Broadband-dielectric-spectroscopy study of molecular dynamics in a mixture of itraconazole and glycerol in glassy, smectic-A, and isotropic phases.

Itraconazole (ITZ) is a thermotropic liquid crystal that exhibits isotropic, nematic, and smectic phases on cooling towards the glass transition upon melting. Over the years, new aspects regarding the liquid-crystalline ordering of this antifungal drug were systematically revealed. It has been shown recently that the temperature range of individual mesophases in ITZ can be modified by adding a small amount of glycerol (GLY). Moreover, above the critical concentration of 5% w/w, a smectic to nematic transition can be avoided. Here we go one step further, and we used broadband dielectric spectroscopy to investigate the new phase behavior of the ITZ-GLY mixture (5% w/w). To confirm the phase transformations of the ITZ-GLY mixture, differential scanning calorimetry was also employed. The analysis of molecular dynamics of the ITZ-GLY mixture in the glassy and isotropic phases revealed features similar to those observed for neat ITZ. Two relaxation processes were identified in the smectic-A phase, with similar temperature dependence, most likely related to the fast rotations around the long axis of a molecule. Additionally, the derivative analysis revealed another low-frequency process hidden under DC conductivity ascribed to the slow rotations about a short axis. We will show that the differences in the molecular organization in the smectic-A and isotropic phases leave a clear fingerprint on the temperature behavior of relaxation times and other dielectric parameters, such as DC conductivity and dielectric strength, for which a pretransition effect has been detected.

[Devastated bladder outlet-suprapubic catheter vs. reconstruction]. / Der zerstörte Blasenauslass ("devastated bladder outlet") ­ suprapubischer Katheter vs. Rekonstruktion.

The combination of a severe urethral sphincter defect with simultaneous development of recurrent bladder outlet obstruction characterizes a "devastated bladder outlet", which often is not surgically reconstructable. Clinically, quality of life is considerably compromised in affected patients with a wide variance of symptoms, mostly complete incontinence, but also urinary retention. This condition is usually preceded by multiple endoscopic interventions or even open surgical procedures, occasionally also in combination with radiotherapy of the pelvic region as part of multimodal oncological therapy. Treatment of these cases is complex and limited to few promising procedures. A potential therapy should primarily include the decision about the possibility of preserving the urinary bladder. In individual cases, this can result in simple therapy options while at the same time maintaining an acceptable quality of life for those affected. If there is no possibility of a refunctionalization of the original bladder, supravesical urinary diversion is indicated as a last-resort therapy. This paper provides a review as well as the limits and possibilities of conservative and surgical treatment options for a devastated bladder outlet.

Soft modes of the dielectric response in the twist-bend nematic phase and identification of the transition to a nematic splay bend phase in the CBC7CB dimer.

The dielectric spectra of the twist-bend nematic phase (NTB) of (the bent-shaped) achiral liquid-crystal dimer 1''-,7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) are studied for the determination of the different relaxation modes. Two molecular processes and one collective process were observed in the megahertz frequency range. Two molecular processes were assigned: one to the precessional rotation of the longitudinal components of the cyanobiphenyl groups and the second one to the spinning rotation of the transverse component of the CB7CB dimer. The peak, at a frequency of about 1 MHz, shows a peculiar temperature behavior at the NTB to N transition, reminiscent of the soft mode at the transition from the SmA to the SmC phase. This peak can be assigned to a collective fluctuation of the tilt angle of the coarse grained director N with respect to the pseudo-layer normal. This corresponds well with the electro-clinic effect observed as a response to an electric field in electro-optic experiments. The low frequency relaxation process, observed in the frequency range of 1 Hz-102 Hz can be identified as a Goldstone mode, related to long-scale fluctuation of the cone phase. The frequency drop of the mode on increasing the bias field is interpreted as unwinding of a helix and an indication of the formation of a field induced nematic splay bend phase (NSB). This finding is also confirmed by birefringence data in the presence of strong bias fields.

[Bilateral intrauterine testicular torsion in a mature newborn]. / Bilaterale intrauterine Hodentorsion bei einem reifen Neugeborenen.

