The detection of molecular markers in stool samples is a potential strategy for colorectal cancer (CRC) screening. This study evaluated the feasibility of detecting miR-21 and miR-92a in stool ...samples of patients with CRC or polyps.
The reproducibility of detection and stability of stool-based microRNA were evaluated. Stool samples were collected from 88 patients with CRC, 57 patients with colorectal polyps and 101 healthy controls. MiRNA levels in CRC tissues and stool samples were detected by real-time quantitative reverse transcription PCR. Stool miR-21 and miR-92a levels were compared before and after the removal of tumour or advanced adenoma.
The study demonstrated that stool-based miRNA were stable with highly reproducible detection. The expression of miR-21 and miR-92a was significantly higher in CRC tissues compared with their adjacent normal tissues (p<0.0001). Patients with CRC had a significantly higher stool miR-21 level (p<0.01) and miR-92a level (p<0.0001) compared with normal controls. Stool miR-92a, but not miR-21, was significantly higher in patients with polyps than in controls (p<0.0001). At a cut-off value of 435 copies/ng of stool RNA, miR-92a had a sensitivity of 71.6% and 56.1% for CRC and polyp, respectively, and a specificity of 73.3%. In addition, the stool miR-92a level demonstrated a higher sensitivity for distal CRC than proximal CRC (p<0.05), and a higher sensitivity for advanced adenoma than minor polyps (p<0.05). Removal of tumour resulted in reduced stool miR-21 and miR-92a levels (p<0.01), and the removal of advanced adenoma resulted in a reduction of the stool miR-92a level (p<0.05).
Stool miRNA are useful for screening CRC and polyps.
We present an investigation of the dependence of H2O maser detection rates and properties on the mid-IR active galactic nucleus (AGN) luminosity, LAGN, and the obscuring column density, NH, based on ...mid-IR and hard X-ray photometry. Based on spectral energy distribution fitting that allows for decomposition of the black hole accretion and star formation components in the mid-infrared, we show that the megamaser (disk maser) detection rate increases sharply for galaxies with 12 m AGN luminosity greater than 1042 erg s−1, from 3% ( 2%) to ∼12% (∼5%). By using the ratio of the observed X-ray to mid-IR AGN luminosity as an indicator of NH, we also find that megamaser (disk maser) detection rates are boosted to 15% (7%) and 20% (9%) for galaxies with NH ≥ 1023 cm−2 and NH ≥ 1024 cm−2, respectively. Combining these column density cuts with a constraint for high (≥1042 erg s−1) predicts further increases in the megamaser (disk maser) detection rates to 19% (8%) and 27% (14%), revealing unprecedented potential increases of the megamaser and disk maser detection rates by a factor of 7-15 relative to the current rates, depending on the chosen sample selection criteria. A noteworthy aspect of these new predictions is that the completeness rates are only compromised mildly, with the rates remaining at the level of ∼95%(∼50%) for sources with NH ≥ 1023 cm−2 (NH ≥ 1024 cm−2). Applying these selection methods to current X-ray AGN surveys predicts the detection of 15 new megamaser disks.
Sarcopenia is an important factor of functional impairment related to aging. This study is conducted to investigate the prevalence of sarcopenia and sarcopenic obesity in Korean population.
...Representative Korean men (4,486) and women (5,999) aged 20 years or older were analyzed from the Fourth Korean National Health and Nutritional Examination Surveys. Sarcopenia was classified into Class I defined relative skeletal muscle mass loss within 1-2 SD of the gender-specific mean for healthy young adults and Class II below 2 SD. Relative skeletal muscle mass was represented by the appendicular skeletal muscle mass adjusted by height and body weight. Sarcopenic obesity was considered present in Class II sarcopenic participants whose waist circumference was more than or equal to 90 cm for men and more than or equal to 85 cm for women, respectively.
The prevalence of Class II sarcopenia in the Korean elderly population was 12.4% for men and 0.1% for women by height-adjusted definition and 9.7% for men and 11.8% for women by weight-adjusted definition. The prevalence of sarcopenic obesity was 7.6% for men and 9.1% for women by weight-adjusted definition but nearly zero for men and women by height-adjusted definition. The prevalence of sarcopenia increased with age for men but for women only when applied with weight-adjusted definition.
