IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Dating of polyhalite: a difficult 40Ar/39Ar dating tool of diagenetic to very low-grade metamorphic processes.

Halite already deforms at surface temperatures. A valuable universal dating tool to constrain the timing of sedimentary, diagenetic, or deformational structures is still missing. The evaporite mineral polyhalite can be dated by the 40Ar/39Ar method. On the example of the extremely deformed halite deposits of the Eastern Alps, polyhalite was tested to date early diagenetic stages of the deposits. The sedimentological investigation of the present study indicates that some of the macrostructures of polyhalite had a syn-depositional origin during the late Permian. It is supposed that polyhalite originated during reflux of brines. All samples selected for age dating represent characteristic microfabric types of euhedral to subhedral polyhalite crystals. Intact macro- and non-recrystallized looking microstructures of polyhalite can be expected to give plateau ages. However, nearly all measurements produced overdispersed data that do not define an age. The oldest age steps thus represent only minimum ages. A closer look revealed grain boundary migration, subgrain rotation recrystallization, twinning, and fluid-supported grain size increase. These recovery processes obscured the original ages and/or reflect the origin of new polyhalite in place of the original individuals. Based on these microstructures, the age data are supposed to reflect the circulation of aqueous fluids. Just extremely careful separation of individual crystals or in situ age dating under the microscope will be successful in dating polyhalite. Nevertheless, polyhalite can potentially serve to date deformational events of halite deposits due to its easy recrystallization property. Supplementary Information: The online version contains supplementary material available at 10.1007/s00531-022-02219-9.

AEPUS: a tool for the Automated Extraction of Pennation angles in Ultrasound images with low Signal-to-noise ratio for plane-wave imaging.

The penetrating ability of ultrasound (US) com-bined with its real-time operation make it the perfect tool for investigating muscle contraction mechanics during complex functional tasks, e.g., locomotion. Changes in fascicle lengths and pennation angles of muscle fascicles strongly correlate with the capacity of skeletal muscles to produce forces, thereby represent fundamental parameters to be tracked. While the gold standard for extracting these features from US images is still based on manual annotation, the availability of recording devices capable of generating big data of muscle dynamics makes such manual approach unfeasible, setting the need for automated muscle images annotation tools. Existing approaches, however, are seriously limited, also in view of the continuous developments and technology ad-vancements for ultrafast US and plane-wave imaging. In fact, they rely on conventional (slow) B-mode imaging, make use of point tracking approaches (which often fail due to out-of-plane motion), or can only operate on very high quality images. To overcome all these limitations, we present AEPUS, an automated image labeling tool capable of extracting pennation angles from low quality images using a very small number of plane waves, therefore making it capable of exploiting all the benefits of ultrafast US. Clinical Relevance - Ultrasound is a standard research tool to investigate alterations of spastic muscles in children with Cerebral Palsy. We propose a reliable and time-efficient method to track muscle features in ultrasound images and support clinical biomechanists in their analyses.

Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism.

OBJECTIVE: It is suggested that iodide organification defects account for 10% of all cases with congenital hypothyroidism (CH). One candidate gene for these defects is the thyroid peroxidase (TPO) gene. DESIGN: Exons 2, 8-10 and 14 of the TPO gene were examined in 30 patients with permanent CH without a family history of CH. This group was characterized by the presence of an orthotopic thyroid gland and elevated TSH levels. METHODS: The mutational screening was performed by single-strand conformational polymorphism followed by sequence analysis of fragments with abnormal migration patterns and by restriction enzyme analysis. RESULTS: In four patients we were able to identify mutations on both alleles which have not been described so far. One patient was a carrier of a new homozygous point mutation in exon 9 resulting in an exchange from Leu to Pro at codon 458. Another patient was found to be compound heterozygous for two mutations, a 20 bp duplication in exon 2 and a new mutation in exon 9 (Arg491His). Two brothers of consanguineous parents showed a homozygous T deletion in exon 14 at position 2512. CONCLUSIONS: Our findings confirm the genetic heterogeneity of TPO defects and support the suggested prevalence of organification defects.