Bilateral intrauterine testicular torsion is an extremely rare emergency and can be difficult to diagnose due to its diverse manifestation and potential differential diagnoses. In time surgical intervention is crucial for the retention of testicular function. We present a newborn with a bilateral testicular torsion, in which one testicle could be saved after detorsion. The contralateral side showed hemorrhagic infarction and was removed. Since organ preservation is rarely successful, the surgical therapy is discussed controversially.

Molecular orientational distribution function of a chiral de Vries smectic liquid crystal from birefringence measurements.

An alternative method for determining the orientational distribution function and the order parameter from the electric field-induced birefringence measurements of a chiral liquid crystal compound in its Smectic A* is being introduced. A chiral mesogen based on a 5-phenyl-pyrimidine benzoate core terminated by a trisiloxane group on one side and the chiral alkyloxy chain on its opposite side is designed and synthesized to exhibit the "de Vries" smectic characteristics. The compound exhibits first order Smectic A*-Smectic C* phase transition, evidenced by the results of differential scanning calorimetry. The material is being investigated by electro-optical experiment in its smectic phases. We present a model that incorporates the generalised Langevin-Debye model which includes the Maier-Saupe effective mean-field potential term in order to explain the change in birefringence with the electric field. A good agreement between the experimental results and the predictions from the model leads to the determination of the molecular orientational distribution function in Smectic A phase. Furthermore, the temperature dependency of the Saupe orientational order parameter ⟨P2⟩ is obtained using the parameters of the model. Based on the experimental and theoretical results, we show that de Vries Smectic A* phase exhibits a broad volcano-like tilt angle distribution with the two maxima occurring at finite tilt angles closer to the Smectic A*-Smectic C* transition temperature, and a sugarloaf-like distribution occurs in the tilt for temperatures close to the Isotropic-Smectic A* phase transition.

Assessment of the bacterial viability of chlorine- and quaternary ammonium compounds-treated Lactobacillus cells via a multi-method approach.

AIMS: The assessment of the bacterial viability of chlorine- and quaternary ammonium compounds (QACs)-treated Lactobacillus cells by culture-dependent and -independent methods. METHODS AND RESULTS: Lactobacillus isolates (Lactobacillus plantarum G1, Lactobacillus plantarum B1, Lactobacillus brevis S1 and Lactobacillus paracasei W1) in biofilm and planktonic cell suspensions were treated with chlorine-based (0·018 and 0·18%) and QACs-based (0·2 and 2·0%) disinfectants for 5 min and then analysed by plate counting, flow cytometry (FCM) and fluorescence activated cell sorting (FACS). The reaction of sessile cells to disinfectants was assessed with the confocal laser scanning microscopy (CLSM). Plate counts revealed L. paracasei W1 to be substantially inactivated by both disinfectants, while counts of the other isolates to be significantly reduced only by QACs, with L. plantarum B1 and L. brevis S1 showing a greater difference between QACs concentrations and cell types. In several cases, the disinfectants caused slightly higher inactivation of planktonic than biofilm cells, with L. plantarum B1 being significantly less sensitive to QACs in biofilm cells (P < 0·05). Following FCM with a Syto® 9/PI assay, which addresses cell membrane integrity, the emergence of damaged (Syto® 9- PI+ ) and injured (Syto® 9+ PI+ ) subpopulations was often observed in cells when they were treated with QACs, whereas intact (Syto® 9+ PI- ) and unstained (Syto® 9- PI- ) subpopulations were mostly encountered in chlorine-treated cells. Except Syto® 9- PI+ , all subpopulations were recovered on agar plates following FACS, with biofilm cells showing higher culturability irrespective of conditions, probably because of the residues of the biofilm matrix which serve as a protective cover for the bacteria. The CLSM revealed a substantial cell membrane damage within the QACs-treated biofilms, however, some cells deep in the biofilm were still intact and thus remained protected against this disinfectant. CONCLUSION: We found that FCM/FACS proved useful in the analysis of lactobacilli membrane integrity in disinfection experiments as well as in recovery evaluation of planktonic-biofilm cell subpopulations. In turn, CLSM was particularly useful in investigating the resistance mechanism when Lactobacillus cells were embedded in biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the need for treatment optimization on a case-by-case basis to avoid the emergence of cells in intermediate states with recovery potential and to reach and, thus, kill all bacteria in already developed lactobacilli biofilms.

