Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal ...cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epithelium of UC patients with high-grade dysplasia (HGD) or cancer (UC progressors). We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. Multiple biopsies of varying histologic grade were collected along the colon of nine UC progressors and analyzed for telomere length, DNA damage, senescence, p53, p16, and chronic and acute inflammation. Twenty biopsies from four UC nonprogressors and twenty-one biopsies from control individuals without UC were also analyzed. Short telomeres and increased DNA damage, senescence, and infiltrating leukocytes were observed in biopsies located less than 10 cm from HGD or cancer. Low-grade dysplasia (LGD) had the shortest telomeres along with the highest levels of senescence and infiltrating leukocytes, whereas HGD biopsies showed the opposite pattern. The expression of p16 and p53 was low in nondysplastic biopsies but progressively increased in LGD and HGD. In addition, high levels of infiltrating leukocytes were associated with telomere shortening, senescence, and reduced p53 expression. These results suggest that dysplasia arises in a preneoplastic field of chronic inflammation, which leads to telomere shortening, DNA damage, and senescence. Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC.
High filtration for ultrafine particles (UFPs) has many potential energy-saving and environmental applications. In this study, riblet surfaces with different geometries were investigated for their ...enhanced UFPs deposition in duct flow conditions for the first time. Polydisperse sodium chloride (NaCl) particles as UFPs were used and tested in a wide range of Reynolds numbers, ranging from laminar to fully turbulent flow. The upstream and downstream size-resolved particle concentrations of the NaCl particles were measured. Experimental results show that deposition velocity increased with Reynolds numbers and decreased with particle size for both empty duct and duct furnished with riblet surfaces. Duct with riblets surface had the highest enhanced deposition velocity ratio for UFPs in the laminar regime, which could reach about 7.0 times for particles less than 20 nm, and about 4.8 times for particle size between 20 nm and 50 nm. The experimental results reveal that the friction factors of the duct with riblet surfaces were close to that of the empty duct in the turbulent flow, while higher pressure drop penalty was observed for riblet surfaces in the laminar flow. The performance index of riblet surfaces by combining enhanced UFPs deposition and high frictional drag was also evaluated. The results show that the highest performance ratio of riblets could be up to 4.0. In addition, the riblet surface with largest protrusion height generally give the best performance.
Patients with recurrent gliomas (n = 14) were treated with bevacizumab and carboplatin, cpt-11, or etoposide. Follow-up MRI scans were obtained 2 to 6 weeks after initiation of treatment. ...Contrast-enhancing tumor shrank in 7 patients, with reductions evident in as little as 2 weeks after initiation of therapy. Treatment seemed more effective for heterogeneously enhancing tumor compared with solidly enhancing tumor.
In this pilot study, twisted tape (TT) was first used for deposition enhancement for ultrafine particles (UFPs). The particle removal enhancement of TT was measured experimentally. Polydisperse ...sodium chloride (NaCl) particles were used as ultrafine particles (UFPs). The upstream and downstream size-resolved particle concentrations of the NaCl particles were measured, and the results were used to compute the particle deposition velocity ratio achieved by TT for 5 different size groups. The duct with a TT insert recorded a higher particle deposition velocity ratio than that without the insert, peaking at 3.3 times for particles size group between 50 nm–100 nm. The experimental results reveal that the friction factors of the ducts with TT inserts were higher than those of the empty duct. Parameter such as the performance ratio was also calculated. Discussion on the deposition performance was also addressed.
•Enhanced particle filtration by twist tapes were studied experimentally.•Particle deposition velocity ratio can be up to 3.3 times.•Particle removal performance ratio and pressure drop penalty were measured.