Addition of nitric oxide to oxygen improves cardiopulmonary function in patients with severe COPD.

STUDY OBJECTIVE: To assess the effect of nitric oxide inhalation on pulmonary hemodynamics and oxygenation in patients with COPD receiving long-term oxygen therapy (LTOT). DESIGN: Prospective study. SETTING: ICU of a university medical center. PATIENTS: A total of 18 (6 female, 12 male) patients with COPD, spontaneously breathing with LTOT. INTERVENTIONS: Oxygenation and hemodynamic variables were measured and calculated at an inspired oxygen fraction (FIO2) adjusted to mimic LTOT conditions (control), and then 1 h after each sequential addition of 5, 10, and 20 ppm nitric oxide to the gas mixture. A newly developed device (Pulmonox) provided both the delivery and continuous analysis of nitric oxide and oxidative nitric oxide products. MEASUREMENTS AND RESULTS: There was a significant improvement in oxygenation at 5 ppm nitric oxide (PaO2/FIO2 ratio improved from 244+/-37 to 303+/-59, p<0.05), but no further improvement at higher doses (ceiling effect). There was a dose-dependent improvement in hemodynamic variables that was maximal at 20 ppm nitric oxide (mean pulmonary artery pressure decreased from 29+/-7 to 24+/-5 mm Hg, pulmonary vascular resistance index decreased from 565+/-321 to 392+/-215 dyne x s x cm(-5) x m(-2), and right ventricular ejection fraction improved from 34+/-6 to 39+/-7%, all p<0.05). CONCLUSION: Prior studies have demonstrated that inhaled nitric oxide may improve or worsen oxygenation in patients with COPD. Our data show an unequivocal improvement in oxygenation (albeit with a ceiling effect at 5 ppm) and pulmonary hemodynamics (dose dependent) in COPD patients receiving LTOT. Further studies are warranted to examine the usefulness of inhaled nitric oxide during acute exacerbations of COPD, or even the possibility of long-term application in patients receiving LTOT.

Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man.

In a randomized, double-blind, placebo-controlled, cross-over study 24 healthy volunteers were examined before and 2 h after oral administration of 80 mg (R,S)-, 40 mg (R)- and 40 mg (S)-propranolol.HCl; 8 of them received placebo in an additional run. During exercise on a bicycle ergometer and a rest period the rate pressure product was decreased by 80 mg (R,S)-propranolol.HCl (-32.8% p less than 0.0001) and 40 mg (S)-propranolol.HCl (-32.3%; p less than 0.0001), whereas 40 mg (R)-propranolol.HCl as well as placebo showed no effect. Corresponding binding inhibition experiments using (-)-(125I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation yielded a eudismic ratio of 179 for (S)- over (R)-propranolol. 2 h after oral application, stereospecific HPLC analysis revealed different individual concentrations in plasma of (R)- 22.3 +/- 21.7 ng/ml) and (S)-propranolol (30.4 +/- 26.9 ng/ml) when 80 mg of (R,S)-propranolol.HCl was administered. The plasma levels were similar when 40 mg of the pure enantiomer of (R)- (22.7 +/- 20.3 ng/ml) or (S)-propranolol.HCl (28.7 +/- 22.5 ng/ml) was applied. (R)- and (S)-propranolol are two substances with different pharmacodynamic and pharmacokinetic properties. As there are methods available to produce the optically pure enantiomers, they should be used rather than the racemic mixture.

Patterns of increased and decreased ingestive behavior after injections of lithium chloride and 2-deoxy-D-glucose.

In previous research, 750 mg/kg 2DG yielded a number of effects suggesting a postdrug nausea; and the present experiments revealed that the illness-inducing agent LiCl similarly produced taste aversion learning at 7.5 mg/kg, inhibited drinking in water-deprived animals at 30 mg/kg, depressed feeding in hungry rats at 60 mg/kg, and evoked food intake and pica at 120 mg/kg. The appearance of eating and pica at the same dosage suggested that rats may eat food as well as a nonnutritive substance as a species-specific reaction to illness and that postdrug feeding, including that observed after 2DG, is an insufficient condition for concluding that a treatment produces no internal distress. A liquid diet that reportedly ameliorates the glucoprivic feeding deficits produced by lateral hypothalamic and zona incerta lesions theoretically could produce its effects if lesions made rats more reactive to 2DG-induced malaise and if this diet were more palatable to animals experiencing internal distress. However, this liquid diet failed to facilitate food intake after LiCl, nor did it reduce the inhibited eating produced by LiCl in food-deprived subjects. Liquid diet effects in lesioned animals, therefore, may not be explained by factors related to a 2DG-induced malaise.