Distortions in structures of the twist bend nematic phase of a bent-core liquid crystal by the electric field.

The dielectric spectra of the twist bend nematic phase (N_{TB}) of an achiral asymmetric bent-core liquid crystalline compound are studied for determining the various relaxation modes. Dielectric measurements are also carried out under the bias field E up to 8 V/µm. Two molecular and two collective relaxation processes are observed. The orientational order parameters with respect to the local and the main directors determined using molecular modes are used to find the heliconical angle. The results also show that the order parameter with reference to the main director reverses its trend from increasing to decreasing at temperatures of a few degrees above the N_{TB} to N transition. The collective relaxation modes are assigned to (a) distortions of the local director by the electric field at a frequency of ∼100kHz while the periodic helical structure remains unaltered (mode attributed to flexoelectricity); (b) changes in the periodic structure arising from a coupling of the dielectric anisotropy with the electric field at the lowest frequency in the range of 100 Hz-10 kHz. Frequency of the higher frequency collective mode (∼100kHz) depends primarily on the heliconical angle and has anomalous softeninglike behavior at the N-N_{TB} transition. The lowest frequency mode is studied under the bias field E; the modulus of the wave vector gradually vanishes on increasing E (except for an initial behavior, E^{2}<0.1V^{2}/µm^{2}, which is just the opposite). The transition from the twist bend to splay bend structure is observed by a sudden drop in the frequency of this mode, followed by a linear decrease in frequency by increasing E. The results agree with the predictions made from the currently proposed models for a periodically distorted N_{TB} phase.

Observation of the de Vries behavior in SmA* phase of a liquid crystal using polarised Raman scattering and infrared spectroscopy.

Two approaches exist in the literature for describing the orientational distribution function (ODF) of the molecular directors in SmA* phase of liquid crystals, though several models are recently proposed in the literature for explaining the de Vries behaviour. These ODFs correspond to either the conventional unimodal arrangements of molecular directors arising from the mean field theory that leads to the broad or sugar-loaf like distribution or to the "diffuse-cone-shaped" type distribution proposed by de Vries. The hypothesis by de Vries provides for a realistic explanation as to how at a molecular level, a first-order SmA* to SmC* transition can occur where the uniform molecular director azimuthal distributions condense to values lying within a narrow range of angles; finally these condense to a single value while at the same time ensuring a little or no concomitant shrinkage in the layer spacing. The azimuthal distribution of the in-layer directors is probed using IR and polarized Raman spectroscopic techniques. The latter allows us to obtain the ODF and the various order parameters for the uniaxial and the biaxial phases. Based on the results of these measurements, we conclude that the "cone-shaped" (or volcano-shaped) de Vries type of distribution can most preferably describe SmA* where "a first-order phase transition from SmA* to SmC*" and a low layer shrinkage can both be easily explained.

Phase behavior and characterization of heptamethyltrisiloxane-based de Vries smectic liquid crystal by electro-optics, x rays, and dielectric spectroscopy.

A heptamethyltrisiloxane liquid crystal (LC) exhibiting I-SmA^{*}-SmC^{*} phases has been characterized by calorimetry, polarizing microscopy, x-ray diffraction, electro-optics, and dielectric spectroscopy. Observations of a large electroclinic effect, a large increase in the birefringence (Δn) with electric field, a low shrinkage in the layer thickness (∼1.75%) at 20 °C below the SmA^{*}-SmC^{*} transition, and low values of the reduction factor (∼0.40) suggest that the SmA^{*} phase in this material is of the de Vries type. The reduction factor is a measure of the layer shrinkage in the SmC^{*} phase and it should be zero for an ideal de Vries. Moreover, a decrease in the magnitude of Δn with decreasing temperature indicates the presence of the temperature-dependent tilt angle in the SmA^{*} phase. The electro-optic behavior is explained by the generalized Langevin-Debye model as given by Shen et al. [Y. Shen et al., Phys. Rev. E 88, 062504 (2013)10.1103/PhysRevE.88.062504]. The soft-mode dielectric relaxation strength shows a critical behavior when the system goes from the SmA^{*} to the SmC^{*} phase.

