Abstract The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO +) as an ...entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO + that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO −). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO + and RPO − cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO + tumors were compared with that of age -and gender-matched CRC RPO − evaluated by The Cancer Genome Atlas. CRC RPO + cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO −. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO −. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO + and RPO − cases. Likewise, gene expression patterns are indistinguishable between the RPO + and RPO − cases. We have confirmed that CRC RPO + is clinically and biologically similar to CRC RPO − and may be utilized as a model of the adenoma to carcinoma transition.
Nonvolatile Molecular Memory
In article number 2000306, Sib Sankar Mal, Partha Pratim Dasa and co‐workers attempt to build ultrafast and nonvolatile molecular memory using highly redox‐active ...vanadium based polyoxometalate (POM) clusters. POMs are large reservoir of electrons and they can undergo fast reduction–oxidation process through electron delocalization around its molecular cage. The results presented in this study demonstrate the ability of POMs as an active element to fabricate resistive random‐access memory (RRAM) for high‐density data‐storage applications.
Resistive switching (RS)‐based random access memory has been envisaged as a viable alternative to existing memory technology due to its nonvolatility, high switching speed, high endurance/retention, ...and considerably low operating voltage. Herein, a new uniform, repetitive, and stable RS phenomenon is demonstrated based on very low‐cost two‐terminal metal–insulator–metal stack fabricated using a highly redox‐active vanadium‐based polyoxometalate (POM) molecular clusters, V10O286−—belonging to polyoxovanadate (POV) family. The RS is observed to be unipolar and nonvolatile in nature, and occur at a fairly low operating bias voltage (less than 2 V), making it suitable for low‐power operations. The switching event is attributed to the cycling between formation and rupture of tiny conductive nanofilaments formed due to trapping and detrapping of positively charged ionized oxygen vacancy sites present in the active switching layer of V10O286−. POMs, in their rich abundance, are highly stable early transition‐metal oxide nanosized clusters, capable of storing as well as releasing a large number of electrons. In addition, they can undergo fast and reversible redox reactions (both in solid and liquid electrolyte media) in “stepwise” manner—a property that makes them a promising candidate for ultrafast and multi‐level nonvolatile molecular memory for high‐density data storage. Preliminary investigations on the POV‐based memory cells result in device resistance ratio ≈25, endurance for more than 200 cycles, and stable retention time around 2200 s, in fully open air condition.
Highly redox‐active vanadium‐centric polyoxometalate (POM) clusters are exploited for building ultrafast and nonvolatile molecular memory. POMs are large reservoir of electrons and they can undergo fast reduction–oxidation process through electron delocalization around its molecular cage. The results presented here demonstrate the ability of POMs as an active element to fabricate resistive random‐access memory (RRAM) for high‐density data‐storage applications.
Abstract only
Background:
Many studies of outcomes in peripartum cardiomyopathy (PPCM) are limited by short-term follow-up of 6-12 months. Long-term mortality rates and outcomes are largely unknown. ...Prior research has also suggested under-utilization of implantable-cardioverter defibrillators (ICD) in this population.
Methods:
Patients with PPCM at a tertiary care center were retrospectively identified using ICD9 code 674.5x from 2000-2011, and each chart was manually reviewed. Clinical, demographic, and echocardiographic data were reviewed, with follow-up through November 2016. Recovery was defined as ejection fraction (EF) >= 55%.
Results:
Of 60 patients, 35 were white (58.3%) and 16 were black (26.7%). Mean age at diagnosis was 29.6 years (range 18-44 years) and average follow-up was 5.8 years. Mean EF at time of diagnosis was 20.2 +/- 4%, at 6-months follow-up it was 39.6 +/- 4%, and at final follow-up was 38.7 +/- 3%. Recovery (EF>=55%) occurred in 38%. Of those who did not recover (62%), the final mean EF was 25%. ICD was placed in 19 patients (51%). Only one patient with an ICD later recovered at one year follow-up. LVAD or transplant occurred in 8 patients, and death occurred in 7 patients with a mean survival of 4.4 +/- 1.4 years. Five patients experienced subsequent deterioration in their EF (with a range of 10-35%) in the absence of a subsequent pregnancy, with a mean decrease in EF of 23.2%. Three of these patients had achieved full recovery (EF>=55%) prior to subsequent decline.