True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene.

A number of genes are known to control the development of the testis but the transcription factor SRY encoded on the Y-chromosome is considered to play the major role in initiating the first step in determining testicular differentiation. Mutations in this gene usually result in gonadal dysgenesis, but it is interesting to note that at least three of these mutations have been found to be familial. Furthermore, fewer than 10% of true hermaphrodites carry an XY karyotype, and so far only two patients have been documented to carry a mutation in the SRY gene. We have identified a familial mutation in the SRY gene involving a previously described locus. The index patient was born with severely ambiguous genitalia and on histological examination the gonads revealed true hermaphroditism, containing ovarian as well as testicular tissue. The father, his three brothers, and his first-born son carry the identical mutation. The severely feminized XY individual was diagnosed shortly after birth, gonadectomized and raised as female. SRY was determined by PCR and subsequently sequenced using cycle sequencing. A previously published point mutation was identified at nucleotide position 680 resulting in a non-conservative exchange of the amino acid iso-leucine at position 90 into methionine. This position represents a mutational 'hot spot', which seems to retain a certain amount of protein activity, enabling normal male development in some individuals. The patient is the third one reported in whom a mutation in the SRY gene results in ovarian-like development. Since ovarian development in XY individuals is extremely rare, its mechanism is of great interest. Further studies in this family might allow the identification of factors initiating and stimulating ovarian development. How far these infantile ovaries would have developed normally, however, is merely speculative.

Rhabdomyosarcoma of the bile ducts.

Rhabdomyosarcoma is a rare malignant neoplasm of the biliary tract. Including all the historical recent probable, and established cases that are carefully classified by Hayes and Synder, only 24 cases have been reported to date. Because of the extreme rarity of this tumor in this location, correct diagnosis was not made until second laparotomy or autopsy in several reported cases. The present report describes a child who recently underwent excision of such a tumor at our institution.

Production of a novel pyranose 2-oxidase by basidiomycete Trametes multicolor.

During a screening for the enzyme pyranose 2-oxidase (P2O) which has a great potential as a biocatalyst for carbohydrate transformations, Trametes multicolor was identified as a promising, not-yet-described producer of this particular enzyme activity. Furthermore, it was found in this screening that the enzyme frequently occurs in basidiomycetes. Intracellular P2O was produced in a growth-associated manner by T. multicolor during growth on various substrates, including mono-, oligo-, and polysaccharides. Highest levels of this enzyme activity were formed when lactose or whey were used as substrates. Peptones from casein and other casein hydrolysates were found to be the most favorable nitrogen sources for the formation of P2O. By applying an appropriate feeding strategy for the substrate lactose, which ensured an elevated concentration of the carbon source during the entire cultivation, levels of P2O activity obtained in laboratory fermentations, as well as the productivity of these bioprocess experiments, could be enhanced more than 2.5-fold.

Death certification in patients whose primary treatment for oral and oropharyngeal carcinoma was operation: 1992-1997.

The aim of this study was to report the cause and place of death of patients with oral cancer as recorded by death certification and their survival with regard to comorbidity and age. From the departmental head and neck oncology database, 322 patients were identified with previously untreated oral and oropharyngeal squamous cell carcinoma diagnosed between 1992 and 1997 inclusive. Three-hundred were matched with the Office for National Statistics (ONS) and copies of death certificates generated on 6 March 1999. Of the 286 patients primarily treated by operation, 203 were alive and 83 had died. In 56 (68%), oral cancer was a contributory factor to the patient's death. Patients with a medical history recorded on their admission for operation had similar survival curves compared to those having no problems recorded. Although most patients (n= 46 55%) died in hospital, only 13 (16%) died in the Regional Maxillofacial Unit. Almost half of those patients who died were not recorded as dead on the departmental oncology database. This study shows that it is useful to link with the ONS to obtain accurate data on date and place of death. The death certificate also gives a useful indication of the cause of death and this seems unrelated to preoperative comorbidity.