[Fistulas of the urogenital tract after radiotherapy]. / Fisteln des Urogenitaltraktes nach Strahlentherapie.

BACKGROUND: Radiotherapy plays a substantial role in the treatment of malignancies. More than 2/3 of all oncologic patients undergo radiotherapy during their specific treatment. Besides manifold side effects of radiotherapy, radiogenic fistulas of the urogenital tract are a potential severe complication. These fistulas might affect the female genital tract and the urinary tract. THERAPY: Potential manifold variety of radiogenic urogenital fistulas requires a specific therapy. Radiation tissue damage includes severely disturbed local blood supply. Consequently, in some cases extremely complex reconstructive techniques are necessary to restore the functionality of the urinary tract. CONCLUSION: The treatment of radiogenic urogenital fistulas is challenging. A successful therapy can only be achieved by local improvement of the blood supply in the damaged area.

Non-invasive high-intensity focused ultrasound treatment of the placenta: a preliminary in-vivo study using a simian model.

OBJECTIVE: To demonstrate the feasibility and efficacy of high-intensity focused ultrasound (HIFU) for the non-invasive creation of placental lesions in a simian model. METHODS: Eight pregnant monkeys were exposed to HIFU treatment after anesthesia, using a toroidal HIFU 2.5-MHz transducer with an integrated ultrasound imaging probe. Lesions on the placental tissue were created non-invasively by placing the HIFU probe on the skin surface. Fetal and maternal parameters, such as maternal heart rate, fetal heart rate and subcutaneous and intra-amniotic fluid temperature, were recorded during HIFU exposure. Cesarean section was performed immediately after the procedure to extract the placenta and examine the fetus and the maternal abdominal cavity. Placental HIFU lesions were assessed by ultrasound, gross pathology and histology. RESULTS: The mean gestational age of the monkeys was 72 ± 4 days. In total, 13 HIFU procedures were performed. The acoustic power and exposure time were increased progressively. This gradual increase in total energy delivered was used to determine a set of parameters to create reproducible lesions in the placenta without complications. Five placental lesions were observed with average diameters of 6.4 ± 0.5 mm and 7.8 ± 0.7 mm and an average depth of 3.8 ± 1.5 mm. Ultrasound examination of the placentae revealed hyperechoic regions that correlated well with macroscopic analysis of the HIFU lesions. Necrosis of placental tissue exposed to HIFU was confirmed with macroscopic and microscopic analysis. There was no significant variation in maternal and fetal parameters during HIFU exposure. CONCLUSIONS: This study demonstrates the feasibility of HIFU applied non-invasively to the placental unit in an in-vivo pregnant monkey model. The technique is safe in the immediate short term and is potentially translatable to human pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[Treatment of long-term radiation injuries in the urinary tract]. / Therapie von Strahlenspätschäden am Harntrakt.

BACKGROUND: Radiotherapy plays a substantial role in the treatment of malignancies. The side effects and long-term sequelae of radiotherapy are manifold and depend on the single doses and the total dosage, the time interval between two doses, the size of the irradiated tissue area and the radiation sensitivity of individual tissues. The urological complications following radiotherapy include inflammatory alterations of the bladder (radiation-induced hemorrhagic cystitis), fibrosis with subsequent radiogenic shrunken bladder, stenosis of the ureter and formation of secondary retroperitoneal fibrosis. In addition, the formation of necrosis can result in rectourethral, uterovaginal and vesicovaginal fistulas up to formation of a cloaca. THERAPY: The main problem following radiotherapy is microangiopathy in the irradiated area. The therapy of radiation injuries in the urogenital tract depends on the extent and localization of the radiation damage. In particularly severe cases extremely complex reconstructive techniques are necessary for restoration of functionality of the urinary tract and preservation of renal function. CONCLUSION: Radiation injuries can remain asymptomatic for a long time so that a closely controlled urological surveillance is indispensable. The correct selection of the intestinal segments for surgical removal of radiation injuries in the urogenital tract is of pivotal importance.

High-intensity focused ultrasound applied to the placenta using a toroidal transducer: a preliminary ex-vivo study.