Conclusions:
Patients with PPCM who have initial improvement in EF or even full recovery, can later suffer deterioration, even in the absence of subsequent pregnancy. This finding warrants continued surveillance and raises the question whether lifelong medical therapy may be indicated despite recovery. This study also shows a higher rate of ICD utilization than prior reports.
Abstract only
Background:
Few studies have evaluated temporal trends in outcomes and risk factors for peripartum cardiomyopathy (PPCM). Prior research using administrative data could only assess ...short-term in-hospital adverse events. It has also been hypothesized that the incidence of PPCM is rising due to advancing maternal age and increased risk factors. Therefore, we examined long-term outcomes and prognostic factors to determine if there has been any change over the past decade.
Methods:
Patients seen at a tertiary care center between 2000 and 2011 with a diagnosis of PPCM were identified by ICD9 code 674.5x and confirmed by manual chart review. Year of diagnosis, clinical and demographic variables, echocardiographic data, and outcomes including myocardial recovery (defined as EF>=55%), ICD placement, LVAD, transplant, and death were reviewed for follow-up through November 2016.
Results:
Of 60 patients, 31 (52%) were diagnosed recently (2006-2011) and 29 (48%) were diagnosed prior to 2006 (1996-2005). There were no significant differences in the recent group compared to the past group in initial EF (19% vs 22%), final EF (39% vs 39%), and final recovery status (52% vs 48%). Similarly, there were no differences in rates of ICD implantation, LVAD/transplant, mortality, and years of survival. There were no differences in age at diagnosis or in rates of hypertension, smoking, or diabetes. Few patients in either category underwent a subsequent pregnancy. Mean years of follow-up (through 2016) were longer for those diagnosed prior to 2006 (8.3 years vs 3.4 years, p<0.001).
Conclusions:
There has been no improvement in outcomes for patients diagnosed with PPCM in the past decade. Maternal age and risk factors do not appear to be increasing. Despite advances in heart failure treatment and increased awareness of PPCM, more research about the management and follow-up of young mothers with PPCM is needed.
Long-term Outcomes in Peripartum Cardiomyopathy Mahowald, Madeline K; Basu, Nivedita; Subramaniam, Latha ...
The open cardiovascular medicine journal,
01/2019, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background:
Prior studies of Peripartum Cardiomyopathy (PPCM) are limited by short-term follow-up. Contemporary long-term outcomes and change in myocardial function over time are poorly ...characterized.
Methods and Results:
This retrospective cohort study included women with PPCM at the University of Michigan (2000-2011), with follow-up on March 31, 2017. Subsequent pregnancies were excluded. Recovery was sustained left ventricular Ejection Fraction (EF) ≥55%. Major Adverse Events (MAE) included death, cardiac transplantation, left ventricular assist device, or inotrope-dependence. A total of 59 women were included (mean SD age at diagnosis, 29.5 6.8; 28.8% Black), with a mean follow-up of 6.3 years. Recovery occurred in 22 women (37%); of these, 8 women (36%) had delayed recovery (>12 months). All cause mortality was 20% (12/59) with median survival 4.2 years; of these, 9 women (75%) died after the first year (range 2 - 10 years). MAE occurred in 19 women (32%); of these, 11 women (42%) had MAE >12 months from time of diagnosis (range 2-20 years). Deterioration in EF by >10% from the time of diagnosis occurred in 16 women (27%). This group had worse long-term outcomes, including lower final EF (mean 25
vs
42%, p=0.010), less recovery (12
vs
46%, p=0.016), and higher rates of death (38
vs
14%, p=0.046) and MAE (56
vs
23%, p=0.016).
Conclusion:
Women with PPCM have long-term risks of mortality, MAE, and subsequent decline in EF, even in the absence of a subsequent pregnancy. Deterioration in EF is associated with adverse events; thus, long-term management is important.
Abstract
Aims
Left atrial (LA) function helps to preserve cardiac output and to control pulmonary capillary wedge pressure in the setting of left ventricular (LV) impairment, but little is known ...about the contribution of the LA function to ventricular arrhythmia. We sought whether LA booster pump function was associated with arrhythmias in patients undergoing primary prevention implantable cardioverter-defibrillator (ICD) implantation for non-ischaemic dilated cardiomyopathy (NICM), independent of global longitudinal strain (GLS) and mechanical dispersion (MD).
