Clinical characteristics of gyrate atrophy compared with a gyrate atrophy-like retinal phenotype.

INTRODUCTION: Gyrate atrophy (GA) is a rare retinal dystrophy due to biallelic pathogenic variants in the ornithine aminotransferase (OAT) gene, causing a 10-fold increase in plasma ornithine levels. It is characterized by circular patches of chorioretinal atrophy. However, a GA-like retinal phenotype (GALRP) without elevated ornithine levels has also been reported. The aim of this study is to compare the clinical characteristics of GA and GALRP and to identify possible discriminators. METHODS: A multicenter, retrospective chart review was performed at three German referral centres on patient records between 01/01/2009 and 31/12/2021. Records were screened for patients affected by GA or GALRP. Only patients with examination results for plasma ornithine levels and / or genetic testing of the OAT gene were included. Further clinical data was gathered where available. RESULTS: Ten patients (5 female) were included in the analysis. Three suffered from GA, while seven had a GALRP. Mean age (± SD) at onset of symptoms was 12.3 (± 3.5) years for GA compared with 46.7 (± 14.0) years for GALRP patients (p = 0.002). Mean degree of myopia was higher in GA (-8.0 dpt. ± 3.6) compared to GALRP patients (-3.8 dpt. ± 4.8, p = 0.04). Interestingly, all GA patients showed macular oedema, while only one GALRP patient did. Only one patient with GALRP had a positive family history, while two were immunosuppressed. DISCUSSION: Age of onset, refraction and presence of macular cystoid cavities appear to be discriminators between GA and GALRP. GALRP may encompass both genetic and non-genetic subtypes.

Ultrasound aids in intraoperative assessment of deep resection margins of squamous cell carcinoma of the tongue.

We wanted to find out whether ultrasound (US) can be used to assess the deep resection margins after excision of squamous cell carcinoma (SCC) of the tongue, as intraoperative feedback on their condition might help to prevent them being too close. Resected specimens of cancers of the tongue from 31 patients with SCC of the tongue were suspended in US gel and scanned with a small 5-10MHz US probe. The tumour was readily visible and US could differentiate it from muscle tissue. The margin of normal tongue musculature surrounding the tumour was measured on the US images, and the minimal resection margin was noted and compared with that reported by the histopathologist. The mean (SD) deep resection margins measured on the US images differed by 1.1 (0.9) mm from those reported by the histopathologist (Pearson's correlation coefficient: 0.79, p<0.01). The US measurements took a maximum of five minutes. It is feasible to use US to assess resection specimens of SCC of the tongue as an adjunct to existing strategies (such as frozen section analysis) to help achieve the desired deep surgical margins. The method is easy to incorporate into surgical routine as it does not take long.

The oral cavity tumor thickness: Measurement accuracy and consequences for tumor staging.

INTRODUCTION: In the 8th edition of the AJCC/UICC cancer staging system (AJCC8), the depth of invasion (DOI) of the oral cavity tumor is the discriminative factor in tumor staging over the previously used greatest dimension (GD). In order to obtain a complete representation of how accurate we stage oral cavity cancer clinically, we evaluated the accuracy of measurements of the tumor dimensions on ultrasound (US) and magnetic resonance (MR) imaging by comparing this with the histopathology as the "golden standard". Secondly, we compared the pathological tumor staging of these tumors according to the AJCC7 and AJCC8, to evaluate the effect of the incorporation of the DOI in the AJCC8. MATERIALS AND METHODS: In a retrospective analysis, including 85 oral cavity tumors, the GD and tumor thickness (TT) measured on US and MR, were compared to histopathology with a Pearson correlation coefficient (R) and a Bland-Altman plot. The tumors were staged according to both the AJCC7 and AJCC8. RESULTS: TT was more reliably measured with US (R = 0.67, limits of agreement = 10.7 mm), whereas GD was more reliably measured with MR (R = 0.69, limits of agreement = 25.7 mm). The AJCC8 staging resulted into a higher tumor stage in 21% of the cases, compared to the AJCC7. CONCLUSION: For preoperative tumor staging, the TT is best estimated by the use of US. The incorporation of DOI in the AJCC8 can result in a higher tumor stage in more than twenty percent of the patients, with an associated worse prognosis for the patient.

Detection of extranodal spread in head and neck cancer with [18F]FDG PET and MRI: improved accuracy?