OBJECTIVE: To demonstrate in an ex-vivo model the feasibility of applying high-intensity focused ultrasound (HIFU) using a toroidal transducer for the creation of placental lesions. METHODS: In this study we used a toroidal transducer, composed of 32 ring-shaped emitters with an ultrasound probe at the center, operating at a frequency of 2.5 MHz. We examined 45 human placentae, following either normal vaginal delivery or medical termination of pregnancy between 17 and 40 gestational weeks. First, the attenuation coefficients of 12 human placentae were measured and integrated into a numerical model for simulating HIFU lesions. Then, using acoustic parameters from this preliminary study, we performed ex-vivo experiments with 33 human placentae, each overlain with an animal abdominal wall to simulate the maternal wall. We created single HIFU lesions in 25 of these placentae, and a series of six juxtaposed lesions in eight, studying these both sonographically and macroscopically. RESULTS: Human placental attenuation coefficients of the 12 human placentae ranged from 0.072 to 0.098 Np/cm/MHz, according to gestational age. The 25 single HIFU lesions created had an average diameter of 7.1 ± 3.2 mm and an average depth of 8.2 ± 3.1 mm. The average diameter of the eight series of six juxtaposed HIFU lesions was 23.0 ± 5.0 mm and the average depth was 11.0 ± 4.7 mm. The average thickness of the abdominal walls was 10.5 ± 1.8 mm. No lesions or damage were observed in intervening tissues. CONCLUSION: This study demonstrates, using an ex-vivo model, the feasibility, reproducibility, harmlessness and effectiveness of HIFU applied to the human placenta.

Dielectric and electro-optic studies of a bimesogenic liquid crystal composed of bent-core and calamitic units.

A bimesogen, BR1, composed of a bent-core and calamitic unit, linked laterally via a flexible spacer is investigated by dielectric and electro-optic techniques. X-ray results show the presence of clusters in the nematic phase, and the cluster size is of the order of the thickness of a single layer. The splitting of the small-angle scattering Δχ/2 is about 50°, which indicates SmC like clusters with a significant tilt of the molecules in the quasilayers. The sign reversal of the dielectric anisotropy Δε' is observed as a function of frequency; the behavior is rather similar to that exhibited by the conventional dual frequency nematics, composed of a calamitic mesogen, with the exception that it occurs at much lower frequencies in this material. Interestingly, as the bimesogen enters its nematic phase, the average permittivity decreases as the temperature is lowered. This indicates the onset of antiparallel association of some of the dipoles in the system, and this type of association is much more prominent in BR1 in comparison to other bent-core liquid crystalline systems composed of the same bisbenzoate core unit. The analysis of the dielectric spectra using the Maier-Meier model confirms the onset of an antiparallel correlation of dipoles occurring at the isotropic to nematic phase transition temperature. Additionally these results support a model of the cluster where the transverse dipole moments in the neighboring layers are antiparalleled to each other.

[Management and prevention of complications in open urethral surgery. End-to-end anastomosis and buccal mucosa urethroplasty]. / Management und Prävention von Komplikationen bei offener Harnröhrenchirurgie. End-zu-End-Anastomose und Mundschleimhauturethroplastik.

Open operative procedures for urethral reconstruction (i.e. stricture resection with primary end-to-end anastomosis and buccal mucosa urethroplasty) are established and proven techniques with a low complication profile and high success rates. The aim of this operative technique is removal of the urethral obstruction to avoid far-reaching complications for the whole urinary tract. Despite excellent long-term results, complications are not completely avoidable in both techniques. A successful complication management requires the complete spectrum of reconstructive techniques in addition to appropriate operative expertise in order to be able to achieve the optimal result even in cases of complications. Simultaneously the recognition of potential risks contributes to a further reduction of early and delayed complications both in the approach to the operative intervention as well as intraoperatively.

Molecular dynamics of itraconazole at ambient and high pressure.

