[Interdisciplinary surgery to the central skull base-current status]. / Interdisziplinäre Chirurgie der zentralen Schädelbasis ­ aktueller Stand.

BACKGROUND: The skull base is a surgically complex unit and is often only accessible via combined access routes. Newly developed surgical techniques using microsurgical visualization procedures and active instruments ("powered instruments") as well as multiport accesses enable new, less traumatic surgical corridors. This requires close interdisciplinary cooperation between ENT and neurosurgeons. Currently established access routes to the central skull base are systematized based on the authors' own clinical experience, and discussed in relation to the entity and the current study situation. MATERIALS AND METHODS: A retrospective, qualitative, and descriptive evaluation of the surgical reports of patients with pathologies of the central skull base who were jointly treated by neurosurgery and otorhinolaryngologic/head and neck surgery between 2006 and 2019 was performed. RESULTS: The surgical access routes to the central skull base can be categorized as so-called multiport access routes, partly also in combination, as follows: transnasal-transsphenoidal, subfrontal, subtemporal, transzygomatic, transpterygonal, transpetrous, translabyrinthine, and suboccipital. The choice of access route was based on the location and type of pathology, its inflammatory or space-occupying (benign or malignant tumor) nature, and the possibilities of functional preservation and complete removal. CONCLUSION: Due to the complexity of central skull base structures, the different tumor entities, and the required expertise of different medical specialties, surgery of the central skull base remains a challenge and should only be performed at special competence centers certified according to the criteria of the German Society of Skull Base Surgery.

[Cochlear nerve continuity preservation during retrosigmoid ablative osteotomy of the internal auditory canal for advanced vestibular schwannomas]. / Kontinuitätserhalt des Nervus cochlearis bei der retrosigmoidalen ablativen Osteotomie des inneren Gehörgangs bei fortgeschrittenen Vestibularisschwannomen.

The data of 86 patients with retrosigmoid microsurgical resection of vestibular schwannoma in tumor stage Koos II-IV were evaluated. In more than two thirds of the cases it was shown that the cochlear nerve followed the facial nerve, which is easily identified by electroneurography, in recurrent similar patterns in the region of the internal auditory canal. Starting from the fundus, this facilitated early identification and thus preservation of continuity of the cochlear nerve in the course of the internal auditory canal. This was of particular importance when safe functional preservation could not be guaranteed due to tumor size or formation despite intraoperative derivation of somatosenoric potentials, but when the possibility of subsequent hearing rehabilitation with a cochlear implant should be granted. Preoperative MRI sequences gave an indication of the possible nerve courses in some cases, but intraoperative imaging in the internal auditory canal was superior to MRI.

Effect of feeding histidine and ß-alanine on carnosine concentration, growth performance, and meat quality of broiler chickens.

The high growth rates of modern broiler breeds increased the risk for novel breast muscle myopathies as serious quality issue, relevant for the industry. In affected muscles, a depletion of the dipeptides carnosine and anserine was reported. Therefore, this study was performed to test whether a supplementation of the precursors histidine and ß-alanine, alone or in combination can increase the dipeptide content in the breast muscle and improve meat quality. Ross 308 broiler chickens were supplemented with 3 different histidine:lysine ratios (0.44, 0.54, 0.64) of standardized ileal digestible amino acids (SID) combined with 0 or 0.5% ß-alanine in total. The birds' performance was recorded at different ages: birds were slaughtered in 2 batches after 33 and 53 d of life. Meat quality was tested at different time points after slaughter on breast fillets stored aerobically. The concentration of the dipeptides and amino acids in blood plasma and muscle tissue was tested postmortem at 35 and 54 d. All performance and meat quality data, as well as peptide and amino acid concentrations, of the 2 × 2 × 3 randomized block design were analyzed separately for the influence of both supplements and for slaughter age. Moreover, the influence of storage time was analyzed separately for meat quality parameters. At both slaughter ages, lesser feed intake (P ≤ 0.005) and breast yield (P ≤ 0.05) were observed in the birds receiving ß-alanine. A greater SID histidine:lysine ratio increased the carnosine concentrations in blood plasma (P < 0.001) and in skeletal muscle (P < 0.001), whereas ß-alanine increased carnosine in plasma at 35 d only (P = 0.004). Anserine was increased in plasma and muscle of older birds (P = 0.003), whereas carnosine was reduced in muscle tissue (P < 0.001). The main impact on meat quality parameters was seen for the age of the birds and storage time of the fillets. In conclusion, the supplementation of histidine increased carnosine in breast muscle but both supplements showed only minor effects on meat quality.