The prevalence of sarcopenia and sarcopenic obesity differs by gender and definition criteria. The height-adjusted definition may tend to underestimate the prevalence of sarcopenia and sarcopenic obesity, especially in women.
Doxorubicin (DOX) is a widely used anticancer drug for solid tumors and hematologic malignancy, but its active use is hampered by serious adverse effects, including thrombocytopenia. Although bone ...marrow toxicity of DOX has been suggested to be the sole mechanism underlying the reduced platelet counts, the direct effects of DOX on platelets have never been examined.
Here, we investigated the DOX-induced platelet cytotoxicity and its underlying mechanism in an effort to elucidate the contribution of platelet cytotoxicity to DOX-induced thrombocytopenia.
In freshly isolated human platelets, DOX induced platelet cytotoxicity in a time-dependent and concentration-dependent manner. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent protein thiol depletion were shown to underlie the DOX-induced platelet cytotoxicity. Conspicuously, DOX-treated platelets displayed apoptotic features such as caspase-3 activation, reduced mitochondrial transmembrane potential, and phosphatidylserine exposure. Decreased glutathiolation of procaspase-3 was shown to be a link between protein thiol depletion and caspase-3 activation. It is of note that DOX-mediated platelet cytotoxicity was significantly enhanced by shear stress, a common complicating factor in cancer patients. These in vitro results were further confirmed by an in vivo animal model, where administration of DOX induced a platelet count decrease, ROS generation, caspase-3 activation, protein thiol depletion, and damaged platelet integrity.
We demonstrated that DOX can directly induce platelet cytotoxicity through ROS generation, decreased glutathione levels, and protein thiol depletion. We believe that this study provides important evidence for the role of DOX-induced platelet cytotoxicity in the development of thrombocytopenia in DOX-treated patients.
Memory or transistor devices based on an electron's spin rather than its charge degree of freedom offer certain distinct advantages and comprise a cornerstone of spintronics. Recent years have ...witnessed the emergence of a new field, valleytronics, which seeks to exploit an electron's valley index rather than its spin. An important component in this quest would be the ability to control the valley index in a convenient fashion. Here we show that the valley polarization can be switched from zero to 1 by a small reduction in density, simply tuned by a gate bias, in a two-dimensional electron system. This phenomenon, which is akin to Bloch spin ferromagnetism, arises fundamentally as a result of electron-electron interaction in an itinerant, dilute electron system. Essentially, the kinetic energy favors an equal distribution of electrons over the available valleys, whereas the interaction between electrons prefers single-valley occupancy below a critical density. The gate-bias-tuned transition we observe is accompanied by a sudden, twofold change in sample resistance, making the phenomenon of interest for potential valleytronic transistor device applications. Our observation constitutes a quintessential demonstration of valleytronics in a very simple experiment.
Summary
Background Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated.
Objectives To evaluate ...the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥ 5% body surface area in children or measuring ≥ 20 cm in adults.
Methods In total, 131 patients with GCMN were enrolled, with a mean age of 10·3 years (range: birth–70 years).
Results The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients < 4 years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6‐year‐old girl, a 14‐year‐old girl and a 70‐year‐old man), and the incidence rate was 990 per 100 000 person‐years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma.
Conclusions We should be aware of melanoma development from GCMN, and lifelong follow‐up is required due to the risk of melanoma arising in GCMN.
