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.     

Association of Physical Function and Survival in Older-Adult Renal Transplant Recipients

There is an increase in older-adult renal transplant recipients in United States. The objective of this study was to assess the association between physical function (PF) and patient survival in renal transplant recipients who are aged 65 years or older. Using United Network for Organ Sharing (UNOS) data from 2007 to 2016, renal transplant recipients aged 65 years or older were included. Multivariable Cox regression was used to assess associations between survival and functional status adjusted for age, sex, race, donor quality, diabetes, and dialysis vintage. The study identified 26,721 patients. Patient survival was significantly higher in recipients who needed no assistance and lowest in patients in need of total assistance (P < .0001). In deceased donor (DD) transplants, the relative risk for mortality was 2.06 (1.74-2.43) for total assistance and 1.17 (1.08-1.28) for moderate assistance compared to no assistance (P < .0001). In living donor (LD) transplants, the relative risk of mortality was 1.38 (0.78-2.42) for patients needing total assistance and 1.37 (1.14-1.65) for patients needing moderate assistance compared to patients who did not need assistance (0.003). PF is an independent predictor of post-transplant mortality. Assessment of older potential renal transplant recipients should include assessment and standardization of functional status to counsel about post-transplant survival.     

Research on the Release of Dangerous Compounds from the BTEX and PAHs Groups in Industrial Casting Conditions

The assessment of the harmfulness of moulding and core sands is mainly based on investigations of compositions of gases emitted by liquid casting alloys during the mould pouring. The results of investigations of moulding sands obtained under industrial conditions are presented in this paper. A unique research stand was designed and built for this aim. It allowed us to determine emissions of gases at individual stages of casting a mass up to 50 kg. This approach enables simulation of foundry conditions. Moulding sands bound by organic binders (phenol-formaldehyde; furan), inorganic binders and green sand, were subjected to investigations. The composition of gases that evolved during the individual stages, pouring, cooling and knocking out, was tested each time, and the contents of Polycyclic Aromatic Hydrocarbons (PAHs) and benzene, toluene, ethylbenzene, and xylenes (BETX) were analysed. Investigations indicated that the emission of gases from sands with inorganic binders is negligible when compared with the emission of gases from sands with organic binders. The emission of gases from green sand is placed in the middle of the scale. As an example: the sand with furan resin emitted 84 mg of BTEX (in recalculation for 1 kg of sand) while from sands with inorganic binders there was a maximum of 2.2 mg (for 1 kg of sand). In the case of sands with inorganic binders, MI and MC sands indicated comparable and very low emissions of gases from the PAHs group, at the level of 0.018 mg and 0.019 mg for 1 kg of sand, respectively. The higher emission of PAHs from MG sand is the result of its different way of hardening (a binder was of an organic character) than of sands MI and MC.     

High frequency of macrophages expressing elevated level of CD80, PD-Ls and TLR1 in nasal polyps of CRS patients

Identification of the association between tissue biomarkers, their surrogates in blood and clinical features, could provide new diagnostic tools and facilitate adequate choices of therapeutic interventions for selected patients suffering from CRS. The aim of present study was the assessment of macrophages in the polyp tissue and monocytes in the peripheral blood in the course of CRSwNP, and their functional immunophenotype. We analyzed 31 patients with CRSwNP. Nasal mucosa tissue was obtained via functional endoscopic sinus surgery (FESS). The control group included 10 patients with deviated nasal septum (DNS). Fluorochrome stained cells were proceed to acquisition using FACS Canto flow cytometer, and the results were analyzed using the software FACS Diva. In our study, we observed a significantly higher level of CD80, CD274, CD273 and TLR1 in nasal polyps compared to blood samples from patients with CRSwNP. This finding may suggest the importance of the PD-1 pathway as a therapeutic target in CRS and an important role for TLR1 in nasal polyp formation and maintenance. Our results may provide some insight into potential future targets of recurrent nasal polyp treatment and contribute to a better understanding of the inflammatory process in Chronic Rhinosinusitis.