Ganglioneuroma suprarrenal gigante: Reporte de Un caso

Resumen El ganglioneuroma (Gn) es una neoplasia benigna, rara, derivada de la cresta neural, compuesta de células ganglionares maduras y células de Schwann. Solo una pequeña proporción de Gn se origina en la médula suprarrenal, siendo esta localización más frecuente en niños y adultos jóvenes. Hemos encontrado menos de 30 publicaciones reportadas en la literatura. Presentamos el caso de una paciente femenina de 37 años de edad, con dolor intermitente en fosa renal izquierda y flanco ipsilateral de 5 meses de evolución, sin otros síntomas acompañantes. Se realizó ecografía abdominal, tomografía axial computada (TAC) y resonancia magnética nuclear (RMI) abdomino pélvica, en las cuales se identificó formación expansiva solida, de 85 x 58 x 74 mm, de contornos definidos, adyacente a riñón izquierdo. Las características por imagen no permitieron descartar lesión benigna. Se realizó perfil hormonal completo para despistaje de funcionalidad. Dadas las características imagenológicas y el tamaño de la lesión, se decide tratamiento quirúrgico, considerando a feocromocitoma silente como principal diagnóstico presuntivo pre quirúrgico. La evolución postoperatoria fue excelente. Al examen microscópico, se observa proliferación nodular, de bordes delimitados, formado por células fusadas, con núcleos bipolares y citoplasmas elongados con aisladas células ganglionares. En la inmunomarcación presenta aisladas células ganglionares positivas para Cromogranina A y Sinaptofisina, proteína S100 positivo difuso, hallazgos consistentes con ganglioneuroma suprarrenal. El hallazgo de una masa suprarrenal en paciente joven, sin síntomas específicos, con características no sugestivas de adenoma, debe considerar el diagnostico de ganglioneuroma como parte de las lesiones incidentales adrenales y destacamos la importancia del diagnostico diferencial con feocromocitoma y carcinoma adrenal ya que comparten similares características imagenológicas. El tratamiento de elección es la resección quirúrgica completa, con pronóstico excelente en la mayoría de los casos.

Lepra histioide o de Wade: Presentación de un caso clínico / Wade histioid leprosy: A case report

La lepra histioide de Wade, es una forma clínico-histopatológica especial de lepra multibacilar, caracterizada por la presencia de tubérculos (lesiones papulosas o nodulares) correspondientes a lepromas formados por histiocitos de morfología fusiforme. La misma es una variante infrecuente de lepra lepromatosa, que se desarrolla generalmente como recaída, en pacientes que recibieron monoterapia con dapsona, aunque se reportó su presentación de novo. En el presente trabajo, se comunica el caso clínico de una paciente de sexo femenino de 45 años de edad, con diagnóstico tardío de lepra histioide. Además, se examinan las características principales de esta forma particular de expresión de la lepra, sus diferencias con la forma clásica de presentación, los diagnósticos diferenciales que deben considerarse y la importancia de tener a esta patología entre las sospechas diagnósticas, para comenzar el tratamiento adecuado y evitar su propagación.

Wade's hystioid leprosy is a special clinical-pathological form of multibacillary leprosy, characterized by papular and nodular lepromas that consist of spindle histiocytes. It is a variant of lepromatous leprosy. Most of the cases have been related to dapsone resistance in the context of longterm monotherapy. De novo cases, not associated with previous anti-leprosy treatment, have been less frequently reported. This article presents the case of 45 years old female, with late diagnosis of histoid leprosy. There will be explained the main features of this particular form of leprosy, its differences with the classic presentation, the differential diagnoses to be considered, and the importance of having this pathology among diagnostic suspicions to begin adecuate treatment.

EPSPS variability, gene expression, and enzymatic activity in glyphosate-resistant biotypes of Digitaria insularis.

