Effect of Helicobacter pylori Eradication Therapy on the Incidence of Noncardia Gastric Adenocarcinoma in a Large Diverse Population in the United States.

BACKGROUND & AIMS: High-quality data regarding the effect of Helicobacter pylori eradication on the risk of noncardia gastric adenocarcinoma (NCGA) remain limited in the United States. We investigated the incidence of NCGA after H pylori eradication therapy in a large, community-based US population. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent testing and/or treatment for H pylori between 1997 and 2015 and were followed through December 31, 2018. The risk of NCGA was evaluated using the Fine-Gray subdistribution hazard model and standardized incidence ratios. RESULTS: Among 716,567 individuals with a history of H pylori testing and/or treatment, the adjusted subdistribution hazard ratios and 95% confidence intervals of NCGA for H pylori-positive/untreated and H pylori-positive/treated individuals were 6.07 (4.20-8.76) and 2.68 (1.86-3.86), respectively, compared with H pylori-negative individuals. When compared directly with H pylori-positive/untreated individuals, subdistribution hazard ratios for NCGA in H pylori-positive/treated were 0.95 (0.47-1.92) at <8 years and 0.37 (0.14-0.97) ≥8 years of follow-up. Compared with the Kaiser Permanente Northern California general population, standardized incidence ratios (95% confidence interval) of NCGA steadily decreased after H pylori treatment: 2.00 (1.79-2.24) ≥1 year, 1.01 (0.85-1.19) ≥4 years, 0.68 (0.54-0.85) ≥7 years, and 0.51 (0.38-0.68) ≥10 years. CONCLUSION: In a large, diverse, community-based population, H pylori eradication therapy was associated with a significantly reduced incidence of NCGA after 8 years compared with no treatment. The risk among treated individuals became lower than the general population after 7 to 10 years of follow-up. The findings support the potential for substantial gastric cancer prevention in the United States through H pylori eradication.

Ultrasonic optic nerve sheath diameter can be used as a diagnostic measure after accidental dural puncture during cesarean section: a case report.

BACKGROUND: Parturients are prone to postdural puncture headache (PDPH) after epidural puncture. Cerebral venous sinus thrombosis (CVST) is a fatal complication of PDPH. The main symptom of both is headache, however, the mechanism is not similar. For persistent PDPH, early differential diagnosis from CVST is essential. Optic nerve sheath diameter (ONSD) measurements can be used to identify changes in intracranial pressure as an auxiliary tool to distinguish the cause of headache. CASE PRESENTATION: The dura of a 32-year-old woman undergoing cesarean section was accidentally penetrated while administering epidural anesthesia, and the patient developed PDPH the subsequent day. The patient refused epidural blood patch (EBP) treatment and was discharged after conservative treatment. Fourteen days post-discharge, she was readmitted for a seizure. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) indicated low cranial pressure syndrome and superior sagittal sinus thrombosis with acute infarction. The next morning, the EBP was performed with 15 ml autologous blood. Subsequently, the headache symptoms decreased during the day and worsened at night. ONSD measurement suggested dilation of the optic nerve sheath, and subsequently, the patient showed intracranial hypertension with papilledema. After dehydration and anticoagulant treatment, the patient's symptoms were relieved and she was discharged from the hospital 49 days later. CONCLUSIONS: Headache is the main symptom of PDPH and cerebral venous thrombosis, which are difficult to distinguish. ONSD measurement may help to estimate the intracranial pressure, and early measurement may be helpful for women with PDPH to avoid serious complications, such as CVST.

Mid-term Incidence of Tarsometatarsal Joint Arthrodesis Following Open Reduction With Internal Fixation (ORIF) of Lisfranc Injuries.