AIM: Preoperative detection of extranodal spread (ENS) in head and neck cancer can have important consequences for patient management. The aim of this study was to determine whether 18-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) or a combination with Magnetic Resonance Imaging (MRI) could more accurately predict ENS, especially with the near availability of fully integrated [18F]FDG PET/MRI scanners. METHODS: In retrospective cohort design a total of twelve patients, with 18 lymphnode metastases were studied with [18F]FDG PET and MRI. Presence of ENS was scored on MRI, and [18F]FDG PET images using a SUV max cut-off point of 12. Histopathology results were used as reference standard. Sensitivity, specificity and accuracy were calculated. RESULTS: The sensitivity, specificity and accuracy of [18F]FDG PET for ENS reached 70%,100% and 83%, respectively. The mean SUVmax of ENS positive lymphnodes was 13.6 versus 8.7 for lymphnode metastases without ENS (P=0.03). The sensitivity, specificity and accuracy of MRI for ENS were 70%, 100% and 83%, respectively. When the [18F]FDG PET and MRI findings were combined sensitivity, specificity and accuracy were 80%, 100% and 89%, respectively. Thus, accuracy increased from 83% to 89%. CONCLUSION: When there is no ENS or doubt of ENS on MRI, [18F]FDG PET seems to have additional value since it improves sensitivity and resolves uncertainty in case of high FDG uptake. This benefit needs to be confirmed prospectively in a larger cohort.

Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes.

Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.

Value of MR and CT Imaging for Assessment of Internal Carotid Artery Encasement in Head and Neck Squamous Cell Carcinoma.

Objective. This study was conducted to assess the value of CT and MR imaging in the preoperative evaluation of ICA encasement. Methods. Based upon three patient groups this study was performed. Retrospective analysis of 260 neck dissection reports from 2001 to 2010 was performed to determine unexpected peroperative-diagnosed encasement. Two experienced head and neck radiologists reviewed 12 scans for encasement. Results. In four out of 260 (1.5%) patients undergoing neck dissection, preoperative imaging was false negative as there was peroperative encasement of the ICA. Of 380 patients undergoing preoperative imaging, the radiologist reported encasement of the ICA in 25 cases. In 342 cases no encasement was described, 125 of these underwent neck dissection, and 2 had encasement peroperatively. The interobserver variation kappa varied from 0.273 to 1 for the different characteristics studied. Conclusion. These retrospectively studied cohorts demonstrate that preoperative assessment of encasement of the ICA using MRI and/or CT was of value in evaluation of ICA encasement and therefore contributively in selecting operable patients (without ICA encasement), since in only 1.5% encasement was missed. However, observer variation affects the reliability of this feature.

Pilot randomised controlled trial of face-down positioning following macular hole surgery.

OBJECTIVE: This was a pilot randomised controlled trial (RCT) to investigate the effect of post-operative face-down positioning on the outcome of macular hole surgery and to inform the design of a larger definitive study. METHODS: In all, 30 phakic eyes of 30 subjects with idiopathic full-thickness macular holes underwent vitrectomy with dye-assisted peeling of the ILM and 14% perfluoropropane gas. Subjects were randomly allocated to posture face down for 10 days (posturing group) or to avoid a face-up position only (non-posturing group). The primary outcome was anatomical hole closure. RESULTS: Macular holes closed in 14 of 15 eyes (93.3%; 95% confidence interval (CI) 68-100%) in the posturing group and in 9 of 15 (60%; 95% CI 32-84%) in the non-posturing group. In a subgroup analysis of outcome according to macular hole size, all holes smaller than 400 µm closed regardless of posturing (100%). In contrast, holes larger than 400 µm closed in 10 of 11 eyes (91%; 95% CI 58-99%) in the posturing group and in only 4 of 10 eyes (40%; 95% CI 12-74%) in the non-posturing group (Fisher's exact test P=0.02). CONCLUSION: Post-operative face-down positioning may improve the likelihood of macular hole closure, particularly for holes larger than 400 µm. These results support the case for a RCT.

Spectral identification of diffuse resonances in H2 above the n = 2 dissociation limit.

The resonance structure in molecular hydrogen above the n = 2 dissociation limit is experimentally investigated in a 1 XUV + 1 VIS coherent two-step laser excitation process, with subsequent ionization of H(n = 2) products. Diffuse spectral features exhibiting widths of several cm(-1) in the excitation range of 118,500-120,500 cm(-1) are probed. Information on angular momentum selection rules for parallel and crossed polarizations, combination differences, the para-ortho distinction, extrapolation from rovibrational structure in the bound region below the n = 2 threshold, and mass-selective detection of H(2)(+) parent and H(+) daughter fragments is used as input. This allows for an assignment of the diffuse resonances observed in terms of (1)Σ(g)(+), (1)Π(g), and (1)Δ(g) states, specified with vibrational and rotational quantum numbers.

Spectroscopic observation and characterization of H(+)H(-) heavy Rydberg states.