Weed resistance to herbicides is a natural phenomenon that exerts selection on individuals in a population. In Brazil, glyphosate resistance was recently detected in Digitaria insularis. The objective of this study was to elucidate mechanisms of weed resistance in this plant, including genetic variability, allelism, amino acid substitutions, gene expression, and enzymatic activity levels. Most of these have not previously been studied in this species. D. insularis DNA sequences were used to analyze genetic variability. cDNA from resistant and susceptible plants was used to identify mutations, alleles, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) expression, using real-time quantitative reverse transcription-polymerase chain reaction. In addition, EPSPS activity was measured. We found a decrease in genetic variability between populations related to glyphosate application. Substitutions from proline to threonine and tyrosine to cysteine led to a decrease in EPSPS affinity for the glyphosate. In addition, the EPSPS enzymatic activity was slightly higher in resistant plants, whereas EPSPS gene expression was almost identical in both biotypes, suggesting feedback regulation at different levels. To conclude, our results suggest new molecular mechanisms used by D. insularis to increase glyphosate resistance.

5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress.

Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. Similarly, the 5-HT1A receptor-mediated inhibition of evoked inhibitory postsynaptic currents (IPSCs) of granule cells was only reduced in single stress exposed animals. This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.

Impact of gas formation kinetics on dough development and bread quality.

The baking performance and gas retention capacity of wheat dough depends on production rate and total volume of CO2 during fermentation. This study aims to examine the effect of the CO2 formation kinetics and the gas volume fraction on the structural integrity of wheat dough and the resulting bread quality. The gas release characteristics were evaluated using a rheofermentometer with varied concentrations of compressed yeast and instant dry yeast (CY and IDY respectively). For this purpose, the maximum CO2 formation rate was calculated through the derivation of hydrostatic pressure curves measured in the rheofermentometer. For CY, the time when gas escapes the dough matrix (Tx, time of porosity) as well as the corresponding gas volume depended on the gas formation rate, whereas the gas retention capacity of wheat dough leavened with IDY was not affected by the CO2 formation rate. Although the dough leavened with IDY showed improved extensibility during fermentation, the specific bread volume was 21% below that of the samples leavened with CY. These results indicate that an increase in the maximum gas formation rate considerably affects the structural integrity of the dough matrix. Because of the reduction of the loaf volume, the effect is reinforced by the application of IDY.

The contribution of glutathione to the destabilizing effect of yeast on wheat dough.

Any factor which impairs the development of the gluten network affects the gas retention capacity and the overall baking performance. This study aimed to examine why rising yeast concentrations (Saccharomyces cerevisiae) decrease the dough elasticity in an asymptotic manner. Since in 27 commercial fresh and dry yeasts up to 81 mg glutathione (GSH) per 1g dry sample were found. Through the addition of reduced GSH in dough without yeast, the extent of dough weakening was analysed. Indeed rheological measurements confirmed that yeast-equivalent levels of GSH had a softening effect and during 3h fermentation the weakening coefficient increased from 0.3% to 20.4% in a Rheofermentometer. The present results indicate that free -SH compounds, as represented by GSH, considerably contribute to the softening of dough through dead yeast cells.

Glioblastoma tumor initiating cells: therapeutic strategies targeting apoptosis and microRNA pathways.

Glioblastoma (GBM) is a highly malignant primary brain tumor known for its invasiveness and aggressive resistance to standard treatment. It is currently the most common primary brain tumor which is associated with a high mortality rate. Tumor initiating cells (TICs) are a subpopulation of GBM stem cells which are capable of self-renewal and apoptotic resistance, and are thought to account for GBMs aggressive nature. Recent efforts have focused on therapies which target key intracellular apoptotic pathways which may confer tumor resistance, such as Akt, p53, Bcl-2 family proteins, caspase family proteases, and more recently microRNAs. Research into microRNA's role in GBM has shown that microRNAs play a key regulatory role in the GBM apoptotic pathway, making it a potential therapeutic target. In this review we summarized the molecular mechanisms involved in the signaling pathways of human GBM TIC apoptosis and microRNAs, the contemporary treatments involving different members of the signaling cascade, and the future direction of GBM treatment strategies.

Approximating the set of local minima in partial RNA folding landscapes.