Origin of deformed halite hopper crystals, pseudomorphic anhydrite cubes and polyhalite in Alpine evaporites (Austria, Germany).

The Alpine Haselgebirge Formation represents an Upper Permian to Lower Triassic evaporitic rift succession of the Northern Calcareous Alps (Eastern Alps). Although the rocksalt body deposits are highly tectonised, consisting mainly of protocataclasites and mylonites of halite and mudrock, the early diagenetic history can be established from non-tectonised mudrock bodies: Cm-sized euhedral halite hopper crystals formed as displacive cubes within mud just during shallow burial. The crystals were deformed by subsequent compaction. Later, migrating fluids led to the replacement of halite by anhydrite retaining the shapes of deformed halite cubes. Polyhalite formed from subsequent enhanced fluid migration. Mudrock provided water by dewatering, while potassium and magnesium were dissolved from primary salt minerals. When these fluids interacted with sulphates, polyhalite precipitated. 40Ar/39Ar analyses date the polyhalite from within the retaining shapes of deformed halite hopper-shaped cubes from two localities to ca. 235-232 Ma (Middle Triassic). At this time, ca. 20-25 Ma after sedimentation, polyhalite crystallised at shallow levels.

Reliability of posturographic measurements in the assessment of impaired sensorimotor function in chronic low back pain.

UNLABELLED: The evaluation of postural stability using posturography could be both a valuable functional diagnostic and treatment outcome monitoring tool in rehabilitation practice of patients with chronic low back pain (cLBP). No evidence, however, seems to exist, whether or not such posturographic measures are reliable in these patients and therefore clinically and scientifically useful. The aims of this study were manifold and aimed at investigating (1) differences of posturographic measures between cLBP patients and healthy controls (HCs), (2) short- (intrasession-) and long-term (intersession-) reliability of these measurements, and (3) the relationship between both pain intensity and test-related feelings and significant learning effects of the posturographic measures in cLBP. A total of 32 cLBP patients and 19 non-sportive HCs completed (1) comprehensive clinical examination, (2) quantitative posturographic testing (SMART EquiTest, Neurocom International, Clackamas, Oregon) that included all the sensory organisation test (SOT), the motor control test (MCT) and the adaptation test (ADT) and (3) psychological ratings of pain as well as posturographic test related personal feelings and fear associated beliefs. Of these, 22 cLBP patients who received no therapy repeated all measurements and examinations on a second day, 2-3 weeks later. Results revealed significant differences between cLBP patients and HCs in the more demanding postural test conditions of the SOT and the SOT composite score only. Intra-session reliability testing demonstrated significant improvements of the SOT and ADT measures for both HCs and cLBP patients. Results of long-term reliability testing showed significant improvements of the more challenging SOT conditions and SOT composite score. VAS ratings of pain, feelings and fear associated beliefs were not associated with such longitudinal changes. CONCLUSION: Our findings suggest that the significant learning effects observed for the SOT conditions may limit the clinical application of SMART EquiTest postural stability measures for cLBP patients in rehabilitation everyday practice. Further development in software processing will be necessary to identify new postural parameters that are less prone to learning effects.

[Does virus diagnosis open new ways for the classification and treatment of sudden deafness, unilateral vestibular loss and idiopathic facial paralysis?]. / Eröffnet die Virusdiagnostik neue Wege für die Zuordnung und Behandlung des Hörsturzes, des einseitigen isolierten Vestibularisausfalles sowie der idiopathischen Facialisparese?

Paired sera from 51 patients with sudden deafness, 21 patients with acute vestibular loss and 28 patients with Bell's palsy were examined for antibodies against mumps-, echo-, herpes simplex- and coxsackie viruses. Only two serum samples showed a significant titer increase or decrease. So viral etiology of sudden deafness, acute vestibular loss and Bell's palsy seems to be unlikely and does not change the assignment and therapy of this disease.