Open reduction with internal fixation (ORIF) of Lisfranc injuries are associated with an increased risk for secondary surgery including hardware removal and salvage arthrodesis. In the current literature, rates of salvage arthrodesis vary due to small sample sizes and a low incidence of Lisfranc injuries. There is little evidence to identify specific surgical and patient-related variables that may result in later arthrodesis. The purpose of this study is to determine the rate of tarsometatarsal joint arthrodesis following Lisfranc ORIF in a relatively large sample size. This retrospective review included patients who underwent ORIF for a Lisfranc injury between January 2007 and December 2012. A total of 146 patients met our criteria. Trans-articular fixation was used in 109 (74.6%) patients, 33 (22.6%) received percutaneous fixation and 4 (2.7%) extraarticular fixation. Five out of 120 (4.2%) patients required a salvage arthrodesis for post-traumatic arthritis that had a follow-up greater than 5 y but up to 10 y. The mean age of patients who underwent arthrodesis after ORIF was 24.5 ± 11.95 (16-48) y compared to 40.9 ± 15.8 (16-85) y. Patients who required an arthrodesis also had earlier hardware removal than patients who did not have an arthrodesis, 71.2 ± 28.3 (38-100) days and 131.4 ±101.2 (37-606) days, respectively. Patients who required salvage arthrodesis tended to be younger and hardware was removed earlier compared to those patients who did not require an arthrodesis. Four of the 5 patients who underwent a secondary arthrodesis had a loss of correction after hardware removal.

[Mechanism of ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix regulates HIF-1α signaling pathway mediated by renal hypoxia to ameliorate renal fibrosis in DKD rats].

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.

Selective inhibition of HDAC6 promotes bladder cancer radiosensitization and mitigates the radiation-induced CXCL1 signalling.

BACKGROUND: Although trimodality therapy resecting tumours followed by chemoradiotherapy is emerged for muscle-invasive bladder cancer (MIBC), chemotherapy produces toxicities. Histone deacetylase inhibitors have been identified as an effective strategy to enhance cancer radiotherapy (RT). METHODS: We examined the role of HDAC6 and specific inhibition of HDAC6 on BC radiosensitivity by performing transcriptomic analysis and mechanism study. RESULTS: HDAC6 knockdown or HDAC6 inhibitor (HDAC6i) tubacin exerted a radiosensitizing effect, including decreased clonogenic survival, increased H3K9ac and α-tubulin acetylation, and accumulated γH2AX, which are similar to the effect of panobinostat, a pan-HDACi, on irradiated BC cells. Transcriptomics of shHDAC6-transduced T24 under irradiation showed that shHDAC6 counteracted RT-induced mRNA expression of CXCL1, SERPINE1, SDC1 and SDC2, which are linked to cell migration, angiogenesis and metastasis. Moreover, tubacin significantly suppressed RT-induced CXCL1 and radiation-enhanced invasion/migration, whereas panobinostat elevated RT-induced CXCL1 expression and invasion/migration abilities. This phenotype was significantly abrogated by anti-CXCL1 antibody, indicating the key regulator of CXCL1 contributing to BC malignancy. Immunohistochemical evaluation of tumours from urothelial carcinoma patients supported the correlation between high CXCL1 expression and reduced survival. CONCLUSION: Unlike pan-HDACi, the selective HDAC6i can enhance BC radiosensitization and effectively inhibit RT-induced oncogenic CXCL1-Snail-signalling, thus further advancing its therapeutic potential with RT.

Germline Genetic Testing Among Women ≤ 45 Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System.

BACKGROUND: We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. METHODS: A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. RESULTS: A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. CONCLUSION: In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.

[Characterization of genetic variants in children with refractory epilepsy].

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ2 = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ2 = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION: 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Discovering the processes of undergraduate hospitality students' acceptance of facebook teaching interventions.

Technology drives innovation and reform in hospitality education, and Facebook has become a popular educational tool to facilitate students' classroom interactions. Understanding hospitality students' attitudes toward Facebook teaching interventions is important. Based on a survey of 289 undergraduate hospitality students, first, we expand the scope of the technology acceptance model (TAM) in this study, which integrates the two factors of social interaction and information exchange into the research structure. Second, this study also proposes a new moderated mediation model to account for the internal mechanism underlying Taiwanese undergraduate hospitality students' acceptance of Facebook teaching interventions in terms of perceived usefulness and ease of use. We illuminate the foundation of the application of Facebook media technology to teaching in hospitality higher education. The theoretical contributions and educational implications of this research are also discussed.