MOTIVATION: We study a stochastic method for approximating the set of local minima in partial RNA folding landscapes associated with a bounded-distance neighbourhood of folding conformations. The conformations are limited to RNA secondary structures without pseudoknots. The method aims at exploring partial energy landscapes pL induced by folding simulations and their underlying neighbourhood relations. It combines an approximation of the number of local optima devised by Garnier and Kallel (2002) with a run-time estimation for identifying sets of local optima established by Reeves and Eremeev (2004). RESULTS: The method is tested on nine sequences of length between 50 nt and 400 nt, which allows us to compare the results with data generated by RNAsubopt and subsequent barrier tree calculations. On the nine sequences, the method captures on average 92% of local minima with settings designed for a target of 95%. The run-time of the heuristic can be estimated by O(n(2)Dνlnν), where n is the sequence length, ν is the number of local minima in the partial landscape pL under consideration and D is the maximum number of steepest descent steps in attraction basins associated with pL.

Sources and significance of variation in the dose estimates of 36Cl biosphere transfer models: a model intercomparison study.

A range of performance assessments have indicated that the long-lived activation product (36)Cl will be among the more significant contributors to dose following release to the biosphere from deep or near-surface repositories for radioactive wastes. Described here are results of a BIOPROTA model intercomparison study, investigating dose assessment uncertainties and variability on the basis of six (36)Cl models from three countries. The models share a compartmental approach with transfers between compartments handled on the basis of empirical transfer factors (IMARC, ERB2A, Aquabios), on the basis of defined specific activities (AquaCl36, SA_36Cl), or on a combination of these methods (MTA_Cl36). The dose estimates that these models produce for a consensus well-water irrigation scenario, as well as the effect of altering certain critical assumptions, are reported, and the causes of variation examined. For the scenario considered, the calculated doses are within a factor of 15 of each other. Major differences were attributable to the data used for stable Cl concentrations and (36)Cl transfer parameter values, both typically site-specific parameters. Additional critical assumptions were studied such as the impact of stable chloride in the diet on dose coefficients, the effect of irrigating pasture with contaminated water on (36)Cl concentrations in animal products, and the explicit consideration of foliar uptake.

[The QuIK-Registry of the German Society of Cardiologists in private practice: countrywide and benchmarking quality assurance in invasive cardiology]. / Das QuIK-Register des Bundesverbands Niedergelassener Kardiologen. Flächendeckende vergleichende Qualitätssicherung in der Invasivkardiologie.

QuIK is the German acronym for QUality Assurance in Invasive Cardiology. It describes the continuous project of an electronic data collection in Cardiac catheterization laboratories all over Germany. Mainly members of the German Society of Cardiologists in Private Practice (BNK) participate in this computer based project. Since 1996 data of diagnostic and interventional procedures are collected and send to a registry-center where a regular benchmarking analysis of the results is performed. Part of the project is a yearly auditing process including an on-site visit to the cath lab to guarantee for the reliability of information collected. Since 1996 about one million procedures have been documented.

Population-based local search for protein folding simulation in the MJ energy model and cubic lattices.

We present experimental results on benchmark problems in 3D cubic lattice structures with the Miyazawa-Jernigan energy function for two local search procedures that utilise the pull-move set: (i) population-based local search (PLS) that traverses the energy landscape with greedy steps towards (potential) local minima followed by upward steps up to a certain level of the objective function; (ii) simulated annealing with a logarithmic cooling schedule (LSA). The parameter settings for PLS are derived from short LSA-runs executed in pre-processing and the procedure utilises tabu lists generated for each member of the population. In terms of the total number of energy function evaluations both methods perform equally well, however, PLS has the potential of being parallelised with an expected speed-up in the region of the population size. Furthermore, both methods require a significant smaller number of function evaluations when compared to Monte Carlo simulations with kink-jump moves.

Stochastic protein folding simulation in the three-dimensional HP-model.

We present results from three-dimensional protein folding simulations in the HP-model on ten benchmark problems. The simulations are executed by a simulated annealing-based algorithm with a time-dependent cooling schedule. The neighbourhood relation is determined by the pull-move set. The results provide experimental evidence that the maximum depth D of local minima of the underlying energy landscape can be upper bounded by D

Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT).

The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon-carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI)> or = 3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.