Methods and results
We identified 124 NICM patients (56 ± 13, 67 male) who underwent echocardiography pre-ICD implantation for primary prevention. The main outcome measure was appropriate ICD therapy (anti-tachycardia pacing or shock). The mitral A-wave was used as an LA functional marker. MD was defined as standard deviation of time to peak strain of each segment. Over a median follow-up of 3.8 ± 2.2 years, 36 patients had appropriate ICD therapy, including 23 shocks. Patients with appropriate ICD therapy had lower A-wave velocity (P < 0.001), larger LA volume (P < 0.001), and impaired circumferential MD (P = 0.006), but similar ejection fraction (EF) (P = 0.40) and GLS (P = 0.11). In sequential Cox proportional hazards models, A-wave, E/A ratio, and GLS were significantly associated with outcomes, independent of age, sex, and cardiac resynchronization therapy defibrillator or left bundle branch block. In nested Cox models, mitral A-wave had a prognostic value incremental to models with LV systolic (EF and GLS) and diastolic functional parameters (E/A, E/e′, and LA volume) and MD.
Conclusion
LA booster pump function was an independent and incremental predictor of arrhythmias in NICM over GLS and MD, and may aid better risk stratification in this population.
A new electrochemical hybridization transduction pathway, obtained by coupling electrochemical adsorption and long‐range electron transfer through double‐stranded DNA, was investigated using ...ultramicroelectrode (UME). The results show that long‐range electron transfer does not occurs exclusively throws well‐packed and organized self‐assembled DNA monolayers. This approach is used to investigate long‐range electron transfer properties of both single‐ and double‐ stranded short synthetic DNA and DNA plasmids. Single mismatch electrochemical detection protocol of non‐labelled short synthetic DNA, without heating or probe labelling, in a 10 minutes protocol, was in fine performed.
Platinum oxide thin film (100 nm) deposited using an optimized reactive ion sputtering process revealed p-type semiconducting behavior with a band-gap of 1.5 eV, resistivity of 0.16 Q-m, and ...activation energy of 0.22 eV. XPS spectra indicated the presence of PtO phase (32%) along with PtO 2 phase (68%). The XRD spectra indicated the formation of α-PtO 2 phase. arrays of simple, two terminal sensors were fabricated on transparent, flexible, and acetate substrates with platinum oxide thin film forming the active layer (8.0 mm × 60 μm) for DNA detection. The sensor operated on the principle of conductance change resulting from the change in charge carrier density due to attachment of DNA to the platinum oxide surface. The DNA attachment onto platinum oxide was experimentally verified by performing Fourier transform infrared spectroscopy and optical fluorescence measurements. The binding constant of DNA to platinum oxide was found to be 7.35 pM for every percentage increase in fluorescence intensity. The sensor arrays showed a DNA concentration-dependent current change that was linear over a large dynamic range and sensitivity down to 0.5 nM. The label-free platinum oxide DNA sensors showed reproducibility with a coefficient of variation of less than 10%.
Here we report for the first time that proteins can function as unique reducing agents to produce gold nanoparticles from gold salts. We demonstrate that three different proteins, namely, bovine ...serum albumin (BSA), Rituximab (RIT--an anti-CD20 antibody) and Cetuximab (C225--anti-EGFR antibody), reduce gold salts to gold nanoparticles (GNP). Interestingly, among all the three proteins tested, only BSA can reduce gold salts to gold nanotriangles (GNT). BSA-induced formation of GNT can be controlled by carefully selecting the reaction condition. Heating or using excess of ascorbic acid (AA) as additional reducing agent shifts the reaction towards the formation of GNP with flower-like morphology, whereas slowing down the reaction either by cooling or by adding small amount of AA directs the synthesis towards GNT formation. GNT is formed only at pH 3; higher pHs (pH 7 and pH 10) did not produce any nanoparticles, suggesting the involvement of specific protein conformation in GNT formation. The nanomaterials formed by this method were characterized using UV-visible (UV-vis) spectroscopy and transmission electron microscopy (TEM). This is an important finding that will have uses in various nanotechnological applications, particularly in the green synthesis of novel nanomaterials based on protein structure.
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