Background & Aims: Telomere shortening is implicated in cancer and aging and might link these 2 biologic events. We explored this hypothesis in ulcerative colitis (UC), a chronic inflammatory disease ...that predisposes to colorectal cancer and in which shorter telomeres have been associated with chromosomal instability and tumor progression. Methods: Telomere length was measured by quantitative polymerase chain reaction in colonocytes and leukocytes of 2 different sets of UC patients and compared with normal controls across a wide range of ages. For a subset of patients, telomere length was measured in epithelium and stroma of right and left colon biopsy specimens. A third set of biopsy specimens was analyzed for phosphorylation of histone H2AX (γH2AX), a DNA damage signal, by immunofluorescence and for telomere length by quantitative fluorescence in situ hybridization. Relationships between telomere length, γH2AX intensity, age, disease duration, and age of disease onset were explored. Results: Colonocyte telomeres shorten with age almost twice as rapidly in UC patients as in normal controls. This extensive shortening occurs within approximately 8 years of disease duration. Leukocyte telomeres are slightly shorter in UC patients than in controls, but telomeres of colon stromal cells are unaffected. γH2AX intensity is higher in colonocytes of UC patients than in controls and is not dependent on age or telomere length. Conclusions: Colonocytes of UC patients show premature shortening of telomeres, which might explain the increased and earlier risk of cancer in this disease. Shorter leukocyte telomeres and increased γH2AX in colonocytes might reflect oxidative damage secondary to inflammation.
Currently available methods for the diagnosis of cutaneous leishmaniasis (CL) have low sensitivities or are unable to quantify the number of viable parasites. This constitutes a major obstacle for ...the diagnosis of the disease and for the study of the effectiveness of treatment schedules and urges the development of improved detection methods. In this study, quantitative nucleic acid sequence-based amplification (QT-NASBA) technology was used to detect and quantify Leishmania parasites in skin biopsy samples from CL patients. The assay is based on the detection of a small subunit rRNA (18S rRNA), which may allow for the detection of viable parasites. The QT-NASBA assay was evaluated using in vitro-cultured promastigotes and amastigotes and 2-mm skin biopsy samples from Old and New World CL patients. The study demonstrated that the lower detection limit of the QT-NASBA was two parasites per biopsy sample. Parasites could be quantified in a range of 2 to 11,300,000 parasites per biopsy sample. The QT-NASBA could detect levels of parasites 100-fold lower than those detected by conventional PCR. Test evaluation revealed that the QT-NASBA had a sensitivity of 97.5% and a specificity of 100% in the present study. The QT-NASBA is a highly sensitive and specific method that allows quantification of both Old and New World Leishmania parasites in skin biopsy samples and may provide an important tool for diagnosis as well as for monitoring the therapy of CL patients.
Background
A common-stem origin of lenticulostriate arteries (CS-LSAs) is an anatomical variation that supplies a moderate to large section of the basal ganglia. We hypothesized that CS-LSAs with a ...patent orifice are located at distal positions of the acute-occluded middle cerebral artery (MCA) and that the blood flow of CS-LSAs is supplied by pail arterial anastomoses and results in hypoperfusion of CS-LSAs, similar to a deep watershed (DWS) infarction.
Objective
Our study evaluated the possibility of CS-LSAs in patients with DWS infarction and MCA occlusion and also assessed the safety of endovascular therapy (ET) in these patients.
Methods
A cohort of consecutive patients with DWS infarction and MCA occlusion and in whom full recanalization via ET was achieved were identified. Patients were divided into two groups based on the presence of CS-LSAs observed during ET. In addition, radiological and clinical data were retrospectively analyzed.
Results
Thirty-three patients were included, and CS-LSAs were observed in 48.5% (16/33) of patients. The possibility (72.2%, 13/18) of CS-LSAs was high in patients with DWS infarction companied with basal ganglia infarction. A good clinical outcome was similar in patients with CS-LSAs and basal ganglia infarction and in patients without CS-LSAs and basal ganglia infarction (69.2% vs. 81.8%,
P
= 0.649).
Conclusions
The possibility of CS-LSAs was 48.5% in patients with DWS infarction and MCA occlusion, and the revascularization procedure was safe and feasible in these patients despite the moderate-to-large basal ganglia infarction.
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