Comprehensive molecular dynamics studies of vitrified and cryogrounded itraconazole (Itr) were performed at ambient and elevated pressure. DSC measurements yielded besides melting and glass transition observed during heating and cooling of both samples two further endothermic events at around T = 363 K and T = 346 K. The nature of these transitions was investigated using X-ray diffraction, broadband dielectric spectroscopy and Density Functional Theory calculations. The X-ray measurements indicated that extra ordering in itraconazole is likely to occur. Based on calculations and theory derived by Letz et al. the transition observed at T = 363 K was discussed in the context of formation of the nematic mesophase. In fact, additional FTIR measurements revealed that order parameter variation in Itr shows a typical sequence of liquid crystal phases with axially symmetric orientational order; i.e. a nematic phase in the temperature range 361.7 K to 346.5 K and a smectic A phase below 346.5. Moreover, dielectric measurements demonstrated that except for the structural relaxation process, there is also slower mode above the glass transition temperature in both vitrified and cryogrounded samples. We considered the origin of this mode taking into account DFT calculations, rod like shape of itraconazole and distribution of its dipole moment vectors. For the dielectric data collected at elevated pressure, evolution of the steepness index versus pressure was determined. Finally, the pressure coefficient of the glass transition temperature was evaluated to be equal to 190 K GPa(-1).

Oncological outcome of primary versus secondary muscle-invasive bladder cancer is comparable after radical cystectomy.

BACKGROUND: High-risk non-muscle-invasive bladder cancer (NMIBC) progressing to muscle-invasive bladder cancer (MIBC) is associated with adverse tumour biology. It is unclear, however, whether outcome of NMIBC progressing to MIBC is adverse compared to primary MIBC and whether NMIBC of higher risk of progression to MIBC is adverse compared to NMIBC of lower risk. OBJECTIVE: Our objective was to assess cancer-specific survival (CSS) following radical cystectomy (RC) for primary MIBC and for NMIBC progressing to MIBC in dependence of EORTC risk score. MATERIALS AND METHODS: Clinical and histopathological characteristics and CSS of 150 patients were assessed. Secondary MIBCs were stratified by EORTC risk score at the last transurethral resection of bladder tumour for NMIBC. RESULTS: CSS did not differ significantly between primary and secondary MIBC (p = 0.521). Secondary MIBC with high EORTC score had significantly shorter CSS compared to secondary MIBC with intermediate EORTC score (p = 0.029). In multivariable analysis, pathological tumour stage (HR = 3.77; p = 0.020) and lymph node stage (HR = 2.34; p = 0.022) were significantly correlated with CSS. CONCLUSION: While the outcome of secondary MIBC is not generally adverse compared to primary MIBC, the EORTC risk score not only reflects high risk of progression of NMIBC to MIBC, but also worse outcome following RC for secondary MIBC. Timely RC should thus be debated in high-risk NMIBC.

Increasing the donor and recipient pool-expanded criteria in living kidney donors.

To increase the donor and recipient pool in living related renal transplantation, kidneys from expanded criteria living donors are used more frequently to reduce the general problem of organ shortage. This article presents an overview of the current literature concerning this topic to further improve donor selection and transplant decision making.

[Use of bowel segments for ureter reconstruction]. / Harnleiterersatz unter Verwendung von Darmsegmenten.

When ureter damage is extensive or affects the midureter continuity can be restored using bowel segments. The principle issues of these techniques comprise reconstruction of the urinary tract preserving renal function in a long-term setting. The safety of ureters reconstructed from bowel segments has been validated in several large series as a reliable last resort solution with favorable results and low complication rates. Ureter reconstruction with bowel segments is doomed to fail in patients with short-bowel syndrome or Crohn's disease. Furthermore, the applicability in children and patients with progressive renal deficiency is severely limited. To prevent renal deterioration the use of retubularized bowel segments as a substitute for ureter defects has been postulated. Whereas antirefluxive implantation seems unnecessary in patients with a native bladder in situ or orthotopic bladder substitution, it is recommended in continent bowel reservoirs with cutaneous stoma.

Urinary incontinence due to the presence of necrotic adult Schistosoma haematobium parasite in the bladder following travel to Egypt.

A case of seronegative urinary Schistosomiasis is reported in a 68-year-old Caucasian male presenting with urgency of micturition and incontinence several months after bathing in a chlorinated pool of a first class hotel in Egypt. The symptoms were initiated by a necrotic adult Schistosoma haematobium parasite found in the urinary bladder following a cystoscopic examination. The purpose of this report is to describe this probable and uncommon source of Schistosomiasis, to demonstrate that Schistosoma parasites can also be found in the urinary bladder and to emphasize the importance of travel history.