Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

Detailed pathological changes of human lumbar facet joints L1–L5 in elderly individuals

Facet joints play an important role in intervertebral load transmission and are crucial for rotational kinematics. Clinically, the role of facet joints as a possible source of low back pain is seen as controversial and at present is not sufficiently investigated. In this study, human lumbar facet (zygapopyhysial) joints from donors with advanced age were analyzed macroscopically, for degenerative changes. The aim was to determine the extent and morphology of degenerative changes in these joints. Lumbar facet joints (L1–L5) of 32 donors were studied (mean age 80.1±11.2 years). Joint capsules were carefully removed and joint surfaces (5 zones) examined using magnifying glasses and probes. In the result, the majority of facet joints showed cartilage defects of varying extent. Defects were located mostly at the margins of the articular surface, the central zone being relatively well preserved. Defect localization was different between superior (most cartilage defects in superior zone) and inferior (most defects inferiorly) facets. Further, defects were more severe caudal (level of L5) and in older persons. Osteophytes were present in up to 30%, located mostly at the latero-dorsal enthesis of the joint capsule on the superior facet. In conclusion, most margins of the articular facets are subject to degenerative changes in the lumbar spine of elderly persons, the topographical pattern being different in superior and inferior facets. This observation can be explained by the segmental motion patterns during extension/flexion movements of the facets. Sometimes, due to the marginal extension, it is obvious that not all changes can be assessed by CT or MRI.     

Die Aufklärungspflicht bei endoskopischen Operationen

Ohne Zusammenfassung     

Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia

Background  

While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality.     

Unilateral neglect: further validation of the baking tray task.

OBJECTIVE: The Baking Tray Task is a comprehensible, simple-to-perform test for use in assessing unilateral neglect. The aim of this study was to validate further its use with stroke patients. METHODS: The Baking Tray Task was compared with 2 versions of the Behaviour Inattention Test and a test for personal neglect. A total of 270 patients were subjected to a 3-item version of the Behaviour Inattention Test and 40 patients were subjected to an 8-item version of the Behaviour Inattention Test, besides the Baking Tray Task and the personal neglect test. RESULTS: The Baking Tray Task was more sensitive than the 3-item Behaviour Inattention Test, but the 8-item Behaviour Inattention Test was more sensitive than the Baking Tray Task. The best combination of any 3 tests was Baking Tray Task, Reading an article, and Figure copying; the 2 last-mentioned being a part of the 8-item Behaviour Inattention Test. CONCLUSION: Multi-item tests detect more cases of neglect than do single tests. However, it is tiresome for the patient to undergo a larger test battery than necessary. It is also time-consuming for the staff. Behavioural tests seem more appropriate when assessing neglect. The Baking Tray Task seems to be one of the most sensitive single tests, but its sensitivity can be further enhanced when it is used in combination with other tests.     

Tibial fractures following Maquet's tuberosity advancement. Apropos of 2 clinical case reports

Although accustomed to using the Maquet tibial tuberosity advancement, the authors had two similar and rare complications in which a fracture of the tibial shaft occurred at the end of the vertical osteotomy. Both incidents arose from a mechanical incision effect. This can be prevented by making a larger circular hole in the distal portion of the osteotomy.     

The course of the superficial temporal artery. Anatomic studies as a prerequisite to arterial biopsy

The superficial temporal artery, together with its branches, was dissected in 161 half-heads, and the course of these vessels mapped against a newly-developed grid which can be adapted to conform to the proportions of each individual skull. The practical aim of this investigation was to establish the position of that incision which has the highest probability of being well-placed for taking a biopsy from the frontal branch of the artery. In 86.3% of the authors' specimens it was possible to reach this vessel through a 2.5 cm incision running up-ward and posteriorward at an angle of 45 degrees to the "upper horizontal line" from a point 1-1.5 cm behind the intersection of this line with the "lateral border of the orbit". The commonest type of ramification, with two terminal branches, was found in 94.6% of the specimens. Type 2 (with three terminal branches) occurred in 2.5% and Type 3 (with a single terminal branch) also in 2.5% of the cases. The level of the bifurcation of the superficial temporal artery varied between a point 2 cm below the "German horizontal line" and a second point 2 cm above the "upper horizontal line". The main trunk of the vessel was found to make an angle of 82.2 degrees with the "German horizontal line", its frontal branch running upward and anteriorward at an angle of 40 degrees to this line.     

An azurocidin-like protein is induced in Trichoplusia ni larval gut cells after bacterial challenge

Trichoplusia ni immune genes up-regulated in response to bacterial infection have been isolated using differential display polymerase chain reaction. Here we report the cloning and characterisation of a gut-specific immune gene encoding an azurocidin-like protein. The deduced protein is 317 amino acid residues long with a hydrophobic C-terminus and a predicted 17-residue signal peptide. The mature T. ni protein shows 30% identity to human azurocidin, an antibacterial protein. Like azurocidin, the T. ni protein contains two amino acid substitutions in the active site triad normally present in serine proteases. The T. ni protein was synthesised with a six-histidine C-terminal extension using the baculovirus expression system. Sequencing of the recombinant azurocidin-like protein confirmed the predicted cleavage of the signal peptide. Northern blots show that T. ni azurocidin-like protein is expressed solely in the larval gut and that expression is up-regulated by injecting or feeding bacteria. Expression reaches its highest level at 10 h after bacteria injection.