Prenatal Ultrasound Diagnosis of Persistent Hyperplastic Primary Vitreous with Retinoblastoma.

INTRODUCTION: Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities characterized by the presence of a vascular membrane behind the lens. Retinoblastoma is a life-threatening intraocular malignancy that can cause blindness, eye loss, or even death. PHPV and retinoblastoma are extremely rare prenatal diseases. CASE PRESENTATION: Here, we present a case of fetal PHPV with retinoblastoma diagnosed using prenatal ultrasound. The unilateral lenses were hyperechoic, and irregular echogenic bands between the lenses and posterior eye walls were observed. In cases where the blood flow signal continues in the band-shaped hyperechoic area, PHPV with retinoblastoma should be suspected. CONCLUSION: PHPV with retinoblastoma can be prenatally diagnosed.

The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer.

BACKGROUND: Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1-M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. METHODS: Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. RESULTS: We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1ß and TGF-ß1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, ß-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. CONCLUSIONS: We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that "re-education" of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

Diagnosis of Double-chambered Left Ventricle of Superior-inferior Type by Echocardiography: A Retrospective Study of 9 Subjects across Two Heart Centers.

BACKGROUND: Double-chambered left ventricle (DCLV) is extremely rare. Challenges remain in accurate diagnosis of DCLV by echocardiography, because it is easily confused with left ventricular diverticulum, left ventricular aneurysm, ventricular septal defect, etc. Herein, we reviewed echocardiographic characteristics of DCLV and evaluated the accuracy of echocardiographic diagnosis. METHODS: Clinical and echocardiographical databases of two heart centers were reviewed. Nine children with DCLV of superior-inferior arrangement were studied retrospectively. RESULTS: Normal elliptical geometry of LV cavity is preserved in DCLV. Fibromuscluar bundles separate LV into the main chamber and the accessory chamber. The associated malformations included ventricular septal defects, mitral regurgitation, mitral valve stenosis, pulmonary stenosis, and left ventricular noncompaction in our study. Eight of nine subjects with DCLV of superior-inferior arrangement were diagnosed correctly by initial echocardiographic examination, and one case was mistaken as left ventricular diverticulum. CONCLUSIONS: Double-chambered left ventricle could be diagnosed and followed up by echocardiography. The morphological classification is a simplified way to improve diagnostic accuracy.

The Analysis of Phenolic Compounds in Walnut Husk and Pellicle by UPLC-Q-Orbitrap HRMS and HPLC.

Husk and pellicle as the agri-food waste in the walnut-product industry are in soaring demand because of their rich polyphenol content. This study investigated the differential compounds related to walnut polyphenol between husk and pellicle during fruit development stage. By using ultra-high performance liquid chromatography-quadrupole-orbitrap (UHPLC-Q-Orbitrap), a total of 110 bioactive components, including hydrolysable tannins, flavonoids, phenolic acids and quinones, were tentatively identified, 33 of which were different between husk and pellicle. The trend of dynamic content of 16 polyphenols was clarified during walnut development stage by high-performance liquid chromatography (HPLC). This is the first time to comprehensive identification of phenolic compounds in walnut husk and pellicle, and our results indicated that the pellicle is a rich resource of polyphenols. The dynamic trend of some polyphenols was consistent with total phenols. The comprehensive characterization of walnut polyphenol and quantification of main phenolic compounds will be beneficial for understanding the potential application value of walnut and for exploiting its metabolism pathway.

Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study.

Background: Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied. Objective: To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors. Design: Retrospective cohort study. Setting: A large, diverse, community-based health care system. Participants: 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016. Measurements: Diagnostic yield of different LS screening strategies. Results: Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC. Limitation: Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics. Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed. Primary Funding Source: Kaiser Permanente Northern California Division of Research.