[Transient, direction changing spontaneous and provocation nystagmus in the course of visceral lupus erythematosus]. / Flüchtiger, richtungswechselnder Spontan- und Provokationsnystagmus im Verlaufe eines Lupus erythematodes visceralis.

Vestibule dizziness in the course of Lupus erythematodes visceralis has not been investigated to any depth up until now. The observation of a transient, directional changing spontaneous and provoked nystagmus during an acute phase of the disease indicates that homogeneous short episodes of dizziness are probably not so rare, but the vestibular symptom, which possibly may be objectified only by Frenzel glasses examination, becomes not realized or disregarded. Pathogenesis and formanalysis of nystagmus are discussed.

[Differential diagnosis of tumor-like changes in the external ear]. / Zur Differentialdiagnose tumorförmiger Ohrmuschelveränderungen.

Tumor-shaped auricular affections are rare. Usually the case history is little abounding, the symptoms are trifling in contrast to the local findings and the etiology is frequently settled in the borderdistrict to the internal medicine, the dermatology and the neurology. Therefore differential diagnosis can meet with difficulties. Basic on a relevant observation indications are given of the delimitation of such tumor-shaped auricular affections from each other.

Purification and characterization of pyranose oxidase from the white rot fungus Trametes multicolor.

We purified an intracellular pyranose oxidase from mycelial extracts of the white rot fungus Trametes multicolor by using ammonium sulfate fractionation, hydrophobic interaction, ion-exchange chromatography, and gel filtration. The native enzyme has a molecular mass of 270 kDa as determined by equilibrium ultracentrifugation and is composed of four identical 68-kDa subunits as determined by matrix-assisted laser desorption ionization mass spectrometry. Each subunit contains one covalently bound flavin adenine dinucleotide as its prosthetic group. The enzyme oxidizes several aldopyranoses specifically at position C-2, and its preferred electron donor substrates are D-glucose, D-xylose, and L-sorbose. During this oxidation reaction electrons are transferred to oxygen, yielding hydrogen peroxide. In addition, the enzyme catalyzes the two-electron reduction of 1,4-benzoquinone, several substituted benzoquinones, and 2,6-dichloroindophenol, as well as the one-electron reduction of the ABTS [2,2'-azinobis(3-ethylbenzthiazolinesulfonic acid)] cation radical. As judged by the catalytic efficiencies (k(cat)/K(m)), some of these quinone electron acceptors are much better substrates for pyranose oxidase than oxygen. The optimum pH of the pyranose oxidase-catalyzed reaction depends strongly on the electron acceptor employed and varies from 4 to 8. It has been proposed that the main metabolic function of pyranose oxidase is as a constituent of the ligninolytic system of white rot fungi that provides peroxidases with H(2)O(2). An additional function could be reduction of quinones, key intermediates that are formed during mineralization of lignin.

Early detection of anastomotic leaks after low anterior resection of the rectum.

PURPOSE: Lysozyme destroys the mucopolysaccharide chains of the cell wall of gram-negative bacteria. It is a component of local defense and is formed in macrophages. Determination of lysozyme content in the wound seems to be the most reliable method for early recognition of wound infection. METHODS: In a prospective randomized study on the efficacy of single vs. double staple technique in anterior rectum resection, the effluent from the pelvic drain was examined with regard to its lysozyme activity. RESULTS: Lysozyme activity in drained secretion remained stable for more than 24 hours at room temperature. When the single staple technique was used, enzyme activity was sharply increased (mean, 9.6 mg/dl on the first postoperative day) compared with the double staple technique (mean, 5.5 mg/dl on the first postoperative day). The difference was statistically significant (P < 0.0001). Mean lysozyme activity was increased in those patients with clinically (18 mg/dl on the first postoperative day) and radiologically (15.3 mg/dl on the first postoperative day) detected dehiscence (P < 0.0001). CONCLUSION: Lysozyme determination may be reproduced by detection of enzyme stability in drained secretion. Determination of lysozyme content seems to be a new possibility for early recognition of anastomotic dehiscence.