenerkrankungen bei HIV-Infektion.

BACKGROUND AND OBJECTIVE: Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART). PATIENTS AND METHODS: Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period). RESULTS: 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease. CONCLUSION: The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population.

Acute kidney injury caused by tenofovir disoproxil fumarate and diclofenac co-administration.

OBJECTIVES: The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells. METHODS: A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out. RESULTS: Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086). CONCLUSIONS: Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.