[Qualitative and quantitative analysis of quassinoid diterpenoids from Eurycoma longifolia by UPLC-Q-TOF-MS combined with UPLC-QQQ-MS/MS].

In this work, a sensitive and efficient method was established and validated for qualitative and quantitative analysis of major quassinoid diterpenoids constituents from the extract of Eurycoma longifolia by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometry(UPLC-QQQ-MS/MS). The UPLC-Q-TOF-MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×100 mm,1.8 µm) column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The UPLC-QQQ-MS/MS analysis was performed on an Agilent Eclipse Plus C_(18) RRHD(2.1 mm×50 mm, 1.8 µm)column with acetonitrile and 0.1% formic acid water as mobile phase by gradient elution. The data was collected by electrospray ionization in positive mode. According to the contrast of the reference standards and the accurate masses of molecules, a total of 32 quassinoid diterpenoids in E. longifolia extract were identified by UPLC-Q-TOF-MS. For quantitative the linear range of 4 detected quassinoid diterpenoids were good(r≥0.999 6), and the overall recoveries ranged from 90.35% to 106.4%, with the RSD ranging from 1.8% to 3.6%. The method was accurate, reliable and efficient, and could comprehensively reflect the chemical constituents and content of E. longifolia, and could provide a reference for further elucidating its pharmacological basis and quality control.

Assessment of right ventricular systolic function in children with repaired tetralogy of Fallot by multiple-view from single acoustic window with speckle tracking echocardiography.

BACKGROUND: Challenges remain in quantitative evaluation of right ventricular (RV) function by echocardiography. Multiple-view assessment is believed to provide a more comprehensive quantification of RV function than conventional single-view analysis. Peak systolic longitudinal RV strain (RVLS) measured by speckle tracking echocardiography (STE) has clinical and prognostic value. No study has investigated RV systolic function in the repaired tetralogy of Fallot (rTOF) using a standardized four-view iRotate model from one apical view. Herein, we examined the feasibility and accuracy of the four-view analysis from apical window in quantitation of RVLS among children with rTOF. METHODS: Thirty-seven children with rTOF and 37 age- and gender-matched controls were prospectively enrolled. Tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TDI-S' ) and fractional area change(FAC) were obtained. RVLS of four free-walls were analyzed by dedicated RV speckle tracking software. Echocardiographic parameters were compared with the right ventricular ejection fraction (RVEF) measured by the cardiac magnetic resonance (CMR) in children with rTOF. RESULTS: Multi-view RVLS analysis from apical window was feasible in 35 children with rTOF and all the controls. Compared with age- and gender-matched controls, RVLS of the anterior, lateral, inferior-a, and inferior-b walls were significantly reduced in children with rTOF (P < 0.001). RVLS of the anterior, lateral, inferior-a, and inferior-b walls correlated well with CMR-RVEF in children with rTOF (r = -0.667, -0.743, -0.808, -0.695, P < 0.001). CONCLUSIONS: Multi-view analysis of RVLS from apical window can be applied to evaluate the RV function in children with rTOF. RVLS of the inferior wall-a in the aortic view is a novel and accurate indicator of RV function because of its good reproducibility and strong correlation with CMR-RVEF.

Diagnosis and predictors of sessile serrated adenoma after educational training in a large, community-based, integrated healthcare setting.