Background: Although stent assisted angioplasty is an effective treatment for coronary and peripheral arterial disease, its efficacy in intracranial arteriosclerotic disease has not been verified. ...Objectives: To assess the radiographic and clinical outcome of stent assisted angioplasty for symptomatic middle cerebral artery (MCA) stenosis. Methods: We attempted stent assisted angioplasty in 14 patients with symptomatic high grade stenosis (>60%) on the proximal portion of the MCA, who had experienced either recurrent transient ischaemic attacks (TIAs) resistant to medical therapy or one or more stroke attacks. Patient records were analysed for angiographic characteristics, degree of stenosis, pre-procedural regimen of anti-platelet and/or anti-coagulation agents, use of devices, procedure related complications, pre-operative and post-operative single photon emission computed tomography (SPECT) findings, and clinical and radiographic outcomes. Results: Stent assisted angioplasty was successfully performed in 8 of 14 patients without any serious complications and unsuccessful in 2 of 14 patients due to the tortuous curve of the internal carotid artery siphon. Four patients had complications. Two patients had an arterial rupture; one patient was rescued by an additional stent and balloon tamponade, the other patient died. Complications in the other two patients included thrombotic occlusion and distal thrombosis. Residual stenosis was less than 50% in diameter in all the patients. All eight patients who underwent follow up cerebral angiography had no restenosis. Follow up SPECT showed improved perfusion in the affected MCA territory in all the tested patients with TIA and in one of three stroke patients. Using the modified Rankin Scale at follow up, four of five TIA patients and five of six stroke patients were assessed as functionally improved or having a stable clinical status. Conclusion: Although the re-stenosis rate in stent assisted angioplasty seems to be better than in primary balloon angioplasty as reported previously, the complication rate is still high. Elective stenting is an alternative therapeutic method for the prevention of secondary ischaemic stroke in stroke patients with MCA stenosis, and seems to be a potentially effective but also hazardous therapeutic technique in patients with recurrent TIAs. This study indicates the need for randomised control trial data of this intervention. Additionally, long term follow up data and additional clinical experience are required to assess the durability of this procedure.
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with ...Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
Macrophages, T cells, and B cells of the immune system are central targets of deoxynivalenol (DON) and other trichothecenes-mycotoxins that can be immunostimulatory or immunosuppressive depending on ...dose, exposure frequency and timing of functional immune assay. Notably, low dose trichothecene exposure transcriptionally and post-transcriptionally upregulates expression of cytokines, chemokines and inflammatory genes with concurrent immune stimulation, whereas high dose exposure promotes leukocyte apoptosis with concomitant immune suppression. DON and other trichothecenes, via a mechanism known as the ribotoxic stress response, bind to ribosomes and rapidly activate mitogen-activated protein kinases (MAPKs). The latter are important transducers of downstream signaling events related to immune response and apoptosis. Using cloned macrophages, our laboratory has identified two critical upstream transducers of DON-induced MAPK activation. One transducer is double-stranded RNA-(dsRNA)-activated protein kinase (PKR), a widely-expressed serine/theonine protein kinase that can be activated by dsRNA, interferon, and other agents. The second transducer is hematopoetic cell kinase (Hck), a non-receptor associated Src family kinase. Inhibitors and gene silencing studies have revealed that Hck and PKR play roles in DON induced gene expression and apoptosis. Future studies should focus on the molecular linkages between these kinases and trichothecene toxicity.
An accurate and comprehensive assessment of lymph node metastasis in patients with head and neck squamous cell cancer is crucial in daily practice. This study constructed a predictive model with a ...risk scoring system based on CT characteristics of lymph nodes and tumors for patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis.
Data included 476 cervical lymph nodes from 191 patients with head and neck squamous cell carcinoma from a historical cohort. We analyzed preoperative CT images of lymph nodes, including diameter, ratio of long-to-short axis diameter, necrosis, conglomeration, infiltration to adjacent soft tissue, laterality and T-stage of the primary tumor. The reference standard comprised pathologic results. Multivariable logistic regression analysis was performed to develop the risk scoring system. Internal validation was performed with 1000-iteration bootstrapping.
Shortest axial diameter, ratio of long-to-short axis diameter, necrosis, and T-stage were used to develop a 9-point risk scoring system. The risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increased scores. Areas under the curve of the risk scoring systems were 0.886 (95% CI, 0.881-0.920) and 0.879 (95% CI, 0.845-0.914) in internal validation. The Hosmer-Lemeshow goodness-of-fit test indicated that the risk scoring system was well-calibrated (
= .160).
We developed a comprehensive and simple risk scoring system using CT characteristics in patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis. It could facilitate decision-making in daily practice.
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