A series of discrete resonances was observed in the spectrum of H2, which can be unambiguously assigned to bound quantum states in the 1/R Coulombic potential of the H+H- ion-pair system. Two-step laser excitation was performed, using tunable extreme ultraviolet radiation at lambda = 94-96 nm in the first step, and tunable ultraviolet radiation in the range lambda = 310-350 nm in the second step. The resonances, detected via H+ and H2+ ions produced in the decay process, follow a sequence of principal quantum numbers (n = 140-230) associated with a Rydberg formula in which the Rydberg constant is mass scaled. The series converges upon the ionic H+H- dissociation threshold. This limit can be calculated without further assumptions from known ionization and dissociation energies in the hydrogen system and the electronegativity of the hydrogen atom. A possible excitation mechanism is discussed in terms of a complex resonance. Detailed measurements are performed to unravel and quantify the decay of the heavy Rydberg states into molecular H2+ ions, as well as into atomic fragments, both H(n = 2) and H(n = 3). Lifetimes are found to scale as n3.

Evolutionary algorithms to solve complicated NMR spectra.

The complexity of (1)H NMR spectra of solutes in partially ordered solvents such as liquid crystals increases rapidly with the number of spins. Spectra of simple solutes with sufficient symmetry and containing not too many spins (typically

Endovascular treatment of calcified plaque in the thoracic aorta after recurrent massive embolization.

A 65 year old female patient was admitted with acute onset of severe intermittent claudication in the right lower extremity. Angiography revealed embolic material in the right femoral artery and peripheral arterial thrombosis in the right leg. She was treated with thrombolysis first, thereafter calcified embolic material was removed by open embolectomy. A CT scan showed massive calcification in the thoracic aorta at the level of the occluded left subclavian artery, obviously the origin of embolization. On the second postoperative day she developed critical ischemia in the left lower limb. Angiography showed massive embolization in the left common and external iliac arteries. Following open embolectomy, stentgrafting of the descending thoracic aorta was performed. At one year the patient is in good condition.

Observation of a Rydberg series in H+H-: a heavy Bohr atom.

We report on the realization of a heavy "Bohr atom," through the spectroscopic observation of a Rydberg series of bound quantum states at principal quantum numbers n=140 to 230. The system is made heavy by replacing an electron inside a hydrogen atom by a composite H- particle, thus forming a H+H- Coulombically bound system obeying the physical laws of a generalized atom with appropriate mass scaling.

Interactions of the 3ppi u c1Pi u(v=2) Rydberg-complex member in isotopic N2.

The 3ppi u c1Pi u-X 1Sigmag+(2,0) Rydberg and b' 1Sigmau+-X 1Sigmag+(7,0) valence transitions of 14N2, 14N15N, and 15N2 are studied using laser-based 1 extreme ultraviolet (XUV)+1' UV two-photon-ionization spectroscopy, supplemented by synchrotron-based hotoabsorption measurements in the case of 14N2. For each isotopomer, effective rotational interactions between the c(v=2) and b'(v=7) levels are found to cause strong Lambda-doubling in c(v=2) and dramatic P/R-branch intensity anomalies in the b'-X(7,0) band due to the effects of quantum interference. Local perturbations in energy and predissociation line width for the c(v=2) Rydberg level are observed and attributed to a spin-orbit interaction with the crossing, short-lived C 3Pi u(v=17) valence level.

HD as a probe for detecting mass variation on a cosmological time scale.

The strong electronic absorption systems of the B1 Sigma u+-X1 Sigma g+ Lyman and the C1Pi u-X1 Sigma g+ Werner bands can be used to probe possible mass-variation effects on a cosmological time scale from spectra observed at high redshift, not only in H2 but also in the second most abundant hydrogen isotopomer HD. High resolution laboratory determination of the most prominent HD lines at extreme ultraviolet wavelengths is performed at an accuracy of delta lambda/lambda approximately 5 x 10(-8), forming a database for comparison with astrophysical data. Sensitivity coefficients Ki = d ln lambda i/d ln mu are determined for HD from quantum ab initio calculations as a function of the proton-electron mass ratio mu. Strategies to deduce possible effects beyond first-order baryon/lepton mass ratio deviations are discussed.

Complications of polyalkylimide 4% injections (Bio-Alcamid): a report of 18 cases.

Injectable filler materials can be valuable to aesthetic surgeons. To date, hardly any short-term and no long-term complications of polyalkylimide injections (Bio-Alcamid) have been reported. We present and discuss the history of 18 patients who had such complications. The patients were between 31 and 55 years of age. The time between injection and the onset of complications of polyalkylimide ranged from 1 month to 3 years. Additional invasive therapy at, or near, the site of injections triggered the onset of infection in 10 patients. By use of T2-weighted MRI with fat suppressing spectro-presaturation inversion recovery (SPIR) the filler material can be visualised. Once infection or migration of the permanent filler occurs, the therapeutic options are limited to surgical removal by a direct approach. Polyalkylimide should be handled under strict antiseptic circumstances. This does not only apply at the time of initial injections, but even more during any subsequent invasive treatment such as evacuation of surplus deposits or additional surgical procedures at, or near, the site of injection.

Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells.

Activation of the type I insulin-like growth factor receptor (IGF-IR) regulates several aspects of the malignant phenotype, including cancer cell proliferation and metastasis. Phosphorylation of adaptor proteins downstream of IGF-IR may couple IGF action to specific cancer phenotypes. In this study, we sought to determine if insulin receptor substrate-1 and -2 (IRS-1 and -2) mediate distinct biological effects in breast cancer cells. Insulin receptor substrate-1 and IRS-2 were expressed in T47D-YA breast cancer cells, which lack IRS-1 and -2 expression, yet retain functional IGF-IR. In the absence of IRS-1 and -2 expression, IGF-IR activation was unable to stimulate proliferation or motility in T47D-YA cells. Expression of IRS-1 resulted in IGF-I-stimulated proliferation, but did not affect motility. In contrast, expression of IRS-2 enhanced IGF-I-stimulated motility, but did not stimulate proliferation. The alphaIR-3, an inhibitor of the IGF-IR, was unable to affect these IGF-stimulated phenotypes unless IRS-1 or -2 was expressed. Thus, IGF-IR alone is unable to regulate important breast cancer cell phenotypes. In these cells, IRS proteins are required for and mediate distinct aspects of IGF-IR-stimulated behaviour. As multiple agents targeting the IGF-IR are currently in early clinical trials, IRS expression should be considered as a potential biomarker for IGF-IR responsiveness.

Molecules with large-amplitude torsional motion partially oriented in a nematic liquid crystal: ethane and isotopomers.

An NMR study on ethane and five isotopomers dissolved in the nematic liquid crystal Merck ZLI 1132 is performed. A consistent set of dipolar and quadrupolar couplings is obtained. The dipolar couplings are corrected for harmonic vibrational effects, while the contribution from the torsional motion is incorporated classically. The corrected dipolar couplings cannot be understood in terms of a reasonable molecular structure unless effects of the reorientation-vibration interaction are taken into account. Assuming that the reorientation-vibration contributions that are known for the methyl group in methyl fluoride are transferable to ethane, excellent agreement between observed and calculated dipolar couplings is obtained on the basis of the ethane gas-phase structure. The observed and calculated deuterium quadrupolar couplings show discrepancies supporting the notion that average electric field gradients are important in liquid-crystal solvents. An important consequence of the transferability of the reorientation-vibration correlation is that in other molecules with a methyl group the same procedure as for ethane can be followed. Inclusion of this effect generally removes the need to interpret changes in observed dipolar couplings in terms of elusive chemical effects.

NMR as a tool in the investigation of fundamental problems in ordered liquids.

An overview is presented of modern NMR techniques and a variety of experimental and theoretical tools employed in the study of solutes dissolved in liquid crystals. The NMR techniques involve multiple quantum and spectral subtraction methods. In addition, various experimental and theoretical tools are discussed, including: the theoretical background of observed order parameters; the use of 'magic mixtures' to separate orientational contributions; the reorientation-vibration interaction; the use of model calculations based on size and shape of the various solutes; and the use of computer simulations. Applications to the benchmark probe molecules hydrogen, methane, ethane, and butane and their isotopomers are treated.

Dynamic polarization in the strong-field ionization of small metal clusters.

We report on the strong field ionization of small transition metal clusters (nickel, Ni(n) n=1-36) within the quasistatic regime at an infrared wavelength of 1.5 microm and at intensities up to 2 x 10(14) W/cm(2). From ion yields in a constant axial intensity beam, we obtained saturation intensities for the individual Ni(n) clusters. As compared to quasistatic, single active electron calculations, a dramatic suppression of ionization was observed. Dynamic polarization in the laser field likely leads to strong multielectron screening of the "active" electron. Representing the metal clusters as classical conducting spheres, we obtained, via a barrier suppression calculation, the classical ionization rates. Agreement was obtained for larger clusters with n>10 when the dynamic polarization was taken into account, emphasizing the multielectron nature of the ionization suppression.

Absolute ionization rates of multielectron transition metal atoms in strong infrared laser fields.

We report on nonresonant strong field ionization of the multielectron transition metal atoms V, Nb, Ta, Ni, and Pd. Operating in the adiabatic regime (lambda = 1.5 microm), we quantitatively determined both (i) the first charge state saturation intensities and (ii) the absolute ionization rates for intensities ranging from threshold up to 3 x 10(14) W/cm2. We observed a dramatic suppression of ionization relative to single active electron approximation expectations. We suggest that this derives from dynamic polarization or screening effects within the multielectron atom, stressing a need for many-body theories of strong field ionization.