Genome-Wide DNA Methylation Profiling as a Prognostic Marker in Pituitary Adenomas-A Pilot Study.

BACKGROUND: The prediction of the regrowth potential of pituitary adenomas after surgery is challenging. The genome-wide DNA methylation profiling of pituitary adenomas may separate adenomas into distinct methylation classes corresponding to histology-based subtypes. Specific genes and differentially methylated probes involving regrowth have been proposed, but no study has linked this epigenetic variance with regrowth potential and the clinical heterogeneity of nonfunctioning pituitary adenomas. This study aimed to investigate whether DNA methylation profiling can be useful as a clinical prognostic marker. METHODS: A DNA methylation analysis by Illumina's MethylationEPIC array was performed on 54 pituitary macroadenomas from patients who underwent transsphenoidal surgery during 2007-2017. Twelve patients were excluded due to an incomplete postoperative follow-up, degenerated biobank-stored tissue, or low DNA methylation quality. For the quantitative measurement of the tumor regrowth rate, we conducted a 3D volumetric analysis of tumor remnant volume via annual magnetic resonance imaging. A linear mixed effects model was used to examine whether different DNA methylation clusters had different regrowth patterns. RESULTS: The DNA methylation profiling of 42 tissue samples showed robust DNA methylation clusters, comparable with previous findings. The subgroup of 33 nonfunctioning pituitary adenomas of an SF1-lineage showed five subclusters with an approximately unbiased score of 86%. There were no overall statistically significant differences when comparing hazard ratios for regrowth of 100%, 50%, or 0%. Despite this, plots of correlated survival estimates suggested higher regrowth rates for some clusters. The mixed effects model of accumulated regrowth similarly showed tendencies toward an association between specific DNA methylation clusters and regrowth potential. CONCLUSION: The DNA methylation profiling of nonfunctioning pituitary adenomas may potentially identify adenomas with increased growth and recurrence potential. Larger validation studies are needed to confirm the findings from this explorative pilot study.

Effect of flow fluctuation on water pollution in drinking water distribution systems.

The detachment of biofilm caused by changes in hydraulic conditions is an essential reason for the pollution of water in the drinking water distribution system (DWDS). In this research, the effect of flow fluctuation on bulk water quality was studied. The turbidity, iron concentration, manganese concentration, the total number of bacteria, biodegradable dissolved organic carbon (BDOC), bacterial community structure, and pathogenic genes in bacteria of bulk water were analyzed. The results indicate that the detachment of biofilm caused by fluctuant flow and reverse flow (especially instant reverse flow) can lead to the pollution of water. Throughout the entire experimental period, the turbidity under fluctuant flow velocity is 4.92%∼49.44% higher than that under other flow velocities. BDOC concentration is 5.68%∼53.99% higher than that under low and high flow velocities. The flow fluctuation increases bacterial regrowth potential (BRP) and reduces the biological stability of the bulk water. Low flow velocity is more conducive to the expression of pathogenic functional genes. In the short term, the water quality under low flow velocity is the best. Nevertheless, in a long-term operation (about seven days later), the water quality under high flow velocity is better than that under other flow velocities. This research brings new knowledge about the fluctuant hydraulic conditions on the bulk water quality within the DWDS and provides data support for stable drinking water distribution.

Comparison between ferrihydrite adsorption and full-scale advanced drinking water treatment processes for controlling bacterial regrowth potential.

Bacterial regrowth in drinking water systems is a threat to public health. In this study, ferrihydrite (Fh) adsorption was compared with advanced drinking water treatment processes (ADWTP) during one and a half years of sampling to test the reduction in assimilable organic carbon (AOC) and bacterial regrowth potential (BRP). Dissolved organic matter (DOM) was removed by Fh through ligand exchange and electrostatic interaction. The DOM removal was higher below pH 6 due to protonation of Fh surfaces. The ADWTP exhibited higher removal rates of DOM than Fh and lower phosphate removal rates than Fh. Excitation-emission matrix (EEM) and size exclusion chromatography (SEC) revealed that Fh removed aromatic DOM larger than 1000 Da, while the biological activated carbon (BAC) of ADWTP could remove DOM smaller than 1000 Da. These differences of organic compositions resulted in the lowest AOC of BAC treated water, and the lowest BRP of Fh-treated water, indicating that it was the most biostable water. Phosphate addition experiments illustrated that phosphorus was the primary rate limiting nutrient, indicating that the higher phosphate removal of Fh made it possible to produce waters with lower BRP than ADWTP. Therefore, BRP is considered to be a better indicator of bacterial regrowth than AOC when phosphorus is a rate-limiting nutrient, as is the case with the Fh treatment.

Exploring the biological stability situation of a full scale water distribution system in south China by three biological stability evaluation methods.

Bacterial regrowth especially opportunistic pathogens regrowth and contamination in drinking water distribution systems (DWDS) have become an emerging threat to public health in the whole world. To explore bacterial regrowth and biological stability, assimilable organic carbon (AOC), biodegradable dissolved organic carbon (BDOC) and bacterial regrowth potential (BRP) were evaluated in a full scale DWDS and bench tests in South China. A significant correlation between BRP and AOC in both water treatment processes (WTP) and DWDS was obtained. For BRP and BDOC, the correlation was more significant in WTP than in DWDS. Both AOC and BRP were significantly correlated with UV254, total organic carbon (TOC), and heterotrophic plate count (HPC) (p < 0.01), whereas BDOC was only significantly associated with UV254, temperature and chlorine residual (p < 0.01). Through a bench test, when chlorine was higher than 0.5 mg/L, the HPC level was low and AOC concentration almost unchanged. On contrary the HPC level increased quickly and declined slightly, with chlorine lower than 0.15 mg/L, which was in accordance with the large amount of biological stability data obtained from DWDS. Through another bench test, the HPC level was positively correlated to AOC concentration and when AOC was below 135 µg/L, the growth rate of HPC was low, which was verified by the analysis of biological stability data from DWDS.

Assessing microbiological water quality in drinking water distribution systems with disinfectant residual using flow cytometry.

Flow cytometry (FCM) as a diagnostic tool for enumeration and characterization of microorganisms is rapidly gaining popularity and is increasingly applied in the water industry. In this study we applied the method to obtain a better understanding of total and intact cell concentrations in three different drinking water distribution systems (one using chlorine and two using chloramines as secondary disinfectants). Chloramine tended to result in lower proportions of intact cells than chlorine over a wider residual range, in agreement with existing knowledge that chloramine suppresses regrowth more efficiently. For chlorinated systems, free chlorine concentrations above 0.5 mg L(-1) were found to be associated with relatively low proportions of intact cells, whereas lower disinfectant levels could result in substantially higher percentages of intact cells. The threshold for chlorinated systems is in good agreement with guidelines from the World Health Organization. The fact that the vast majority of samples failing the regulatory coliform standard also showed elevated proportions of intact cells suggests that this parameter might be useful for evaluating risk of failure. Another interesting parameter for judging the microbiological status of water, the biological regrowth potential, greatly varied among different finished waters providing potential help for investment decisions. For its measurement, a simple method was introduced that can easily be performed by water utilities with FCM capability.