BACKGROUND AND AIMS: Sessile serrated adenomas (SSAs) are precursors of 15% to 30% of colorectal cancers but are frequently underdiagnosed. We sought to measure the SSA detection rate (SDR) and predictors of SSA detection after educational training for community gastroenterologists and pathologists. METHODS: Colonoscopy and pathology data (2010-2014) from 3 medical centers at Kaiser Permanente Northern California were accessed electronically. Gastroenterologists and pathologists attended a training session on SSA diagnosis in 2012. Mean SDRs and patient-level predictors of SSA detection post-training (2013-2014) were investigated. RESULTS: Mean SDRs increased from .6% in 2010-2012 to 3.7% in 2013-2014. The increase in the detection of proximal SSAs was accompanied by a decrease in the detection of proximal hyperplastic polyps (HPs). Among 34,161 colonoscopies performed in 2013 to 2014, SDRs for screening, fecal immunochemical test positivity, surveillance, and diagnostic indication were 4.2%, 4.5%, 4.9%, and 3.0%, respectively. SSA detection was lower among Asians (adjusted odds ratio [aOR], .46; 95% confidence interval [CI], .31-.69) and Hispanics (aOR, .59; 95% CI, .36-.95) compared with non-Hispanic whites and higher among patients with synchronous conventional adenoma (aOR, 1.46; 95% CI, 1.15-1.86), HP (aOR, 1.74; 95% CI, 1.30-2.34), and current smokers (aOR, 1.78; 95% CI, 1.17-2.72). SDRs varied widely among experienced gastroenterologists, even after training (1.1%-8.1%). There was a moderately strong correlation between adenoma detection rate (ADR) and SDR for any SSA (r = .64, P = .0003) and for right-sided SSAs (r = .71, P < .0001). CONCLUSIONS: Educational training significantly increased the detection of SSA, but a wide variation in SDR remained across gastroenterologists. SSA detection was inversely associated with Asian and Hispanic race/ethnicity and positively associated with the presence of conventional adenoma, HP, and current smoking. There was a moderately strong correlation between ADR and SDR.

Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification.

OBJECTIVE: Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand. APPROACH AND RESULTS: We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71; P=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14; P<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13; P=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135). CONCLUSIONS: The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.

Variations in dosimetric distribution and plan complexity with collimator angles in hypofractionated volumetric arc radiotherapy for treating prostate cancer.

PURPOSE: Hypofractionated radiotherapy can reduce treatment durations and produce effects identical to those of conventionally fractionated radiotherapy for treating prostate cancer. Volumetric arc radiotherapy (VMAT) can decrease the treatment machine monitor units (MUs). Previous studies have shown that VMAT with multileaf collimator (MLC) rotation exhibits better target dose distribution. Thus, VMAT with MLC rotation warrants further investigation. METHODS AND MATERIALS: Ten patients with prostate cancer were included in this study. The prostate gland and seminal vesicle received 68.75 and 55 Gy, respectively, in 25 fractions. A dual-arc VMAT plan with a collimator angle of 0° was generated and the same constraints were used to reoptimize VMAT plans with different collimator angles. The conformity index (CI), homogeneity index (HI), gradient index (GI), normalized dose contrast (NDC), MU, and modulation complexity score (MCSV ) of the target were analyzed. The dose-volume histogram of the adjacent organs was analyzed. A Wilcoxon signed-rank test was used to compare different collimator angles. RESULTS: Optimum values of CI, HI, and MCSV were obtained with a collimator angle of 45°. The optimum values of GI, and NDC were observed with a collimator angle of 0°. In the rectum, the highest values of maximum dose and volume receiving 60 Gy (V60 Gy ) were obtained with a collimator angle of 0°, and the lowest value of mean dose (Dmean ) was obtained with a collimator angle of 45°. In the bladder, high values of Dmean were obtained with collimator angles of 75° and 90°. In the rectum and bladder, the values of V60 Gy obtained with the other tested angles were not significantly higher than those obtained with an angle of 0°. CONCLUSION: This study found that MLC rotation affects VMAT plan complexity and dosimetric distribution. A collimator angle of 45° exhibited the optimal values of CI, HI, and MCSv among all the tested collimator angles. Late side effects of the rectum and bladder are associated with high-dose volumes by previous studies. MLC rotation did not have statistically significantly higher values of V60 Gy in the rectum and bladder than did the 0° angle. We thought a collimator angle of 45° was an optimal angle for the prostate VMAT treatment plan. The findings can serve as a guide for collimator angle selection in prostate hypofractionated VMAT planning.

Reprogramming of the human intestinal epigenome by surgical tissue transposition.

Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue's exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of -0.37% per month (P < 0.01, Pearson = -0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment.